Bij patiënten met diabetes type 2
Postbus 581, 2003 PC Haarlem - Tel. 0800-9999 000 - www.msd.nl, www.univadis.nl - E-mail: [email protected]
• De eerste DPP-4 remmer
• Sterke HbA1C-verlaging1
• Wereldwijd > 50 miljoen recepten2
e
26 Internistendagen
Abstractboek
(Abstracts submitted to the Annual Meeting of the Netherlands Association of Internal
Medicine, 23-25 April 2014, Maastricht, the Netherlands)
23-25 april 2014
MECC
Maastricht
Raadpleeg de volledige productinformatie
(SPC) alvorens JANUVIA of JANUMET voor
te schrijven.
Voor meer productinformatie zie verkorte SPC elders in dit blad.
DIAB-1033712-0117
26e Internistendagen • Abstractboek • 23-25 april 2014 • MECC • Maastricht
Kracht, bewijs
en ervaring
Referenties: 1. Nauck MA, Meininger G, Sheng D, et al; for the sitagliptin
study 024 group. Efficacy and safety of the dipeptidyl peptidase-4
inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in
patients with type 2 diabetes inadequately controlled on metformin
alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes
Metab. 2007;9(2):194–205. 2. IMS Health, NPA ™Monthly, TRx’s,
October 2006 – January 2013
INHOUD
26e Internistendagen
Abstractboek
23-25 april 2014
MECC, MAASTRICHT
Voorwoord
3
Presentations “Schop de Heilige Huisjes omver!”
4
I
Oral Presentations Research en Case reports
10
II
Endocrinology Research
33
III
Endocrinology Case reports
33
IV
Diabetes Mellitus Case reports 39
V
Diabetes Mellitus Research
39
VI
Haematology Research
41
VII
Haematology Case reports
45
VIII
Oncology Research
61
IX
Oncology Case reports
64
X
Vascular Medicine Research
69
XI
Vascular Medicine Case reports
73
XII
Gastro-Enterology Research
77
XIII
Gastro-Enterology Case reports
78
XIV
Infectious Diseases Research
79
XV
Infectious Diseases Case reports
83
XVI
Nephrology Research
97
XVII
Nephrology Case reports
100
XVIII
Intensive Care Research
106
XIX
Intensive Care Case reports
110
XX
Rheumatology Research
114
XXI
Rheumatology Case reports
114
XXII
Immunology/Allergology Research
117
XXIII
Immunology/Allergology Case report
118
XXIV
Other Research
119
XXV
Other Case reports
121
XXVI
General Internal Medicine Research
121
XXVII General Internal Medicine Case reports
122
Index
134
1
Voorbereidingscommissie
An Reyners - voorzitter
Paul van Daele
Kees Hovingh
Harry Koene
Robin Peeters
Hilde Royen
Patricia Stassen
Roderick Tummers-de Lind van Wijngaarden (JNIV)
Joost Wiersinga
Deelnemende verenigingen
Nederlandse Internisten Vereniging (NIV)
Internistisch Vasculair Genootschap
Juniorafdeling Nederlandse Internisten Vereniging
Nederlandse Federatie voor Nefrologie
Nederlandse Vereniging voor Allergologie
Nederlandse Vereniging voor Endocrinologie
Nederlandse Vereniging voor Gastro-Enterologie
Nederlandse Vereniging voor Haematologie
Nederlandse Vereniging voor Immunologie
Nederlandse Vereniging voor Klinische Farmacologie
en Biofarmacie
Nederlandse Vereniging voor Medicale Oncologie
Nederlandse Vereniging voor Medical Onderwijs
NIV Sectie Acute Interne Geneeskunde
NIV Sectie Intensive Care
NIV Sectie Ouderengeneeskunde
Vereniging voor Infectieziekten
Organiserende vereniging
Nederlandse Internisten Vereniging
(Medicinae Internae B.V.)
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Fax: 030-282 32 25
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© 2014
Overname van delen uit dit abstractboek kan alleen
plaatsvinden na schriftelijke toestemming van de
uitgever.
ISBN: 978-90-8523-153-0
2
VO ORWO OR D/INTR O D U C TION
Met genoegen presenteren wij u het Abstractboek van de 26e Internistendagen, gehouden van 23-25 april 2014 in het
MECC te Maastricht.
De abstracts betreffen zowel wetenschappelijk onderzoek als ‘case reports’. Uit alle windrichtingen zijn de abstracts
in grote getale ingestuurd. Er zijn 232 abstracts ingediend, die zijn opgenomen in dit Abstractboek. Uit deze abstracts
werden 40 abstracts geselecteerd voor orale presentatie. Deze worden eerst vermeld (de ‘O’-nummers), gevolgd door de
overige abstracts (de ‘C’-nummers), geclassificeerd per vakgebied. De selectie is gebaseerd op wetenschappelijke inhoud,
originaliteit en presentatie. De selectie gebeurt anoniem (auteurs en instituut worden geblindeerd) door drie leden van de
commissie. De abstracts met de hoogste scores zijn geselecteerd voor orale presentatie. Dit jaar is er voor gekozen om de
abstracts zoveel mogelijk per onderwerp te bundelen met een algemene inleiding door de voorzitters.
Het grote aantal ingezonden abstracts onderschrijft dat dit een belangrijk onderdeel is van de Internistendagen. In de
eerste plaats voor de arts-assistenten omdat de Internistendagen een uniek podium zijn om resultaten van onderzoek of
bijzondere observaties te presenteren aan een enthousiast publiek. In de tweede plaats voor de toehoorders, die kunnen
vernemen wat er gebeurt aan het front van de Interne Geneeskunde in Nederland en in de derde plaats om de diverse
onderzoeksgebieden binnen de Interne Geneeskunde met elkaar in contact te brengen. Ook dit jaar zal per sessie een
winnaar worden aangewezen die een prijs van 500 euro overhandigd zal krijgen!
Ook zullen de vier uitgekozen Heilige Huisjes in dit Abstractboek worden vermeld. Tijdens de plenaire sessie op vrijdagochtend 25 april zullen de auteurs proberen hun Heilige Huisje omver geschopt te krijgen.
Namens de hele Commissie Internistendagen wens ik u veel plezier toe met het lezen maar vooral aanhoren van de vaak
gloednieuwe onderzoeksresultaten en het oplossen van de leerzame puzzels in de case reports uit alle klinieken van
Nederland!
An Reyners
Voorzitter Commissie Internistendagen
This abstract book contains all abstracts that have been submitted to the Annual Meeting of the Netherlands Association of
Internal Medicine, 23-25 April 2014 in Maastricht, the Netherlands.
Both research abstracts and case reports are included, representing all disciplines of Internal Medicine. 40 abstracts have
been selected for oral presentation. These abstracts are printed first, in the order of presentation. The remainder of abstracts is
categorized according to discipline.
An Reyners
Chairman Organizing Committee
3
criteria runs a high risk of misdiagnosis.3 Furthermore,
patients either fulfill or not fulfill classification criteria. In
clinical practice, this “yes or no option”is not acceptable,
since a physician needs a flexible and open mind during
the diagnostic process in order to decide on definite,
probable or possible presence of a disease.3 This nuance
is not included in the current sepsis criteria and this
may again lead to misdiagnosis of sepsis. Also, criteria
developed for diagnosis of a disease with high mortality
(i.e. sepsis) should have a high sensitivity in order to
identify as many patients as possible (low rate of false
negative patients). Conversely, classification criteria should
have a high specificity in order to prevent that patients
without the target disease are classified.
Second, it is debatable whether the sepsis criteria are
robust enough to even meet the requirements of either
diagnostic or classification criteria. After development of
a candidate criteria set, the candidate criteria set should
be validated in patients suffering from the disease. The
expert physician’s diagnosis is often used as a gold
standard. We could identify only one article that validates
the sepsis criteria in the emergency department. In a
prospective study of Gille-Johnson et al., 72% of patients
in which SIRS was observed at first presentation on the
emergency department, had no (severe) sepsis at follow-up.
Furthermore, 23% of patients with severe sepsis within
24 hours after admission did not present with SIRS. 4
These results show that the sepsis criteria lack acceptable
discriminative ability and that a criteria set that has not
been validated before implementation runs an even higher
risk of misdiagnosis.
Last, applying the sepsis criteria in individual patients
can lead to circular reasoning. A patient fulfils the sepsis
criteria when there are signs of SIRS in addition to a
documented or presumed infection. However, clues that
point in the direction of a presumed infection are often
the signs of SIRS. For instance, a physician suspects that a
patient has pneumonia because of a respiratory rate > 20/
min and a white blood cell count > 12 x 10E9, but these
manifestations are also listed signs of SIRS.
In conclusion, we underscore the need to have robust
sepsis criteria – both diagnostic and classification criteriathat will be able to reduce sepsis related mortality and
morbidity. However, we were surprised to notice that
the sepsis criteria have not been validated in the target
population. They should therefore most certainly not be
used as diagnostic criteria and not be applied in individual
patients, since the current sepsis criteria run a high risk
of misdiagnosis.
How should we apply the sepsis criteria at this moment?
One can use the sepsis criteria for pattern recognition.
The physician is the only one that can consider all relevant
features in an individual patient, even those features
that are not represented in the sepsis criteria. Relying on
PRESENTATIONS “Schop de Heilige Huisjes omver!”
(Sessie vrijdag 25 april 08.45 - 09.45 uur Auditorium 1)
HH1 The sepsis criteria: blessed but not yet holy!
M.G.B. van Onna, P. Stassen, A.E.R.C.H Boonen
Maastricht University Medical Center, Department
of Internal Medicine, Rheumatology, P. Debyelaan
25, 6229 HX MAASTRICHT, the Netherlands, e-mail:
[email protected]
Sepsis is a systemic inflammatory response syndrome
(SIRS), caused by an infection. The condition is associated
with a mortality up to 25%, which emphasizes the need
for early diagnosis and adequate treatment.1 Criteria to
define sepsis are now part of composite clinical practice
guidelines, the Surviving Sepsis Campaign (SSC)1,2 As
a result of the SSC, the sepsis criteria have become
an important diagnostic screening tool, also in the
Netherlands and fulfilment of the sepsis criteria often
leads to the start of a more intensive antibiotic regimen.
We want to draw attention to the incorrect use of the sepsis
criteria, since these criteria have not been thoroughly
validated in the emergency care setting and application of
the sepsis criteria in the individual patient might result in
misdiagnosis, overexposure to (broad spectrum) antibiotic
regimens and a false sense of security.
Why do we want to develop criteria sets as physicians?
Most diseases or syndromes, like sepsis, lack a single
distinguishing feature. Therefore, a combination of
clinical, laboratory and radiological manifestations is
needed to identify the disease. The most important
manifestations of a disease can be merged into a criteria
set.3 Criteria sets can roughly be divided into 2 categories,
namely diagnostic and classification criteria. The group
of experts that developed the sepsis criteria however
state that “the criteria should be broadly useful both to
clinicians caring for patients at the bedside”(diagnosis)
and “to researchers designing observational studies and
clinical trials”(classification).2 There are 3 major concerns
regarding this statement.
First, there are crucial differences between diagnostic and
classification criteria sets. Diagnostic criteria are used
to make a diagnosis and the clinical value is therefore
highly dependent on the prevalence of the disease.
Classification criteria are applied to patients in whom
the clinical diagnosis has already been made and aim to
create homogeneous groups of patients, which facilitates
comparisons of clinical studies.3 Prevalence of the disease
is not important when using classification criteria, because
all patients already have the disease, since they have
been previously diagnosed as such. Therefore, making a
diagnosis because a patient fulfills certain classification
4
ulcer, familial bleeding disorder, PE, unfractionated
heparin (UFH) ≥ 18 hours, inability to treat with LMWH,
noncompliance, geographic inaccessibility, deficiency of
antithrombin III, protein C, protein S or pregnancy.
Patients were assigned to ambulatory treatment with
1 mg enoxaparin per kilogram subcutaneously twice daily
or in-hospital treatment with UFH with a bolus dose of
5000 units and targeted aPTT of 60-85 seconds. Study
medication was discontinued with minimal five days
of treatment when targeted INR (2.0-3.0) was reached,
after which warfarin was prescribed for a duration of
3 months. Follow-up was three months and included
impedance plethysmography. Principal outcome events
were symptomatic recurrent VTE and bleeding during
study medication or within 48 hours after discontinuation.
2230 consecutive patients were screened, 1491 excluded
and 239 refused participation remaining 500 participants.
Duration of study treatment was comparable (5.8 ± 1.8
LMWH vs 5.5 ± 1.2 days UFH) as was the percentage of
time INR in the therapeutic range (63% vs 62%). Both
symptomatic recurrent VTE and bleeding events did not
differ between the groups (5.3% LMWH vs 6.7% UFH, p =
0.57 and 2.0% vs 1.2%, p = 0.50).1
Koopman conducted a RCT in patients with acute
proximal DVT diagnosed by venography or ultrasonography. Exclusion criteria were VTE within preceding 2
years, suspected PE, treatment with UFH ≥ 24 hours,
geographic inaccessibility, life expectancy ≤ 6 months,
post-thrombotic syndrome or pregnancy. Patients were
assigned to ambulatory treatment with nadroparin twice
daily adjusted for body weight or in-hospital treatment
with UFH with a bolus of 5000 units and targeted aPTT
1.5 to 2 times the mean value in normal subjects. Study
medication was discontinued when targeted INR was > 2.0
two consecutive days with minimal five days of treatment
after which oral anticoagulant treatment was started for
3 months. Follow-up was three months and in cases of
suspected recurrent DVT venography or ultrasonograpy
was performed. Primary analysis involved recurrent VTE
during the first six months. Secondary outcome events
were incidence of major bleeding in the first three months.
From 692 eligible patients, 216 were excluded and 76
refused participation remaining 400 participants. In both
groups, 68% of the participants had thrombi of the femoral
vein or more proximal veins. Duration of study treatment
was comparable as was the percentage of time INR in the
therapeutic range. Both recurrent VTE and incidence of
major bleeding events did not differ between the groups.2
Belcaro conducted a RCT in patients with acute proximal
DVT diagnosed by color duplex ultrasonography. Exclusion
criteria were previous ≥ 2 episodes with VTE, active
bleeding, ulcers, familial bleeding or coagulation disorder,
PE, UFH ≥ 48 hours, geographic inaccessibility, patients
with malignancy requiring surgery or chemotherapy
criteria without evaluating the context of these criteria
sends the wrong message to future/young physicians.
More efforts should therefore be made to train and educate
physicians about the full range of symptoms associated
with the concept of sepsis, including the clinical manifestations of infection.
In a nutshell, before the sepsis criteria can officially be
declared holy, one or two miracles still need to happen.
References
1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis
Campaign: international guidelines for management of
severe sepsis and septic shock, 2012. Intensive Care Med.
2013;39:165-228. doi: 10.1007/s00134-012-2769-8.
2 Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/
ACCP/ATS/SIS International Sepsis Definitions Conference.
Crit Care Med. 2003;31:1250-6.
3. Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis
and classification in early ankylosing spondylitis: do we need
new criteria? Arthritis Rheum. 2005;52:1000-8.
4. Gille-Johnson P, Hansson KE, Gårdlund B. Severe sepsis and
systemic inflammatory response syndrome in emergency
department patients with suspected severe infection. Scand
J Infect Dis. 2013;45:186-93.
HH2 Deep venous thrombosis in the iliac veins: in
hospital treatment or ambulatory care?
B. de Jong, R. Heijligenberg, E. de Kruijf
Gelderse Vallei, Department of Internal Medicine, Willy
Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
[email protected]
To prevent pulmonary embolism (PE) and recurrent
thrombosis most patients with deep venous thrombosis
(DVT) are treated with low molecular weight heparin
(LMWH) and oral anticoagulants on an outpatient basis.
However, especially with thrombi in the external iliac or
common iliac vein some physicians assume an increased
risk for complications such as acute PE and decide to admit
the patient for treatment and observation. We critically
appraised this topic by defining the following ‘question of
the week’: will ambulatory treatment of patients with a first
iliac DVT lead to more morbidity and mortality compared
to in-hospital treatment? PubMed was searched using the
query ‘ambulatory care AND deep venous thrombosis’. 449
items were found and titles and abstracts were screened
for relevance. Four articles were selected prospectively
randomizing adult patients to in- or outhospital treatment
for a proximal DVT.
Levine conducted a RCT in patients with acute proximal
DVT confirmed by venography or duplex ultrasonograpy.
Exclusion criteria were previous ≥ 2 episodes with venous
thromboembolism (VTE), active bleeding, active peptic
5
HH3 Reassuring patients, internists primary task of the
future? Not by ordering (even more) diagnostic tests!
following 3 months, participants with likelihood of low/no
compliance, pregnancy and platelet count < 100 x 109/L.
Patients were assigned to ambulatory treatment with
subcutaneously nadroparin 100 IU per kg or subcutaneous calcium heparin 12.500 IU twice daily or in-hospital
treatment with intravenous UFH with a bolus of 5000
units and targeted aPTT 60-85 seconds or subcutaneously
nadroparin. Study medication was (LMWH, UFH) discontinued when targeted INR was > 2.0 for 2 consecutive days
after which oral anticoagulant treatment was started for
3 months. Follow-up was 3 months and included ultrasonography. Main outcome events were recurrent DVT,
bleeding during study medication or within 48 hours
after discontinuation, PE, days of hospitalization and
number of patients without admission. 589 patients were
screened, 264 excluded and 54 patients refused participation remaining 325 participants (66% were outpatients).
Main outcome events did not differ.3
Finally, Boccalon conducted a RCT in patients with
proximal DVT diagnosed by venography or ultrasonography. Exclusion criteria were thrombus in inferior
vena cava, floating thrombus, previous PE, DVT within
preceding 6 months, necessity for hospitalization,
contraindication for anticoagulant treatment, UFH ≥ 48
hours, pregnancy, geographic inaccessibility or logistical
problems. Patients were assigned to in or outhospital
treatment with LMWH and an oral anticoagulant.
Follow-up was 6 months and included ultrasonography.
Primary endpoints were DVT recurrence, PE or major
bleeding. 204 patients were enrolled in the study. 65% had
a femoral and 18% an iliac thrombosis. Primary endpoints
did not differ between both groups. 4
Several other prospective and retrospective cohort studies
and case series confirm the safety and effectivity of
ambulatory care of patients with proximal DVT.5-11
A systematic review recommends outpatient treatment
with LMWH in patients with acute DVT(level 1 evidence).12
A multicenter prospective cohort study selected patients
with acute PE for outpatient treatment which was
effective and safe irrespective of the presence of iliac vein
thrombosis.13
To assess whether the question to admit a patient with
thrombosis in the iliac veins is only an issue in our
hospital, we interviewed 20 internists (university medical
centers, medium and large (non)teaching hospitals). Nine
internists stated that they would treat and observe these
patients on an in-patient basis.
Conclusion: Proximal DVT confined to the iliac veins
often leads to admittance for the patient for observation
and treatment. Presumably because the treating internist
perceives an increased risk for complications. However,
the available evidence advocate outpatient treatment with
a level of evidence 1A. 4
B.P.A. Spaetgens, E. Fonseca Wald, P.M. Stassen
Maastricht University Medical Center+, Department of Internal
Medicine, P. Debyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected]
Introduction: Reassuring patients is one of the essential
medical competences (communication) of today’s
physician. It is also (one of) the main task(s) of the
internist, especially in the outpatient clinics, where more
than one-third of the patients present theirselves with
symptoms for which no apparent organic pathology can
be found.1,2 Limited research on this subject has been
performed and therefore the factors that contribute to
successful reassurance of patients are largely unknown.
This is an interesting finding, because not being able to
reassure patients has significant clinical (psychological)
and financial consequences.3 It is therefore even more
interesting that physicians tend to reassure patients by
using diagnostic tests, even in patients with a low pretest
probability of disease. The ordered diagnostic tests vary
from simple blood testing to magnetic resonance imaging
(MRI), depending on the main complaint. In one study, the
number two reason for ordering tests is to reassure patients
(the number 1 reason is “to exclude other diseases”). 4
After several experiences with patients who were not
reassured after unnecessary diagnostic testing (“the doctor
just does not know yet what I have!”), we have reasonable
doubt about the use of diagnostic testing to reassure
patients with low pretest probability of disease. Last,
but certainly not least, we express our doubt because
unnecessary testing may lead (leads?) to higher costs, to
possible complications (e.g. anaphylactic shock after iodine
contrast) and to false-positive test results, which make it
even harder to reassure patients.2,3
This led to the following clinical question:
Does diagnostic testing, when applied in low pretest
probability of disease, reassure patients in case of a
negative test result?
This question was critically appraised using the following
PICO:
Patient: Patients at the outpatient clinics internal medicine
with a low pretest probability of disease after anamnesis
and physical examination
Intervention: Perform diagnostic testing
Control: Do not perform diagnostic testing OR perform
testing, but not revealing results to the patient
Outcome: Reassurance as measured by: 1) Health-Related
Quality of Life: Illness concern, anxiety and symptom
persistence; 2) Health care resource utilization (and costs).
Search strategy: A literature search of PubMed was
performed. Search terms were: 1) Reassurance AND
6
Diagnostic Techniques and Procedures (Mesh-term).
2) Limits: Humans AND Systematic Review OR
Meta-Analysis OR Randomized Controlled Trial OR
Comparative study. There were 220 hits and after screening
titles and abstracts, 2 articles (systematic review and metaanalysis) seemed useful to answer the clinical questions.
Results: In 2011, van Ravesteijn et al. performed a wellconducted systematic review of randomised controlled
trials (RCT) that studied the efficacy of using diagnostic
tests to reassure patients.5 After an adequate, welldescribed literature search, they included 5 RCTs that
met the inclusion criteria. The RCTs studied different
diagnostic tests, which were: laboratory tests in patients
with fatigue, radiography or MRI lumbar spine in patients
with low back pain, MRI brain in patients with headache
and ECG and laboratory tests in patients with chest pain.
In this systematic review, no differences in level of
reassurance were found in the short-term (within
3 months, in 4 of the 5 RCTs) nor in the long-term (after
3 months, in all 5 RCTs), regardless of the diagnostic test
that was performed.
Another systematic review and meta-analysis by Rolfe et
al. studied the effect of diagnostic testing on reassurance
as well.6 After an adequate and well-described search, they
included 14 RCTs. In this study, reassurance was measured
using questionnaires about worries on illness, anxiety and
symptom persistence, both in the short- (within 3 months)
and long-term (after 3 months), They also included RCTs
on the effect of diagnostic testing on health care resource
utilization. In the RCTs, the following diagnostic tests
were performed: testing for dyspepsia (endoscopy or
Helicobacter Pylori-testing), radiography or MRI in back
pain, MRI in headache and lab testing in patients with
chest pain and palpitations.
They showed that performing diagnostic tests did not
reduce worries (short-term Odds Ratio (OR): 0.90; 95% CI
0.51-1.59; long-term OR: 0.87;95% CI 0.55-1.39) or symptom
persistence (short-term OR: 0.92; 95% CI 0.60-1.41;
long-term OR: 0.99; 95% CI 0.85-1.15). On the contrary,
there was even more anxiety in the investigation group
(vs. control group) as shown by a higher standardized
mean difference (SMD) in anxiety score: short-term SMD:
0.06 (-0.16-0.28); long-term SMD: 0.21 (-0.02-0.44).
Subsequent health care resource utilization was slightly
lower in the investigation group, mainly because of lower
number of primary care visits. However, this reduction in
health care utilization required several patients (varying
from 16 to 26) to undergo further diagnostic testing in
order to prevent only one primary care visit.
In conclusion, the presented systematic reviews are
elegantly performed and of sufficient quality and showed
that performing diagnostic tests to reassure patients
with a low pretest probability of disease is not useful.
In practical terms, this means that the ‘after-testing’
statement: “everything is normal”is insufficient to reassure
most patients. The postulated mechanism behind this is
that patients already develop negative ideas and beliefs
about their possible disease and thus reassurance is less
effective.7 This shows/confirms communication is very
important and patients should be educated about normal
test results in advance, which already had been shown
effective in one study.8
References
1. Hatcher S, Arroll B. Assessment and management
of
medically
unexplained
symptoms.
BMJ.
2008;336(7653):1124-8.
2. Bass C, Sharpe M. Medically unexplained symptoms in
patients attending medical outpatient clinics. In: Weatherall
DA, Ledingham JG, Warrell DA, eds. Oxford textbook
of medicine. 4th ed. Oxford: Oxford University Press,
2003:1296-303.
3. Winterberg D, Krol L. Effectief geruststellen. Medisch
Contact. 2005;271-3.
4. Boven van K, et al. Defensive testing in Dutch family
practice. Is the grass greener on the other side of the ocean?
J Fam Pract. 1997;44:468-72.
5. Van Ravestijn H, et al. The reassuring value of diagnostic
tests: A systematic review. Patient Educ Couns. 2012;86:3-8.
6. Rolfe A, Burton C. Reassurance after diagnostic testing with
a low pretest probability of serious disease. JAMA Intern
Med. 2013;173:407-16.
7. Donkin L, et al. Illness perceptions predict reassurance
following negative exercise testing result. Psychol Health.
2006;21:421-30.
8. Petrie KJ, et al. Effect of providing information about normal
test results on patients’ reassurance: randomised controlled
trial. BMJ. 2007;334(7589):352.
HH4 Should all immunocompomised patients recieve
PJP-prophylaxis? To measure is to know..
J.C.H. van der Hilst1, S Cuyx2
Jessaziekenhuis, Department of Infectious Diseases and
Immunity, Stadsomvaart 11, 3500 HASSELT, Belgium,
e-mail: [email protected], 2Katholieke Universiteit
Leuven, LEUVEN, Belgium
1
Introduction: Pneumocystis jirovecii is a fungal
organism, primarily known as the cause of pneumonia
in HIV-infected patients with CD4+ T-lymphocytopenia.
However, in recent years the incidence of Pneumocystis
jirovecii pneumonia (PJP) in immunocompromised
non-HIV patients is rising (1). The PJP risk in some patient
categories can be as high as 5-15% (2). This increased
incidence should be seen in context of the expansion of
therapeutic options with more aggressive chemotherapies
in solid tumors and hematological malignancies, and
7
count was 61 cells/mm3 (median: 118 cells/mm3). 91%
of patients had CD4+ counts < 300/mm3, prompting the
suggestion of using this threshold to guide initiation
of chemoprophylaxis (24). Several other studies found
similar results. A study by Glück showed a mean CD4+
count of 90.6/mm3 (median 80/mm3) in 7 patients who
developed PJP during immunosuppressive treatment for
various underlying diseases. Seeing only a minor shift
in the CD4+/CD8+ ratio, the authors conclude that the
absolute number of T-helper cells, but not the CD4+/CD8+
ratio nor the underlying disease determines the risk of PJP
(25). In a retrospective descriptive study by Fily et al., CD4+
count was available for 26 PJP cases in non-HIV-infected
patients. Here, the mean CD4+ count was 338 cells/
mm3 (median: 107/mm3). The authors suggest regularly
monitoring CD4+ counts in moderate risk patients and
acknowledge its role in the decision to start prophylaxis
(3). Roblot et al. found a mean of 200 CD4+ cells/mm3
(median: 100 cells/mm3) in 25 immunocompromised
non-HIV patients, suggesting further investigations into
the usefulness of this parameter (6). In another study
performed by Roblot et al. in non-HIV immunocompromised patients, a mean of 210 CD4+ cells/mm3 was found
in 14 patients. However, 42.9% of patients had counts
> 200 cells/mm3. Therefore, the authors conclude that
the critical CD4+ count is different from that in HIV,
but assessing the amount of CD4+ cells should still be
considered to determine the level of immunodeficiency (5).
Martin-Garrido et al. found data on 10 PJP patients treated
with Rituximab, showing a median of 25.5 CD4+ cells/mm3
(26), while De Castro et al. found a median of 131/mm3 in 8
patients after allogeneic stem cell transplantation (23). In a
case report by Kane et al., a patient on weekly methotrexate
had a CD4+ count of 150 cells/mm3, leading the authors
to suggest that suppression of CD4+ counts could be the
mechanism for development of PJP (8).
In the absence of CD4+ counts being measured, low
lymphocyte counts have often been reported, being a
possible surrogate marker (17, 22, 27-29). Of particular
interest is the finding by Godeau et al. in patients being
treated for granulomatosis with polyangiitis that the risk
of PJP was significantly associated with only the severity
of pretreatment lymphocytopenia at a cutoff of 800/mm3
and the lymphocyte count during the first 3 months of
treatment, with 10/12 PJP patients showing counts under
the threshold of 600/ml at least once. Lymphocyte subsets
were not measured in this study (27).
Conclusion: Chemoprophylaxis against PJP in various
groups of immunocompromised patients is effective.
The available data shows that, similar to in HIV patients,
CD4+ counts strongly correlate with the risk of developing
PJP. We suggest to measure CD4+ counts in all patients
taking immunosuppressive medication and only initiating
prophylaxis when CD4+ counts are < 300 CD4+ cells/mm3.
immunosuppressant and immunomodulating medications
in inflammatory diseases and transplantation medicine
(3-6). The presentation of PJP in non-HIV patients is more
severe and mortality is higher than in patients with HIV.
Symptoms and signs include a non-productive cough,
dyspnea, low-grade fever, tachypnea, tachycardia, and often
normal auscultation of the lungs (3-5).
CD4+ lymphocytes play a crucial role in the defense
against PJP. The AIDS epidemic in the early 80’s has
taught us that the risk of developing PJP dramatically
increases when CD4+ counts drop < 200 cells/mm3. In
concordance with the guidelines, prophylaxis is started
in all HIV-infected patients when CD4+ counts are
< 200 cells/mm3 (7). In contrast, no such guidelines yet
exist for other immunocompromised patients. Ideally,
and analogous to guidelines for HIV-infected patients,
a biomarker with a specific threshold could be used
to determine whether to start prophylaxis in these
patients, while simultaneously preventing overtreatment
and minimizing the occurrence of side effects and
development of drug resistance. Considering CD4+ count
for this purpose seems evident.
Clinical question: Can CD4+ counts select those non-HIV
immunocompromised patients that benefit from PJP
prophylaxis?
Methods: A Pubmed search was performed using the
keywords “Pneumocystis”, “non-HIV”, AND “Prophylaxis”.
Limits were set to English language, humans and adults.
The title and abstract of 26 articles were screened.
References and related citations were examined. 29 articles
were selected to answer the question.
Results: In the 1990’s, several case reports suggested CD4+
lymphocytopenia as the cause of PJP in non-HIV patients
(8-11). In a Cochrane review by Green et al., it was shown
that the administration of antibiotic prophylaxis with
trimethoprim/sulfamethoxazole significantly reduces the
occurrence of PJP by 91% and the PJP mortality with 83%
in immunocompromised non-HIV patients. Studies demonstrating the potentially beneficial effect of chemoprophylaxis have been performed in patients with inflammatory
bowel disease (12), connective tissue disease (13), immunemediated dermatologic conditions (14), hematologic malignancies and solid tumors (15), rheumatic disease (16), in
transplant recipients (2, 17), in patients receiving some
form of immunosuppressive medication (18-22), and after
allogeneic stem cell transplant (23). However, CD4+ count
was measured in only one of these studies.
In a prospective observational study by Mansharamani et
al., CD4+ counts were found to be significantly reduced
in patients with active PJP, in high clinical risk groups
(< 6 months after organ transplantation, patients receiving
chemotherapy) and in a subset of patients with low or
undefined risk (namely those on long-term corticosteroid
therapy). At the time of PJP diagnosis the mean CD4+
8
HH5 Is thiamine administration before glucose infusion
in patients with suspected thiamine deficiency really
necessary?
opinions (n = 2), case reports (n = 13) and animal models
(n = 4).
Results: The case reports were all descriptions of patients
which suspected thiamine deficiency. Including alcoholics,
anorexia from gastritis, kidney failure, pseudo-obstruction
and people on a starvation diet. Most of the cases already
showed symptoms of thiamine deficiency before glucose
infusion. There was no thiamine given before or after
the start of glucose infusion. In the next two to twelve
days the symptoms worsened after the glucose infusion.
After thiamine infusion the symptoms were less severe or
disappeared.1
Discussion: No evidence above the level of case reports
were found. Furthermore there were no case reports about
lactate acidosis and the research done in animal models
cannot be extrapolated to humans.
In reviewing the case reports, there is no sufficient
information to ascertain whether patients’ conditions
worsened due to the progression of their underlying
disease or due to the supposed effects of glucose on the
depletion of thiamine stores that could induce Wernicke’s.
Mounting evidence from case reports does seem to show
that prolonged glucose administration
without the addition of thiamine can be a risk factor for the
development or worsening of Wernicke
encephalopathy. But, there is no research done about
thiamine suppletion before compared with thiamine
infusion after the glucose infusion.
Conclusion: There is no evidence that thiamine supplementation is required before the glucose infusion.
Recommendation: Do not delay the glucose infusion. Give
patients with a suspected thiamine deficiency thiamine
supplementation after or concurrent with the start of
glucose infusion
E.M. Assenberg van Eijsden1, P.H.P. Groeneveld2
Isala klinieken, Zwolle, Department of Internal Medicine,
Dokter van Heesweg 2, 8025 AB, 8302 WJ EMMELOORD,
the Netherlands, e-mail: [email protected], 2Isala
klinieken, ZWOLLE, the Netherlands
1
Introduction: Wernicke encephalopathy is a neurological
disorder caused by prolonged thiamine
(vitamin B1) deficiency. It is most commonly seen in
alcoholics, but can also be found in any malnourished
state; patients with hyperemesis gravidarum, intestinal
obstruction, acquired immunodeficiency syndrome, gastric
bypass, and malignancies are commonly cited.1
Thiamine acts as a coenzyme for the decarboxylation of pyruvate to acetyl coenzyme A; this bridges
anaerobic glycolysis and the Krebs cycle. Thiamine is
also a coenzyme within the Krebs cycle and in the
hexose monophosphate shunt.2 A lack of thiamine causes
inhibition of anaerobic glycolysis. Besides Wernicke
encephalopathy, accumulation of toxic intermediates
including lactate occur, which can cause lactate acidosis.3
Medical school curricula and medical textbooks teach
clinicians that it is very important to supplement thiamine
before administering glucose in patients with possible
thiamine deficiency. 4,5,6
Harrison’s 18th edition page 2260; “Thiamine should
be given prior to treatment with IV glucose solutions.
Glucose infusions may precipitate Wernicke’s disease in a
previously unaffected patient or cause a rapid worsening of
an early form of the disease.”
Clinical question: Is thiamine administration before
glucose infusion required in patients with suspected
thiamine deficiency to prevent Wernicke encephalopathy
and lactate acidosis?
This clinical question was critically appraised using the
following PICO:
- Patient: Patients with suspected thiamine deficiency and
infusion of glucose – Intervention: Thiamine infusion
before glucose infusion – Control: No thiamine infusion
before glucose infusion – Outcome: Wernicke encephalopathy and lactate acidosis
Methods: A literature search was performed in
different databases; including the National guideline of
Clearinghouse, TRIP Database, Cochrane library and
PubMed.
Search terms were: Thiamine AND glucose AND Wernicke
OR Lactate
There were 144 hits and after screening abstracts, 1 article
seemed useful. A systematic review from 2008 with expert
References
1. Schabelman E, et al. Glucose before thiamine for wernicke
encephalopathy: a literature review. The Journal of
Emergency Medicine, Vol. 42, No. 4, pp. 488-494, 2012
2. Watson AJ, et al. Acute Wernickes encephalopathy precipitated by glucose loading. Ir J Med Sci. 1981;150:301-3.
3. Kuo SH, Debnam JM, Fuller GN, de Groot J. Wernicke’s
encephalopathy: an underrecognized and reversible
cause of confusional state in cancer patients. Oncology.
2009;76:10-8.
4. Keffer MP. Diabetic emergencies. In: Ma OJ, Cline DM,
Tintinalli JE, Kelen GD, Stapczynski SJ, eds. Emergency
medicine manual. 6th ed. New York: The McGraw-Hill
Companies, Inc. 2004:607-11.
5. Harrison’s 18th edition; p. 2260.
6. Van der Meer Interne geneeskunde, 2005; p. 261.
9
HH6 Respiratory alkalosis and Gram-negative
bacteraemia: is there an unique relationship?
bacteraemia. The assumption of this exclusive relationship
is based on historical studies with a bias in inclusion of
patients, which can be understood at the background of
medical history.
A.G. Vos, S.U.C. Sankatsing
Diakonessenhuis, Bosboomstraat 1, 3583 KE UTRECHT, the
Netherlands, e-mail: [email protected]
References
1. Waisbren BA. Bacteremia due to Gram-negative bacilli
other than Salmonella. Archives of Internal Medicine
Background: It is generally accepted in current medicine
that a bacteraemia with a Gram-negative organism should
be considered in case of a respiratory alkalosis. In the
‘Acute boekje’ of the ‘Nederlandse internisten vereniging’
an early bacteraemie, especially of Gram-negative
organism, is mentioned as a possible cause of a respiratory
alkalosis.This suggested relation is based on historical
studies. In 1951 a review of 29 cases related Gram-negative
bacteraemia to different clinical patterns of shock.1
Subsequent reviews of patterns and clinical and laboratory
findings of shock were performed. Most studies included
only patients with a Gram-negative bacteraemia. From the
late 50’s it became possible to perform blood gas analysis
on a larger scale. Respiratory alkalosis was observed
as a frequent concomitant sign of septic shock. It was
postulated that stimulation of the central respiratory center
and peripheral baroreceptors by bacterial endotoxins,
especially or exclusively of Gram-negative microorganisms, could induce hyperventilation.
To investigate if there is an unique relation between
respiratory alkalosis and Gram-negative bacteraemia, a
systematic literature search was performed.
Methods: A PubMed and EMBASE search was conducted
using the following synonyms in title or abstract: sepsis
OR shock OR SIRS OR ‘systemic inflammation’ AND
alkalosis AND ‘Gram negative’. Thirteen studies were
identified. After screening for relevance and checking the
references, six studies 2-7 remained.
Results: Al studies were observational, dating from 1960
till 1993, the number of patients ranged from 11 till 50.
Study quality was marginal. In all but one inclusion criteria
were not clear. 4 out of 6 studies included only patients
with a proven Gram-negative bacteraemia.2-5 Moments of
inclusion were heterogeneous, varying from bacteraemia
without shock till late, refractory shock. 3 studies5-7 included
patients with early shock or bacteraemia without shock.
A respiratory alkalosis was observed in 60 - 93% of the
patients. 2 out of these 3 studies included both patients
with a Gram-positive and a Gram-negative bacteraemia. No
difference in prevalence of respiratory alkalosis between
Gram-positive and Gram-negative bacteraemias was found.
Of the remaining 3 studies 2-4 2 included patients with late
or refractory shock and one with both early and late shock.
No correlation with respiratory alkalosis was found.
Conclusion: Respiratory alkalosis seems to be related
to bacteraemie without shock or with early shock. This
phenomenon is not exclusively related to Gram-negative
1951;88:467-88.
2. Blair E. Hypocapnia and gram-negative bacteremic shock.
Am J Surg. 1970;119:433-9.
3. Blair E, Cowley RA, Wise A, Mackay AG. Clinical physiology
of late (refractory) gram-negative bacteremic shock. Am J
Surg. 1969;117:573-86.
4. Elisaf M, Theodorou J, Pappas H, Siamopoulos KC.
Acid-base and electrolyte abnormalities in febrile patients
with bacteraemia. Eur J Med. 1993;2:404-7.
5. Simmons DH. Nicoloff J. Guze LB. Hyperventilation and
respiratory alkalosis as signs of gram-negative bacteremia.
JAMA 1960:174:2196-9.
6. MacLean LD, Mulligan GW, et al. Alkalosis in septic shock.
Surgery 62:655, 1967.
7. Winslow EJ, Loeb HS, Rahimtoola SH, Kamath S, Gunnar
RM. Hemodynamic studies and results of therapy in 50
patients with bacteremic shock. Am J Med. 1973;54:421-32.
I
ORAL PRESENTATIONS RESEARCH AND CASE
REPORTS
O01 Clinical value of serum IgG4 subclass levels in
patients with idiopathic retroperitoneal fibrosis
L.G. Pelkmans, E. Vermeer, T.R. Hendriksz,
E.F.H. van Bommel
Albert Schweitzer Hospital, Albert Schweitzerplaats
25, 3318 AT DORDRECHT, the Netherlands, e-mail:
[email protected]
Objective: In patients with idiopathic retroperitoneal
fibrosis (iRPF), inflammation and fibrosis may be a
manifestation of IgG4-related disease. As such, serum
IgG4 levels may be of value as parameter of IgG4-related
inflammation and in predicting treatment response.
Design: Prospective, observational study of 29 consecutive
iRPF patients who were seen at our tertiary care referral
centre from September 2010 through November 2013.
Measurements: Clinical, laboratory and radiological investigation was performed at presentation and at repeated
follow-up. All but 2 patients were treated with tamoxifen.
Treatment success was defined as such satisfactory clinical,
laboratory and radiological response to tamoxifen during
follow-up that there was no need to alter therapy. Treatment
outcome analysis included patients who had at least
10
42 g/L, ASAT 23 U/L, ALAT 18 U/L, total bilirubin 6
umol/L, GGT 19 U/L, alkaline phosphatase 88 U/L,
lactate dehydrogenase (LDH) 181 U/L, CRP 3.9 mg/L,
iron 15.3 umol/L, total iron binding capacity 40.2 umol/L,
transferrin saturation 38%, ferritin 109 ug/L, haptoglobin
< 0.10 g/L and TSH 2.0 m U/L. The direct agglutination
test (Coombs) was negative twice.
HIV serology was negative, cerulosplasmin levels were
normal and no thalassemia could be found. There was
no evidence of paroxysmal nocturnal hemoglobinuria,
erythrocytic enzymes were present in normal levels and
no splenic abnormalities were seen by echography. While
haptoglobin remained undetectably low with normal LDH
and bilirubin and Hb remained stable at 7.5 mmol/L, it was
concluded there was no hemolysis. Subsequent determination of hemopexin showed a normal value of 1010 mg/L
(500-1150 mg/L), indicating absence of severe or chronic
hemolysis. The diagnosis congenital anhaptoglobinemia
was made.
An- or hypohaptoglobinemia can both be acquired or
congenital. The acquired condition is due to increased
consumption in hemolysis or decreased synthesis in liver
dysfunction. Congenitally allelic deletion in the Hp-gene
cluster leads to decrease or absence of haptoglobin.
Hemopexin levels can differentiate between the two
forms: since hemopexin binds free heme its level decreases
after saturation of the hemoglobin-binding capacity of
haptoglobin. When haptoglobin is low in absence of
hemolysis hemopexin levels are normal.
Different fenotypes of congenital haptoglobin deficiency
exist. In true anhaptoglobinemia a silent allele with no
gene product is inherited (Hp 0). Hp 0-0 phenotype is
present in approximately 1 in 1000 Caucasians. In black
people (especially from West Africa) anhaptoglobinemia
is more frequent (> 30%).
Diagnosing hypohaptoglobinemia has important clinical
consequences since it is associated with heme accumulation resulting in iron-driven oxidative stress and vitamin
C depletion. In addition, it predisposes for allergic
transfusion reactions containing traces of haptoglobin
when haptoglobin antibodies are present.
4 months of follow-up and who underwent at least the
first CT scan follow-up. Second-line treatment consisted
of corticosteroids, either alone or combined with other
immunosuppressants.
Results: Overall, 13 patients (44.8%) had IgG4 levels above
the normal range of 1.4 g/L. In patients with elevated
IgG4 levels, locoregional lymphadenopathy (53.8% vs.
18.8%; p < 0.01) and to lesser extent atypical mass localisation (30.7% vs. 6.3%; p = 0.14) was observed more
frequently compared to that in patients with normal range
levels. Fibrotic mass thickness did not differ between
patients with normal range or elevated IgG4 levels
(median 28.0 [IQR 21.5-43.5] mm vs. 34.5 [IQR 16.5-50.3]
mm; p = 0.72). Males tended to have higher IgG4 levels
compared to females (1.66 [0.7-4.1] g/L vs. 0.53 [0.4-1.3]
g/L; p = 0.09). Eleven of 24 patients (45.8%) who received
tamoxifen eventually switched to second-line treatment.
Success rate in tamoxifen-treated patients with normal
range or elevated baseline IgG4 levels did not differ.
However, non-responders to tamoxifen had higher baseline
IgG4 levels compared to patients who responded satisfactorily to tamoxifen (1.31 g/L [0.7-7.3] g/L vs. 0.64 [0.3-1.7]
g/L, p = 0.05). All patients (100%) who had treatment
failure were men, compared to 57% of patients with
treatment success (p = 0.02). In patients who had treatment
failure with tamoxifen, IgG4 levels did not decrease until
after switch to second-line treatment (∆IgG4 0.55 [0.1-2.5]
before switch vs. 1.86 [0.6-7.2] after switch, p = 0.01).
Eleven of 13 patients had success of second-line therapy.
Conclusions: iRPF patients with elevated IgG4 levels
may present more often with atypical mass localisation and particularly locoregional lymphadenopathy.
Non-responders to tamoxifen had higher IgG4 levels
than responders. Females seem to respond better to
tamoxifen therapy, which might be explained by their lower
IgG4 levels.
O02 Low haptoglobin, reflex: hemolysis!
H.F. Dresselaars, K.G. van der Hem
Zaans Medical Centre, Department of Internal Medicine,
Koningin Julianaplein 58, 1506 DV ZAANDAM, the
Netherlands, e-mail: [email protected]
O03 Multi-organ toxicity due to chronic occupational
heavy metal exposure
A 56 year-old female Creole patient was referred by her
general practitioner because of a mild normocytic anemia.
Her medical history consisted of recurrent urinary tract
infections in the past. She did not use any medications.
Anamnesis and physical examination were unremarkable.
Laboratory results showed Hb 7.1 mmol/L, MCV 87 fl,
leukocytes 4.2 x 10E9/L with normal differentiation,
platelets 315 x 10E9/L, ESR 20 mm after 1 hour, reticulocytes 55.60 x 10^9/L, creatinin 77 micromol/L, albumin
D.J.L. van Twist, C.V. Hoge, G.H. Koek, H. ten Cate
Maastricht University Medical Centre, Department of Internal
Medicine, P. Debyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected]
Case: A 59-year-old man without relevant medical
history was referred to our hospital because of recently
diagnosed type 2 diabetes mellitus and thrombocyto-
11
O04 Microbial Strangulation After a Chinese Dinner?
penia. The patient complained of recurrent episodes of
general weakness, myalgia, feverishness, and dry cough.
Physical examination revealed purpura of the lower legs
and decreased sensibility of both feet. Routine blood
count showed thrombocytopenia (100*109/L), elevated
erythrocyte sedimentation rate (100 mm/hour), and
normochromic anemia.
As we suspected a systemic vasculitis, a biopsy from the
purpura was taken. This demonstrated leukocytoclastic
vasculitis with perivascular C3 depositions. Chest CT-scan
showed mediastinal lymphadenopathy and abdominal
ultrasound revealed livercirrhosis and splenomegaly with
extensive collaterals, suggesting portal hypertension.
Auto-immune serology and viral hepatitis tests were
negative. Levels of ceruloplasmin, serum copper and
iron were normal, and no nodular abnormalities or
iron depositions were found on MRI of the liver. As the
patient used no medication, drugs, or alcohol and liver
biopsy was not possible due to the thrombocytopenia and
presence of extensive collaterals, the etiology of the ChildPugh-A liver cirrhosis remained unclear. Propranolol was
initiated because of esophageal varices, but this resulted
in substantial edema and weight gain. Echocardiography
indeed revealed decreased left ventricular ejection fraction
(30%).
When asked, he mentioned running a galvanizing and
enameling company for art production for over thirty
years. Under suspicion of a heavy metal intoxication we
performed blood tests. Indeed, high levels of metals were
found: aluminium 0.58 (normal < 0.3) mmol/L, lead 2.02
(< 0.14) mmol/L, cadmium 8.0 (< 6.5) nmol/L, manganese
111.5 (< 11.3) nmol/L, nickel 86.5 (< 13) nmol/L, and cobalt
33.7 < 7) nmol/L.
The patient interrupted the galvanizing and enameling
activities, resulting in a significant decrease in metal
levels within a few months, but also in a spectacular
improvement of his general performance: skin abnormalities, mediastinal lymphadenopathy, and anemia
disappeared and ESR normalized. Interestingly, behavioral
and cognitive changes were noted: Whereas we formerly
saw an apathetic and lethargic patient with memory difficulties, he now made jokes, had good memory, and took
initiative to undertake activities.
Discussion: We describe a unique case of multi-organ
involvement of chronic intoxication with several heavy
metals due to chronic occupational exposure. This induced
an inflammatory reaction (leukocytoclastic vasculitis,
mediastinal lympheadenopathy and so-called ‘metal fume
fever’) and chronic damage to liver, nervous system
(behavioral and cognitive changes and polyneuropathy),
and (probably) heart. This case illustrates the risks of
chronic heavy metal exposure and the importance of
obtaining a thorough occupational history in each patient.
J. Vergragt1, T.J. Blokhuis2, D.W. Lange, de2
1
Ikazia Hospital, Department of Intensive Care,
Coornhertstraat 1, 3521 XE UTRECHT, the Netherlands,
e-mail: [email protected], 2University Medical Centre
Utrecht, UTRECHT, the Netherlands
A 55 year old male presented to the Emergency department
with headache, swelling of the upper lip and tachycardia.
Initially he was treated for an alleged allergic reaction to
the Chinese meal he consumed the evening before.
Absence of improvement led to consultation of the
neurologist and ENT specialist. After CT-scanning a
cerebral sinus thrombosis could not be ruled out, so he
received therapeutic dose of low molecular weight heparin.
Despite feeling relatively well, the swelling worsened. With
a modest fever as the only sign of infection, antibiotics
were added. As any diagnosis was still lacking, he was
observed on a medium care unit.
About 15 hours post admission, things started to go
downhill. He was feeling dyspnoeic, the swelling prevented
normal speech and saturation dropped. He was put on
100% oxygen and taken to the operating theatre to perform
urgent fiberoptic nasal intubation. With exceptional skill
and a sheer dose of luck the anesthesiologist could secure
the airway without adverse events.
Still clueless we “strongly observed” the clinical course
on the ICU. Then, at first daylight, we noticed a spreading
reddish discoloration of the left thorax. Meanwhile his need
for hemodynamic support also increased. The, at that time,
spot-diagnosis was necrotizing fasciitis.
Within minutes, he was back in the operating theatre to
undergo extensive debridement of the thoracic fasciae.
Remarkably, the face and neck remained totally unaffected
by the necrotic process. After 41 days in the hospital, our
patient recovered quite well.
Necrotizing fasciitis is very well known for its destructive
power, although the incidence is very low. The typical
presentation is excruciating pain, oedema and rapidly
spreading erythema. Later, the affected area becomes
anaesthetic, due to thrombosis.
However, less then 50% of cases presents classically, and
the average time to reach diagnosis is 24-48 hours. Why
then, the impressive airway obstruction without infection
of the neck? Older literature describes oedema outside
the affected area, but the underlying pathophysiological
mechanisms still need to be elucidated.
Although it almost killed him, the airway obstruction
served as an early warning something was seriously wrong.
Should we have done better and reach the diagnosis at an
earlier stage? Most authors agree having a high degree of
suspicion or trusting your gut feeling is superior to any
12
O06 Drug induced fatal hepatic toxicity after 1 week
nitrofurantoin
scoring system. Our case illustrates that, when in doubt,
the best way is to stick with your patient until things have
become clear.
N.C.W. Laurenssen1, M. Kramer1, R. Aydinli2, J. Gisolf1,
J. Verhave1
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected], 2Health Centre Velperweg,
ARNHEM, the Netherlands
O05 Constipation and coloured urine: the diagnostic
challenge of acute intermittent porphyria
C.H.M. Leenen, M. Westerman, C.E.H. Siegert, J. Veenstra
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: Nitrofurantoin is commonly used in urinary
tract infections(UTI). Hepatotoxicity associated with nitrofurantoin is rare. We report the case of a 64 year old male,
presenting with fatigue and jaundice beginning 1 week
after treatment with nitrofurantoin for a UTI. Severe
hepatotoxicity secondary to nitrofurantoin was diagnosed.
This made us question the indication of nitrofurantoin for
UTI in elderly men.
Case: A 64 year old man with a history of type 2 diabetes
and gastric ulcer, was treated with nitrofurantoin for a
UTI. After 1 week he suffered from fatigue, nausea and
jaundice. Laboratory tests showed elevated cholestatic liver
enzymes and decreased liver functions . The diagnosis
nitrofurantoin associated cholestatic hepatotoxicity was
made by exclusion of other causes of liver disease. During
admission the patients clinical condition deteriorated
rapidly and he developed multi-organ failure. He died
2 months after hospital admission of severe sepsis.
Discussion: In this case nitrofurantoin was prescribed by
the general practitioner who followed the Guideline for
Urinary Tract Infections of the DutchCollege of General
Practitioners (NHG-guideline). This guideline advises
a 7 day treatment with nitrofurantoin in men with UTI
without systemic symptoms. The NHG state in case of no
signs of tissue invasion, pyelonephritis or prostatitis, there
is no reason to use different antibiotics in men compared
to women. The SWAB suggests that only in young men
below 40, a UTI may be considered as uncomplicated.
UTI in young men is rare and data from trials are lacking.
An epidemiological study from Norway, reported 6 to 8
uncomplicated UTIs per year in 10 000 men in the age
range 21-50 years.There are several arguments to consider
UTI in men as complicated. In men with a UTI there
is often a concurrent prostatitis. Prostate involvement
occurres in more than 90% of men with febrile UTI, even
without clinical signs of acute pyelonephritis. Prostatitis
is not easy to diagnose since patients don’t always have a
fever or pain during rectal examination. Also most UTI’s
occurring in men are associated with urological abnormalities, bladder outlet obstruction or instrumentation. Finally
men with UTIs are more at risk to develop a bacteremia.
Conclusion: In our patient nitrofurantoin had a severe
adverse effect and led to fatal cholestatic hepatotoxicity.
We argue that nitrofurantoin is not the first choice for
Introduction: acute intermittent porphyria (AIP) is one
of a cluster of rare metabolic disorders. It is an autosomal
dominant condition, characterized by a reduced activity
of one of the enzymes in the heme biosynthetic pathway
resulting into an array of symptoms characterized by
autonomous dysfunction.
Case: a 23-year old woman with an unremarkable medical
history was admitted to our hospital with complaints of two
weeks duration of abdominal pain and constipation. Prior
to admission she visited four medical doctors, including
three general practitioners and the emergency department.
However, the initiated treatment consisting of laxatives
and analgesics was ineffective. Upon admission vital signs
and temperature were normal. On abdominal examination
normal bowel sounds were heard and palpation was not
painful. Laboratory tests revealed an acute kidney injury
(creatinine 111 mmol/L, GFR using MDRD 53 ml/min), low
sodium (sodium 131 mmol/L), increased creatinine kinase
(CK 1200 U/L) and a microcytic anemia (hemoglobin
6,5 mmol/L). Abdominal ultrasound was normal. During
admission the striking discovery was done that her
urine was dark-red coloured. Additional urine analysis
showed increased levels of porphyrines, especially a
high delta-aminolevulinic acid level (336,3 umol/L) and
porphobilinogen level (500,0 umol/L), suggestive for AIP.
Furthermore, it appeared she had a positive family history
for AIP. In two affected sisters of her father a mutation
in the HMBS gene was detected. Her father had never
experienced any attacks and had therefore never been
tested. Treatment with glucose (10%) intravenously and
morphine was immediately started after which the patient
fully recovered. This first episode of AIP was probably
initiated by an urinary tract infection for which she
received intravenously ceftriaxone. In literature, five other
cases of rhabdomyolisis and AIP have been reported.
Conclusion: In case of unexplained abdominal pain
with constipation and unexpected biochemical changes
including low sodium levels, rhabdomyolysis and/or
microcytic anemia, AIP should be considered.Family
history is of great importance.
13
chromosome. However, there is a great variety in clinical
presentation. The classic combination of hypoparathyroidism, thymic hypoplasia and facial dysmorphism is
also called diGeorge syndrome. Although 22q11.2 deletion
syndrome is fairly common the diagnosis is often missed
as physicians are unaware of the syndrome or see only one
part of the cardinal features.
Conclusion: The finding of hypocalcaemia in a patient with
a considerable medical history should trigger one to think
of a 22q11.2 deletion syndrome, even at the age of 42.
treating a UTI in elderly men. There is often a concurrent
prostatitis or urological abnormality and nitrofurantoin has
insufficient tissue penetration.
O07 A nice CATCH!
S. Indhirajanti, J. Alsma, P.L.A. van Daele
Erasmus Medical Centre, Department of Internal
Medicine – Vascular diseases, ’s-Gravendijkwal 230,
3015 CE ROTTERDAM, the Netherlands, e-mail:
[email protected]
O08 From endocrine to cardiac storm: ventricular fibrillation in a young patient with thyrotoxicosis and
Brugada syndrome
Case report: A 42-year old Caucasian man presented at
the emergency department with a painful shoulder with
restricted movement. His complaints had started spontaneously and traumatic injury was absent. His medical
history revealed mental retardation and cardiac anomalies;
a ventricular septal defect corrected at the age of two, an
aortic coarctation and an aorta valve stenosis. Despite
previous testing no specific syndrome had been found.
Physical examination not only revealed signs of a fractured
shoulder, but also subtle facial dysmorphisms (hypertelorism and hyperplastic gingivae) and prominent
pulsations on the right side of the neck. Auscultation of
the heart revealed a systolic murmur in accordance to the
aortic valve stenosis.
Laboratory results included a severe serum hypocalcaemia
of 1.41 mmol/L (normal range 2.20 - 2.65 mmol/L).
Ionized calcium was 0.67 mmol/L (1.15 - 1.29 mmol/L).
Serum albumin level was normal. Serum phosphate was
high at 1.91 mmol/L (0.80 - 1.40 mmol/L). There were
a mild thrombocytopenia and anemia. His white blood
cell count was slightly elevated with a normal differentiation. Renal function was normal. Both urinary calcium
and parathyroid hormone (PTH) concentration were low
(0.10 mmol/L (1.0 - 5.0 mmol/L) respectively 1.2 pmol/L
(1.4 – 7.3 pmol/L)). Furthermore 25-OH-D was low. A
shoulder X-ray revealed a fractured humerus.
The diagnosis of hypoparathyroidism was made. The
combination of hypoparathyroidism, facial dysmorphisms
and cardiac anomalies were highly suggestive for 22q11.2
deletion syndrome. Calcium and vitamin D suppletion
were initiated and the patient underwent surgery for the
humerus fracture without any complications. The result
of the chromosomal analysis to confirm the diagnosis is
awaited.
Discussion: The 22q11.2 deletion syndrome affects between
1 in 2000 and 1 in 4000 live births. The microdeletion leads to a defective development of the pharyngeal
pouch system. The acronym CATCH-22 summarizes
the clinical features Cardiac Abnormality, Abnormal
facies, Thymic aplasia, Cleft palate and Hypocalcemia/
Hypoparathyroidism, where “22” represents the affected
L. Both, J.P.H. van Wijk
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
[email protected]
Background: Graves disease is the most common cause of
thyrotoxicosis. Thyroid storm is a rare but life-threatening
complication of Graves disease. We present a case of a
19-year-old male who was hospitalized for ventricular fibrillation due to thyrotoxic storm
Case: A 19-year-old man was admitted to the emergency
room due to an out-of-hospital cardiac arrest. Ventricular
fibrillation was noted on electrocardiographic monitoring
and reverted to sinus rhythm after repeated defibrillation
and basic life support. He had a history of Graves’ hyperthyroidism for 3 years and was treated with radioactive
iodine 4 months before admission. Block-and-replacement
therapy (strumazol 30 mg and levothyroxine 100 mcg)
resulting in euthyroidism was given until 2 weeks
before admission when it was stopped on our advice..
On admission, laboratory examinations revealed elevated
free thyroxine (62 pmol/L, normal 10-24 pmol/L) and
suppressed thyroid-stimulating hormone (< 0,01 mIU/L,
normal 0,3-4,5 mIU/L). Thyroid storm due to recurrent
Graves disease, presenting with ventricular fibrillation was
diagnosed. He was treated with propylthiouracil 200 mg
every 4 hours, propranolol 40 mg every 8 hours, hydrocortisone 100 mg IV every 6 hours, acetaminophen 500 mg
every 6 hours and, after propylthiouracil was given, Lugol
solution 20 drops every 8 hours. Free thyroxine levels
normalized within a few days.
Initial post resuscitation echocardiography revealed
generalized ventricular failure which complete recovered
after reaching euthyroidism. Coronary angiography
revealed no abnormalities. Cardiac MRI suggested left
ventricular hypertrophy, normal RV and no signs of
fibrosis. Post resuscitation electrocardiography showed
an incomplete right bundle branch block and upsloping
14
ST-segment in V2 and V3. Family history was negative
for sudden death or cardiac arrhythmias. With Ajmaline
the right precordial leads changed to a type 2 Brugada
repolarization pattern. Brugada syndrome is a hereditary
arrhythmia characterized by specific electrogardiographic
changes due to mutations in sodium channels of the heart
(SCN5A) and increased risk of sudden cardiac death.
The patient fully recovered. An implantable defibrillator was implanted to treat eventual further cardiac
arrhythmias before discharge. The patient was referred for
genetic linkage analysis. In the future, total thyroidectomy
will be performed.
Conclusion: Thyroid storm is a rare, but treatable, potential
fatal emergency. In rare cases, ventricular fibrillation is the
presenting symptom of a thyroid storm. In our case, the
presence of Brugada syndrome probably predisposed to the
near-fatal ventricular arrhythmia.
O10 Olmesartan causing prominent diarrhea and
malabsorption
J.J.B. Janssen1, P. Nijeboer2, C.J.J. Mulder2
St. Elisabeth Hospital, Department of Internal Medicine,
Hilvarenbeekse weg 60, 5022 GC TILBURG, the Netherlands,
e-mail: [email protected], 2VU University Medical
Centre, AMSTERDAM, the Netherlands
1
O09 Secondary causes for osteoporosis significantly
contribute to fracture risk in patients with osteopenia
and a recent fracture
Introduction: Diarrhea is a frequently reported complaint
and has a broad differential diagnosis. The differential
diagnosis of diarrhea in combination with villous atrophy
is much narrower and mainly includes coeliac disease.
Here we present an olmesartan induced enteropathy.
Case description: A 63-year-old man, with a history of
hypertension and paroxysmal atrial fibrillation presented
with recurring symptoms of severe diarrhea (7,5-10 liters
a day), acute renal failure (creatinine 692 umol/L and
a GFR 7 ml/min/1) and a metabolic acidosis (pH 7.19,
PCO2 1,9kpa, PO2 14kpa, Bic 5,1mmol/L) which required
several hospitalizations. Psychical examination showed no
diagnostic clues, only signs of dehydration. Differential
diagnosis included infectious diseases (viral, bacterial
and parasitic) and inflammatory diseases (M. Crohn,
colitis ulcerosa and coeliac disease). Stool cultures were
repeatedly negative, ultrasound showed no thickened
bowel wall and coloscopy only atypical redness of the
flexura lienanis, with a chronic aspecific inflammation,
without signs of an inflammatory bowel disease after
pathological examination. Gastroscopy showed a radially
antrumgastritis and a mild duodenitis. Pathological
work-up revealed a total villous atrophy (Marsh IIIC),
but no other deviations (no tropheryma whipplei, giardia
lamblia, collagenic enteritis or TBC). Coeliac serology
was repeatedly negative, with a HLA-DQ2 haplotype.
MRI-enteroclyse showed no deviations, especially no signs
of lymphoma. Because of the possibility of seronegative
coeliac disease, a gluten free diet was started. This did
not have any effect on the episodes of severe diarrhea.
Antihypertensive medications were temporarily discontinued at every admission, and restarted at discharge
because of ascending blood pressures. This in combination
F. Malgo, N.A.T. Hamdy, N.M. Appelman-Dijkstra
Leiden University Medical Centre, Department of
Endocrinology & Metabolic Diseases, Albinusdreef 2, 2333 ZA
LEIDEN, the Netherlands, e-mail: [email protected]
15
met recent literature eventually raised the suspicion of
an association between the severe enteropathy and the
anti-hypertensivum olmesartan. And indeed, permanent
withdrawal of olmesartan resulted in a total and persistent
clinical response.
Discussion: Olmesartan is a selective type I angiotensinII-receptor-antagonist and procurable in the Netherlands
since 2008. Recent American and German literature
describes case series of similar patients with olmesartanassociated enteropathy, even after months to years of
usage. Since this side effect is reported more often, other
causes of villous atrophy were excluded and the symptoms
disappeared after discontinuation and reappeared after
restarting olmesartan, we consider this, according to
the Naranjo causality scale, as a probable ‘adverse drug
event’. The pathophysiological mechanism underlying
olmesartan-associated enteropathy is still unknown,
although cell-mediated immunity is suspected to play
a role. Since olmesartan is increasingly prescribed in
the Netherlands, it should be considered as a cause for
diarrhea. Treatment consists of discontinuation of the
olmestartan.
both phases, and after 3 and 6 months. Steatorrhea-related
symptoms were assessed with a scoring system, consisting
of questions regarding stool frequency, consistency,
stickiness, and abdominal cramps and/or flatulence. The
scale ranged from 0-8, with higher scores indicating more
severe symptoms.
Results: Ten patients were included (50% male; median
age 53). With flexible dosing, the CFA went up from
87% to 90%. The mean enzyme dose increased from 3
to 10 capsules per day (p-value < 0.001) and the mean
steatorrhea score improved from 5 to 3 (p-value 0.004).
Both effects remained present after 3 and 6 months. The
BMI did not change during the first 9 weeks of the study
(23.5 and 23.7 respectively), but increased significantly after
3 and 6 months (24.5 and 25.0 respectively), compared
to phase I (p-values 0.008 and < 0.001, respectively).
Fat-soluble vitamin deficiencies, however, had not yet
resolved after 6 months.
Conclusion: In exocrine insufficiency, patient-education
and flexible enzyme dosing improved steatorrhea related
complaints and bodyweight, and should therefore be
routinely applied.
O11 Exocrine insufficiency in chronic pancreatitis;
flexible dosing of pancreatic enzymes improves
treatment outcome
O12 Juvenile haemochromatosis in a 30-year old patient
with heterozygous beta-thalassemia
J.E. Tijmensen, H. van Houten
Haga Hospital, Department of Internal Medicine, Sportlaan
600, 2566 MJ THE HAGUE, the Netherlands, e-mail:
[email protected]
E.C.M. Sikkens1, D.L. Cahen2, J. de Wit2, C.W.N. Looman2,
F. Kubben3, M.J. Bruno2
1
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected], 2Erasmus Medical
Centre, ROTTERDAM, the Netherlands, 3Maasstad Hospital,
ROTTERDAM, the Netherlands
Introduction: In exocrine insufficiency, pancreatic
enzyme supplementation can prevent steatorrhea-related
symptoms and malnutrition. The optimal dose varies,
according to individual patient characteristics and dietary
fat content. However, many patients use a fixed dose
regimen. We prospectively evaluated if patient-education
and flexible dosing improves treatment efficacy in exocrine
insufficiency.
Methods: Between August 2010 and October 2012, chronic
pancreatitis patients were included if they were treated
with a fixed dose of 25,000 to 150,000 units of lipase
per day. During the first 4 weeks of the trial, this fixed
dose was continued (phase I). In week 5, patients were
educated on flexible dosing, which was applied in the last
4 weeks of the trial (phase II). The faecal fat absorption
(CFA) was measured at the end of each phase. The enzyme
dose, steatorrhea-related symptoms, BMI, and presence of
fat-soluble vitamin deficiencies were assessed at the end of
16
Hb-electrophoresis showed no evidence for a hemoglobinopathy. Hereditary spherocytosis (HS) was not ruled
out: BAND 3 expression was just below the cut-off value,
however spectrine percentage was normal. A bone
marrow biopsy showed dyserythropoiesis with multinucleated erytroblasts and chromatin bridges. There was
a homozygote SEC23B mutation.
Conclusion: This patient was admitted for choledocholithiasis due to hemolysis caused by CDA type II based
on homozygote SEC23B mutation. Two sisters of our
patient are probably affected as well. CDA type II is a rare
disorder with autosomale recessive inheritance, leading to
ineffective erytropoiesis. Chromatin bridges are in most
cases described in CDA type I. A SEC23B mutation is
associated with hypoglycosylation of BAND3 in vivo. CDA
is often misdiagnosed as hemolytic anemia, thalassemia
or hereditary spherocytosis. Iron overload is a common
problem in CDA, this explains the high ferritin level in
our patient.
O13 Case Report: A Turkish family with congenital
dyserytropoietic anaemia type II
S. Wiebers, T.M. van Maanen, W.G. Meijer
Westfries Gasthuis, Department of Internal Medicine/Oncology,
Maelsonstraat 3, 1624 NP HOORN, the Netherlands, e-mail:
[email protected]
O14 Iron inflammation, and early death in adults with
sickle cell disease
Introduction: Congenital hemolytic anemias are classified
by causative mechanism. The most common types are
genetic conditions of the red bloodcell (RBC) membrane
(heriditairy spherocytosis, heriditairy elliptocytosis,
heriditairy pyropoikilocytosis, heriditairy stomatocytosis),
enzyme defects of the RBC (glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency) or hemoglobinopathies (sickle cell anemia, thalassemia). We report
on a family with a rare heriditary hemolytic anemia due to
congenital dyserythropoietic anemia (CDA) type II.
Case report: A 37-year old man was admitted for right
upper quadrant abdominal pain, dark urine and discolored
stools. His medical history reported M. Bechterew and a
mild congenital hemolytic anaemia, not further specified.
The patients family is of Turkish background. Two of his
sisters (eight siblings) were also diagnosed with hemolytic
anaemia. On physical examination there was jaundice and
upper abdominal tenderness, vital signs were normal.
Laboratory results showed hemoglobin 8.0 mmol/L, mean
corpuscular volume 87 fl, platelets 148*109/L, leukocytes
6.5*109/L, blood smear showed no abnormalities, C-reactive
protein 2 mg/L, reticulocytes 13 promille, haptoglobin
< 0.10 g/L, alkaline phosphatase 142 U/L, gamma-glutamyltransferase 326 U/L, bilirubine conjugated 253 mmol/L,
billirubin unconjugated 176 mmol/L, aspartate transaminase 185 U/L, alanine transaminase 279 U/L, lactate
dehydrogenase 195 U/L, ferritin 1196 mg/L. Ultrasound
showed choledocholithiasis and splenomegaly. On
endoscopic retrograde cholangiopancreatography bile ducts
were not dilated and no concrements were visualized. A
transient gallstone seemed the most probable cause.
Further tests were performed to investigate the cause of
the hemolytic anemia. Enzymedeficiencies were absent.
E.J. van Beers1, Y. Yang2, N. Raghavachari2, D. Allen2,
J. Nichols2, L. Mendelsohn2, S. Nekhai3, V.R. Gordeuk3,
J.G. Taylor Vi2, G.J. Kato2
1
Academic Medical Centre, Department of Clinical
Hematology, Meibergdreef 9, 1105 AZ AMSTERDAM, the
Netherlands, e-mail: [email protected], 2National
Heart, Lung and Blood Institute, BETHESDA, MD, USA,
3
Howard University, WASHINGTON, DC, USA
Introduction: Patients with sickle cell disease are marked
by a state of chronic inflammation but the cause of this
inflammation and the relevance to patient survival are
unknown.
Aim od the study: To assess the relationship between iron,
inflammation and early death in sickle cell disease.
Materials and methods: Registry study of sickle cell
disease patients that were followed from February 1, 2001,
through January 2011 at the NIH Campus, Bethesda,
with a nested case control genetics substudy, supplemented with a hypothesis generating gene expression
study. (ClinicalTrials.gov identifier NCT00011648 and
NCT00072826)
Results: Using peripheral blood mononuclear cell
transcriptome profile hierarchical clustering we classified
24 patients and 11 controls in clusters with significantly
different expression of genes known to be regulated by
iron. Subsequent gene set enrichment analysis showed
that many genes associated with the high iron cluster
were involved in the toll like receptor system (TLR4, TLR7
and TLR8) and inflammasome complex pathway (NLRP3,
17
NLRC4, and CASP1). Quantitative PCR confirmed the
microarray based classification and showed that PBMC
ferritin light chain, TLR4 and interleukin-6 expression
was more than 100-fold higher in patients than in controls
(p < 0.001) and highly correlated to each other (p < 0.001).
In a cohort of sickle cell disease patients (n = 161), plasma
levels of interleukin-6 were most strongly correlated
with the inflammatory C-reactive protein (rho = 0.496,
p < 0.001). In a Mendelian randomization experiment 14
sickle cell disease patients with a ferroportin variant that
causes intracellular iron accumulation, had significantly
higher levels of interleukin-6 and C-reactive protein
compared to 14 patients with the wildtype allele, implying
a causal effect.(p < 0.05) Finally, in a cohort of 412 patients
with sickle cell disease followed for a median period of
47 months, (IQR 24-82, range 2-132), C-reactive protein
was strongly and independently associated with early death
(hazard ratio 3.0, 95% CI 1.7-5.2, p < 0.001).
Conclusion and relevance: Gene expression markers of
high intracellular iron in patients with SCD are associated
with markers of steady state inflammation and mortality.
The results support a hypothetical model in which intracellular iron promotes clinically significant inflammatory
pathways such as TLR system and the inflammasome,
identifying important new pathways for therapeutic
intervention.
transferrin, serum iron, serum vitamin B12, serum folic
acid, gamma GT, LDH, creatinin and CRP. Furthermore, a
complete hospital chart review (e.g. report on alcohol abuse
and medication) was conducted and any additional examinations (e.g. bone marrow examination) were analysed.
Results: A total of 2738 patients with a newly diagnosed
anaemia were included. Of these patients 190 (6.9%)
displayed macrocytic anaemia (MCV ≥ 100 fl). In 159 of
these 190 patients (83.7%) underlying causes could be
established. Seven of these 159 patients (4.4%) displayed
two causes for their macrocytic anaemia. Classic causes
of macrocytic anaemia (haemolysis, possible bone marrow
disease, vitamin B12 deficiency, folic acid deficiency and
documented alcohol abuse) were found in 85 patients
(44.7%). Alternative causes (anaemia of chronic disease,
iron deficiency, renal anaemia and other) were found in 77
patients (40.5%). [ML1]
Overall survival of the macrocytic population was
57 months (95% CI 52.6-61.4) after entry into the study.
Patients diagnosed with nutrient deficiency displayed a
shorter survival (41.8 months, 95% CI 33.2-50.3, p = 0.024)
and patients with an unknown cause displayed a longer
survival (68.6 months, 95% CI, 60.7-76.5, p = 0.042) than
the residual cohort.
Conclusion: The causes of macrocytic anaemia are diverse
and include both classic and alternative causes. Therefore
we consider a broad diagnostic work-up necessary to
elucidate the underlying cause.
O15 Macrocytic anaemia in patients with newly
diagnosed anaemia: factors influencing diagnosis
and prognosis
O16 Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss
syndrome) and granulomatosis with polyangiitis
(GPA; Wegener’s granulomatosis) patients
M.D. Levin1, K. Stouten1, P. Sonneveld2, J. Riedl1
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert schweitzerplaats 25, 3018 AT DORDRECHT, the
Netherlands, e-mail: [email protected], 2Erasmus Medical
Centre, ROTTERDAM, the Netherlands
1
M.R. Hazebroek, M.J. Kemna, S. Schalla, S. Sanders-van Wijk,
S.C. Gerretsen, R. Dennert, H.P. Brunner-la Rocca,
P. van Paassen, J.W. Cohen Tervaert, S. Heymans
Maastricht University Medical Centre, Department of
Cardiology, P. Debyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected]
Introduction: The frequency of underlying causes of
macrocytic anaemia is unclear in medical literature. In
addition, the prognosis of underlying causes of macrocytic
anemia still have to be established.
Aim of the study: To clarify causes and prognosis of
macrocytic anemia in a prospectively studied cohort of
patients with newly discovered anemia.
Materials and methods: Patients with a newly discovered
anemia from 63 general practitioners were prospectively
studied from the 1st of February 2007 to the 1st of February
2013, with the follow-up period ending on the 1st of July
2013. Patients with macrocytic anemia (i.e. MCV ≥ 100
fl) were included in the study. For each patient a standardised laboratory work-up was performed, which included:
haemoglobin, MCV, erythrocytes, erythrocyte sedimentation rate, reticulocytes, thrombocytes, leukocytes, ferritin,
Introduction: Cardiac involvement in ANCA-associated
vasculitides (AAV), i.e. eosinophilic granulomatosis with
polyangiitis (EGPA; Churg-Strauss syndrome) and granulomatosis with polyangiitis (GPA; Wegener’s granulomatosis) patients is an important predictor of mortality, but
its prevalence remains unclear.
Aim of the study: To investigate the prevalence of cardiac
involvement in a large population of ambulatory EGPA and
GPA patients in sustained remission.
Material and Methods: To address the cardiac involvement
in a phenotypical well characterized and large prospective
cohort study of EGPA and GPA patients, we included
18
50 consecutive EGPA patients (aged 59 ± 11 years) and
41 consecutive GPA patients (aged 60 ± 11 years) in
sustained remission and without previous in-depth cardiac
screening. The latter comprised clinical evaluation,
electrocardiography (ECG), 24-hour Holter registration,
echocardiography and cardiac magnetic resonance
imaging (CMR). Control subjects included fifty age- and
sex-matched subjects, randomly selected from a population
study undergoing ECG and echocardiography. Cardiac
involvement characterized by major ECG abnormalities,
pericardial effusion, (peri)myocarditis, focal or diffuse
myocardial fibrosis and/or edema, wall motion abnormalities, valvular regurgitation ≥ grade 3, pulmonary hypertension (sPAp > 45 mmHg), diastolic dysfunction grade
≥ 2, or significant coronary stenosi(e)s ≥ 70%.
Results: Age, sex and cardiovascular risk factors were
similar between the EGPA, GPA and control group. ECG
and echocardiography demonstrated cardiac involvement
in 54% EGPA and 34% GPA patients as compared to 8%
in controls (both p < 0.002). Adding CMR as diagnostic
modality increased the prevalence of cardiac involvement
to 66% in EGPA and 61% in GPA patients. CMR detected
cardiac involvement in all AAV patients demonstrating ECG
and/or echocardiographic involvement. In patients without
such abnormalities, CMR additionally demonstrated cardiac
involvement in over 30% of EGPA and 41% of GPA. In 52%
EGPA and 44% GPA patients without cardiac symptoms
and with normal ECG, cardiac involvement was present.
With respect to ANCA detection, cardiac involvement was
equally frequent in ANCA negative versus ANCA positive
patients (71% (24/34) ANCA- versus 56% (9/16) ANCA+
EGPA patients, p = 0.53; 0% (0/1) ANCA- versus 63%
(25/40) ANCA+ GPA patients). Endomyocardial biopsy
performed in 11 EGPA and 2 GPA patients demonstrated
chronic or acute myocarditis in all but one patient.
Conclusion: This large prospective and well characterized
cohort reveals an up to 66% cardiac involvement in AAV
patients in remission, even in the absence of cardiac
symptoms or ECG abnormalities. Therefore, the use of
imaging techniques, especially CMR, is recommended for
cardiac evaluation of EGPA and GPA patients.
x
O17 Persisting arthralgias after a stay in Brazil: an
unfamiliar infectious risk for visitors to the 2014
FIFA World Cup
O18 A comparison of the diagnostic value of MRI and
FDG-PET/CT in suspected spondylodiscitis
I.J.E. Kouijzer 1 , C. Smids2 , F.J. Vos3 , T. Sprong 4 ,
A.J.F. Hosman2, W.J.G. Oyen2, C.P. Bleeker-Rovers2
1
Jeroen Bosch Hospital, Department of Internal Medicine,
Henri Dunantstraat 1, 5223 GZ DEN BOSCH, the
Netherlands, e-mail: [email protected], 2Radboud
University Medical Centre, NIJMEGEN, the Netherlands, 3St
Maartens Clinic, NIJMEGEN, the Netherlands, 4CanisiusWilhelmina Hospital, NIJMEGEN, the Netherlands
C.A.D. Slegers,M.Keuter,A.V.vanderVen,Q.deMast
Radboud University Medical Centre, Department of
Internal Medicine, Postbus 9101, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected]
In de gedrukte versie van dit abstractboek is een onjuiste
inhoud vermeld. De juiste versie treft u als aparte bijlage aan.
19
Introduction: Spondylodiscitis is becoming more common
in an increasingly ageing population. Early and accurate
detection is crucial for successful management and improved
neurological outcome. Contrast enhanced MRI is the
modality of choice in current clinical practice, but sensitivity
is suboptimal in the early stage of infection. We hypothesized
that FDG-PET/CT might be more accurate by using pathophysiology instead of depending on anatomical changes.
Aim of the study: The purpose of this study was to evaluate
the value of FDG-PET/CT and contrast enhanced MRI in
diagnosing spondylodiscitis and its complications.
Materials and methods: From January 2006 to August 2013
patients with a clinical suspicion of spondylodiscitis, with
an infection or with fever of unknown origin were retrospectively included if they underwent both FDG-PET/CT
and MRI of the spine within two weeks from each other.
Results were compared to the final clinical diagnosis.
Results: 70 patients were included of whom 50 were finally
diagnosed with spondylodiscitis. MRI showed an overall
sensitivity of 64% and specificity of 85%. Diagnostic
accuracy improved from 56% when MRI was performed
within two weeks after start of symptoms to 80% when MRI
was performed after two weeks. FDG-PET/CT showed a
significantly higher sensitivity of 98% and specificity of 95%
resulting in a significantly higher overall accuracy (97% vs.
70% for MRI), with no differences when performed either
within or after two weeks from start of symptoms. MRI
showed to be the modality of choice in diagnosing epidural
and spinal abscesses with a sensitivity of 94% (vs. 44% for
FDG-PET/CT). FDG-PET/CT showed a higher sensitivity in
diagnosing paravertebral (95%) and psoas abscesses (100%),
as compared to MRI (63% and 62%, respectively).
Conclusion: As compared to MRI, FDG-PET/CT has
superior diagnostic value for early detection of spondylodiscitis within two weeks after first symptoms. After
two weeks, both techniques have a similar yield. MRI
showed highest sensitivity in diagnosing epidural en
spinal abscesses while FDG-PET/CT was more sensitive in
diagnosing paravertebral and psoas abscesses.
(A-team), aiming at improved use of antibiotics, has
been recommended by the Dutch Working Party on
Antibiotic Policy for every hospital in the Netherlands. The
A-team has a multifaceted approach: optimizing adequate
and appropriate antibiotic use, review and feedback on
prescriptions and epidemiologic surveillance of antibiotic
resistance.
Aim of the study: To investigate the impact of the review
and feedback method.
Materials and methods: In our 715-bed university hospital,
two surgical wards (41 respectively 32 beds) with high rate
of antibiotic prescription were selected. Prescriptions of
antibiotics were extracted and gathered from the electronic
prescribing software system. Every prescribed course
of antibiotic was defined as one antibiotic event. These
events were scored for appropriateness and adequacy with
respect to antibiotic use. Appropriateness was defined as
prescription according to local guidelines. An antibiotic
event was adequate if the antibiotic was appropriately
prescribed and was deemed effective based on the identification of the microorganism and susceptibility pattern.
Adequacy also involved minimizing unnecessary use of
broad-spectrum antibiotics. The study was composed by
two consecutive arms of 6 weeks. First, a single-blinded
observation arm in which there was no intervention.
Followed by, an intervention arm in which observed
deviations for appropriate and adequate antibiotic use were
reviewed and in which feedback on improved antibiotic use
was given.
Results: During the observation period 122 antibiotic events
were reviewed: 46% were classified as appropriate and 42%
were adequate. Throughout the intervention period 164
antibiotic events were reviewed: in 80 events feedback was
given. The review and feedback strategy resulted in a 56%
appropriate use of antibiotics, a relative increase of approximately 22% when compared to the observation period.
Moreover, adequacy use was improved to 63%, a relative
increase of approximately 50%. The measured workload for
these two wards was 10 hours per week.
Conclusion: The implementation of a review and feedback
strategy by our A-team resulted in an improvement of
appropriateness and adequacy of the antibiotic treatment
of respectively 22% and 50% in comparison with antibiotic
use during the observation period.
O19 Maastricht’s experience in implementing an
Antimicrobial Stewardship program
J.M.L. de Kort, R.F.J. Benus, A.A. Moens, F.H. van Thiel,
D. Posthouwer
Maastricht University Medical Centre, Department of
Infectieziekten, P. Debyelaan 25,, 6229 HX MAASTRICHT,
the Netherlands, e-mail: [email protected]
O20 Plasmodium falciparum malaria recrudescence
occuring 2.5 years after leaving an endemic country
M.A.H. Berrevoets1, A.S.M. Dofferhoff2
Radboud University Medical Centre, Department of Internal
Medicine, Geert grooteplein zuid 8, 6500 HB NIJMEGEN,
the Netherlands, e-mail: [email protected], 2CanisiusWilhelmina Hospital, NIJMEGEN, the Netherlands
1
Introduction: Inappropriate antimicrobial use is strongly
associated with emergence of antimicrobial resistance,
thereby increasing difficulties in treating infections.
To address this problem Antimicrobial stewardship
20
Case report: A previously healthy 48-year-old man
was admitted to the Canisius-Wilhelmina Hospital in
Nijmegen, the Netherlands with a 5-day history of general
malaise, fever, chills, profuse transpiration and diarrhea.
Originally from Burkina-Faso, he immigrated to the
Netherlands 8 years before presentation. The patient had
not visited his homeland or any other malaria-endemic
country in the previous 2,5 years. No recurrent fever
episodes were noted during this period. The last time he
took malaria prophylaxis was in 1997. There was no history
of blood transfusions. No friends or relatives from Burkina
Faso had visited him for the last two months.
Physical examination revealed a sick, icteric patient. He
was alert and oriented. Body temperature was 36.8°C,
blood pressure 135/85 mmHg, pulse 90 beats/min.
Oxygen saturation was 96% with a respiratory rate of 40/
min. There was no rash or lymphadenopathy. Cardiac
examination revealed normal heart sounds without
murmurs. The lungs were clear to auscultation. There
were no palpable abdominal masses, nor hepato- or splenomegaly. Neurologic examinations were normal.
Laboratory results were as follows: C-reactive protein
149 mg/L, haemoglobin 7,8 mmol/L, thrombocytes 14
x 109/L, leucocytes 9,1 x 109/L, lactate 4,9 mmol/L,
glucosis 5,3 mmol/L, creatinine 184 mcmol/L, bilirubine
218 mcmol/L, lactate dehydrogenase 441 U/I, aspartate
aminotransferase 69 U/L, alanine aminotransferase 56
U/L, alkaline phosphatase 99 U/L. HIV antigen/antibody
test was negative.
Ultrasound of the abdomen showed an enlarged spleen of
17.5cm. The chest x-ray was normal. A blood smear was
performed and showed ring-shaped trophozoites consistent
with Plasmodium falciparum (PF) with a parasite density
of 3.2% and the presence of schizonts. The rapid antigen
detection test was positive.
The diagnosis of PF malaria was confirmed by real-time
PCR. No other pathogens were identified.
The patient was admitted to the intensive care unit because
of tachypnea, acute renal failure and lactic acidosis.
Treatment with intravenous artemisin was started and
he recovered quickly. Parasite density was < 0,1% after
24 hours treatment. By day 3 of treatment, no malarial
parasites were seen and treatment was switched to
oral atovaquon/proguanil. Follow-up was uneventful.
Kidney function recovered completely and splenomegaly
disappeared within 6 months.
Conclusion: This case illustrates the importance of malaria
suspicion as a cause of illness in immigrants from malariaendemic countries. Even when these immigrants did not
travel for a long time, malaria should be considered in
patients with typical symptoms.
O21 Direct and delayed ICU admission in elderly patients
E. Pijpers, M. Bosch, A. Zwietering, P. Stassen
Maastricht University Medical Centre, Department of Internal
Medicine, P. Debeyelaan 25, 6202 AZ MAASTRICHT, the
Netherlands, e-mail: [email protected]
Introduction: The number of elderly people (≥ 65 years)
in the emergency department (ED) population is quickly
increasing. Therefore, the number of critically ill elderly
patients are rising accordingly.
Aim of the study: To compare mortality rates between
elderly patients admitted to the ICU either from the ED
(direct admission) or from the general ward (delayed
admission). To compare the reason of admission to the
hospital, and the vital signs during stay at the ED were
secondary goals.
Materials and methods: We performed a retrospective
cohort study of elderly patients admitted to the ICU of the
MUMC+ for internal medicine in the year 2011.
Delayed admission was defined as admission to the ICU
after admission to a general ward.
Results: Data on 1396 elderly patients admitted for internal
medicine (mean age 77.6 years) were retrieved. Only 21
patients (1.5%) were directly admitted to the ICU and only
54 (3.5%) were admitted from a general ward. The group of
patients with a delayed admission to the ICU less often had
cardiopulmonary problems or abnormal vital signs (low
blood pressure, tachypnea, hypoxia or low GCS scores) in
the ED compared to the group of patients directly admitted
to the ICU.
Mortality rates were higher in patients with a delayed
admission to the ICU than in those who were directly
admitted, however the difference between the two groups
was not significant (19.0% (n = 4) versus 38.9% (n = 21), p
= 0.55) at 28 days and 42.9% (n = 9) versus 66.7% (n = 36,
p = 0.24) at one year.
Conclusion: The number of elderly people presented at
the ED who are admitted to the ICU either directly or via
delayed admission is very low. Admission to the ICU of
the patients in the direct admission group is consistent
with the cardiopulmonary status and abnormal vital signs
in this group.The admission to the ICU of the group of
patients with a delayed admission could not be predicted
from their cardiopulmonary status and vital signs during
stay at the ED. The mortality rates after 28 days and
one year are high in both groups, but seem to be higher
in patients with a delayed admission to the ICU than
in patients directly admitted to the ICU, although the
difference between the two groups is not significant.
21
O23 Does the ‘weekend effect’ exist in elderly internal
medicine patients visiting the Emergency
Department?
O22 Effect of oxygen status on innate immune functions
in human endotoxemia
H.D. Kiers, J. John, E. Janssen, G.J. Scheffer,
J.G. van der Hoeven, P. Pickkers, M. Kox
Radboud University Medical Centre, Department of Intensive
Care, Geert Grooteplein 10, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected]
S.H.A. Brouns, J.J.H. Wachelder, F.S. Jonkers,
S.L.E. Lambooij, H.R. Haak
Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631
BM EINDHOVEN/VELDHOVEN, the Netherlands, e-mail:
[email protected]
Introduction: Preclinical studies have shown that hypoxia
and hyperoxia influence the innate immune response. In
vitro, hypoxia has been shown to exert pro-inflammatory
effects, supposedly mediated by the transcription factor
hypoxia inducible factor 1a (HIF1a), whereas hyperoxia
is related to immune suppression. Therefore, hypoxia
and hyperoxia could be cheap, non-pharmacological,
non-invasive treatment modalities to modulate inflammatory conditions. However, the effects in humans in vivo
have hitherto not been investigated.
The aim of this study: To evaluate the effects of hypoxia
and hyperoxia on the innate immune response during
experimental endotoxemia in healthy volunteers.
Methods: 30 healthy, male volunteers were randomized
to hypoxia, normoxia or hyperoxia (n = 10 per group).
Subjects were exposed to a total of 3,5 hours of hypoxia
(arterial oxygen saturation 80-85%), normoxia or hyperoxia
(fraction of inspired oxygen > 95%). 1 hour into oxygen
status adjustment, a bolus injection of 2 ng/kg purified E.
coli endotoxin was administered to induce systemic inflammation. Saturation, hemodynamics, blood gas analysis,
leukocyte differentiation circulating cytokines and intracellular HIF-1a expression in neutrophils, monocytes and
lymphocytes were determined.
Results: Hypoxia (SaO2 81.9 (± 0.5)%) was induced using
an FiO2 of 11.5 (± 0.8)%. Hyperoxia (FiO2 97.9 (± 0.2)%)
resulted in a mean PaO2 of 54.1 (± 4.1) kPa. Endotoxemia
induced neutrocytosis and resulted in a transient monocytopenia. Hypoxia potentiated the increase in neutrophils
and also increased monocyte number (p < 0.0001),
whereas hyperoxia did not affect leukocyte counts(p =
0.44). Endotoxin administration resulted in increase
in all measured plasma cytokines. Hypoxia attenuated
endotoxin-induced plasma pro-inflammatory cytokines
TNFa, IL-6 and IL-8 (p < 0.0001) and potentiated antiinflammatory IL-10 production (p = 0.001). Hyperoxia
did not alter endotoxemia induced cytokines. HIF-1a
expression was increased in circulating neutrophils 2,5 and
6 hours after endotoxin administration, and after 6 hours
in circulating lymphocytes in all three groups but hypoxia
or hyperoxia did not affect HIF-1a expression.
Conclusion: Hypoxia in healthy humans attenuates endotoxininduced systemic inflammation, whereas hyperoxia does
not affect this response. Endotoxemia increases HIF-1a in
neutrophils and lymphocytes independent of oxygen status.
Introduction: Staffing levels and availability of diagnostic
resources are reduced during weekends, which may
compromise the quality of emergency care. This
phenomenon, labeled as the “weekend effect”, has been
identified as a risk factor of poor health outcome. Weekend
delay could influence the Monday mortality rate, due to
increased severity of illness of patients presenting to the
ED on this day. Elderly patients are underrepresented in
research on the “weekend effect”.
Aim of the study: To compare the in-hospital and 2-day
mortality rate between ED patients aged 65 years and
older admitted on weekends compared with weekdays.
Assessment of the effect of admission on Monday was a
secondary goal.
Material and methods: A retrospective cohort study of
ED encounters of internal medicine patients ≥ 65 years
presenting to Máxima Medical Centre between 1 September
2010 and 31 August 2011 was conducted. Data on
demographic and clinical characteristics at ED presentation,
ED diagnosis and treatment, and patient outcome were
obtained from patient records. The weekend was defined as
the period from midnight on Friday to midnight on Sunday.
Results: Data on 1784 ED visits by elderly internal
medicine patients (mean age 77.5 years) were included.
1300 ED visits (72.9%) resulted in hospitalization, of
which 267 admissions (20.5%) occurred on weekends.
Comorbidity and urgency level were higher in patients
admitted on weekends.
The in-hospital mortality rate was 11.2% for patients
admitted on weekends compared with 10.3% on weekdays
(p = 0.654). Eight patients hospitalized on weekends (3.0%)
died within 2 days of admission compared with 26 patients
(2.5%) on weekdays (p = 0.657). Admission on weekends
was not associated with increased in-hospital or 2-day
mortality rate (OR 1.1, 95% CI 0.7-1.7 and OR 0.9, 95%
CI 0.4-2.1, respectively). In-hospital and 2-day mortality
rate in elderly ED patients were similar among patients
admitted on Monday or the rest of the week (respectively,
OR 1.3 95% CI 0.8-2.2 and OR 1.0 95% CI 0.4-2.4).
Conclusion: The in-hospital and 2-day mortality rates
were comparable among elderly patients hospitalized
on weekends or on weekdays following an ED visit.
Emergency care for the elderly is not compromised by the
changed logistics during the weekend.
22
O24 Organizational factors induce prolonged Emergency
Department length of stay in elderly patients
with organizational factors, such as the number of tests or
specialities involved and low seniority of the ED physician.
Optimization of the organization of emergency care is
vital to better accommodate the needs of the continuously
growing burden of the elderly population on the ED.
S.H.A. Brouns1 , S.L.E. Lambooij1, J. Dieleman 1,
I.T.P. Vanderfeesten2, P.M. Stassen3, H.R. Haak1
1
Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631
BM EINDHOVEN/VELDHOVEN, the Netherlands, e-mail:
[email protected], 2Eindhoven University of Technology,
EINDHOVEN, the Netherlands, 3Maastricht University
Medical Centre, MAASTRICHT, the Netherlands
O25 A shocking finish of the ‘Dam tot Damloop’
J.A.J. Douma, R.J.L.F. Loffeld
Zaans Medical Centre, Department of Internal Medicine,
Koningin Julianaplein 58, 1502 DV ZAANDAM, the
Netherlands, e-mail: [email protected]
Introduction: Prolonged Emergency Department Length of
Stay (ED-LOS) is associated with delay in treatment, poor
medical outcome and patient dissatisfaction. ED-LOS is
regarded as an important quality indicator of emergency
care. The impact of prolonged ED-LOS has been studied in
various conditions and populations. However, information
on ED-LOS in elderly patients is limited.
Aim of the study: To gain insight into ED-LOS in elderly
(≥ 65 years) ED patients and into the organizational factors
that influence ED-LOS.
Materials and methods: A retrospective cohort study
of internal medicine patients, who visited the ED of
Máxima Medical Centre between September 2010 and
September 2011, was performed. All patients ≥ 65 years
and a random sample of patients < 65 years were included.
Data on demographic and clinical characteristics and
ED-LOS were obtained from patient and hospital records.
ED-LOS was defined as the time between ED arrival and
ED discharge or hospital admission. Odds ratios (OR)
with 95% confidence intervals (CI) were calculated using
logistic regression analysis.
Results: Data on 1782 ED visits of elderly patients and
a random sample of 597 ED visits of patients < 65 years
(25.0%) were included. Median ED-LOS was 171 minutes in
patients ≥ 65 years and 147 minutes in patients < 65 years
(p < 0.001). Multivariate analysis showed an association
between prolonged ED-LOS in elderly patients and the
number of specialities involved (OR 3.0 95% CI 2.2-4.1),
the number of diagnostic tests (OR 1.2 95% CI 1.2-1.3),
evaluation by an intern or non-trainee resident (OR 4.4
95% CI 2.1-9.2 and OR 2.4 95% CI 1.4-4.0, respectively)
and admission to the hospital (OR 1.9 95% CI 1.1-3.5).
Weekend or night time arrival and high urgency triage
levels were associated with shorter ED-LOS (OR 0.7 95%
CI 0.5-0.96, OR 0.4 95% CI 0.2-0.7 and OR 0.4 95% CI
0.2-0.6, respectively) in elderly patients. In patients < 65
years, involvement of more specialities was associated with
ED-LOS (OR 2.6 95% CI 1.4-4.8). In both age groups, no
association was found between baseline characteristics,
such as gender, Charlson comorbidity index and presenting
complaint, and ED-LOS.
Conclusion: ED-LOS was considerably longer in elderly
patients than in patients < 65 years and was associated
Case report: A 32-year old female was admitted to our
hospital. After the finish line of the “Dam tot Dam loop”
she collapsed, without signs of epileptic activity. The
patient was admitted and didn’t had any complaints. Blood
pressure was normal, with a pulse rate of 112, her core
temperature was 37.8 oC. Shortly after arrival the patient
became unconscious, with rhythmic movement of the eye
lids and extremities. An epileptic seizure was diagnosed
and intravenous benzodiazepines were given, with only
partial and shortlasting effect. The patient was admitted to
the ICU-department and treated with phenytoin, sedation
and ventilator support. Laboratory investigation showed
mild renal insufficiency with a creatinin of 113 umol/L,
a maximum creatinin kinase of 1695 U/L, a corrected
calcium of 2.06 mmol/L and a severe hypophosphatemia
of 0.30 mmol/L. Arterial blood gas examination revealed
a metabolic acidosis, with a pH of 7.31, pCO2 35 mmHg,
bicarbonate 17.6 mmol/L and a lactate of 2.6 mmol/L.
Intravenous administration of phosphate was initiated. The
next day the patient was doing well and did not show any
signs of epileptic activity. A MRI-scan of the brain showed
no abnormalities. An EEG showed no focal abnormalities
and no signs of epileptic activity. Vitamin D level was
normal. Three months later, calcium and phosphate levels
in blood and urine were normal. The final diagnosis was a
severe exercise-induced hypophosphatemia, with epileptic
seizures.
Discussion: Hypophosphatemia as a result of exercise is
rarely reported in the literature. In one study participants
with collapse after a running competition had a significant
hypophosphatemia compared with runners who did not
collapse. The cause is unknown. Rapid absorption of
inorganic phosphate into the muscles to replenish the
depleted stores of phosphocreatinin after heavy exercise
is one of the possible mechanisms. Also some of the
inorganic phosphate is sequestered in the hexophosphates
and triose-phosphates of the glycolytic pathway. Another
factor could be the high level of circulating catecholamines
during severe exercise, what can cause a phosphate shift
from extracellular tot intracellular. Hypophosphatemia is
23
with AKI than in those without AKI (35 vs. 12%, p =
0.007). The presence of septic shock (OR 18: 95% CI 2-150,
p = 0.007), and not the administration of gentamicin or
AKI at presentation, was an independent predictor for AKI.
Conclusion: Our study did not revealan increased risk
of AKI after a single-dose of gentamicin in internal
medicine patients who were admitted via the ED. The
occurrence of AKI was associated with septic shock and
not with the administration of gentamicin. When AKI
occurs in-hospital mortality is higher. Our study shows
that single-dose gentamicin can – with regard to renal
function – be safely administered in ED patients with
sepsis.
related to different forms of neurologic dysfunction, like
confusion, generalized weakness, neuropathy, seizures
and coma. The mechanism that leads to neurological
dysfunction in hypophosphataemic patients is unclear.
Maybe it is caused by diminished oxygen delivery in
neurologic tissue, as a consequence of lower concentrations of 2,3-DPG and ATP in red blood cells. In conclusion,
heavy exercise can cause severe hypophosphatemia with
serious neurological dysfunction.
O26 The incidence of acute kidney injury (AKI) after
a single-dose of gentamicin in the emergency
department.
J.M.L. de Kort, M. Cobussen, P.J.L. Heuvelmans,
S.H. Lowe, P.M. Stassen
Maastricht University Medical Centre, Department of
Infectieziekten, P. Debyelaan 25, 6229 HX MAASTRICHT,
the Netherlands, e-mail: [email protected]
O27 Hydration prior to CT-pulmonary angiography is not
required for prevention of contrast induced-acute
kidney injury: The Randomized Nefros Trial
J.K. Kooiman1 , Y.W.J. Sijpkens2 , M. van Buren3 ,
J.H.M. Groeneveld 4, S.R.S. Ramai1, A.J. van der Molen1,
N.J.M. Aarts2, C.J. van Rooden3, S.C. Cannegieter 1,
H. Putter1, T.J. Rabelink1, M.V. Huisman1
1
Leiden University Medical Centre, Department of Trombose
en Hemostase, Albinusdreef 2, postzone C7-Q, 2333 ZA
LEIDEN, the Netherlands, e-mail: [email protected],
2
Bronovo Hospital, DEN HAAG, the Netherlands, 3Haga
Hospital, DEN HAAG, the Netherlands, 4Medical Centre
Haaglanden, DEN HAAG, the Netherlands
Introduction: Sepsis is associated with high mortality.
Empirical therapy with beta lactam (B-lactam) antibiotics
and an aminoglycoside can have a survival benefit
compared to broad-spectrum B-lactam only. However,
aminoglycosides may induce nephrotoxicity. Although data
are lacking on the renal safety of a single dose of aminoglycosides in septic patients attending the emergency
department (ED), the use of single-dose aminoglycosides
is widely accepted in the Netherlands.
Aim of the study: To investigate the occurrence of Acute
Kidney Injury (AKI) after a single-dose of gentamicin
(5 mg/kg intravenously) and to evaluate possible risk
factors.
Materials and methods: We retrospectively examinedall
patients attending our internal medicine ED and fulfilling
sepsis criteria from June 2011 until January 2012. Serum
creatinine and eGFR (MDRD) were determined at presentation and evaluated during 2 weeks. AKI was defined
according to the RIFLE criteria.
Results: In total 303 patients were included, 179 in the
combination group and 124 in the B-lactam monotherapy
group, with a mean age of 67 ± 17 and 69 ± 16, respectively. The monotherapy group consisted of patients with
pneumonia. Baseline creatinine was 144 ± 113 vs 121 ±
94 mmol/L in the combination vs. monotherapy group
(p = 0.08). Prior to treatment 21% presented at the ED
with AKI. AKI after treatment occurred in 12 (7%) of the
patients who received gentamycin compared to 5 (4%) in
the monotherapy group (p = 0.32). The severity of AKI was
comparable in both groups “Risk” 2 vs. 2%, “Injury” 3 vs.
2%, “Failure” 2 vs. 1%. The risk of AKI was highest within
48 hours after admission; 12 (4%) vs. 4 (1%) after 48 hours
(p = 0.002). In-hospital mortality was higher in patients
Introduction: Hydration to prevent contrast induced-acute
kidney injury (CI-AKI) results in a diagnostic delay when
performing CT-pulmonary angiography (CTPA) in patients
presenting with clinically suspected acute pulmonary
embolism (PE). The aim of our study was to analyze
whether withholding hydration is non-inferior to one hour
250ml 1.4% sodium bicarbonate (Na-bic) hydration prior to
intravenous contrast administration for CTPA in patients
with a GFR < 60 ml/min.
Methods: Primary outcome of this randomized trial
was the increase in serum creatinine 48-96 hours post
CT. Secondary outcomes were the incidence of CI-AKI
(increase in serum creatinine > 25%/ > 0.5 mg/dl),
recovery of renal function, and the need for dialysis.
Withholding hydration was considered non-inferior if the
mean relative serum creatinine increase was at most 15%
higher compared with Na-bic.
Results: From 2009-2013, 135 patients with clinically
suspected PE undergoing CTPA (mean age 70.4 years
range 69, mean GFR 41.9 range 51) were randomized.
Mean relative serum creatinine increase for no hydration
was -3.3%(SD20.5) and -3.0%(SD17.2) for Na-bic (mean
difference -0.4%, 95% CI-7.0 to 6.3, P non-inferiority
< 0.001). CI-AKI occurred in 9(7.0%) patients; 4(6.5%)
24
of more than 25% in mean weekly ESA dose adjusted for
body weight. The relation between iron administration
patterns and mortality was studied in order to quantify the
effect of differential drop-outs. All models were adjusted
for variables representing clinical clusters responsible
for potential confounding, based on clinical reasoning:
demographic, clinical and treatment parameters (age, sex,
race, ethnicity, cause of end stage renal disease, rGFR,
BMI, comorbidity and year of dialysis initiation), iron dose
(total iron dose during the exposure period), measures
of iron stores (Hb, TSAT and ferritin at the start of the
exposure period and mean weekly ESA dose during the
exposure period) and recent history of pro-infectious and
pro-inflammatory parameters (vascular access, serum
albumin, serum creatinine and infection).
Results: The maintenance group included 4511 patients;
non-maintenance 8458. Maintenance iron administration
was not associated with achieving a Hb between 10-12g/dL
[adjusted Odds Ratio (OR): 1.01 (95% Confidence
Intervals (CI) 0.93-1.09)], less than 10g/dL [OR: 1.03
(95% CI 0.89-1.19)] or greater than 12g/dL [OR: 0.98
(95% CI 0.91-1.07)] compared with non-maintenance Hb.
Maintenance administration was associated with a higher
odds of achieving a 25% reduction in patients’ mean
weekly ESA dose (1.15 (1.02-1.30) and lower mortality [OR
0.70 (95% CI 0.60 to 0.84)].
Conclusion: Maintenance administration of IV iron does
not appear to be associated with achievement of target
hemoglobin goals but may reduce patients’ESA requirements and mortality.
did not receive hydration, 5 (7.5%) were treated with Na-bic
(p = 0.82). Two patients with CI-AKI in the no hydration
arm died of causes other than renal failure and one CI-AKI
patient in the Na-bic arm started pre-planned dialysis
within two months post CTPA. Renal function recovered
in all other CI-AKI patients within two months.
Conclusion: Withholding hydration was non-inferior to
Na-bic hydration prior to CT-PA, with a similar risk of
CI-AKI in both groups. Therefore, our study results
demonstrate that preventive hydration can be safely
withheld in daily practice of chronic kidney disease
patients undergoing acute CTPA for symptomatic PE.
O28 The effect of intravenous iron dosing patterns
on anemia management in chronic hemodialysis
patients
W.M. Michels1 , B.G. Jaar 2 , P.L. Ephraim 2 ,
Y. Liu2, D.C. Miskulin3, N. Tangri 4, S.M. Sozio2, T. Shafi2,
D.C. Crews2, J.J. Scialla5, W.L. St.Peter6, A. Mcdertmott2,
K. Bandeen-Roche2, L.E. Boulware2
1
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: [email protected], 2Johns Hopkins
University School of Medicine, BALTIMORE, USA, 3Tufts
University School of Medicine, BOSTON, USA, 4Seven Oaks
General Hospital, University of Manitoba, WINNIPEG,
Canada, 5University of Miami Miller School of Medicine,
MIAMI, USA, 6University of Minnesota College of Pharmacy,
MINNEAPOLIS, USA
O29 Metastatic breast cancer: What is the real benefit of
chemotherapy in clinical practice?
Introduction: Efforts to decrease the use of costly and
potentially harmful erythropoietin stimulating agents
(ESAs) for treatment of anemia in hemodialysis (HD)
patients have contributed to increased intravenous (IV)
iron use in clinical practice. Administration of IV iron
using a maintenance pattern has shown conflicting results
with respect to anemia management including possible
reduction of ESA use when compared with non-maintenance IV iron administration.
Aim of the study:To explore the association of maintenance
versus non-maintenance IV iron administration with
patients’ achievement of anemia management goals
(hemoglobin (Hb) and ESA use) in a contemporary sample
of adult HD patients.
Materials and methods: We included patients who initiated
chronic hemodialysis in Dialysis Clinic Inc. centers between
2003 and 2009 and who were eligible to receive predefined
IV iron administration patterns. We defined maintenance
as any regularly occurring pattern of IV iron administration and used logistic regression models to calculate the
association between iron administration patterns and the
achievement of an Hb target (10 to 12 g/dL) or a decrease
J.L. Bakker1, K. Wever1, J.H. van Waesberghe2, A. Beeker1,
H. Meijers2, I.R. Konings2, H.M.W. Verheul2
1
Spaarne Hospital, Department of Internal Medicine,
Spaarnepoort 1, 2130 AT HOOFDDORP, the Netherlands,
e-mail: [email protected], 2VU University Medical Centre,
AMSTERDAM, the Netherlands
Background: Efficacy of chemotherapeutic treatment in
patients with metastatic breast cancer (MBC) is frequently
determined in clinical trials. Inclusion criteria are
stringent and these data do not reflect clinical practice
Objective: The purpose of this study is to describe chemotherapeutic treatment and determine benefit of it in an
unselected cohort of patients with MBC.
Methods: In this retrospective analysis, the chemotherapeutic treatment of 91 patients diagnosed with MBC
between January 2005 and January 2009 in two hospitals
in the Netherlands was studied until their death.
25
Results: The median overall survival of patients with
MBC after start of chemotherapy was 24 months (95%
CI 20.3-27.7). Analysis showed that patients received
a multitude of therapy lines; 30% of patients received
five lines or more. First line chemotherapy was mostly
anthracycline-based, followed by taxanes, capecitabine and
vinorelbine. The objective response rates (ORR) decreased
from 20% in the first line to 0% upon the fourth line. The
clinical benefit rate (CBR; at least stable disease at first
evaluation) was 85% in the first line and decreased to 54%
upon the fourth line. Progression at first evaluation of a
chemotherapeutic line affected the choice of treatment
afterwards. Sixty-two percent of patients with progressive
disease at first evaluation in previous line, compared to
23% in the group of patients without progression at first
evaluation in previous line, did not receive a subsequent
new chemotherapeutic agent and finally deceased. If
the clinician did continue with a subsequent line of
chemotherapy, the outcome was not significantly worse
between these two groups of patients. This suggests that
the clinicians were able to select those patients with a
favourable clinical outcome for continuation of chemotherapeutic treatment.
Conclusion: This retrospective study describes the use
of chemotherapy in MBC in clinical practice in the
Netherlands. In contrast to phase III studies, the data give
a complete insight in the chemotherapeutic treatment of an
unselected heterogeneous group of MBC patients.
in a large and unselected cohort of older breast cancer
patients.
Materials and methods: We included patients from the
population-based FOCUS cohort, which comprises all
incident breast cancer patients aged 65 years or older
diagnosed in the geographically defined Comprehensive
Cancer Center Region West in the Netherlands between
January 1997 and December 2004. Predicted 10-year
overall survival and cumulative recurrence rates were
compared with observed 10-year OS and CR using
one-sample T-tests. Discriminatory accuracy was tested
by composing ROC-curves and calculating corresponding
c-indices; calibration was tested using Poisson regression
models.
Results: Overall 2,012 patients were included. Predicted
and observed 10-year overall survival strongly differed
(48·8% versus 39·0%, difference 9·8, 95% Confidence
Interval (CI) 5·9 to 13·7, p < 0·001), as did 10-year
cumulative recurrence (predicted 26·9%, observed 18·2%,
difference 8·7, 95% CI 6·7 to 10·7, p < 0·001). The
discriminatory accuracy of Adjuvant! Online was moderate
for overall survival (C-index 0·75, 95% CI 0·72 to 0·77,
p < 0·001) and poor for cumulative recurrence (C-index
67, 95% CI 0·65-0·71, p < 0·001), as was calibration
(p < 0·001 for both overall survival and cumulative
recurrence).
Conclusion: Adjuvant! Online does not accurately predict
overall survival and recurrence in older breast cancer
patients and should be interpreted with caution. This is in
sharp contrast with current guidelines and recommendations in which use of Adjuvant! Online is recommended
in older patients. Improved prediction tools are needed in
this growing group of older breast cancer patients, thereby
individualizing clinical decision making and optimizing
outcome.
O30 Limited value of the online Adjuvant! program in
older breast cancer patients
N.A. de Glas1 , W. van de Water 1, E.G. Engelhardt 1,
E. Bastiaannet1, A.J.M. de Craen1, J.R. Kroep1, H. Putter1,
A.M. Stiggelbout 1, N.I. Weijl2, C.J.H. van de Velde1,
J.E.A. Portielje3, G.J. Liefers1
1
Leiden University Medical Centre, Department of Surgery,
PO Box 9600, 2300 RC LEIDEN, the Netherlands, e-mail:
[email protected], 2Bronovo Hospital, DEN HAAG, the
Netherlands 3Haga Hospital, DEN HAAG, the Netherlands
O31 Oncogenic osteomalacia associated with a B-cell
non-Hodgkin lymphoma
J.H. Elderman, M. Wabbijn, F.E. de Jongh
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: [email protected]
Introduction: Adjuvant! Online is a prediction tool that
can be used to aid clinical decision making in breast
cancer patients. Both the Dutch Guidelines as well as
the recommendations of the International Society of
Geriatric Oncology advise to use Adjuvant! Online for
adjuvant treatment decisions in older breast cancer patients
specifically. However, Adjuvant! Online was developed
in a relatively young population, and validation studies
included small numbers of older patients.
Aim of the study: Since older breast cancer patients differ
from younger patients in many aspects, the aim of this
study was to investigate the validity of Adjuvant! Online
Introduction: Oncogenic, or tumour-induced osteomalacia
is a rare paraneoplastic disease characterised by hypophosphatemia due to renal phosphate wasting, caused by
excessive fibroblast growth factor 23 (FGF-23) production
by -usually benign mesenchymal- tumours. In addition,
FGF23-producing colon, prostate and thyroid cancers have
been reported. To our knowledge, the present case is the
first report of oncogenic osteomalacia associated with
non-Hodgkin lymphoma (NHL).
26
Case report: A 68-year-old woman was admitted with
a 3-month unexplained pain of her left hip. Apart from
unintentional weight loss (20 kg in five years) she reported
no other symptoms. During admission intermittent fever
was observed for which no infectious cause was found. The
most remarkable laboratory finding was severe hypophosphatemia (0.22 mmol/L) with excessive urinary phosphate
loss (tubular phosphate reabsorption 56% [ref > 95%]).
Serum levels of calcium, albumin, parathyroid hormone,
creatinine and 25-OH-vitamin D were 1.84 mmol/L
[ref 2.20-2.65 mmol/L], 35 g/L [ref 35-50], 10.6 pmol/L
[1.0-7.0], 44 mmol/L [ref 55-95 pmol/L] and 36 nmol/L [ref
50-200 nmol/L] respectively. Additional testing revealed a
markedly increased FGF-23 serum concentration. Imaging
studies (PET- and octeotride-scintigraphy) showed diffuse
activity in the right proximal humerus and the neck of the
left femur without pathological masses on CT-scan. Biopsy
of an intraoral lesion showed diffuse large B-cell NHL. The
patient was treated with R-CHOP immunochemotherapy
resulting in objective tumour response and normalisation
of FGF-23, calcium and phosphate levels; phosphate supplementation was stopped without deterioration of phosphate
homeostasis.
Discussion: We report a case of oncogenic osteomalacia associated with a B-cell NHL. Attempts to show
FGF-23 expression in tumour tissue are underway. Clinical
features of oncogenic osteomalacia include bone pain,
fractures, gait disturbance and muscle weakness. The
(patho)physiology of FGF-23 will be discussed. Adequate
anti-tumour therapy is the treatment of choice for
oncogenic osteomalacia. If this is not possible (e.g. in case
of an undetectable tumour), treatment with active vitamin
D and phosphate supplementation is usually successful.
Conclusion: In case of unexplained hypophosphatemia,
calculation of the fractional renal phosphate excretion
is strongly recommended. We present a case of tumourinduced osteomalacia associated with diffuse large B-cell
NHL.
be carefully considered. Individual patients weigh
these harms and benefits differently and mostly make
a treatment decision in consultation with the treating
physician. The willingness to accept chemotherapy for both
patients and healthcare professionals in the Netherlands
is unknown. The primary aim of this prospective survey
was to assess minimal required benefits to accept chemotherapy and compare these between patients with and
without cancer and healthcare professionals. In addition,
in view of the recent concerns about rising expenditure for
cancer treatments, the opinion of patients and healthcare
professionals about maximally acceptable costs for society
were examined.
Methods: Preferences were examined using a questionnaire consisting of two hypothetical scenarios based on
a classical study 1. Subjects were asked to indicate the
minimal benefit in terms of chance of cure, life prolongation and relief of symptoms they would require to
undergo such chemotherapy. In two other scenarios,
opinions about monthly costs for chemotherapy treatment
were examined.
Results: 139 patients with cancer, 82 patients without
cancer and 155 healthcare professionals completed the
survey. Minimal benefits to make chemotherapy acceptable
did not differ between cancer and non-cancer patients,
with respect to chance of cure (mean 57%), life prolongation (median 24 months) and symptom relief (mean
50%), healthcare providers were likely to accept chemotherapy at lower thresholds (p < 0.01). Education level was
an important explanatory variable and the differences
between patients and healthcare providers disappeared
when correction for education level was applied. Opinions
about the maximum acceptable costs for chemotherapy
displayed a large spread within the groups. The maximum
cost that healthcare professionals considered acceptable
was lower in comparison to both cancer and non-cancer
patients.
Conclusion: The minimal benefit to accept chemotherapy
is not different in cancer and non-cancer patients, but
is beyond what generally can be achieved. Healthcare
professionals were willing to accept chemotherapy for less
benefit. This difference may be attributed to difference in
education level between the groups. Healthcare professionals rated the maximal acceptable societal cost for
chemotherapy lower than patients.
O32 Willingness to undertake chemotherapy and
attitudes towards costs for therapy in the
Netherlands
A.T. Zuur 1 , E.F.M.M. van Dijk 1, M. Coskuntürk 2 ,
J. van der Palen1, E.M. Adang 3, P.F.M. Stalmeier2,
T.N.H. Timmer-Bonte2, A.N.M. Wymenga1
1
Medical Spectrum Twente, Enschede, Merelstraat
14, 7523 ZR ENSCHEDE, the Netherlands, e-mail:
[email protected], 2 Radboud University Medical Centre,
NIJMEGEN, the Netherlands
References
1. Slevin ML, Stubbs L, Plant HJ, Wilson P, Gregory WM,
Armes PJ, et al. Attitudes to chemotherapy: comparing views
of patients with cancer with those of doctors, nurses, and
general public. BMJ. 1990;300:1458-60.
Introduction: When making treatment decisions regarding
chemotherapy, harms and benefits of therapy should
27
Conclusion: This case illustrates that severe symptomatic
hypocalcemia and hypomagnesemia can occur in
association with extensive osteoblastic metastases in
prostate cancer. Calcium and in lesser extent magnesium,
are consumed in large amounts through new metastatic
bone formation, the so-called hungry bone syndrome.
Hypocalcemia-induced dilating cardiomyopathy improved
after calcium supplementation. In conclusion, clinicians
should be aware of osteoblastic metastases as a cause of
severe hypocalcemia.
O33 Severe symptomatic hypocalcemia in a patient with
metastatic prostate cancer: hungry bone syndrome
associated with extensive osteoblastic metastases
P.W. Holm, M. Tascilar
Isala Clinics, Department of Internal Medicine, Dokter van
Heesweg 2, 8025 AB ZWOLLE, the Netherlands, e-mail:
[email protected]
Introduction: Hypocalcemia is a relatively common finding
in patients with active malignancy and is mostly mild and
asymptomatic. In most cases hypocalcemia is the result
of hypoalbuminemia, vitamin D deficiency, bisphononate
use, tumor lysis syndrome or treatment with chemotherapy. Another cause of hypocalcemia may be calcium
utilisation by extensive osteoblastic metastases, mostly
seen in prostate cancer or breast cancer. Severe or lifethreatening hypocalcemia however is uncommon. We
present a case of severe hypocalcemia due to osteoblastic
metastases in prostate cancer.
Case: A 66-year old Caucasian man was referred for
admission to the cardiology department with dyspnea,
muscle weakness and paresthesia. His medical history
included Crohn’s disease for which an ileocecal resection
was performed in 2007 due to complicated fistulae. On
admission, the patient was confused and not able to
walk. Trousseau’s sign was positive. Chest X-ray showed
signs of pulmonary edema. Electrocardiography showed
a prolonged QT interval (504 ms) and inverted T waves
in leads II, III and aVF. Echocardiography was performed
subsequently and showed a severe dilating cardiomyopathy and mitral valve regurgitation with a poor left
ventricular function. Laboratory investigation showed a
total calcium value of 0,91 mmol/L with a normal serum
albumin and a serum magnesium value of 0,20 mmol/L.
Initially gastrointestinal malabsorption was interpreted as
the cause of the electrolyte disturbances and intravenous
supplementation of calcium and magnesium was started.
Raising electrolyte levels proved to be difficult however.
Further laboratory tests showed an alkaline phosphatase
value of 534 U/L, indicating increased bone turnover.
A bone scintigraphy was performed and was evaluated
as a so called ‘superscan’ an intense symmetric activity
in the bones with diminished renal activity, highly
suspicious for diffuse metastatic disease. Prostate cancer
was suspected and the prostate-specific antigen (PSA)
level was 3370 mg/L. Prostate biopsy showed adenocarcinoma, Gleason 4+3 and treatment with leuprorelin and
bicalutamide was initiated. After prolonged intravenous
supplementation of calcium and magnesium, serum
values started to normalize. Subsequent echocardiography
showed significant improvement of the left ventricular
function. Calcium and magnesium values eventually
remained stable under oral supplementation.
O34 Preventing misdiagnosis of Fabry disease: a
consensus recommendation for improved diagnosis
in adults presenting with kidney disease or left
ventricular hypertrophy and mutations of unknown
clinical significance
B.E. Smid1, L. Tol van der1, M. Biegstraaten1, F. Cecchi2,
R.H. Lekanne Dit Deprez1, P.M. Elliott3, S. Florquin1,
D.A. Hughes4, R.A. Lachmann5, J.P. Oliveira6, A. Ortiz7,
P.G. Postema1, E. Svarstad8, W. Terryn9, J. Timmermans10,
C. Tøndel8, L. Vogt 1, S. Waldek 11, C. Wanner 12 ,
A.C. Wal van der 1, F. Weidemann12 , M.L. West 13 ,
M.A. Bergh Weerman van den 1, G.E. Linthorst 1,
C.E. Hollak1
1
Academic Medical Centre, Department of Endocrinology &
Metabolisme, Meibergdreef 9, 1105 AZ AMSTERDAM, the
Netherlands, e-mail: [email protected], 2Careggi Hospital,
FLORANCE, Italy, 3Heart Hospital, LONDON, United
Kingdom, 4Royal Free & University college medical school,
LONDON, United Kingdom, 5National Hospital for Neurology
and Neurosurgery, LONDON, United Kingdom, 6Hospital
São João, PORTO, Portugal, 7IIS-Fundacion Jimenez Diaz,
MADRID, Spain, 8Haukeland University Hospital, BERGEN,
Norway, 9 Gent University Hospital, GENT, Belgium,
10
Radboud University Medical Centre, NIJMEGEN, the
Netherlands, 11LONDON, United Kingdom, 12University
Hospital Wurzburg, WURZBURG, Germany, 13Dalhousie
University, HALIFAX, Canada
Introduction: Genetic screening is increasingly employed,
but will impose major diagnostic dilemmas on clinicians.
Screening for Fabry disease (FD), an inherited lysosomal
storage disorder, in subjects with kidney disease and left
ventricular hypertrophy (LVH) reveals an unexpectedly
high prevalence of FD. Often, a diagnosis of FD is
uncertain because characteristic clinical and biochemical
features lack and mutations of unknown clinical significance in the alpha-galactosidase A (GLA) gene are
identified. The societal impact of a misdiagnosis is large,
as it causes inappropriate counselling and initiation of
exorbitantly expensive and burdensome enzyme therapy.
28
Background: Lack of physical activity leads to detrimental
changes in body composition and metabolism, functional
decline and increased risk of disease in old age. The
potential of Web-assisted interventions for increasing
physical activity and improving metabolism in older
individuals holds great promise, but has thus far not been
studied.
Aim of the study: To assess whether a web-based intervention increases physical activity and improves metabolic
health in inactive older adults.
Methods: We conducted a 3-month randomized, waitlistcontrolled trial in a volunteer sample of 235 inactive adults
aged 60 - 70 years without diabetes. The intervention
group received the Internet program Philips DirectLife,
which was directed at increasing physical activity using
monitoring and feedback by accelerometer and digital
coaching. The primary outcome was relative increase
in physical activity measured objectively using ankleand wrist-worn accelerometers. Secondary outcomes of
metabolic health included anthropometric measures and
parameters of glucose metabolism. Sub-analyses included
the effectiveness of the intervention in those who successfully completed the intervention study, and a dose-response
analysis.
Results: Two-hundred and twenty-six participants (97%)
completed the study. At the ankle, activity counts increased
by 46% (standard error (SE) 7%) in the intervention group,
compared to 12% (SE 3%) in the control group (pdifference
< 0.001). Measured at the wrist, activity counts increased
by 11% (SE 3%) in the intervention group and 5% (SE 2%)
in the control group (pdifference = 0.11). After processing of
the data, this corresponded to a daily increase of 11 minutes
in moderate-to-vigorous activity in the intervention group
versus 0 minutes in the control group (pdifference = 0.001).
Weight decreased significantly more in the intervention
group compared to controls (-1.5 kg vs. -0.8 kg respectively,
p = 0.046), as did waist circumference (-2.3 cm vs. -1.3 cm
respectively, p = 0.036) and fat mass (-0.6% vs. 0.07%
respectively, p = 0.025). Furthermore, insulin and Hba1c
levels were significantly more reduced in the intervention
group compared to controls (both p < 0.05). Of the 34%
of participants who successfully reached their personal
physical activity target, all results were more outspoken
compared to the total intervention group.
Conclusion: This was the first study to show that in
inactive older adults, a 3-month Web-based physical
activity intervention was effective in increasing objectively
measured daily physical activity and improving metabolic
health. Findings demonstrate the large potential of
web-based interventions for improving health in the aging
population by increasing physical activity.
Aim of the study: To develop diagnostic algorithms for
adults presenting with chronic kidney disease or LVH, a
GLA mutation and an uncertain diagnosis of FD.
Methods: A modified Delphi method was used to reach
consensus between FD experts. Criteria for a definite and
uncertain diagnosis and the gold standard for FD were
defined. We performed a systematic review selecting
imaging and laboratory criteria to confirm or exclude FD.
Results: A definite diagnosis of FD was defined as: a
GLA mutation with ≤ 5% GLA enzyme activity (males
only) with≥ 1 characteristic FD symptom (acroparesthesia, cornea verticillata, angiokeratoma following strict
definitions) orincreased plasma (lyso) Gb3 (in classical
male range) or family members with definite FD. Subjects
with a GLA mutation and chronic kidney disease (KDIGO
guideline) or LVH (maximal wall thickness > 12 mm)
failing these criteria have an uncertain diagnosis of FD.
The gold standard was defined as characteristic storage on
electron microscopy (EM) in a heart or kidney biopsy, in
the absence of medication use inducing a similar storage
pattern. Microvoltages on ECG and severe LVH (maximal
wall thickness > 15 mm) before the age of 20 years exclude
FD. Other cardiac or nephrological criteria were rejected.
A PQ interval < 120 ms on ECG, hypertrophied papillary
muscles, myocardial late enhancement in infero-posterolateral regions on cardiac MRI, urinary Maltese Cross
sign and high urinary Gb3 were considered useful in daily
practice as a red flag to suspect FD.
Conclusion: We propose diagnostic guidelines for adults
with chronic kidney disease or LVH and an uncertain
diagnosis of FD. When LVH is present, microvoltages and
severe LVH at young age can exclude FD. In all remaining
instances, a biopsy of the heart or kidney with EM analysis
should be performed to confirm or reject FD.
O35 Effects of a web-based intervention on physical
activity and metabolism in older adults: randomized
controlled trial
C.A. Wijsman1, R.G.J. Westendorp2, E.A.L.M. Verhagen3,
M. Catt 4, P.E. Slagboom2, A.J.M. de Craen2, D. Vroege2,
K. Broekhuizen5, W. van Mechelen3, D. van Heemst 2,
F. van der Ouderaa6, S.P. Mooijaart2
1
Bronovo Hospital, Department of Internal Medicine,
Bronovolaan 5, 2598 AX DEN HAAG, the Netherlands,
e-mail: [email protected], 2Leiden University
Medical Centre, LEIDEN, the Netherlands, 3EMGO Institute,
VU Medical Centre, AMSTERDAM, the Netherlands,
4
Institute for Ageing and Health, Newcastle University,
NEWCASTLE UPON TYNE, United Kingdom 5Institute for
Evidence Based Medicine in Old Age (IEMO), LEIDEN, the
Netherlands, 6Netherlands Consortium for Healthy Ageing
(NCHA), LEIDEN, the Netherlands
29
O36 Age-adjusted d-dimer cut-off levels to rule out
pulmonary embolism: a prospective outcome study:
the ADJUST study
value between the conventional cut-off of 500 mg/L and
their age-adjusted cut-off did not undergo CTPA and were
left untreated and formally followed for a three-month
period.
Results: 3,346 patients with suspected PE were included.
The prevalence of PE was 19%. Among the 2,898 patients
with a non-high or an unlikely clinical probability, 817
(28.2%) had a D-Dimer < 500 mg/L, and 337 additional
patients (11.6%) had a D-Dimer comprised between
500 mg/L and their age-adjusted cut-off. The three-month
failure rate in patients with a D-Dimer > 500 mg/L but
below the age-adjusted cut-off was 1/331: 0.3%, (95% CI 0.1
to 1.7%). Among the 766 patients aged 75 years or older,
of whom 673 had a non-high clinical probability, using
the age-adjusted cut-off instead of the 500 mg/L cut-off
increased the proportion of patients in whom PE could be
excluded on the basis of D-Dimer from 43/673 (6.4%) to
200/673 (29.7%), without any additional false-negative test.
Conclusions: Combined with pretest clinical probability
assessment, the age-adjusted D-Dimer cut-off increased
the number of patients in whom PE can be safely excluded
without additional imaging. This was particulary true in
elderly patients in whom the adjusted cut-off increased
the diagnostic yield of D-Dimer five-fold without compromising safety.
P.L. den Exter1, J. van Es2, M. Righini3, P.M. Roy4,
F. Verschuren5, A. Ghuysen6, O. Rutschmann3, O. Sanchez7,
M. Jaffrelot8, A. Trinh-Duc9, C. Le Gall10, J. Schmidt11,
A. Principe12, A.A. van Houten13, M. ten Wolde14, R.A. Douma2,
G. Hazelaar15, P.M.G. Erkens16, K.W. van Kralingen17,
M.J. Grootenboers18, M. Durian19, Y.W. Cheung14, G. Meyer7,
H. Bounemeaux3, M.V. Huisman1, P.W. Kamphuisen20,
G. Le Gal21
1
Leiden University Medical Centre, Department of Thrombosis
and Haemostasis, Albinusdreef 2, 2300 RC LEIDEN, the
Netherlands, e-mail: [email protected], 2 Academic
Medical Centre, AMSTERDAM, the Netherlands, 3Geneva
University Hospital, GENEVE, Switzerland, 4University
Hospital of Angers, ANGERS, France, 5Cliniques
Universitaires St-Luc, BRUSSEL, Belgium, 6Liege University
Hospital, LUIK, Belgium, 7Hôpital Européen Georges
Pompidou, PARIJS, France, 8Brest University Hospital,
BREST, France, 9 Centre Hospitalier d’Agen, AGEN,
France,10Centre Hospitalier d’Argenteuil, ARGENTEUIL,
France, 11Centre Hospitalier Universitaire de ClermontFerrand, CLERMONT-FERRAND, France, 12 Centre
Hospitalier de Morlaix, MORLAIX, France, 13Maasstad
Hospital, ROTTERDAM, the Netherlands, 14Flevo Hospital,
ALMERE, the Netherlands, 15Rijnstate Hospital, ARNHEM,
the Netherlands, 16Maastricht University Medical Centre,
MAASTRICHT, the Netherlands, 17Van Weel Bethesda
Hospital, DIRKSLAND, the Netherlands, 18Amphia Hospital,
BREDA, the Netherlands, 19Erasmus Medical Centre,
ROTTERDAM, the Netherlands, 20University Medical Centre
Groningen, GRONINGEN, the Netherlands, 21Ottawa Health
Research Institute, OTTAWA, Canada
O37 Outcome of patients with idiopathic retroperitoneal
fibrosis treated with tamoxifen or corticosteroid
monotherapy
F.E. van der Bilt, W.A.G. van der Meijden, T.R. Hendriks,
E.F.H. van Bommel
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert schweitzer plaats 24, 3300 AK DORDRECHT, the
Netherlands, e-mail: [email protected]
Introduction: D-Dimer measurement is an important step
in the diagnostic strategy of clinically suspected acute
pulmonary embolism (PE) but its clinical usefulness is
limited in elderly patients.
Aim of the study: To prospectively validate whether an
age-adjusted D-Dimer cut-off, defined as age x 10 in
patients aged 50 years or more, can safely increase the
diagnostic yield of D-Dimer in elderly patients with
suspected PE.
Materials and methods: We performed a multicentre
multinational prospective management outcome study
in 19 centers in the Netherlands, Belgium, France, and
Switzerland between January 1, 2010 and February 28,
2013. All consecutive outpatients with clinically suspected
PE were assessed by a sequential diagnostic strategy based
on the assessment of clinical probability, higly sensitive
D-Dimer measurement and computed tomography
pulmonary angiography (CTPA). Patients with a D-Dimer
Objective: Idiopathic retroperitoneal fibrosis (iRPF) is a
rare chronic inflammatory disorder of unknown etiology.
Although corticosteroids are used most often as primary
therapy, tamoxifen might be a suitable alternative, particularly in the presence of contra-indications for long-term
use of corticosteroids. No comparative data of these two
drugs as monotherapy are available. We compared outcome
of iRPF patients treated with corticosteroid or tamoxifen
monotherapy for first presentation.
Methods: Of all patients with iRPF disease who were
referred to our tertiary care referral centre from February
1999 through December 2011, 118 patients were eligible
for this retrospective study. Treatment success was defined
as the composite of: (1) amelioration of symptoms; (2)
CT-documented mass regression; and, if applicable
(3) definitive removal of ureteral stent or nephrostomy
tube. Recurrence was defined as recurrence of signs and
30
symptoms and/or CT-documented mass increase after
initial treatment success with primary treatment.
Results: Presenting signs and symptoms did not differ
between patients treated with corticosteroids (CS) (n = 50)
or tamoxifen (TAM) (n = 68). In patients treated with
corticosteroids, median (IQR) ESR (CS, 64 40-95 mm/h
vs. TAM, 42 15-79 mm/h; p < 0.01) and CRP levels (CS, 44
16-99
mg/L vs. TAM, 10 5-34 mg/L; p < 0.001) were higher at
presentation. Serum creatinine level did not differ between
groups (CS, 128 90-205 mmol/L) vs. TAM, 111 92-141 mmol/L; p
= 0.19). Time to resolution of symptoms after treatment
initiation was shorter in corticosteroid-treated patients (CS,
2.0 [0.8-3.8] wk vs TAM 4.0 [2.0-6.0] wk; p < 0.01). Mass
regression at first follow-up CT scan tended to be observed
more frequently in patients treated with corticosteroids
compared to patients treated with tamoxifen (CS, 84.0%
vs. TAM, 68.3%; p = 0.054). Median time-interval from
treatment initiation to first follow-up CT scan did not differ
between groups (CS, 5 2-7 mo vs. TAM, 4 4-5 mo; p = 0.34).
Treatment success did not differ significantly between
patient groups (CS, 72.7% vs. TAM, 58.3%; p = 0.15).
In patients with initial treatment success with primary
treatment, recurrence rate was lower in patients treated
with tamoxifen (CS, 62.5% vs. TAM, 21.4%; p < 0.01)
Conclusion: More rapid resolution of symptoms and
more frequent mass regression at first follow-up CT scan
was observed in patients treated with corticosteroids.
Percentage of treatment success was non-significantly
higher in corticosteroid-treated patients. Conversely, in
patients who had initial treatment success with primary
treatment, recurrence rate was lower in tamoxifen-treated
patients.
and mixed hyperlipidemia. To date, ~140 CESD patients
have been reported while the prevalence of the disease has
been estimated to be ~1:40,000, which would translate
in ~400 patients in the Netherlands. The discrepancy in
reported and estimated number of patients is likely to
be caused by phenotypical variation of the disease and
unawareness among medical professionals. We here
report two family cases with an unusual presentation of
CESD. Case 1. A 23 year old female was diagnosed with
a clinical phenotype of primary hypercholesterolemia
(TC 13.1; LDL-C 10.6; HDL-C 1.75; TG 1.69mmol/L).
Family screening revealed 2 affected siblings, while
parental lipid levels were normal (brother LDL-C 7.7;
monozygotic twin LDL-C 10.0; father LDL-C 3.2; mother
LDL-C 4.2 mmol/L). No mutation was identified in one of
the well annotated genes for either autosomal dominant
or recessive hypercholesterolemi (LDLR, APOB, PCSK9
or LDLRAP). Homozygosity for the E8SJ mutation in
LIPA was identified upon exome sequencing (Stitziel et
al. ATVB 2013), leading to the diagnosis of CESD which
was biochemically confirmed by a residual LAL activity
of 8% in the proband. ALT levels were mildly increased
upto 56 U/L. Magnetic Resonance Spectroscopy showed
hepatic cholesteryl-ester accumulation without hepatosplenomegaly. Case 2. A 34 year old male with a medical
history of hypercholesterolemia (TC 9.0mmol/L, TC/
HDL ratio 16.3) from childhood onwards, was referred
because of upper abdominal pain, diarrhea and anal blood
loss. Signs of portal hypertension were identified during
endoscopy. The combination of bone marrow cytology
(‘sea blue histiocytes’ and vacuolated macrophages), liver
histology (microvesicular steatosis, bridging fibrosis and
lipid laden macrophages), increased LDL-C, and decreased
HDL-C levels led to the diagnosis of CESD. Mutation
analysis revealed compound heterozygosity for mutations
in exon 8 (E8SJM) and exon 10 (T1107G) in LIPA. Family
screening also led to this diagnosis in two of probands’
siblings. Conclusion. In patients with hypercholesterolemia
of unknown origin, LIPA mutations should be considered.
Since the phenotypic characteristics of CESD seem to
be largely underreported and the natural course of this
disease is (partly) unknown, systematic patient follow-up
including both lipids and liver parameters (i.e. transaminases and MRS) is recommended.
O38 Cholesteryl-Ester Storage Disease: Two family cases
of an underreported and underdiagnosed disease
B. Sjouke1 , M.A. Alleman2, J.W.J. van der Stappen2,
J.E.M. Groener3, A. Pepping2, R. Wevers4, A. Gouw2,
B.D. Dikkeschei2, G.S. Mijnhout2, G.K. Hovingh1
1
Academic Medical Centre, Department of Vascular Medicine,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: [email protected], 2Isala Clinics, ZWOLLE, the
Netherlands, 3Leiden University Medical Centre, LEIDEN,
the Netherlands, 4Radboud University Medical Centre,
NIJMEGEN, the Netherlands
O39 Delayed progression of carotid intima media
thickness in patients with rheumatoid arthritis:
1-year results of the FRANCIS study
Introduction: Cholesteryl-Ester Storage Disease (CESD)
is a rare recessive disease caused by mutations in the
LIPA gene, encoding lysosomal acid lipase (LAL). LAL
deficiency typically results in intra-cellular accumulation
of cholesteryl-esters and triglycerides in hepatic, adrenal
and intestinal cells. By virtue of this pathological substrate,
CESD is characterized by hepatomegaly, splenomegaly
D.F. van Breukelen-van der Stoep1, D. van Zeben1,
B. Klop1, M.A. de Vries1, N. van der Meulen1, J. van der Arend1,
G.J.M. van de Geijn1, H.W. Janssen1, C. van Casteren-Messidoro1,
E. Birnie1, J.M.W. Hazes2, M. Castro Cabezas1
31
1
St Franciscus Gasthuis, Department of Rheumatology,,
Kleiweg 500, 3045 PM ROTTERDAM, the Netherlands,
e-mail: [email protected], 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands
O40 Liraglutide reverses insulin-associated weight gain,
improves glycemic control and decreases insulin
dose in patients with type 2 diabetes. Results from a
26-week, randomized, controlled trial (ELEGANT)
Introduction: Rheumatoid arthritis (RA) is recognized as
an independent cardiovascular risk factor. Guidelines for
cardiovascular risk (CVR) management, advise aggressive
treatment in RA. Tight treatment for CVR factors in RA is
not standard care and there are no prospective data.
Aim of the study: To investigate the efficacy of CVR intervention in RA patients participating in the FRANCIS
study. FRANCIS is a prospective, randomized, single
centre study in RA, initiated before the guidelines
advocating CVR treatment in RA patients became
available.
Material and Methods: RA patients ≤ 70 years old with
a CVR score < 20% and without the presence of clinical
cardiovascular disease or diabetes mellitus were included.
Patients were randomized to a treat-to-target (TTT) or
standard care. TTT consisted of dietary and lifestyle
advice and a targeted intervention for blood pressure,
lipids and glucose. Patients in the standard care group
were referred to their general practitioner with a letter
containing treatment advice. Patients underwent a
standard physical examination, measurement of carotid
intima media thickness (cIMT) and determination of the
rheumatoid arthritis activity score (DAS28). Standard
laboratory measurements including a complete lipid profile
were measured. Both groups visited the outpatient clinic
every six months.
Results: In total 318 patients were included of whom 219
patients (69%) had a completed baseline and 1-year follow
up data set. 106 patients received standard care and 113
treat-to-target. At baseline there was no difference between
usual care and tight control in systolic BP, LDL-C HDL-C
apoB, triglycerides, glucose cIMT and DAS28. After 1-year
of follow up, the LDL-C, apoB levels and systolic BP were
lower in both groups. The decrease in LDL-C after one
year was significantly greater in the treat-to-target group
compared to standard care (-0.7 ± 0.8mmol/L vs. -0.2 ±
1.0mmol/L; p < 0.001). The change in systolic BP was
not significantly different (-4.7 ± 15,2 mmHg vs. -4.1 ±
18.3mmHg; p = 0.79). cIMT increased significantly in the
standard care group (+0.019 ± 0.013mm; p = 0.01), but not
in the treat-to-target group (+0.010 ± 0.059mm; p = 0.09).
Conclusion: This is the first prospective study in RA
showing that a structured cardiovascular intervention
program leads to lower LDL-C levels, and delayed
progression of cIMT after 12 months.
H.M. de Wit 1 , G.M.M. Vervoort 1, H.J.J. Jansen 2 ,
W.J.C. de Grauw1, B.E. de Galan1, C.J. Tack1
1
Radboud University Medical Centre, Department
of General Internal Medicine, section Diabetes, PO
Box 9101, 6500 HB NIJMEGEN, the Netherlands,
e-mail: [email protected], 2Jeroen Bosch Hospital,
’S-HERTOGENBOSCH, the Netherlands
Introduction: Weight gain, which is often encountered
within the first 9-12 months after introducing insulin
therapy in patients with type 2 diabetes, is obviously
undesirable and may offset the beneficial effects of insulin.
Whether addition of a GLP-1 analogue is efficacious in this
situation is currently unknown.
Aim of the study: To determine whether the addition of
liraglutide to insulin therapy can reverse insulin-associated
weight gain while maintaining glycemic control in patients
with type 2 diabetes.
Materials and methods: The ELEGANT trial was conducted
in the outpatient departments of 1 academic and 1 large
nonacademic teaching hospital in the Netherlands, from
February to October 2013. Adult patients with type 2
diabetes on short-term (≤ 16 months) insulin therapy with
> 4% associated weight gain were randomized between
open-label addition of liraglutide 1,8 mg/day (n = 26) and
continuation of standard therapy (n = 24) during 26 weeks.
They were evaluated every 4-6 weeks for weight, glycemic
control and adverse events. Primary outcome was betweengroup weight difference after 26 weeks (intention to treat
analysis).
Results: Of 64 eligible patients, 50 (mean age 58 years,
BMI 33 kg/m2, HbA1c 7.4%) were randomized: 25 patients
(96%) in the liraglutide group and 22 patients (92%) in the
standard therapy group completed the study. Body weight
decreased 4,5 kg with liraglutide and increased 0,9 kg with
standard therapy (mean difference -5.2 kg [95% CI, -6.7 to
-3.6 kg]; p < 0.001). The respective change in HbA1c was
-0.77% and +0.01% (difference -0.74% ([95% CI, -1.08 to
-0.41%]; p < 0.001); respective changes in insulin dose
were -29 U/day and +5 U/day (difference -33 U/day, [95%
CI, -41 to -25 U/day]; p < 0.001). In 5 patients (19%), insulin
could be completely discontinued. Liraglutide was well
tolerated, only 1 patient withdrew because of side effects.
No severe adverse events or severe hypoglycemia occurred.
Conclusion: In patients with pronounced insulinassociated weight gain, the addition of liraglutide to
insulin therapy reverses weight, decreases insulin dose
and improves glycemic control, compared to continuation
of standard insulin therapy. These findings suggest that
32
Conclusion: Scientific knowledge about the importance
of case-mix factors for diabetes indicators has become
available for HbA1c values, but is still very limited for
the other indicators. As arbitrarily adjustment may be
accompanied by inaccurate quality information, case-mix
tools, especially for outcomes, need to become more
evidence-based.
adding liraglutide in patients with pronounced insulinassociated weight gain is a reasonable therapeutic option.
II
ENDOCRINOLOGY RESEARCH
C001 Case-mix adjustment for diabetes indicators.
A systematic review of risk factors and their
importance
III
J.G.M. Markhorst1 , D.R. Calsbeek 2, D.R. Voerman 2,
D.R. Braspenning2
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected] 2Radboud University Medical Centre,
NIJMEGEN, the Netherlands
ENDOCRINOLOGY CASE REPORTS
C002 Latrogenic Cushing’s syndrome and secondary
adrenal insufficiency in a Hiv patient receiving
fluticasone and ritonavir
I.N. Vlasveld, M.O. van Aken, C. van Nieuwkoop
Haga Hospital, Department of Internal Medicine, Leyweg
275, 2545 CH DEN HAAG, the Netherlands, e-mail:
[email protected]
Introduction: Case-mix adjustment models are considered
to be necessary for fair quality-of-care comparisons.
However, little is known about what case-mix variables
should be included in these models. In order to assess
the status of diabetes case-mix adjustment and to advance
appropriate and valid case-mix adjustment, researchers and
quality assessors may benefit from an overview of case-mix
variables that are ideally included for specific indicators.
Aim of the study: We therefore aimed to review the
literature on the selection and empirical base of case-mix
variables for the six most commonly used diabetes quality
indicators, that is HbA1c, LDL cholesterol and blood
pressure (measurements and outcomes). The results can
contribute to more evidence-based use of risk-adjustment
that can give us a more accurate assessment of the quality
of diabetes care.
Materials and methods: We performed a systematic review
of observational studies (published up to June 2013) to
identify case-mix variables for six diabetes indicators.
Variables were categorized into fundamental domains
(demographic, diabetes-related, comorbidity, generic
health, geographic, and care seeking factors) and evaluated
on their selection motives and impact on indicator scores
and ranking.
Results: Thirteen studies were included. They focused
particular on HbA1c values. There was a large variation
among the applied case-mix variables, concerning mostly
demographics and diabetes-related factors. Introduction of
these variables was hardly evidence-based. Twelve studies
examined the need for case-mix adjustment for outcomes,
revealing most robust evidence for the effect of marital
status and BMI on HbA1c value. For LDL value and blood
pressure the available evidence was conflicting or scarcely
studied. Eight studies examined the impact of case-mix
adjustment for process indicators, showing minimal
evidence for case-mix adjustment.
Introduction: Ritonavir, a protease inhibitor (PI), is
commonly used in the treatment of HIV positive patients
and is an extremely potent inhibitor of CYP3A4 activity.
Because of these pharmacological characteristics the
metabolism of other commonly used drugs may be
affected. Fluticasone is a substrate of hepatic CYP3A4 and
the interaction with ritonavir can lead to systemic steroid
accumulation. We present a case of iatrogenic Cushing’s
syndrome and secondary adrenal suppression due to this
drug interaction.
Case presentation: A 55 year old HIV positive patient
receiving a ritonavir based antiretroviral therapy (cART)
complained of progressive fatigue, generale bone pains
and an ongoing predominant rise in his waist circumference On physical examination he had pronounced
central adiposity and obvious atrophic muscles of the
lower extremities. Serum morning levels of cortisol and
adenocorticotrophic hormone (ACTH) were extremy low
and a 24-hours urinary examination showed a reprising
low cortisol excretion. A short synthetic ACTH test showed
a blunted response. A bone density scan showed skeletal
oesteopenia. On inquiry the patient told that he was using
intranasal and inhaled fluticasone for over ten years that
was prescribed by his general practitioner. We stopped the
fluticasone ans started steroid replacement therapy.
Discussion: The strong interaction between fluticasone
and ritonavir resulted in an iatrogenic Cushing’s syndrome
with osteopenia and secondary adrenal suppression in
our HIV positive patient. The frequent clinical phenotype
of lipodystrophy due to antiretrovirals may maske the
diagnosis of Cushing’s syndrome. A thorough medication
history gave the clue to the diagnosis. The pharmacokinetics of fluticasone increases the likelihood of systemic
33
to be intubated and mechanical ventilation was started.
Electromyography was normal and anti-Yo, ANA, ANCA,
ENA and anti-TPO antibodies were negative. Muscle
biopsy showed both necrotic myopathy and fibre atrophy.
On day 7 CK had dropped to 719 IU/L, but started to raise
again to a maximum of 4896 IU/L. The same time FT4
dropped to 6 pmol/L and TSH increased to 80,51 m U/L.
Under the suspicion of malabsorption L-thyroxine orally
was converted to 150 mg intravenously. A gastro-duodenal
endoscopy revealed villous atrophy of the duodenum,
biopsy was inconclusive. Anti endomysial antibodies
were negative but tTg-IgA was 103 U/ml. Under the
suspicion of celiac disease the patient was treated with a
gluten-free diet. The Patient slowly recovered, CK levels,
renal function, TSH and FT4 normalised. He could be
weaned from ventilation and was discharged from the ICU
after 45 days.
Discussion: In this case rhabdomyolysis was caused
by a combination of statins and (sub)clinical hypothyroidism. Malabsorption of L-thyroxine due to unknown
celiac disease was probably the reason of his overt
hypothyroidism.
steroid accumulation in HIV patients using a ritonavir
based cART. Compared to other inhaled corticosteroids
(ICS), like budesonide and beclomethasone, fluticasone
is the most lipophlic ICS with the longest glucocorticoidreceptor binding haflife. To manage the results of the
systemic steroid accumulation ritonavir can be replaced
with another antiretroviral or the fluticasone can be
substituted by another inhaled or intranasal steroid. Every
patient with iatrogenic Cushing’s syndrome should be
assesed for the need of oral steroids replacement therapy
after withdrawal of fluticasone.
Conclusion:This case highlights the strong drug
interaction between fluticasone and ritonavir leading
to iatrogenic Cushing’s syndrome with osteopenia and
secondary adrenal suppresion.
C003 Simvastatin induced rhabdomyolysis and a clinical
link with (sub)clinical hypothyroidism due to malabsorption with primary unknown celiac disease
S. van Roosmalen, C.A.E. Watervoort, J.A.H. van Oers
St. Elisabeth Hospital, Department of Intensive Care,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: [email protected]
C004 Pericardial effusion associated with severe
autoimmune hypothyroidism
Introduction: Although rare, rhabdomyolysis as a result
of statin therapy is a well known complication. Overt or
subclinical hypothyroidism is known to be a risk factor. We
describe the case of a patient with massive rhabdomyolysis
requiring mechanical ventilation and CVHH at the ICU.
Case: A 67-year old man was admitted to the hospital with
swallowing problems, weight loss and increasing fatigability. There was severe myalgia and weakness of arms
and legs. Patient denied vigorous exercise and alcohol
use. Family history revealed no neuromuscular disease.
His medical history revealed hypothyroidism of unknown
cause and dyslipidemia. His medication consisted of
daily 125 mg L-thyroxine and 40 mg simvastatin. Physical
examination revealed a cachectic patient, BP 160/70, HR
81/min, temperature 36,8 oC. Neurological examination
revealed symmetrical weakness of facial muscles and
atrophic muscles of arms and legs and reduced deep
tendon reflexes. Laboratory measurements revealed: CK
66796 IU/L, (n < 171), urea 13.4 mmol/L (N 2.9-7.5),
creatinine 187 mmol/L (N 60-110), K 5.9 mmol/L (N
3.5-5.0), TSH 15,18 m U/L (N 0.3-3.3), FT4 13 pmol/L
(N10-24). The patient was transferred to the ICU for
250 ml/h Ringers Lactate intravenous fluid replacement,
statins were stopped and L-thyroxine was continued
orally. CK dropped, but because of the development
of ATN with anuria CVVH therapy had to be started
on de second day. Due to insufficient coughing and
progressive proximal muscle weakness the patient had
S.S.G. Guillen, R.A. Carels, A.A.M. Zandbergen
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: [email protected]
Case report: A 49-year old Hindu woman was admitted
because of nausea, vomiting, alternating defecation, loss
of appetite and unintentional weight loss for one month.
Her medical history reported autoimmune hypothyroidism
since 2006. She repeatedly admitted to be non-compliant
in taking her medication.
Physical examination revealed a blood pressure of
90/65mmHg, a heart rate of 56 beats per minute, a
temperature of 35,5 degrees Celsius and no signs of
myxedema.
ECG showed low voltages. Laboratory results showed severe
hypothyroidism, TSH > 74mIU/L (normal range 0.4-4.0),
f T4 < 4.0 pmol/L (normal range 12-22).
A thoracic and abdominal CT scan was performed to
exclude malignancy as a cause of weight loss. Striking
was the large amount of pericardial effusion. No other
abnormalities were seen. There were no signs of cardiac
tamponade on echocardiogram.
We concluded that the patient had severe hypothyroidism
complicated by pericardial effusion. The weight loss was
most likely caused by vomitus and loss of appetite resulting
from constipation secondary to hypothyroidism.
34
of TSH 2,85 m U/L (0,30-3,90 m U/L) a FT4 level of 25
pmol/L (10-24 pmol/L) and a T3 level of 1,8 nmol/L (1,2-2,9
nmol/L) and an elevated erythrocyte sedimentation rate
of 92mm/h (0-29 mm/h). We performed a scintigraphy
showing inhomogeneous attenuated tracer uptake in an
enlarged left thyroid lobe and a homogeneous enhanced
uptake in the right lobe. However, the clinical presentation was very suspect for a thyroiditis and we decided to
wait watchfully. The focus of therapy was pain treatment
including non-steroidal anti-inflammatory drugs and the
palpitations were treated with propranolol.
Fifteen days later the patient presented with pain that had
shifted to the right side of the throat. At this time there
was overt hyperthyroidism with a TSH level smaller than
0.02 m U/L and a FT4 of 40 pmol/L. The scintingraphy
was repeated at this time and the image showed a diffuse
enlarged thyroid gland without obvious accumulation. The
activity in the right lobe was not present anymore. The
patient eventually felt better, the pain disappeared and she
developed sequentially a subclinical hypothyroidism and
euthyroidism.
Conclusion: The combination of pain in the region of the
thyroid and an elevated erythrocyte sedimentation rate is
suspect for thyroiditis even when ultrasound and scintigraphy suggest other possible causes. Although there are
hardly case reports of hemithyroiditis, a study book reports
an incidence of 30% of a one sided or hemithyroiditis at
the beginning with progression to a thyroiditis involving
both lobes.
She was treated with laxatives and thyroxine was started
in a low dose, slowly titrated to a higher dose. The cardiologist frequently performed echocardiograms following
the development of the pericardial effusion.
Our patient recovered slowly and was discharged 2 weeks
later. After three months of compliantly taking her
medication, she appeared to be euthyroid, the pericardial
effusion disappeared and she had no complaints.
Discussion: Autoimmune hypothyroidism is a common
disorder, presenting classically with fatigue, weight gain
and constipation.
Pericardial effusion secondary to hypothyroidism
nowadays is a rare complication, present in less than 5% of
the patients and is related to the severity and duration of
the hypothyroidism. It is more common when myxedema
is present, which itself has become relatively rare.
Moderate to large pericardial effusion due to hypothyroidism seldom results in cardiac tamponade, presumably
because of pericardial distensability and slow accumulation
of fluid, allowing time for the pericardial sac to distend
without hemodynamic compromise. Thus, pericardiocentesis is hardly indicated. Once treated with thyroid
hormone replacement, pericardial effusion regresses slowly
and finally disappears within several months.
Despite massive pericardial effusion, patients should
receive standard treatment starting with low dose
regimen to prevent adverse cardiac events, since thyroxine
stimulates cardiac contractility resulting in increased
oxygen consumption. However, recurrence of pericardial
effusion can still occur, thus close monitoring is essential.
Conclusion: Pericardial effusion secondary to hypothyroidism is rare and should be treated with thyroid hormone
replacement instead of pericardiocentesis.
C006A 66-year-old man with an ‘Xtraordinary’ cause of
osteoporosis
D.M. Cohn, S. van Wissen
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Postbus 95500, 1090 HM AMSTERDAM, the
Netherlands, e-mail: [email protected]
C005 A shifting one-sided painful thyroid gland
K.C.C. Blokken, C.A.R.O.L Klomp
Twee Steden Hospital, Department of Internal Medicine, Dr.
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected]
A 66-year-old Caucasian male was referred to our
outpatient clinic for assessment of risk factors for osteoporosis, since he had recently been diagnosed with multiple
thoracic vertebral compression fractures. He had a history
of asthma and a single episode of idiopathic deep venous
thrombosis of the leg. DXA-scanning showed a reduced
bone mineral density (T-score was -3.4 at the lumbar spine
and -1.6 at the femoral neck). A mistakenly reported level
of luteinizing hormone showed considerably increased
levels (45 IU/L; normal value 2-9 IU/L). The patient
was diagnosed with primary hypogonadism, given the
accordingly increased level of follicle stimulating hormone
and a decreased level of free testosterone (49 IU/L;
normal value 2-18 IU/L and 0.078 nmol/L; normal value
0.2-0.62 nmol/L, respectively). Karyotyping showed a
Introduction: Subacute granulomatous thyroiditis
is characterized by neck pain or discomfort, a tender
diffuse goiter and a predictable course of thyroid function
evolution.
Case: A Caucasian 60-year old woman with a medical
history of rheumatoid arthritis and Raynaud’s disease
presented at the outpatient clinic with pain since two
weeks on the left side of her throat while swallowing and
palpitations. There was no episode of fever or illness in
the recent past. The ultrasound showed an inhomogeneous pattern in the bottom pole of the left lobe of the
thyroid gland. The blood results showed a normal level
35
48, XXYY/47, XYY mosaicism. The diagnosis “48, XXYY
syndrome” shares features with Klinefelter’s syndrome, but
is associated with more complications such as asthma and
deep venous thrombosis.
result, meaning that the persistent high f T4 reported by
the immune-assay was either the result of interfering
antibodies in the immune-assay or abnormal thyroid
hormone binding proteins in the patient. We did not
discriminate between the two options.
Conclusion: When there are unusual thyreoid function
tests in a patient with few complaints and who appear to
be in a euthyroid state, assay interference by antibodies or
abnormal binding globulins should be considered.
C007 Elevated free T4 levels, not always thyrotoxicosis
M.J. Noeverman1 , A.H.L. Mulder2 , N.E.T. Rikken1,
R. Hoekstra1
1
ZGT, Department of Internal Medicine, Zilvermeeuw
1, 7609 PP ALMELO, the Netherlands, e-mail:
[email protected], 2Medlon BV, clinical
chemistry laboratory, ENSCHEDE, the Netherlands
C008Getting high, running low: opioid effects on the
gonadal axis
H.E. Boersma, J.M.G. Cobben, M.J.M. Diekman
Deventer Hospital, Department of Internal Medicine, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected]
Case report: A 75-year-old woman was referred to our
outpatient clinic because of increasing f T4 levels with
a normal TSH value. She was known with elevated
f T4 levels since 4 years. In addition medical history
revealed an adrenal incidentaloma and a liver abscess. She
had no complaints, except for some recent restlessness
and agitation, as well as hot flashes and palpitations.
Physical examination showed no abnormalities. Laboratory
examination revealed an elevated f T4 level of 35 pmol/L
(normal 10-24 pmol/L) and a normal TSH of 1.0 m U/L,
both measured with immuno-assays on the Cobas 6000
(Roche Diagnostics). Since TSH levels were not suppressed
a TSH-secreting pituitary adenoma was initially suspected
and additional screening was performed. Further laboratory
examination revealed normal LH, FSH and oestradiol levels
(consistant with postmenopausal state) and normal cortisol
and ACTH levels. Catecholamines, steroids and cortisol
were measured in 24-hour urine and were all normal. The
normal test results, history of prolonged elevation of f T4
and lack of symptoms prompted us to analyse f T4 levels
using equilibrium dialysis (ED) resulting in an f T4 level
of 22 pmol/L (normal 8-22 pmol/L). It was concluded that
patient had a euthyroid state with falsely elevated fT4 levels,
if measured with a routinely used immune assay.
Discussion: Whenever there is a high f T4 with a normal
TSH, diffential diagnosis should consider drugs interference (like amiodarone of heparine), non-thyroidal illness
or assay interference. If these are excluded, more rare
causes should be considered like TSH-secreting pituitary
adenoma, resistance to thyroid hormone or disorders of
thyroid hormone transport or metabolism.
The patient did not take any medication which could
interfere, and since high f T4 levels were present for a
long time, non-thyroidal illness seems unlikely. To rule
out assay interference in the TSH assay the sample can
be diluted and re-measured. Assay interference in the f T4
assay is preferably ruled out by hormone measurement
after ED. In this particular case ED was performed at
Radboud UMC Nijmegen and showed a normal f T4
Case: A 69-year-old man, presented with episodes
of flushing and sweating. He suffered from a severe
neuropathic pain syndrome after failed back surgery
18 years ago. Pharmaceutical treatment consisted of
gabapentine, baclofen, diazepam, clonazepam,
paracetamol, codeine, doxazosin and since 14 years by
administration of intrathecal morfin. Physical examination
revealed small testes and sparse body hair, the remaining
examination was unremarkable. Laboratory investigation revealed normal hematology, electrolytes and
renal function, but decreased testosterone (1,3 nmol/L),
LH (1,4 IU/L) and FSH (7,9 IU/L) levels with normal
SHBG (48 nmol/L) and albumin (38 g/L); cortisol, thyroid
function, prolactin and IGF1 were within their reference
ranges. A diagnosis of opioid induced hypogonadotropic
hypogonadism was made. After transdermal testosterone suppletion the vapeurs disappeared and his vitality
improved considerably with even better pain control.
Discussion: Opioid-induced endocrine dysfunction is
common in methadone users, but is also seen in patients on
intrathecal opioids. It is a less common side effect with use
of oral or transdermal opioids. Opioids can have inhibitory
effects on the hypothalamic-pituitary-gonadal (HPG) and
hypothalamic-pituitary-adrenal (HPA) axes. They inhibit
the HPG axis by decreasing the secretion of GnRH. An
inhibitory effect on other parts of the axis may also play a
role. The effects on the HPA axis are less well understood.
In China, during the Ming dynasty in the late 1400s, opium
was transformed from a medicinal herb into a luxury good
with recreational value and was seen as an aphrodisiac. Many
items, which claim to arouse and intensify sexual desire, have
misty operating mechanisms (alike the mythic existence of
Aphrodite who lived with Zeus in the haze surrounding the
Olympus). Although opioids can induce a euphoric mood and
get your high, their reported endocrine effects on the HPG
36
axis result in low levels of sex steroids. It is hard to understand
how opioids can strengthen sexual performance.
Conclusion: Opioid induced hypogonadotropic hypogonadism
is not widely recognized, is clinically difficult to diagnose in
chronic pain patients and can decrease quality of life.
in haemochromatosis, chelation therapy is likely to be
an effective alternative for patients who cannot tolerate
phlebotomy. The success of this therapy was convincingly
shown in our patient.
Conclusion: Porphyria cutanea tarda can be the first
manifestation of underlying haemochromatosis. Treatment
consists of repeated phlebotomy. Although no systematic
research on treatment with desferasirox for this indication
has been performed, it has solid rationale and clear observations such as ours in small numbers of cases should lead
to the conclusion that it is not necessary to await further
confirmation in RCT’s in the situation that desferasirox
is used as a ‘last resort’ therapy in phlebotomy-intolerant
haemochromatosis patients with PCT.
C009Porphyria cutanea tarda as presenting feature of
haemochromatosis
L.R. Woittiez, B.L.J. Kanen
Zaans Medical Centre, Department of Internal Medicine,
Koningin Julianaplein 58, 1502 DV ZAANDAM, the
Netherlands, e-mail: [email protected]
A 53 year old female was referred for analysis of possible
porphyria cutanea tarda (PCT). She had wounds and
blisters on the hands since several months and dark
colored urine. She had no other complaints. She drank half
a liter of alcohol per day.
On physical examination we saw a healthy looking woman.
On her hands crustae and dry blisters were seen.
Laboratory investigation showed elevated liver enzymes
and a ferritin of 1718 ug/L with TIBC 64,0 mmol/L and
iron saturation 56%. Urine was positive for porphyrins
(4853 nmol/L). Genetic analysis showed a compound
heterozygote C282Y/H63D genotype. Porphyria with
underlying haemochromatosis was diagnosed.
Treatment with phlebotomy was complicated, and hydroxochloroquine was not an attractive alternative. Therefore
chelation therapy was started with desferasirox and the
patient was advised to quit alcohol. The ferritin level
dropped and the symptoms improved.
Discussion: Haemochromatosis is a systemic disease
characterized by iron overload. There are primary genetic
forms and secondary forms. Early disease manifestations
are atypical, but later symptoms related to excessive iron
deposition in tissues predominate.
The cause of PCT is a deficiency of hepatic uroporphyrinogen
decarboxylase (UROD). Genetic changes combined with
environmental factors can cause the development of PCT,
which is associated with an increased level of porphyrins.
The most important manifestations are cutaneous and
hepatic. Haemochromatosis is associated with PCT, because
the increased level of iron inhibits UROD. This can induce
PCT in genetically susceptible patients.
PCT and hemochromatosis are both best treated with
repeated phlebotomy. In PCT low dose hydroxychloroquine can be considered. This patient could not tolerate
phlebotomy and hydroxychloroquine would not treat the
underlying haemochromatosis. Therefore we treated her
with chelation therapy using desferasirox, although this
therapy has not been systematically investigated for this
indication. Because of the pathogenesis of porphyria
C010 An epileptic seizure due to urinary retention
K.L. Moek, K. Bolhuis, C.R.G.M. Daemen-Gubbels
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
Introduction: Hyponatremia is a frequently seen electrolyte
disturbance in general medicine. We present a patient with
a severe symptomatic hyponatremia due to the syndrome
of inappropriate antidiuretic hormone secretion (SIADH)
provoked by urinary retention.
Case: A 73 year old female presented herself to the
emergency room with an epileptic seizure. Her medical
history was significant for a depressive disorder for which
she was using citalopram and mirtazapine. On physical
examination, she was bradyphrenic and showed a distinct
tremor of her arms and legs. Glasgow coma scale was 14,
vital signs were normal. On abdominal examination a
bladder distention was found. Blood tests showed a severe
hyponatremia of 108 mmol/L and a decreased serum
osmolality of 236 mOsmol/kg. Urinalysis revealed an
osmolality of 259 mOsmol/kg and a sodium excretion of
43 mmol/L. Other blood tests were normal. MRI of the
brain showed no abnormalities. Because of the suspicion
of SIADH, the patient was treated with a fluid restriction
and because of the bladder distention a catheter was placed.
Immediately the patient became poly-uric, with an urine
production exceeding 250 cc an hour. Within seven hours
the sodium raised to a value of 122 mmol/L, an increase
of 14 mmol/L! An intravenous dextrose 5% solution was
started and in the next week the sodium value slowly
normalized, as did the urine production.
Discussion: SIADH is a frequently diagnosed condition,
especially in the elderly. This syndrome is usually
provoked by infections, malignancies or abnormalities
of the central nervous system. In this case, however, it
was caused by urinary retention. Two pathophysiologic
37
mechanisms for this have been described. First, bladder
distention may lead to functional obstructive uropathy
and the inability to secrete urine and, consequently, a
hyponatremia. Second, the pain caused by the bladder
distention itself may stimulate an excessive and inappropriate arginine-vasopressin secretion. The exact pathophysiologic mechanism, however, is not yet fully understood.
Our patient used citalopram and mirtazapine and these
medications may have contributed to the development of
the severe hyponatremia. Since these drugs were continued
while the hyponatremia dissolved we like to suggest urinary
retention as the cause of this SIADH induced hyponatremia.
Conclusion: A symptomatic and severe hyponatremia can
be the result of SIADH provoked by urinary retention.
Bladder catheterization leads to a fast recovery of the
electrolyte disturbances. In order to prevent central pontine
myelinolysis a 5% dextrose solution may be warranted.
may be present and their thyroid often shows changes
similar to goitre. RTH in patients from families unknown
to have a mutation is often diagnosed with delay or misdiagnosed as auto-immune hyperthyreoidism or multinodular
goiter. In general treatment of RTH is supportive although
in children and pregnant women follow-up and treatment
may be warranted. Thyroid ablation should be avoided.
The general practitioners guideline (NHG) recommends
measuring only TSH when thyroid disease is suspected
and further testing if abnormal. Frequently RTH will
not be detected unless TSH ánd f T4 are measured. The
guideline recommends against routinely testing for thyroid
dysfunction in patients with anxiety disorders.
Conclusion: Taken into account the relatively high
prevalence of RTH many cases remain unrevealed when
following the current NHG guideline. Given the fact that
measuring TSH and f T4 is not expensive, there is no need
to exclude patients with anxiety disorders from testing
thyroid function. Testing should include measurement of
TSH ánd f T4.
C011 TSH measurement alone is insufficient for
diagnosing thyroid dysfunction
C012 Non-compaction cardiomyopathy and large feet
E.C. Hamoen, P.H.L.M. Geelhoed-Duijvestijn
Medical Centre Haaglanden, Department of Internal
Medicine, Lijnbaan 32, 2512 VA DEN HAAG, the Netherlands,
e-mail: [email protected]
W.G. Melsen, M.J. van Dam
University Medical Centre Utrecht, Heidelberglaan
100, 3584 CX UTRECHT, the Netherlands, e-mail:
[email protected]
Case: A 42 year old patient with a history of anxiety disorder
and rheumatoid arthritis was referred to the outpatient clinic
because of hyperthyroidism. He complained of tremor,
sweating, palpitations and weight loss of 10 kilograms in the
past 2 months after an episode of pain in his throat without
fever. Family history for thyroid disease was negative.
Physical examination showed no objective signs of hyperthyreoidism. Laboratory investigation repeatedly showed
elevated free T4, a normal T3 and non-supressed TSH. Thyroid
antibodies were negative. The TRH stimulation test showed a
normal TSH response and TSH alfa-subunits were normal.
Therefore central hyperthyroidism was excluded. A DNA test
for thyroid receptor mutation showed a c.1286G > A mutation
in the THRB gene which causes resistance to thyroid
hormone. Whether the patient’s transient complaints are
due to this mutation, a concurrent thyreoiditis or anxiety
remains unclear. Patient’s daughter was recently referred
to a paediatrican because of obesity and abnormal thyroid
function. She also has an elevated fT4 concentration with
high normal TSH. Analysis of THRB mutation will follow.
Discussion: We describe a new case of resistance to
thyroid hormone (RTH). The prevalence of RTH is 1 of
40.000 live births. It is due to mutations in the thyroid
hormone receptor bèta (THRB) gene in 85% of cases and
inherited as an autosomal dominant trait. Frequently
patients present with nonspecific complaints like anxiety or
ADHD-like symptoms (33-75% of cases). Thyroid antibodies
Introduction: Non-compaction cardiomyopathy (NCC) is
a rare disorder, the reported prevalence ranges between
0.014 to 1.26%. NCC was previously also named spongy
myocardium or hypertrabeculation syndrome. It is
classified as a primary genetic cardiomyopathy by the
American Heart Association. Acromegaly (ACR) is an
unusual disorder with an annual incidence of around 6
cases/ million. We present an extraordinary association
between NCC and ACR.
Case report: A 59-year-old man, known with a NCC, was
admitted in September 2013 to the ICU with respiratory
insufficiency caused by congestive heart failure. The
patient was intubated, mechanically ventilated and treated
with furosemide and dobutamine. Despite intensive
therapy no clinical improvement was achieved and he
received a LVAD (implantable left ventricular assist device).
After conquering infection and delirium the patient
recovered and was weaned from the ventilator. 100 days
after admission he was discharged to the ward.
Earlier, at physical examination large hands, large feet and
enlarged facial features were observed. First, these features
were explored with patient’s partner. She had not noticed
changes in his appearance the last years. When the patient’s
delirium was adequately treated we questioned the patient.
He indicated that indeed the last three years his feet had
38
1,25-OH vitamin D < 3.8 nmol/L, M-protein and Bence
Jones were negative. Parathyroid hormone related peptide
was not determinated because of the low clinical suspicion
of a malignant cause. Because she was symptomatic and
had a high risk of developing cardiac and neurologic
symptoms she was treated with rehydration therapy, salmon
calcitonin every 6 hours 100 IE subcutaneously and after
three days administration of bisfosfonate.
Results: In eleven hours corrected calcium levels decreased
from 5.66 mmol/L to 4.23 mmol/L and after 32 hours to
3.07 mmol/L. After 1 week, serum calcium was almost
normal (2.68 mmol/L).
Discussion: Most likely the severe hypercalcaemia
was caused by oversuppletion of dihydrotachysterol by
increasing the dosage managed by low 25-OH vitamin D
levels. Dihydrotachysterol intoxication could not be detected
with laboratory testing of 1,25-OH vitamin D and 25-OH
vitamin D. Calcitonin is safe in use, also in patients with
heart failure and kidney failure. It lowers serum calcium
by a maximum of 0,3-0,5 mmol/L within four to six hours
after administration. Calcitonin is only effective in de first
48 hours until the maximum of one week and plays an in
the first 48 hours of therapy. Calcitonin had a low toxicity
profile, is inexpensive and it is save to use4,7-8. In cases of
severe hypercalcaemia we consider therapy with calcitonin,
however we think calcitonin should be standard therapy as
a brigde to the long term bisfosfonate effect has occured.
Conclusion: Calcitonin should play a more important role
in the treatment of serious symptomatic severe hypercalcaemia > 3,50 mmol/L, especially in the prevention
and treatment of serious cardiac and neurologic effects.
More research is needed to investigate long term effects
of calcitonin therapy on morbidity and cost effectiveness.
grown from size 47 to size 50. These changes appeared
before his heart problems surfaced. Because of a suspicion
of acromegaly IGF-1 was measured: 102.4nmol/L (SD 9.24).
A CT-scan of the pituitary gland showed a macroadenoma.
Further investigation of the other pituitary functions
showed failure of the gonadotropic axis. Patient was started
on octeotride as pituitary surgery was not possible. It
was questioned whether there was a relation between his
acromegaly and his non-compaction cardiomyopathy.
The diagnosis of NCC was made by echocardiography in
January 2011. He presented with dyspnea d’effort since
December 2010. Extensive genetic screening showed no
DNA abnormalities. Intitially patient had a good exercise
tolerance, decreasing only the last few months.
Conclusion: We report a rare association of ACR en NCC.
As these are unusual diseases we questioned if they are
completely unrelated. In the literature one case report of a
24 year old male with ACR and NCC is described. It was
described that considering the incidence of each one, the
chance of independently having both is about 1.5 in one
billion. Further investigation, for example genetic investigation, is needed to elucidate the underlying mechanisms
of the association between ACR and NCC.
IV
DIABETES MELLITUS CASE REPORTS
C013 Treatment of a patient with salmon calcitonin with
severe hypercalcaemia caused by dihydrotachysterol
oversuppletion
M. Smits, H. Jansen
Jeroen Bosch Hospital, Department of Internal Medicine, Sint
Annastraat 186D, 6525 GW NIJMEGEN, the Netherlands,
e-mail: [email protected]
V
Introduction: We describe a patient with dihydrotachysterol-intoxication who was successfully treated
with calcitonin injection combined with rehydration
and bisfosfonate therapy. This case illustrates the
role of calcitonin injection therapy in patients with
dihydrotachysterol-intoxication.
Case report: A 46-year old woman with a medical history
of persistent hypoparathyroidism after strumectomy,
presented with a symptomatic severe hypercalcemia, most
likely cause by dihydrotachysterol-intoxication. Patient used
calciumcarbonate, dihydrotachysterol and levothyroxin. On
physical examination, a maximum Glasgow coma score was
measured, she was stable with respect to hemodynamics
and there were no signs of hyporeflexia. Laboratory findings
revealed a corrected hypercalcaemia of 5.66 mmol/L,
parathyroid hormone level of < 0.25, potassium 2.5 mmol/L,
normal thyroid function, 25-OH vitamin D 19 nmol/L and
DIABETES MELLITUS RESEARCH
C014 Eating behavior is associated with long-term weight
loss following GLP-1 RA treatment in type 2 diabetes
on insulin: 2 years real life follow-up data
S.A. de Boer1, D.J. Mulder1, J.D. Lefrandt1, K. Hoogenberg2
1
University Medical Centre Groningen, Department of
Vascular Medicine, Hanzeplein 1, 9713 GZ GRONINGEN, the
Netherlands, e-mail: [email protected], 2Martini Hospital,
GRONINGEN, the Netherlands
Introduction: Glucagon-like peptide-1 receptor agonists
(GLP-1 RA) added to insulin in type 2 diabetes (T2DM)
patients improves glycemic control and reduced body
weight in short term studies, although the individual
response greatly varies. Previously it was shown that GLP-1
RA attenuates binge eating in healthy obese men.
39
Aim of the study: We evaluated the 2 year follow-up
effects in T2DM patients on insulin who started GLP-1 RA
(Exenatide or liraglutide) and examined whether eating
behavior (restrained, emotional, and external) is associated
with weight reduction.
Materials and methods: Eating behavior of 151 overweight
T2DM patients was classified according to a validated
questionnaire (Dutch Eating Behavior Questionnaire) which
has a scale on restrained eating (10 items: e.q. “Do you try to
eat less at mealtimes than you would like to eat”), emotional
eating (13 items: e.q. “Do you have a desire to eat when you
are irritated?”) and external eating (10 items: e.q. “If food
smells and looks good, do you eat more than usual?”).
Results: 120 patients completed the 2 years follow-up (FU);
21 stopped after ≤ 6 months due to side-effects or a lack of
effect, 9 patients were lost to FU, and 1 patient died. Body
weight changed from 117.9 ± 22.1 to 107.9 ± 22.9 kg (mean
± SD) (p < 0.0001). HbA1c changed from 8.1 [7.9-8.3] to
7.6 [6.9- 8.3]% [geometric mean, 95% CI] (p < 0.0001),
TDD from 90 (56-150) to 60 (0-100) Units/day (median,
IQR) (p < 0.0001) and 30% (n = 36) patients were able to
stop insulin treatment. According to eating behavior, body
weight was significantly reduced in all groups: external (n
= 17) 117.8 ± 18.7 kg to 114.4 ± 20.4 kg (-3.1%, p < 0.022),
emotional (n = 37) 113.8 ± 19. to 103.9 ± 19.0 kg (-8.5%, p
< 0.001), restrained (n = 41) 123.8 ± 22.7 kg to 111.3 ± 22.5 kg
(-10.3%, p < 0.001), indifferent (n = 25) 114.6 ± 25.4kg to
103.8 ± 24.8 kg (-9.6%, p < 0.001). Weight change differed
significantly between groups (p < 0.001), independently of
baseline weight, HbA1c, and TDD (MANOVA, < 0.001) but
changes in HbA1c and TDD did not.
Conclusion: GLP-1 RA added to insulin treatment in
overweight T2DM patients results in long-term
improvement of glycemic and weight control in a real life
setting. Interestingly, the magnitude of weight reduction
was associated with the type of eating behavior, with the
greatest effects observed in restrained eaters, in whom
binge eating is common.
Aims: Complement factor 3 (C3) is an emerging risk factor in
obesity-related metabolic and cardiovascular diseases. Several
cross-sectional studies have shown that C3 levels are associated
with insulin resistance (IR) and type 2 diabetes mellitus
(T2DM), but longitudinal studies on this subject are scarce.
Therefore, we investigated whether C3 levels were longitudinally associated with IR in muscle, liver, and adipocytes over
a 7-year follow-up period. In addition, we examined whether
baseline C3 levels were associated with incident T2DM.
Methods: Prospective cohort study, in which plasma
C3 levels were determined at baseline in 545 individuals
and after 7 years follow-up in 394 individuals (60% men,
age 59 ± 6.9 years, BMI 28.5 ± 4.3). Oral glucose tolerance
tests with measurement of glucose and insulin were
performed at baseline and follow-up. Using generalized
estimating equations, linear regression analyses, and
logistic regression, we investigated associations between
(changes in) plasma C3 levels and (changes in) indices of
muscle, liver, and adipocyte insulin resistance, as well as
(changes in) glucose intolerance.
Results: Over the 7-year period, plasma C3 levels (per 0.1g/L)
were longitudinally associated with higher HOMA2-IR
(b = 8.71% [95% CI 6.49-10.98]), hepatic IR (b = 3.85%
[95% CI 2.41-5.32]), adipocyte IR (b = 8.04% [95% CI
5.25-10.90]), and AUCglucose (b = 2.23% [95% CI 1.23-3.23])
after adjustment for several covariates, including inflammatory markers. In addition, larger changes in C3 (per
0.1g/L) were associated with larger changes in HOMA2-IR
(b = 0.08 [95% CI 0.02-0.15]), and larger changes in hepatic
IR (b = 0.87 [95% CI 0.12-1.61]) over 7 years. Finally, baseline
plasma C3 levels (per 0.1g/L) were associated with incident
T2DM during 7 years (OR 1.51 [95% CI 1.13-2.04]).
Conclusions: Plasma C3 levels concentrations were longitudinally associated with the degree of IR in muscle,
liver and adipocytes, and were prospectively associated
with incident T2DM. Whether C3 causally contributes to
the development of IR and T2DM, or rather represents a
marker of IR in several tissues, remains to be investigated.
C015 Complement factor 3 is longitudinally associated
with insulin resistance, glucose intolerance, and
incident type 2 diabetes mellitus over a 7-year
follow-up period: the CODAM study
C016 Glucagon-like peptide-1 receptor agonist therapy in
patients with long-standing type 2 diabetes mellitus
in clinical practice is beneficial: a retrospective
cohort study
N. Wlazlo1 , M.M.J. van Greevenbroek 2, I. Ferreira 2,
E.J.M. Feskens3, C.J.H. van der Kallen2, C.G. Schalkwijk2,
B. Bravenboer4, C.D.A. Stehouwer2
1
Catharina Hospital, Department of Internal Medicine, PO
Box 1350, 5602 ZA EINDHOVEN, the Netherlands, e-mail:
[email protected], 2Maastricht University Medical Centre,
MAASTRICHT, the Netherlands, 3Wageningen University,
WAGENINGEN, the Netherlands, 4Regional Hospital St
Maria, HALLE, Belgium
P.C. Oldenburg-Ligtenberg1, J.C.L. Notohardjo1, S.I. Lok1,
L.T. Dijkhorst-Oei1, P.C.M. Pasker-de Jong1, H.W. de Valk2
1
Meander Medical Centre, Department of Internal Medicine,
Maatweg 3, 3813 TZ AMERSFOORT, the Netherlands, e-mail:
[email protected], 2University Medical Centre,
UTRECHT, the Netherlands
Background: Glucagon-like peptide-1 receptor agonists
(GLP-1 RAs) have been shown to provide promising results
40
Introduction: Atherosclerosis in type 2 diabetes mellitus
(T2DM) is characterized by a chronic inflammatory
response in which activation of leukocytes plays a central
role. Acute and chronic hyperglycemia may be involved in
this leukocyte activation.
Aim of the study: The aim of this study was to investigate
the role of acute and chronic glycaemia on leukocyte
activation in patients with a wide range of insulin
sensitivity.
Methods: Classical cardiovascular risk factors and
leukocyte activation markers were determined at baseline
and after ingestion of 75 gram glucose in subjects with
T2DM, familial combined hyperlipidemia (FCH) and
healthy controls. Leukocyte activation markers were
measured by flow cytometry using fluorescent labeled
monoclonal antibodies. Postprandial changes up to 2 hours
were calculated as the area under the curve (AUC).
Results: A total of 51 subjects (20 T2DM, 17 FCH and 14
controls) participated in the study. Fasting neutrophil
CD66b expression was 36% higher in T2DM than in
controls (p < 0.05). Neutrophil CD66b-AUC was 39%
higher in T2DM patients than in healthy controls (p
< 0.05). Monocyte CD11b-AUC was 26% higher in T2DM
than in controls (p < 0.05). Fasting neutrophil CD66b,
neutrophil CD66b-AUC and monocyte CD11b-AUC was 7,
13 and 15% higher in FCH patients than in controls, respectively, although this did not reach statistical significance.
Glucose-AUC correlated positively with baseline neutrophil
CD66b expression (Spearman’s rho 0.437, p = 0.008).
HbA1c correlated positively with baseline neutrophil
CD66b expression (rho 0.458, p = 0.004) and neutrophil
CD66b-AUC (rho 0.328, p = 0.047). The expression of
these markers was independent of the use of statins, since
withdrawal of these drugs in 55 subjects did not influence
the leukocyte activation.
Conclusion: Acute and chronic hyperglycemia due to
insulin resistance as seen in T2DM and FCH are associated
with increased leukocyte activation, independent from
statin use.
for the treatment of patients with type 2 diabetes (T2DM)
in clinical trials. However, data regarding the long-term
effectiveness of GLP-1 RAs in clinical practice are limited.
It this real-life setting, discontinuation of treatment may
be more prevalent. The aim of the present study was to
investigate the long-term effectiveness of GLP-1 RAs in
obese patients with long-standing T2DM, in which most
of the patients were treated with insulin prior to GLP-1
RA therapy, and to evaluate predictors associated with the
continuation of treatment. < b > Methods: < /b > All obese
patients (defined as BMI > 35 kg/m2) with T2DM, receiving
GLP-1 RAs between February 2010 and September
2013 were enrolled in this retrospective study. Clinical
parameters were collected from charts assessed at baseline
and 3, 6, 12 and 24 months after initiating treatment. The
primary endpoints were changes in glycated hemoglobin
levels (HbA1c) and body weight from baseline. Secondary
endpoints included the change in systolic blood pressure
(SBP) and diastolic blood pressure (DBP), low density
lipoprotein cholesterol (LDLc) and high density lipoprotein
cholesterol (HDLc) from baseline. Furthermore, data
on discontinuation rate, fasting C-peptide, duration of
diabetes, and medication use at baseline were also noted.
Results: A total of 172 patients who started on liraglutide
(97%) or exenatide (3%) were enrolled in the study.
GLP-RAs were found to result in a significant reduction of
body weight (11.0 ± 2.8 kg) at 2 years of follow-up, and in
HbA1c levels, SBP and DBP after one year. No beneficial
effects on LDLc and HDLc were found. Overall, 35% of
the patients discontinued treatment, mainly because
of inadequate HbA1c levels (69%) and gastrointestinal
disorders (14.7%). The use of metformin at baseline was a
strong predictor for treatment continuation. Age, duration
of diabetes and weight at baseline were inversely correlated
with treatment continuation.
Conclusion: This is the first ‘real life’ study in patients
with long-standing T2DM previously treated with
insulin therapy showing that GLP-1 RA therapy leads to
meaningful long-term reductions in body weight after
two years. Beneficial changes in HbA1c levels, SBP and
DBP were noted after one year of treatment. No additional
beneficial effects on lipid profile were observed. GLP-1 RAs
are preferably prescribed in combination with metformin.
VI
HAEMATOLOGY RESEARCH
C018 Quality of life more impaired in younger than
in older diffuse large B-cell lymphoma survivors
compared to a normative population: A study from
the population-based PROFILES registry
C017 Postprandial glucose-dependent leukocyte activation
in patients with different ranges of insulin sensitivity
M.A. de Vries1, A. Alipour 1, B. Klop1, G.J.M. Geijn1,
T.L. Njo1, J.W. Janssen1, A.P. Rietveld1, A.H. Liem1,
W.W. de Herder2, M. Castro Cabezas1
1
St Franciscus Gasthuis, Kleiweg 500, 3045 PM
ROTTERDAM, the Netherlands, e-mail: [email protected],
2
Erasmus Medical Centre, ROTTERDAM, the Netherlands
M.W.M. van der Poel1, S. Oerlemans2, H.C. Schouten1,
F. Mols3, J.F.M. Pruijt 4, H. Maas5, L.V. van de Poll-Franse3
1
University Hospital Maastricht, Department of Internal
Medicine, PO Box 5800, 6202 AZ MAASTRICHT, the
Netherlands, e-mail: [email protected],
41
2
Methods: Inpatients and outpatients who have undergone a
compression ultrasound for the suspicion of DVT from July
2012 till July 2013 were included in this study. The Wells
score have been determined retrospectively for all patients.
The main outcomes were sensitivity, specificity, positive and
negative predictive value of the Wells score and the D-dimer
test, the latter extended with an age-adapted cut-off point
(age x 10mg/L). The secondary outcome was the predictive
value of the individual risk factors of the Wells score.
Results: 178 patients were included. DVT prevalence
was 30%. The Wells score showed a sensitivity of 83%;
combined with a D-dimer test (at score ≤1) sensitivity
raised to 86%. The D-dimer test alone showed a sensitivity
of 100% for all patients with a proximal DVT, not using
anticoagulants. The specificity of the D-dimer test was
15% and doubled by using the age-adapted cut-off point
for patients ≥ 50 years, thereby reducing the amount of
compression ultrasounds with 10%. Excluding patients
with certain characteristics (malignancy, pregnancy,
postoperative, using anticoagulants) increased the
diagnostic value of D-dimer. In the analysed population
only the Wells score’s risk factors malignancy and
difference in calf circumference > 3cm were predictive for
a DVT with Odds ratios of 3.2 and 2.2.
Conclusion: A D-dimer test alone is superior to a
combination of the D-dimer test and the Wells score
in safely ruling out a DVT. Efficacy of the D-dimer
test increases with selection of patients and use of an
age-adapted cut-off point.
Comprehensive Cancer Centre South, EINDHOVEN, the
Netherlands, 3Center of Research on Psychology in Somatic
Diseases (CoRPS), Tilburg Universit, TILBURG, the
Netherlands, 4Jeroen Bosch Hospital, ’S HERTOGENBOSCH,
the Netherlands, 5Twee Steden Hospital, TILBURG, the
Netherlands
Purpose: The objective of this study was to compare
Health-Related Quality of Life (HRQOL) between Diffuse
Large B-Cell Lymphoma (DLBCL) survivors of different
age categories (18-59 years/ 60-75 years/ 76-85 years) and
to compare their HRQOL with an age- and sex-matched
normative population.
Methods: The population-based Eindhoven Cancer
Registry was used to select all patients diagnosed with
DLBCL from 1999 to 2010. Patients (n = 363) were invited
to complete the EORTC QLQ-C30 questionnaire and
307 survivors responded (85%). Data from an age-and
sex-matched normative population (n = 596) were used for
comparison.
Results: DLBCL survivors aged 18-59 years scored better
on physical functioning, quality of life, appetite loss and
constipation than survivors of 76-85 years old (all p <
.05). Financial problems more often occurred in survivors
aged 18-59 years compared to survivors of 76-85 years
old (p < .01). Compared to the normative population,
DLBCL survivors aged 18-59 years showed worse scores
on cognitive and social functioning and on dyspnea and
financial problems (p < .01, large and medium size effects).
In survivors of the other age categories only differences
with trivial or small size effects were found.
Conclusion: Although younger DLBCL survivors have
better HRQOL than older survivors, the differences found
between younger survivors and the normative population
were the largest. This suggests that having DLBCL has a
greater impact on younger than on older survivors andthat
the worse HRQOL observed in older DLBCL survivors in
comparison with younger survivors is caused mostly by age
itself and not by the disease.
C020 Relation of the quotient transferrin / log (ferritin)
and bone marrow iron content
J. Baan1, R. Castel1, J. Droogendijk1, P. Sonneveld2, J. Riedl1,
P. Berendes1, M.D. Levin1
1
Albert Schweitzer Hospital, Department of Internal
medicine – hematology, Albert Schweitzerplaats 25,
3318 AT DORDRECHT, the Netherlands, e-mail:
[email protected], 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands
C019 Role of Wells score and D-dimer test in diagnosing
deep venous thrombosis
Introduction: Iron deficiency is a frequently encountered
problem in clinical practice and is present in 2 to 5%
of people in developed countries. The diagnosis of iron
deficiency is often not clear because the “gold standard”
bone marrow iron content is often not performed and other
laboratory values, i.e. ferritin, transferrin, serum iron,
serum transferrin receptor, iron saturation or hepcidin,
are not reliable, because of interference of acute phase
response, or not easily executed.
Recently a new quotient of transferrin divided by the
logarithm of ferritin (T/Log(F)) proved to be reliable and
easily performed in routine practice for iron deficiency
I.T. Hazenberg, V. Coopman, A.J.J. Woittiez
ZGT, Department of Internal Medicine, Zilvermeeuw 1, 7600
SZ ALMELO, the Netherlands, e-mail: [email protected]
Introduction: The value of diagnostic tests, such as Wells
score and D-dimer test, for deep venous thrombosis (DVT)
have been discussed frequently, especially because of their
varying sensitivity. This study analysed the efficacy and
reliability of these tests in a Tubantian population.
42
Aim: To identify the adherence to guidelines for best
available care for patients with newly discovered IDA.
Materials and materials: Patients selected for this study
were males above 18 years of age and females above 50
years in order to exclude postmenopausal blood loss as
the prominent cause of IDA. From the charts of the GPs
all additional diagnostics and treatment within 4 months
of the diagnosis of the new anemia were registered and
classified. In addition, all additional work-up and treatment
in hospital were registered too.
Results: From Februari 1st 2007 to Februari 1st 2013 317
patients diagnosed with IDA were selected from 48 GPs.
Reason for taking blood in patients with IDA were atypical
complaints in 48.7% of the patients and specific GI tract
discomfort in 20.9% of patients. In 49.7% of cases with
IDA no examination of the GI tract is performed. In
addition, 6% of patients received a gastroscopy, 7% received
a colonoscopy and 29.7% of patients with IDA received a
full GI tract examination. In 70.6% of cases with IDA,
patients received iron supplementation. Survival and
discovery of GI focus of the IDA in follow-up will discussed
during the presentation.
Conclusion: The adherence of GPs to the NHG guideline is
low, resulting in an underdiagnosis of the GI tract.
anaemia. (Castel et all, The transferrin/Log(ferritin) ratio:
a new tool for the diagnosis of iron defi ciency anemia, Clin
Chem Lab Med 2012;50(8)) This study will describe the
relation between T/Log(F) and bone marrow iron content.
Materials and methods: All patients from 01-01-2006 to
01-01-2012 with anaemia (female Hb < 7,5 mmol/L and
male < 8,5 mmol/L), in whom a bone marrow without
signs of abnormalities and an iron status (transferrin,
ferritin, serum iron) was performed (within 6 months
before or after bone marrow examination), were included
in the study. The bone marrow iron content was scored
by 3 independent observers using the Gale grading scale.
Grade 0 and 1 are classified as being iron deficient, 2 and
more are classified as not iron deficient. Variations in
classification between observers was predefined, the most
frequent observation was leading for the definite bone
marrow iron content.
Results: The primary endpoint of the study is to evaluate
if there is a correlation between bone marrow iron content
and the T/Log(F) ratio less than 1,7. Secondary endpoint is
to correlate other iron parameters (ferritin, transferring,
iron saturation and serum iron) with the bone marrow
iron content as well, to see which parameter best predicts
iron deficiency. ROC-curves are shown for T/Log(F) ratio,
ferritin, transferrin, iron saturation and serum iron in
relation to bone marrow iron content and the optimal
cutt-off value for these parameters is shown.
Conclusion: Optimal diagnostics for iron deficiency
anemia using T/Log(F), ferritin, transferrin, iron
saturation and serum iron in relation to bone marrow iron
content is demonstrated.
C022 Cytogenetics in myelodysplastic syndrome (MDS): a
predictive model to promote appropriate laboratory
testing
P.A.F. Geerts, L.W. Tick, P.H.M. Kuijper
Máxima Medical Centre, Department of Internal Medicine,
De run 4600, 5504 DB VELDHOVEN, the Netherlands,
e-mail: [email protected]
C021 Adherence to guidelines in patients with newly
discovered iron deficiency anemia
Background: Myelodysplastic syndrome (MDS) is a
malignant disease of the bone marrow, in which one or
more myeloid cell lineages show dysplasia. A number
of specific risk factors are known, that can predict the
prognosis (for example the IPSS risk score) or determine
the treatment protocol. Here, cytogenetics are of important
value. To assess cytogenetics in all patients is not necessary
and expensive. A second bone marrow examination is a
great burden to the patient. To more thoughtfully decide
on forehand whether cytogenetic examination should be
performed directly at a first bone marrow examination,
we intended to create a model to predict MDS in a patient.
Methods: We evaluated all bone marrow examinations
in the period of August 2010 to February 2013, that were
evaluated for MDS. We formulated a set of potential risk
factors for MDS. These data were collected retrospectively
and with logistic regression analysis a predictive model
was constructed.
A. Schop, K. Stouten, M.D. Levin
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3318 AT DORDRECHT, the
Netherlands, e-mail: [email protected]
Introduction: A new case of anemia is frequently
encountered in general practice. One of the most common
types of anemia is iron deficiency anemia (IDA). In
4-15% of patients with IDA, when menstrual blood loss is
excluded, a malignancy of the GI tract is present.
In order to find the underlying cause of IDA, it is essential
that general practitioners (GPs) define a new case of
anemia as a potential harming symptom and that they
provide best available care for the patients. The Dutch
college of General Practitioners (NHG) provides guidelines
for GPs to perform best available care. When a new case of
IDA is determined, a thorough examination of the GI tract
and iron supplements has been assigned standard practice.
43
Results: In 118 analyzed bone marrow examinations, MDS
(n = 16) or AML (n = 7) were diagnosed in 23 patients
(19%). Significant predictive factors were leukocytes
< 4,0*109/L, neutrophil granulocytes < 1,5*109/L, thrombocytes < 150*109/L, MCV > 100fl and RDW > 14,5%. The
best predictive model (neutrophil granulocytes < 1,5*109/L
and RDW > 14,5%) had a sensitivity of 58% and specificity
of 91%. The positive predictive value was 65% and the
negative predictive value 88%.
Conclusion: Our retrospective data showed that with two
predictive factors, MDS in this study population can be
ruled out with a 91% certainty. The sensitivity of 58%
might also be of use considering a possible cost reduction.
In the future, ideally, this model and the other evaluated
possible risk factors should be validated prognostically.
12.2% of received oral iron supplements. In 41.4% of cases
the underlying cause of ACD was not found by either the
GP or specialists after referral.
Survival and therapeutic strategies of GPs by the ACD
patients in follow-up will be discussed during the
presentation.
Conclusion: The adherence of GPs to the NHG guideline is
low, resulting in overtreatment with oral iron supplements
in 12.2% of patients with ACD. No cause of ACD could be
established in 41.4% of patients.
C023 Adherence to guidelines in patients with newly
discovered anemia of chronic disease
W. Plattel1, A. van den Berg2, Z. Alsada2, A. Diepstra2,
G.W. van Imhoff2, L. Visser2
1
Medical Centre Leeuwarden, Department of Internal
Medicine, LEEUWARDEN, the Netherlands, e-mail:
[email protected], 2University Medical Centre
Groningen, GRONINGEN, the Netherlands
C024 Comparison of serial plasma Galectin-1, sCD163
and sCD30 with plasma TARC levels as circulating
biomarkers for response evaluation in classical
Hodgkin lymphoma
A. Schop, K. Stouten, M.D. Levin
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert Schweitzerplaats 25, 3318 AT DORDRECHT, the
Netherlands, e-mail: [email protected]
Introduction: Plasma Thymus and Activation Regulated
Chemokine (TARC), sCD30 and more recently Galectin-1
and sCD163 have been reported to be elevated in plasma
or serum of untreated classical Hodgkin Lymphoma
(cHL) patients. Especially for sCD30, Galectin-1 and
sCD163 limited data exist on the applicability of these
biomarkers as disease response markers.
Aim of the study: The aim of this study was to compare the
clinical applicability of plasma TARC, sCD30, Galectin-1
and sCD163 as biomarkers in cHL response evaluation.
Materials and methods: Plasma samples were collected
before and after treatment in 63 newly diagnosed cHL
patients and in healthy controls. TARC, Galectin-1,
sCD30 and sCD163 levels were determined by ELISA
and compared to clinical characteristics and treatment
response.
Results: Pre-treatment plasma TARC, Galectin-1 and
sCD30 but not sCD163 were significantly elevated among
cHL patients compared to healthy controls. Plasma TARC
could most accurately discriminate patients from controls
with pre-treatment samples being elevated in 94% of
patients. Plasma TARC significantly correlated with stage
of disease and plasma TARC, sCD163 and sCD30 also
correlated with metabolic tumor volume as measured
by quantification of pre-treatment FDG-PET scans. All
biomarkers correlated with presence of B-symptoms. In the
entire group, plasma TARC, Galectin-1 and sCD30 levels
significantly decreased, while sCD163 significantly
increased after treatment compared to pre-treatment.
Plasma TARC levels decreased to normal levels in all
Introduction: A new case of anemia is frequently
encountered in general practice. One of the most common
types of anemia is anemia of chronic diseases (ACD). ACD
is mainly caused by increased production of hepcidin by
the liver, which eventually prevents the release of iron
from iron stores and inhibits iron uptake from the GI tract.
Increased production of hepcidin is seen by chronic illness
such as infections, malignancy and autoimmune diseases,
but frequently the underlying cause of ACD is unclear. The
Dutch college of General Practitioners (NHG) provides
guidelines for GPs to perform best available care. When
a new case of ACD is determined, it is essential that the
patients does not receive oral iron supplements and further
investigations are performed.
Aim: To identify the adherence to guidelines for best
available care for patients with newly discovered ACD.
Materials and methods: From Februari 1st 2007 to Februari
1st 2013 patients with a newly discovered anemia were
selected for this study. Only males above 18 years of
age and females above 50 years were selected. From the
charts of the GPs all additional diagnostics and treatment
within 4 months of the diagnosis of the new anemia were
registered and classified. In addition, all additional work-up
and treatment in hospital were registered too.
Results: From Februari 1st 2007 to Februari 1st 2013 319
patients diagnosed with IDA were selected from 48 GPs. In
27.6% and 27,3% of cases antibiotics or anti-inflammatory
medicines were given because of an assumed infection or
other inflammation, respectively. Of the patients with ACD
44
of issues related to NOAC are critical in this case. Firstly,
rivaroxaban is, like VKA, a substrate for P-glycoproteïn and
CYP3A4. Concomitant use of strong CYP3A4-inducers,
such as rifampicin, can induce up to 50% reduction in the
area under the curve, with a presumed parallel decrease in
pharmacodynamic effect.2 Secondly, although a prolonged
PT can be used as an insensitive surrogate marker of the
use of a factor Xa-inhibitor, no linear relation between a
prolonged PT and the intensity of the anticoagulant effect
of NOAC exists.1 In emergencies, quantitative assessment
of the exact level of anti-coagulation may be pivotal to
estimate the effectiveness of this therapy. Only through
increased awareness of all physicians treating patients
with NOAC, an effective treatment with these promising
new drugs can be achieved, without the risk for potential
complications.
responsive patients and remained high in the three
non-responsive patients. sCD30 remained high in two
of the three non-responsive patients and Galactin-1 and
sCD163 did not correlate with treatment response.
Conclusion: In conclusion, in our cohort pre-treatment
plasma levels of TARC, Galectin-1 and sCD30 were significantly elevated in cHL patients but only plasma TARC
accurately correlated with treatment response.
VII
HAEMATOLOGY CASE REPORTS
C025 Clinical challenges related to novel oral anticoagulants – drug-drug interactions and monitoring
R. Kornalijnslijper-Altena1, H. de Wit1, M. Hoogendoorn2
University Medical Centre Utrecht, Department of Internal
Medicine, Heidelberglaan 100, 3584 CX UTRECHT, the
Netherlands, e-mail: [email protected],
2
Medical Centre Leeuwarden, LEEUWARDEN, the Netherlands
References
1
1. Mueck W, et al. Clin Pharmacokinet. 2011;50:675-85.
2. http://www.ema.europa.eu/docs/en _GB/document _
library/EPAR_-_Product_Information/human/000944/
WC500057108.pdf.
Introduction: Novel oral anticoagulants (NOAC) are an
effective, safe and patient-friendly alternative to vitamin K
antagonists (VKA) in an expanding range of indications.
A major disadvantage of NOAC is the inability to quantitatively assess the level of anticoagulant effect.
Case: A 67-year old female was admitted because of
thoracic pain. Her medical history comprised coronary
artery disease and atrial fibrillation. Two months earlier,
she received a hip prosthesis after traumatic femoral
fracture. Recovery was complicated by a wound infection,
for which she was treated with ciprofloxacin and rifampicin
for a total duration of 3 months. Three weeks prior to
presentation she was switched from acenocoumarol to
rivaroxaban 20mg once daily because of labile international normalized ratio levels. Upon admittance a working
diagnosis of acute coronary syndrome was established;
pulmonary embolism was considered unlikely because of
the actual rivaroxaban use with prolonged prothrombin
time (PT, 21.6 sec) at presentation. She rapidly deteriorated and died. Upon autopsy she had extensive central
pulmonary embolisms.
A plasma rivaroxaban concentration at presentation was
measured retrospectively. At this time-point, two hours
after oral intake of rivoraxaban 20 mg, the concentration
was 178 ng/mL. Although limited data exist on the most
effective plasma concentration of rivaroxaban, this peak
plasma concentration is just below the 5th percentile of
what would be predicted, based on pharmacokinetic and
-dynamic studies.1
Conclusion: This case of fatal pulmonary embolism may
be related to sub-therapeutic levels of rivaroxaban, through
the interaction of rifampicin with rivaroxaban. A number
C026 Acute myeloid leukaemia (AML) during second and
third trimester of pregnancy
L.M. van der Burg, M. van Marwijk Kooy, L.F. Verdonck
Isala Clinics, Department of Internal Medicine, Dokter van
Heesweg 2, 8025 AB ZWOLLE, the Netherlands, e-mail:
[email protected]
Introduction: The occurrence of AML during pregnancy
is an uncommon phenomenon that leads to serious consequences for mother and fetus. Treatment should start
as soon as possible and frequently causes many, serious
medical and ethical problems. We present two patients
with AML during pregnancy.
Cases: Patient A, a 26-year-old G2P1, was referred with
a gestational age of 41 weeks for hematoma and thrombocytopenia. The laboratory showed pancytopenia and
myeloblasts with Auer rods. The coagulation status was
compromised. Bone marrow aspirate showed the classic
picture of acute promyelocytic leukemia, with 84%
promyelocytes with faggots and Auer rods. Translocation
t(15;17) was present.All-trans-retinoic acid (ATRA) was
started immediately together with fresh frozen plasma
(FFP)and platelet transfusions. Three days later the
patient gave birth to a healthy daughter. Despite of
normal coagulation status before birth there was severe
hemorrhagia of 11 litre post-partum.Only after embolization of the internal iliac arteries the hemorrhage came
to halt. The patient was given massive blood, platelet and
FFP transfusions as well as NovoSeven® and minrin.
Prolonged admission at ICU was complicated by acute
45
The patient then received R-CVP and R-CHOP therapy.
Because of persistent symptoms the patient was re-treated
with Rituximab and Chloorambucil. In October 2012 this
maintenance treatment stopped until the recurrence in
March 2013.
Because of the poor response, the patient started with
the proteasome inhibitor Bortezomib and high dose
dexamethasone on an every 21-day cycle. However, the
patient complained of sudden onset of bilateral, painless
visual loss and headache on day 6 in this third cycle.
Blood pressure was 160/95 mmHg. Physical examination
demonstrated pupils in normal size, equal and reacted
to light. Neurologic examination and laboratory testing
showed no serious abnormalities. IgM lambda was 7.3
g/L. Approximately 1 hour later, the patient developed two
generalized tonic clonic seizures, treated with diazepam
rectal. Blood pressure was 200/100 mmHg.
Computed tomography brain scan including venogram
showed bilateral hypo densities in the parieto-occipital
regions. Magnetic resonance brain imaging demonstrated
bilateral occipital edema high suggestive for Bortezomib
induced PRES. Therefore the Bortezomib was withheld and
antihypertensives were started. Dexamethason was also
discontinued. The tonic clonic seizures were controlled
with phenytoin, levetiracetam and clonazepam. The
patient’s vision gradually improved over a several days,
although it never returned to normal. Unfortunately,
the Waldenström macroglobulinemia progressed further
during the recovery from PRES. No further treatment
was undertaken and the patient died from progressive
Waldenström macroglobulinemia some weeks later.
Conclusion: In this case report: a woman with
Waldenström macroglobulinemia developed PRES after
the third cycle Bortezomib/Dexamethasone treatment.
The pathogenesis of posterior reversible encephalopathy
syndrome remains unclear, but alteration in the integrity
of the vascular endothelium through NF-kb pathway,
is postulated as the underlying pathophysiology in
Bortezomib associated PRES.
tubular necrosis requiring dialysis, severe pulmonary
embolism with hemodynamic instability requiring thrombolysis and CPR. A week later treatment was started with
Idarubicin and ATRA. During all treatments that followed
many complications occurred and molecular relapse
was observed. More than three years after diagnosis the
patient is now in remission and her daughter develops
normally. Patient B, a 28-year-old, G3P1, presented at
a gestational age of 26 weeks with thrombocytopenia.
There were no abnormalities at physical examination. The
laboratory tests showed pancytopenia and some blasts
containing Auer rods typical for AML. The bone marrow
biopsy confirmed the diagnosis. Chromosomal translocation t(8;21) associated with ‘good risk’ was present.
Multidisciplinary consultation between hematologist,
gynaecologist and perinatologist decided for treatment with
idarubicin and cytarabine with frequent monitoring of the
fetus. Betamethasone was given for lung maturation of the
fetus. The first course of treatment was uncomplicated and
CR was obtained. At 32 weeks, before the second round of
chemotherapy, a healthy girl was born who was admitted
to the NICU. The second course was complicated by febrile
neutropenic and severe anxiety. More than three years after
diagnosis the patient is still in complete remission and her
daughter develops normally.
Conclusion: These cases of AML during pregnancy showed
that despite accurate and multidisciplinary treatment
approaches extensive and very serious complications can
occur. Both daughters develop normally.
C027 Bortezomib-induced posterior reversible encephalopathy syndrome (PRES) in a patient with
Waldenström macroglobulinemia
A.J.W. Gulpen, L.W. Tick
Máxima Medical Centre, Department of Internal Medicine,
De run 4600, 5504 DB VELDHOVEN, the Netherlands,
e-mail: [email protected]
Introduction: Posterior reversible encephalopathy
syndrome is an uncommon neurological syndrome that
is increasingly reported in association with anti-neoplastic
treatments. Symptoms are headache, visual disturbances,
altered mental status and seizures. Neuroimaging is
essential to the diagnosis. Characteristic radiologic features
are cerebral white matter edema, which typically involve
the parieto-occipital regions. It is usually reversible if the
underlying causative condition is eliminated.
Case: A 55-year-old woman with recurrent Waldenström
macroglobulinemia was admitted for her third cycle of
Bortezomib in August 2013. She was diagnosed in 2010
and received treatment with plasmapheresis followed by
chemotherapeutic agents chloorambucil and Rituximab.
C028 An unusual cause of liverabcesses
B.M.J. Scholtes, F.L.G. Erdkamp, F.P.J. Peters
Orbis Medical Centre, Department of Internal Medicine, Dr.
H. van der Hoffplein 1, 6162 BG SITTARD-GELEEN, the
Netherlands, e-mail: [email protected]
Introduction: Gastrointestinal stromal tumors (GISTs)
are the most common mesenchymal neoplasm of the
gastrointestinal tract, constituting only 1% of primary GI
malignancies. GISTs are generally discovered incidentally,
although they can become symptomatic. Pyogenic liverabscesses are most commonly related to hepatobiliary disease
46
(40-60%). We describe a case of liverabcesses induced by a
gastric GIST tumor combined with liverabscesses.
Case report: A 63-year-old woman presented to our
emergency department with fever 38.0 °C and dyspnea.
Because the X-ray was normal, a computed tomography
was performed to exclude pulmonary embolism.
Accidentally, we found a significantly enlarged liver
with multiple large hypodense structures suspect for
liver metastases. Blood cultures on admission showed
Streptococcus intermedius and the patient was treated with
intravenous antibiotics during two weeks. A liverbiopsy
showed no signs for malignancy, no cardiac souffle was
heared. To find a source for the probable liverabscesses
a colonoscopy was performed without abnormalities.
Finally, PET-CT revealed a large mass originating from
the stomach, located near the liver with the presence of
multifocal cystic necrotic livermetastases. A gastroscopy
showed a submucosal mass, but mucosal biopsies of
the lesion were nondiagnostic. A second liverbiopsy and
a laparoscopy were also nondiagnostic, only pus was
seen without grow of micro-organism . Clinically the
patient was not sick and afebrile without antibotics. To
obtain submucosal biopsies, we performed an endoscopic
ultrasound which confirmed a GIST measuring 6x6.5cm
and resection was performed. Follow-up computer
tomography after two months of antibiotic therapy showed
hardly no residual disease in the liver.
Discussion: This case shows that it is important to keep a
broad differential diagnosis, even if there is an initial strong
suspicon for metastases. S.intermedius has a tendency to
cause abscesses, commonly found in the liver and brain.
It is rarely the etiologic agent in infective endocarditis.
Furthermore, we know from the small amount of literature
that regardless of size and malignancy status, GISTs have
a tendency to disrupt gastrointenstinal mucosal integrity,
thereby allowing colonizing microorganism to gain access
to the circulation and spreading to the liver.
When confronted with a S. intermedius bacteraemia, one
should therefore always consider the possibility of a GIST
with liverabscesses.
which he received intensive chemotherapy followed by
autologous stem cell transplantation.
Five years later a CT examination revealed new pelvic and
intra-abdominal nodular lesions with largest diameters
21 and 15 millimeters, respectively. Under suspicion of a
second relapse, we decided to perform a CT-guided biopsy
of these lesions. During this procedure the localisation
of the lesions was found to have changed, but their size
remained the same. His medical history revealed that he
had undergone a laparoscopic cholecystectomy the year
before with intraoperative perforation of the gallbladder.
Thinking of gallstones in the free abdominal cavity, an
ultrasound was performed. The tumors were mobilisable
and had an acoustic shadow. This finding combined with
the history of cholecystectomy led to the diagnosis of free
gallstones in the abdominal cavity.
Even after a diagnose of relapsed Hodgkin’s lymphoma
not all masses have to be malignant and other differential
diagnosis must be kept in mind.
C030 Venetian Ball: underlying JAK2V617F mutation in a
patient with splenic vein thrombosis
E.H.C.C. Janssen, A.A.M. Ermens, R.S. Boersma,
J.W.J. van Esser
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
[email protected]
Introduction: Splanchnic vein thrombosis (SVT), which
includes splenic vein thrombosis, is associated with myeloproliferative disorders, therefore testing for JAK2V617F
mutation in patients with idiopathic SVT becomes more
and more accepted. We want to present a patient with
splenic vein thrombosis who had normal peripheral blood
counts without thrombocytosis, a positive JAK2V617F
mutation and abnormal megakaryopoiesis on bone marrow
biopsy.
Case description: A thirty-one year old woman, without
significant previous medical history, was referred because
of left flank pain. Abdominal ultrasound showed splenic
vein thrombosis. Full blood count was normal. INR,
aPTT, protein C, S and antithrombin levels were normal.
Testing for lupus anticoagulant, cardiolipin antibodies,
factor V Leiden- and prothrombin mutation were negative.
JAK2V617F mutation appeared to be positive and bone
marrow examination showed atypical megakaryopoiesis,
compatible with essential thrombocytosis, however without
peripheral thrombocytosis. Treatment consisted of vitamin
K antagonist for one year, followed by acetylsalicylic acid.
Follow up ultrasound showed complete resolution of
splenic vein thrombosis.
C029 Mobile tumors in a patient with Hodgkin’s
lymphoma
B.M.J. Scholtes, F.P.J. Peters, F.L.G. Erdkamp
Orbis Medical Centre, Department of Internal Medicine, Dr.
H. van der Hoffplein 1, 6162 BG SITTARD-GELEEN, the
Netherlands, e-mail: [email protected]
We present a 37-year-old man, who was diagnosed with
stage IIIB nodular sclerosing Hodgkin’s lymphoma seven
years ago. Complete remission had been reached after 6
ABVD cycles, but a year later a relapse was diagnosed for
47
Discussion: This case underlines the important role
of JAK2V617F mutation in idiopathic SVT in a patient
without thrombocytosis. A systematic review showed that
49% of patients with idiopathic SVT appeared to have
JAK2V617F mutation. 52.4% of patients with SVT and
JAK2V617F mutation ultimately developed a myeloproliferative disorder during follow-up. Screening for JAK2V617F
mutation in patients with SVT seems to be justified.
the temperature normalized. After 6 days the ESR and
CRP were decreased to 34 mm/hr and 6 mg/L respectively.The pathologist was asked to reconsider the lung
biopsy material. Pathological findings then proved to be
compatible with a diagnosis of vasculitis.
Conclusion: Despite thorough examination no infectious
agent was determined in this HCL patient. Clinical signs
of temporal arteritis led to the explanation of the persistent
fever and interstitial lung disease, namely vasculitis.In the
literature an association between HCL and vasculitis is
described. There are also some reports on vasculitis as a
complication of treatment with cladribin. The time course
in this patient suggests that the vasculitis was provoked by
administration of cladribin. Prednisone gave immediate
improvement.
C031 Temporal arteritis and hairy cell leukemia: a
coincidence?
J.A.L. van Kempen, J. Markhorst, J.M.M. Raemakers,
E.J.M. Mattijssen
Rijnstate Hospital, Department of Internal Medicine,
Postbus 9555, 6800 TA ARNHEM, the Netherlands, e-mail:
[email protected]
C032 Erythroderma: from drug eruption to malignancy
M. Smits, H.T.J. Roerdink
Twee Steden Hospital, Department of Internal Medicine,
Doctor Deelenlaan 5, 5042 AD TILBURG, the Netherlands,
e-mail: [email protected]
Introduction: Hairy Cell Leukemia (HCL) is a rare variant
of Chronic Lymphatic Leukemia. The most common
problem of patients with HCL is immunosuppression.
Depending on the degree of suppression, treatment with
the purine analogue cladribin is necessary. This treatment
causes temporary further deterioration of the immune
system with suppression of mainly CD4+lymphocytes.
Hence, the most common side effects of this treatment are
fever and opportunistic infections.We here describe that
other serious causes of fever should also be considered.
Case: A 73-year old male patient with HCL started with
cladribin therapy. At the start, he had no complaints, no
fever, and a blood count with Hb 6.0 mmol/L, leucocytes
1.0 x 109/L (neutrophils 0,29 x 109/L, monocytes < 0,10 x
109/L), and platelets 45 x 109/L. At the fifth day of cladribin
therapy, he developed fever and was admitted to the
hospital.At presentation, the patient was not acutely ill
with a temperature of 38.9oC. He had an already longer
existing rash on his back. Blood tests showed anemia
(Hb 4.5 mmol/L), leucopenia (0.6 x 109/L), a high ESR
(125 mm/hr), and a high CRP (329 mg/L). Chest X-ray
and a subsequently made HR-CT of the lungs showed
interstitial lung disease. Empiric antibiotic therapy with
Ceftazidim was started. Cultures remained negative, there
was no evidence for mycobacterial disease. Because of
deteriorating pulmonary abnormalities, a bronchoalveolar
lavage with bronchoscopic biopsy was done after rigorous
platelet substitution. No pathogens were found.In the
meantime the patient developed a progressive stinging
headache located right fronto-temporal with an enlarged,
pulsing and painful right temporal artery. The echo-duplex
of the temporal artery was normal. ANA and ANCA were
both negative. Because the clinical presentation was
suspicious for temporal arteritis prednisone 60 mg daily
was started. The next day the headache disappeared and
Introduction: The diagnosis in patients with erythema
is frequently difficult. Erythroderma is a rare diffuse
erythema involving skin of more than 90% of the total
body surface area. The differential diagnosis is broad,
including cutaneous systemic and malignant diseases.
Primary cutaneous anaplastic T cell lymphomas have low
incidence. We present a patient with progressive diffuse
erythema, who was admitted at the cardiology department
with dyspnea and peripheral oedema.
Case: A 79-year old patient was admitted with dyspnea
and peripheral oedema after placing a pacemaker two
weeks before. He had developed a rash since two months
after using a cream for actinic keratosis. Because of polypharmacy the dermatologist diagnosed a drug eruption and
the patient was treated with antihistamines.
During hospitalisation lymphadenopathy, crepitations over
his lungs, peripheral edema in his legs, arms en scrotum
and erythroderma of total body surface area developed.
Blood tests showed leukocytosis and elevated lactate
dehydrogenase. CT-scan of the neck, thorax and abdomen
showed generalised lymph node enlargement. Biopsy
of a lymph node indicated anaplastic T-cell lymphoma.
In bone marrow aspirate, ceribriform lymphocytes were
seen. Considering the trias of erythroderma of total
body surface area, generalised lymphadenopathy and
ceribriform lymphocytes, the diagnosis Sezary syndrome
was made.
Considering patient was older than sixty, Karnofsky
performance status was low (30) and elevated lactate
dehydrogenase (453 U/L), it was decided to start continuous
48
C034 A skin lesion that catches the eye
chlorambucil in combination with prednisone. Peripheral
oedema and pulmonary oedema disappeared and erythroderma reduced. The patient was able to walk again and
was discharged with daily chlorambucil and prednisone.
Conclusion: This case underlines an important lesson.
In the differential diagnosis of erythroderma, Sezary
syndrome although rare, should be considered. What
looks like a simple rash, can be a fatal malignant disorder
in the end.
L. Louter, I. Botden, R.F.J. Schop
IJsselland Hospital, Department of Internal Medicine, Prins
Constantijnweg 2, 2906 ZC CAPELLE A/D IJSSEL, the
Netherlands, e-mail: [email protected]
Case Report: A 72-year-old female patient presented with
fever, night sweats and multiple skin lesions. Multiple
erythematous cutaneous nodules were present on the
upper extremities and abdomen. During admission a
subconjunctival lesion appeared and progressed rapidly.
Laboratory results showed: haemoglobin 7.2 mmol/L,
leucocytes 1.3 x 10^9/L, thrombocytes 99 x 10^9/L, lactate
dehydrogenase 857 IU/L and haptoglobin < 0.1 g/L. Viral
and autoimmune serology were negative. Computed axial
tomography of chest and abdomen revealed multiple
solid nodular lesions in both kidneys. Histopathological
examination of skin biopsy revealed infiltration of atypical
lymphocytes with hyper chromatic irregular nuclei.
Immunophenotyping by immunohistochemical analysis
characterised the infiltrate as CD2+, CD3+, CD4-, CD5-,
CD7-, CD8-, CD 20-, CD30- and CD56-. Polymerase chain
reaction amplification revealed clonal rearrangement of the
T-cell receptor gamma chain gene. Clonal gamma-delta
T-cells were also detected by immunohistochemical
analysis of peripheral blood and bone marrow. These
findings together were consistent with stage IV primary
cutaneous gamma-delta T-cell lymphoma (PCGD-TCL)
accompanied by multiple extra nodal manifestations
(renal and subconjunctival). Our patient was treated with
two cycles of CHOP (cyclophosphamide, doxorubicin,
vincristine and prednisone). Unfortunately, her clinical
condition deteriorated rapidly. She declined further therapy
and died within three months of initial presentation.
Discussion: PCGD-TCL is rare and only represents 1% of
all cutaneous T-cell lymphomas. To our knowledge, only
40 cases have been described. PCGD-TCL is composed of
a clonal proliferation of mature, activated gamma-delta T
cells with a cytotoxic phenotype. In 70%, cells show clonal
rearrangement of the T-cell receptor gamma gene. It often
presents with generalized skin lesions, preferentially
affecting the extremities. There is a well-documented
association with haemophagocytic syndrome. PCGD-TCL
is often resistant to chemotherapy and radiotherapy.
Systemic multi-agent chemotherapy CHOP has previously
been used. In young patients allogeneic haematopoietic
stem cell transplantation should be considered. Most case
reports describe an aggressive clinical course with an
estimated mean survival of 15 months.
Conclusion: Primary cutaneous gamma-delta T-cell
lymphoma is a very rare and aggressive lymphoma
with poor prognosis, which is often associated with
heamophagocytic syndrome.
C033 An unusual cause of jaundice: stick to the whole
picture
H.K. van Halteren, K. Moor, H.J. Agteresch
Admiraal de Ruijter Hospital, Department of Internal
Medicine, Postbus 3200, 4380 DD VLISSINGEN, the
Netherlands, e-mail: [email protected]
Case: A 70-year old woman was admitted to the hospital
because of jaundice and upper abdominal pain. In the
past year, she had been treated with chemotherapy for ISS
stage I multiple myeloma (very good partial response) and
she had undergone radiotherapy for an extramedullary
plasmacytoma of the right cheek.
A month prior to hospitalization she had developed a numb
chin; Brain-MRI showed multiple bone lesions, including
the base of the skull, and radiotherapy had been planned.
Laboratory results were compatible with disease progression
and second line systemic therapy was anticipated. At hospitalization the patient reported loss of appetite, discolored
stools and brown-colored urine. At physical examination
she revealed no fever, but an enlarged liver.
Laboratory results were: ASAT 238 u/L, ALAT 251 u/L,
LD 463 u/L, conjugated bilirubin 163 umol/L, alkaline
phophatase 737 u/L. CT-scan revealed bilateral pulmonary
nodules, a space-occupying lesion in the pancreatic head
with obstruction of intra- and extrahepatic bile ducts and
multiple nodular liver lesions. The most likely diagnosis
at that time was a pancreatic malignancy with hepatic
and pulmonary metastases, but infiltration by multiple
myeloma had to be excluded. Weekly high dose dexamethasone was initiated and a liver biopsy was planned. A
few days after the first dexamethasone gift the bilirubin
concentration started to return back to normal. The liver
biopsy showed a homogeneous population of CD138positive cells, which was compatible with an extramedullary plasmacytoma.
Discussion: Simultaneous involvement of pancreas, liver
and lungs is very rare in multiple myeloma. Most case
reports of organ infiltration include the liver and reported
patients usually had a very poor disease outcome. Every
doctor should bear in mind that multiple myeloma can
mimick advanced solid malignancies.
49
C035 ITP with a touch of Japan (This presentation comes
with images of the X-ray, the CT and photos of the
patient)
submit an adult with a hematological condition, an intellectual disability and/or dysmorfic features to a clinical
geneticist.
S.E. de Boer1, J.J. Wegman1, A.S. Brooks2
Deventer Hospital, Department of Internal Medicine, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected], 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands
1
C036 A ‘cyclic’ neutropenia due to adulterated cocain
N.S. Vos, E.A.F. Haak, O.C. Leeksma
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: [email protected]
A 34-year old male was referred to the hospital because
of thrombopenia, discovered by his general practioner
which he visited because of wet and dry purpura. His
medical history was remarkable for mild intellectual
disability, recurrent pateller dislocations and hearing
loss with unilateral microtia. He used no medications.
During physical examination, it was noted that he not
only had unilateral microtia, but also a remarkable face
and a short fifth finger on both hands. The laboratory
results were found to be normal, apart from a low platelet
count: 9 per nanoliter. An X-ray of the chest showed a
spherical abnormality on the right side of the pericardium
and a partial relaxation of both hemidiaphragma. A
CT-scan showed that the abnormality on the right side
of the pericardium was actually a delusion, caused by an
eventration of the right diaphragm that was filled with
liver. The patient was diagnosed with immune thrombocytopenia (ITP) and successfully treated with prednisone.
We were curious to find out if there was a syndromal
diagnosis that could explain the medical history, the
remarkable face and fingers, the eventration of the right
diaphragm and the ITP. Therefore, we consulted a clinical
geneticist. Her spot diagnosis was that the patient had
Kabuki syndrome; a rare disorder that was first described
in 1981 in Japan. The syndrome is characterized by
unusual facial features, skeletal abnormalities and intellectual disability. Autoimmune abnormalities have also
been described in several patients. All of our patients’
features were described in literature. The name of this
disorder comes from the resemblance of its characteristic
facial appearance to stage makeup used in traditional
Japanese theater called Kabuki. In 2010, it was discovered
that 66-75% of the patients had a mutation of the
MLL2-gene; a gene that codes for a protein important in the
epigenetic control of active chromatin states. Our patient
had a mutation of this gene. Because patients with the
Kabuki syndrome often have eye and / or heart problems,
our patient was seen by an ophthalmologist and a cardiologist. Luckily, he had no eye or heart problems.
We think that most hematologists are familiar with
syndromes that are accompanied by hematological
disorders at a young age, like Down syndrome with
leukemia and Noonan syndrome with myelodysplastic
syndrome. This case shows that it also can be worthful to
Background: Since 2009, a warning for cocain adulterated
with levamisole has been issued, mainly in the USA
and Canada. Levamisole is a drug, originally developed
as an antihelmintic agent, and used in the 1970s as an
immunomodulatory agent in the treatment of cancer
and in veterinary medicine. Agranulocytosis was well
recognized as an idiosyncratic reaction, occurring in 3-10%
of patients exposed to levamisole. A strong association was
seen between the HLA-B27 genotype and susceptibility to
levamisole-induced agranulocytosis. The mechanism of
HLA-B27 associated levamisole-induced agranulocytosis is
unknown as well as the role of subtypes of HLA-B27. The
prevalence of HLA-B27 in the Caucasian population is 9%.
The percentage of cocain samples containing levamisole
has increased in recent years. In 2012, 62% of random
samples were tested positive for levamisole by the ‘Trimbos
Instituut’ in the Netherlands.
Case description: A 36-year-old male was referred because of
an episode of high fever and infections on hands, mouth and
ears. A diagnostic laboratory test showed a leucocyte count of
1.4 x 10^9/L with a neutrophil count of 0.002 x 10^9/L. After
treatment with antibiotics, the infections and neutropenia
recovered. Additional diagnostic blood and radiology analyses
to explain the neutropenia did no show any abnormalities
and it was ascribed to NSAID use. One and a half month
later, the patient presented with the same symptoms and a
leucocyte count of 2.3 x 10^9/L with a neutrophil count of 0.1
x 10^9/L, without using NSAID’s. Bone marrow aspiration
showed a hypo- to normocellular marrow and a myelodysplastic syndrome could not be excluded. In the meanwhile,
the patient was admitted to the emergency care unit with
signs of an intoxication. A urine test showed the presence
of metabolites of cocain and the presence of levamisole was
demonstrated by additional blood analysis. Later this patient
was tested positive for HLA-B27. After discontinuing cocain
use and treatment of the infections with antibiotics, the
neutropenia fully recovered and did not recur. Six months
later, the patient is still in good health.
Conclusion: This is a case of acquired agranulocytosis, due
to the use of cocain adulterated with levamisole. In case
of an apparently idiopathic neutropenia, the possibility of
adulterated narcotics must be considered.
50
C037 A very rare cause of polycythemia: unilateral renal
lymphangiectasia
neous or laparoscopic aspiration, marsupialization of larger
cyst or nephrectomy. Our patient underwent nephrectomy
because of polycythemia, hypertension and a decreased
function of the diseased kidney.
A. Breedijk, L.J.M. Reichert
Rijnstate Hospital, Department of Internal Medicine,
Wagerlaan 55, 6800 TA ARNHEM, the Netherlands, e-mail:
[email protected]
C038 Haemophagocytic syndrome due to an extranodal
NK/T-cell lymphoma
Case: A 19-year old women was referred by the cardiologist
to our outpatient clinic with dyspnea and polycythemia.
A cardiac origin was ruled out. She had no significant
previous medical history. Physical examination revealed
mild hypertension (142/92mmHg). Blood tests showed
increased hemoglobin (12.1 mmol/L) and haematocrit
(0.58 L/L) with normal white cell and platelet counts.
Serum erythropoietin was in the upper level of normal
(15.6 U/L). A JAK2 mutation was absent. A primary form
of polycythemia therefore seemed unlikely. There were no
clues suggesting hypoxia or cardiopulmonary disease as a
cause of secondary polycythemia. Ultrasonographic images
of the abdomen revealed an enlarged abnormal right
kidney with multiple cysts in the periphery and peripelvic
area. These findings were consistent with the diagnosis of
unilateral renal lymphangiectasia. In addition, a CT scan
showed an abnormal abdominal venous anatomy. Most
prominent was an abnormal trajectory of the vena cava
inferior on the left side of the aorta and the absence of the
right renal vein. Renography showed a severe decreased
function of the right kidney. Our patient was first treated
with phlebotomy, aspirin and ACE inhibition. Eventually,
she underwent a laparoscopic nephrectomy of the right
kidney.
Discussion: Renal lymphangiectasia is an extremely rare
benign disorder characterized by developmental malformation of the perirenal lymphatic system. Patients can
present at any age, typically with acute symptoms of
abdominal pain and distention, accompanied variously by
hypertension, erythrocytosis, hematuria, proteinuria, or
renal dysfunction. The lesions are almost always bilateral
(> 90%) but may present as a unilateral mass.
The unilateral renal lymphangiectasia probably originates
from failure of the developing renal lymphatic tissue to
establish normal communication with the remainder of
the lymphatic tissue. Ultimately, this leads to formation
of cysts. However, our patient had abnormal venous
anatomy with agenesis of the right renal vein, most likely
congenital. Thrombosis in utero of the right renal vein
cannot be excluded. Impaired drainage of the right kidney
and ectasia of the intrarenal lymphatic channels led to the
formation of cysts. Increased production of erythropoietin
by this abnormal kidney resulted in polycythemia. This
abnormality has been reported in a few cases.
Treatment is not required in the majority of cases.
However, complicated cases may be treated with percuta-
S.J.C. van Bergeijk, M. Westerman, F. Stam
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: [email protected]
Introduction: Haemophagocytic syndrome (HFS) is a life
threatening, rare disorder, characterised by an extreme
systemic inflammatory response, cytopenias, hepatosplenomegaly, hyperferritinemia and haemophagocytosis.
This is due to pathological immune activation by dysfunctional natural killer (NK) and/or cytotoxic T-cells, causing
persistent cytokine release, proliferation and activation of
macrophages. HFS can be divided in a primary, genetic
form and a secondary form, associated with infections,
haematological malignancies or auto-immune diseases.
Diagnosis is often delayed because early signs and
symptoms are nonspecific.
Case: A 48-year old man, with an unremarkable medical
history, presented at the emergency ward with fever,
night sweats and fatigue during the last 10 days. Physical
examination showed no abnormalities except for a slightly
enlarged spleen. Laboratory results revealed pancytopenia
(haemoglobin 6.3 mmol/L, leucocytes 2.9 x 109 mmol/L,
thrombocytes 41 x 109 mmol/L), atypical lymphocytes,
elevated transaminases and C-reactive protein (41 mg/L).
On suspicion of a viral infection, serologic testing was
performed and an outpatient appointment was made.
However, after 3 days the patient was readmitted because
of persistent fever, left upper quadrant abdominal pain
and collapse. Physical examination showed a haemodynamically instable patient (blood pressure 90/50 mmHg,
pulse 135 bpm, temperature 39.6° Celcius). Laboratory
results revealed severe lactic acidosis, progression of
anaemia, further increase of transaminases and lactate
dehydrogenase, acute renal failure and signs of diffuse
intravasal coagulation. Computertomography showed
a haemoperitoneum with an inhomogeneous enlarged
spleen without active bleeding. Because of systemic
inflammatory response syndrome (SIRS), multi-organ
failure, pancytopenia and splenomegaly with spontaneous
bleeding, HFS was suspected. This was confirmed by
enormous elevation of the ferritin-level (56,990 ug/L),
decreased fibrinogen (0.8 g/L) and increased triglycerides
(3.5 mmol/L). In addition, bone marrow investigation
showed haemophagocytosis. Because of the haemodynamic
51
instability a splenectomy was performed and treatment
with dexamethason, etoposide and cyclosporine according
to the HLH-2004 protocol was started. This resulted
in clinical improvement and an impressive decrease in
ferritin (1088 ug/L) after 4 days. Serological analysis
showed IgG, and not IgM, against Epstein Barr Virus
(EBV) and an EBV viral load of 193.000 IU/L. Pathological
analyses of the resected spleen revealed the presence of an
extranodal NK/T-cell lymphoma. This is an extremely rare,
EBV related lymphoma with poor prognosis. It is highly
associated with HFS because of dysfunctional monoclonal
NK/Tcells.
Conclusion: It is important to consider HSF in patients with
pancytopenia, hepatosplenomegaly and SIRS. Ferritin levels
of more than 10.000 ug/L are sensitive and specific for
HFS, especially if combined with other diagnostic criteria.
(with only one non-serious infectious complication), a
FDG-PET scan showed complete remission in August 2013.
Discussion: Approximately 10 percent of HIV-infected
patients will develop a malignant lymphoma. More than
90 percent of HIV-related lymphomas are highly aggressive
diffuse large B cell lymphomas and Burkitt lymphoma. A
CD4 count below 100 cells/microL is a risk factor, as well
as coinfection with Epstein Barr virus. In our patient the
presentation appeared to be compatible with a small cell
MALT type gastric lymphoma. Although there is recent
evidence that the incidence of indolent lymphomas appear to
increase in HIV-infected patients, although very rare when
CD4 counts are below 100 cells/microL, they represent only
a very small proportion of HIV-related lymphomas. We want
to highlight the importance of reconsidering the diagnosis
of indolent lymphoma in a HIV positive patient, especially
if based on gastric biopsies with its inherent cumbersome
interpretation, and to stress the need for rebiopsy. A critical
reconsideration might change diagnosis and the associated
important therapeutic consequences and prognosis.
C039 Indolent lymphoma in a HIV-positive patient: keep
your mind open
T. Vrijmoeth, J.M.M. Raemaekers
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
C040 Vegetables are not always healty
B. Santbergen, M. Durian
St. Elisabeth Hospital, Hilvarenbeekseweg 60, 5022 GC
TILBURG, the Netherlands, e-mail: [email protected]
Case: We describe a 57-year old homosexual male who
presented with upper abdominal pain since 6 months. His
medical history was unremarkable. He used pantoprazole
since a few months without signifcant improvement. At
physical examination there were no abnormalities found.
Laboratory results showed thrombocytopenia of 82 x
10^9/L, H.pylori serology was positive At gastroscopy a
gastric ulcer was found suspected for H.pylori infection
and eradication therapy was given with some clinical
improvement. Histologic examnination of the various
gastric mucosal biopsies however showed no active H.
pylori infection but a predominantly small cell (with some
interspersed large cells) MALT-type malignant lymphoma.
The HIV status proved to be positive with a CD4 count of
80 cells/mul. Because HIV-positive patients – in general
– develop aggressive types of lymphomas, a renewed
endoscopy was performed: a residual ulceration was seen
and renewed biospy specimens now showed a diffuse
large B-cell lymphoma, EBER positive. In retrospect and
after extensive review the original biopsy specimens could
already been regarded as large cell lymphoma. Staging
procedures revealed a CS IIIA disease with accompanying
FDG-PET positive abdominal, axillary and mediastinal
lymphadenopathy and less intense inguinally, while bone
marrow was negative The patient started on antiretroviral
therapy and received 8 cycles of chemotherapy consisting
of rituximab, cyclophosphamid, doxorubicin, vincristin
and prednison (RCHOP21). After 8 cycles of chemotherapy
Introduction: Almost 7,5% of the world population has a
mutation in the glucose-6-phospate-dehydrogenase (G6PD)
gene. This can result in a phenotype with G6PD-deficiency,
presenting with hemolysis in periods of oxidative stress,
caused by infections, medications or other agents
Case: A 55-year old man of Congolese origin, presented at
our emergency room because of tiredness and dyspnoea
d’effort. He had a medical history of HIV (treated with
truvada and viramune) and a cryptococcol meningitis 6
years ago, which was treated with amphotericin B and
fluconazol. In 2011 he was admitted at our hospital because
of haemolysis. Investigations at that time didn’t confirm a
diagnosis. The treating physician thought it could be evoked
by fluconazol. The haemolysis appeared to be self limiting.
Now, at physical examination, no lymphadenopathy or
splenomegaly was present. Blood investigation showed
a normocytic anaemia of 2,8 mmol/L. Leucocytes and
trombocytes were normal. Haptoglobuline wasn’t detectable
and reticulocytes were very low. Lactatedehydrogenase
was elevated up to 8000 u/L and bilirubine was normal.
In conclusion our patient had a haemolytic anaemia.
Levels of vitamin B12 and folic acid were normal. Direct
antiglobulin testing (DAT) was negative. Results for viral
infections were also negative (EBV, CMV, mycoplasma,
parvoB19). By suspicion of a disorder in the membrane or
enzymatic function of the erythrocyte, further testing of the
52
erythrocyte was ordered . Before we achieved results of this
testing, again the haemolysis resolved. Our tests showed
a very low level of glucose-6-phosphate-dehydrogenase
(G6PD). So we thought the haemolytic anaemia in our
patient was caused by a G6PD-deficiency.
Hemolysis due to G6PD-deficiency is most frequently
evoked by infections, medications . But also less common
reasons can induce hemolysis, like henna and broad beans.
Our patient did not have signs of an infections and literature
didn’t show truvada of viramune causing haemolysis by a
G6PD-deficiency. In a telephone call with the HIV-nurse the
patient admitted he had eaten many broad beans in the past
few weeks. So finally we had found the cause of haemolysis
in our patient. This disorder is also called favism.
Conclusion: In G6PD-deficiency, hemolysis is caused
because of the reduced activity of the G6PD and therefore
less protection of erythrocytes against oxidative stress. It
isn’t clear in which way broad beans cause the oxidative
stress. Hemolysis due to G6Pd-deficiency can be treated
by removing the evoking agents. In our patient, after
admission and discontinuing eating broad beans, the
hemolysis disappeared.
of the G6PD enzyme in response to oxidative stress.
G6PD is X-linked and is inherited according to Mendel’s
laws. At least 186 mutations are known. G6PDd can be
subdivided into five classes. Class II (mainly prevalent in
Mediterranean countries and Asia) and III (Africa and
Asia) are by far the most prevalent classes and are selflimiting. Class II can result in severe anaemia. In class III
there is still a substantial residual enzymatic activity at the
time of AHA, resulting in only mild symptoms.
The estimated prevalence of cal II and III G6PDd ranges
from < 1% to 32.5% in African and Asian countries.1 In
countries with a high prevalence, neonates are screened
for G6PDd. In the Netherlands, G6PDd is not part of the
neo-natal screening. With an increasing number of second
generation immigrants, the prevalence of undetected
G6PDd in the Netherlands will likely increase.
Conclusion: G6PD deficiency is a highly prevalent
deficiency that results in AHA in response to common
oxidative stress factors. As it is most commonly selflimiting, it is very well possible that patients are diagnosed
at older age. This is especially relevant in Western European
countries, such as the Netherlands, where G6PD is not part
of the neo-natal screening.
Howes et al. PLos One 2012 doi:10.1371/journal.
pmed.1001339
C041 G6PD deficiency important beyond infancy
R. Knevel, R. Klinkenberg, F.H. Heyning
Medical Centre Haaglanden, Department of Internal
Medicine, Lijnbaan 32, 2512 VA DEN HAAG, the Netherlands,
e-mail: [email protected]
C042 A patient with megaloblastic anemia and hemolysis
I.H.A. Zegers, E.A.M. Beckers
Maastricht University Medical Centre, Department of
Hematology, Martin lamkincour 37, 6225 EM MAASTRICHT,
the Netherlands, e-mail: [email protected]
Introduction: Glucose-6-phosphatase dehydrogenase
(G6PD) is an enzyme that is essential for the stability of
erytrocytes. G6PD deficiency (G6PDd) causes haemolytic
anaemia as a result of oxidative stress such as infections
or medication use. Generally, G6PDd is conceived as a
diagnosis made in childhood. We present a patient that
we diagnosed with G6PD deficiency at the age of 60.
Subsequent literature research demonstrated that this case
was not as surprising as one may think.
Case report: A 60-year old Indonesian male was presented
at the emergency room with elevated inflammation
parameters due to an urinary tract infection. In addition,
he had a haemolytic anaemia and methehemoglobinemia.
Subsequent analyses demonstrated lowered G6PD levels.
Research question: How likely is the detection of a G6PD
deficiency in adulthood?
Methods: To answer this question a literature research
in PubMed was performed using ‘Glucosephosphate
Dehydrogenase eficiency/diagnosis’[Mesh][quotrightB].
This resulted in 564 hits, of which 74 reviews.
Results: With a prevalence of 400 million, G6Pd is one of
the most commonest enzyme deficiency world-wide. Acute
haemolytic anaemia (AHA) can occur due to an instability
Introduction:The diagnostic work-up of hemolytic anemia
might be challenging, but is essential to start adequate
treatment. We report a rare, albeit well-known, cause of
hemolysis.
Case-report: A 45-year old man presented with fatigue and
malaise. There was an estimated unexplained weight loss
of eight kilograms in the past six months.. There were no
complaints of vomiting, no defecation problems, fever or
night sweats.
Medical history revealed a young stroke, hypertension and
hypercholesterolemia. He used dipyridamol, telmisartan,
pantozol and calciumcarbasalaat. An intolerance for statins
had been established. He smoked 20 cigarettes/day, denied
any use of alcohol.
At presentation he appeared anemic; hemodynamic
stable, BMI of 37. Physical examination of heart, lungs,
abdomen was unremarkable; without lymphadenopathy or
hepatosplenomegaly.
Hemoglobin (Hb) was 4.0mmol/L, mean corpuscular
volume (MCV) of 130fL; normal white blood cell and
53
platelet count. Absolute reticulocytes were low: 10 x
10*9/L. Peripheral blood smear showed hypersegmentation, toxic granulations, megalocytes, some tear drop
cells, no fragmentocytes or spherocytes. Lactate dehydrogenase (LD) was elevated: 2678U/L, bilirubin 14.8umol/L,
haptoglobine < 0.10g/L. A hemolytic work-up was started:
direct antiglobulin test was negative. In serum no autoantibodies nor monophasic/biphasic antibodies were found.
Flow cytometry of peripheral leukocytes was normal,
excluding PNH or monoclonal B-and T-lymphocytes.
Vitamin B12 level was normal, but folic acid appeared low:
2.5nmol/L (normal range 3-20).
Clinical course: The lack of adequate reticulocyte response
was attributed to the low folic acid concentration. Because
of symptomatic anemia the patient was transfused with
two units of packed cells. Simultaneously suppletion
with folic acid 5 mg qd was started. Subsequently acute
Infections with cytomegalovirus, parvovirus B19 and
epstein barr virus were excluded.
After three days of suppletion with folic acid the expected
rise in reticulocyte count did not appear. Bone marrow
examination showed hypercellularity with left shift of the
erythropoiesis and myelopoiesis, indicating active hematopoietic recovery. There were no signs of Myelodysplastic
syndrome or myeloproliferative neoplasia. Cytogenetic
analysis showed a normal karyotype. On day 7 the expected
increase in reticulocytes was observed yet: absolute 413
x 10*9/L. Three weeks later Hb achieved a value of
7.4mmol/L and MCV 111fL. LD had normalized to 172 U/L.
Conclusion: Despite marginally lowered folic acid level
this patient exhibited a severe megaloblastic anemia with
hemolysis as signs of ineffective erythropoiesis, which
fully recovered after folic acid suppletion. Most probably,
by the absence of specific drug interactions and his
persistent denial of alcohol abuse, the cause of the folic acid
deficiency is purely nutritional.
recipients. In both non-renal solid organ and in non-transplant recipients BKVAN is extremely rare. We describe
a histologically confirmed BKVAN in a patient with
Waldenström’s macroglobulinaemia (WM) with deteriorating renal function. Despite therapy with leflunomide
and gammaglobulin infusion correcting hypogammaglobulinaemia chronic hemodialysis was inevitable.
C044 Unusual cause of prolonged aPTT and PT
L. Both, G.A. Velders
Gelderse Vallei Hospital, Department of Internal Medicine,
Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, e-mail:
[email protected]
Introduction: The occurrence of inhibitors to coagulation
factors is rare. Auto-antibodies directed against factor V are
extremely rare. The clinical presentation may vary greatly,
from asymptomatic presentation with only laboratory
abnormalities to life-threatening bleeding. We present a
case of an 82-year old woman with an acquired factor V
inhibitor.
Case: An 82-year old female was admitted to our hospital
with a bilateral pneumonia. She had a history of a
rectumcarcinoma and a cervixcarcinoma, both surgically
resected and followed by postoperative radiotherapy. In
2012 she underwent transurethral resection of a bladder
tumour. She was treated with acenocoumarol because
of a cross-over bypass. On admission the international
normalized ration (INR) was greater than 8 for which
vitamin K 10 milligrams was administered orally resulting
in an INR of 2.1 the following day. The pneumonia was
treated with cefotaxim and ciprofloxacin intravenously. On
day 3 the INR was again greater than 8. Repeated doses of
intravenous vitamin K and protrombin complex did not
normalize INR. No signs of disseminated intravascular
coagulation of liver failure were found. Laboratory tests
revealed a prolonged aPTT (166 seconds) and prolonged
PT (101 seconds and a normal fibrinogen (4.8 g/L).The
presence of an inhibitor to factor V, II or X seemed likely.
A CT scan was performed. No signs of a malignancy were
found. No serum m-protein was measured. At Sanquin
(Amsterdam, the Netherlands) the coagulation factors were
measured showing an undetectable level of factor V with
an inhibitor of 100 Bethesda units. Patient was started on
prednisone 1 mg/kg orally. Besides prolonged bleeding
time after venapunction, she did not have any clinically
relevant bleeding. In this patient the acquired factor V
inhibitor was most likely due to the use of antibiotics
(cefotaxim or ciprofloxacin).
Discussion: Inhibitors of coagulation factors should be
suspected in patients with no response to administration
of sufficient coagulation factors. The presence of factor V
C043 BK virus associated nephropathy in a patient with
macroglobulinaemia
D.J.T.H. Tjwa1, E. Steenbergen2, G.S.M. Madretsma1,
J.N.M. Barendregt1
1
Gelre Hospital, Department of Internal Medicine, Albert
Schweitzerlaan 31, 7334 DZ APELDOORN, the Netherlands,
e-mail: [email protected], 2Radboud University Medical
Centre, NIJMEGEN, the Netherlands
Polyomavirus BK (BKV) has ubiquitous presence in
the general population but is usually asymptomatic
in immunocompetent individuals. In immunodeficient patients BKV accounts for various disorders. BK
virus associated nephropathy (BKVAN) is a well-known
complication in approximately 8% of renal transplant
54
Discussion: This case shows the classical signs of a
multicentric form of CD, probably triggered by HHV-8infection. CD is a very rare disorder with a variable
clinical course, ranging from asymptomatic to aggressive,
rapidly fatal presentations. Aggressive forms of CD are
predominantly associated with HIV-infections, but may
occur in HIV-negative patients. Severe courses are mainly
caused by inflammatory syndromes, auto-immune disease,
multi-organ failure and malignancies (e.g. NHL, Kaposi
sarcoma). Thus far, there is no specific treatment for this
heterogeneous disease. Therapeutic options like cytoreductive chemotherapy, rituximab, anti IL-6 antibodies
(tocilizumab) show remarkable disease stabilization
in HIV-negative patients. The role of antiviral therapy
remains unclear. However, results of all regimens in
fulminant, aggressive CD are disappointing.
Conclusion: This dramatic case underlines the necessity of
an urgent extensive work-up, when the clinical presentation
and effect of treatment in hemolytic anemia is uncommon
or ineffective.
inhibitor is exceedingly rare and occurs most often after
the use of antibiotics such as B-lactams, aminoglycosides,
cephalosporins and chinolones. It is also associated with
malignancies or auto-immune diseases. The level of
the inhibitor does not correlate with bleeding tendency.
In the event of bleeding transfusion of trombocytes
as well as activated factor VIIa can be administered.
Immunosuppressive agents as corticosteroids as single
agent or in combination with Cyclophosphamide or
Rituximab have been described to successfully suppress
auto-antibody production. Plasmapheresis can also be
attempted.
C045 Severe hemolytic anaemia: a fatal case with an
unlikely cause
J.M. de Feijter, D.R.S.G. Mostard, D.R.J. Buijs
Atrium Medical Centre, Department of Internal Medicine,
Henri Dunantstraat 5, 6419 PC HEERLEN, the Netherlands,
e-mail: [email protected]
Introduction: Anemia is a frequently encountered
symptom in the Emergency Room. In a minority of
cases anemia is due to hemolysis. This entity has a broad
differential diagnosis, including vitamin deficiencies,
auto-immune disease, hereditary disorders, infection and
malignancy. We describe a case of a patient with severe
untreatable hemolytic anemia in Castleman’s disease (CD).
Case: A 63-year old Bulgarian man, presented with
complaints of fatigue, headache, nausea, vomiting,
progressive abdominal pain, icterus and fever. Other
than an anemic, slightly icteric appearance and minimal
pressure pain in his right abdomen clinical evaluation
showed no abnormalities. Initial blood tests showed
hemoglobin 3.1 mmol/L, hematocrit 0.5 L/L, MCV 110 fl,
reticulocytosis, bilirubin 48.1 umol/L, normal vitamin
B12, and signs of inflammation. Chest X-ray and ECG
were normal. Direct antigen test (Coombs) turned out
to be positive, showing many aspecific warm and cold
auto-antibodies, which complicated transfusion. With
a differential diagnosis of hemolytic anemia, possibly
provoked by infection, he was treated with corticosteroids
and antibiotics. Despite this treatment, combined with
several blood transfusions, hemoglobin levels remained
below 3.0 mmol/L. Bone marrow biopsy revealed active
erythropoiesis, possibly accompanied by localization of
plasmacytoma. Hepatitis-, mycoplasma-, EBV-, CMV-, HIV-,
parvo-B19- and HHV-8 serology remained negative. A
CT-scan of the abdomen showed massive lymphadenopathy.
Histology of an abdominal lymph node showed a hyaline,
vascular type of Castleman’s disease (CD), with presence of
HHV8-virus. The clinical condition quickly deteriorated,
leading to multi-organ failure and death within a few days.
C046 Remission of a case of acquired von Willebrand
disease after treatment for multiple myeloma
R.F. Crane, R. Fijnheer
Meander Medical Centre, Department of Internal Medicine,
Maatweg 3, 3813 TZ AMERSFOORT, the Netherlands, e-mail:
[email protected]
Introduction: Von Willebrand factor (vWF) plays an
important role in primary hemostasis by facilitating
adhesion of platelets both to damaged endothelium and
to adjacent platelets. It also contributes to secondary
hemostasis, being a carrier protein for factor VIII.
Qualitative or quantitative defects in vWF cause bleeding
disorders collectively known as von Willebrand disease
(vWD). As an inherited disorder, usually autosomal
dominant, vWD is relatively common. Acquired vWD
is much rarer but should be suspected in patients with
a negative family history or a recent onset of bleeding
disorders.
Case: We present a 67-year old male patient who was
admitted with persistent severe bleeding after a knee
arthroscopy for septic arthritis. His medical history
included a hemorrhagic stroke four years prior, but no
bleeding complications after surgical or dental procedures.
Family history was negative for bleeding diathesis.
Analysis for coagulation disorders showed a qualitative
defect in vWF with a marked reduction in large vWF
multimers on gel electrophoresis, leading to a diagnosis
of type 2A vWD. Meanwhile, a monoclonal IgG kappa
prompted a bone marrow examination showing 24%
plasma cells, leading to a diagnosis of multiple myeloma.
55
After induction chemotherapy (velcade, thalidomide,
dexamethasone), a very good partial remission was
achieved. Repeated coagulation analysis yielded completely
normal coagulation parameters and a normal vWF
multimer pattern.
Discussion: Our patient had a bleeding diathesis caused
by an acquired vWD secondary to a multiple myeloma.
While the exact pathogenesis of acquired vWD in hematological malignancy is unclear, several mechanisms have
been postulated. These include specific uptake of vWF
by plasma cells, binding of the monoclonal antibody to
either GP1a or the binding site of vWF (thereby inhibiting
platelet adhesion), and clearance of large multimers from
the circulation by binding of the monoclonal antibody
to the vWF-fVIII complex. In this patient, the normal
vWF antigen activity and vWF propeptide combined with
a marked reduction in large multimers and ristocetin
cofactor activity suggests type 2A vWD. This was
supported by a relative, short-lasting normalization of both
VIII and ristocetin cofactor activity after administration
of Haemate P. The acquired nature of the disorder was
suggested by the patient and family history and confirmed
by the normalization of coagulation after remission of
the multiple myeloma. The presence of an acquired vWD
should be suspected in adults presenting with a recent
onset of bleeding disorders and a negative family history,
and should prompt evaluation for an underlying hematological malignancy.
and scleral icterus. Abdominal examination showed a
significant splenomegaly. Laboratory results revealed a low
hemoglobin level of 2,7 mmol/L with signs of hemolysis.
There were no signs of a bacterial or viral infection.
Peripheral blood smear showed howell jolly bodies and
teardropcells. Ultrasound confirmed a spleen of approximately 25 centimeters. Hemolytic anemia was concluded,
most likely in context of thalassemia. Additional genetic
research showed HbH disease (aa/-- SEA, pointmutation
Hb constant spring). We started with folic acid and
attempted to start blood transfusion, however patient
appeared to have Vel-antibodies. Vel negative blood is rare
and one of the most difficult blood types to supply in many
countries. Patients develop Vel antibodies after pregnancy
or a tranfusion. Transfusion started after Vel-negative
blood was found, nevertheless patient developed an acute
transfusion reaction with dyspnea, tachycardia and chest
pain. A few days she remained stable and pending of
international research of the antibodies she is discharged,
her hemoglobin concentration was 2,4 mmol/L. A week
later we were notified patient endured a miscarriage with
bloodloss a few days earlier. Her hemoglobin level is
checked and found 2,7 mmol/L. Until now international
research of the antibodies yielded no results. Discussion:
This case contains two important clinical lessons. The
first one is not to be afraid of a low hemoglobin level in
a patient with thalassemia, since it problably reflects a
chronic adaptation process. The need for transfusion isn’t
as urgent as it seems. The second keypoint is to always
exclude all factors which can elicit your clinical problem.
In this case no one was aware of a pregnancy. Most likely
this pregnancy evoked the anemia.
C047 Significant anemia in HbH-thalassemia complicated
by transfusion and anamnestic difficulties
M.R. Wetter1, F. Croon-de Boer1, B. van der Matten1,
J.A. Riedl2
1
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: [email protected], 2 Albert Schweitzer
Hospital, DORDRECHT, the Netherlands
C048 Double trouble: TTP, complicated by HIT
R. Besseling, B.S. van der Veen, M. Hoogendoorn
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: [email protected]
Case: A 27-year-old Thai woman presented at the ER with
dyspnea d’effort and jaundice for several days. Her medical
history included thalassemia, diagnosed in Thailand.
She did not use any medication. She married a Dutch
man, together they have had one daughter of 2,5 years
old. In a small hospital in Thailand, she received four
transfusions, last one when she was twenty years old.
The first three times she received her mothers blood
without any problems, last time she received blood of
unknown donor complicated by fever. The patient lost
one brother and one sister in childhood, cause of death
unknown. She still has a healthy brother and healthy
parents, they never needed a bloodtransfusion. Physical
examination showed a young Thai woman with jaundice
Introduction: Thrombocytopenia is a major diagnostic
criterium for thrombotic thrombocytopenic purpura (TTP)
and is used as parameter for treatment outcome. We
describe a case with TTP where response evaluation was
diffused by heparin-induced thrombocytopenia (HIT).
Case description: A 47-year-old Caucasian female was
referred because of anemia and aphasia. Blood examination
revealed haemoglobin 3.2 mmol/L (N 7.5-10 mmol/L),
reticulocytes 431 x 109/L (N 20-100 x 109/L) thrombocytes
9 x 109/L (N: 150-400 x 109/L), haptoglobin < 0.1 g/L (N
0.2-1.8 g/L), LDH 1390 U/L (N: < 250 U/L), a negative
direct antiglobulin test and in the peripheral bloodsmear
schistocytes. Fibrinolytic activity was low.The combination
56
cell count was 75 x 109/L (95% lymphocytes). A CT scan
revealed extensive generalised lymphadenopathy with no
hepatosplenomegaly. Monthly treatment with rituximab,
cyclophosphamide and oral fludarabine (R-FC) was
commenced. Four days following the start of treatment,
the patient was acutely admitted to our intensive care
unit (ICU) with lethargy, vomiting and hypotension.
His electrocardiogram showed a bradycardia of 20 bpm
with broad QRS complexes and inverted T waves. He
was severely hyperkalaemic (potassium: > 10 mmol/L)
and acidotic (pH 6.89). Further laboratory tests revealed
acute renal failure with (creatinine of 448 umol/L),
hyperuricaemia (uric acid 2.7 mmol/L) and hyperphosphataemia (phosphorus 8.38 mmol/L). Haematological
studies on admission showed a leukocyte count of 8.8
x 109/L. The diagnosis of TLS with acute renal failure
following treatment with oral fludarabine therapy was
made. Treatment with Intravenous fluids, calciumgluconate, insulin and glucose infusion were promptly started.
Cardiac arrest occurred and a short interval of resuscitation was necessary. After the patient was stabilized he
was started on continuous venovenous haemofiltration
(CVVH). Normalisation of potassium level and correction
of the metabolic acidosis was achieved within 7 hours after
presentation and the patient was able to be discharged from
ICU 48 hours after admission. There was a remarkable full
remission of his lymphadenopathy. The subsequent cycle
R-FC was administered with hydration therapy and oral
allopurinol and was completed uneventful. Currently the
patient remains in good general condition and he appears
to be in complete remission.
Discussion: Fludarabine induced TLS has been reported
with intravenous and oral administration. Considering
the rapid response to fludarabine, CLL patients with a
high tumour mass may be at increased risk for developing
TLS. Prior to commencing treatment with oral fludarabine
precautions with hydration and allopurinol appear to be
warranted in high risk patients.
of neurological symptoms, microangiopathic hemolysis
and thrombocytopenia was highly suggestive for the
diagnosis TTP and treatment with plasmapheresis and
prednisone was immediately initiated. TTP was confirmed
by a ADAMTS-13 activity < 1% (N 30-200%) and positivity for
anti-ADAMTS-13 antibodies. After six days of plasmapheresis
complete response was achieved with a normal thrombocyte
count of 208 x 109/L without clinical signs. Unexpectedly,
at day 7 the thrombocyte count decreased gradually to a
nadir of 44 x 109/L on day 9 without concurrent increase
in haemolysis or recurrence of clinical symptoms. The
frequency of plasmapheresis was increased to twice daily
and rituximab was administered. Because refractory or
rebound TTP was regarded unlikely, a heparin lock was
used for plasmapheresis, and the clinical probability score
(4T-score) for the diagnosis HIT was 4 points. HIT was
suspected and confirmed by immunologic and functional
assays (ELISA 0,62; (n < 0.19)) and HIPAA positive). After
replacement of the heparin lock by a citrate lock on day 15,
thrombocytes recovered to normal on day 19. Serial analyses
of ADAMTS-13 during plasmapheresis with thrombocytopenia showed normal levels (84-89%) compatible with a TTP
in remission. Plasmapheresis, rituximab, and the dosage of
prednisone could be phased out uneventfully.
Conclusion: HIT, as complication of treatment in a TTP
patient has never been reported. As demonstrated in this
case, heparine locks in catheters should be abandoned
to prevent HIT. Our case further illustrates that
measurement of ADAMTS-13 can be useful for treatment
evaluation thereby preventing under or overtreatment.
C049 Life-threatening acute tumour lysis syndrome during
oral fludarabine treatment for chronic lymphocytic
leukaemia
F.E. Vos, G.J. Timmers, H.J. Voerman
Hospital Amstelland, Department of Internal Medicine, Laan
van der Helende Meesters 8, 1186 AM AMSTELVEEN, the
Netherlands, e-mail: [email protected]
C050 A by life untraceable disease
Background: Since fludarabine has been demonstrated to
be superior to alkylating based agents in inducing clinical
and haematological remissions in chronic lymphocytic
leukaemia (CLL) patients, it has become a frequently used
therapy. Acute tumour lysis syndrome (TLS) is a very rare
complication of any form of therapy in CLL and reports of
fludarabine induced TLS are anecdotal.
Case: A 65 year old male with a history of B-CLL/small
lymphocytic leukaemia (SLL) stage 4 had previously been
treated with chlorambucil with good response. Recently,
the patient was seen with progressive lymphadenopathy,
lymphocytosis and recurrent night sweats without evidence
of Richter’s transformation. At the time, the white blood
C.M.P. van Dongen, E.T.P. Keulen, F.L.G. Erdkamp
Orbis Medical Centre, Department of Internal Medicine, Dr.
H. van der Hoffplein 1, 6162 BG SITTARD, the Netherlands,
e-mail: [email protected]
Case report: An 84-year-old patient, with a history of
peripheral arterial disease and an aorto-iliac bifurcation
prosthesis, was several times admitted to our hospital.
He presented with a bi-frontal headache, loss of appetite,
weight loss, fatigue, intermittent fever and muscle and
abdominal aches. Clinical investigation revealed no abnormalities; there was no lymphadenopathy, no skin leasions,
57
and treated with rituximab, cyclophosphamide, vincristine
and prednisone (R-CVP). Sixteen days after the first dose,
the patient presented with neutropenic fever and severe
arthralgias. She was treated with meropenem intravenously
and recovered fully in several days. Three weeks after the
first dose, the second dose was given: 2 mg clemastine
and 10 mg dexamethasone were administered, followed
by CVP and finally rituximab. Shortly after the onset of
rituximab infusion, the patient suddenly developed severe
upper abdominal pain, tachypnea and bright red rectal
bleeding. She was normotensive and had no fever or
arthralgia. At laboratory examination, patient had an acute
thrombocytopenia of 8·109/L (two days earlier 121·109/L).
Abdominal ultrasound examination was normal with no
sign of thrombosis in the portal or hepatic veins. Tests for
viral hepatitis, HIT and TTP were negative. The rituximab
infusion was stopped and fluid resuscitation and thrombocyte
transfusion were performed. As serum sickness could not be
ruled out, the high dose prednisone of R-CVP was continued.
The next day, patient developed severe liver damage (alanine
aminotransferase 5578 IU/L, aspartate aminotransferase
10870 IU/L, bilirubin 78 umol/L), and acute renal failure with
oliguria (peak plasma creatinine 524 umol/L 6 days after the
second dose). Anti-rituximab IgG (40 AU/ml) antibodies were
slightly elevated and C1q binding was normal. In the course of
2 weeks, the patient fully recovered except for persistent renal
failure (eGFR 35 ml/min/1.73m2). Chemotherapeutic therapy
will be continued without rituximab.
Discussion: Rituximab often causes infusion reactions,
with symptoms such as fever, nausea, urticaria and
bronchospam. In rare cases, infusion reactions can be
severe and even fatal. Such serious reactions are usually
seen in patients with a high circulating tumour load and/
or high CD20 expression. Here we describe a unique case
of unrecognised possible serum sickness after the first
dose of R-CVP, followed by severe acute trombopenia, liver
failure and renal failure after the second dose of R-CVP,
in a patient with extreme splenomegaly. Serum sickness
could not be confirmed by laboratory examination. Our
case supports the recently proposed hypothesis that
extreme splenomegaly is a risk factor for severe infusion
reactions to rituximab.
no organomegaly and there were no signs of infection.
Laboratory results showed an constantly elevated CRP
around 200 mg/L (normal range < 10 mg/L).
Our differential diagnosis consisted of: endocarditis lenta,
arteriitis temporalis, polymyalgia rheumatica, systemic
vasculitis or an infect of his prosthesis, tuberculosis and
neoplastic disorders. A vascular biopsy of the a. temporalis
turned out to be negative. Several chest x-rays, ultrasounds
of abdomen and heart and blood- and urinecultures
didn’t show a focus for an infection. Two PET-CT-scans,
performed in a couple of months time, revealed no
major abnormalities. There was no arterial obstruction
or ischemia on a CT-angiography of the abdomen. A bone
marrow biopsy was not performed because we didn’t
suspect bone marrow abnormalities.
Suddenly – after intravenous antibiotics for a suspected
pneumonia – patient had a respiratory arrest and
bradycardia. He was succesfully reanimated. Afterwards,
patient had a paraplegia of his lower extremities. The
neurologist considered an anterior spinal artery syndrome.
However after a MRI-scan of the lumbar spine the
paraplegia remained unexplained. A couple of days later
the patient died due to clinical detoriation. Obduction
showed both endo- and perivascular involvement of intravascular large B-cell Non Hodgkin lymphoma, localised
in the vessels of the heart, lungs, spleen, kidney, adrenal
glands, vertebra and bonemarrow.
Discussion: Intravascular large B-cell Non Hodgkin
lymphoma (IVLBCL) is an uncommon type of extranodal
B-cell lymphoma. There is a selective growth of malignant
cells in primarily small vessels and capillaries of the affected
organs. Clinical manifestations can vary widely. The absence
of lymphadenopathy, an agressive course, often with a fatal
outcome, and a delay in diagnosis are features of this rare
malignancy. This case illustrates that despite our diagnostic
efforts IVLBCL was by life untraceable in this patient.
C051 A severe infusion reaction to rituximab with thrombocytopenia and multi-organ failure in a patient with
extreme splenomegaly
D.J. Stenvers, J.P. Baars, K. de Heer
Flevo Hospital, Department of Internal Medicine,
Hospitaalweg 1, 1315 RA ALMERE, the Netherlands, e-mail:
[email protected]
C052 Assembling the pieces of the puzzle: the diagnosis
of a rare form of leukaemia
A. Kleinjan, A.M.T. van der Velden, W. Deenik
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
Introduction: Rituximab is a chimeric monoclonal
antibody against the human B-cell specific antigen CD20.
The addition of rituximab to chemotherapy has greatly
enhanced survival in B-cell lymphomas.
Case: A 60 year old woman with an extreme splenomegaly and pancytopenia was diagnosed with a splenic
marginal zone lymphoma with bone marrow localisation
Case: A 68-year old man was admitted because of severe
tiredness and a rapid decline in condition. His medical
58
C053 ‘Pacman’ syndrome: a case series of an extraordinary
hematological disease
history was unremarkable. Laboratory abnormalities
included a leucocytoses of 26 x 109/L with a left shifted
granulopoiesis with metamyelocytes, myelocytes and
6% blasts in the differential count. A bone marrow
aspiration and biopsy was performed. Two days later,
patient returned to the hospital with complaints of muscle
weakness and anorexia. Laboratory tests showed a hypercalcemia of 4.0 mmol/L (corrected for albumin) with a
phosphate of 1.25 mmol/L. Leukocyte count was 32.9 x
109/L, haemoglobin 9.8 mmol/L and platelets were 74 x
109/L. Ultrasonography showed an increased size of the
spleen without lymphadenopathy. Results of bone marrow
aspiration revealed 11% blasts, negative with the Sudan
black stain. Immunophenotypic staining of these cells was
positive for CD36, CD41 and CD42b, supporting megakaryocytic differentiation. Bone marrow biopsy indicated acute
leukaemia with blast numbers in most regions above 20%
and extensive myelofibrosis. Furthermore, cytogenetics
showed trisomy of chromosomes 10, 14, 15 and 19 and a
translocation between chromosome 9 and 22. Patient was
treated with hydration, corticosteroids and bisphosphonates, after which the calcium level decreased to normal.
Patient’s condition did not allow intensive chemotherapy
and therefore treatment with dasatinib was initiated. He
has now received 3 weeks of treatment with some signs of
improvement.
Conclusion: By combining information from results from
the peripheral blood smear and bone marrow (morphology,
immunofenotyping and cytogenetics), the diagnosis of
acute megakaryoblastic leukemie according to the WHO
classification was established. Although the distinction
with chronic myeloid leukaemia in blast crises is difficult
as there are no strict criteria, the clinical picture most
resembles acute megakaryoblastic leukaemia. In adults, the
disease accounts for less than 5% of all cases of AML and
is usually characterised by an acute presentation, extensive
myelofibrosis and poor prognosis. Cytogenetics often
reveals complex anomalies. The Philadelphia chromosome
(i.e. t(9;22)) is rare in AML, but the incidence in acute
megakaryoblastic leukaemia seems to be much higher.
The presence of this mutation enabled treatment with
dasatinib, an oral tyrosine kinase inhibitor which specifically targets the Philadelphia chromosome. Finally, the
hypercalcaemia in haematological malignancies is usually
due to increased production of 1,25dihydroxyvitamin D, in
contrast to hypercalcaemia in solid malignancies.
This case report illustrates the importance of cytogenetics in the diagnosis of leukaemia, sometimes enabling
targeted treatment. Furthermore, hypercalcaemia can be
one of the manifestations of AML, caused by a specific
mechanism.
P.M. Smit, G.S. Madretsma, G.S. Schaar
Gelre Hospital, Department of Internal Medicine, Albert
Schweitzerlaan 31, 7334 DZ APELDOORN, the Netherlands,
e-mail: [email protected]
This case series describes four patients with a similar
disease presentation of acquired hemophagocytic lymphohistiocytosis (HLH or ‘Pacman’ syndrome). The clinical
presentation, course and individual treatment results
are presented. In addition, pathogenesis, current HLH
diagnostic criteria and the HLH-94 treatment protocol are
reviewed. In 2013 - within a six month period – a cluster
of four patients were diagnosed with acquired HLH in our
hospital: a 46 year old woman after allogeneic stem cell
transplantation for severe aplastic anemia, a 59 year old
woman with B-cell chronic lymphocytic leukemia, a 75-year
old woman with splenic marginal zone lymphoma (SMZL),
and a 71 year old man with a history of lymphoplasmacytic
lymphoma. All presented with fever of unknown origin
and pancytopenia; the first three patients had splenomegaly. Additional laboratory testing revealed hypertriglyceridemia in addition to seriously elevated ferritin and
soluble interleukin-2 receptor (sIL-2R) levels in all. These
patients were consequently diagnosed with acquired HLH
according to HLH-2004 diagnostic criteria. Treatment with
etoposide, cyclosporin A and dexamethasone according to
HLH-94 protocol was initiated in the first two patients with
successful results; therapy was discontinued after 13 and 10
weeks, respectively. Fever resolved and both patients had
clinical improvement, although chronic norovirus infection
and disseminated varicella infection developed as as a
complication in each patient respectively. The patient with
SMZL started with R-COP lymphoma treatment followed
by impressive clinical improvement and resolution of fever.
The man with a history of lymphoplasmacytic lymphoma
died of Enterococcus faecium sepsis at the ICU before any
therapy for HLH could be initiated. In conclusion, this case
series elucidates the disease histories of four patients with
an extraordinary syndrome – hemophagocytic lymphohistiocytosis or ‘Pacman syndrome’. This presentation illustrates
that early diagnosis and prompt treatment of acquired HLH
are required for an optimal result and prognosis.
59
C054 Hodgkin’s lymphoma after IgG4-related systemic
disease
C055 A female with extremely painful skin lesions: what
is your diagnosis?
S. Altenburg, E.J. Libourel, W.K. Lam-Tse
St Franciscus Gasthuis, Department of Internal Medicine,
Kleiweg 500, 3045 PM ROTTERDAM, the Netherlands,
e-mail: [email protected]
A. Lahdidioui
Haga Hospital, Department of Internal Medicine, Leuweg
275, 2545 CH DEN HAAG, the Netherlands, e-mail:
[email protected]
Case: A 45-year old patient presented with fatigue and
weight loss. Laboratory testing showed an elevated BSE
and CRP, a microcytic anaemia and elevated gamma
globulins. Additional subtyping of IgG shows an almost
tenfold elevated IgG4. A CT scan of the thorax and
abdomen showed multiple pathological mediastinal lymph
nodes. Pathological examination showed reactive lymph
nodes with strong plasmacytosis, no classifying diagnosis,
Castleman disease may be considered. A few years later the
PA material is revised. It is noted that there is an excess
of polyclonal IgG4-positive plasma cells. The diagnosis is
now IgG4-related systemic disease (IgG4-RSD). Treatment
with prednisolone was started. Few weeks after start of
the treatment symptoms of the patients deteriorated.
A new CT scan showed an increase of the mass in the
mediastinum. Pathological examination now showed a
Hodgkin’s lymphoma.
Clinical features: IgG4-related systemic disease can present
in various organs and the organ involvement does not have to
run simultaneously. Initially malignancy is often considered.
Pathological features: IgG4-RSD is characterized histological by infiltration of inflammatory cells and in particular
IgG4-positive plasma cells. Not only interleukin-10 and
T-helper-2 cells are involved, but also regulatory T cells, so
that there appears to be an allergic reaction. In contrast to
an allergic reaction IgG4 does not activate complement, and
scarcely binds to the constant region of IgG. However, the
exact mechanism remains unclear.
Diagnosis: The diagnosis IgG4-RSD is based on elevated
serum IgG4 levels (> 1.35g/L) and pathological examination
involving infiltration of lymphocytes and at least 30-50%
IgG4 positive plasma cells.
Treatment: Most patients respond within weeks
to treatment with glucocorticoids. In general, it is
recommended to start with an oral dose of about 40 mg
of prednisone per day treatment. Response is seen within
two to four weeks. Effectiveness of the treatment can be
measured by radiological follow-up or by serum concentration of IgG4.
Prognosis: The natural course of IgG4 disease is still
unknown. In some patients, a spontaneous remission
occurs, usually followed by a relapse over time. Treatment
with glucocorticoids is successful, but also relapse after
stopping a treatment is observed. Additional studies for
the long-term prognosis are necessary.
Introduction: Fenprocoumon is a commonly used anticoagulant. We describe a patient who presented with a rare
but very serious, cutaneous side effect.
Case report: A 43-year-old obese female with a history of
unprovoked deep vein thrombosis as well as an episode of
thrombophlebitis presented at the emergency department
with extremely painful skin lesions. Her family history
was notable with thrombosis associated with factor
V Leiden mutation and prothrombin gene-mutation.
Recently, she developed a second episode of thrombophlebitis and low molecular weight heparin (LMWH) as
initial treatment was prescribed. Four days after stopping
LMWH and starting Fenprocoumon she developed areas
of dark discoloration surrounded by an erythematous
lesion on both thighs as well as on the skin of the
epigastric region and the lower abdomen. The pain was
accompanied by paraesthesia. Haemorrhagic blisters
or clear signs of gangrene were not present.An initial
concern regarding a possible hematoma or abscess was
dismissed because of the absence of trauma, fever and/
or increased inflammatory parameters. Laboratory investigation showed normal platelet count, prothrombin time
49.7 seconds (ref range: 9.0-12.0 sec), activated partial
thromboplastin time 32 seconds (24-34 sec), factor V
activity 120%. Because the diagnosis [quotright]coumadin
induced skin necrosis[quotrightB]was considered,
the patient was admitted and the Fenprocoumon was
stopped immediately. Vitamin K was administered for
ten days. The pain resolved over three days, the patient
was treated with non-steroidal anti-inflammatory drugs.
All lesions resolved after four weeks during follow up
in the outpatient clinic. The level of protein C and S
turned out to be low, respectively 68% (70-140%) and
48% (60-140%). This increases the susceptibility to this
complication. If the skin necrosis is identified and treated
early on, like in our case, the affected tissue usually heals
well. Otherwise, noticeable scars or limb necrosis can
form requiring extensive surgical debridement or even
limb amputation. The novel oral anticoagulants (NOACs)
could be a good alternative.
60
VIII ONCOLOGY RESEARCH
Conclusions: The correlation of 2D-echocardiographies
with 3D-echocardiographies in prospectively studied
patients treated with HER2Neu-receptor blocking agents
will be presented.
C056 Relation of 2D and 3D-echocardiography in patients
with HER2Neu positive breast cancer treated with
chemotherapy and HER2Neu-receptor blocking
agents
C057 Treatment of patients with HER2Neu positive breast
cancer with chemotherapy and HER2Neu-receptor
blocking agents: Detection of cardiotoxicity by the
use of serum biomarkers, 3D-echocardiography and
cardiac MRI
C. Liesting1, M.J.M. Kofflard2, J. Bakker2, J.J. Brugts1,
J. Kitzen2, H. Boersma1, M.D. Levin2
1
Erasmus Medical Centre, Department of Cardiology,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: [email protected], 2 Albert
Schweitzer Hospital, DORDRECHT, the Netherlands
C. Liesting1, J.J. Brugts1, M.J.M. Kofflard2, J. Kitzen2,
M. Fouraux2, J. Bakker2, H. Boersma1, M.D. Levin2
1
Erasmus Medical Centre, Department of Cardiology,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: [email protected], 2 Albert
Schweitzer Hospital, DORDRECHT, the Netherlands
Introduction: Chemotherapy has proved to be a helpful
and efficient modality of treatment in advanced malignant
disease in both adjuvant and palliative settings. With the
advent of monoclonal antibodies directed against tumor
antigens newer strategies are explored to further improve
remission and survival rates. As such, Trastuzumab and
Lapatinib have evolved as promising agents in the treatment
of breast cancer over-expressing the human epidermal
growth factor receptor 2 protein (HER2Neu). A well-known
downside of chemotherapeutic agents has always been
the increased incidence of cardiotoxic side effects. The
incidence of these effects vary between < 1% to > 10% in
different series treated with HER2Neu-receptor blocking
agents. The cardiac function in these patients is regularly
measured by MUGA-scan or 2D-echocardiography. The
reliability of 2D-echocardiography is often discussed
in literature and is unknown in patients treated with
HER2Neu-receptor blocking agents.
Aim of the study: Outcome of 2D-echocardiography in
relation to 3D-echocardiography with respect to cardiac
failure of patients treated with HER2Neu-receptor blocking
agents.
Materials and methods: In this prospective single centre
study, successive HER2Neu positive breast cancer patients
starting with chemo-immunotherapy are included in
the HERBAS study. Trastuzumab and Lapatinib in
combination with chemotherapy are prescribed in two
different groups: adjuvant and palliative. Systolic and
diastolic function by 2D- and 3D-echocardiography for
the start and during adjuvant or palliative treatment are
assessed.
Results: From January 2008 to December 2013 103
patients are included in the study. Overall 545 2D and 548
3D-echocardiographies are made. The correlation systolic
and diastolic function of results of 2D-echocardiographies
are correlated with 3D-echocardiographies with respect
to left ventricular ejection fraction, wall motion abnormalities, E/A-ratio and E/É-ratio.
Introduction: Chemotherapy has proved to be a helpful
and efficient modality of treatment in advanced malignant
disease in both adjuvant and palliative settings. With the
advent of monoclonal antibodies directed against tumor
antigens newer strategies are explored to further improve
remission and survival rates. As such, Trastuzumab and
Lapatinib have evolved as promising agents in the treatment
of breast cancer over-expressing the human epidermal
growth factor receptor 2 protein (HER2Neu). A well-known
downside of chemotherapeutic agents has always been
the increased incidence of cardiotoxic side effects. The
incidence of these effects vary between < 1% to > 10% in
different series with HER2Neu-receptor blocking agents.
Aim of the study: Detection of cardiotoxicity by the use
of serum cardiac biomarkers, 3D-echocardiography and
cardiac MRI.
Materials and methods: In this prospective single
centre study, successive HER2Neu positive breast
cancer patients starting with chemo-immunotherapy
are included in the HERBAS study. Trastuzumab
and Lapatinib in combination with chemotherapy are
prescribed in two different groups: adjuvant and palliative.
Cardiac biomarkers are prospectively measured during
treatment. In addition, systolic and diastolic function by
3D-echocardiography for the start and during adjuvant or
palliative treatment are assessed. The cardiac function and
morphology will also be assessed by cardiac MRI before
and after six months of treatment.
Results: From January 2008 to December 2013 103 patients
are prospectively included in the study. Overall 548
3D-echocardiographies are studied in combination with
618 cardiac biomarkers measurements. The correlations of
cardiac biomarkers and outcome of 3D-echocardiographies
are reported. In addition, the results of cardiac MRI before
61
2% and 0% in cis100 and cis40 patients, respectively. In
the cis100 group 3/40 patients developed chronic renal
dysfunction, versus 0/104 in the cis40 group.
Conclusion: This retrospective study shows that significantly less nephrotoxicity occurs in the cis40 CRT group in
comparison with the cis100 CRT group. Furthermore, the
CTC v 4.03 is more appropriate in scoring nephrotoxicity
than the CTC v 3.0. Until recently the CTC v 3.0 was used,
which has lead to an underscoring of nephrotoxicity in
studies using cisplatin-containing CRT schedules.
and during treatment with Her2Neu-receptor blocking
agents will be presented.
Conclusions: The predictive value of cardiac biomarkers
in relation to 3D-echocardiographies and changes on MRI
in breast cancer patients treated with HER2Neu-receptor
blocking agents will be presented.
C058 Nephrotoxicity of two cisplatin-based chemoradiotherapy schedules for treatment of patients with
locally advanced head and neck cancer
C.M.L. Driessen, M.J.M. Uijen, W.T.A. van der Graaf,
J.H.A.M. Kaanders, T. Nijenhuis, C.M.L. van Herpen
Radboud University Medical Centre, Department of Medical
Oncology, Geert Grooteplein Zuid, 6500 VC NIJMEGEN, the
Netherlands, e-mail: [email protected]
C059 Unplanned hospital admissions in a prospective
cohort of elderly cancer patients receiving
chemotherapy
J.N.H. Timmer-Bonte, M. Coskuntürk, J. van Wijck,
P. Notten, W.T.A. van der Graaf
Radboud University Medical Centre, Department of
Medical Oncology, Postbus 9101, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected]
Introduction: Concomitant chemoradiotherapy (CRT)
with cisplatin 100 mg/m2 on days 1, 22 and 43 (cis100) is
the standard treatment for patients with locally advanced
head and neck cancer (LAHNC) and nasopharyngeal
cancers (NPC). An alternative CRT schedule consists
of cisplatin 40 mg/m2 weekly during six weeks (cis40).
The cure rate of both schedules is approximately 50%.
Nephrotoxicity is one of the main toxicities of cisplatin,
leading to dose reduction, or preliminary stopping, which
can be detrimental for prognosis, or inducing chronic renal
dysfunction. We compared the development of cisplatininduced nephrotoxicity between these two CRT schedules
using various criteria for nephrotoxicity.
Materials and methods: We studied all patients treated
with CRT for LAHNC or NPC from 2003 until 2011 in
the Radboudumc retrospectively. One hundred forty-four
patients were included, of which 40 received cis100 and
104 received cis40. We collected serum creatinine and
glomerular filtration ratio (GFR) using the CKD-EPI
formula at baseline, the maximal rise during treatment
and the maximal rise after a year follow up. An increase
of 25% was seen as clinically relevant. Moreover we scored
nephrotoxicity according to the Common Terminology
Criteria for Adverse Events (CTCAE) version 3.0 and (the
latest) version 4.03.
Results: During treatment in the cis40 group, 17,3%
developed an increase of serum creatinine over 25% versus
77,5% in the cis100 group (p < 0.05). During treatment
an increase of 25% of GFR estimated by CKD-EPI was
observed in 2,9% in the cis40 group and 32,5% in the
cis100 group (p < 0.05). According to the CTCAE version
4.03, nephrotoxicity grade 1 occurred in 40% and 68%,
grade 2 in 53% and 7% grade 3 in 5% and 0% and grade 4
in 2% and 0% in cis100 and cis40 patients, respectively.
Conversely, scoring according to CTCAE v 3.0 showed
grade 1 in 42% and 5%, grade 2 in 8% and 0%, grade 3 in
Introduction: The world population is aging rapidly. With
growing age, the risk of cancer development, cancer
mortality and treatment-related adverse events increases.
At present insight into characteristics of the heterogeneous
elderly cancer patient towards the risk of serious toxicity
due to systemic treatment is limited
Aim of the study: To provide a comprehensive description
of a senior cancer patient population starting chemotherapy and their outcome defined as unplanned hospital
admissions (UHA).
Material and Methods: Between May 2011 and May 2013,
all consecutive patients aged 70 years or older starting
chemotherapy (including targeted therapy) were included
(n = 83) and prospectively followed during treatment.
Participants were subjected to a geriatric assessment
commonly used in primary care (Easycare1) to collect
structural information about current condition and
unforeseen problems in physical, social and emotional
domains. Characteristics of admitted patients were
compared to patients without an UHA.
Results: This cohort of senior cancer patients had a median
age of 73 years (range 70-89), showed great heterogeneity
on domains assessed by Easycare, 48% were male and
77% had a KS performance score > 80 prior to start of
chemotherapy. Predominant cancer types were gastrointestinal and uro-genital (47% and 35% respectively).
Most patients received prior cancer treatment (surgical
74%, radiotherapy 30%) and started chemotherapy full
dose. Treatment intent was palliative in 55%. Thirty
patients (36.1%) experienced an UHA, mostly therapyrelated (83.3%) and in first treatment cycle (47%). Fever
or gastro-intestinal symptoms resulting in dehydration
62
For rectal cancer, these percentages were 2.1% and 5.6%
for loco-regional recurrence and 4.8% and 13.4% for
distant recurrence. The risk of developing a recurrence
was highest between 0.5 - 2 years after surgery. Prognostic
factors for loco-regional and distant recurrences for colon
cancer were complications requiring readmission, T3 -T4
tumours and positive lymph nodes. Emergency surgery
was only a prognostic factor for loco-regional recurrence.
For rectal cancer, T3 -T4 and N2 tumours were prognostic
factors for distant recurrences.
Conclusions: Colorectal cancerrecurrences continue to be
a serious concern with an incidence up to 15% in 3 years.
Next to known prognostic factors, complicated operations
seem to have an impact on the rate of recurrences. Clearly,
operative complications have long term detrimental effects
on colorectal cancer outcome and reducing operative
complications may improve recurrence rates.
were most common (60%). Cardiovascular events were
less frequent (capecitabine-related myocardial infarction
in 3 patients, cerebrovascular accident in 2 patients). In
one-third of the admitted patients adverse events existed
for > 3 days before admission (and were not reported prior
to admission). Predictors for UHA were dependency in
keeping up personal appearance (p = 0.012), bathing (p
= 0.030), preparing meals (p = 0.008) and no regular
exercise (p = 0.010) at start of treatment. The odds ratio of
UHA in curative and palliative treatment intent was 0.68
and 0.48, respectively.
Conclusion: One third of chemotherapy-treated senior
cancer patients encounter unscheduled hospitalisation,
mainly due to therapy-related toxicity and regardless of
treatment intent. A better understanding of patients’
characteristics is essential to optimise treatment in this
heterogeneous elderly population. The next step in caring
for chemotherapy-treated geriatric cancer patients should
investigate whether home based nurse-led interventions,
early toxicity reporting and early interventions aimed at
nutrition and physical activities can prevent UHA.
1
www.nationaalprogrammaouderenzorg.nl
C061 Gamma Knife Surgery in patients with brain
metastases from breast cancer: overview and
difference in breast cancer phenotype
A.M.T. Huijben, S.J. van den Boogerd, P. Hanssens,
L.V. Beerepoot, J.M.G.H. van Riel
St. Elisabeth Hospital, Department of Internal Medicine,
Hilvarenbeekseweg 60, 5022 GC TILBURG, the Netherlands,
e-mail: [email protected]
C060Higher risk for recurrences in colon cancer patients
with postoperative complications
A.J. Breugom1, E. Bastiaannet1, C.B.M. van den Broek1,
J.W.T. Dekker2, L.G.M. van der Geest 3, C. Puylaert 1,
W.H. Steup4 , C.J.H. van de Velde1, G.J. Liefers1,
J.E.A. Portielje4
1
Leiden University Medical Centre, Department of Surgery
Oncology, Postbus 9600, 2300 RC LEIDEN, the Netherlands,
e-mail: [email protected], 2Reinier de Graaf Gasthuis,
DELFT, the Netherlands,3Comprehensive Cancer Centre the
Netherlands, UTRECHT, the Netherlands, 4Haga Hospital,
THE HAGUE, the Netherlands
Introduction: Breast cancer is the second most common
cause of brain metastases. Time has proven radiosurgery
to be a very useful tool in the management of brain
metastases, with a high local tumor control rate. The
aim of our research was to study the clinical outcome of
patients with brain metastases of breast cancer (BC) treated
with gamma knife surgery (GKS) regarding the different
intrinsic subtypes of BC.
Methods: We performed a retrospective pilot study in
25 women with brain metastases of BC who underwent
GKS between 2002 and 2011 at the St.ElisabethHospital.
Subjects with a proven second malignancy were excluded.
Subjects were divided in 4 subgroups depending on the
different intrinsic subtypes: ER,PR positive/HER2NEU
negative (n = 6); HER2NEU positive/ER,PR negative (n =
8); ER,PR positive/HER2NEU positive (n = 6) and triple
negative (n = 4). At time of intracerebral metastases we
defined the BC as uncontrolled when the extracranial
disease wasn’t under control with the current treatment.
Results: There was no difference between the subgroups
in age at primary diagnoses and in age at occurrence
of extracranial and intracerebral metastases. There was
a trend of a higher number of brain metastases in the
subgroup HER2NEU positive / ER,PR negative compared
to the other subgroups with a mean of 4.75 ± 3.01 in the
Background: Colorectal cancer is a major health problem,
with a high recurrence rate. This study aimed to describe
the incidence of loco-regional and distant recurrence
among patients with colorectal cancer in the Netherlands
and to identify prognostic factors for recurrences.
Material and methods: All 646 patients operated with
curative intent for stage I-III colorectal cancer between
January 1, 2006 and December 31, 2008 in one university
and two teaching hospitals in the western region of the
Netherlands were analysed. Cumulative incidences of locoregional and distant recurrence were computed with death
as competing risk. To identify prognostic factors, Cox’s
proportion hazards regression model was used.
Results: For colon cancer, the 1-year and 3-year cumulative
incidences were 3.1% and 8.0% for loco-regional
recurrence and 8.6% and 15.1% for distant recurrence.
63
HER2NEU positive/ER,PR negative (p:0.06). There was
no significant correlation between the number of brain
metastases and survival. There was a significant difference
in mean survival (months) after development of intracerebral metastases: ER,PR positive/HER2NEU negative 25.2
± 7.94, HER2NEU positive / ER & PR negative 20.7 ± 2.74,
ER,PR positive/HER2NEU positive 45.54 ± 10.79 and triple
negative 13.08 ± 2.89 (p: 0.016). The triple negative had a
trend for worst survival after the first GKS (12.7 months,
p: 0.17). 75% of the subgroup triple negative had uncontrolled extracranial disease at time of occurrence of intracranial metastases. Overall the subjects with uncontrolled
extracranial disease at time of intracranial metastases
have a trend of decreased median survival compared to
the controlled disease (mean 16.6 months vs 29.7 months,
p: 0.19)
Conclusion: In the different intrinsic subtypes of BC
triple negative has significant the worst survival after
development of intracerebral metastases with a trend to
the worst prognosis after the first GK. One explanation
is the uncontrolled extracranial disease. As distinct from
other studies we find no relation between number of brain
metastases and survival. We extended the pilot study to
about 220 subjects of which the results will follow.
data about oxaliplatin administration and acute CIPN
during treatment was extracted from the medical files.
They filled in the EORTC QLQ-CIPN20. The EORTC
QLQ-CIPN20 subscales were analyzed with analysis of
covariance and separate experienced neuropathy symptoms
were analyzed with logistic regression analysis.
Results: Oxaliplatin was given for a median 6 cycles
(range 1-12) at a mean cumulative dose of 680 mg/m2
(SD 265). Patients who received a cumulative oxaliplatin
dose of ≥ 842 mg/m2 had a significantly worse EORTC
QLQ-CIPN20 sensory score compared to those who
received a low cumulative dose of < 421 mg/m2 (mean 18.9
vs. 7.8; p = 0.026). High dose patients more often reported
tingling toes/feet (14% vs. 1% respectively; p = 0.008).
Patients who received a dose reduction after the 6th cycle
of oxaliplatin reported more severe neuropathy symptoms
than patients who received a dose reduction before the 6th
cycle of chemotherapy. The EORTC QLQ-CIPN20 sensory
scale was significantly worse in patients with documented
acute neurotoxicity (n = 144) in comparison with patients
who had no acute neurotoxicity (n = 28) (mean 16.4 vs.
9.2, p = 0.02).
Conclusion: Cumulative dose of oxaliplatin is associated
with long-term CIPN in CRC survivors 2-11 years after
diagnosis. Monitoring during treatment is important as
the risk of developing long-term CIPN could be minimized
by applying dose reduction on time or by minimizing the
cumulative dose of oxaliplatin. Future studies should focus
on identifying patients who are at risk of developing CIPN.
C062 Adjuvant oxaliplatin dose and dose reductions are
associated with severity of neuropathy symptoms
among 2-11 year colorectal cancer survivors; results
from the population-based PROFILES registry
A.J.M. Beijers1 , F. Mols2 , V.C. Tjan-Heijnen3 ,
L.V. van de Poll-Franse4, G. Vreugdenhil1
1
Máxima Medical Centre, Department of Internal Medicine,
Run 4600, 5500 MB VELDHOVEN, the Netherlands, e-mail:
[email protected], 2CoRPS – Center of Research on Psychology
in Somatic diseases, TILBURG, the Netherlands,3Maastricht
University Medical Centre, MAASTRICHT, the Netherlands,
4
Comprehensive Cancer Centre the Netherlands (CCCN),
Eindhoven Cancer Registry, EINDHOVEN, the Netherlands
IX
ONCOLOGY CASE REPORTS
C063 An underreported severe complication of cisplatin
chemotherapy
B.M.J. Scholtes, B.P.C. van Oijen, C. Mestres Gonzalvo,
F.L.G. Erdkamp
Orbis Medical Centre, Department of Internal Medicine, Dr
H. van der Hoffplein 1, 6130 MB SITTARD-GELEEN, the
Netherlands, e-mail: [email protected]
Introduction: Chemotherapy-induced peripheral
neuropathy (CIPN) is a dose-limiting side effect of
oxaliplatin. CIPN may have a major impact on quality of
life of cancer survivors, if not reversible.
Aim of the study: We aimed to study the influence of
the cumulative dose of adjuvant oxaliplatin on long-term
severity and prevalence of CIPN among colorectal cancer
(CRC) survivors.
Materials and methods: A total of 188 patients diagnosed
with CRC between 2000 and 2009 who underwent
adjuvant treatment with oxaliplatin, were included. Patients
were identified by the Eindhoven Cancer Registry and
included 2-11 years after diagnosis. After informed consent,
Cisplatin is a platinum-based antineoplastic agent that
inhibits DNA synthesis by the formation of DNA crosslinks. It is most used to treat solid tumours, for example
metastatic bladder, ovaria, testis and lung cancer.
Case report: A 47-year old woman was diagnosed with
urothelial carcinoma of the bladder for which neo-adjuvant
chemotherapy was started. The treatment consisted of
cisplatin and gemcitabine every three weeks.
Within one day after the second cisplatin dose the patients’
feet turned pale but she experienced no pain. After three
days she presented at the Emergency Room (ER) with pain
64
and pallor complaints of both feet. On doppler ultrasonography, three-phasic flow patterns on both tibial arteries
were visible and she was discharged from the ER without
a diagnosis. No differential diagnosis was mentioned and
no possible relation to the cisplatin chemotherapy was
considered.
Thirteen days after the second cisplatin dose her
complaints exaggerated and she came to our out-patient
clinic. Physical examination showed bullae and pallor
on both feet, sensory and motor functions were absent,
and no palpable pulses below the popliteal artery could
be determined. A magnetic resonance angiography was
performed; it showed thrombi in the aorta and the arteria
iliaca with hardly any outflow in both lower legs. An
endarteriectomy was performed, as well as a selective
embolectomy of both lower legs which was not successful.
Additional laboratory tests showed no other underlying
coagulopathy. Due to septic deterioration both legs had to
be amputated below the knees within the next three days.
The chemotherapy was not continued and she is still in
rehabilitation.
Discussion: Arterial thrombosis is a rare complication
which may have far-reaching consequences.
In this report we describe a case with arterial occlusion
that is strongly suspected to be related to the cisplatin
chemotherapy. We searched our hospital database and
found three other recent cases. However, it is striking
that only four cases regarding this complication have been
reported to the Netherlands Pharmacovigilance Centre
Lareb during the last year, despite the fact that since 2007
health care providers are required by law to report serious
adverse events. Thus, there still is a significant underreporting of serious adverse events.
By reporting these side effects also other medical
specialists become more familiar with them and can,
therefore, be more alert in an early stage of presentation.
So the old adage still stands: what you do not know is very
difficult to recognise (on time).
The last 6 days, she developed cramps between her
shoulders, tingling feelings in both arms and tongue
numbness. She had difficulty swallowing and a disability
to talk. Symptoms were intermittent, but increasing and
at the day of presentation leading to progressive airway
obstruction. She didn’t have any typical features of capecitabine toxicity nor were there other focal (neurological)
signs. Laboratory findings were normal. No co-medication
was used, in particular no dopamine antagonists.
A diagnosis of oromandibular dystonia due to capecitabine
was made, and capecitabine was stopped.
The anticholinergic drug biperiden (Akineton) 10 mg
was given intravenously, after which speaking and tongue
movements improved within 20 minutes.
After cessation of biperiden symptoms recurred in 12
hours in the same intensity as before. Again, she was
successfully treated with biperiden intravenously.
After the patient was able to swallow, she was treated with
1 mg of oral trihexyfenidyl (Artane) once daily during 3
days and symptoms did not reappear. Pharmacogenetic
counseling showed a normal 5-FU drug metabolism.
Discussion: We report an extremely rare, but clinically
highly relevant, case of capecitabine induced oromandibular dystonia leading to airway obstruction without
other neurological signs.
We concluded that this was due to capecitabine use,
because after discontinuing bipiriden symptoms
reappeared and after cessation of capecitabine she
recovered completely and complaints never recurred.
This is the first reported case of capecitabine induced
oromandibular dystonia in Caucasians. In an earlier
described case a Chinese male developed oromandibular
dystonia nine days after consuming capecitabine which
resolved spontaneously after three days. To the best of our
knowledge oromandibular dystonia is never reported after
the administration of other forms of 5-FU.
The mechanism by which oromandibular dystonia
occurs upon capecitabine intake is unclear. One plausible
explanation is that capecitabine may pass through the
blood brain barrier which may lead to a disruption within
the basal ganglia, the center for movement control. This
is seen in other types of dystonia and other causes of
oromandibular dystonia. The quick improvement after
anticholinergic drugs, the first choice of treatment in these
other types of dystonia, underlines a similar pathogenesis.
Conclusion: Capecitabine may cause oromandibular
dystonia, which may be treated with anticholinergic drugs.
More research is needed to clarify the pathogenesis.
C064Capecitabine may cause oromandibular dystonia
J.M. van Pelt-Sprangers, E.C.T. Geijteman, J. Alsma,
I.A. Boere, R.H.J. Mathijssen, S.C.E. Schuit
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: [email protected]
Case: A 56-year-old Caucasian woman diagnosed with
T3N2M0 rectal cancer, underwent chemotherapy with
capecitabine (1,500 mg BID), and presented at the
emergency department after 10 days of treatment.
65
C065 Epithelioid angiosarcoma of the aorta after endovascular aneurysm repair
C066An uncommon cause of pelvic pain in patients with
a history of uterine cancer
W.A.G. van der Meijden, J.E. Roeters van Lennep,
H.J.M. Verhagen
Erasmus Medical Centre, Department of Internal Medicine,
’s-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: [email protected]
A.M. Newsum, S.A. Luykx-de Bakker
Tergooi Hospital, Department of Internal Medicine – Oncology,
Van Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
Introduction: When patients with a history of malignancy
complain of pelvic pain, the first cause considered is
skeletal metastasis. However, as radiotherapy increases
the risk of late-onset pelvic insufficiency fracture,
this relatively uncommon diagnosis also needs to be
considered. We present two patients with extensive pelvic
insufficiency fractures after radiotherapy for uterine
cancer.
Case 1: A 71-year old woman presented with a three
month history of severe pain in the lower back. Two years
earlier she underwent surgical removal of the uterus and
adnexa for treatment of endometrial carcinoma followed
by adjuvant brachytherapy. An MRI-scan was performed
which showed an abnormal aspect of the sacrum, suspect
for a fracture. A CT-scan revealed a bilateral fracture of
the sacrum, probably an insufficiency fracture. Treatment
was started with analgesics and an orthopaedic brace.
Six months later she reported increased pain. MRI- and
CT-scan showed a new fracture of the left pubic bone
and an extensive bilateral communitive fracture of the os
ilium. To rule out a pathologic fracture caused by bone
metastases, a biopsy was performed, which showed no
evidence of malignant cells. A DEXA-scan showed mild
osteopenia, for which treatment was started with calcium/
vitamin D and a bisphosphonate. In addition, she was
referred to a rehabilitation clinic.
Case 2: A 79-year old woman was referred to the
department of internal medicine because of lower
back- and pelvic pain with osteolytic lesions on pelvic
radiography. Four years earlier, she was diagnosed with
a uterine carcinosarcoma (malignant mixed mullerian
tumor) for which removal of the uterus and adnexa
had been performed, followed by adjuvant internal and
external radiotherapy. CT-scan revealed destruction of
the pubic bone and bilateral fractures of both the os ilium
and sacrum. Additional evaluation with a bone scan
was in accordance with insufficiency fractures. She was
treated with analgesics, calcium/vitamin D and a bisphosphonate. Later CT-scans showed a stable situation, without
significant healing tendency.
Discussion: Radiotherapy in the pelvic region leads to
an increased risk of pelvic insufficiency fractures, with
cumulative 5-year prevalence rates estimated to be 5-15%,
dependent on the type of radiotherapy (definitive or
adjuvant). Additional risk factors are female sex and osteoporosis. Treatment is usually conservative with analgesics.
Introduction: Primary tumors of the aorta are rare.
Implantation of foreign bodies have been shown to induce
sarcomas in experimental animals, but it has only rarely
been reported in humans. We present a patient with an
epithelioid angiosarcoma of the abdominal aorta after
endovascular repair of an infrarenal aneurysm.
Case: A 82-year-old male was seen in consultation at the
surgical ward for fatigue, fever and weight loss. Seven years
previously an infrarenal aneurysm was successfully treated by
EVAR (endovascular aneurysm repair). Three months before
consultation, a routine echo was performed, which showed
growth of the aneurysm from 3,8cm to 9,1cm in 15-months.
The combination of back pain, fever and the image on a
CT-scan lead to the working diagnosis of contained rupture
of a mycotic aneurysm after EVAR for which IV antibiotics
were administered and an urgent re-EVAR was performed..
This did not alleviate his complains, fever persisted while
blood cultures remained negative. On physical examination
a tender mass was palpable in mid-abdomen. Laboratory
investigation revealed leukocytosis, elevated C-reactive-protein
and liver enzymes. Additional CT-scanning showed a correct
position of the prosthesis, no endoleak, with no shrinkage
of the aortic wall. There were no signs of fat infiltration or
pathological lymph nodes, but two nodules in the left lung
were noted. A PET-scan revealed no FDG uptake of the
aortic mass, but increased uptake at the height of lumbar
3, dorsal of the prothesis, one lesion para-iliac and one
pulmonary nodule. Histological examination of the biopsy
of the mass dorsal of the prothesis, showed a epithelioid
angiosarcoma. Immunohistochemical staining was positive
for pancytokeratin, the endothelial marker CD-30, ERG
transcription factor and factor VIII. The clinical condition
of patient worsened and he died six week after admission.
Postmortem examination showed a periaortic epithelioid
angiosarcoma with metastases to liver and lung with also
pleural sarcomatosis.
Conclusion: This case present a patient with a strong
suspicion for an infected vascular graft who ultimately
had a epithelioid angiosarcoma with multiple metastases.
Reviewing the literature, this is the sixth patient who
developed a sarcoma adjacent to endovascular repair of
an aneurysm. Although there is no definitive proof of an
association between the foreign material and the tumor,
increasing published cases in the literature with a history
of EVAR should raise suspicion for a causal link.
66
When this is insufficient or there is no healing tendency,
operation may be considered.
Conclusion: Pelvic insufficiency fractures as a late complication of radiotherapy can be extensive and can lead to
severe morbidity.
Conclusion: Polymyositis as a paraneoplastic phenomenon
due to a kidney tumour.
C067 Polymyositis as a paraneoplastic phenomenon in
renal cell carcinoma
B.A.M. de Weijer, K.M. Beekman, M.E.M. Rentinck
Tergooi Hospital, Department of Internal Medicine,
Vanriebeeckweg 12, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
C068Posterior reversible encephalopathy syndrome
(PRES)
H. van der Wijngaart, M.P. Hendriks
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: [email protected]
Introduction: Posterior reversible encephalopathy
syndrome (PRES) is a clinical syndrome that consists of
a headache, signs of encephalopathy, visual symptoms
and seizures. The clinical presentation is nonspecific;
the diagnosis can be confirmed by magnetic resonance
imaging (MRI) showing abnormalities in the white matter
of the posterior cerebral hemispheres. The pathogenesis is
unknown. The syndrome may be caused by hypertension
and the use of cytotoxic and immunosuppressive drugs. A
hypothesis is that severe hypertension exceeds the limits of
autoregulation and causes endothelial dysfunction, leading
to cerebral edema. The clinical and neurological symptoms
are reversible after adequate blood pressure management.
Therefore it is important to recognize PRES on time.
Case: A 66-year old Caucasian woman was treated
with R-CHOP therapy (rituximab, cyclophosphamide,
vincristine, and prednisone) for the first time because of
a mantle cell lymphoma stage IV, located in the stomach,
lymph nodes and bone marrow. Before the first course
of chemotherapy, she received aggressive fluid hydration
to prevent tumor lysis syndrome. On day 10 after the
first chemotherapy she was admitted to the hospital
because of neutropenic fever pitting edema of the legs
and hypertension (200/100 mmHg). Her medical history
revealed type 2 diabetes and prior pulmonary embolism.
On admission, ceftazidime was started because of the
fever and neutropenia and furosemide because of the
peripheral edema. Shortly after admission she developed
a period of confusion, aphasia, apraxia and neglect of her
right side. A MRI scan of her brain showed white matter
edema in the parietal and occipital regions. A lumbar
puncture was unremarkable. Urine dipstick was positive
for proteinurea (2+). Fundoscopic examination showed
hypertensive retinopathy grade 2. nifedipine was added to
the medication. Within days the complaints disappeared,
a second MRI scan showed improvement of the abnormalities described earlier.
Although chemotherapy (especially rituximab or
vincristine) might have contributed to the development
of PRES in our patient, she continued treatment with
R-CHOP after 2 weeks, under strict blood pressure
monitoring, without any problems.
Introduction: Paraneoplastic features in renal cell carcinoma
are not rare. However, polymyositis is rarely described.
Case: A 70-year old woman was admitted with muscle
weakness of the proximal extremities, dyspnea and a
subfebrile temperature. Her medical history included
hypertension and asthma. Blood pressure and heart
rate were normal, her temperature was 38.2 degrees
Celsius. Laboratory results showed elevation of creatine
kinase (11256 U/L) and lactate dehydrogenase (1592 U/L),
creatinine was 99 mmol/L with no electrolyte disorders.
Serum transaminases were elevated. C-reactive protein was
28 mg/L and there was a mild leucocytosis. Haemoglobin
and trombocytes were normal. Urine analysis was normal.
A CT scan of the chest showed subsegmental pulmonary
embolisms. The patient was treated with low molecular
weight heparin. Intravenous fluid suppletion was started
for the reason of rhabdomyolysis.
During admission, she developed a fever. No microorganisms were identified in the multiple cultures that
were taken from her blood, urine, sputum and bronchoalveolar fluid and there was no response to broad-spectrum
antibiotics. Auto-immune serological tests were negative.
A PET-CT showed FDG-avid infiltration in both lungs,
also a 1 cm lesion in the right kidney, suspicious for renal
cell carcinoma. Large biopsies of the lesion were taken
previous to radiofrequency ablation (RFA). The results of
these biopsies were inconclusive.
For the polymyositis, a treatment with azathioprine and
corticosteroids was started and as a result, creatinine
kinase values normalized, although the patient remained
dependant on steroids. After RFA treatment, we were able
to lower the corticosteroid dose while the condition of the
patient improved. The polymyositis remained in remission.
Discussion: As auto-immune causes and infectious causes
for polymyositis were excluded, we concluded that the
polymyositis occurred secondary to the cT1N0M0 kidney
tumour. After RFA, the azathioprine and corticosteroids
could be tapered off and ultimately discontinued. The
polymyositis remained in remission.
67
Conclusion: Consider the diagnosis PRES when sudden
high blood pressure occurs in combination with lesions
in the white matter, because the diagnosis has important
therapeutic and prognostic implications, the reversibility
of the clinical and radiologic abnormalities depends on
prompt control of blood pressure.
testinal tract. Because there was no curative option for
metastasized adenocarcinoma and palliative chemotherapy
would only be possible after stenting of the common bile
duct and continued dialysis, active treatment was stopped.
The patient died four days later.
Conclusion: The jaundice (“yellow”) and acrocyanosis
(“blue”) markedly influenced the diagnostic strategy in
this case. A treatable autoimmune disease was suspected
and led to additional diagnostic procedures and therapy.
In retrospect, the patient’s clinical course is compatible
with metastatic adenocarcinoma originating from the
gastrointestinal tract and paraneoplastic auto-immune
acrocyanosis, which is rare.
It was difficult to obtain pathological proof of the
underlying disease, but in the end we obtained an accurate
diagnosis and prognosis.
C069Yellow and blue: a colourful story
W. Roukema, T.W. van Hal, C.G. Vermeij, L.W. Kessels,
M.M. Smits
Deventer Hospital, Department of Internal Medicine, Nico
Bolkensteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected]
Introduction: In an era of advancing laboratory investigations and imaging techniques, a patient’s history and
physical examination remain the cornerstones of medical
diagnosis. Occasionally however, noticeable symptoms on
physical examination may alter the presumed diagnosis
and lead to sidetracks in the diagnostic process.
Case: A 76-year-old woman with a history of hysterectomy
and hypertension presented with diminished appetite,
abdominal discomfort and weight loss. On physical
examination jaundice and a palpable abdominal mass
were noted. Laboratory evaluation showed Coombs negative
haemolytic anaemia, acute renal failure and elevated liver
enzymes. Abdominal ultrasound showed pathologically
enlarged hepatic hilar lymph nodes compressing the
common bile duct. Because metastatic digestive tract
tumour or malignant lymphoma were suspected, CT
scan was performed showing pathologically enlarged
mediastinal and abdominal lymphadenopathy and
thickened wall of the ascending colon. Mucosal biopsies
during colonoscopy showed no malignancy. Meanwhile
renal failure progressed. On repeat physical examination
acrocyanosis of the hands and feet was noted. This,
combined with hypertension, haemolytic anaemia and
renal failure led to a presumed diagnosis of autoimmune
disease (e.g. scleroderma or SLE), thrombotic microangiopathy (HUS) or vasculitis. Renal biopsy showed tubular
damage suggestive of acute tubular necrosis. ANF was
positive (anti Scl-70 antibodies).
Cytological examination of an ultrasound-guided biopsy
of the hepatic lymphadenopathy was inconclusive. Further
investigations were cancelled due to further clinical deterioration and anuric renal failure. Because no malignancy
had yet been demonstrated, it was decided to start haemodialysis and high dose prednisolone.
When the patient had improved sufficiently, endoscopic
biopsy of the mediastinal lymphadenopathy was
performed. Pathological examination revealed metastasis
of an adenocarcinoma, most likely from the gastroin-
Reference
• Acrocyanosis: the Flying Dutchman; Kurlinsky et al. Vasc
Med 2011 Aug 16(4): 288-301
C070 Lethal toxicity of capecitabine due to dihydropyrimidine dehydrogenase (DPD) deficiency
V.L. Schouten, C.J. van Groeningen
Amstelland Hospital, Department of Internal Medicine, Laan
van de Helende Meesters 8, 1186 AM AMSTELVEEN, the
Netherlands, e-mail: [email protected]
Background: Capecitabine is a frequently used chemotherapy agent for gastro-intestinal and breast cancer. Every
year around 8.000 people in the Netherlands are treated
with capecitabine, an oral prodrug of 5-fluorouracil (5-FU).
5-FU is catabolised by the enzyme DPD. Patients with a
DPD deficiency may experience severe toxicity of 5-FU.
In 3-5% of the Caucasian population intermediate DPD
activity is present. Enzyme activity less than 60-70% of
normal leads to a clinically significant higher chance of
toxicity.
Case: Our patient was a 79-year-old male with metastatic
adenocarcinoma of the rectum. He received capecitabine palliative chemotherapy plus bevacizumab. Two
weeks after the start of the treatment he was seen at the
Emergency Department with severe mucositis and diarrhea
more than ten times a day. His vital signs were normal,
his temperature was 36.7 °C. He had severe skin lesions
on his extremities, abdomen and back. The white blood
cell count was 5.2 x 109/L with a normal differential, the
C-Reactive Protein was 29 mg/L, the alkaline phosphatase
was 161 mmol/L and the gamma-glutamyltransferase
115 mmol/L.
Severe capecitabine induced toxicity (grade IV) was
suspected and treatment with intravenous fluids was
given. Four days after admission he deteriorated with
68
tumor necrosis factor a and sICAM-1). Biomarkers were
combined into overall scores (higher scores indicating
worse function). Measurements were performed at
baseline and after (median) 7 years. Longitudinal data
were analyzed with generalized estimating equations
and adjusted for sex, age, glucose metabolism status,
energy intake, body mass index, physical activity, alcohol
consumption and smoking status.
Results: Higher consumption of fish (per 100 g/wk), but
not vegetables, fruit, alcohol-containing beverages or dairy
products, was associated with a lower overall endothelial
dysfunction score over 7 years: b (95% CI) -0.027 (-0.051;
-0.004). No associations were observed with the overall
low-grade inflammation score. Further food component
analyses indicated that consumption of more lean fish
and raw vegetables, and less high-fat dairy products was
associated with less endothelial dysfunction. Consumption
of more fresh fruit and wine, and less high-fat dairy
products was associated with less low-grade inflammation.
Conclusion: These data suggest that dietary modification
of endothelial dysfunction and low-grade inflammation,
processes that are important in atherothrombosis, is
possible.
the occurrence of fever (temperature 38.4), hypotension
and tachycardia. Labresults revealed severe neutropenia.
Antibiotic treatment with meropenem was started for
neutropenic fever. Because of the severe toxicity blood was
drawn for a possible DPD deficiency. The next day patient
further deteriorated, he was in septic shock and the blood
cultures were positive for E coli. Patient died a few hours
later.
Discussion: An intermediate DPD activity is seen in 3-5%
of the Caucasian population and in 0,1-0,2% a complete
DPD deficiency. Fifty percent of these patients have a
so-called DPYD*2A mutation which can be investigated by
genotyping. Also, previous studies have shown that toxicity
in DPD deficiency is less severe when capecitabine dose is
reduced. Since capecitabine is prescribed to a significant
number of patients in the Netherlands we should be more
aware and consider screening for DPD deficiency.
X
VASCULAR MEDICINE RESEARCH
C071 A healthy diet is associated with less endothelial
dysfunction and less low-grade inflammation over a
7-year period – the CODAM study
C072 HCN2/SkM1 gene transfer into canine left bundle
branch induces stable, autonomically responsive
biological pacing at physiological heart rates
B.C.T. van Bussel1 , R.M.A. Henry 1, I. Ferreira1,
M.J. van Greevenbroek1, C.J.H. van der Kallen1, J.W.R. Twisk2,
E.J.M. Feskens3, C.G. Schalkwijk1, C.D.A. Stehouwer1
1
Maastricht University Medical Centre, Department of Internal
Medicine, P.debyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected], 2VU University
Medical Centre, AMSTERDAM, the Netherlands,3WUR,
WAGENINGEN, the Netherlands
G.J.J. Boink1, L. Duan2, B.D. Nearing3, I.N. Shlapakova2,
E.A. Sosunov 2 , E.P. Anyukhovsky 2 , E. Bobkov 2 ,
Y. Kryukova 2 , N. Ozgen 2 , P. Danilo2 , I.S. Cohen 4 ,
R.L. Verrier3, R.B. Robinson2, M.R. Rosen2
1
Academic Medical Centre, Department of Internal Medicine,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: [email protected], 2Columbia University, NEW YORK,
USA 3Harvard University, BOSTON, USA, 4Stony Brook
University, STONY BROOK, USA
Introduction: A healthy diet rich in fish, fruit and
vegetables, but low in alcohol and dairy products, has been
associated with less incident cardiovascular disease (CVD),
but the mechanisms are unclear. Endothelial dysfunction
and low-grade inflammation play important roles in the
development of CVD. A healthy diet might modify these
phenomena.
Aim of the study: To investigate the association between
the above food groups and overall biomarker scores of
endothelial dysfunction and low-grade inflammation in a
7-year longitudinal study.
Material and methods: In 557 participants with increased
CVD risk, we determined diet by food frequency questionnaire and measured biomarkers of endothelial dysfunction
(von Willebrand factor, soluble vascular cell adhesion
molecule 1, soluble endothelial selectin, soluble thrombomodulin, soluble intercellular adhesion molecule 1
(sICAM-1)) and of low-grade inflammation (C-reactive
protein, serum amyloid A, interleukin 6, interleukin 8,
Introduction: Gene-based biological pacemakers display
effective in vivo pacemaker function. However, approaches
used to date have failed to manifest optimal pacemaker
properties, defined as basal beating rates of 60 to 90
beats/min, a brisk autonomic response achieving maximal
rates of 130 to 160 beats/min, and low to absent electronic
backup pacing.
Aim of the study: This study sought to test the hypothesis
that hyperpolarization-activated cyclic nucleotide-gated
(HCN)-based biological pacing might be improved
significantly by hyperpolarizing the action potential (AP)
threshold via coexpression of the skeletal muscle sodium
channel 1 (SkM1).
Materials and methods: We implanted adenoviral SkM1,
HCN2, or HCN2/SkM1 constructs into left bundle
69
Conclusion: This study provides the first evidence that
blood pressure in patients with AF can be reliably tracked
and measured non-invasively. Non-invasive pulse pressure
excursions were only slightly attenuated. This validation
of non-invasive beat-to-beat blood pressure measurements
opens many possibilities for further blood pressure-related
studies in patients with AF.
branches (LBB) or left ventricular (LV) epicardium of
atrioventricular-blocked dogs.
Results: During stable peak gene expression on days 5 to
7, HCN2/SkM1 LBB-injected dogs showed highly stable
in vivo pacemaker activity superior to SkM1 or HCN2
alone and superior to LV-implanted dogs with regard
to beating rates (resting approximately 80 beats/min;
maximum approximately 130 beats/min), no dependence
on electronic backup pacing, and enhanced modulation
of pacemaker function during circadian rhythm or
epinephrine infusion. In vitro isolated LV of dogs overexpressing SkM1 manifested a significantly more negative
AP threshold.
Conclusions: LBB-injected HCN2/SkM1 potentially
provides a more clinically suitable biological pacemaker
strategy than other reported constructs. This superiority
is attributable to the more negative AP threshold and
injection into the LBB.
C074 Determination of apolipoprotein B by the general practitioner: Diminished referral to the outpatient clinic
A.L.M. van de Ven1, B.P.M. Imholz1, J. de Graaf2
Twee Steden Hospital, Department of Internal Medicine,
Dr Deelenlaan 5, 5042 AD TILBURG, the Netherlands,
e-mail: [email protected], 2Radboud University Medical Centre,
NIJMEGEN, the Netherlands
1
Introduction: Unlike the Dutch guidelines, apolipoprotein
B (apoB) is recommended in the European guidelines for
Cardiovascular Risk (CVR) Management alongside measuring
traditional lipid profile. Advantages include 1. more accurate
determination of number and type of (atherogenic) lipoprotein
particles thereby facilitating diagnosis and 2. assessing CVR
and thereby indication for therapy.
Aim of the study: Determining the potential role of apoB
in the decision making of GP’s to refer to the lipid clinic.
Material and Methods: Retrospectively, we collected data
from all patients who visited the lipid clinic of the Twee
Steden Hospital in Waalwijk in years 2008-2009. We
recorded reason for referral, lipid profile and use of lipid
lowering medication. ApoB was determined after first
visit and used to assess diagnosis (using the diagnostic
apoB algorithm by de Graaf et al.), CVR and indication for
(change in) therapy.
Results: Fifty-eight patients were included. In 13 patients
the GP couldn’t make correct diagnosis or CVR estimation
because of TG > 4.5 mmol/L. Measuring apoB revealed
that in 9 patients hypertriglyceridemia was due to elevated
VLDL (n = 6) and/or chylomicrons (n = 3) with apoB
< 1.2 g/L. Taking into account primary and secondary
prevention (n = 4 on statin therapy), apoB targets were
present with no indication (for change) lipid lowering
therapy. The other four patients, without statin, had apoB
> 1.2 g/L with combined dyslipidemia based on VLDL+LDL
with an increased CVR and indication for treatment.
Thirty-one patients presented with elevated TG (1.5dyslipidemia was based on LDL (n = 9) or LDL+VLDL (n =
14) with apoB > 1.2 g/L. Because of increased CVR an
indication to start (n = 16) or raise (n = 7) lipid lowering
therapy was present in all 23 patients. In 8 patients dyslipidemia was based on elevated VLDL with apoB < 1.2 g/L
with indication for therapy dependent on CVR assessment.
Four high-risk patients already used statins.
C073 Blood pressure in atrial fibrillation can be accurately
measured using a non-invasive finger cuff method
Y.M. Smulders, G.F.N. Berkelmans, A.M.E. Spoelstra-Deman,
M.C. de Waard, B.E. Westerhof, Y.M. Smulders
VU University Medical Centre, Department of Internal
Medicine, Balearenlaan 34, 1060 TL AMSTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: Routine manual and automated blood
pressure measurements cannot reliably assess blood
pressure in patients with atrial fibrillation (AF), which
changes with every heartbeat. This seriously impairs
selection of AF patients for antihypertensive treatment,
as well as their follow-up. Non-invasive beat-to-beat blood
pressure measurement devices are available, but have not
been validated for use in patients with AF.
Methods: We included hemodynamically stablepatients in
the ICU or medium care unit, who had sustained AF and
intra-arterial blood pressure monitoring. We compared
their beat-to-beat blood pressure values with measurements obtained for 15 minutes via a finger cuff (Nexfin®,
Edwards Lifesciences BMEYE, Amsterdam). A control
group of patients in sinus rhythm was included as well.
Patients with compromised peripheral perfusion, high
vasopressor doses and/or peripheral edema were excluded.
Results: Mean difference in beat to beat fluctuations
(non-invasive vs intra-arterial) was extremely low in both
patient groups: -0.001 ± 0.007 mmHg in AF, and 0.006
± 0.009 mmHgin sinus rhythm, regardless of frequency.
In patients with atrial fibrillation, the mean difference
(non-invasive vs intra-arterial) in systolic blood pressure
was -5.8 ± 6.7 mmHg, and 2.3 ± 9.7 mmHg for diastolic
blood pressure.
70
Fourteen patients presented with triglycerides < 1.5 mmol/L
and apoB < 1.2 g/L under current statin treatment. Ten
patients were referred for genetic FH-screening. Four
high-risk patients had not reached LDL < 2.6 mmol/L;
1 patient had an apoB of 0.68 g/L, so no need to adjust
treatment.
Conclusion: In 28 out of 58 patients measurement of apoB
contributed to a more accurate determination of number
and type of (atherogenic) lipoprotein particles thereby
facilitating diagnosis, assessing CVR and indication for
therapy. It may facilitate the GP less referral to the lipid
clinic, especially in patients with TG > 4.5 mmol/L.
the other adjustments, nor the newly derived CDR, resulted
in a higher efficiency with an acceptable failure rate.
Conclusions: The standard CDR combined with the
age-adjusted D-dimer threshold resulted in a limited
increase of efficiency with an acceptable failure rate. Our
additional attempts to safely reduce the high need for
CTPA were unsuccessful.
C076 Coronary leukocyte activation as predictor of cardiovascular events in young subjects: five year follow-up
data
M.A. de Vries, A. Alipour, B. Klop, T.L. Njo, J.W. Janssen,
A.H. Liem, E. Birnie, M. Castro Cabezas
St Franciscus Gasthuis, Kleiweg 500, 3045 PM ROTTERDAM,
the Netherlands, e-mail: [email protected]
C075 Optimization of the diagnostic management of
clinically suspected pulmonary embolism in hospitalized patients
T. van der Hulle1 , P.L. den Exter 1, I.C.M. Mos1,
P.W. Kamphuisen2, M.M.C. Hovens3, M.J.H.A. Kruip4,
J. van Es5, H. ten Cate6, M.V. Huisman1, F.A. Klok1
1
Leiden University Medical Centre, Department of Thrombosis
and Haemostasis, Albinusdreef 2, 2300 RC LEIDEN, the
Netherlands, e-mail: [email protected], 2University
Medical Centre Groningen, GRONINGEN, the Netherlands,
3
Rijnstate Hospital, ARNHEM, the Netherlands, 4Erasmus
Medical Centre, ROTTERDAM, the Netherlands, 5Academic
Medical Centre, AMSTERDAM, the Netherlands, 6Maastricht
University Medical Centre, MAASTRICHT, the Netherlands
Introduction: Although leukocyte activation has been
linked to atherogenesis, there is little in vivo evidence in
humans for its role in the progression of atherosclerosis.
Aim of the study: We evaluated the predictive value
of leukocyte activation markers for future cardiovascular events in patients scheduled to undergo coronary
angiography (CAG).
Materials and methods: Classical cardiovascular risk
factors were measured in patients scheduled to undergo
CAG. Monocyte CD11b and neutrophil CD66b expression
in different vascular regions (coronary arteries, abdominal
aorta, femoral artery and peripheral vein) were determined
by flow cytometry. Patients were divided into four groups,
based on their age (older or younger than 65 years
at inclusion) and level of leukocyte activation in the
coronaries (above or below the median of the total group).
Data are given as mean ± SEM.
Results: A total of 91 subjects was included, of which 63
had coronary artery disease (CAD) at inclusion. The mean
duration of follow-up was 1847 ± 27 days. The prevalence
of CAD did not differ between patients with high or low
leukocyte activation, but patients aged above 65 years more
frequently had CAD than the younger patients. Young
patients with high monocyte CD11b expression in the
coronaries (37.9 ± 1.9 au, n = 30) developed an event more
often than young patients with low monocyte CD11b (29.5
± 1.9, n = 19) (40% versus 5%, Log Rank test p = 0.016). In
the elder patients, the rate of events did not differ between
the groups with high or low monocyte CD11b expression
(17% versus 22%, p = NS). Similar trends were seen for
monocyte CD11b expression in the other sampling sites, as
well as for neutrophil CD66b expression in all sampling
sites, without reaching statistical significance.
Conclusion: Increased monocyte CD11b expression in
the coronaries is associated with incident cardiovascular
disease in patients younger than 65 years. This provides
Background: Identical diagnostic algorithms for suspected
pulmonary embolism (PE) (clinical decision rule (CDR)
followed by D-dimer testing and/or computed tomography
pulmonary angiography (CTPA)) are used for in- and
outpatients, while D-dimer levels, risk factors and pre-test
probability for PE differ. We firstly evaluated the efficacy of
the standard algorithm in a validation cohort of inpatients
and secondly aimed to optimize the algorithm in this
cohort combined with a previous cohort of inpatients.
Methods and results: Efficiency (number of CTPAs) and
safety (3-month venous thromboembolism (VTE) incidence
rates) of the standard algorithm were studied in a validation
cohort. We further studied the potential of increasing
the D-dimer threshold and/or the CDR threshold in this
and a previous cohort and derived a new CDR based
on a multivariate regression analysis. In the validation
cohort (n = 140),only 2% (3/140; 95% CI 0.4-6.1) were
managed without CTPA. Combining two cohorts (n = 624),
overall PE prevalence was 25%, standard management
resulted in a 3-month VTE incidence rate of 0.0% (95% CI
0.0-7.3) and 92% of patients underwent CTPA. Applying
an age-adjusted D-dimer threshold resulted in a -4.5
percentage points (95% CI 1.2-7.8) reduction of CTPAs with
a VTE incidence rate of 1.9% (95% CI 0.9-3.6%). None of
71
C077 Echocardiographic evaluation of patients referred to
the department of emergency medicine because of
chest pain discomfort after completing a marathon
We were unable to demonstrate transient impairment of
RV function due to marathon running, as reported in
several previous studies. Absence of 3D echocardiography
in our institution prompted us to evaluate the RV function
with robust conventional parameters such as TAPSE not
allowing us to detect more subtle changes by performing
a measurement of the RV-EF.
J.M.J.B. Walpot, J. van Zwienen
Admiraal de Ruijter Hospital, Department of Cardiology,
Koudekerkseweg 88, 4380 DD VLISSINGEN, the Netherlands,
e-mail: [email protected]
C078 dvanced Glycation Endproducts (AGE’s) measured
subcutaneously do not reflect atherosclerotic abnormalities in the FH population
in vivo evidence for the involvement of leukocyte activation
in atherogenesis.
S. Smit, B.P.M. Imholz
Twee Steden Hospital, Department of Internal Medicine, Dr
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected]
Background: The goal of our analysis was to describe
the echocardiographic findings of patients referred to
the department of Emergency Room because of chest
discomfort due to marathon running.
Methods: In this retrospective observational study, the
data of patients referred to our hospital because of chest
pain complaints due to participating a local marathon
were analyzed. The transthoracic echocardiography studies
(TTE) were performed by an experienced ultrasonographer
or an echo cardiologist. The dimensions were measured:
IVSd, LVIDd and LVIDs. The left ventricular function was
assessed by determining the LV-EF by LVEF Automated
Biplane planimetry. The assessment of the diastolic
function was performed by the following measurement:
E, A, E’, E/E’ ratio and MV dec T. The right ventricular
function was assessed by TAPSE, RV S’ and the RVSP.
Results: Four patients were referred to our hospital because
of chest pain complaints due to marathon running. In 3 out
of 4 patients, an increased Troponin I level was observed.
The ECG repolarization patterns of all patients were
abnormal. In 3 patients, the coronary arteries were normal.
The TTE studies were performed within 24 hours after
admission. The measurements were as follows:
Dimensions: I VSd 9.3 mm (range 9-10); LVIDd 58.2 mm
(55-64); LVIDs 36.7 mm (range 32-39); LV Systolic function:
LVEF Automated Biplane planimetry: 59%(range 53-61) and
absence of focal left ventricular kinetic disturbances; Diastolic
function: E 58.8 cm/s(range 43-74), A 58.8 cm/s(range 44-68),
MV dec. T 226 ms (range 156-266), E’ 9.75 cm/s(range 9-11),
E/E’ 5.88 (range 4.33-7.22); Right Ventricular function and
pressures: TAPSE 12.2mm (range 20-25), RV S’ 11.5cm/s(range
11-12), RVSP 22.7 mm Hg(19-26).
Conclusion: In the three patients with increased troponin
I or changing abnormal ECG patterns and documented
absence of coronary heart disease, the LV systolic function
was preserved in 2 patients and mildly diminished in 1
patient. This is in agreement with previous studies, which
could not document temporarily alterations in systolic LV
function due to endurance sporting. In contrast to another
study, we were not able to detect impairment of LV diastolic
function after completing the marathon.
Introduction: To predict CV-risk, measurement of Advanced
Glycation Endproducts are introduced. The AGEreader
(Diagnoptics, Groningen, Netherlands) measures AGES
subcutaneously at the underarm by means of auto-immunofluorescence and predicts CV-risk. The device gives the
measured AF value as a percentile for the patients age; which
are believed to represent higher risk for CV disease at higher
AF-values. In a Familial Hypercholesterolemia population we
measure common carotid Intima Media Thickness (ccIMT)
as a measure of progression of atherosclerosis.
Methods and Data analysis: To compare the ability to
assess the extent of atherosclerosis by both methods, the
percentiles of AGES and ccIMT were compared in 320
consecutive patients visiting the Vascular Unit outpatient
department.Scatterplots were made between age and
ccIMT and age vs AGES. In addition percentiles of AGES
were plotted against ccIMT percentiles. Correlation coefficients were determined.
Results: The fig shows the% ccIMT on the x-axis and
the simultaneously measured%-AGES on the y-axis. It
is evident that there is no relation between the two
measures of atherosclerosis. We also compared the groups
with low and high risk in ccIMT (p80) and determined
the% of agreement of risk by the AGES. In the high risk
pccIMT subjects we counted 230/320 subjects. In 35 of
these subjects (15,2%) high risk was confirmed with the
AGEreader; 40 of the high risk ccIMT had a low risk
pAGES (17.4%). The only subject with a low pccIMT value,
had an incongruent p80 value!
Conclusions: The AGEreader offers easy measurement
of CV risk. However, in an established high-risk FH
population the outcome does not reflect the established
atherosclerotic alterations in ccIMT.Further research is
needed to use the elegant AGEREADER device as a tool for
prediction of CV-risk in high risk patients.
72
XI
C080A skin lesion as a sign of a rare, Possible severe
complication of treatment with low molecular weight
heparins
VASCULAR MEDICINE CASE REPORTS
C079 Painless and pulseless: don’t forget the aortic trunk
A.J.W.M. Brouns1, K.S.G. Jie2
Atrium Medical Centre, Department of Internal Medicine,
Henri Dunantstraat 5, 6419 PC HEERLEN, the Netherlands,
e-mail: [email protected], 2 Atrium Medical Centre/
Zuyd University of Applied Sciences, HEERLEN, the
Netherlands
1
D.J.L. van Twist, M.M.H. Hermans
Viecuri Medical Centre, Department of Internal Medicine,
Postbus 1926, 5900 BX VENLO, the Netherlands, e-mail:
[email protected]
Case: A 49-year old male without relevant medical history
and without medication presented on the emergency
department because of a collapse. He complained of an
acute right-sided headache since several hours. By mistake,
he took 10 mg of nifedipine (a calcium channel blocker)
assuming it was an analgetic. Thirty minutes later he
felt light-headed and collapsed. On physical examination
no abnormalities were found, except for a low blood
pressure of 75/45 mmHg, which was attributed to the use
of nifedipine. Routine blood tests (including CRP and
blood count), electrocardiogram, and CT-scan of the head
were normal. The patient was admitted to the neurology
ward for observation, where the headache disappeared
within a few hours. Because of persistent hypotension
despite 5 liters of 0.9% saline infusion over 8 hours (blood
pressure remained 75/45 mmHg,) we were consulted.
We saw a patient without complaints, except for a little
nausea. Thorough physical examination revealed absent
radial and brachial pulses of the right arm, and a soft
(grade 1/6) systolic murmur over both carotid arteries and
the right hemithorax (at the level of the nipple line). On
suspicion of abnormalities of the aortic trunk a CT-scan of
the chest was performed which demonstrated a dissection
of the ascending aorta and the left carotid artery. With
a diagnosis of type A aortic dissection the patient was
transferred to a cardiothoracic surgery centre where he
underwent an emergency ascending aortic replacement.
Discussion: Acute aortic dissection classically presents as a
sudden, severe chest, back or abdominal pain. Early diagnosis
is important, as a mortality rate of 1-2% per hour during the
first 48 hours of presentation has been reported in patients
with type A dissection. In this case, the patient presented with
atypical complaints of headache and collapse (and later only a
little nausea), which resulted in a serious delay in diagnosing
this highly lethal illness. According to some small case-series,
an atypical, painless presentation is described in 6 - 17% of
the aortic dissections. Sometimes, only subtle clues at physical
examination (as in this case one-sided absence of radial
pulse and a soft thoracic murmur) point towards an aortic
dissection. Although the ingestion of nifedipine obviously
puts the doctors on the wrong track, this case illustrates the
importance of thorough physical examination and awareness
for signs of aortic pathology.
Introduction: Low molecular weight heparins (LMWHs)
are widely used for the prevention and treatment of venous
thromboembolism (VTE). Although this treatment is
considered to be safe, heparin induced thrombocytopenia
(HIT) could cause life threatening complications.
Case report: A 36-year old female was hospitalized because
of a malignancy associated thrombosis of the right
femoral vein. Daily subcutaneous injections of tinzaparin
were started pending further diagnostic evaluation. On
admission the platelet count was 197*109/L, 15 days later her
platelet count decreased to 49*109/L. She also developed a
localized, painful erythema on her upper left leg of 10 by
10 centimeters after 16 days treatment with tinzaparin. The
differential diagnosis of this erythema consisted of a skin
infection, cutaneous delayed-type hypersensitivity reaction
to heparin or heparin induced skin lesions. Because of a
high probability score (six out of eight points) on the 4T
pretest scoring system for HIT a heparin-induced platelet
aggregation (HIPAA) and PF-4 heparin ELISA test were
performed. Both were strong positive, confirming the
diagnosis of HIT due to LMWHs. Subsequently tinzaparin
was replaced by fondaparinux and five days later the platelet
count increased to 155*109/L and the skin lesions decreased.
Discussion: The incidence of HIT in patients treated for
at least five days with LMWHs is lower than in those
treated with unfractionated heparins (UFHs), 0-0.8%
versus 0,8-2.7%. Administration of heparins can trigger an
antibody response, provoked by heparin and the heparin-PF4
complex. This complex binds to and activates platelets,
followed by aggregation and prematurely removing from
the circulation. Simultaneously, generation of procoagulant platelet derived microparticles results in thrombin
formation and thrombosis. Skin lesions in patients with
HIT due to LMWHs are rare and have only been reported
in few case reports. These lesions are caused by intradermal
microvascular thromboses. Mainly the microvasculature
of the superficial dermal layer is affected, because only the
vasculature of this layer bear FcgRIIa receptors involved in
platelet activation. Typically five days or more after heparin
initiation, the skin lesions begin as erythematous lesions
with initial involvement at injections sites followed by sites
of high fat content. In the majority of the cases discontinuation of heparin treatment and changing to non-heparin
73
anticoagulants leads to an uneventful clinical course. But
unrecognized extensive cutaneous necrosis can occur.
Conclusion: The incidence of skin lesions in patients with
HIT due to LMWHs is low. However, early recognition
and appropriate treatment replacement prevents severe
complications.
also shown to contribute to the development of early atherosclerosis3. As well, severe hypertriglyceridaemia increases
the risk of developing pancreatitis. Triglycerides in this
range are, however, uncommon with acitretin therapy,
and usually occur when other secondary causes or genetic
disorders are present.
Routine monitoring of the lipid spectrum during treatment
with acitretin is necessary4. In patients with a moderate
elevation in the triglycerides, lifestyle-interventions should
be advised, especially when acitretin is only used for a
short period. When there are multiple cardiovascular risk
factors present or when a patient is at risk for a triglycerideinduced pancreatitis, treatment with a fibrate should be
considered.
Conclusion: Hyperlipidaemia during acitretin therapy is
a common side effect for which routine monitoring of the
lipid spectrum is indicated.
C081 Acitretin-induced hyperlipidaemia
C.J.G. Lap, H.J. Jansen
Jeroen Bosch Hospital, Department of Internal Medicine,
Henri Dunantstraat 1, 5223 GZ ’S HERTOGENBOSCH, the
Netherlands, e-mail: [email protected]
Introduction: Acitretin is a retinoid, which is frequently
prescribed for the treatment of severe skin disorders. Three
patients are described who developed hyperlipidaemia after
starting treatment.
Cases: A 52-year-old male, diagnosed with dyskeratosis
follicularis in 2008 and under treatment with acitretin
since then. A progressive hyperlipidaemia developed
with a high-density-lipoprotein (HDL) of 0.9 mmol/
Liter, low-density-lipoprotein (LDL) of 4.6 mmol/Liter
and triglycerides of 3.5 mmol/Liter. We concluded that
acitretin was the cause for the hyperlipidaemia, possibly
with a genetic predisposition because of his positive family
history. We recommended lifestyle-changes.
A 55-year-old woman, diagnosed with lichen rubor planus
and under treatment with acitretin for a few months. A
lipid spectrum showed triglycerides of 9.4 mmol/Liter
with an apolipoprotein B of 1.29 gram/Liter. We concluded
that her hypertriglyceridaemia was caused by acitretin
combined with central obesity (BMI 37kg/m2) and insulin
resistance. After discontinuation of acitretin, her lipid
spectrum improved to acceptable values.
A 22-year old male, diagnosed with severe psoriasis and
under treatment for six months with acitretin. His lipid
spectrum showed a HDL of 0.8 mmol/Liter, LDL of
2.8 mmol/Liter and triglycerides of 4.8 mmol/Liter. We
concluded that acitretin had induced the hypertriglyceridaemia and recommended life-style changes.
Discussion: Hyperlipidaemia during treatment with
acitretin is caused by the combination of decreased tissue
lipase activity as well an increase in the production of
triglyceride-rich VLDL particles1. Although the largest
increase is seen in triglycerides (20-40% of patients),
a small increase in LDL (10-20%) with a decrease in
HDL (30%) can be observed as well. In addition, most
changes are dose-dependent and normally reverse after
discontinuation2.
Although an elevated LDL is associated with an increased
risk for cardiovascular disease, hypertriglyceridaemia has
C082 Two patients with homozygous Dunnigan-type
familial partial lipodystrophy (FPLD) with ischemic
colitis of unknown origin
F.M.F. Alidjan, J. Langendonk
Erasmus Medical Centre, Department of Vascular Medicine,
S-Gravendijkwal 230, 3015 CE ROTTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: Individuals with Dunnigan-type familial
partial lipodystrophy (FPLD) gradually lose fat from the
upper and lower extremities resulting in a muscular
appearance with prominent superficial veins. Metabolic
abnormalities include insulin-resistant, diabetes
mellitus,hypertriglyceridemia and can result in premature
atherosclerosis. We present two homozygous siblings with
FPLD with ischemic colitis of unknown origin.
Case report: Patient A is a 32-year-old female was admitted
to our hospital because of acute abdominal pain and
bloody diarrhoea. Her medical history was homozygous
FPLD,hypertension,dyslipidaemia. Physical examination
showed a temperature of 37.1, normal blood pressure and
abdominal examination was unremarkable. Laboratory
assessment revealed normal CRP < 1 mg/L, LDH 131 U/L,
Lactate 3.1 mmol/I, Leucocyte 14.2 x 10E9/I, Hemoglobine
8 mmol/I. Abdominal CT revealed swollen walls of the
colon ascendens with fat infiltration, without signs of
mesenteric ischemia or atherosclerotic abnormalities of
the aorta or mesenteric arteries. Colonoscopy showed a
segmental colitis of 35-55 cm and pathology showed signs
of ischemic colitis with no sign of inflammatory bowel
disease. Blood and faeces cultures were negative. After
several days of conservative therapy, symptoms gradually
stopped, and she was discharged symptom free.
74
C083 A young woman with a rare cause of hypertension
absent. No blood pressure could be measured at the lower
extremities. These abnormalities led us to look for an
aortic coarctation. Laboratory tests and urine analysis were
normal. Chest radiography showed bilateral notching of the
distal margins of the 3rd to 8th ribs possibly due to erosion by
intercostal collateral arteries and a prominent aortic arch.
CT angiography of the thorax and abdomen revealed severe
narrowing of the thoracic descending aorta, distal of the
insertion of the left subclavian artery, and extensive collateral
circulation. Adnexa were normal. MRI of the heart showed a
bicuspid aortic valve without aortic valve stenosis (valve area
4.4cm2) and an aortic coarctation with prestenotic, stenotic
and poststenotic diameters of 2 cm, 6 mm and 2.2 cm
respectively. The patient had an ankle brachial pressure index
of 0.52 at the right and 0.53 at the left side at rest.
The patient was referred to the cardiac surgeon for
correction of the coarctation and will undergo covered stent
implantation in the near future.
Discussion: This case illustrates a 33-year-old woman with
therapy-resistant hypertension caused by a congenital
post-ductal coarctation of the aorta. This congenital defect
is a major cause of hypertension in young children. It can
be asymptomatic and remain undiagnosed until adulthood.
It may be associated, as in this case, with bicuspid aortic
valve. The preductal type is associated with Turner’s
syndrome. Karyotyping was not conducted because adnexa
seemed normal. Late detection and treatment of aortic
coarctation profoundly affects survival rate.Therefore,
specific physical findings such as discrepant blood
pressure in the upper and lower extremities and a weak or
absent femoral pulse require considering this diagnosis.
J. Ursinus, J.T. Keijer, P.J. de Vries
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
C084 Case-report: diagnostic and therapeutic dilemmas
in a young patient with an unlikely cause of an
abdominal mass
Patient B is her 35-year-old-brother, admitted one year
later with acute abdominal pain and bloody diarrhoea. His
medical history was homozygous FPLD, Diabetic mellitus
type 2, appendectomy. Physical examination revealed
normal vital signs and on abdominal examination diffuse
tenderness. Laboratory results showed CRP 13 mg/L, LDH
208 U/L, Lactate 6.3 mmol/I, Leucocytes 13.2 x 10E9/I,
Hemoglobine 10.3 mmol/I. Abdominal CT showed a
stenotic lesion of the origo of the truncus coeliacus
probably due to a diaphragm band, but no signs of
atherosclerotic lesions of the aorta or mesenteric arteries.
Colonoscopy showed also signs of severe ischemic colitis
which was also confirmed by pathology. He was initially
treated with rehydration and aspirin therapy. After several
days with supportive care, he was discharged without
symptoms and remained so to date.
Conclusion: FPLD is an autosomal dominant disorder
and is associated with increased risk of premature athero­
sclerosis and consequently can lead to symptomatic cardiovascular disease. In both patients FPLD is based on
homozygous mutation and well established cardiovascular
risk factors. In both patients aortic or mesenteric atherosclerosis could not be identified, while mesenteric ischemia
was proven by colonoscopy findings and pathology
analysis.Ischemic colitis could be caused by a transient
low flow hemodynamic state or venous congestion, or is
ischemic colitis a rare complication due to the remarkable
homozygous status? This still needs to be unravelled.
Introduction: Patients with hypertension are frequently
seen in the department of internal medicine. However,
hypertension in young adults is unusual and may be
caused by coarctation of the aorta.
Case: A 33-year-old woman of Armenic origin, was referred
to the outpatient clinic for evaluation of therapy-resistant
hypertension. Her medical history reported hypertension
since 2005. During 24-hour blood pressure measurement
the mean blood pressure was 154/93 mmHg during daytime
with a physiological decrease to 142/86 mmHg at night.
There were no other complaints. Menarche occurred at
the age of twelve. There had been no pregnancy. Physical
examination revealed unusually short legs, a normal
trunk and no webbed neck. We noticed a holosystolic
murmur at the left second intercostal space. Femoral artery
pulsations were weak; distal lower limb pulsations were
W. Zondag
Rijnland Hospital, Department of Internal Medicine, Simon
smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
[email protected]
Introduction: We present the diagnostic challenges of
a patient with an unlikely cause of an abdominal mass.
Subsequently we’ll discuss the therapeutic dilemmas
regarding the coagulative difficulties that followed the
final diagnosis.
Case: A 35-year-old man was referred to our outpatient
clinic because of abnormal liver biochemistry and a
hepatic hilar mass. He had no prior medical history and
no medication, nor a history of taking alcohol or drugs.
Viral serology was negative. Ultrasonography was
inconclusive regarding the liver hilum and computed
75
embolism was excluded. History revealed treated dyslipidemia since 7 years. His only complaint was fatigue. He
smoked 15-20 cigarettes per day with 36 pack years and
had a positive family history for myocardial ischemia at an
age younger than 50 years. Physical examination revealed
a blood pressure of 150/96 mmHg. His BMI was 25 kg/
m2 and abdominal waist circumference 91 cm. There
were no arcus lipoides nor tendon xanthomas, but slight
xanthelasmata at the eye lids. Laboratory investigation
showed dyslipidemia. Genetic analysis showed no familiar
hypercholesterolemia. We advised him to quit smoking and
treated hypertension and dyslipidemia adequately with life
style changes and medication. At this time, we supposed to
have treated all identified risk factors explaining the TIA.
Three months later, patient was referred to the ophthalmologistbecause of vision disturbances with straight
lines in his left eye and round forms in his right eye. The
ophthalmologist found angioid streaks in both eyes with
subretinal neovascularisations in the left eye suspect for
pseudoxanthoma elasticum (PXE). Repeated evaluation
at our ward showed multiple characteristic yellow papules
in his armpits. Skin biopsy and DNA analysis confirmed
the diagnosis PXE. At this time patient also had developed
pitting edema. Laboratory evaluation showed selective
proteinuria of 10.9 g/day with hypoalbuminemia. Serum
creatinin and urinary sediment were normal. Protein
electrophoresis showed MGUS IgG kappa of 4.7 g/L.
Kidney biopsy revealed membranous glomerulopathy
(Churge stage 2). Anti-PLA2R antibodies were positive.
Conservative renal treatment was continued since the low
urinary excretion of IgG and alpha-1-microglobulin was
compatible with a good renal prognosis.
Our case showed cardiovascular disease due to life style in
combination with PXE and nephrotic syndrome by primary
membranous glomerulopathy. PXE is a rare inherited
disease. An association with membranous glomerulopathy
has never been described. The increased risk for visual
complications, gastro-intestinal bleeding and vascular
dissection requires careful follow up and family screening.
Intensification of treatment targets must be considered
although literature is lacking. So this case emphasizes the
importance of total body inspection, even of the skin and
armpits during CVRM evaluation to prevent premature
conclusions.
tomography(CT) yielded an aspecific mass near the hepatic
hilar area. Fludeoxyglucose(FDG)-positron emisson
tomography(PET)-CT revealed no FDG activity near the
hilar mass but did show some irregularity at the distal
esophagus. Upper endoscopy showed extensive esophageal
varices matching a diagnoses of portal hypertension. A
liver biopsy yielded no primary liver pathology. 4-phase-CT
of the liver hilum however revealed portal thrombosis with
extensive collaterals resulting in cavernous transformation.
In the additional work-up a slight thrombocytosis and a
positive JAK-2 were found. The bone marrow investigation
demonstrated characteristics of essential thrombocytosis.
Because of the risk of variceal bleeding the patient was
started on propranolol and aspirin instead of coumarines.
Nonetheless two months later he presented to the
emergency department with massive variceal hemorrhage.
The aspirin treatment was temporarily terminated. We
referred him for evaluation for a transjugular intrahepatic
portosystemic shunt (TIPS) procedure. Unfortunately
this was no option because of the extensiveness of the
thrombus towards the splenic vein, superior mesenteric
vein, left gastric vein and partial thrombosis of the
esophageal varices. He was started on coumarins to
prevent extension of the thrombosis and try to achieve
recanalisation of the portal vein in order to save the liver
and therefore take the risk of another serious variceal
bleeding. In the following 6 months no additional variceal
hemorrhage occurred and the thrombosis stabilized. TIPS
could not yet be performed because of the lack of a suitable
connecting vessel.
Conclusion: This case demonstrates that portal cavernoma
can be the cause of an unexplained abdominal mass.
A portal cavernoma is the result of a cavernous transformation of a portal thrombosis. Diagnosis of portal
thrombosis in a young patient should lead to further
examination especially for malignancy or coagulation
disorder like in this case JAK-2 positive essential thrombocytosis. Despite the patients high risk of variceal
bleeding he was treated with oral anticoagulants because
progression of the mesenteric thrombosis was considered
to be a more serious complication.
C085 Don’t forget the armpit during cvrm evaluation
M.H. Hemmelder, G. Helfrich, F.L. Ubels
Medical Centre Leeuwarden, Department of Internal
Medicine, H. Dunantweg 2, 8934 AD LEEUWARDEN, the
Netherlands, e-mail: [email protected]
C086Superior vena cava syndrome; consider PTA and
stenting
K. Bolhuis, M.J.M. Herenius, S.A. Luykx- de Bakker
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
A 53 years old man was referred for cardiovascular risk
management (CVRM) after a transient ischemic attack.
Plaque formation in the carotid artery and hypertension
were already established by the neurologist and cardiac
76
XII
Superior vena cava syndrome is most commonly seen
in patients with a malignancy and can be due to local
compression of the superior vena cava by the tumor,
an invasive growth of the tumor into the vessel wall or
the formation of a venous thrombus. Other causes are
mediastinal fibrosis, infection and aortic aneurysms. A
rise in the use of intravascular catheters and devices is
increasing the prevalence of this syndrome due to a superior
vena cava thrombus. Symptoms derive from an insufficient
drainage of the veins of the upper extremities, thorax and
head into the right atrium. Symptoms include dyspnea,
chest pain, cough, dysphagia, facial swelling, arm swelling,
headaches, and cyanosis. The symptoms can be acute, debilitating and sometimes life-threatening. When anticoagulant
therapy, radiotherapy or chemotherapy does not relieve
the symptoms or when an acute intervention is needed, a
percutaneous transluminal angioplasty (PTA) with stenting
instead of surgical bypass should be considered.
Case: A 54-year old woman was seen at our emergency ward
because of a swollen face. She was known to have a central
venous access device in the jugular vein for suppletion of
minerals after a duodenal switch operation. Her medical
history was significant for an infiltrative ductal adenocarcinoma in 2010 which was successfully treated with a
local resection, radiotherapy and adjuvant chemotherapy.
There are no signs of recurrent malignancy. An ultrasound
and CT-scan were performed and showed a thrombus in
the left jugular vein in relation with the central venous
access device. Anticoagulant therapy was started with low
molecular weight heparin, adjusted to her weight. The
central venous access device was removed. After 12 days she
was seen in our outpatient clinic. Instead of a reduction of
symptoms, the symptoms had worsened with progressive
facial swelling and plethora, swelling of arms and multiple
dilated chest veins. She had gained 10 kg. Additional
venography was performed and showed progression of the
thrombus by occlusion of the proximal superior vena cava
with an extensive network of collateral veins. After PTA
with stenting of the superior vena cava a relief of symptoms
was achieved, within days. We are continuing the low
molecular weight heparin for another six months.
Conclusion: Superior vena cava syndrome can be debilitating and sometimes life-threatening. Consider PTA and
stenting of the superior vena cava when anticoagulant
therapy is not effective or instant relief of symptoms is
needed.
GASTRO-ENTEROLOGY RESEARCH
C087 Endoscopic proof of mucosal improvement 5 years
after prostate irradiation with endorectal balloon
R. Krol1, G.M. Mccoll1, W.P.M. Hopman1, E.N.J.T. van Lin2,
R.J. Smeenk1
1
Radboud University Medical Centre, Department of
Gastroenterology & Hepatology, Postbus 9555, 6800 TA
ARNHEM, the Netherlands, e-mail: [email protected],
2
MAASTRO Clinic, MAASTRICHT, the Netherlands
Introduction: Gastrointestinal complaints are the most
frequently seen adverse events of external beam radiotherapy for prostate cancer. Daily inserted endorectal
balloons (ERB) during radiotherapy are used to diminish
rectal toxicity. The aim of this prospective follow-up study
was to compare objective rectal toxicity between patients
treated with and without ERB by means of repeated sigmoidoscopy for a period of 5 years.
Methods: Forty-eight patients (mean age 71 years) were
randomly assigned to the ERB-group or no ERB group (24
patients in both groups). After radiotherapy endoscopies
were performed on settled time points with a follow-up of
5 years. Rectal toxicity was scored by the Vienna Rectoscopy
Score. After 5 years there were 16 patients left in both
groups. Endoscopists were blinded for treatment group
and prior results.
Results: In total, 160 sigmoidoscopies, creating over
2500 mucosal regions of interest (ROI) were analysed.
Telangiectasias were most often found. The highest
percentage of toxicity was seen after one year (45% of ROIs
and 33% in the no-ERB group and ERB group, respectively),
and decreased to 27% and 11% after 5 years. Patients in
the ERB group had more mucosal areas irradiated to low
radiation(< 40Gy) compared to patients in the no ERB
group.
After irradiation with ERB there was less rectal toxicity
observed compared to irradiation without ERB in areas
which received the same dose. Furthermore, patients
irradiated with ERB reported less symptoms compared to
patients irradiated without ERB.
Conclusion: After radiotherapy, rectal mucosal damage
improves 5 years after treatment. There were less ROIs
with low grade and high grade toxicity in the ERB group
compared to the no-ERB group. Furthermore, patients
in the ERB group experienced less toxicity compared to
patients in the no-ERB group of the same dose bin. These
observations suggest a beneficial effect of ERBs in prostate
radiotherapy.
77
XIII GASTRO-ENTEROLOGY CASE REPORTS
the increasing number of surgical procedures performed
for morbid obesity, basic knowledge of the currently used
techniques and the associated complications is important to
diagnose and treat these complications adequately.
C088 Heavy feelings in the stomach
M.C. van Boreen, J.M. Conchillo, E.G. Gerrits
Maastricht University Medical Centre, Department of Internal
Medicine, P Debeyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected]
C089An uncommon cause of pylephlebitis
J. Eising, M.R. Douma, J. Schmidt, J.H. Heijs, W.G. Meijer
Westfries Gasthuis, Department of Internal Medicine,
Maelsonstraat 3, 1624 NP HOORN, the Netherlands, e-mail:
[email protected]
Introduction: Worldwide, laparoscopic adjustable gastric
banding has gained increasing popularity amongst all
bariatric procedures, because of its safety and effectiveness
to control morbid obesity. Major complications of gastric
banding are relatively rare, but not inconceivable. Erosion of
the band into the gastric lumen is an uncommon, but serious
complication which in most cases leads to surgical revision or
removal of the band. Here we present a case of band erosion
with serious complications after gastric banding.
Case report: A 40 year-old man was referred to our
emergency department because of sudden onset of bloody
stools. One year ago he underwent a second gastric
banding procedure because of morbid obesity. The first
gastric band was placed five years ago and had to be
removed because of band erosion after three years. Due
to ongoing gastrointestinal bleeding on the emergency
department, clinical deterioration with hypovolemic shock
developed quickly within an hour after admission. After
resuscitation and stabilization of the patient, a gastroscopy
was performed because of high suspicion of upper gastrointestinal bleeding. Gastroscopy showed signs of gastrointestinal bleeding. Most impressive was the fully eroded
gastric band over 25 percent of the circumference. There
was no endoscopically treatable cause of bleeding, so we
consultated the surgeon who performed a total gastrectomy
with Roux-en-Y reconstruction. During surgery bleeding
from the arteria gastrica sinistra was noted. One week
after the major surgical reconstruction the patient could
be discharged from the hospital in good clinical condition.
The incidence rate of band erosion after gastric banding
is 1-3%. Clinical presentation of this problem is variable
and in most cases not acute. However, epigastric pain and
hematochezia could be alarm symptoms of erosion which
can become life-threatening. It is thought to occur as a
result of either gastric wall ischemia from a tight band
caused by compression, mechanical trauma related to
the band buckle or thermal trauma from electrosurgical
energy sources used during band placement. Infection of
the wound after placement associated with the access port
could be an important etiological factor as well.
Discussion: An unusual cause of bleeding like band erosion
must be considered in patients with a former gastric banding
procedure, presenting to the emergency department with
a life-threatening gastrointestinal bleeding. In light of
Description of the case: A 77 year old woman presented with
a 3 days history of fever and a 2 months history of right upper
quadrant abdominal pain. The medical history shows an
uterus extirpation and hypertension. She takes hydrochloorthiazide, acetaminophen and tramadol. On examination
vital signs are normal, there is no fever. The abdomen reveals
some tenderness of the right upper quadrant. Laboratory
findings were a C-reactive protein of 347 mg/L (normal
< 5 mg/L) a gamma glutamyl transpeptidase of 149 U/L
(normal < 40 U/L), a total bilirubin of 24 umol/L (normal < 17
umol/L) and aspartate aminotransferase of 76 U/L (normal
< 30 U/L). CAT scan of the abdomen showed thrombosis of
the portal vein and the superior mesenteric vein. Some wall
thickening was seen of the ascending colon. Blood cultures
yielded streptococcus hominis and streptococcus milleri. Our
patient was diagnosed with pyleflebitis and was subsequently
treated with piperacilline/tazobactam and low molecular
weight heparin in therapeutic dosage. Abdominal CAT scan
was repeated after one week. No residual abnormalities of the
ascending colon were apparent. At this stage the aetiology of
the pylephlebitis remained uncertain.
However, two months after her initial presentation she was
hospitalized for a rectal bleeding. A colonoscopy showed
a cocktail stick stabbed in a sigmoidal diverticulum. The
cocktail stick was removed by endoscopy. Reviewing the
initial CAT scan revealed the cocktail stick in the thickened
area of the ascending colon. We hypothesized that the
cocktail stick first perforated the colonic wall and caused an
abdominal infection leading to a pylephlebitis. Eventually
the cocktail stick migrated to the sigmoid colon and caused
a lower gastrointestinal bleeding.
Discussion: Pylephlebitis is a septic thrombophlebitis of
the portal and/or mesenteric vein caused by an abdominal
infection. Diverticulitis is the main underlying condition,
whereas appendicitis was the most prevalent cause in earlier
days. Pylephebitis has significant morbidity and mortality.
Clinical features depend on the aetiology of the abdominal
infection, but fever and abdominal pain are almost always
present. Complications are liver abscesses and bowel
ischemia. Therapy consist of antibiotic treatment guided by
blood cultures. The role of anticoagulation remains uncertain.
78
the Netherlands, e-mail: [email protected], 2Rijksinstituut
voor Volksgezondheid en Milieu (RIVM), BILTHOVEN, the
Netherlands, 3Central Veterinary Institute (CVI), LELYSTAD,
the Netherlands, 4Haven Hospital, ROTTERDAM, the
Netherlands
Conclusion: This case report shows a foreign body as an
uncommon cause of pylephebitis.
C090A presentation of secondary deposits of small-cell
lung carcinoma in the colon
Introduction: Enteric fever is caused by Salmonella enterica
enterica serovar Typhi(S. Typhi) and Paratyphi A, B and
C (S. Paratyphi). Because of the occurrence of multidrug
resistance (resistance to ampicillin, chloramphenicol
and trimethoprim) and emergence of decreased ciprofloxacin susceptibility (DCS), treatment options are limited.
Azithromycin is now often used as first line treatment
for enteric fever, although clinical breakpoints and epidemiologic data are lacking. The objective of our study
was to investigate trends in antibiotic resistance over
time in isolates collected between 1999 and 2012 in the
Netherlands.
Methods: All confirmed human S. Typhi and S. Paratyphi
isolates from the Netherlands sent in to the Salmonella
National and Community Reference Laboratory (RIVM)
in the period January 1999 to December 2012 were
included in this study. MICs for different antibiotics were
determined by the broth microdilution method. Isolates
with a known country of acquisition were divided into
geographical regions. Trends over time of the cumulative
one year incidence of antibiotic resistance were determined
by weighted linear regression analysis.
Results: From 1999 until 2012, 354 isolates were collected;
177 S. Typhi isolates, 98 S. Paratyphi A isolates, 78 S.
Paratyphi B isolates and one S. Paratyphi C isolate. A
significant increase in DCS (MIC 0.125-1.0 mg/L) or
ciprofloxacin resistance (CR) (MIC > 1.0 mg/L) was found
from 0% in 1999 to 64% in 2012 (p < 0.001). In 16.1% of
all isolates and in 23.8% of isolates with elevated MICs for
fluoroquinolones the MIC for azithromycin was increased
above wild type (> 16 mg/L). Resistance to ampicillin,
chloramphenicol and trimethoprim was observed in
respectively 9.9, 7.6 and 9.3% of the isolates. In none of the
isolates resistance to third-generation cephalosporins was
observed. Travel history was available for 195 cases. 78.5%
of the isolates were acquired in Asia, 16.9% in Africa,
2.6% in Latin America and 2.1% in Europe. The highest
percentages of elevated MICs for azithromycin were
observed in isolates acquired in regions with concurrent
high proportions of DCS/CR isolates (Southern Asia).
Conclusion: Besides elevated MICs for fluoroquinolones,
typhoidal Salmonella isolates in ill returned Dutch
travellers also show a high percentage of increased MICs
for azithromycin. Because the highest proportions of
increased MICs for azithromycin are found in DCS/CR
isolates and in regions where DCS/CR is already widely
prevalent among typhoidal Salmonella isolates, this may
further limit future treatment options for enteric fever.
D.E. Agterhuis, R.A.A. van Zanten
ZGT, Department of Internal Medicine, Zilvermeeuw 1, 7609
PP ALMELO, the Netherlands, e-mail: [email protected]
Introduction: Lung cancer is the most common cancer
worldwide and about 50% of cases have distant metastasis
at the time of diagnosis. The most common sites are the
liver, adrenal glands, bones and brain. We present a case of
small cell lung cancer (SCLC) that presented with solitary
metastasis to the colon.
Case-report: A 72-year old man with a previous history
of diverticulosis, presented with complaints of a bloated
stomach and changed stools. There was no loss of appetite
or change in weight. He quit smoking 20 years ago.
Physical examination of the abdomen was normal. The
laboratory results included a slight normocytic anaemia.
A faecal occult blood test was negative. On colonoscopy
two for malignancy suspicious sessile polyps of 25 and
30 millimetres were seen in the sigmoid. Biopsies showed
localisation of small cell neuro-endocrine carcinoma
(TTF-1 positive) in both polyps. A CT-thorax and abdomen
revealed a hilair mass in the left lung. This resulted in the
diagnosis primary small cell lung carcinoma with solitary
metastasis to the colon.
Discussion: Metastasis of lung cancer to the colon are rare.
So far, 40 cases have been published. Only 5 of these cases
were SCLC. Nevertheless, the incidence may be much higher
as symptoms and signs are frequently considered to be side
effects of chemotherapy. A higher incidence has been found
in post-mortem studies. The most common presenting
symptoms are abdominal pain, intestinal obstruction, weight
loss, bloody stools and diarrhoea. Expert opinion suggests
that therapy of choice is (surgical) resection if there is no
evidence of further tumour spread. However, intestinal
metastasis of lung cancer is associated with a poor prognosis.
XIV INFECTIOUS DISEASES RESEARCH
C091 Antimicrobial resistance in ill returned travellers
with enteric fever in the Netherlands, 1999 - 2012
R.J. Hassing1, W.H.F. Goessens1, W. van Pelt2, D.J. Mevius3,
B.H.C.H. Stricker1, A. Verbon1, P.J.J. van Genderen 4
1
Erasmus Medical Centre, Department of Internel Medicine &
Infection diseases, ’s-Gravendijkwal 230, 3015 CE ROTTERDAM,
79
C092 Experience on structured bedside consultations for
patients with Staphylococcus aureus bacteremia in a
large non-academic hospital
C093 Infectious complications and hospital admissions
following transrectal ultrasound guided biopsy – an
increasingly encountered clinical problem
R.M. Nijmeijer, E.H. Gisolf, E. Rengers, C. Veenstra,
M.E. Hoefman, C. Richter, J.E. Lindeboom, C.M.A. Swanink
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
T.J.C. Langeveld, J.W. van ’t Wout, M.A. Leversteinvan Hall
Bronovo Hospital, Department of Internal Medicine,
Bronovolaan, 2597 AX DEN HAAG, the Netherlands, e-mail:
[email protected]
Introduction: Staphylococcus aureus bacteremias (SAB)
are often complicated with endocarditis, spondylodiscitis
or other metastatic disease. These complications influence
patient outcome and duration of antibiotic treatment.
According to recent publications lower mortality rates are
found in patients who received bedside consultation by an
Infectious Diseases consultant. Even in uncomplicated
SAB, guidelines on antibiotic treatment are not followed in
a substantial percentage of patients. We therefore initiated
bedside consultations in all patients with SAB in the
beginning of 2012. With the introduction of the Antibiotic
Stewardship team (A-team) in 2014, bedside consultations
in SAB patients are presented as one of the five initial aims
of the A-teams.
Methods: Since the beginning of 2012, all new SAB are
not only reported to the treating physician, but also to
the resident Infectious Diseases or consultative Internal
Medicine resident. Every week, an email is sent to
re-check. The bedside consultation is done according to a
written protocol. The visit is supervised by the Infectious
Disease specialist. Also the cardiologists are involved in
this protocol. As soon as the consultant finds an increased
risk for complications or cardiac murmur, the cardiologist
is consulted to perform an ultrasound. We retrospectively
collected data on SAB patients in 2011 for comparison.
Results: In 2011, 61 patients were identified with a SAB,
in 2012 75. Sixty percent of all of these patients was male.
Mortality was 26% in 2011 and 31% in 2012 (16 vs. 23
patients). In 2012, 10 of the 23 patients who died (43%),
did not undergo additional diagnostic investigations. In
2012, more ultrasounds of the heart were performed in
comparison to 2011 (64 vs. 44%). In 2012, more patients
were treated correctly when compared to 2011 (81 vs. 57%
of patients). Results of 2013 are pending.
Conclusion: Structured consultation in SAB patients results
in an adequate treatment of SAB in a higher percentage
of patients. So far we were not able to show a decrease in
mortality rate. A large proportion of patients was already
withdrawn from therapy because of severe comorbidity or
died before additional investigations could be done. In these
patients, no improvement of bedside consultation can be
expected. The system of bedside consultations is vulnerable
because of personnel changes and the involvement of many
people. Continuous education is needed.
Background: Transrectal ultrasound guided biopsy
(TRUSB) is an essential procedure used to obtain a
histological diagnosis of prostatic carcinoma. It is well
established that antibiotic prophylaxis is effective in
preventing infectious complications following TRUSB and
current guidelines suggest that fluoroquinolone antimicrobials are the agents of choice. Recent reports suggest
an increasing incidence of infectious complications and
emerging association between TRUSB and subsequent
infection with fluoroquinolone-resistant Escherichia coli,
thereby challenging current prophylactic regimens.
Aim: To evaluate infectious complications and hospital
admissions within 30 days following TRUSB.
Patients and methods: We retrospectively reviewed all
consecutive TRUSBs between January 2012 and June 2013
in the Bronovo Hospital and collected data on infectious
complications and hospital admission.
Results: A total of 388 patients underwent TRUSB of whom
25 (6.4%) sought medical attention because of infectious
complications requiring antibiotic treatment. All patients
had received ciprofloxacin prophylaxis according to current
guidelines, except for one patient. Febrile complications
occurred in 21 patients (5.4%) and hospital admission subsequently followed in 18 (4.6%). Sepsis was seen in 6 patients
(1.5%) and all had positive blood cultures with Escherichia
coli, 2 of which were ciprofloxacin resistant and 1 extendedspectrum beta-lactamase (ESBL) positive. One of the patients
with a fluoroquinolone-resistant Eschericia coli sepsis
required admission to our Intensive Care Unit (ICU). There
were no biopsy related deaths. Regarding the known patientspecific risk factors 2 patients had diabetes mellitus, but there
were no recent hospitalizations. Furthermore, histological
findings of prostatic carcinoma were present in 11 patients.
Conclusion: Febrile complications and hospital admissions
within 30 days following TRUSB are important because of
associated patient morbidity. Despite antibiotic prophylaxis
> 5% of patients in our hospital experienced an infective
complication, of whom 1.5% developed bacteremia and
coexisting sepsis. Our findings are comparable to the
2-6% and 0.1-2.2% reported in current literature, respectively. Given the large number of biopsies performed, the
population and economic burden is substantial, and perhaps
underestimated as we have solely evaluated patients who
sought medical attention. We are not able to draw definitive
80
conclusions regarding the position of fluoroquinolon-resistant
Escherichia coli in our hospital, as there were only 2 patients.
However, one patient being the only individual requiring ICU
admission. The role of targeted antimicrobial prophylaxis
therefore remains a key question. Further evaluation is
required whether prebiopsy screening for resistant pathogens,
followed by culture-directed antimicrobial prophylaxis, might
be clinically useful and cost-effective.
and the third patient suffered from a inoperable mycotic
aneurysm and died.
Conclusion: PET-CT scanning in patients without fever but
elevated inflammatory markers has a high yield for detection
of clinically relevant diagnoses. In our study 50% (25/49)
could be diagnosed with an underlying condition. Patients
with an auto-immune disease or an abscess (14) could receive
appropriate care but in the patients with a malignancy the
diagnosis did not positively influence their prognosis. The
use of a PET-CT-scan can provide patients and clinicians with
a diagnosis but in this retrospective study a positive effect on
the prognosis of the patient could not be found.
C094The role of PET-CT-scan in patients with elevated
inflammatory markers without fever?
E. Bons, T. Sprong, A.S. Dofferhoff
Canisius-Wilhelmina Hospital, Department of Internal
Medicine, Weg door Jonkerbos 100, 6532 SZ NIJMEGEN, the
Netherlands, e-mail: [email protected]
C095 A retrospective cohort study on spondylodiscitis:
patient characteristics, causes and treatment
E.H. Gisolf, B. Franssen, T. van Zwet, E. de Visser
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 53, 6813 AD ARNHEM, the Netherlands, e-mail:
[email protected]
Introduction: A PET-CT -scan is often used in the
diagnostic work-up of patients with fever of unknown
origin. Little is known about the role of the PET-scan in
the diagnosing process of patients without fever but with
elevated inflammatory markers.
Aim of the study: The first aim of this study is to
determine the effectiveness of PET-CT-scan in diagnosing
the cause of elevated inflammatory markers (C reactive
protein and/ or BSE). The second aim was to investigate
the effect of the diagnosis on the prognosis of the patient.
Methods: We retrospectively analysed the data of patients with
elevated CRP and/ or BSE without fever that had undergone
a PET-CT-scan between 01-01-2011 and 31-12-2012.
Results: 49 patients were included (26 male, 23 female).
Age 31-86 (mean: 64,5) years. 34 patients were newly
referred to our outpatient clinic.
In 20 of these patients, the elevated inflammatory markers
were the reason for referral.
The reason for PET-CT-scan was elevated CRP (9), elevated
BSE (13) and elevated BSE and CRP (27).
In 30 patients (61%) the PET-CT-scan showed a significant
abnormality. In 25 of these patients a disease, that was
seen as the cause of the elevated inflammatory markers,
was diagnosed.
13 (27%) patients were diagnosed with an auto-immune
disease, 9 (18%) patients with a neoplasm and 3 (6%)
patients with an infection.
Patients with an auto-immune disease (vasculitis (6)
polymyalgia rheumatica (5) and rheumatoid arthritis (2))
were all treated successfully with prednisone.
9 patients were diagnosed with a neoplasm, of which
one patient with a benign thyroid neoplasm. The other 8
patients were found to have extensive malignancies. None
of these patients were eligible for curative treatment.
In 3 patients an infection was found, of which one patient
with a pelvic abscess, one patient with diverticulitis,
Introduction: Spondylodiscitis is a serious disease
with high mortality and morbidity. Diagnosis is often
delayed, because of rarity of the disease and the aspecific
symptoms. Currently, there are no national guidelines on
diagnosis and treatment of spondylodiscitis.
Aim of the study: to describe the diagnoses, found microorganisms and treatment of patients with spondylodiscitis
in a large non-academic hospital.
Methods: This is a retrospective single-center cohort study.
All patients over 18 years of age who were diagnosed with
spondylodiscitis in the last 6 years were included.
Results: Forty-nine patients were included. Mean age
was 69 years (range 40-89). Most patient had a MRI to
confirm the diagnosis. In 39 patients a micro-organism
could be isolated. Most frequently found bacteria were
Staphylococcus aureus (n = 14), streptococci (n = 11) and
gramnegative bacteria (n = 11). All patients were treated
with antibiotics. Thirty-seven patients were treated at least
6 weeks, 17 patients 12 weeks or longer. Thirteen patients
were not treated adequatly with empiric therapy and had
to be switched when culture data became available. Eleven
patients underwent surgery for decompression and/or
stabilization. Two patients had a recurrent infection.
Conclusion: With every suspicion of spondylodiscitis a
thorough physical examination including neurological
examination, blood cultures and radiological imaging is
needed. MRI is the test of choice, followed by a PET-CT,
if results are inconclusive. A CT guided biopsy should be
performed before starting antibiotics, whenever possible.
Empiric therapy only directed on Gram positive bacteria
will lead to inadequate treatment in a substantial portion
of patients. Multidisciplinary collaboration between
81
Conclusion: Doctors related treatment delay occurs
regularly in patients presenting with Legionellosis. This
may well be related due to presentations with less specific
symptoms of Legionellosis. However, a need for better
doctor’s recognition of Legionellosis seems questionable, as
treatment delay does not seem to affect patient’s outcome.
orthopedic surgeon, neurologist, radiologist, microbiologist and internist-infectiologist is mandatory. A
national guideline on spondylodiscitis would be helpfull
in succesfull finding and managing these patients with
this serious disease.
C096Treatment delay in Legionellosis
C097 Diagnostic and therapeutic aspects of general
internal medicine ward admissions for presumed
infectious disease
J.M. de Koning Gans, N.D. van Burgel, T.A.C. Nizet,
C. van Nieuwkoop
Haga Hospital, Department of Internal Medicine, Leyweg
275, 2545 CH DEN HAAG, the Netherlands, e-mail:
[email protected]
T.W. van Hal, F.W. Sebens, C.G. Vermeij
Deventer Hospital, Department of Internal Medicine, Nico
Bolkensteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected]
Introduction: At initial presentation in a hospital,
Legionellosis is commonly considered as a cause of
community acquired pneumonia (CAP) and diagnosed in
approximately 3% of cases. However, treatment delay may
occur when, based on clinical judgment, the diagnosis is
initially considered unlikely or an alternative diagnosis is
preferred.
Aim of the study: To examine the frequency, patient
characteristics and impact of treatment delay in
Legionellosis.
Materials and methods: A retrospective chart review of all
adult patients diagnosed in our hospital with Legionellosis
by a positive legionella urinary antigen test (LUAT),
between February 2007 and October 2013. Treatment delay
(TD) was defined as the absence of empirical treatment for
Legionellosis at initial presentation. Patient characteristics
for treatment delay were assessed. The outcome measures
were 30-day mortality, need for ICU-admission and length
of hospital stay (LOS).
Results: Of 1759 LUATs performed, 56 (3.2%) patients
tested positive. The median age was 63 years (IQR 59-73
years), 66% were male, 43% had gastro-intestinal symptoms
and 16% had neurological symptoms. With respect to
environmental risk factors for Legionellosis, 28 (50%) cases
were foreign travel related; 6 (11%) were water related and
22 (39%) had no risk factor. TD was present in 12 patients
(21%) with a maximum length of 3 days. In 2 (4%) cases,
the initial diagnosis was gastro-enteritis instead of CAP.
TD patients more frequently were male (83% vs 61%),
less frequently they had an environmental risk factors
for Legionellosis (50% vs 64%) and less frequently they
presented with hyponatremia (50% vs 71%) and neurological symptoms (8% vs 18%). There were no differences
with respect to age, presence of gastro-intestinal symptoms
or severity of CAP as classified by the pneumonia severity
index. Clinical outcomes between patients with and
without TD did not differ significantly; these were need for
ICU-admission 16% vs 25%, median LOS 8 vs 8 days and
30-day mortality 17% vs 14%, respectively.
Background: Many admissions to general internal medicine
wards are for presumed infectious diseases. In these
patients, after initial diagnostic work-up in the emergency
ward, empiric antibiotic therapy is usually started. In our
hospital, doctors are encouraged to adhere to the local
SWAB-based prescription guidelines. However, during
day-to-day practice, we noticed that many patients admitted
to the general internal medicine ward for presumed
infectious diseases received empiric ceftriaxon. We decided
to evaluate the accuracy of the initial diagnosis and appropriateness of empiric antibiotic therapy in these patients.
Methods: In a pilot study, for 7 weeks all consecutive
patients with infectious disease as the main diagnosis and
reason for admission to the general internal medicine ward
were included. Demographic data, results of diagnostic
procedures, antibiotic therapy and outcome were obtained
from the medical files.
Results: In the study period, 73 patients were admitted with
infectious disease as the main initial diagnosis: urinary
tract infection (UTI) (37%), pneumonia (P) (25%), gastroenteritis (GE) (15%) and skin infection (SI) (12%). In three
patients (4%) no cultures had been taken upon admission.
Based on the patient’s clinical course and laboratory and
radiological studies, the initial diagnosis was confirmed
in 54 patients (75%). Four patients appeared to have
auto-immune diseases instead of infection, three patients
were subsequently diagnosed with biliary tract infections.
In 1 patient PSI was not calculated; this patient had a
hospital acquired pneumonia (HAP). Of 15 patients with a
community-acquired pneumonia (CAP) only three (20%)
received amoxicillin monotherapy, while only one patient
had a PSI-score which warrants a different antibiotic
regime. Nine of 18 pneumonia patients were treated with
ceftriaxon. Reasons to differ from the protocol were: HAP
(3/18), admittance to ICU (2/18), concurrent UTI (1/18) or
failed amoxicillin treatment (2/18). In one patient, no reason
was given.
82
Conclusion: This analysis shows us some examples on how
we may improve our initial evaluation of infectious patients.
The diagnostic accuracy in patients admitted to the general
internal medicine for infectious diseases is fair. However, in
the majority of patients with CAP, empiric antibiotic therapy
was not prescribed according to the SWAB-guideline. A
possible explanation may be that patients referred to the
internal medicine department are not “typical” pneumonia
patients, but have concurrent disease which leads to empiric
treatment with ceftriaxon. In these patients, additional
diagnostic procedures may be warranted, especially if
symptoms have persisted despite empiric antibiotic therapy.
XV
and temporary discontinuation of the MMF. The eschar
gradually disappeared over the course of several weeks.
Conclusion: a spider bite should be considered in patients
presenting with an eschar, next to infectious causes like
Rickettsiosis, tularemia and cutaneous antrax.
C099Dexamethason induced Pneumocystis jirovecii
pneumonia
J.E. Tijmensen, C. van Nieuwkoop
Haga Hospital, Department of Internal Medicine, Sportlaan
600, 2566 MJ THE HAGUE, the Netherlands, e-mail:
[email protected]
INFECTIOUS DISEASES CASE REPORTS
Introduction: Systemic glucocorticoid therapy is frequently
used to relieve symptoms of local edema caused by primary
brain tumours or brain metastasis. Glucocorticoid therapy
is associated with a dose-dependent increased risk of
infection. Infectious complications are usually caused
by common pathogens, but opportunistic infections, like
Pneumocystic jirovecii pneumonia (PCP), may occur;
especially in patients with concomitant immunodeficiency.
However, when glucocorticoids are given for extended
period of time, PCP should be considered in individual
cases, as is demonstrated here.
Case description: A 73-year old male presented to the
emergency department with fever since 2 days. There were
no chills or specific symptoms except for some dyspnea.
Recently he had been diagnosed with cerebellar metastasis
of an unknown primary tumour. This was treated with
dexamethasone 8 mg/day with response regarding his
headache and disturbed gait. In the next six weeks
dexamethasone was tapered to 3 mg/day.
Physical examination showed a respiratory rate of 30/minute
and a peripheral saturation of 95%. His blood pressure was
125/70 mmHg, the pulse 100/minute and temperature
38.4 °C.
A chest X-ray revealed interstitial infiltrates which was
confirmed by chest CT-scan showing bilateral, predominantly basal consolidations with surrounding ground
glass. An atypical pneumonia was considered most
likely, especially because patient had a parrot at home.
Doxycycline was started. A broncho-alveolar lavage (BAL)
was performed during admission to rule out PCP. PCP was
considered less likely because the patient improved quickly
and became afebrile. He was discharged awaiting the final
microbiological results.
Three days later, he was readmitted because of progression
of dyspnea and recurrence of fever. PCP was now strongly
considered; high dose trimethoprim-sulfamethoxazole
was started. Because of progressive respiratory failure,
the patient was transferred to the Intensive Care Unit for
non-invasive ventilation. He died a few days later.
C098Fever and an eschar after a holiday to Spain
M.A.H. Berrevoets, Q. de Mast
Radboud University Medical Centre, Department of Internal
Medicine, Geert grooteplein zuid 8, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected]
Case report: A 65-year old female patient was admitted
to the rheumatology ward with a persistent fever despite
antibiotic treatment with amoxicillin/clavulanic acid and
ciprofloxacin. Her history revealed systemic sclerosis with
interstitial lung disease for which she was treated with
mycophenolate mofetil (MMF).
She had returned from Spain about 3 weeks ago. Except
for a mild headache and a black skin lesion on her right
lower arm, she did not report localizing symptoms. The
skin lesion had started as a small, itchy lesion four weeks
earlier. She could not remember an insect bite. Physical
examination revealed a fever and an eschar with a diameter
of approximately 1.5 cm. There were no other skin abnormalities. Laboratory results showed a leucopenia, mild liver
enzyme abnormalities and a normal CRP level (< 5 mg/L).
A skin biopsy showed findings consistent with an ulcer
but tested negative for fungi, atypical mycobacteria and
leishmaniasis.
With the suspicion of a possible Rickettsia conorii infection
(Mediterranean spotted fever) she was treated with
doxycyclin without an effect on the fever. Other causes of
an eschar in the differential diagnosis were a spider bite
(necrotic arachnidism due to the bite of a Brown Recluse
spider), cutaneous anthrax and tularemia. The latter two
were considered unlikely. A medical professional in the
Spanish city she had stayed in was consulted who found
the clinical picture highly suggestive for a spider bite.
Necrotic arachnidism is usually not associated with fever
and this was ultimately found to be the result of a primary
cytomegalovirus infection which was treated by ganciclovir
83
The PCR as well as specific stainings of the BAL were
positive for PCP. An HIV-test was negative.
Conclusion: Systemic glucocorticoid therapy without any
other form of immunosuppression is not sufficient to
cause a substantial risk of PCP on a population-wide basis.
However, when glucocorticoids are given to old people at high
dose for extended period, as in our patient, PCP should always
be considered in case of fever and respiratory symptoms.
replacement is necessary in about 50% of cases. Antibiotic
treatment with amoxicillin and gentamycin seems to be
most effective. Since 1985 the mortality of L. monocytogenes
endocarditis decreased and is now estimated at 12%.
Conclusion: Endocarditis due to L. monocytogenes infection
is a rare and in many cases severe disease that may lead to
valve dysfunction and heart failure. Aggressive antibiotic
treatment is necessary.
C100 A rare cause of prosthetic valve endocarditis
C101 A surprising diagnosis with a challenging
complication
A.H. Calf1, M.G.A. van Vonderen1, J.H. van Zeijl2, K. Urgel1
1
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: [email protected], 2Izore Centre for
Infectious Diseases, LEEUWARDEN, the Netherlands
T.C. Veenstra, C. Richter
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6800 TA ARNHEM, the Netherlands, e-mail:
[email protected]
Introduction: The most frequently encountered pathogens
in patients with prosthetic valve endocarditis are staphylococci and streptococci. We describe a case of L. monocytogenes endocarditis in an immunocompromised patient
with a mitral valve prosthesis.
Case: A 63-year old male presented with malaise. His
medical history included psoriatic arthritis for which he used
methotrexate, S. aureus endocarditis for which he underwent
implantation of a mitral valve prosthesis, as well as former
alcohol- and drug abuse. He experienced intermittent febrile
episodes since three weeks, complained of loss of appetite
and unintentional weight loss of 5 kg. Physical examination
showed a pale man with a blood pressure of 95/61 mmHg,
heart rate of 86 beats per minute, temperature of 36.3°C,
and no other abnormalities. Leucocytes were 6.7 x 109/L,
and C-reactive protein 169 mg/L. The patient was admitted
for observation and blood cultures were performed. A
transesophageal echocardiography showed a small vegetation
on the mitral prosthetic valve. We started gentamycin
and vancomycin according to national guidelines. Three
blood cultures demonstrated Listeria monocytogenes, and
we switched to amoxicillin and gentamycin . The patient
responded well to antibiotic therapy and valve replacement
proved unnecessary. Except for the use of an immunosuppressive agent, we found no other immunocompromising
disorder or underlying disease. HIV serology was negative.
The patient did not recall eating soft cheese or any other
potentially contaminated products.
Discussion: L. monocytogenes is an aerobic, gram-positive
coccobacillus, which is found frequently in raw and
unprocessed food products. Infection does not occur unless
host factors promoting invasive disease are present, or the
amount of bacteria is great enough to overwhelm local gastrointestinal barriers. Worldwide, 23 cases of prosthetic valve
endocarditis due to L. monocytogenes have been described, of
which 40 percent in immunocompromised patients. Valve
Introduction: It is well known that tuberculosis can manifest
in multiple organs. Presentation of an extra pulmonary
infection with Mycobacterium tuberculosis can be surprising
and treatment can be difficult. We report a case of a very rare
form of tuberculosis in a Brazilian woman.
Case: A 51 year old Brazilian woman, living in the
Netherlands for three years, was sent by the radiologist
to the emergency department because of an abnormal
chest X-ray with elevated right hemidiaphragm without
other abnormalities. She was complaining of night sweats,
weight loss and abdominal pain for several weeks without
cough or fever. Her medical history revealed an unknown
treatment for liver cysts six years ago in Brazil. At physical
examination we found a painless palpable mass in her
right abdomen. Laboratory evaluation revealed a Hb
6.4mmol/L, ESR 110mm, CRP 78 mg/L, AF 219 U/L and
GGT 97 U/L. Ultrasonography imaging of the abdomen
raised the suspicion of a 20cm large echinococcus cyst
and treatment was started with albendazol. However,
echinococcus antibodies were negative and a magnetic
resonance imaging was compatible with a liver abscess.
Surgical exploration followed, 3500ml of pus removed
with a negative bacterial culture, but a positive culture
for M. tuberculosis, sensitive for all anti-tuberculostatic
drugs. HIV infection was excluded. Standard TB treatment
was initiated, but unfortunately after one month the
cyst reappeared. In the following year we needed to
repeat a percutaneous cyst aspiration for three times. All
cultures remained negative for M. tuberculosis, cytological
examination revealed no malignant cells. Because we had
no evidence of non-compliance or any resistant form of
tuberculosis we considered the re-appearance of the cyst
as a paradoxical reaction during TB treatment. This is a
clinical deterioration during anti tuberculosis therapy in
patients who initially showed improvement. We continued
anti-TB treatment without addition of glucocorticoids for
84
Patient was treated with high dose doxycycline as well
as plaquenil and showed good clinical improvement,
with resolution of fever and malaise as well as decline
of inflammation and improvement of anemia. Initially
the hemolysis was attributed to mechanic erythrocyte
damage by increased turbulence as a consequence of
vegetations of decreased valvular function. However, the
low-grade hemolysis resolved during treatment, no clear
vegetations nor valvular dysfunction were apparent and
direct Coombs test was positive, therefore the hemolysis
is more likely attributable to the infection with Coxiella
Burnettii; autoimmune hemolytic anemia is of its unusual
manifestations.
Conclusion: In case of (repeated) culture negative endocarditis, consider causes of sterile endocarditis and atypical
pathogens such as Coxiella Burnettii, also in non-rural
area’s like Amsterdam. Atypical endocarditis may be
accompanied by unusual clinical manifestations. These, as
well as extensive history may be important clinical clues.
one year. Because of ongoing mechanical complaints in
the abdomen we finally performed an aspiration sclerotherapy with 100cc ethanol 96%. With this treatment, the
diameter of the cyst decreased and the complaints of the
patient resolved.
Discussion: Isolated hepatic tubercular abscess is an
uncommon manifestation of tuberculosis, in the literature
only described in case reports. In our case a paradoxical
reaction during treatment complicated the case finally
leading to the need for aspiration sclerotherapy. Awareness
of TB remains essential in patients with liver abscess
in patients from TB endemic countries. This case also
illustrates that paradoxical reactions during TB treatment
can be longstanding.
C102 Unexpected cause of endocarditis and hemolysis in
a Moroccan patient in Amsterdam
M.E. Hellemons, K. Brinkman
Onze Lieve Vrouwe Gasthuis, Department of Internal Medicine,
Oosterpark 1, 1091 AC AMSTERDAM, the Netherlands, e-mail:
[email protected]
C103 Sepsis, thrombocytopenia and peripheral embolization causes by parainfluenzae endocarditis
E. Gieteling, P.H.P. Groeneveld
Isala Clinics, Department of Internal Medicine, Dr. van
Heesweg 2, 8025AB ZWOLLE, the Netherlands, e-mail:
[email protected]
Case report: A 42 year old man was admitted with
fever and suspicion of recurrent endocarditis, without
clinical endocarditis stigmata or other clinical complaints
indicating the origin of the fever. His medical history was
remarkable for complicated re-re-re-Bentall placement and
mitral valve replacement after an episode of rheumatic
valvular heart disease as a child, and an episode of
endocarditis one year previous with unknown pathogen.
Laboratory examination revealed anemia with low grade
hemolysis (Hb 5.8 mmol/L, MVC 81 fl, LDH 321 U/L,
Haptoglobin < 0.01 mmol/L) new compared to several
months earlier (Hb 8.0 mmol/L), some inflammation
(Leucocytes 11.3*10-9/L, CRP 53 mg/L) and was otherwise
unremarkable. Echocardiography did not show valve
vegetations nor abscess formation, and unaltered function
of mitral and aortic valve. Additional PET-scan revealed
increased FDG-uptake along the caudal part of the Bentall
prosthesis and no other signs of inflammation. As, like
the previous episode of endocarditis, repeat cultures were
negative, differential diagnosis included endocarditis
with unknown pathogen, sterile endocarditis as seen in
Libman-Sacks endocarditis (as part of systemic lupus
erythematosus), Behçet-associated endocarditis given
his origin, rheumatic fever associated endocarditis given
his history or endocarditis with less common pathogens.
Additional testing was performed. Serology tests showed
very high titers of Coxiella Burnettii. Despite living in
Amsterdam patient revealed visiting his family in a
cattle-rich mountainous area in Morocco annually for
several months.
Introduction: Diagnosing bacterial endocarditis remains a
difficult clinical problem, especially when blood cultures
stay negative in slow growing pathogens.
Case: A 19-year old woman was admitted to the emergency
department because of fever and malaise. Medical
history mentioned bowel surgery in early childhood. She
complained about fever with cold chills, headache, sore
throat and diffuse myalgia for one week. On admission
to our hospital, she was very ill and weak. She had
blood pressure of 94/55mmHg, a pulse of 130/min, a
the respiratory rate of 18/min, oxygen saturation of 97%
and the temperature was 39.0 °C. Physical examination
revealed a grade III pansystolic murmur at lower left
sternal border, and no other abnormalities, especially
no skin lesions. Significant laboratory findings included
thrombocytopenia of 22 x 109/L and CRP 227 mg/L.
Urine-analysis and chest X-ray were normal. After taking
blood and urine cultures we started treatment according
to our sepsis protocol with Amoxicillin/Clavulanic acid
and Gentamicin. In the days after admission her condition
slowly improved, but some fever spikes remained. Blood
cultures were still negative, the CRP decreased and the
thrombocytes increased slowly. On the fourth day she
developed a painful erythematous swelling on her right
hand palm. We considered endocarditis because of the
85
possible septic embolism, the heart murmur and the
ongoing fever. A transthoracic and transoesophageal
echocardiogram showed severe, eccentric mitral valvular
insufficiency and a mobile structure at the valve. After
6 days blood cultures became positive for Haemophilus
parainfluenza. With two minor and two major Dukes
criteria we now diagnosed infectious endocarditis. She
underwent a mitral valve repair and was treated according
to the susceptibility profile with Cefotaxime for six weeks.
She recovered well. Additional anamneses reported dental
inflammation and procedure performed 6 months before
presentation.
Discussion: H. parainfluenzae is a member of the HACEK
group. Haemophilus species count 0.8% to 1.3% of all
endocarditis cases. H. parainfluenzae constitutes part of the
oral and upper respiratory tract flora in about 10% of the
population. It’s a fastidious organism that is often difficult
to isolate and identify from blood culture H. parainfluenzae
endocarditis often produces bulky valvular lesions and is
frequently complicated by arterial embolization. Some
cases with deep thrombocytopenia are described. This case
shows the importance of diagnosing endocarditis even if
blood cultures are initially negative. The cardiac murmur,
ongoing fever and septic embolism are important early
clues.
malignancy but rather signs of yeast infection. Although
there were no clinical signs of meningitis, this finding
made us decide to hospitalize the patient and perform
lumbar punction because of the suspicion of disseminated
yeast infection. Treatment with liposomal amphotericin
B and flucytosine was initiated immediately. Lumbar
punction showed clear spinal fluid, with 46 x 10^6/L
leukocytes, 0.46 g/L protein, and 3.3 mmol/L glucose.
Cultures of liquor, blood and urine later all revealed
Cryptococcus neoformans.
Discussion: This renal transplant patient suffered from
disseminated cryptococcal infection. Infection is an
important differential diagnostic consideration in any
immunocompromised patient with a pulmonary lesion,
irrespective of presence of systemic dissemination.
C. neoformans is an encapsulated yeast that can be isolated
from bird excreta. Infection occurs via the respiratory
tract. Cryptococcal infection most frequently manifests as
meningitis, but can affect virtually any organ (e.g. lungs,
skin, urogenital tract). Among the spectrum of cryptococcal
disease, especially meningitis has a high mortality. Therefore,
lumbar puncture is warranted in any patient with disseminated infection, with or without neurological symptoms.
Treatment of cryptococcal infection consists of induction
therapy with both liposomal amphotericin B and
flucytosine, maintenance therapy with fluconazole, and
secondary prevention with low-dose fluconazole. Another
important component is minimizing immunosuppressive
treatment. Fluconazole, especially when taken orally,
causes inhibition of CYP3A4 and, therefore, warrants
dose reduction of calcineurin inhibitors (e.g. tacrolimus,
cyclosporine).
Conclusion: Cryptococcal infection affects immunocompromised patients from various backgrounds; not only HIV
seropositive patients. Awareness and early diagnosis and
treatment can be of vital importance.
C104 An unexpected cause of disseminated disease in a
smoking renal transplant recipient
W.E. van Spil, Y.P. de Jong, C.M.A. Swanink, C. Richter,
R.P. Aliredjo, J.C. Verhave
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
Introduction: A pulmonary mass with signs of disseminated disease may suggest a metastasized malignancy.
However, certain differential diagnoses should be
considered, particularly in specific patient groups.
Case: A 73-year old man presented with unexplained
weight loss, diarrhea, and pain in his right shoulder and
buttock. He had a history of nicotine abuse and chronic
obstructive pulmonary disease and had 17 years ago
received a renal transplant for which he was currently
using tacrolimus and prednisone.
Chest radiography identified a pulmonary mass in the left
lower lung lobe, showing FDG uptake on a subsequent
FDG-PET scan. Other FDG positive lesions were identified
in the right ilium, right clavicle, and transverse process of
the second thoracic vertebra. Altogether, a metastasized
pulmonary malignancy was suspected and biopsy of both
the pulmonary lesion and the lesion in the right ilium was
performed. Surprisingly, biopsies did not demonstrate
C105 An ‘unfamiliar’ cause of anemia in a family
S. Raaijmakers, E.F. Schippers
Haga Hospital, Department of Internal Medicine, Leyweg
275, 2545 CH DEN HAAG, the Netherlands, e-mail:
[email protected]
Case: Two brothers were send to the outpatient clinic
because of anemia with unknown cause. The first of the
two was a 17 year old boy. He had complaints of fatigue
since almost three months. The complaints commenced
after an episode of headache and muscle aches. He didn’t
take his temperature, but he thought he might have had a
fever. Physical examination was unremarkable. His 15 year
old brother also experienced an illness consisting of muscles
aches, headache and a possible fever in the same time frame.
86
On physical examination a systolic heart murmur was
found. Laboratory results, ordered by their general physician,
revealed mild normocytic anemia and a slightly elevated
LDH. There were no iron or vitamin deficiencies. Serology
for Hepatitis A, B, C, EBV and CMV was not suggestive for
recent infection. Full blood counts, performed several years
before this presentation, were normal in both brothers.
Further history taking revealed that both boys were born
and raised in Ghana for the first years of their lives before
they moved to the Netherlands. Five years ago they moved
back to Ghana and returned to the Netherlands three
months before presentation. Laboratory tests showed mild
hemolytic anemia. Chest X-rays were normal. Blood smear
was positive for plasmodium falciparum with low parasite
counts of 0,12% and 0,06%, respectively. After treatment
with artemether/Lumefantrine (Riamet) the symptoms
resolved and the hemoglobuline levels returned to normal.
Conclusion: Two cases of mild hemolytic anemia caused by
plasmodium falciparum infection with low parasite counts
in two boys originating from Ghana.
Discussion: People from regions were malaria is endemic,
especially West-Africa, build up (partial) immunity against
malaria after recurrent infections in childhood. This
will lead to a more indolent illness. A frequent finding
in these patients is anemia. The clinical presentation of
malaria with fever and acute illness in returning travelers
is well known. These two cases illustrate a presentation of
malaria, occurring in people originating from endemic
regions, that is much less frequently encountered in the
Netherlands and sometimes overlooked.
C106 Fever and muscle pain after localised trauma: think
of pyomyositis!
Laboratory tests revealed increased inf lammatory
parameters. Ultrasound and Computed Tomography (CT)
revealed diffuse swelling of (and small hypodense area
in) the internal oblique muscle, that could not be further
specified. The following day CRP had increased (from
95 mg/L to 272 mg/L), and the CK level was 855 U/L. MRI
demonstrated muscle enlargement of the internal oblique
muscle and gluteus maximus with discrete hyperintense
T2-weighted areas in these two muscles, consistent with an
early stage of (multifocal) pyomyositis. Empiric antibiotic
treatment was started, which was switched to high-dose iv
flucloxacillin after blood cultures showed Staphylococcus
aureus. Infective endocarditis was excluded. After two
weeks, oral antibiotic treatment with cotrimoxazole was
given for four weeks. He recovered completely, and inflammatory parameters returned to normal.
Discussion: Damaged muscle is easily susceptible
for haematogenous invasion by bacteria, as a result
pyomyositis can arise. Predisposing factors beside muscle
trauma are: intravenous drug use, concurrent infection,
malnutrition and immunodeficiency. The most common
pathogen is Staphylococcus aureus, and it is likely that
skin lesions in our patient functioned as a potential
source for bacteraemia. Pyomyositis presents with fever
and cramping pain localised to a muscle group. It can
be divided into 3 clinical stages. In stage 1 an abscess is
not present, but is apparent in stage 2. Stage 3 is characterised by systemic complications of bacteraemia. Often,
pyomyositis is not recognised before stage 2, however, with
MRI it can be diagnosed as early as stage 1.
We think clinicians should be triggered to evaluate
patients with fever, muscle pain and elevated inflammatory
parameters for pyomyositis, also those who are immunocompetent and living in a temperate climate.
R.E. Vleut, P.M. Stassen, B.P.A. Spaetgens
Maastricht University Medical Centre, Het Struweel 2, 5501 AS
VELDHOVEN, the Netherlands, e-mail: [email protected]
C107 Fever and dyspnea after BCG-immunotherapy: a
manifestation of a disseminated infection
M.J. van Es, F.J.S. Netters, F.G.H. van der Kleij
Scheper Hospital, Department of Internal Medicine,
Boermarkeweg 60, 7824 AA EMMEN, the Netherlands,
e-mail: [email protected]
Introduction: Pyomyositis is a purulent infection of
skeletal muscle originating from haematogenous spread
that usually results in abscess formation. In the tropics
pyomyositis is common, and incidence in temperate
climate is increasing. We want to warn doctors living in
a temperate climate for the increasing problem of the
unfamiliar disease, pyomyositis.
Case report: A healthy 48 year-old construction worker
was presented to our Emergency Room with pain in the
left flank and fever after minor local trauma. Physical
examination revealed an acutely ill male in pain, with a
temperature of 38.8°C. The pain in the left flank could not
be provoked by palpation, and local examination revealed
no apparent muscle swelling. He had (healed) wounds
on multiple fingers, obtained during his profession.
Introduction: Intravesical administration of Bacillus
Calmette-Guerin (BCG), a live attenuated strain of
Mycobacterium bovis, has become a commonly used
adjunctive therapy for superficial bladder cancer. Local side
effects, such as dysuria, polykiuria and a low-grade fever,
are frequently seen, but systemic complications are rare.
Case: A 70-year old man with a medical history
of recurrence urothelial carcinoma of the bladder
was admitted to our hospital with relapsing fever,
hematuria and dyspnea. The symptoms started 3 weeks
87
after BCG-immunotherapy. Laboratory tests revealed
elevated liver enzymes, decreased kidney function
and an elevated C-reactive protein of 118 mg/L. Chest
radiography and abdominal ultrasound did not showed
any abnormality. Antibiotic treatment with augmentin
and ciproxin was unsuccessful and all the cultures were
negative. The clinical course was complicated by further
deterioration and increased dyspnea. Therefore the
BCG-immunotherapy was discontinued.
Additional analyses including CT of the abdomen and HR
CT of the chest showed mediastinal lymphadenopathy
with symmetric reticulonodular pulmonary opacities and
multiple retroperitoneal masses of lymphadenopathy.
Bronchoscopy with a biopsy was performed and additional
PCR on mycobacterium tuberculosis and acid-fast bacilli were
negative. The histopathologic assessment showed granuloma.
Another biopsy taken by endo-ultrasonography of a node
between the pancreas and truncus coeliacus showed an
urothelial carcinoma which confirmed the diagnosis disseminated BCG infection with metastatic urothelial carcinoma.
Treatment with isoniazid, moxifloxicin and prednisolone
were started. Chemotherapy was not possible.
After several weeks CT of the chest and abdomen shows
a large reduction of the mediastinal lymphadenopathy.
Abdominal there was a progression of the lymphangitis
carcinomatosa.
Conclusion: The presented case illustrates the importance
of diagnosing a disseminated BCG-infection. Specimens
should be obtained to stain for acid-fast bacilli, culture and
PCR testing for mycobacterial DNA in any patient with
suspected disseminated BCG infection. Even though all of
these procedures can be negative, empiric therapy may be
instituted when the clinical suspicion is high.
2011 he received a kidney transplantation. He used oral
prednisolon 12,5 mg, and 750mg’s of mycophenolic
acid (MPA) twice daily. On physical examination the
right lateral malleolus was swollen and red, resembling
erysipelas. On the left leg there were five round erythemateus lesions. The patient had a temperature of 38,1
degrees Celsius and a C-Reactive Protein of 27. The general
practitioner had started amoxicillin and clavulanate,
without success . An infection seemed most probable.
Antibiotics were changed to clindamicine.
After 2 weeks the lesions progressed. Differential
diagnostic were opportunistic infections, TBC, CMV, ABV,
M.Whipple more likely. The differential diagnosis included
auto-immuun diseases such as sarcoidoses, SLE or vasculitis.
Paraneoplastic and medicine-effects were possible.
A skin biopsy was taken from the right foot, which showed
a erythema nodosum. Laboratory-tests such as rheum
factor, anti CCP, IGRA and ANA were all negative. His
corticosteroids were doubled.
A few weeks later band-shaped purpura developed on his
back and his body temperature rose to 39 degrees Celsius.
There was a skin biopsy taken from his back. In the skin
biopsy granuloma’s were seen. The skin biopsy and the
blood was cultured for tuberculoses. In both we found
NTM. While waiting for the determination we started
azitromycine and ethambutol. Rifampicine was not started,
because of the interference with mycophenolic acid. After
the culture of M. Haemophilum, we changed the antibiotic
regime to claritromycine, ethambutol and rifabutin (this
has no interference with mycophenolic acid).
Conclusion: NTM bacteria infections are rare and can
present with a great variety of symptoms. In this case we
describe a typical mycobacterium haemophiluminfection
which was cultured from blood and skin.
C108 Disseminated Mycobacterium haemophilum infection
in a immunocompromised patient
C109 ITP as presenting symptom of extrapulmonary
tuberculosis
F.J. Borm, L.J.M. Reichert, C. Richter
Rijnstate Hospital, Department of Infectious Diseases/
Nephrology, Wangerlaan 55, 6800 TA ARNHEM, the
Netherlands, e-mail: [email protected]
M. Radersma, A.M. de Kreuk, D.R. Veenstra
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: Mycobacterium haemophilum is an acid-fast
bacillus (AFB) belonging tot the Group of nontuberculous
mycobacteria (NTM). An infection with M. Haemophilum
is rare and mostly seen in immunocompromised hosts. We
present a patient with a kidney transplantation who presented
with different skin leasions due to M. Haemophilum .
Case report: A 64-year old male presented at the emergency
department with progressive erythema and joint pain on
the lower extremities. His past medical history revealed
an anti-GBM antibody disease. Treatment was unsuccessful and renal replacement therapy was begun. In
Introduction: Immune thrombocytopenic purpura (ITP)
is associated with auto-immune diseases and various viral
infections, such as HIV, EBV and CMV. We report a rare
case of a 50 year old male with ITP as presenting symptom
of extrapulmonary tuberculosis.
Case: A 50-year old male, born in Burkina Faso, presented
with a history of recurrent mucosal bleeding since one
week. Besides the mucosal hemorrhages there were no
other bleeding sites. There was no history of cough with
expectoration, fever, loss of appetite, or weight-loss. Two
88
(29g/L) and a mild elevated C-reactive protein (43 mg/L).
CD4+-count was zero and the HIV viral load was 302066
copies/ml. Chest X-ray showed bilaterally reticular
opacities, mediastinal widening and left-sided pleural
effusion. Histopathologic examination of the skin lesions
confirmed the diagnosis of cutaneous Kaposi sarcoma.
Additional serology demonstrated a latent syphilis of
unknown duration and a cleared hepatitis-B-virus infection.
A bronchoscopy with bronchoalveolar lavage (BAL) was
performed because of a high suspicion of Pneumocystis
jiroveci pneumonia, which showed hyperemic bronchial
epithelia. There were no signs of intrapulmonary Kaposi
Sarcoma. Bacterial cultures of blood and urine were
negative. However specific stainings and PCR of the
BAL fluid were negative for Pneumocystis jiroveci and
a M. tuberculosis infection was ruled out by PCR and
culture. Subsequently, because of the persisting fever and
unexplained pulmonary abnormalities a High Resolution
(HR)-CT-scan and a lymph node excision were done.
HR-CT showed interlobular congestion, hilar lymphadenopathy and pleural effusion. Histopathologic examination
of an axillairy lymph node revealed a plasmacellular type
of Castleman disease and also signs of Kaposi sarcoma.
Human herpes virus-8 (HHV-8) DNA could be detected in
plasma, showing a high viral load. Rituximab was started
to treat the Castleman disease and the patient was put on
anti-retroviral therapy. During this combined treatment
the viral load of HIV and HHV-8 diminished and after a
few weeks of admission the patient could leave our hospital.
Discussion: HIV-associated Multicentric Castleman
Disease (MCD) is a rare lymphoproliferative disease caused
by an infection with HHV-8. A characteristic clinical
finding of MCD is an abnormal chest X-ray with bilateral
reticular or ground glass opacities, mediastinal widening
and pleural effusion, compatible with the chest X-ray of our
patient, which can be easily misinterpreted as PCP. The
diagnosis of MCD is based on histopathologic findings.
There is no standardized treatment for MCD.
Conclusion: Besides an infectious cause, also think of
MCD in case of perihilar pulmonary abnormalities on a
chest X-ray in a HIV-positive patient.
months earlier the patient was analyzed for transient pleural
fluid, but no diagnosis was made. Physical examination
showed mucosal bleeding but no other abnormalities.
Laboratory evaluation revealed anemia (Hb 5.3 mmol/L)
and a thrombocytopenia (platelet count of 3*10^9/L). A new
x-ray was normal. The patient received a platelet transfusion
which resulted in a temporary rise of the platelet count to
22 but dropped to 7 again the next morning. Intravenous
immunoglobulins were administered with a good response,
restoring the platelet count to normal over the following
days. No prednisolone was given. The good response
to immunoglobulins suggested ITP as a cause for the
thrombocytopenia. Results of HIV- testing, CMV and EBV
were negative. To rule out splenomegaly, an abdominal
ultrasound was performed. The spleen size was normal,
but an undefined intra-abdominal mass of 23 x 9,5 cm was
found. The mass was sampled; cytological and histological
testing showed no abnormalities. After 3 weeks the patient
returned with dyspnea. A new x-ray showed a large amount
of pleural fluid. Additional testing revealed no growth and
no tumor cells. One day later the mystery was solved: after
4 weeks of incubation the culture of the sample of the
abdominal mass showed growth of Mycobacterium tuberculosis. Tuberculostatic therapy was initiated resulting in a
decrease of pleural fluid. The abdominal mass decreased in
size as well and his platelet count remained normal.
Discussion: The association of ITP and TBC is well
known because of the frequent reactivation of TBC after
immunosuppressive treatment for ITP. Only a few cases
have been described in which TBC presents with thrombocytopenia without prior steroid treatment. In some of
these cases antiplatelet antibodies were demonstrated
in the serum. The production of circulating antibodies
against platelets might be induced by the Mycobacterium
tuberculosis infection.
Conclusion: In a case of ITP, TBC should be considered as
an underlying disorder.
C110 HHV-8: King of the Castle(man)
J.L. Witmer, A. Riezebos-Brilman, S. van Assen
University Medical Centre Groningen, Department of
Internal Medicine/Infectious disease, Hanzeplein 1,
9700 RB GRONINGEN, the Netherlands, e-mail:
[email protected]
C111 Descending mediastinitis in Epstein-Barr virus
infection
J.W.H.J. Geerts, M.J.F.M. Janssen
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
[email protected]
Case report: A 33-year-old male originally from Iran was
admitted to our hospital because of a newly diagnosed
HIV-infection and fever. On physical examination there
were jugular and axillairy lymphadenopathy and brownish
skin lesions on abdomen, left forearm and back suggestive
of Kaposi sarcoma. Laboratory testing showed a microcytic
anemia, leukopenia (2,2 x 10^9), a mild hypoalbuminemia
Introduction: Epstein – Barr virus (EBV) is a common
disease with usually mild symptoms including fever (98%),
sore throat (85%), fatigue and enlarged lymph nodes. In
89
Introduction: Primary infections with strongyloïdes
stercoralis infections in immune competent hosts generally
occur asymptomatic. These acute infections are rarely
observed in endemic regions and only a few case reports
describe symptoms of acute strongyloidiasis.
Case: A 26-year old – previously healthy – man was seen
at our hospital 19 days after returning from a 15-day
roundtrip in Thailand. During his stay he had transient
diarrhea. In the last 72 hours he suddenly felt unwell
with abdominal pain, fever up to 40°C, muscle ache,
and headache. A rash arose on his abdomen. Physical
examination on presentation showed a mild fever (38.6°C)
and patchy erythematous papulous rash on his abdomen
and flanks. Laboratory results included; CRP 223 mg/L,
Leucocytes 8.0*10e9/L with 3% eosinophils, Thrombocytes
173*10e9/L. Initially a presumptive diagnosis of rickettsiosis, e.g. louse-born typhoid fever, was made and
accordingly he was treated with doxycycline.
During the follow-up the rash disseminated and he
developed leukocytosis (23.9*10e9/L) with marked eosinophilia up to 17*10e9/L while the CRP decreased to 16 mg/L.
Rickettsia serology and serial blood cultures remained
negative.
Examination of fresh stool samples (Baerman test), four
weeks after initial presentation, revealed rhabditiform
larvae of strongyloides stercoralis. He was treated with
ivermectine (12g at day one and seven) with swift
resolution of both signs and symptoms. In retrospect the
patient told that during his holidays he walked barefoot on
the feces littered banks of the River Kwai.
Discussion: After the filariform larvae of strongyloides
stercoralis, present in materials contaminated with human
feces, penetrate the skin of the host the larvae migrate
to the lungs. The larvae subsequently are swallowed
after reaching the tracheobronchial tree. In the gastrointestinal tract the larvae develop into adults and the
rhabditiform larvae will appear, about three to four weeks
after initial infection, in the feces. In immunocompetent
hosts strongyloides infections can persist for years – due to a
phenomenon called auto-reinfection – without symptoms.
Our patient however developed a cutaneous reaction,
probably shortly after the initial infection, followed by
hypereosinophilia. As expected strongyloides rhabditiform
larvae were detected not till four weeks later in stool
samples.
Conclusion: Primary strongyloides stercoralis infections
rarely cause acute symptoms in immunocompetent hosts
and are characterized by hypereosinophilia, fever and rash.
Since diagnosis is difficult in the first phase, serologic and
stool tests should be performed at least 4 weeks after the
initial symptoms.
limited cases, complications can arise including rupture of
the spleen, myocarditis, pancreatitis, acute kidney failure
or neurological disorders. We present a case of a young
patient with an EBV infection complicated by descending
mediastinitis.
Case: The patient was a previously healthy 34-year old
male, who was referred to our emergency department
by his general practitioner. He complained of fever and
a sore throat since 2-3 weeks and had been diagnosed
with EBV infection (positive IgM and IgG). Because of
pain in his upper abdomen and dysfagia he consulted his
general practitioner again. At the emergency room the
patient was hemodynamically unstable with a relatively low
blood pressure, tachycardia and a high respiratory rate. At
inspection the tonsils were enlarged, with white exudate. On
examination of the neck, the throat was swollen and painful
at palpation, but no redness was seen. With pulmonary
auscultation pleural rubs were heard. Palpation of the upper
abdomen was painful. The laboratory investigations revealed
leucocytosis, elevated CRP and elevated liver enzymes. Chest
X-ray showed a minor infiltrate and cervical and mediastinal
emphysema. The patient was started on Augmentin and the
intensive care was consulted. A CT-scan of the thorax and
of the neck showed cervical and mediastinal emphysema,
cellulitis, mediastinitis and a peritonsillar abscess. The
emphysema could have come from a gas-producing bacteria
(fasciïtis necroticans) or from a defect in the trachea or
oesophagus. The diagnosis was descending mediastinits
after a peritonsillar abcess. Because of respiratory distress
the patient was intubated and he was transferred for
evaluation for thoracic surgery. The patient was treated
with broad spectrum antibiotics and underwent extensive
surgery, i.e. debridement of the mediastinum and multiple
surgical drainage procedures for pleuritic empyema. After
a 60 day period in hospital, including 26 days in intensive
care, the patient was discharged.
Discussion: In the literature two mechanisms for this
complication of EBV infection are described, both based
on a peritonsillair abscess. The first mechanism is a breakthrough of the abscess through a space between the alar
and prevertebral space, the second is a septic thrombophlebitis (syndrome of leMierre). Descending mediastinitis is
a complication of EBV infection, which can be fulminant
even in healthy young individuals. Early recognition and
treatment are vital.
C112 A rare case of acute strongyloides stercoralis
infection acquired during a stay in Thailand
S. de Bie, J.J. van Hellemond, P.J. Wismans
Haven Hospital, Department of Internal Medicine,
Haringvliet 2, 3011 TD ROTTERDAM, the Netherlands,
e-mail: [email protected]
90
C113 Renal impairment due to an improved immune
system; the return of sarcoidose in HIV.
granulomatous inflammation in sarcoidosis in these
patients. Thusfar two HIV-infected patients with renal
insufficiency due to sarcoidose have been described. This
case illustrates the rare co-occurrence of renal sarcoidosis
and HIV in a patient treated with HAART. In HIV positive
patients with a near normal immunefunction and renal
impairment sarcoidosis should be considered in the differential diagnosis.
T.A.M. Claushuis, K. Lettinga, C.E.H. Siegert, J. Veenstra
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: In HIV-infected patients with progressive
renal impairment, HIV-related conditions such as HIVAN
and HIV-tubulopathy as well as causes unrelated to the
HIV infection should be considered. In the pre-HAART
era, the co-occurrence of HIV and sarcoidosis was
uncommon. We report a case of progressive renal
impairment due to renal sarcoidosis in a HIV infected
patient treated with HAART.
Case: A 40 year old man, with a history of HIV-infection
(CD4 count 140/uL) and a Kaposi sarcoma, and treated
with nevirapine and emtricitabine/tenofovir since 2008,
was seen in our outpatient clinic for a routine follow up.
Previously, his renal function had been normal (serum
kreatinine: 104umol/L, GFR(MDRD): 69 ml/min) when
a progressive decline in renal function was observed
during the last 9 months. Patient also reported symptoms
of weight loss, coughing and fever as well as subcutaneous skin lesions, present over the last few months. His
family history revealed sarcoidosis diagnosed with his
father. On physical examination multiple subcutaneous
nodules were seen, without erythema. Laboratory results
showed:kreatinine 252umol/L, GFR (MDRD): 25 ml/
min and ESR of 58mm/1hour. Urinalysis was positive for
protein (1.8g/24hours) and negative for (glomerular) erythrocytes and calciuria. IGRA was negative and HIV viral
load was < 20.0 copies/ml with a CD4 count of 420/uL.
ANA was positive, and ANCA, anti-dsDNA and anti-GBM
antibodies were negative and no monoclonal gammopathy
was found.
Previous examinations had shown stationary mediastinal
lymphadenopathy but despite CT, PET, bronchoscopy,
BAL and EBUS no diagnosis was made. Because of the
progressive nature of the renal insufficiency we performed
a renal biopsy which revealed a granulomatous interstitial nephritis. Additional staining ruled out infectious
causes and renal sarcoidosis was deemed most likely. A
skinbiopsy revealed no granulomas. Patient was treated
with 60mg prednison, after which his renal function
markedly improved (kreatinine:128umol/L, GFR (MDRD):
54ml/min).
Conclusion: Sarcoidosis in HIV-positive patients with low
cellular immunity is rare. A CD4 count of > 200cell/uL
is considered necessary to develop sarcoidosis. Since the
availability of HAART, the incidence of sarcoidosis in
HIV-infected patients has increased. It has been hypothesized that the restoration of cellular immunity induces
C114 Do not forget the pet!
N. Carpaij, H.J. Bloemendal
Meander Medical Centre, Department of Internal Medicine,
De Maatweg 3, 3813 TZ AMERSFOORT, the Netherlands,
e-mail: [email protected]
Introduction: According to the Dutch National Institute of
Public Health and the Environment (RIVM) approximately
60% of families in the Netherlands have a domesticated
animal. These two million dogs, three million cats, one
million rabbits, five million birds and 19 million fishes can
serve as a potential reservoir for pathogens, such as Methicillin
Resistant Staphylococcus aureus, Extended Spectrum
Beta-lactamase producing bacteria, Rabies or bird-flu. All
these pathogens might cause serious infections in human.
Casus: Here, we present a case of a 17-year old woman
who consulted the outpatient department of internal
medicine with skin lesions on her left middle finger, which
appeared four weeks after a small trauma while cleaning
an aquarium. Over two months the lesions expanded to
her upper arm. Physical examination showed an erythematous papule and two small maculae on the left middle
finger. Furthermore, proximal to the left elbow one nodus
and on the ulnar side five noduli were seen. The patient
did not report episodes of fever. Laboratory results showed
a leukocyte count of 5.9 x 109/L and a C-reactive protein
of smaller than 1 mg/L. Biopsy of the lesions showed a
granulomatous infection, suspect for aquarium granuloma,
which was confirmed by a positive culture of Mycobacterium
marinum. After two months treatment with antibiotics the
aquarium granuloma disappeared completely.
Discussion: Aquarium- or swimmer’s granuloma is caused
by the nontuberculous, M. marinum. This rare granulomatous skin infection typically follows from minor hand
trauma and contact with fresh fish, salt water or contaminated swimming pool-water. For that reason infections
should be sought in people who experienced contact
with fresh fish or cleaned an aquarium. The incubation
period varies between two and six weeks. The diagnostic
process of infections with M. marinum is hampered by the
requirement for specific culture conditions. Furthermore,
elevated inflammatory markers may be absent. These
aspects could make a physician less aware of an infectious
91
Discussion: In ALA, seropositivity can be delayed, but
persistent negative serology on ELISA with a repeated
positive PCR on a sample of the abscess has not been
previously described. Our patient presented with
symptoms of only two days duration and received metronidazole the next day. The presence of antibodies to
cytomegalovirus and Epstein-Barr Virus indicate than an
impaired immune response as an explanation is unlikely.
Therefore we hypothesize that this very early presentation
(as illustrated by the solid material on first biopsy with
subsequent pus formation ten days later) and consecutive
early therapy prevented an antibody response strong
enough to produce seropositivity. Earlier PCR would have
made an earlier diagnosis, thereby avoiding prolonged
empiric antibiotic therapy.
Conclusion: After early therapy of a recent amoebic liver
abscess a serologic response may fail to occur. Entamoeba
histolytica PCR of the aspirated material might lead to an
early accurate diagnosis.
cause. Nevertheless, untreated infection with M. marinum
can lead to serious morbidity, including loss of joint
mobility due to osteomyelitis and even amputation of the
affected side. Especially, but not exclusively, immunecompromised patients are at risk for a complicated course,
which emphasizes the awareness for this disease.
In conclusion, when a patient presents with papulae on the
extremities, be suspicious for an aquarium granuloma and
ask for potential triggers, because delayed diagnosis might
result in significant morbidity.
C115 Amoebic liver abscess; the role of PCR in the absence
of a serologic reaction
M.G. Caris1 , P.G.H. Peerbooms1, L. van Lieshout 2 ,
J. Veenstra1
1
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM,
the Netherlands, e-mail: [email protected], 2Leiden
University Medical Centre, LEIDEN, the Netherlands
C116 ‘Homebred’ Hepatitis E
Introduction: In patients with hepatic abscesses differentiating between pyogenic and amoebic aetiology can
be challenging. Microscopy and culture of the so-called
‘anchovy paste’, derived by aspiration of an amoebic
liver abscess (ALA), has low diagnostic yield; trophozoites are rarely seen on microscopy and are difficult to
grow. Enzyme Linked Immunosorbent Assay (ELISA)
for detection of antibodies to E. histolytica is currently
considered the superior diagnostic method. However,
polymerase chain reaction (PCR) on aspirated material
has proven very sensitive in extra-intestinal amoebiasis,
specifically in ALA.
Case-report: Our patient, a 37-year-old Italian male,
presented late 2012 with severe abdominal pain in the
upper right quadrant since two days. In 2005 he had spent
one year in Egypt; he had returned from Italy two weeks
before. Laboratory investigations showed leucocytosis
and elevated C-reactive protein, liver function tests were
normal. Ultrasonography revealed multiple liver lesions.
Serology for Entamoeba histolytica was negative. Blood
cultures showed no growth, HIV was negative. Aspiration
of the abscess revealed solid material that was not cultured,
histologic examination showed signs of purulent inflammation but no microorganisms. Symptoms improved
with ceftriaxone/metronidazole. To exclude malignancy,
a second liver punction after ten days showed pus, but
no bacteria on Gramstaining and culture. PCR on this
material was strongly positive for E. histolytica. A repeated
ELISA two months after the start of symptoms remained
negative. PCR on the first biopsy material was positive for
E. histolytica as well, making a false-positive result unlikely.
E. Kloeze, S. van Assen, A. Riezebos-Brilman
University Medical Centre Groningen, Department of Internal
Medicine, Hanzeplein 1, 9700 RB GRONINGEN, the
Netherlands, e-mail: [email protected]
Introduction: Hepatitis E virus (HEV) hepatitis has until
recently mainly been regarded as a travellers’ disease:
an acute, sometimes fulminant, hepatitis, oral-fecally
transmitted in endemic areas, and usually self-limiting.
The following case illustrates that presence of HEV,
however, should also be considered in non-travellers
presenting with acute hepatitis.
Case: A 58-year old male, with a past medical history of
gout and diabetes mellitus type 2, presented with pain
in the upper abdomen and nausea. Bowel habits were
unchanged. Fever was not present. No family members
were ill. He did not travel abroad. Three days before
admission he underwent cataract surgery, whereafter his
complaints started. In addition, three weeks earlier he had
suffered a gout attack for which he received diclofenac
followed by co-amoxiclav for seven days and prednisolone.
On physical examination the patient did not appear acutely
ill and hemodynamically stable. Temperature was 37.6
°C. The upper abdominal region was tender on palpation.
Blood counts were normal except for a mild thrombocytopenia (113.10^9/L (range 150-350.10^9/L). Biochemical tests
revealed elevated transaminases (maximum AST 3147 U/L
(range 0-40 U/L), ALT 2742 U/L (range 0-45 U/L)). Lactate
dehydrogenase was 2139 U/L (0-250 U/L). Bilirubin,
glucose and coagulation tests were within normal range.
92
Within a week the patient recovered fully. Diagnosis
at discharge was toxic hepatitis caused by propofol or
co-amoxiclav. However, additional diagnostic tests were
performed to exclude viral causes of hepatitis, showing
positive IgM antibodies against HEV in serum along with
a high plasma viral load of HEV RNA (10e6 copies/ml).
Sequence analysis revealed a HEV genotype 3.
Discussion: Non-travel related HEV hepatitis is an underdiagnosed emerging infection in developed countries.
The screening of healthy blood donors in the Netherlands
recently demonstrated an overall seroprevalence of 27%.
The route of transmission of these “home-bred” hepatitis
E infections, generally genotype 3, is not fully unravelled.
Due to its generally asymptomatic and self-limiting course
it often remains unrecognized in the general population.
Yet, missing the diagnosis could harm patients either by
withholding drugs (in this case propofol and co-amoxiclav),
risk of organ rejection (in solid organ transplant recipients)
or unnecessary use of steroids. Further studies are
necessary to investigate treatment options and consequences, infection prevention and source control.
Conclusion: Hepatitis E should always be considered as a
cause of acute hepatitis, in immunocompetent as well as
immune-compromised patients with unexplained impaired
liver tests. Serology and PCR are the diagnostic tools to
confirm the diagnosis.
sharp wave complexes, cerebrospinal fluid(CSF) analyse for
14-3-3-protein and tau protein and the MRI image.
Case presentation: A 57 years old female presented
at neurology with symptoms of an altered speech,
involuntary movements, unstable gait, and anxiety. By
physical examination the only odd symptom is a mild
ataxia. She presented one month earlier at the emergency
department with an uncontrollable right leg and a right
sided disturbance of sensibility. Despite extensive research
in the form of a MRI scan cerebrospinal fluid analyse no
explanation was found. The conclusion is: The complaints
are an expression of a conversion disorder.
She is admitted to the psychiatric ward. There was started
with medication. During the next two weeks patient’s
condition deteriorated rapidly, she became catatonic
.Treatment consists of benzodiazepines and electroconvulsive therapy. Also she develops a fever, the only source
of the fever is a urinary tract infection.
Because the rapidly decline in condition and the
observation of a myoclonus spontaneous in response to
tactile stimuli, the possibility of a CJD emerges. A third
evaluation follows with a new MRI, EEG and analyse of
liquor for 14-3-3-protein and tau protein followed. The
MRI showed an image of increased signal intensity at the
nucleus caudatus and the putamen. The EEG shows sharp
wave patrons. The liquid is tested positive for 14-3-3 protein
and tau protein, strongly supporting the diagnosis of CJD.
Because there are no therapeutic options, palliative care
was started.
This case underlines the difficulties with diagnosing CJD
especially when there are also psychiatric symptoms. Also
it shows the rapid decline in condition.
C117 A very rare cause explanation of a psychiatric
symptoms; Creutzfeldt-Jakob Disease
H. van der Valk, P.H.P. Groeneveld
Isala Clinics, Department of Internal Medicine, Dokter
Heesweg 2, 8025 AB ZWOLLE, the Netherlands, e-mail:
[email protected]
C118 A dangerous home coming celebration dinner
A. Vellinga, L. Scheven, R.S. van Rijn
Medical Centre Leeuwarden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: [email protected]
Introduction: Creutzfeldt-Jakob disease (CJD) is an
ultimately fatal, neurodegenerative disease caused by
misformed prion aggregation and accumulation. CJD has
a worldwide incidence of around 1 in 1,000,000. Currently
five human prion diseases are recognized: kuru, CJD,
variant CJD, Gerstmann-Sträussler-Scheinker syndrome
(GSS), and fatal familial insomnia. Prion diseases share
certain neuropathologic features including neuronal loss,
proliferation of glial cells, absence of an inflammatory
response and the presence of a spongiform encephalopathy. CJD accounts for more than 90% of all cases. It
is a rapidly progressive disorder associated with dementia,
focal cortical signs, rigidity, and myoclonus. There is no
treatment. Death occurs usual within a year after the
first symptoms. Brain biopsy remains the gold standard
diagnostic test for CJD. The clinical diagnosis based on
the clinical picture and specific EEG patrons with periodic
Introduction: it is a common reaction of cancer patients
who are motivated to survive, to change their diet into a
more healthy one. Such a diet usually contains less alcohol,
more fruit, vegetables, lean meat and fat fish once a week.
However, many patients become immune compromised
due to immune suppressive medication, such as chemotherapy and steroids. And in that case, how healthy is their
‘healthy diet’ ?
Case: a 61 year old man, with a history of a glioblastoma
for which he recently underwent surgery and still used
dexamethasone, presented to our hospital because of
persistent pain in his left hip. Furthermore, he mentioned a
93
Case: A 65-year old Caucasian male presented with long
standing general malaise, fever, severe arthralgias, muscle
weakness, and palpable purpura. His medical history
reported COPD, CABG, and an EVAR procedure for a AAA.
There was high CRP, normocytic anaemia, and elevated IgM
rheumatoid factor (RF). Blood cultures and infection serology
were negative. Total body PET-CT did not show any signs of
inflammation or malignancy. The patient was referred to
the Maastricht University Medical Center under suspicion of
cryoglobulin mediated small vessel vasculitis. The extremely
high IgM RF (> 10000 IU/L) was confirmed, with type II
cryoglobulins (monoclonal IgM/kappa with polyclonal IgG).
Complement was slightly elevated. Hepatitis C PCR was
negative. Blood cultures, ANCA and antiphospholipids were
negative. Urinary sediment showed dysmorphic erythrocytes and low proteinuria. Kidney biopsy showed necrosis
of capillary loops, and IgM, IgA, and C3 deposition. Plasma
exchange, corticosteroids and mycophenolic acid was started,
followed by rituximab. The patient improved, but was again
admitted 15 months later with shortness of breath and fever.
Blood cultures remained negative. Echocardiography showed
aortic-valve stenosis and mitral-valve insufficiency, but no
vegetations. Subsequently, the patient underwent aorticvalve replacement. Coxiella burnetii PCR of the native valve,
surprisingly, was positive. Patient underwent treatment with
doxycycline and hydroxychloroquine.
Discussion: Most likely this patient suffered from chronic
Q fever, with formation of type II cryoglobulins, small
vessel vasculitis, endocarditis, and kidney involvement.
According to the literature, the incidence of endocarditis
due to Coxiella burnetii is low (1 per 1000000) and in these
patients only 5% appeared to have cryoglobulin formation.
Typically, these patients appeared to have a prosthetic valve.
The slow, indolent course of disease during strong immunosuppression in our patient is remarkable. In type II cryoglobulinemia patients, lymphoma, systemic autoimmune disease,
and hepatitis C have to be excluded first. Our case history,
however. strongly illustrates that a meticulous search for the
presence of chronic Q fever may be difficult, but is necessary
before starting immunosuppressive treatment.
period of nightly non-bloody diarrhea a week before hospital
admission. Physical examination showed a vital man with
an erythematous, warm and swollen left buttock. Passive
movements of the hip were extremely painful. Laboratory
analysis showed a C-reactive protein level of 429 mg/L.
X-ray showed a normal hip bone. Ultrasound examination
showed a thickened synovium with a little fluid around
the joint. A synovial fluid aspiration was performed and
purulent fluid was put on culture. Culture results showed
the presence of Salmonella group B, consistent with the
diagnosis of Salmonella arthritis. Blood cultures remained
negative. An arthrotomy with drainage was performed, and
iv antibiotics were administered for 6 weeks. The planned
chemo-radiotherapy (Stupp protocol) for glioblastoma was
postponed for several weeks. In the end, the treatment with
antibiotics was successful and he could continue his further
treatment. On retrospective anamnesis he declared to have
eaten salmon more than once week. According to current
trends in cooking he preferred it uncooked, as in sashimi.
Discussion: Spontaneous septic arthritis is uncommon and
usually associated with Staphylococcus Aureus, streptococci
and Haemophilus influenza. Salmonella arthritis is very
rare, presenting in only 1% of all cases, and more commonly
in immunocompromised patients. However, last year there
have been several reports of life-threathening Salmonella
infections caused by contaminated salmon. (see link
below) This case illustrates that it is important to remain
suspicious of uncommon presentations of a common
illness, especially in patients who are immunocompromised. It also illustrates that as a doctor it is important to
be aware of the habits of patients and changes they make
in their life style during all of the therapies they receive.
http://www.nu.nl/binnenland/3632310/salmonellazalmbleef-lang-in-winkels-liggen.html
C119 Vasculitis and cryoglobulins: be aware of the
insidious Q
S.J.M. Vreeswijk 1 , M.J.M. Schonck 1, A.N. Roos1,
A.J.G.H. Bindels1, J. Damoiseaux2, P. van Paassen2
1
Catharina Hospital, Department of Intensive Care,
Michelangelolaan, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: [email protected], 2Maastricht University
Medical Centre, MAASTRICHT, the Netherlands
C120 The sneezing kitten
M. van Dijk, S. Anten
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2352 GA LEIDERDORP, the Netherlands, e-mail:
[email protected]
Introduction: Since outbreaks in 2009, the Netherlands
have become familiar with Coxiella burnetii, an intracellular bacterium, using macrophages as host, making it
difficult to eradicate. Acute exacerbations and chronic
Q fever have been described, with flu-like symptoms,
pneumonia, hepatitis, and/or endocarditis. Kidney
involvement and vasculitis is unusual in these patients,
making the differential diagnosis sometimes difficult.
Case: A 70-year-old male presented to our emergency
department because of fever and chills since several hours.
No other symptoms were present. His medical history
revealed type 2 diabetes, hypertension, stroke because
of atriumfibrillation 4 years ago with hemiparesis and
94
dysarthria and he was diagnosed with sarcoidosis stage
III-IV 2 years ago. On general physical examination the
patient was dyspnoeic, with a respiratory rate of 35/min.
and an O2-saturation of 92%. He had a fever of 39.9
degrees celsius and an irregular tachycardia of 115/min.
Besides the known hemiparesis, no other abnormalities
were noted. Laboratory analysis showed a mild leucocytosis and a lactate level of 5.2 mmol/L. A chest x-ray
revealed old stage III sacoidosis parenchymal disease and
new pulmonary infiltrates in the lingual region and left
lower lobe. Subsequently, the patient was treated with
cefuroxim and gentamycin. Two days later blood cultures
were positive for Pasteurella multocida (P. multocida) and
the antibiotics were switched to amoxicillin. Inquiring the
patient about animal contacts, he mentioned that a couple
of months ago they had bought a kitten because people had
suggested it might lift his spirits after the stroke. A few
weeks before admission, however, the kitten had gotten
sick and started sneezing while sitting on the patients lap.
Discussion and conclusion: Pasteurella spp are gram
negative coccobacilli that are primarily commensals of
animals. These organisms can cause a variety of infections
in humans, usually as a result of cat scratches or cat
or dog bites or licks. The P. multocida is a component
of the normal upper respiratory tract flora of many
mammals, especially felines, and birds. Infections with
the P. multocida can cause a variety of oral and respiratory
infections, usually in the setting of chronic pulmonary
disease. They can also cause soft tissue infections, bone
and joint infections, and other serious invasive infections,
including bacteraemia. In this case most likely the P.
multocida was transmitted aerogenically from the sneezing
cat to the patient. Because of pre-existing sarcoidosis he
was more susceptible for acquiring an invasive pasteurella
infection.
During follow-up complete resolution of the pneumonia
occurred. The kitten was adopted by a family member.
weight loss, night sweats or coughing. The pain responded
well on nonsteroidal anti-inflammatory drugs and a course
of prednisone prescribed by his general practitioner. On
physical examination a non-erythematous swelling was
visible at the cuboid- and cuneiform bone which was
warm and tender on palpation. There was no fever and
no lymphomas were palpable. Laboratory results show
a slightly elevated erythrocyte sedimentation rate and
alkaline phosphatase of 33 mm/hour and 151 u/L respectively. Rheumatoid factor was slightly elevated. PCR for
Chlamydia trachomatis and Neisseria gonorrhoeae as well
as serology for Borrelia burgdorferi were negative. A severe
destructive arthritis of the charcot joint was seen on a three
phase bone scan. No urate crystals were seen in a sample of
fluid aspirated from the affected joint. At this point tuberculosis was considered and a chest X-ray and Interferon
Gamma Release Assay (IGRA) were performed. There
were no signs of active or old tuberculosis. The IGRA was
negative. The orthopedic surgeon was then asked to take
a bone biopsy. The pathology report showed an inflammatory infiltrate without any granulomas, necrosis or
Langhans giant cells. On microscopy the auramine stain
was negative. Culture showed growth of Mycobacterium
tuberculosis.Our patient was treated with rifampicin and
isoniazid for nine months and pyrazinamide for three
months.In this case the physician delay was eight months
of which five and a half months were in-hospital delay.
Discussion: This case illustrates again that a negative
IGRA never excludes active tuberculosis. The majority
of patients with bone tuberculosis present without active
pulmonary tuberculosis. There for it remains important
to perform a chest X-ray to look for old signs of tuberculosis. Negative pathological findings emphasize the
need for combined pathological and microbiological
examination on the tissue including PCR.Conclusion:
Since extra-pulmonary tuberculosis is a rare disease in the
Netherlands the most important step is for the physician to
consider the diagnosis. Furthermore early consultation of
an infectious disease specialist is warranted to give advise
on the diagnostic work-up in order to decrease physician
delay.
C121 Bone tuberculosis: a diagnosis to consider
L. Gil
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
C122 Ceftaroline for MRSA ICD-associated endocarditis
and osteomyelitis
Introduction: Bone tuberculosis is a rare form of extrapulmonary tuberculosis. Patients often present with
non-specific symptoms which can lead to a remarkable
delay in diagnosing the disease and thus the start of
adequate treatment.
Case report: A 51 year old male originally from Sri-Lanka
presented himself at the rheumatologist office with
progressive pain in his left foot. He did not experience any
M.J.A. Visschers, F.M.H.P.A Koene, V.H. Hira, R.P. Peters,
S.H. Lowe
Maastricht University Medical Centre, Department of
Internal Medicine, Dillegaard 168, 6417 HK HEERLEN, the
Netherlands, e-mail: [email protected]
Introduction: Methicillin resistant Staphylococcus aureus
(MRSA) infections cause significant morbidity and
95
C123 The dog; man’s best friend? Pasteurella Multocida
sepsis in an immunocompromised host. A case
report
mortality, and more therapeutic options are urgently
needed. We present a case of a MRSA implantable cardioverter defibrillator (ICD)-associated endocarditis where
ceftaroline was used off-label.
Case: A 68-year old male was readmitted to the surgery
department with intestinal obstruction. Four months before
he had a pancreaticoduodenectomy which was complicated
by intra-abdominal abscesses, requiring antibiotic therapy
until two weeks before readmission. A central venous
catheter (CVC) was inserted. His bowel obstruction was
treated conservatively. After eleven days a catheter-related
infection was suspected; the CVC was removed and
vancomycin was started. MRSA was isolated from initial
blood and CVC tip cultures. After eight days of therapy
bacteremia recurred, the MRSA showing a raised minimal
inhibitory concentration (MIC) of 2 mg/L for vancomycin.
A transesophageal echocardiography (TEE) showed no
indication of ICD-associated endocarditis. Therapy was
switched to teicoplanin and linezolid. Six days later a third
episode of bacteremia occurred and a follow-up TEE showed
a vegetation on the right ventricular lead. At that time the
patient suffered from low back pain and vertebral osteomyelitis was suggested by PET-CT. Transvenous ICD-lead
extraction and ICD-generator removal were performed,
linezolid was discontinued, and intravenous ceftaroline
600mg q8h was added to teicoplanin. Teicoplanin was
discontinued when ceftaroline sensitivity was confirmed by
E-test. The patient improved and ceftaroline was continued
until six weeks after ICD-removal. After three months there
are still no signs of recurrence.
Discussion: Ceftaroline is a fifth generation cephalosporin with activity against MRSA. It is approved for
treatment of complicated skin and soft-tissue infections
and community-acquired pneumonia, and is generally well
tolerated. In this case, an initial MRSA CVC-associated
infection was complicated by endocarditis and osteomyelitis and led twice to recurrence of bacteremia despite
appropriate antimicrobial therapy. ICD removal was
performed as soon as endocarditis became apparent. We
decided to initiate ceftaroline therapy as continuation with
glycopeptides would probably be suboptimal: glycopeptide
therapy failed to suppress the bacteremia even in the early
stage when endocarditis was made less likely by TEE. Also,
some reports suggest a reduced glycopeptide efficacy in a
MIC close to the susceptibility breakpoint. No side effects
of ceftaroline were observed despite the increased dosing
frequency (three instead of two times daily), which was
chosen due to the severity of the infection.
Conclusion: In this case, ceftaroline was an effective
treatment of a MRSA catheter-related infection complicated
by endocarditis and osteomyelitis.
C.S. Hakkers, D.R.P.H.P Groeneveld
Isala Clinics, Vijf hoek 37, 8011 NZ ZWOLLE, the Netherlands,
e-mail: [email protected]
Introduction: Pasteurella Multocida is a commensal of the
upper respiratory tract and oral cavity of most mammals
and fowl. Most Pasteurella species are susceptible for
penicillin. It is transmitted to humans mostly through
cat or dog bites or scratches. In the majority of cases, it
will give a local cutaneous or soft tissue infection. In rare
cases, especially in immunocompromised hosts, it can give
fulminant or generalized infections. We present a case of
a sepsis with Pasteurella Multocida in a patient receiving
chemotherapy.
Case: A 78-year old woman with a history of Chronic
Lymphatic Leukemia for which she received Chlorambucil,
was presented at the emergency room with sepsis; she had
a temperature of 39.5 degrees, a pulse of 100 bpm and her
blood pressure was 110/70. Oxygen saturation was 90%.
Her anamnesis did not give any clues for the etiology of her
sepsis; she had general complaints of lethargy, generalized
pain and drowsiness. Furthermore, her neighbor told
us that her living circumstances were lacking in general
hygiene. Laboratory analysis showed the before known
anemia en leukocytosis, and an increased CRP. Urine and
liquor analysis showed no signs of infection. On a chest
X-ray, there was a possible pneumonia in the left lower
lobe, so she was admitted and treated for a pneumosepsis
with penicillin and ciprofloxacin, after obtaining blood
cultures. After a day, three blood cultures became positive
with gram negative rods. Another day later, these turned
out to be Pasteurella Multocida, susceptible for penicillin.
After further inquiries, the patient turned out to have
three cats who scratched and bit her on a regular basis. At
this time she had already improved much clinically. The
antibiotics were switched to penicillin monotherapy and
after 14 days the patient could be discharged to a nursing
home for revalidation. She was giving advice on hygienically dealing with her cats.
Discussion: The gram-negative coccobacil Pasteurella
Multocida is a micro-organism often found in infections
following dog- or catbites, but even an animal licking intact
skin can give transmission. This case gives an example
of how it can lead to pneumonia and even sepsis in an
immunocompromised host. Contact with animals should
always be included in a thorough history.
96
Aim of the study: To asses if accumulation of nadroparin
occurs during nocturnal hemodialysis.
Materials and methods: We tested Anti-Xa levels in 13
clinically stable patients undergoing nocturnal hemodialysis 4 nights a week (session duration 8 hours). Dosages
nadroparin were administered according to the guidelines
of the Dutch Federation of Nephrology. We assessed anti-Xa
levels at 4 time points during 1 dialysis week. Before the
start of a the first dialysis session of the week (baseline),
prior to (T1) and after the last dialysis session of the week
(T2) and before the first dialysis of the following week (T3).
Secondary outcomes were the clotting and bleeding events
during this week. Anti-Xa levels were measured photometrically using a chromogenic technique. The paired
two-sample t-test was used for the statistical analysis.
Results: Patients received 71-95 IU/kg at the start of dialysis
and 50% of the initial dosage after 4 hours with a total dosage
of 128 ± 24 IU/kg. The mean dosage nadroparin for patients
also using acenocoumarol (n = 5) was 111 ± 15 IU/kg, whereas
it was 139 ± 22 IU/kg in the other 8 patients (p < 0.05). Anti-Xa
levels were 0,017 ± 0.018 IU/ml at baseline. At T1 anti-Xa
levels were significantly elevated (p = 0,026), in comparison
to baseline, by 0,02 IU/ml. At T2 anti-Xa levels were 0,419
± 0,252 IU/ml (p < 0.05 vs B and T1). At T3 anti-Xa levels are
equal to B (p = 0,77). No major clotting or bleeding events
were observed. Standard monthly laboratorium testing
remained stable during the testing period.
Conclusion: The used dosage regime of nadroparin during
nocturnal hemodialysis according to the Dutch guidelines
does not induce accumulation of nadroparin. In addition, it
seems a save and effective dosage in our population.
C124 A case of melioidotic prostatic abscess and nefrotic
syndrome after a trip in Gambia: a case report and
brief review of literature
F. Morelli, S.F.L. van Lelyveld, L. Smeets, H. Boom
Reinier de Graaf Gasthuis, Department of Internal Medicine,
Postbus 5011, 2600GA DELFT, the Netherlands, e-mail:
[email protected]
We describe a case of imported melioidosis in a 63-years
old Caucasian man after a travel in Gambia, Western
Africa. Patient presented with septicemia by a melioidotic
prostatic abscess and Acute Kidney Injury. Melioidosis
is caused by Burgoldheria Pseudomallei, a high-virulent,
gram-negative bacillus which contaminates soil and water
in tropical areas. This disease is endemic in Southeast Asia
and Northern Australia, while a very few is known about
its extend in Africa. Melioidosis has a wide spectrum of
clinical presentations, ranging from local skin infection to
fulminant septicemia. The most common presentation of
melioidosis is community-acquired pneumonia, occurring
in more than a half of all cases and followed by genitourinary infection (14%), skin infection (13%), bacteremia
without evident focus (11%), septic arthritis or osteomyelitis (4%) and neurologic involvement (3%). Visceral
abscesses are often found, generally multiloculated and
affecting more organs at the same time. In our patient,
surgical drainage of the prostatic abscess was performed
beside long-term antibiotic therapy. Patient improved but
kidney function did not recover and hemodialysis was
required. No relationship between the infection and the
occurrence of renal failure was found in this patient.
C126 Intravenous Iron Administration in Peritoneal
Dialysis Patients; the effect on mortality
XVI NEPHROLOGY RESEARCH
W.M. Michels1, B.G. Jaar2, P.L. Ephraim2, J. Luly2,
D.C. Miskulin3, N. Tangri4, S.M. Sozio2, T. Shafi2, D.C. Crews2,
J.J. Scialla5, W.L. St.Peter6, A. Mcdertmott2, K. Bandeen-Roche2,
L.E. Boulware2
1
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: [email protected], 2Johns Hopkins
University School of Medicine, BALTIMORE, USA, 3Tufts
University School of Medicine, BOSTON, USA, 4Seven Oaks
General Hospital, University of Manitoba, WINNIPEG,
Canada, 5University of Miami Miller School of Medicine,
MIAMI, USA, 6University of Minnesota College of Pharmacy,
MINNEAPOLIS, USA
C125 Effect of nadroparin on anti-Xa activity during
nocturnal hemodialysis
E. Buitenwerf, A. Risselada, E.N. van Roon, N. Veeger,
M.H. Hemmelder
Medical Centre Leeuwarden, Department of Nephrology,
Henri Dunantweg 2, 8934 AD LEEUWARDEN, the
Netherlands, e-mail: [email protected]
Background: Nadroparin is used during hemodialysis to
prevent clotting in the extra corporeal system. During
nocturnal hemodialysis patients receive an increased
dosage of nadroparin compared to conventional hemodialysis due to the intensified frequence and duriation of
dialysis. It is unknown whether the prescribed dosage
regime of nadroparin during nocturnal hemodialysis leads
to accumulation.
Introduction: The use of intravenous (IV) iron has risen over
the last decades in order to increase hemoglobin (Hb) levels,
while diminishing the use of potentially harmful erythropoietin stimulating agents (ESA’s). Iron administration has
97
been associated with infection and inflammation and thus
might increase the risk of death. Studies in hemodialysis
(HD) patients have shown conflicting results. Currently, no
specific studies on the association of iron administration on
mortality in peritoneal dialysis (PD) patients are available.
Aim of the study: To study the association of IV iron
administration on mortality among a contemporary cohort
of adult PD patients.
Materials and methods: We studied patients initiating PD
in Dialysis Clinic Inc. centers between 2003 and 2009. We
quantified the association of patients’ use of IV iron versus
no IV iron among two subgroups of patients receiving iron
over 1- and 3-months rolling time intervals with mortality
or switch from PD to HD in Cox proportional hazards
models. We employed marginal structural modeling
to account for time-dependent confounders (including
previous IV iron use, Hb, transferrin saturation, ferritin,
ESA use and oral iron dose). Maximum follow-up was
30 months and patients were censored in case of transplantation, lost-to-follow-up or at the end of follow-up.
Results: Of 1222 PD patients in the 1-month sub-cohort,
372 received IV iron. Of 1084 PD patients in the 3-month
sub-cohort, 438 received IV iron. Median survival was
21 months (range 8 to 30) in the 1-month sub-cohort and
23 months (range 10 to 30) in the 3-months sub-cohort. In
both 1- and 3-month sub-cohorts, IV iron administration
was not associated with all cause mortality [(hazard ratio
(HR) 0.68 (95% confidence interval 0.37 to 1.25) for
1 month and 0.91 (0.55 to 1.54) for 3 month] or cardiovascular [(0.83 (0.41 to 1.66) for 1 month and 0.93 (0.44 to
1.96)) for 3 month] mortality. In the 1 months sub-cohort,
patients administered IV iron had a higher chance of
switching to HD (0.62 (0.45 to 0.88) or a combination of
switching to HD and all cause mortality (0.64 (0.46 to
0.89). This association was not present in the 3-months
sub-cohort (switch to HD: 1.22 (0.80 to 1.88), switch to HD
and all cause mortality (1.11 (0.80 to 1.53).
Conclusion: The use of IV iron was not associated with
mortality in incident PD patients, but might be associated
with a higher chance of switching to HD.
General Hospital, University of Manitoba, WINNIPEG,
Canada, 5University of Miami Miller School of Medicine,
MIAMI, USA, 6University of Minnesota College of Pharmacy,
MINNEAPOLIS, USA
Introduction: Intravenous (IV) iron exposure has been
associated with an increased risk of infectious related
hospitalization in hemodialysis (HD) patients. Peritoneal
dialysis is associated with a lower use of IV iron and
less systemic infections. Whether IV iron exposure also
enhances the likelihood of infectious complications in
peritoneal dialysis (PD) patients in unclear.
Aim of the study: To study the association of IV iron
administration with all-cause hospitalization, infectious
hospitalization and peritonitis among incident PD patients.
Materials and methods: Adults who initiated PD in one of
Dialysis Clinic Inc. centers in the United States between
2003 and 2009 were selected and followed for a maximum
of 30 months. Survival models were used to examine the
time to first event as well as recurrent events due to IV iron
exposure among two sub-cohorts of patients receiving IV iron
over 1- and 3-month rolling intervals. We employed marginal
structural models to account for time-dependent confounders.
Results: IV iron was administered to 194 of a total of 629
PD patients included in the 1-month cohort and 240 of 568
patients included in the 3-month cohort. Median survival
was 22 months (range 8 to 30) in the 1-month sub-cohort
and 24 months (range 10 to 30) in the 3-month sub-cohort.
Receipt of IV iron was not associated with all-cause
or infectious hospitalization in both 1- and 3-month
sub-cohort ((hazard ratio (HR) for all-cause hospitalization
in the 3-month sub-cohort 1.07 (95% Confidence Interval
0.93 to 1.23)). Combining those end-points with death, did
not change the results (HR for all-cause hospitalization or
death in the 3-months sub-cohort 1.03 (CI 0.90 to 1.18)).
There was no association between IV iron administration
and peritonitis in the 3-month sub-cohort) or peritonitis
in combination with death (HR 1.30 (CI 0.98 to 1.73) and
1.07 (0.84 to 1.36) respectively for the 3-month sub-cohort).
Conclusion: The administration of IV iron over 1 and
3-month intervals was not associated with hospitalization
or peritonitis among PD patients. The current data are
reassuring for our PD population.
C127 Intravenous Iron Administration in Peritoneal
Dialysis Patients; the effect on morbidity
W.M. Michels1 , B.G. Jaar 2 , P.L. Ephraim 2 ,
J. Luly2, D.C. Miskulin3, N. Tangri 4, S.M. Sozio2, T. Shafi2,
D.C. Crews2, J.J. Scialla5, W.L. St.Peter6, A. Mcdertmott2,
K. Bandeen-Roche2, L.E. Boulware2
1
Onze Lieve Vrouwe Gasthuis, Department of Internal
Medicine, Oosterpark 9, 1091 AC AMSTERDAM, the
Netherlands, e-mail: [email protected], 2Johns Hopkins
University School of Medicine, BALTIMORE, USA,3Tufts
University School of Medicine, BOSTON, USA, 4Seven Oaks
C128 The diagnostic value of urine microscopic analysis
in patients with kidney disease: a comparison of
nephrologist versus laboratory based interpretation
S.D. van Wieringen, F.G.H. van der Kleij, J. Bodeus,
R.H.H. Nap, J. Pouwels
Scheper Hospital, Department of Internal Medicine,
Boermarkeweg 60, 7824 AA EMMEN, the Netherlands,
e-mail: [email protected]
98
Introduction: Urine microscopic analysis (UMA) is an
important tool to evaluate patients with kidney diseases.
In clinical practice, clinicians often observe differences
between UMA performed by laboratory staff (LS)
compared to UMA performed by a nephrologist. However,
the accuracy of the clinical diagnosis, based on the report
of the UMA is rarely been systematically evaluated.
Aim of the study: We evaluated the difference in the
assesment of a UMA between a nephrologist and LS and
whether this had consequences for the accuracy of the
clinical diagnosis.
Materials and methods: UMA was performed on 47
patients to determine the cause of acute/chronic renal
failure, hematuria and/or proteinuria. A report of the
UMA was made by LS and nephrologist A (NA). NA also
assigned a clinical diagnosis based on his own UMA
report. Another nephrologist (NB), received the report of
both LS and NA in randomized order and assigned the
most likely clinical diagnosis to both reports. NA also
received the reports of the LS in randomized order and
assigned the most likely clinical diagnosis. As golden
standard, the clinical diagnosis of the nephrologist who
cared for the patient was used. To assess the accuracy of
the correct clinical diagnosis, Mc-nemar-test for dichitome
variables was used. Accuracy between different investigators was expressed as Cohen’s-kappa. The differences
in the report of specific cellular elements was tested by
McNemar-Bowker test. A two-sided value of 0.05 was
considered significant
Results: NA correctly diagnosed the clinical diagnosis in
83.0% of the cases (p < 0.001) based on his own report,
compared to 46.8% when diagnosis was based on the LS
UMA report. NB correctly diagnosed the clinical diagnosis
in 70,2% of the cases based on the report of NA, and in
42,6% when based on the report of the LS (p = 0.004).
Accuracy of making a correct diagnosis was good by NA
and NB (kappa 0,661 and 0,517) and significantly better
compared to diagnosis made on the LS report (kappa
0,232). NA reported a greater number of dysmorfic red
blood cells, hyaline and granular casts. Rare blood cell
casts, tubular cells and leucocyte casts which were detected
by NA were not detected by LS.
Conclusion: UMA performed by a nephrologist was
superior to UMA performed by LS in determining the
correct clinical diagnosis. This is probably caused by the
fact that nephrologists recognize specific microscopic
elements better than LS. We advocate more emphasis on
UMA in medical training.
C129 Treatment of metabolic acidosis in hemodialysis
patients with reduced pill burden
N.M.H. Veldhuijzen, K.G. Gerritsen, W.H. Boer,
A.C. Abrahams
University Medical Centre Utrecht, Department of Nefrology,
Heidelberglaan 100, 3584 CX UTRECHT, the Netherlands,
e-mail: [email protected]
Background: Metabolic acidosis in hemodialysis patients
is associated with increased mortality. Guidelines
recommend treatment with oral NaHCO3 and/or individualized dialysate bicarbonate ([HCO3-]d) targeting a
predialysis serum bicarbonate concentration ([HCO3-]s) of
20-22mmol/L.
In our center, until recently, metabolic acidosis was
corrected by oral supplementation and standard [HCO3-]
d of 34mmol/L. To reduce the daily pill burden, we
implemented a new protocol comprising discontinuation
of oral NaHCO3 and upward adjustment of the [HCO3-]d.
We evaluated efficacy and safety of this protocol.
Methods: All hemodialysis patients in our unit treated
with oral NaHCO3 were studied (n = 19). The new protocol
involved two steps: 1)stopping NaHCO3 and increasing
[HCO3-]d by 1-3mmol/L (depending on the NaHCO3 dose),
and 2)weekly titration of [HCO3-]d targeting predialysis
[HCO3-]s of 20-22mmol/L. Acid-base status, electrolytes
and weight were monitored. Results before and after implementation of the protocol are shown (median and IQR).
Results: Daily number of NaHCO3 tablets (500 mg/
tablet) was 3(IQR:0.5-6) before implementation of the new
protocol. After implementation [HCO3-]d was unchanged
in 7 patients, increased by 1mmol/L in 4 patients and
≥ 2mmol/L in 8 patients. Target predialysis [HCO3-]
s was equally achieved (38% before and 37% after) with
a predialysis [HCO3-]s of 22.3(21.0-24.3) and 21.7mmol/
L(20.1-23.0), respectively, (p = 0.21). Postdialysis pH > 7.50
was observed more frequently with the new protocol (21%
versus 5% of the patients), however, not significant (p =
0.34). The new protocol had no influence on postdialysis
and intradialytic change in pCO2, [K+], [Ca2+] and [Na+],
intradialytic weight loss and interdialytic weight gain.
[HCO3-]d was positively related to postdialysis [HCO3-]
s (p = 0.001) and intradialytic increase in [HCO3-] (p =
0.004), but not to postdialysis levels or intradialytic change
of pCO2, [K+] or [Na+]. [HCO3-]d was inversely related to
postdialysis [Ca2+] (p = 0.02), but not to intradialytic
[Ca2+] decrease. The patient with the highest [HCO3-]d
(40mmol/L) had the highest intradialytic increase in pCO2
and [Na+] (11mmHg and 9mmol, respectively),the lowest
postdialysis [K+](2.6mmol/L) and the highest intradialytic
[Ca2+] decrease.
99
Conclusions: Replacing NaHCO 3 by individualized
increased [HCO3-]d is equally effective for achieving target
predialysis [HCO3-]s. Risk profile seems acceptable since
severe metabolic alkalosis with compensatory hypoventilation, amplified intradialytic [K+] and [Ca2+] decrease (due
to respectively increased K+ shift into cells and calcium
binding to albumin) or increased interdialytic weight
gain (due to more intradialytic [Na+] loading) were not
observed. However, larger randomized long-term studies
with clinical endpoints comparing both treatments are
warranted for proper safety assessment.
low intestinal alkaline absorption, low urinary calcium
level and low urine volume. In about 50% of the cases, no
obvious cause can be found. A urine citrate excretion below
1.7 mmol/24 hr in men and 1.9 mmol/24 hr in women is
considered to be diagnostic for hypocitraturia.
There are three ways in which citrate has an effect
on calcium nefrolithiasis. First, citrate complexes with
calcium in the renal tubulus causing a reduction of ionic
calcium concentrations in the urine. Second, these citratecalcium complexes limit calcium supersaturation. Finally,
citrate binds to the crystals surface and prevents calcium
oxalate and calcium phosphate crystal agglomeration and
growth.
When hypocitraturia is found, potassium citrate is the
primary treatment with potassium bicarbonate as an
alternative. Potassium citrate increases urinary citrate
concentration, decreases urinary calcium and enhances the
inhibitory function of Tamm-Horsfall proteins on urine
crystal growth
Conclusion: This case underlines the importance of early
metabolic screening for patients with recurrent nephrolithiasis, and awareness of the diagnosis of hypocitraturia. This approach will help to predict recurrent stone
formation and prevent further complications.
XVII NEPHROLOGY CASE REPORTS
C130 Hypocitraturia: a common but not well known cause
of nephrolithiasis
S. Bos, R.R.H. Nap, R.S.M.E. Wouters, F.G.H. van der Kleij
Leveste Scheper Hospital, Department of Internal Medicine,
Boermarkeweg 60, 7824 AA EMMEN, the Netherlands,
e-mail: [email protected]
Introduction: Nephrolithiasis is a frequent problem
that can cause serious morbidity. In this case we try
to emphasize the need for metabolic screening, with
a focus on hypocitraturia, a less well known cause of
nephrolithiasis.
Case: A 37 year old woman was refered because of
recurring nephrolithiasis. In total she had undergone
fifteen extracorporeal lithotripsyshockwave therapies
and two ureterorenoscopies. Because of limited renal
function of the left kidney and persistent left sided lumbar
pain, a nephrectomy was performed. Laboratory results
revealed normal levels of serum potassium, bicarbonate,
calcium, uric acid and oxalic acid. A 24-hour urine
sampling showed normal calcium, uric acid and oxalic acid
excretion, but a profound hypocitraturia of 0.9 mmol/24h
(2.2-4.4 mmol/24hr). No secondary cause was found.
After treatment with potassium citrate, citrate excretion
normalized with no recurrent nephrolithiasis.
Discussion: Nephrolithiasis is a very common problem
in which calcium stones are most frequently found.
Recurrence rates among idiopathic stone formers is
approximately 40-50% and even higher if an underlying
metabolic disorder is present. A thorough work up will
assess the etiology of nephrolithiasis in up to 30-90%
of patients. Hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia are metabolic disorders that are
most commonly found. Hypocitraturia is estimated to be
present in 20-60% if calcium stones are detected. Several
secondary causes are known; renal tubular acidosis,
malabsorption, metabolic acidosis, potassium deficiency,
C131 An extraordinary cause of hypopotassemia
V.L.M.N. Soomers, E. Wiazy
Twee Steden Hospital, Department of Internal Medicine, Dr
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected]
Introduction: hypopotassemia is a common finding.
Although the differential diagnosis is elaborate, it is
most often due to increased losses of potassium from
the gastrointestinal tract or in the urine. This case report
is meant to remind us of a different cause of persistent
hypopotassemia.
Case: A 53-year old man from Afghanistan was referred
because of hypopotassemia, found by a routine blood check.
Apart from a beta-thalassemia the patient is healthy, does
not use medication and has no complaints. On physical
examination he is found to be hypotensive with a blood
pressure of 100/65 mmHg and regular pulse of 64/min,
with no other abnormal findings.
The lab results confirm a hypopotassemia of 2.7 mmol/L
(3.5-5.0 mmol/L). Also, a mild hypocalciemia is found of
2.10 mmol/L (2.20-2.65 mmol/L) and hypomagnesemia
of 0.41 mmol/L (0.70-1.00 mmol/L). The kidney function
is normal.
Urine analysis shows high sodium excretion of
333 mmol/24h (40-220 mmol/24h), low calcium excretion
of 0.75 mmol/24h (2.50-7.50 mmol/24h) and potassium
100
on a chronic base. Her complaints were fatigue, dyspnea
on exertion, nausea and abdominal pain. She had no
weight loss or artralgia and her pulmonary complaints
were stabile, she had no signs of lung hemorrhage or
hematuria. The urine production was normal. We saw no
abnormalities on physical examination, her temperature
was subfebrile. Laboratory investigation showed, except
the normocytic anaemia and elevated erythrocyte sedimentation rate and C-reactive protein, a renal function decline
(plasma creatinine 274 mmol/L (GFR 15ml/min), which
was 69 mmol/L six months earlier).Postrenal obstruction
was excluded by ultrasonography on the second day.
Urinalysis showed > 50/ul erythrocytes, > 40% dysmorphic
erythrocytes, 25/ul leucocytes and 0.75g/L protein, no
granular casts. Anti-GBM antibodies in the serum were
positive (273 U/ml), also MPO-ANCA was positive. Kidney
biopsy was not performed.We concluded our patient had
an anti-GBM glomerulonephritis, with no pulmonary
involvement since a chest X-ray was normal.On the third
day, treatment was started with plasmapheresis and
methylprednisolon and cyclophosphamide (100 mg/day).
During plasmapheresis, ten seperated exchanges were
done. We started methylprednisolone 1000 mg/day for
three days and then continued the prednisone in a dose
of 60 mg/day. Prophylactic therapy against Pneumocystis
jirovecii pneumonia and osteoporose was started. The
renal function improved slowly and is now stabile on a
serum creatinine of 140 mmol/L (GFR 32 ml/min).After
remission was achieved, we converted the cyclophosphamide to azathioprine. The prednison dosis was slowly
tapered untill a total treatment duration of nine months.
Most patients diagnosed with an anti-GBM glomerulonephritis have a poor recovery of renal function.
Our patient was immediately treated with high dosis
prednisolon, cyclophosphamide and plasmapheresis was
been done. Her renal function improved and stayed stabile,
no signs of recurrence were seen. Early diagnosis and
starting treatment is crucial, since the pretherapy plasma
creatinine concentration and percent of crescents on kidney
biopsy correlate with outcome.
excretion of 102 mmol/24h (25-125 mmol/24h). The transtubular potassium gradient is high, 14.4, indicating there
is a lack of kidney response to serum hypopotassemia.
Since there was no clue for a different explanation for these
findings (like potassium shift into the cell), a renal cause
like Gitelman or Bartter syndrome was proposed. Due to
the low urinary calcium excretion Gitelman syndrom was
more likely. Genetic testing confirmed the diagnosis: a
homozygous mutation of SLC12A3 gene was found. The
patient was already using potassium and magnesium
supplements, and shall now start with spironolactone, of
which the effect has yet to be assessed.
Discussion: hypopotassemia is a common clinical problem,
the cause of which can often be found in the patients’
history and medication use. Most often, it is due to a loss
of potassium from the gastrointestinal tract or in the urine,
due to diuretic use. This case demonstrates that when an
obvious cause cannot be found, less common causes need
to be considdered.
The prevalence of Gitelman syndrom is 1 in 40 000.
The hypopotassemia is due to malfunction of the Na-Cl
cotransporter in the apical membrane of the distal tubule.
This results in mild volume depletion and activation of the
renin-angiotensin-aldosterone system. Hyperaldosteronism
combined with the increased flow and sodium concentration in the collecting tubules, enhances potassium
and hydrogen secretion, leading to hypopotassemia and
metabolic alkalosis.
Conclusion: Gitelman syndrome should be considered as a
cause of persistant hypopotassemia.
C132 Conservation of renal function in a patient with antiglomerular basement membrane antibody disease
S.P.J. Awater, K.J. Parlevliet
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
Circulating antibodies against the glomerular basement
membrane (GBM) are the cornerstone of the pathogenese
of anti-GBM-antibody-mediated disease. It is often
used synonymously with Goodpasture’s disease, when
presenting with glomerulonephritis and pulmonary
hemorrhage. It may present with glomerulonephritis
alone. The antibody production is short-lived due to T-cell
regulatory mechanisms. It results in acute or rapidly
progressive glomerulonephritis, untreated the disease will
progress to end-stage renal failure.
An 69 year old woman was sent to the outpatient clinic for
analyses of a normocytic anaemia and elevated erythrocyte
sedimentation rate. She is known with recurrent
pulmonary infections wherefore she used azithromycin
C133 IgA vasculitis after traumatic pancreatitis with
Staphylococcus aureus infection
J.M. Drijvers, K.C. Koeijvoets
Jeroen Bosch Hospital, Department of Internal Medicine,
Henri Dunantstraat 1, 5223 GZ ’S-HERTOGENBOSCH, the
Netherlands, e-mail: [email protected]
Introduction: Henoch-Schönlein purpura is a systemic
small vessel vasculitis associated with IgA deposition.
Common symptoms are cutaneous manifestations, like
purpura and petechiae, joint pains, gastro-intestinal
101
C134 An unusual cause of renal failure in a patient with
heart failure
complaints, ranging from abdominal pain to intussusception, and renal disease.1 A similar clinical presentation
can be seen in adults after a Staphylococcus infection.
Case: A 53-year old man was transferred to our hospital
with a traumatic pancreatitis with peripancreatic fluid
collections after a laparoscopic adrenalectomy. The
indication for unilateral adrenalectomy had been therapyresistent hypertension caused by primary hyperaldosteronism. Cultures from a percutaneously drained
fluid collection as well as blood cultures had shown
Staphylococcus aureus. In our hospital, the pancreatitis
improved gradually, both clinically and radiologically,
with conservative management and antibiotics. However,
the patient remained ill. The most prominent symptoms
and findings were arthralgias, myalgias, petechiae on
the lower extremities, renal insufficiency (with creatinin
levels of up to 190 mmol/L) and elevated C-reactive protein
(CRP) levels of up to 200 mg/L. Strikingly, these laboratory
abnormalities consistently improved each time a CT
scan was performed, prior to which the patient received
prednisone because of a contrast allergy. The patient’s
general condition deteriorated until he was bedridden and
received feeding through a gastric tube.
Further testing revealed both cryoglobulinemia type III
and elevated IgA levels of about 7 g/L in blood. ANA and
ANCA were negative and complement factors C3 and C4
were in the normal range. In urine, a mild proteinuria and
dysmorphic red blood cells were noticed. A skin biopsy of
the petechiae on the lower extremities showed leukocytoclastic vasculitis, with focal endothelium slightly positive
for IgA. Consecutively, a renal biopsy was performed.
This gave us the final diagnosis of IgA vasculitis. Since
antibiotics alone yielded unsatisfactory response, we
started corticosteroids upon which the patient improved
drastically and renal function and CRP levels normalized
completely.
Conclusion: We present a case of IgA vasculitis following
traumatic pancreatitis with proven Staphylococcus aureus
infection. IgA-dominant glomerulonephritis caused by
staphylococcal infections has to be distinguished from
IgA-dominant glomerulonephritis of Henoch-Schönlein
purpura because of differences in treatment.2 Although
antibiotics are the cornerstone of therapy in Stafylococcus
infection-associated IgA glomerulonephritis, corticosteroids can be considered when there is inadequate response
to antibiotics.
J. Ursinus, S. Lobatto, K. van der Putten, M.S.S. Yo
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
Case: A 74-year-old man was admitted with decompensated
heart failure. He had progressive dyspnea and vomiting
in the past days. His medical history included curative
treatment of sigmoid carcinoma, dilated cardiomyopathy
since 2002 and atrial fibrillation. Physical examination
revealed hypertension (RR 155/95 mmHg), elevated
jugular venous pressure, bilateral basal lung crackles and
peripheral edema. No skin lesions were present. ECG
was normal and chest radiography showed cardiomegaly,
pleural effusion and congestion. Laboratory assessment
revealed acute renal failure with a serum creatinine of
171 umol/L (one month previously: 103 umol/L); normal
electrolytes, normocytic anaemia (Hb 7.7 mmol/L, MCV 84
fl); NT-proBNP of 8610 pg/ml and normal liver enzymes.
Renal ultrasonography was unremarkable.
The patient was treated with diuretics which quickly
resolved his dyspnea, while serum creatinine remained
increased. However, urinalysis repeatedly showed
proteinuria and erythrocytes (protein-to-creatinine ratio
97.5 mg/mmol, erythrocytes 15-50 per high power field)
which raised the suspicion of glomerular disease. ANCA,
anti-GBM and ANA tests were negative, but complement
levels C3 and C4 were decreased (0.49 g/L, 31 mg/L
respectively).We performed renal biopsy which showed
intracapillary polyclonal deposits, predominantly IgM
positive, kappa more than lambda, and little positivity
for IgA. Serum analysis showed cryoglobulins consisting
of polyclonal immunoglobulins (oligoclonal IgM kappa
and a weaker IgG lambda component). These findings
are characteristic for type III mixed cryoglobulinemia.
Extensive serology, including hepatitis B, C and HIV, was
negative and autoimmune serology, including rheumatoid
factor IgM, was normal. PET-CT showed no evidence of
lymphoproliferative disorders. A diagnosis of idiopathic
mixed cryoglobulinemia was made. Mild decompensated
heart failure appeared unrelated.
Treatment with high dose steroids and rituximab was
started. Unfortunately, serum creatinine rapidly increased
to 507 umol/L and the patient developed oliguria.
Hemodialysis and plasmapheresis were initiated. Renal
function quickly improved and hemodialysis was discontinued after two sessions. Plasmapheresis was continued
for 2 weeks after which creatinine stabilised at 194 umol/L.
Discussion: We describe a patient with acute renal failure
caused by idiopathic type III mixed cryoglobulinemia in
the presence of heart failure. Urinalysis indicated possible
References
1. Dedeoglu F. et al. Clinical manifestations and diagnosis of
Henoch-Schönlein purpura (IgA vasculitis). UpToDate 2013.
2. Satoskar AA. et al. Henoch-Schönlein purpuralike presentation in IgA-dominant Staphylococcus
infection – associated glomerulonephritis – a diagnostic
pitfall. Clin Nephrol. 2013;79:302-12.
102
according the recently updated Dutch guideline for FSGS.1,2
This revealed a heterozygous missense mutation c.529C > G
(p.Arg177Cys) of the INF2 gene.
Conclusion: This case illustrates the heterogeneous
expression of a mutation causing familial FSGS. The
recently updated Dutch guideline for FSGS will aid
the internist-nephrologist in when to test which gene.1
Mutational analysis needs especially be considered
when the results will affect treatment decisions (by
avoiding unnecessary corticosteroid treatment), when
the results affect counseling, or when a transplantation is
considered.1,2
glomerular disease, as was confirmed by renal biopsy.
Treatment with steroids, rituximab and plasmapheresis
led to rapid improvement. Although renal failure can be
caused by decompensated heart failure, an alternative
explanation should always be considered. Urinalysis can
indicate renal disease and should always be performed.
C135 Familial focal segmental glomerulosclerosis:
mutation in inverted formin 2 discovered by a new
diagnostic algorithm
I.M. Rood1, I.H.H.T. Klein2, J.F.M. Wetzels1, J.K.J. Deegens1
1
Radboud University Medical Centre, Department of
Nephrology, PO Box 9101, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected], 2Slingeland
Hospital, DOETINCHEM, the Netherlands
References
1. MCD-FSGS, richtlijn en Praktisch advies, 2013. www.nefro.nl.
2. Rood IM, Deegens JKJ, Wetzels JFM. “Genetic causes of
focal segmental glomerulosclerosis: implications for clinical
practice.” Nephrol Dial Transplant. 2012;27:882-90.
Introduction: Focal segmental glomerulosclerosis (FSGS) is
a common pattern of glomerular injury. FSGS is a heterogeneous disease with many underlying causes. Here we
present a family with FSGS. Genetic analysis according
the recently updated Dutch guidelines of FSGS revealed a
mutation in inverted formin-2 (INF2).1
Case report: Patient 1, a 31-year old Caucasian female
presented in the early 1970s with proteinuria (2.7
g/24hours), microscopic hematuria, a normal serum
albumin and renal insufficiency (creatinine clearance
40 ml/min). Family history was positive for an unknown
renal disease in the mother and brother. A renal biopsy
was performed and a diagnosis of focal segmental extracapillary glomerulonephritis was made. Within three years
she progressed to end stage renal disease (ESRD).
Patient 2, (son of patient 1), was referred to the outpatient
clinic because of microscopic hematuria and asymptomatic
nephrotic range proteinuria (5 g/24hours). Serum albumin
and renal function were normal. Renal biopsy was at that
time not conclusive. Based on the family history and the
clinical presentation, an X-linked inherited disease (e.g.
Alport syndrome) was suspected. However, an audiogram
was negative for hearing-loss and genetic analysis showed
no mutations in the COL4A5 gene. Within five years he
progressed to ESRD.
Patient 3, (son of patient 2), was referred to the outpatient
clinic at the age of 17 years because of asymptomic
proteinuria (1.8 g/24 hours). Serum albumin and renal
function were normal. After referral of patient 3 an
autosomal dominant (AD) pattern of inheritance was
suspected. Revision of the renal biopsy of patient 2
showed in light microscopy primarily focal segmental
sclerotic lesions, and additional electron microscopic
examination showed a normal GBM with partial foot
process effacement. A diagnosis of familial AD FSGS was
made. Additional work-up consisted of genetic screening
C136 Recto-vaginal fistula: a rare complication of CMV
colitis
M.G. Dickinson, C. Halma
Medical Centre Haaglanden, Department of Internal
Medicine, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: [email protected]
Case report: A 63 year old woman was admitted because
of diarrhea, fever and weight loss since 4 weeks. Her
history included a hysterectomy (for myomas), cholecystectomy, polycystic kidney disease, peritoneal dialysis
in 2006-2007 and in 2007 a kidney transplantation
(recipient cytomegalovirus (CMV) negative, donor CMV
positive). Her immunosuppressive agents were mycophenolate mofetil (MMF) and prednisolone. In 2010 she was
admitted with fever caused by CMV that was treated with
ganciclovir iv, followed by oral valganciclovir for 4 months.
No seroconversion occurred, however. Two months prior
to admission she was hospitalized twice with an upper
urinary tract infection (E. coli)
Physical examination showed a severely ill, dehydrated,
cachectic woman with extensive decubitus of the perianal
area and vulva due to incontinence for feces. Temperature
was 38 °C, BP 125/80, P 114/min, respiratory rate 28/min.
Laboratory examination revealed a leukocytosis (16.6
10^9/L) with a normal differential, increased C-reactive
protein (109 mg/L), s-creatinin 123 mmol/L, and slightly
increased liver enzymes.
A bacterial gastroenteritis was suspected and she was
treated with ciprofloxacine, iv rehydration, enteral nutrition
through a nasogastric tube and doubling of prednisone
dose. Bacterial feces cultures were negative. Further testing
revealed an active CMV infection (CMV-PCR 2.98 million
copies/ml of plasma; serology positive for IgM, negative for
103
IgG). MMF was discontinued and intravenous ganciclovir
and ciclosporin were administered. The patient remained
incontinent for feces. A rectovaginal fistula was suspected
and confirmed by pelvic examination and a colonoscopy.
This showed multiple superficial ulcerations and redness
throughout the whole colon. No diverticula were seen.
Around the fistula the mucosa appeared normal. Biopsies
of an ulcer showed active ulceration. Tissue samples were
CMV positive based on PCR and immunohistochemistry.
After clinical and virological improvement a temporary
colostomy was placed. Ganciclovir was switched to valganciclovir until seroconversion to IgG occurs. Presently her
case is being reviewed for fistula repair.
Discussion: CMV colitis is very rarely associated with
enterocolic fistulas. These have been reported in patients
with AIDS and after organ transplantation. Rectovaginal
fistulas are usually associated with Crohn’s disease,
malignancy, diverticulitis or vaginal trauma. None of these
conditions was present in this patient. We know only one
case of a rectovaginal fistula due to CMV colitis that has
previously been reported. This was in a non-immunocompromised patient. MMF is known to predispose to CMV
disease, sometimes late after transplantation, occasionally
with unusually severe manifestations. This unique case
serves as a reminder.
laboratory tests showed no deficiencies or hemolysis. His
medication consisted of dexamethasone, pantoprazol,
acenocoumarol and levetiracetam. A computed tomography
(CT) scan showed a new hemorrhage in the subcapsular
space of the left kidney and another large hemorrhage
(8x8cm) in the right kidney. Bilateral Wunderlich
syndrome was diagnosed. After anticoagulant treatment
was stopped, the patient remained dependent on red blood
cell transfusion. He received transfusion of 12 packed red
cells in total. Patient developed new pulmonary embolism,
for which a vena cava filter was placed. PET-CT scanning
showed multiple lesions in the right pleura, stomach, left
adrenal gland, mediastinal lymph nodes and both kidneys,
all compatible with metastatic disease. He was discharged
with palliative care and died about two months later.
The occurrence of nontraumatic, uni- or bilateral renal
hemorrhaging is known as the Wunderlich Syndrome. The
literature is limited to incidental case reports. The bleeding
is spontaneous and is confined to the subcapsular and/
or perinephric space(s). Symptoms often include flank or
back pain, sometimes (gross) hematuria and symptomatic
anemia. In severe circumstances, Wunderlich syndrome is
life-threatening and emergency surgery (i.e. nephrectomy)
is required. In most cases, it is caused by renal neoplasma
such as renal angiomyolipomas, renal cell carcinoma,
oncocytoma or metastatic lesions from rimary tumors
elsewhere.
Conclusion: The Wunderlich syndrome is a rare syndrome
of spontaneous renal bleeding, in most instances
associated with malignant tumours. It may present as
hemorrhagic shock, but also in more subtle ways, as this
case shows.
C137 A case of bilateral Wunderlich syndrome
F.P.J. Brouwers, M.H. Hemmelder, C. Halma
Medical Centre Leeuwarden, Department of Internal Medicine
& Nephrology, Henri Dunantweg 2, 8934 AD LEEUWARDEN,
the Netherlands, e-mail: [email protected]
C138 A monoclonal gammopathy certainly with significance
A 52-year old male was admitted with symptomatic
anaemia (hemoglobin 4.2 mmol/L, MCV 85, latest Hb
5.3 mmol/L 3 weeks before). Thirteen months prior
a T2bN0M0 stadium II sarcomatoid adenocarcinoma
was removed from the upper right pulmonary lobe by
radical pneumonectomy. Following this procedure,
patient received adjuvant chemotherapy with cisplatinum
and vinorelbine. Three months after surgery bilateral
pulmonary embolism was diagnosed, for which oral
anticoagulant treatment was started. Subsequently patient
developed insults due to a solitary bain metastasis. PET
scanning also revealed a metastasis in the right adrenal
gland. Both metastases were treated with radiotherapy.
Four months before the present admission patient had a
hemorrhagic shock caused by bleeding from a segmental
artery in the left kidney, which was succesfully coiled.
Currently, he presented with progressive complaints
of fatigue, dizziness and dyspnea. Patient denied any
preceding trauma. Patient was pale, had normal blood
pressure, tachycardia, and no fever. INR was 2.4 and
H. de Vries1, J.K.J. Deegens2, B.W. Schot1, J.F.M. Wetzels2,
G.D. Laverman1
1
ZGT, Department of Internal Medicine, Zilvermeeuw
1, 7609 PP ALMELO, the Netherlands, e-mail:
[email protected] 2Radboud University Medical Centre,
NIJMEGEN, the Netherlands
Introduction: Patients with low levels of plasma M
protein (“Monoclonal gammopathy of Undetermined
Significance”) may never suffer clinical problems but
have a small risk of developing Multiple Myeloma. That
M proteins, even in low plasma concentration, could cause
renal problems, is demonstrated by this case.
Case Report: A 56 year old man presented with renal
impairment (serum creatinine 219 umol/L, eGFR 27 ml/
min/1,72M2) and a positive urine dipstick for blood and
protein. He experienced peripheral edema, his blood
pressure was 150/85 mmHg. Serum albumin and
104
disappointing result, there are still some indications for
renal artery stenting. Here we describe two patients with
well-known renal artery stenosis, who progressed to acute
renal failure due to complete occlusion in both renal
arteries. Renal artery stenting was followed by recovery of
the renal function.
Case-reports: Patient 1 is a 60 year old women with a
stenotic monokidney (the other kidney was removed due
to fibromuscular dysplasia). Blood pressure and renal
function were normal on treatment with barnidipine
10 mg daily. She developed acute renal failure (eGFR 3 ml/
min) and became dialysis-dependent. Renal angiography
revealed a totally occluded renal artery, which was successfully dilated and stented. Within 7 days dialysis could
be stopped and within 6 weeks renal function returned
to baseline (e GFR50 ml/min). Patient 2, a 76 years old
man with extended atherosclerosis, severe bilateral renal
artery stenosis, chronic kidney disease (eGFR 30 ml/
min) and therapy-resistant hypertension, developed acute
renal failure within two weeks, despite withdrawal of
antihypertensive drugs . Tc MAG 3 nuclear renal scanning
demonstrated uptake of both kidneys. Angiography
revealed total occlusion of both renal arteries. Both were
successfully stented which resulted in recovery of renal
function. Furthermore, blood pressure was no longer
therapy-resistant.
Conclusion: In patients with longstanding renal artery
stenosis who develop acute renal failure, a total renal artery
occlusion should be suspected. Even after several weeks,
an attempt for renal artery stenting is justified because the
stenotic kidney may still be vital through blood supply via
suprarenal arteries.
cholesterol were normal. The history was unremarkable,
except for intermittent skin lesions in the past year.
While the ANCA test was negative and lgG4 not increased,
complement C3 was decreased with normal C4. Kidney
biopsy showed active glomerulonephritis with mesangial
and focal endocapillary proliferation, and only positive
staining for C3. Awaiting test results aimed at diagnosing
a cause of complement system dysregulation, immunosuppressive treatment with endoxan and prednisolone was
initiated, after 2 weeks followed by plasmapheresis with
fresh frozen plasma, unfortunately all without effect on
proteinuria or renal function.
Blood results were negative for C3 nephritic factor or
antibodies against the complement regulating protein
Factor H. Factor H level was in normal range. However,
a plasma M-protein was found (IgM kappa 2g/L) with 5%
plasma cells present in the bone marrow, without further
evidence for multiple myeloma. Skin biopsy of his lower
leg showed leucocytoclastic vasculitis, positive for C3 but
not IgA. Thus, summarizing, the patient both had C3
glomerulopathy, C3 positive leucocytoclastic vasculitis and
monoclonal gammopathy of undetermined significance.
He was then treated with bortezimib and dexamethason
(results of treatment not yet available).
Discussion and Conclusion: C3 glomerulopathy is
recently established as a separate entity in the group of
membranoproliferative glomerulonephritis, characterised
by C3 deposition in capillary walls, usually in absence
of immunoglobulin deposits, and decreased plasma C3
concentration. It may be caused by any factor leading to
dysregulation in the alternative complement pathway.
An association between monoclonal gammopathies
and C3 glomerulonephritis has recently been described,
suggesting that M proteins serve as a dysregulating factor,
hypothetically by acting as an ‘anti factor H’ antibody.
Theoretically, treatment aimed to abolish M protein could
have potential to improve the glomerulonephritis.
We soon hope to report results in our patient if 1) the
IgM kappa serves as a antibody against factor H and 2)
antimyeloma treatment results in preservation of renal
function.
C140 Rapid testing may cause delay
D.E. Sampimon, M. Yo, S. Lobatto, K. van der Putten
Tergooi Hospital, Department of Internal Medicine, Van
Riebeeckweg 212, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
Introduction: The work-up for rapidly progressive glomerulonephritis includes the use of rapid screening assays for
anti-glomerular basal membrane antibodies (anti-GBM)
and anti-neutrophil cytoplasmatic antibodies (ANCA).
We present a case in which the rapid testing showed
discrepancy from the definitive results.
Case report: A 49-year old women was referred to our
department for a 2 month history of headache, nausea,
night sweats and a fever up to 39C since one week.
Medical history was unremarkable. Physical examination
revealed decreased breath sounds in the right lower chest
and mild pain in the right upper abdominal quadrant.
Laboratory work-up showed thrombocytosis, leukocy-
C139 Renal artery stenting in acute renal failure
D.E. Agterhuis, M.M.G. Dekker-Jansen, G.J. Wagenmakers,
A.J.J. Woittiez
ZGT, Department of Internal Medicine, Zilvermeeuw 1, 7609
PP ALMELO, the Netherlands, e-mail: [email protected]
Introduction: The recently published CORAL trial is
the 4th trial demonstrating that stenting of even severe
renal artery stenosis is not superior to medication alone,
also in terms of cardiovascular outcomes. Despite this
105
tosis, an increased c-reactive protein (CRP 224 mg/L)
and a decrease in renal function (creatinine 119 umol/L,
previously 78 umol/L). Urine analysis showed dysmorphic
erythrocytes and proteinuria of 7.7g/day. Chest x-ray
showed some pleural effusion, with a normal cardiothoracic ratio. Abdominal ultrasound showed no pathology.
A diagnostic kidney biopsy was performed. Standard as
well as rapid screening assays for anti-GBM and ANCA
(both ELISA) were performed. The rapid test was positive
for anti-GBM and negative for ANCA.
A working diagnosis of anti-GBM glomerulonephritis was
established. Awaiting definitive test results, treatment was
started with methylprednisolone and plasmapheresis.The
patient improved clinically.
After three days, definitive test results became available.
The anti-GBM assay was negative (1,5 U/mL; negative < 7
U/mL). Anti-nuclear antibodies (ANA) were absent. Both
C3 en C4 were decreased. Renal biopsy showed necrotizing
glomerulonephritis, with full house immunofluorescence
pattern. At that point, plasmapheresis was stopped, and
the patient started treatment for presumed lupus nephritis
with cyclophosphamide and prednisolone.
The rapid test performed has a high sensitivity (99%) and
high specificity (99%) in a study with 39 patients. The
standard test has a sensitivity of 94% and a specificity of
100% in a study with 49 patients.
An additional rapid anti-GBM test, performed at another
laboratory, was repeatedly positive. The cause of the
discrepancy in results remains unresolved. It may have
been caused by the different antigens that are used in
the rapid and the standard anti-GBM test (bovine antigen
versus human recombinant antigens respectively).
Conclusion: Although rapid testing for anti-GBM has been
shown to be reliable and important in clinical practice,
this case underlines the importance of confirmation of
diagnosis with (standard test and) tissue biopsy.
proteinuria (12,1 g/L). Serum albumin was extremely low
(6 g/L). There was hypercholesterolemia (8.0 mmol/L).
Kidney biopsy showed subepithelial deposits with full
house immunohistochemistry (IgG, IgA, IgM, C3,
c1q) consistent with membranous lupus nephropathy
(MLN). Interestingly, ANA was negative, with low titer of
anti-dsDNA autoantibodies (IFT, 1/40). Anti-c1q autoantibodies were present. Complement was normal. The patient
was treated with corticosteroids and tacrolimus.
Interestingly, his 43 year old father presented three years
earlier with nephrotic syndrome, arthritis, and a history of
pericarditis. Kidney biopsy showed proliferative and MLN.
Immune-serology was almost identical to that of his son,
with negative anti-dsDNA autoantibodies, and presence of
anti-c1q autoantibodies.
Discussion: Renal involvement is a major complication of
systemic lupus erythematosus and a strong determinant of
morbidity and mortality. The prevalence of biopsy proven
lupus nephritis is however low. In our Limburg Renal
Registry, started in 1977, 98 patients with biopsy proven
lupus nephritis have been identified, of whom 21 patients
showed a membranous pattern in their biopsy. MLN in
our region in male patients (n = 5 out of 21) is even more
rare. Lupus nephritis is an immune complex mediated
renal disease. The pathogenesis of lupus nephritis has
been attributed to a complex interaction between genetic,
hormonal, and environmental factors. MLN, familial
incidence, and male occurrence are all uncommon in SLE,
and hence MLN in father and son appears to be very rare
in combination. The genetic role in the etiology and pathogenesis of lupus nephritis in our cases will be explored
more in detail.
XVIIIINTENSIVE CARE RESEARCH
C141 Nephrotic syndrome in father and son
C142 Therapy-resistant primary focal segmental glomerulosclerosis: transition from pediatric to adult
nephrology provides new therapeutic options
S.A.M.E.G Timmermans, F. Horuz, J.W. Cohen Tervaert,
P. Paassen van
Maastricht University Medical Centre, Department
of Internal Medicine, P. Debyelaan 25, 6229
HX MAASTRICHT, the Netherlands, e-mail:
[email protected]
D.M. Hotho, J. van der Deure, K. Haring, C.G. Vermeij
Deventer Hospital, Department of Nephrology, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected]
Case: An 18-year old psychomotor retarded boy, known
at the pediatric department for therapy-resistant
nephrotic syndrome due to C1q-nephopathy with focal
segmental glomerulosclerosis (FSGS), was admitted to
the pediatric department with progressive edema. As in
past admissions, the patient was treated with albumin
infusion and intravenous furosemide. Previous immuno-
Case: A 17 year old male Caucasian presented with acute
severe shortness of breath due to pulmonary embolism.
Anticoagulation is started. Subsequently, he developed
generalized edema and high blood pressure. On admission
he appeared nephrotic with 12 kg gain of weight in two
weeks. There was normal renal function, but heavy
106
C143 Prognostication of neurologic outcome in cardiac
arrest patients after mild therapeutic hypothermia:
a meta-analysis of the current literature
suppressive therapies consisting of prednisolon (pulse,
oral), combined with ciclosporin, ciclosporin monotherapy,
and ciclosporin combined with mycofenolate mofetil
had not resulted in sustained clinical improvement.
Nephrology consultation was requested for pre-emptive
kidney transplantation or dialysis. In the five months
prior to admission, serum creatinine had risen from a
previously stable level of 133 micromol/L to 335 micromol/L.
Concurrently, nephrotic syndrome had deteriorated with
severe peripheral edema, ascites and hypoalbuminaemia
(nadir 8.6 g/L). Peripheral edema had recurred increasingly rapid after albumin/frusemide infusions, despite
treatment with oral loop diuretics and high-dose hydrochlorothiazide (TID 50 mg). On consultation, the patient
had hypercalcemia (corrected serum calcium 3.12 mmol/L,
serum albumin 11.3 g/L, serum phosphate 2.90 mmol/L)
due to active vitamin D therapy (QD 1,5 microgram
alfacalcidol). Alfacalcidol was stopped, but hypercalcemia
persisted (corrected serum calcium 3.28 mmol/L), possible
due to hydrochlorothiazide’s hypocalciuric action and
worsening renal function (creatinine 444 micromol/L).
After hydrochlorothiazide was stopped, urinary calcium
excretion increased and kidney function improved slightly.
To investigate whether immunosuppressive therapy might
be effective, repeat kidney biopsy was performed, showing
FSGS-NOS variant with limited global sclerosis. For three
weeks, patient received plasmapheresis thrice weekly and
1000 mg rituximab twice. Peripheral edema resolved and
serum creatinine decreased to 76 micromol/L. Rituximab
has been suggested in adults as treatment of (steroiddependent) nephrotic syndrome due to FSGS1. In pediatric
medicine, rituximab has been suggested for this indication
as well2. However, as there is much debate about both
safety and efficacy, the use of rituximab is definitely not
unambiguously supported3,4.
Conclusions: Gradually developing hypoalbuminaemia
remains a pitfall for detection of hypercalcemia. Secondly,
hydrochlorothiazide can produce hypercalcemia through
impairment of calciuresis. Furthermore, pediatric
evidence-based medicine and adult evidence-based
medicine can differ. In this case, previously therapyresistant primary focal segmental sclerosis showed great
clinical improvement upon treatment with plasmapheresis
and rituximab. Therefore, the transition from pediatric to
adult medicine at the age of 18 should be regarded as an
opportunity to re-evaluate therapeutic options.
1. Ochi A et al, Intern Med, 2012;51(7):759-62. 2.
Nakayama, M. Pediatr Nephrol, 2008: Mar;23(3):481-5. 3.
Ravani P. Kidney Intern, 2013 Nov 84(5):1025-33. 4. Boyer
O, Nat Rev Nephrol, 2013 Oct;9(10):562-3.
M.J.A. Kamps1, J. Horn2, M. Oddo3, J.E. Fugate4, C. Storm5,
T. Cronberg6, C.A. Wijman7, O. Wu8, J.M. Binnekade2,
C.W.E. Hoedemaekers1
1
Radboud University Medical Centre, Department of Intensive
Care, Geert Grooteplein zuid 10a, 6525 GA NIJMEGEN,
the Netherlands, e-mail: [email protected],
2
Academic Medical Centre, AMSTERDAM, the Netherlands,
3
Lausanne University Hospital, LAUSANNE, Switzerland,
4
Mayo Clinic, ROCHESTER, USA, 5 Charité
Universitätsmedizin Berlin, BERLIN, Germany, 6Skåne
University Hospital, LUND, Sweden,7Stanford University
Medical Centre, PALO ALTO, USA, 8Martinos centre for
biomedical imaging, CHARLESTOWN, USA
Introduction: Outcome studies in patients with anoxicischaemic encephalopathy after cardiopulmonary resuscitation focus on the early prediction of an outcome
no better than a vegetative state or severe disability.
Currently used guidelines for prognostication after cardiac
arrest are based on studies in patients not treated with
therapeutic hypothermia.Treatment with mild therapeutic
hypothermia improves neurologic outcome in patients after
out-of-hospital cardiac arrest, and has become standard
of care in most hospitals. Hypothermia also modifies the
metabolism of most sedatives resulting in an unpredictably
prolonged sedative effect. The current guideline identifies
four reliable methods for predicting a poor neurologic
outcome: Clinical neurologic examination, mycoclonic
status epilepticus, somatosensory evoked potential and
neuron-specific enolase serum levels. However, there is
increasing evidence that therapeutic hypothermia alters the
positive and negative predictive value of these parameters.
Aim of the study: To assess the sensitivity and false
positive rate of the currently used parameters to predict
poor outcome in adult patients treated with therapeutic
hypothermia after cardiopulmonary resuscitation
Methods: MEDLINE and EMBASE were searched for
cohort studies describing the association of clinical neurological examination or SSEPs after return of spontaneous
circulation with neurological outcome. Individual data
were collected from all corresponding authors, using a
predesigned data extraction form to provide the necessary
original data.
Results: A total of 1,153 patients from ten studies were
included. The FPR of a bilaterally absent cortical N20
response of the SSEP could be calculated from nine
studies including 492 patients. The SSEP had an FPR of
0.007 (confidence interval, CI, 0.001-0.047) to predict
poor outcome. The Glasgow coma score (GCS) motor
107
Results: Analysis of Variance (ANOVA) between groups
showed no statistically significant difference of age, BMI
(kg/m2), smokers, Euroscore, Extra Corporal Circulation
time and type of cardiac surgery.
In our study no ventilation-related safety issues requiring
interventions were observed. No statistically significant
differences regarding mechanical ventilation time, number
of reintubations and desaturations (SpO2 < 85%) were
observed between the three groups.
Although mechanical ventilation time was short, the number
of interactions was statistically significantly (p < 0.001) lower
with iASV (mean = 1.45) compared to ASV (mean = 2.35) and
conventional ventilation (mean = 2.85).
Conclusion: Our non-inferiority trial confirms that iASV
is as safe and efficient as conventional ventilation and ASV
to ventilate patients after cardiac surgery. More studies
are needed in critical ill and postoperative patients to
fully understand the clinical impact of fully closed-loop
ventilation.
response was assessed in 811 patients from nine studies.
A GCS motor score of 1-2 at 72 had a high FPR of 0.21 (CI
0.08-0.43). Corneal reflex and pupillary reactivity at 72
h after the arrest were available in 429 and 566 patients,
respectively. Bilaterally absent corneal reflexes had an FPR
of 0.02 (CI 0.002-0.13). Bilaterally absent pupillary reflexes
had an FPR of 0.004 (CI 0.001-0.03).
Conclusions: At 72 h after the arrest the motor response to
painful stimuli and the corneal reflexes are not a reliable
tool for the early prediction of poor outcome in patients
treated with hypothermia. The reliability of the pupillary
response to light and the SSEP is comparable to that in
patients not treated with hypothermia. Prognostication
protocols must be changed urgently to avoid unjustified
withdrawal of active treatment in patients with a favorable
prognosis.
C144 Fully automated closed-loop ventilation is safe and
effective in post-cardiac surgery patients
A.J.R. Beijers, A.N. Roos, A.J.G.H. Bindels
Catharina Hospital, Department of Internal Medicine,
Michelangelolaan 2, 5623 EJ EINDHOVEN, the Netherlands,
e-mail: [email protected]
C145 Hyponatremia in elderly Emergency Department
patients: a marker of frailty
S.H.A. Brouns, M.K.J. Dortmans, F.S. Jonkers, S.L.E. Lambooij,
A. Kuijper, H.R. Haak
Máxima Medical Centre, Ds. Th. Fliednerstraat 1, 5631
BM EINDHOVEN/VELDHOVEN, the Netherlands, e-mail:
[email protected]
Introduction: A recent Cochrane review shows that
automated ventilation, like Assisted Support Ventilation
(ASV), may reduce duration of weaning, ventilation, and
ICU stay. The fully automated closed-loop ventilating mode
Intellivent-ASV (iASV) is an extension of ASV. Unlike
ASV, this mode uses automated feedback mechanisms to
constantly ventilate and oxygenate patients based on their
individual needs. Minute ventilation is not only automatically calculated based on ASV’s least work of breathing
concept of Otis, but in combination with the patients
end-tidal CO2 (EtCO2). It also automatically adjusts FiO2
and positive end-expiratory pressure (PEEP) based on the
ARDS network PEEP-FiO2 tables to maintain a target pulse
oxymetry.
Aim of the study: We compared iASV with ASV and
conventional ventilation (Pressure controlled and Pressure
support ventilation). The safety and efficiency of iASV was
assessed based on the number of safety events, interactions
with the ventilator, reintubations within 24 hours and
mechanical ventilation time.
Materials and methods: This prospective non inferior study
included 128 low risk post-cardiac surgery adults, suitable
to wean on the post anesthesia care unit (PACU). Patients
were divided in three groups defined as iASV (n = 53), ASV
(n = 26) and conventional ventilation (n = 49). Excluded
were patients with a positive history of COPD gold > 3,
lung surgery and patients in shock. The ventilation mode
could be changed when current ventilation was inefficient.
Introduction: Details on hyponatremia (serum sodium
level < 135 mmol/L) in the Emergency Department (ED) are
limited, especially regarding older patients, a population
more susceptible to hyponatremia and its effects.
Aim of the study: To gain insight into the prevalence,
etiology, treatment and prognosis of hyponatremia in
elderly ED patients. The impact of the severity of hyponatremia on outcome was a secondary objective.
Materials and methods: A retrospective cohort study of
1438 internal medicine patients aged ≥ 65 years presenting
to the ED between 01-09-2010 and 31-08-2011 was
performed. Data on demographic and clinical characteristics and outcome were obtained from patient records.
Hyponatremia was subdivided into mild (134-130 mmol/L),
moderate (129-125 mmol/L), and severe (< 125 mmol/L).
Results: Three hundred and three elderly patients (21.1%)
were hyponatremic at ED presentation. The main causes
were the use of diuretics, hypovolemia, and syndrome of
inappropriate antidiuretic hormone secretion (SIADH)
(22.1%). Hyponatremia was associated with higher
admission rates (88.8% versus 70.0%) and longer hospital
stay (7 versus 6 days) versus normonatremia. Three-month
survival rate in hyponatremic elderly patients was 74%
(95% CI 68-80%) versus 84% (95% CI 82-86%) in normo-
108
C147 Continuous intravenous glucose monitoring with
GlucoClear in critically ill patients treated with
intensive insulin therapy
natremic elderly patients. Moderate hyponatremia was
associated with an increased risk of death (HR1.6, 95% CI
1.1-2.3) after multivariable adjustment for age, co-morbidity,
and C-reactive protein versus normonatremia. Presence
of hypoalbuminaemie was found to be an important
prognostic covariate in elderly patients.
Conclusion: Hyponatremia, a common electrolyte disturbance
among elderly internal medicine patients presenting to
the ED, was associated with higher admission rates, longer
hospital stay, and higher mortality rates. In particular,
moderate hyponatremia was a marker of underlying frailty
and predictive of mortality. Hypoalbuminaemia may
contribute in identifying patients at risk.
H.S. Moeniralam1, J. van Dam2, E.A. Vlot1, H.S. Moeniralam1
1
St Antonius Hospital, Department of Intensive Care,
Koekoekslaan 1, 3430 EM NIEUWEGEIN, the Netherlands,
e-mail: [email protected], 2University Medical
Centre Utrecht, UTRECHT, the Netherlands
Introduction: Intensive Insulin Therapy (IIT) in hyperglycemic critically ill patients, lowering blood glucose levels to
4.4-6.1 mmol/L, significantly decreased the mortality and
morbidity. In clinical practice, it was difficult to maintain
blood glucose levels in the target range. Hypoglycemic
events and blood glucose fluctuations increased, both
associated with increased mortality. A blood glucose
coefficient of variation (CV) of > 20% is associated with a
9.6-fold increase in mortality compared to less variation.
The current IIT-protocol prescribes continuous insulin
administration with intermittent glucose measurements,
using the same protocol for all patients. The response to
insulin is difficult to predict in Intensive Care (IC) and
Medium Care (MC) patients, differs between admission
type, history of diabetes, severity and duration of illness,
nutrition and administration of drugs interfering with
glucose-metabolism.
Aim of the study: Continuous intravenous glucose
monitoring to quantify the time outside the target range
and the blood glucose CV in critically ill patient treated
according to our local IIT-protocol.
Materials and methods: An observational study in a
mixed 34-beds IC/MC department. The local IIT-protocol
was nurse-driven, aimed at a blood glucose target of
4.4-6.1 mmol/L with intermittent blood glucose measurements (intervals up to 4 hours) by point-of-care and
bloodgas-analyser. For continuous glucose measurements
each included patient received a peripheral intravenous
20G-catheter, in which a disposable, glucose-oxidase
coated sensor (GlucoClear, Edwards LifeSciences) was
introduced, which automatically measured every 5 minutes,
up to 72 hours. The obtained glucose measurements with
the sensor were not allowed to be used for insulin dosage.
Results: Continuous intravenous glucose measurements
were successfully performed in 25 patients(post-surgical,
septic and MC patients). The mean blood glucose value
was 6.3 mmol/L. Mean glucose CV was 22,9%. Severe
hyperglycemia (> 10,0 mmol/L) was observed in 32%,
mild hypoglycemia (< 3,9 mmol/L) in 44% and severe
hypoglycemia (< 2,2 mmol/L) in none of the patients. 96%
of the patients had blood glucose levels outside the target
range of 4.4-6.1 mmol/L, with a total duration of 63% of
the observed period.
C146 Factors influencing diagnosis and prognosis in
patients presenting with severe anaemia in the
emergency ward
M.D. Levin, C. Pellikaan-v.d. Ree, J. Riedl, K. Stouten,
E. Oskam
Albert Schweitzer Hospital, Department of Internal Medicine,
Albert schweitzerplaats 25, 3018 AT DORDRECHT, the
Netherlands, e-mail: [email protected]
Introduction: Little data are available on the most common
causes of anaemia in patients presenting in an emergency
ward. The goal of the study is to give an overview of the
main causes of severe anaemia in adults presenting in an
emergency ward. In addition, we want to determine the
prognosis for all causes separately and to define reliable
survival prediction factors for patients presenting with
anaemia.
Aim of the study: To clarify causes and prognosis of
patients presenting with severe anemia (haemoglobin value
below 5 mmol/L) in the emergency ward.
Methods: All patients (18 years or older), who attended
the emergency ward with a haemoglobin value below
5 mmol/L over a period of five years, were included in the
retrospective study. From all patients extensive data were
collected including laboratory findings at presentation,
hemodynamic condition, medical history and medication
use. Furthermore, the number of needed transfusions and
the final diagnosis were obtained from the medical file.
Results: A total of 222 patients with severe anaemia was
included in the study. The causes of the severe anemia
will be discussed and the subsequent laboratory tests. The
influence of anticoagulation, the number of blood transfusions and survival will be presented. Finally, a multivariate
analysis of factors influencing survival will be presented.
Conclusion: Factors influencing causes and survival and
treatment of severe anemia in the emergency ward will be
presented.
109
Conclusion: Despite extensive experience with IIT in
critically ill patients, it remains difficult to maintain the
blood glucose levels in critically ill patients in the targetrange. Although there were no severe hypoglycemic events,
almost all patients experienced blood glucose levels at both
sides outside the target range with harmful fluctuations.
Continuous blood glucose measurement may be helpful
improving safety and optimizing glucose regulation in
critically ill patients.
not detected and the systolic and diastolic functions were
preserved. One patient developed sustained ventricular
tachycardia and was promptly referred for urgent coronary
angiography. There was one vessel disease with a 95%
stenotic lesion of the proximal LAD. Of the remaining 3
patients coronary artery stenosis were excluded.
Conclusion: Our data show that 0.7% of the local runners
completing the marathon, were admitted to the ER and
subsequently hospitalized because of cardiovascular
problems due to marathon running. All these patients
presented with abnormal ECG patterns. Increased troponin
levels were found in 3 out of 4 patients. Furthermore, in
1 out of 4 patients with chest pain complaints, an acute
coronary syndrome due to a severe coronary artery lesion
caused these findings.
C148 Hospitalization rate of cardiovascular complaints due
to marathon running: the uncertainty regarding to
the interpretation of increased myocardial specific
markers and abnormal ECG patterns in this specific
setting
XIX INTENSIVE CARE CASE REPORTS
J.M.J.B. Walpot, R. Hokken, W.H. Pasteuning, J. van Zwienen
Admiraal de Ruijter Hospital, Department of Cardiology,
Koudekerkseweg 88, 4380 DD VLISSINGEN, the Netherlands,
e-mail: [email protected]
C149 Toxic epidermal necrolysis triggered by minocycline
Objectives: The objective of our study is to measure the
admission rate to the ER and the hospitalization rate
because of suspicion for cardiovascular problems due to
marathon running.
Methods: In this retrospective observational study, the
data of patients having participated to the local marathon
that was organized in the referral area of our hospital were
analyzed. Data concerning the number of participants and
number of runners prematurely leaving the marathon were
collected. According to the list of participants the number
of participant marathon runners, being inhabitants of the
referral area of our hospital, was determined.
Results: There were 1295 participants, of whom 160
runners had left the marathon prematurely. Of these latter,
no one was referred to the hospital because of suspicion
of cardiovascular complaints. Of the 1135 participants
running the complete marathon, 578 (50,9%) runners were
inhabitants of the adherence area of our hospital. Over a
period of 8 hours after completing the marathon, there
were 4 (0.7%) admissions to the ER because of cardiovascular problems due to marathon running. The mean age
was 47.7 years (range 41-53y.). None of the patients had a
medical record of cardiovascular disease. They did not use
medication. All patients presented with abnormal ECG
patterns or increased cardiac Troponin I(cTn I) levels. 3
out of the 4 patients were referred because of chest pain
complaints. One anamnesis was suspected for angina
pectoris. ECG abnormalities were found in all patients
and in 3 out of 4 patients cTn I was above the cut off value
(range 0.2 - 4.6 mg/L; normal: < 0.1mg/L). In all patients an
echocardiographic study was performed within the first 24
hours of admission. Relevant structural abnormalities were
S. Slavenburg, M.J.L.J. van den Elsen, K.D. Lettinga,
J.J. Hoefnagel
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected]
Introduction: Toxic epidermal necrolysis (TEN) or
Lyell’s syndrome is a rare, potentially life-threatening
mucocutaneous syndrome that is usually drug-induced.
It is characterized by massive apoptosis of epidermal
keratinocytes resulting in sloughing of the skin and
mucosa. The pathogenic mechanism involves aberrant
drug metabolism and cell-mediated cytotoxicity. The
mortality rate of TEN correlates with the percentage of skin
surface demonstrating epidermal detachment. We describe
a case of a 35-year old female who developed TEN following
treatment with minocycline.
Case: A 35-year old female was treated with minocycline
for Gougerot-Carteaud syndrome, a rare skin disease
characterized by hyperkeratotic plaques on the trunk.
Two weeks after starting this treatment she developed
burning skin lesions, which first appeared in the neck
and subsequently spread to the face, trunk and arms. In
addition her lips had swollen and she experienced painful
burning of the mouth. Physical examination showed
partly confluent erythematous targetoid lesions on the
face, neck, arms and legs. The lips were swollen with
crusts and erosive lesions in the mouth. Conjunctivae
showed no deviations and the vulva showed enanthema.
At that time a diagnosis of Stevens-Johnson syndrome
(SJS) was made most likely due to minocycline therapy,
which was already discontinued 2 days ago. Patient refused
110
acid production or an inhibited renal acid-excretion had
to be responsible for the acidosis. Nevertheless toxscreen
was performed which was negative for salicylic acid,
methanol, ethanol, aceton and isopropanol. Laboratory
testing showed moderate renal failure (GFR (MDRD):
31 ml/min/1 and creatinin: 149 mmol/L) with stable
serum phospate, sulphate en urate, not changed from
earlier measurements during admission, when blood gas
analysis was still normal. Lactate levels were repeatedly
normal, CK 314 U/L (mildly elevated) and there was
no ketonurie. Patient was treated on the ICU, with the
working diagnosis of 5-oxoprolin accumulation, by discontinuation of paracetamol and administration of acetylcysteïne and sodium bicarbonate. Blood gas analysis became
normal within ten hours and patient recovered. The
5-oxoproline levels in a urine-sample taken on admission
were found to be elevated (qualitative assay positive, quantitative assay will follow).
Discussion: 5-oxyproline accumulation is a rare cause of
metabolic acidosis. Our patient had all the risk factors;
female, alcohol abuses, malnutrition, sepsis, liver and
kidney failure and use of floxapen and paracetamol. The
assumed mechanism is a blockade of the enzyme 5-oxyprolinase (i.a. by flucloxacillin) and an exhaustion of the
intracellular gluthathionstock (i.a. by paracetamol), which
causes a perturbation in the gamma-glutamyl-cycle and an
overproduction of 5-oxoproline.
Conclusion: In a metabolic acidosis with a high anion gap,
5-oxyproline accumulation should be considered, especially
in malnutrited female patients using flucloxacillin and/or
paracetamol.
to be admitted to the hospital. Clobetasol ointment and
lidocaine gel were started. She returned next day at the
outpatient clinic severely ill with fever, a pulse rate of
133 per minute and expanding of the skin lesions > 35%
percent of the body with a positive Nikolsky’s sign. The
oral and urogenital mucosa were affected, but there was
no ocular involvement. The SCORTEN score was 3, with
a mortality rate of 35%. Laboratory findings revealed a
C-reactive protein level of 127 mg/L (< 10), cultures and
serologic tests showed no pathogens. A skin biopsy was
performed and confirmed TEN. Only a few case reports
of SJS/TEN are described after the use of minocycline
therapy. The patient was treated with supportive care by
fluid and electrolyte management on the intensive care
unit. At discharge, she was in good clinical condition with
many post-inflammatory desquamation.
Conclusion: This case illustrates the development of
initially SJS evoluting to TEN triggered by the use of
minocycline. SJS and TEN are considered as two presentations of the same disease but with different degree’s of
severity. Interruption of any drug that possibly can cause
SJS/TEN is crucial for a favorable outcome. Treatment still
remains supportive.
C150 A sour woman
J.J.B. Janssen, M.E.E. van Kasteren
St. Elisabeth Hospital, Department of Internal Medicine,
Hilvarenbeekse weg 60, 5022 GC TILBURG, the Netherlands,
e-mail: [email protected]
Introduction: Metabolic acidosis is a frequent clinical
event, especially in the critical ill patient, which demands
a thorough and structured analysis to achieve the correct
diagnosis and treatment.
Case: A 63-year-old woman, with a history of alcoholabusis and malnutrition, was admitted to the surgical
ward because of a traumatic femur- and tibia fracture.
Both fractures where treated with osteosynthesis. After
eleven days one wound was complicated by an infection
which was treated with intravenous floxapen and insertion
of gentamicin beads. Pain was treated with 4 grams of
paracetamol daily. On day 24 we were consulted because
of acute decreased consciousness and tachypnea. Patient
was hemodynamically stable and neurological E4M6V1.
Arterial blood gas analysis, breathing ambient air, showed
a severe metabolic acidose (pH 7.0; pCO2 2.1 kPa; pO2
12.7 kPa; HCO3 3.7 mmol/L; base excess -26.5 mmol/L).
CT-cerebrum showed no abnormalities. Calculated anion
gap was 30mmol/L (elevated), which excluded causes
like renal tubular acidosis and gastro-intestinal loss.
Calculated osmol gap was 7mmol/L (normal), which
excluded exogenic acid intake. Therefore an endogenic
C151 Co-prevalence of Leriche syndrome and cardiogenic
shock: what to address first?
R.A. Carels, W. Steenselen, W. Kleinherenbrink
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: [email protected]
Case report: A 44-year old Caucasian female with a
schizoaffective disorder presented at the emergency
department with respiratory insufficiency and shock.
Primary assessment according to the ABCDE approach
revealed: Airway: patent. Breathing: no cyanosis,
respiratory rate 46 min using accessory muscles, oxygen
saturation 84% at room air climbing up to 93% with 15L
O2. Circulation: pale and clammy, blood pressure 108/76,
pulse 123 beats per minute, jugular veins not distended,
absent inguinal pulsations and impaired skin perfusion
of the lower extremities. ECG showed no acute ischemia.
We considered acute aortic obstruction. Computed
tomography showed total occlusion of the infrarenal aorta.
111
bowel sounds and hypertension. Central nervous effects
are: disorientation, ataxia, hallucinations, incoherent
speech, seizures and coma. Treatment is systematic.
Case: A 27-year old man and his 28-year old girlfriend
came to the emergency room. They suffered from
progressive disorientation and agitation. Gross hallucinations precluded taking the history of the male patient. The
woman described a simultaneous progressive blurry vision,
palpitations, headache and a dry mouth. The complaints
started two hours after drinking a cup of chocolate milk,
to which they added a herb called Althaea officinalis
(marshmallow). Both patients were healthy, they did not
use any medication or drugs. Both patients developed
mydriasis not reacting to light and a dry oral mucosa. The
physical examination of the man revealed a tachycardia of
148/min, blood pressure of 140/90 mmHg, temperature
37.3 °C, and a score of 13 on the Glascow Coma Scale (GCS).
His abdomen was extended due to a retention bladder of
1.5L. The woman had a maximal GCS, blood pressure
of 140/85 mmHg, and a temperature 37.7 °C. Cardiac
examination revealed a tachycardia of 132/min. Further
physical, neurological and blood examination of both
patients was unremarkable.
Anticholinergic poisoning was suspected. In both
patients the degree of confusion and hallucinations was
progressive, they were admitted to the intensive care unit.
They had to be calmed with benzodiazepines and finally
sedated with intravenous midazolam. Within 24 hours the
complaints diminished and they were discharged. Analyses
of the herbs revealed contamination with the plant Atropa
belladonna containing 0.1 to 1% atropine. The couple had
inserted 20 grams of the herbs, resulting in ingestion of
20 to 200mg atropine. An international press alert was
released followed by withdrawal of the herbs from multiple
European shops.
Conclusion: The cases presented here demonstrate an
anticholinergic syndrome induced after drinking one
cup of chocolate milk containing Atropa belladonna. Both
patients had a striking presentation of symptoms due to
this serious intoxication.
We concluded that the patient suffered from acute Leriche
syndrome and emergency surgery was performed. Upon
operation severe chronic arterial vascular disease was
discovered. However no acute thrombosis was seen so
no surgical intervention was possible. Postoperatively an
echocardiogram revealed ischemic cardiomyopathy and a
left ventricular ejection fraction of only 20%. We revised
our conclusion in cardiogenic shock by ischemic cardiomyopathy combined with chronic central en peripheral
arterial vascular disease. The patient was transferred to
the ICU/CCU. A month after admission the patient died
because of therapy-resistant heart failure and sepsis.
Discussion: Leriche syndrome is a rare variant of atherosclerotic occlusive disease with total occlusion of the
abdominal aorta and/or iliac arteries. The typical triad
of symptoms consists of claudication, impotence and
decreased inguinal pulses. If stenosis develops gradually
collateral vascular circulation is formed as seen in this
patient.
A clinical caveat in this case is that the decreased inguinal
pulsations and the tissue hypoperfusion were caused
by pre-existing ischemic heart failure, which was not
evaluated before surgery. This resulted in delay in the
treatment of cardiogenic shock. Reviewing the literature
we noted that cardiac failure is a common feature in
aorta obstruction. It is recommended to optimize cardiac
function to increase systemic oxygen delivery by starting
dobutamine before surgery when aortic occlusion is
suspected.
Conclusion: Diagnosis of cardiogenic shock in the presence
of Leriche syndrome is a challenge because of overlapping
symptoms. Evaluation and optimization of cardiac function
before surgical intervention is recommended.
C152 European withdrawal of herbs after an intoxication
of Atropa Belladone
B.A.M. de Weijer, G. Innemee, K. Bolhuis, P. de Vries,
S. Luykx
Tergooi Hospital, Department of Internal Medicine,
Vanriebeeckweg 12, 1213 XZ HILVERSUM, the Netherlands,
e-mail: [email protected]
C153 Succinylcholine for electroconvulsive therapy, almost
fatal
Introduction: Atropa belladonna, known as Deadly
Nightshade, is a deadly poisonous plant. The plant
contains: atropine, hyoscyamine and scopolamine. These
chemicals act by blocking the binding of acetylcholine
receptors in the nervous system inducing an anticholinergic syndrome. It is important to recognize the symptoms
which can mimic infection. Peripheral autonomic effects
include: dry skin, and redness of the skin, dilated fixed
pupils, hyperthermia, tachycardia, urinary retention
because of paralyses of the detrusor muscle, diminished
T.D. Koster1, W.E. Kooistra1, A.G. Tuinman2
1
Scheper Hospital, Department of Intensive Care,
Boermarkeweg 60, 7824 AA EMMEN, the Netherlands,
e-mail: [email protected], 2GGZ Drenthe, EMMEN, the
Netherlands
We report a dangerous side effect of succinylcholine. A
42-year-old woman was admitted to our hospital with
an auto-intoxication of an unknown dose of duloxetine,
112
quetiapine and flurazepam. On examination, the Glasgow
coma scale was five, she was bradykinetic and showed
some cogwheel rigidity. She was admitted to the intensive
care unit, intubated and treated with activated charcoal.
Toxicologic screening revealed a desalkyl-flurazepam
concentration of 0.44 mg/L (toxic concentration
> 0,2 mg/L), quetiapine and duloxetine were both in high
therapeutic concentration.
Her mental status remained depressed, probably due to
the long half-life of flurazepam. However, after three days
she deteriorated and developed fever, more rigidity, hypertension and the serum creatine kinase levels increased
from 221 u/L to 709 u/L (reference < 170 u/L). Neuroleptic
malignant syndrome was suspected and electroconvulsive
therapy (ECT) was indicated.
The ECT sessions were performed using succinylcholine
and etomidate. At the fourth session after administering
the same dose of succinylcholine, she developed ventricular
fibrillation and cardiopulmonary resuscitation was
instituted. An arterial blood sample showed a potassium
of 11.6 mmol/L (reference 3,7-4,9 mmol/L), whereas two
hours earlier it was 3.6 mmol/L. Calcium gluconate was
administered and she regained normal rhythm and output.
An electrocardiogram showed widened QRS-complexes
and peaked T-waves. Five minutes later, the potassium
concentration was 4.4 mmol/L and the electrocardiogram
normalized.
Following ECT sessions were performed using
rocuronium. Totally, she received 11 ECT sessions with
ultimately an improved clinical outcome.
Neuroleptic malignant syndrome (NMS) is a potentially
life-threatening toxidrome characterized by fever, muscle
rigidity, autonomic and mental changes. The mainstay
of treatment is supportive care with careful monitoring
of complications. Possible pharmacotherapeutic options
include benzodiazepines and dopaminergic agents.
Electroconvulsive therapy may be an effective treatment if
symptoms are refractory.
In ECT, generalized seizures are induced by electrical
stimuli to the brain. As neuromuscular blocking agent
during a session, succinylcholine is frequently used.
Unfortunately, succinylcholine has several side effects,
including hyperkalemia which can lead to cardiovascular
instability.
Succinylcholine-induced hyperkalemia has mostly been
described in patients with neuromuscular disease,
trauma, infection and associated immobilization. In
these conditions there is an upregulation of nicotinic
acetylcholine receptors. Depolarization with succinylcholine leads to efflux of potassium, leading to an acute
hyperkalemia. In this case we believe that the long period
of immobility due to her intoxication and neuroleptic
malignant syndrome may be related to the hyperkalemia.
In conclusion, we suggest that using succinylcholine
should be avoided in immobilized patients with neuroleptic
malignant syndrome.
C154 Acute recovery of confusion with ‘beginning
dementia’
M.J. Noeverman, A.T. van Rheineck Leyssius, A.M. Moorman,
R.A.A. van Zanten, A. Slootweg, T.H.F. Veneman
ZGT, Department of Internal Medicine, Zilvermeeuw 1,
7609 PP ALMELO, the Netherlands, e-mail:
[email protected]
Case report: A 69 year old woman was presented to the
emergency department with headache and dizziness since
a few hours. She was suffering from generalized weakness
and confusion since a couple of weeks, which, by her
family, was interpreted as “beginning dementia” Since
a few days prior to presentation her oral intake became
reduced, and she had developed diarrhea. Recently, the
patient had been admitted to the cardiology department
because of collapse and fatigue. The EKG showed a
prolonged QTc time and negative T waves in all leads,
improving spontaneously. No clear diagnosis was made.
At examination we noted a restless patiënt, with a bloodpressure of 100/75 mmHg and a pulse of 120 beats per
minute. Oxygen saturation was 97% at room air, with
a respiratory rate of 16 times per minute and a body
temperature of 37.1°C. Auscultation of heart and lungs was
normal, and no cardiac murmurs were heard. Examination
of the abdomen showed sparse peristalsis and mild pain in
the epigastric region.
Laboratory examination revealed major electrolyte
disturbances, in particular serious hypomagnesemia
(< 0.10 mmol/L) and a corrected plasmacalciumconcentration of 1.65 mmol/L.
Shortly after admission to the internal ward, the patient
suffered an epileptic seizure with respiratory depression.
Resuscitation was started and 4 gram magnesiumsulfate was administered, rhythm check showed sinustachycardia with cardiac output. Respiration, however,
remained insufficient, therefore ventilation through a
laryngeal mask (i-gel) was started, untill spontaneous and
adequate breathing returned. Subsequently, the patient
was transferred to the ICU. Magnesium, calcium and
potassium were intravenously suppleted. The next day
plasmamagnesiumconcentration had been normalised
(0.94 mmol/L) whereas the plasmacalciumconcentration
was partially corrected (1.96 mmol/L). The patient’s
clinical condition had strongly improved, she was clear
and adequate. No more signs of “dementia” were present.
Discussion: In this case extreme hypomagnesemia
presented with both cerebral and cardiac symptoms
including seizures and alteration of the EKG, and is
113
Results: Questionnaires were sent to 136 patients (response
rate 111 (82%)). A high CV risk (≥ 20%) was found in 60
(53%) patients, but only 3 (3%) thought that they had an
increased CV risk. In total, 65 (69%) patients followed the
doctors’ suggestions exactly and 71 (75%) patients found it
easy to follow their doctors suggestions exactly. From the 71
(66%) patients who were prescribed medication, 59 (83%)
took all prescribed tablets. Dietary measures were advised
to 46 (42%) patients and 30 (66%) said to adhere to the
diet. Physical exercise was ad vised to 72 (66%) patients
and 42 (58%) said to perform specific physical exercise ≥ 3
days/week. The adherence was not significantly different
between patients with a CV risk < 10%, 10%-20% and/or
> 20%.
Conclusion: RA patients tend to underestimate their
CV risk. Self-reported treatment adherence is 70%,
being suboptimal. The adherence to recommendations
is not associated to patients true CV risk. Better patient
awareness of their CV risk is necessary to improve
adherence.
probably the result of prolonged diarrhea, caused by a
Yersinia infection in combination with the use of a protonpumpinhibitor (omeprazol).
In addition to hypomagnesemia, hypocalcemia was
present, which is a common combination, and generally
caused by inadequate PTH secretion. Hypomagnesemia
has a high but underestimated prevalence because of its
protracted evolution and prolonged latency.
Conclusion: If a patient presents with a combination of
cardiac and neurological symptoms and/or inexplicable
EKG changes, hypomagnesemia should be considered.
In addition, other electrolytes should be checked as well.
XX
RHEUMATOLOGY RESEARCH
C155 Self-reported adherence to cardiovascular risk
reduction intervention of patients with Rheumatoid
Arthritis: Results of the FRANCIS study
D.F. van Breukelen-van der Stoep1, M. Castro Cabezas1,
J. Zijlmans1, N. van der Meulen1, B. Klop1, M.A. de Vries1,
C. van Casteren-Messidoro1, G.J.M. van de Geijn1,
H.W. Janssen1, E. Birnie1, J.M.W. Hazes2, D. van Zeben1
1
St Franciscus Gasthuis, Department of Rheumatology,
Kleiweg 500, 3045 PM ROTTERDAM, the Netherlands,
e-mail: [email protected],m 2Erasmus Medical Centre,
ROTTERDAM, the Netherlands
XXI RHEUMATOLOGY CASE REPORTS
C156 SAPHO; an unknown SKIBO
L. Louter, M.A.C.E. van Kats, D.F.S. Kehrer, H.E. van der Wiel,
A.M. Huisman
IJsselland Hospital, Department of Internal Medicine, Prins
Constantijnweg 2, 2906 ZC CAPELLE A/D IJSSEL, the
Netherlands, e-mail: [email protected]
Introduction: Patients with Rheumatoid Arthritis (RA)
have an elevated cardiovascular (CV) risk, comparable
to the risk in type 2 diabetes mellitus (T2DM). Recent
guidelines suggest strict treatment of CV risk factors. It is
well known that adherence to primary preventive interventions is frequently suboptimal (around 50%).
Aim: To evaluate the self-reported adherence to CV
prevention strategies by patients with RA participating
in the FRANCIS study, a long term, randomized, single
centre intervention study investigating the need for strict
CV prevention strategies in RA.
Methods: Included RA patients who were randomized to
strict CV risk prevention strategies received a validated
questionnaire to evaluate adherence to therapy. All
patients followed a structured CV risk management
program with rheumatologists, vascular specialists,
dieticians and specialized nurses for vascular and RA
care. Strict treatment targets were defined and lifestyle
recommendations, antihypertensive and lipid lowering
drugs were prescribed following a pre-specified protocol.
Questionnaires were sent to patients who had had at
least two visits to our outpatient clinic and a minimum
of 6 months follow up. CV risk was assessed using the
SCORE algorithm.
Introduction: SAPHO is an acronym for Synovitis, Acne,
Pustulosis, Hyperostosis and Osteitis. Since it is an
unknown and heterogeneous entity, it might be underdiagnosed in patients presenting with combined skin and
bone disease (SKIBO).
Case report: A twenty-five year old woman presented with
pain in both shoulders and sternum since four years. There
was a severe rigidity of the lumbar spine, limiting her
range of motion. Her medical history revealed recurrent
episodes of inguinal and axillary hidradenitis for more
than ten years. Physical examination revealed periarthritis
humeroscapularis and severe decreased lumbar flexion
(Schober’s test zero cm). Axillary and inguinal hidradenitis
suppurativa were present. Laboratory results revealed a
mild normocytic anemia with hemoglobin 6.7 mmol/L,
ESR 67 mm/h, CRP 7 mg/ml and 25 (OH) vitamin D was
decreased with 39 nmol/L. Immunoglobulins were normal
and there were no serological signs of autoimmunity.
HLA- B27 was negative. Surprisingly, a dual energy X-ray
absorptiometry (DXA) scan indicated osteoporosis with a
decreased T-score of -2.7 at the level of L1-L4. A 99Tc bone
114
The redness had however expanded to his forehead and
cheeks. His ECG showed PT-depression in leads II and III,
inferolateral ST-elevations without reciprocal depression.
Cardiac markers were increased: CK 928 U/L, CK-MB 73
U/L, Troponin-T 1.2 ng/ml and NTproBNP 996 pg/ml. A
cardiac ultrasound showed hypokinesia of the inferolateral
myocard wall and no pericardial effusion. Coronary disease
was ruled out with an angiography. Based upon these
findings the patient was diagnosed with cardiomyositis.
The patient complained of muscle pain and weakness
since a few months. He had noticed some red spots on
his knuckles and earlier he suffered from an skin rash
on his shoulders. In summary both patients presented
with muscle weakness, raised creatine phosphokinase
and skin lesions. Both patients were diagnosed with
dermatomyositis.
Discussion: Dermatomyositis is a connective-tissue disease
characterized by inflammation of the muscles and skin.
It can also affect joints, esophagus, lungs or heart. The
erythema of the upper eyelid is known as heliotrope
erythema. The second patient also had Gottron’s papules.
These are symmetrical, erythematous or lived atrophic
maculae of the skin overlying the knuckles, elbows,
knees or ankles. Both skin manifestations are characteristic for dermatomyositis and the combination with
muscle weakness supported by elevated creatine phosphokinase, is sufficient for the diagnosis. Treatment is with
immunosuppressiva like corticosteroids or methotrexate.
Dermatomyositis can be a paraneoplastic manifestation
and has an increased risk for malignancy mainly in the
first 3 years. The 5-year survival rate is 75-95%. Mortality
is often due to underlying malignancy or pulmonary and/
or cardiac involvement.
Conclusion: In patients with muscle weakness with characteristic skin findings like heliotrope erythema or Gottron’s
papules, the diagnosis of dermatomyositis can be made on
the spot.
scintigraphy showed increased uptake in the sternocostoclavicular region, compatible with bull’s head sign. She
was diagnosed with the SAPHO syndrome. Treatment
consisted of intra-articular corticosteroids and methotrexate after which the symptoms improved.
Discussion: SAPHO is considered a seronegative spondyloarthritis, although it is also described as a variant of
arthritis psoriatica. The presence of multifocal osteitis
with skin symptoms, or sterile joint inflammation with
pustulosis palmoplantaris or hidradenitis, is sufficient for
the diagnosis. The secondary osteoporosis of the lumbar
spine is due to both disease activity and immobility.
Chronic recurrent multifocal osteomyelitis (CRMO) and
enteropathic variants might be considered as subtypes
of SAPHO. However, differentiation is difficult. The
exact prevalence is unknown. Infective, genetic and
immunologic factors have been suggested as etiology,
but the exact cause and pathogenesis is unknown. In
rare cases Propionibacterium Acnes has been isolated
and suggested as antigenic trigger for a proinflammatory
response of bone marrow, inducing hyperostosis and
sclerosis. 99TC bone scintigraphy is the gold standard for
the diagnosis. Classically it shows a bull’s head sign which
is the increased tracer uptake in the sternocostoclaviculair
region. NSAIDs, corticosteroids, methotrexate, bisphosphonates and biologicals are used in the treatment of SAPHO.
There is no place for antibiotics in the treatment regimen.
Conclusion: SAPHO should be considered in all patients
with combined skin and bone disease, since it is thought
to be an underdiagnosed syndrome with good treatment
possibilities.
C157 A spot diagnosis made based on characteristic skin
findings
M. Ladenius, J.E. Heeg
Isala Clinics, Dokter van Heesweg 2, 8025 AB ZWOLLE, the
Netherlands, e-mail: [email protected]
C158 An indolent case of polyarteritis nodosa
Introduction: It is not very often one can make a diagnosis
on the spot. In this abstract I want to present two patients
whose diagnosis was made upon characteristic findings
of the skin.
Cases: The first patient is a 77 year old men, presenting
with progressive muscle pain and weakness since
weeks. There had been no improvement after stopping
simvastatin. On physical examination there was erythema
of the upper eyelids, forehead and cheeks. His creatine
phosphokinase was markedly increased with 5450 U/L.
The second patient is a 42 year old man, presenting
at the hospital with chest pains. A few days before he
had noticed swelling and redness of his upper eyelids
for which he was treated as a herpes simplex infection.
A. Blazevic, F.E. de Jongh, R.J.T.H. Ouwendijk
Ikazia Hospital, Department of Internal Medicine,
Montessoriweg 1, 3083 AN ROTTERDAM, the Netherlands,
e-mail: [email protected]
Case report: A previously healthy 40-year old man was
referred to our outpatient clinic because of hematochezia.
History revealed he had periods of loose stool and rectal
hemorrhage for several years. Physical examination
was unremarkable except for a blood pressure of
140/100 mmHg. Notably, there was no abdominal
mass or tenderness. Laboratory results showed slightly
elevated serum levels of aspartate aminotransferase,
115
alanine aminotransferase and gamma-glutamyltransferase.
The erythrocyte sedimentation rate, C-reactive protein,
blood cell counts and coagulation tests were normal;
urinalysis showed no abnormalities. Ileocolonoscopy
showed moderate colitis involving the entire colon and
rectum; microscopic examination revealed diffuse chronic
ulcerative inflammation with eosinophilia. Furthermore,
in the transverse colon, a large ulcer (5 x 5 centimeter) was
present. Biopsies from the ulcer showed fibrinoid thrombi
as well as necrosis and inflammation of a blood vessel
wall. As these findings were suggestive of a vasculitic
process; auto-immune (ANF, ANCA), and viral (hepatitis
B, C) serologic tests were ordered and found to be negative.
Treatment with oral budenoside 9 mg once daily was
initiated immediately after colonoscopy, in expectation of
the additional tests. Mesenteric angiography showed the
typical findings of polyarteritis nodosa (PAN).However,
the patient’s condition had markedly improved without
the initiation of intensive immunosuppressive therapy,
and colonoscopy six weeks after presentation showed only
mild diffuse colitis without ulceration. Therefore, this
unusual and mild treatment was continued for a year after
which it was tapered and stopped. Presently, 8 years after
presentation, he is asymptomatic without any immunosuppressive treatment.
Discussion: PAN is a vasculitis that typically affects
medium-sized arteries in many different organ systems.
Most patients present with systemic symptoms. Gastrointestinal involvement occurs frequently (roughly 50%
of the cases) and carriers a poor prognosis. Aggressive
immunosuppressive treatment seems warranted in order
prevent life-threatening complications. Cases of localized
gastro-intestinal vasculitis are rare and a major point
of concern is whether these are an initial manifestation
of a more severe systemic vasculitis. After a complete
evaluation there was no sign of systemic disease and our
patient was successively treated with budesonide and was
spared intensive immunosuppressive treatments, which
have a multitude of side-effects.
Conclusion: Localized gastrointestinal vasculitis is a rare
manifestation of PAN and needs careful consideration
before starting intensive immunosuppressive treatment,
as it can have a remarkable indolent clinical course shown
in this case report.
the Netherlands, e-mail: [email protected],
2
Maasstad Hospital, ROTTERDAM, the Netherlands, 3Leiden
University Medical Centre, LEIDEN, the Netherlands
Introduction: Systemic lupus erythematosus (SLE) is a
systemic autoimmune disease. Central nervous system
involvement occurs up to 50% of patients with SLE.
Transverse myelitis is a rare complication of SLE. More
uncommon is transverse myelitis as presenting symptom
of SLE.
We here present the case of an adult woman diagnosed
with transverse myelitis in SLE.
Case report: A 25 years old female was admitted to our
intensive care unit with malignant hypertension with
papilledema. Her medical history revealed intermittent
self-catheterization because of urine retention since 6
weeks. Patient was referred to a neurologist for analysis
of neurogenic bladder. Before the neurology consultation, patient was admitted to the intensive care unit for
controlled blood pressure regulation.
Laboratory testing revealed anemia (4.6 mmol/L), thrombopenia (61*10^9/L), elevated serum creatinine (122
umol/L), mild hypoalbuminemia (33 g/L), active urinary
sediment and proteinuria, and a positive Coombs test.
During the admission, she rapidly developed saddle
sensory changes, weakness in the legs and fecal incontinence in a few days. MRI of the spine revealed diffuse
edema of the spine cord. A diagnosis of SLE was made,
based on the presenting symptoms (hypertension and
symptoms of transverse myelitis), laboratory findings,
positive antinuclear antibodies and double-stranded DNA,
active urinary sediment and the MRI findings with central
nervous system involvement.
Biopsy of the kidney showed thrombotic microangiopathy
considered to be caused by malignant hypertension.
The patient was treated with high dose methylprednisolone, pulse cyclophosphamide. Subsequently,
hydroxychloroquine was started. There was a significant
improvement in her neurologic and functional status
within one month of therapy. Hydroxychloroquine was
continued throughout the duration of therapy. Patient
was transferred to a rehabilitation centre for further
rehabilitation.
Conclusion: Transverse myelitis is a rare presenting
symptom of SLE. MRI of the spine can be helpful in
prompt diagnosis of SLE with central nervous system
involvement. Early aggressive treatment with steroids,
cyclophosphamide and hydroxychloroquine is essential
to increase the chances of recovery in patients with this
severe complication of SLE.
C159 Hypertension and urinary retention as presenting
symptoms of transverse myelitis in systemic lupus
erythematosus: a case report
L. Huang1 , F. Bonte-Mineur2 , M. Steup-Beekman3 ,
E. Zirkzee3, M. Wabbijn1
1
Ikazia Hospital, Department of Internal Medicine,
Dokkummerstraat 13, 2652 EW BERKEL EN RODENRIJS,
116
C160 Arthralgia and skin lesions in a cocaine-abusing
patient
arise. This is the first report of mesenteric ischemia
leading to acute intussusception. Cocaine abstinence
is of key importance. No consensus exists regarding
additional benefits of immunosuppressives. If abstinence
is improbable and life-threatening complications occur,
immunosuppressive therapy should be considered.
Conclusion: Cocaine/Levamisole-induced vasculopathy
can be a life-threatening systemic disease. Hair testing
and ANCA-elastase antibodies can be helpful diagnostic
aids. When severe complications arise, immunosuppressive
therapy should be considered in addition to cocaine
abstinence.
T. van der Veer, L. Korswagen
St Franciscus Gasthuis, Department of Internal Medicine,
Kleiweg 500, 3045 PM ROTTERDAM, the Netherlands,
e-mail: [email protected]
Introduction: The number of cocaine-associated hospitalizations is rising, and so is the use of adulterants. One of
these adulterants is levamisole, an immunomodulating
agent and veterinary anthelmintic. Recent reports have
pointed to levamisole as the culprit in cocaine/Levamisoleinduced vasculopathy. This syndrome can present with
several symptoms of which skin lesions are most characteristic. Without a history of cocaine use, diagnosis can be
a challenge.
Case: A 42-year-old woman presented at the rheumatology outpatient clinic with severe arthralgia and
malaise. Treatment with NSAIDs was unsuccessful.
Deep ulcerating skin lesions developed. Antibodies to
rheumatoid factor, anti-CCP, ANA/ENA, ANCA-PR3,
ANCA-MPO, lupus anticoagulans, anticardiolipin and
cryoglobulins were negative. Skin biopsies did not show
vasculitis. Cocaine abuse was repeatedly denied and several
urine samples tested negative. A hair sample was then
tested which proved positive for cocaine and levamisole.
Additional ANCA-elastase antibodies were later found
positive. During hospitalization the patient suffered several
complications. She lost the distal part of one finger to
ischemic necrosis. An emergency ileocecal resection had
to be performed due to intussusception of the ileum. While
hospitalized she abstained from cocaine and recovered
without therapy other than NSAIDs. Months later she
had relapsed into cocaine abuse and was readmitted
with recurrent arthralgia and decreased kidney function.
Kidney biopsy showed a glomerulonephritis. Treatment
with cyclophosphamide and high dose corticosteroids was
initiated. Her symptoms resolved and kidney function
normalized.
Discussion: Levamisole is an immunomodulating agent
discontinued in humans because of side-effects. Among
these are purpuric or ulcerating skin lesions, frequently
on the legs and earlobes. Similar skin lesions are a
pronounced feature of the cocaine-induced vasculopathy.
As a histopathological specimen often does not prove
vasculitis, the syndrome is sometimes called cocaineinduced pseudovasculitis. ANCA-MPO and ANCA-PR3
antibodies can be found, sometimes both in one patient.
The ANCA-elastase antibodies that are linked to druginduced ANCA-associated vasculitis are also frequently
positive. Toxicological testing of a hair sample can be
a helpful alternative to urine testing as toxins remain
detectable for months. Ischemic complications can
XXII IMMUNOLOGY/ALLERGOLOGY RESEARCH
C161 Cytokine production assays reveal discriminatory
immune defects in adults with recurrent infections
and non-infectious inflammation
J. ten Oever, F.L. van de Veerdonk, L.A.B. Joosten,
A. Simon, R. van Crevel, B.J. Kullberg, I.C. Gyssens,
J.W.M. van der Meer, M. van Deuren, M.G. Netea
Radboud University Medical Centre, Department of Internal
Medicine, Geert Grooteplein-Zuid 10, 6525 GA NIJMEGEN,
the Netherlands, e-mail: [email protected]
Background: Nadroparin is used during hemodialysis to
prevent clotting in the extra corporeal system. During
nocturnal hemodialysis patients receive an increased
dosage of nadroparin compared to conventional hemodialysis due to the intensified frequence and duriation of
dialysis. It is unknown whether the prescribed dosage
regime of nadroparin during nocturnal hemodialysis leads
to accumulation.
Aim of the study: To asses if accumulation of nadroparin
occurs during nocturnal hemodialysis.
Materials and methods: We tested Anti-Xa levels in 13
clinically stable patients undergoing nocturnal hemodialysis 4 nights a week (session duration 8 hours). Dosages
nadroparin were administered according to the guidelines
of the Dutch Federation of Nephrology. We assessed anti-Xa
levels at 4 time points during 1 dialysis week. Before the
start of a the first dialysis session of the week (baseline),
prior to (T1) and after the last dialysis session of the week
(T2) and before the first dialysis of the following week (T3).
Secondary outcomes were the clotting and bleeding events
during this week. Anti-Xa levels were measured photometrically using a chromogenic technique. The paired
two-sample t-test was used for the statistical analysis.
Results: Patients received 71-95 IU/kg at the start of dialysis
and 50% of the initial dosage after 4 hours with a total dosage
of 128 ± 24 IU/kg. The mean dosage nadroparin for patients
117
also using acenocoumarol (n = 5) was 111 ± 15 IU/kg, whereas
it was 139 ± 22 IU/kg in the other 8 patients (p < 0.05). Anti-Xa
levels were 0,017 ± 0.018 IU/ml at baseline. At T1 anti-Xa
levels were significantly elevated (p = 0,026), in comparison
to baseline, by 0,02 IU/ml. At T2 anti-Xa levels were 0,419 ±
0,252 IU/ml (p < 0.05 vs B and T1). At T3 anti-Xa levels are
equal to B (p = 0,77). No major clotting or bleeding events were
observed. Standard monthly laboratorium testing remained
stable during the testing period.
Conclusion: The used dosage regime of nadroparin during
nocturnal hemodialysis according to the Dutch guidelines
does not induce accumulation of nadroparin. In addition, it
seems a save and effective dosage in our population.
p = 0.01; r = -0.59, p = 0.045; r = -0.71, p = 0.01). Finally,
endotoxin-induced flu-like symptoms were lower in the
intervention group (peak symptom score of 3.8 ± 0.5 vs. 8.6
± 0.6, p < 0.0001).
In conclusion, we demonstrate for the first time that
voluntary activation of the sympathetic nervous system
results in epinephrine release and subsequent suppression
of the innate immune response in humans in vivo.
XXIIIIMMUNOLOGY/ALLERGOLOGY CASE REPORT
C163 Shortness of breath after a peanut butter sandwich;
not always an allergic reaction
C162 Voluntary activation of the sympathetic nervous
system and attenuation of the innate immune
response in humans
W.N.H. Koek, P.L.A. van Daele
Erasmus Medical Centre, Department of Internal Medicine,
Postbus 2040, 3000 CA ROTTERDAM, the Netherlands,
e-mail: [email protected]
J. Zwaag1, M. Kox2, L.T.G.J. van Eijk2, J. van den Wildenberg2,
C.G.J. Sweep2, J.G. van der Hoeven2, R.P. Pickkers2
1
Twee Steden Hospital, Department of Internal Medicine, Dr.
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected], 2Radboud University Medical
Centre, NIJMEGEN, the Netherlands
Case: A 51-year old man was seen at the department of Oral
and Maxillofacial surgery after he fractured his lower right
mandible eating a peanut butter sandwich. X-rays of the
jaw showed a radiolucent lesion in the corpus mandible. A
CT-scan showed a tumor localized to the alveolar process
invading the m.digastricus and the m.mylohyoideus. The
pathological specimen subsequently obtained showed
connective tissue with inflammatory infiltrate containing
predominantly histiocytes and eosinophilic granulocytes.
The histiocytes stained positive for CD1a, S100 and
CD68, confirming the diagnosis Langerhans cell histiocytosis (LCH), upon which the patient was referred to
the immunology outpatient clinic for further evaluation.
Apart from being a heavy smoker, his medical history was
unremarkable. On physical examination no abnormalities
were found. Bone scintigraphy showed no other skeletal
lesions. Remarkably, HR-CT showed interstitial lung
disease with minimal cystic lesions and nodular changes
in upper and middle lobes characteristic for pulmonary
LCH. Pulmonary function test revealed a mild to moderate
impaired diffusion capacity with overall normal lung
function. There were no signs of involvement of other
organs. Initially conservative treatment with bisphosphonates was started and disease progression was monitored.
Unfortunately, despite cessation of smoking his pulmonary
functions tests deteriorated gradually and he experienced
a spontaneous pneumothorax. Therefore therapy was
intensified.
Discussion: LCH is disease characterized by an infiltration
by myeloid dendritic cells expressing the same antigens
as Langerhans cells. The pathogenesis is still unclear,
although some patients have mutations in BRAF. LCH
is rare affecting both adults and children; the prevalence
The autonomic nervous system and innate immune
system are regarded as systems that can not be voluntarily
influenced. We evaluated the effects of a training program
on the autonomic nervous system and innate immune
response.
Volunteers were randomized to either the intervention (n
= 12) or control group (n = 12). Subjects in the intervention
group were trained for 10 days (including breathing
techniques [cyclic hyperventilation followed by breath
retention] and exposure to cold [i.a. immersions in ice
cold water]). The control group did not receive training.
Subsequently, all subjects underwent experimental
human endotoxemia (i.v. administration of 2 ng/kg E. Coli
endotoxin).
In the intervention group, practicing the learned techniques
resulted in intermittent respiratory alkalosis and hypoxia
resulting in significantly increased plasma epinephrine
levels (2.08 ± 0.37 vs. 0.35 ± 0.06 nmol/L, p < 0.0001). In the
intervention group, plasma levels of the anti-inflammatory
cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine
levels (r = 0.82, p = 0.001), and were higher (peak levels
of 791 498-1203 vs. 261 187-684 pg/mL, p = 0.01). Levels of
pro-inflammatory mediators TNF-a, IL-6, and IL-8 were
lower in the intervention group and correlated negatively
with IL-10 levels (peak levels of 213 169-553 vs. 456 281-746 pg/
mL, p = 0.02; 284 157-344 vs. 471 316-703 pg/mL, p = 0.01; 368
266-540
vs. 562 422-647 pg/mL, p = 0.004, respectively; r = -0.71,
118
of LCH in adult is estimated around 1 to 2 cases per
million. The majority of patients with LCH have one or
more lytic bone lesions but other tissues like skin, lymph
nodes, liver, spleen, oral mucosa, lung and the central
nervous system can be involved as well. In patients with
isolated pulmonary involvement there is an association
with smoking and cessation of smoking often leads to
curation. Depending on the number of affected tissues and
involvement of risk organs like the hematopoietic system,
the liver and/or spleen, treatment consists of monitoring
disease progression or starting more aggressive treatment
options involving Cladribine or Cytarabine. Patient with a
V600E mutation in BRAF might benefit from treatment
with BRAF inhibitors.
Conclusion: osteolytic lesions of the jaw with spontaneous
fracture can be a sign of multisystemic LCH and therefore
warrant full investigation of other organ systems known to
be involved in LCH like the lungs.
2008 sera of our patient revealed strongly positive
results to red meat and Galactose-a-1,3-Galactose (a-Gal).
Additional testing in our lab of IgE a-Gal in other
patients with urticaria and anaphylaxis showed the test
is very specific.
The additional history of our patient revealed that she had
been treated a couple of weeks ealier for a tick bite. She also
had a tick bite five years before. We advised patient to avoid
red meat. Provocation testing with red meat is planned.
Discussion: Hereby we present to our knowledge the
first patient in the Netherlands with a confirmed allergy
to a-Gal. A tick bite seems to be a hallmark in the
development of this type of allergy. The diagnosis of red
meat allergy may be difficult because of the delayed onset
of the reaction and the relatively unknown relation with
a-Gal IgE
XXIVOTHER RESEARCH
C164 Delayed anaphylaxis, urticaria and angioedema
caused by red meat: a rare cause
C165 Impaired systolic blood pressure recovery directly
after standing predicts mortality in older falls clinic
patients
R.L. Oei, J.G.R. de Monchy
University Medical Centre Groningen, Department of
Internal Medicine, Hanzeplein 1, 9713 GZ GRONINGEN,
the Netherlands, e-mail: [email protected]
J. Lagro1, Y. Schoon1, I. Heerts1, A. Meel-van den Abeelen1,
B. Schalk1, W. Wieling2, M. Olde Rikkert1
1
Radboud University Medical Centre, Department of
Geriatrics, Reinier Postlaan 4, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected], 2 Academic
Medical Centre, AMSTERDAM, the Netherlands
Introduction: Anaphylaxis can be caused by numerous
causes e.g. food allergens, drugs or insectstings. The
response to food allergens usually occurs within one to two
hours but may also start within minutes after ingestion.
Here we present a case of delayed anaphylaxis induced by
a rare cause, red meat.
Case report: A 61-year old female presented at our
emergency department with all the clinical stigmata of
anaphylaxis, The diagnosis was confirmed by an elevated
serum tryptase value. She was diagnosed 1.5 years earlier
with chronic urticaria. At that time the medical history
did not reveal any plausible causes (food, drugs, exercise).
Allergy skin testing was completely negative. Mastocytosis
was ruled out by absence of any skin abnormalities and a
normal baseline serum tryptase. The patient did not have
any recurrent episodes of anaphylaxis within a follow-up
of 1 year.
About five years later this patient was presented at our
emergency department with a new episode of anaphylaxis
(serologically confirmed) and with history that initially
didn’t reveal any clues except that she had eaten a
hamburger a couple of hours earlier. A few days before she
had developed urticaria after a BBQ dinner.
Alpha-Gal (a-Gal), a protein found in red meat, was
recently reported in the literature as a novel allergen
associated with tick bites. Testing the recent and the
Introduction: Normally, standing up causes a blood
pressure drop within 15 seconds, followed by recovery to
baseline driven by blood pressure control mechanisms.
The prognostic value of this initial blood pressure drop, but
also of the recovery hereafter, is unknown.
Aim: The aim of this study was to examine the prognostic
value of these blood pressure characteristics in response
to standing.
Methods: In a cohort study of 238 consecutive patients
visiting our falls outpatient clinic, we examined the
relation between all-cause mortality and blood pressure
decline and recovery directly after active standing up with
Cox proportional hazards analyses.
Results: Of 238 patients (mean age 78.4 ± 7.8 years), during
a median follow-up of 21.0 months, 36 (15%) patients died.
Neither absolute nor relative (%) initial blood pressure
drop after standing predicted mortality. In contrast, the
magnitude of blood pressure recovery 40 to 60 seconds
after standing was associated with mortality, even after
adjustment for age, co-morbidity and other baseline characteristics. When systolic blood pressure had recovered to
less than 80% of pre-standing baseline after 60 seconds
119
of standing, this was a powerful independent predictor
of mortality (hazard ratio: 3.00; 95% confidence interval:
1.17-7.68).
Conclusions: Failure to recover from blood pressure decline
in the first minute after active standing up is associated
with excess mortality in falls clinic patients. A recovery of
systolic blood pressure to less than 80% of baseline after
60 seconds may be used as an easy available cardiovascular
marker for increased mortality risk in older falls clinic
patients.
of medical care in complex geriatric medical decision
making. Playing GeriatriX also resulted in a better costconsciousness. We therefore encourage wider use of
GeriatriX to teach geriatrics in medical curricula and its
further research on educational and health care outcomes.
C167 Adiposity in myotonic dystrophy: an increased risk
to develop respiratory failure?
C.G.W. Seijger1, G. Drost2, J.M. Posma3, B.G. van Engelen 4,
Y.F. Heijdra 4
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6800 TA ARNHEM, the Netherlands,
e-mail: [email protected], 2University Medical
Centre Groningen, GRONINGEN, the Netherlands3Faculty
of Medical Imperial College, LONDON, United
Kingdom, 4Radboud University Medical Centre, NIJMEGEN,
the Netherlands
C166 A randomized controlled trial on teaching geriatric
medical decision making and cost consciousness
with the serious game GeriatriX
J. Lagro, M. van de Pol, F. Huijbregts-Verheyden, C. Fluit,
M. Olde Rikkert
Radboud University Medical Centre, Department of
Geriatrics, Reinier Postlaan 4, 6500 HB NIJMEGEN, the
Netherlands, e-mail: [email protected]
Introduction: Myotonic dystrophy type 1 (DM1) is the
most common form of adult-onset muscular dystrophy.
Clinically, DM1 is a multisystem disorder with progressive
muscle weakness and myotonia, internal, cardiac and
respiratory pathology. DM1 patients have a low life
expectancy, with a mean age at death of 54 years. The
most frequent cause of mortality is respiratory failure by
pneumonia. Furthermore, lung volumes are markedly
reduced in DM1, likely due to weakness of inspiratory
muscles. In healthy individuals overweight is associated
with reduced total lung capacity (TLC) and increased work
of breathing. With overweight being a common feature in
over half of DM1 patients, we investigated the effects of
overweight on pulmonary function in DM1.
Methods: In 105 DM1 patients pulmonary function tests
were performed and respiratory muscle strength was
measured, body mass index (BMI) was calculated and
fat-free mass index (FFMI) was measured. The effect
of overweight on pulmonary function was evaluated by
stratifying patients into a normal weight (BMI < 25 kg/m2)
and overweight (BMI≥ 25 kg/m2) group. Multiple linear
regression with backward stepwise elimination was used
to find significant contributors for TLC.
Results: Overweight is present in 59%. In overweight
patients (with or without decreased FFMI) the TLC was
decreased significantly compared to the normal weight
patients (TLC respectively 75.4% and 84.1% of predicted, p
= 2.40 x 10 -3). The decreased TLC in overweight patients is
mainly due to a decreased expiratory reserve volume, which
is inversely correlated to BMI (r = -0.59, p = 1.33 x 10 -10).
Multiple linear regression showed that forced inspiratory
volume in 1 second (FIV1) and BMI are the only significant
contributors in predicting TLC. The model is described
by: TLC (% pred.) = 44.54 - 0.55 x BMI + 0.60 x FIV1(%
Introduction: Medical students often lack training in c
Geriatrics omplex geriatric medical decision making.
We therefore developed the serious game GeriatriX, for
training medical decision making with weighing patient
preferences, appropriateness and costs of medical care.
Aim: We hypothesized that education with GeriatriX
improved the ability to deal with geriatric decision making
and also increased cost-consciousness.
Methods: In a randomized, controlled pre-post
measurement design in fifth year medical students we
evaluated the effects of playing GeriatriX on attitudes
toward the elderly, on self-perceived knowledge of geriatric
themes and the self-perceived competence of weighing
patient preferences, appropriateness and costs of medical
care in geriatric decision making. Cost-consciousness was
evaluated with a post-measurement to estimate costs of
different diagnostic tests.
Results: There was no significant change in attitudes
toward the elderly between the intervention (n = 71)
and control group (n = 63). Although the self-perceived
knowledge increased substantial on some geriatric topics,
this improvement was not different between the intervention and control group. There was a large positive
increase in the self-perceived competence of weighing
patient preferences, appropriateness and costs of medical
care in the intervention group (effect sizes of 0.7, 1.0 and
1.2, respectively) which was significant better for the last
two aspects than the control group. The intervention group
performed better on cost-consciousness.
Conclusions: After playing the serious game GeriatriX
medical students have a higher self-perceived efficacy in
weighing patient preferences, appropriateness and costs
120
pred.). P-values for BMI and FIV1 are 5.53 x 10 -4 and 7.14 x
10 -23, respectively.
Conclusion: This study shows that in addition to decreased
inspiratory muscle strength, overweight negatively
influences TLC. Overweight results in increased work of
breathing due to diaphragm displacement and decreased
compliance of the thoracic wall. Due to the weakness of
the inspiratory muscles in DM1 patients it is impossible
to achieve this increased demand. Therefore the threshold
for respiratory muscle fatigue will be reached at an earlier
stage, resulting in an earlier development of respiratory
failure.
Clinical implication: Delaying the onset of respiratory
failure could possibly be achieved by reducing overweight
with maintenance of muscle mass.
zation (TAE)). Blood transfusion and prothrombin complex
concentrate to reverse anti-coagulation were given and
vitamin K antagonist was discontinued. Laboratory tests
improved and neurological symptoms decreased minimally
during admission.
Conclusion: Patients with iliopsoas hematoma often present
themselves with unilateral groin or abdominal pain that
radiates to the lower back or thigh which can lead to
muscle weakness and sensory loss of the lower limb. The
femoral nerve is vulnerable to compression because of
its anatomical route. It emerges from the lateral side of
the psoas muscle where it lies in a narrow canal between
the psoas and iliac muscle, susceptible to compression
by a hematoma. Patients on anticoagulation therapy with
sudden sensibility loss and/or muscle weakness of the lower
limb together with pain in the abdomen, back or thigh need
prompt imaging to rule out iliopsoas muscle hematoma.
XXV OTHER CASE REPORTS
XXVIGENERAL INTERNAL MEDICINE RESEARCH
C168 Spontaneous iliopsoas muscle hematoma with
femoral neuropathy
C169 How to improve the moderate knowledge of venous
thromboembolism prophylaxis?
D. Kortbeek, B.P.M. Imholz
Twee Steden Hospital, Department of Internal Medicine,
Doctor Deelenlaan, 5042 AD TILBURG, the Netherlands,
e-mail: [email protected]
G.J. Dreyer 1 , A.D. Pieterse1, J.M. Baas1, A. Leen 2 ,
L.C.J. te Boome1, F.H. Heyning3, M.J.M. de Vreede1
1
Medical Centre Haaglanden, Department of Internal
Medicine, Abraham amptstraat 8, 2515 LV DEN HAAG, the
Netherlands, e-mail: [email protected], 2Leiden
University Medical Centre, LEIDEN, the Netherlands,3STZ
Hospitals, UTRECHT, the Netherlands
Introduction: Spontaneous iliopsoas hematoma is a rare
complication of anticoagulation therapy which may even
result in significant neurological symptoms.
Case: A 88-year old woman, on oral anticoagulation therapy
because of chronic atrial fibrillation, was admitted to our
department of Internal Medicine due to acute abdominal
pain in the lower left quadrant and deterioration of her
chronic back pain. Furthermore the patient experienced a
sudden loss of sensibility on the anterolateral side of her left
leg with decreased muscle strength which was confirmed
by neurological examination. Besides a left-sided inguinal
hematoma, physical examination was normal. There was
no history of trauma or clearly provocative moment in
time. Laboratory data showed slightly increased infectious
parameters, a deteriorated chronic normocytic anemia (Hb
4.5 mmol/L), elevated creatine phosphokinase (601 U/L) and
an elevated international normalized ratio (7.93). Abdominal
ultrasonography revealed high suspicion of malignancy
regarding the descending colon and the following computed
tomography scan of the abdomen showed an actively
bleeding psoas hematoma instead (size 10 x 7 centimeters).
We diagnosed a spontaneous iliopsoas muscle hematoma
with femoral neuropathy and immediately started conservative treatment due to substantial co-morbidity, compromised
daily functioning and hemodynamic stability instead of an
interventional approach (eg, transcatheter arterial emboli-
Background: Despite clear prophylactic guidelines and
national quality emphasis, a minority of hospitalized
patients receive appropriate prophylaxis for venous
thromboembolism (VTE). Data from the MCH revealed
an unacceptable high incidence of inappropriate VTE
prophylaxis in MCH. In the context of the patient safety
program Medical Centre Haaglanden the aim was to
implement a clear useful local protocol.
Approach: We wrote a complete instrument for the
application of thrombosis prophylaxis. The CBO consensus
‘Diagnosis, prevention and treatment of venous thromboembolism and secondary prevention of arterial thrombosis
(2008)’ was used as a guidance. Two hemostasis employees
were hired. They aligned continuing education, with
quality improvement through formation of an interprofessional, multidisciplinary team to develop strategic
educational and system operational plans to improve
appropriate VTE prophylaxis. We are analyzing the
prophylaxis in patients before the implementation of the
protocol, short after the introduction and 4 months after
the introductions.
121
Outcomes: Before implementation of the protocol the
incidence of inappropriate VTE prophylaxis in a small
study ranged from 16-24%. The results in patients
admitted for operation using oral anticoagulation were
even worse ranging from 45% using antiplatelets - 70%
using vitamin K antagonists . Short after implementation
the inadequate application of prophylaxis already seems to
decrease. We will analyze the data 4 months after introduction to see if there is more improvement.
Next steps: We decided to start with a proper implementation of the first part of the local protocol, VTE
prophylaxis. Aligning continuing education with quality
improvement through an interprofessional, multidisciplinary team approach seems to be associated with an
increase of application of adequate prophylaxis. First
data suggested even worse administration of bridging of
patient using oral anticoagulation. The next challenge for
the authors is to collaborate with the thrombosis care to
implement “bridging chapter”, second part of the protocol.
Conclusion: The knowledge of VTE prophylaxis was
moderate in doctors of all disciplines in the MC
Haaglanden. The implementation of a simplied protocol,
extracted from the CBO consensus, improved the patient
safety.
Objective: To asses the effect of short-term starvation
on pharmacokinetics of S-warfarin in humans and on
CYP2C11 mRNA expression in rat livers.
Methods: Nine healthy human male volunteers were
enrolled in a crossover intervention study. Subjects were
randomly assigned for two sequential interventions: a
single oral subclinical dose of 5 mg warfarin (A1) after an
overnight fast and (A2) after 36h of starvation. After drug
administration serial blood samples were obtained during
336 h for measurement of S-warfarin plasma concentrations by LC-MS. Primary endpoints were pharmacokinetic
parameters of warfarin using nonlinear mixed effects
modeling. In rat livers mRNA CYP2C11 levels were
measured by qPCR after 24h (n = 6) and 36h (n = 6) of
fasting, compared to ad libitum fed rats.
Results: In healthy volunteers, fasting decreased S-warfarine
clearance by 28% (95% CI 38 to 17%; p < 0.001). Also,
fasting reduced S-warfarin volume of distribution by 17%
(95% CI 23 to 11; p < 0.001).
The effect is in accordance with the effects of fasting in
rats, which decreased the relative expression of hepatic
CYP2C11 mRNA after both 24h (Δ-1.30 (p = 0,003, 95% CI
-1,94 to -0,66) and 36h (Δ-1.80 (p = 0,001, 95% CI -2,41 to
-1.18), compared to controls.
Conclusion: Fasting decreases S-warfarine clearance.
This provides proof of concept, that nutritional conditioning, in this case the effect of fasting, contributes
to variability in drug metabolism by CYP 2C9 within
subjects. Consequently, variations in dietary composition
and/or quantity may require dose adjustments of some
drugs, e.g. coumarin anticoagulants.
C170 Short-term fasting decreases warfarin clearance:
proof of concept for the effects of nutritional conditioning on pharmacokinetics
R. Achterbergh, L.A. Lammers, E.M. de Vries,
F.S. van Nierop, H.J. Klumpem, M.R. Soeters, A. Boelen,
R.A.A. Mathôt, J.A. Romijn
Academic Medical Centre, Department of Internal Medicine,
Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands,
e-mail: [email protected]
XXVIIGENERAL INTERNAL MEDICINE CASE
REPORTS
Background: Coumarin therapy requires intensive
monitoring to reach a therapeutic INR. Nonetheless, the
percentage of time patients are within the therapeutic
window is limited, which stresses the importance of identification of determinants of coumarin plasma levels.
Coumarin anticoagulants are metabolized by cytochrome
P450 (CYP) enzymes, i.e. CYP2C9. There are indications
from animal studies suggesting that nutritional conditioning, i.e. the composition of the previous nutrition,
influences the activity of drug metabolizing enzymes
such as CYP2C9. Differences in nutritional status may
therefore lead to altered CYP2C9 metabolism and cause
treatment failure or adverse events. Since S-warfarin (the
more pharmacologically active enantiomer of the racemic
drug) is a selective substrate of CYP2C9 it may be used as a
probe to study CYP2C9 activity. The equivalent of CYP2C9
in rats is CYP2C11.
C171 Elevated serum levels of vitamin B12, not always that
harmless
M.N.T. Kremers, H.J. Jansen
Jeroen Bosch Hospital, Department of Internal Medicine,
Postbus 90153, 5200 ME ’S-HERTOGENBOSCH, the
Netherlands, e-mail: [email protected]
Introduction: In clinical practice, we frequently test
vitamin B12 levels. In a number of patients, elevated
levels of vitamin B12 are displayed. In a subgroup of
these patients, high vitamin B12 levels may be caused by
potential harmful diseases, as we will show using three
cases:
Case A: A 67-years-old male without a relevant medical
history, presented with an elevated serum level of vitamin
B12 (> 1476 pmol/L). He did not have any complaints and
122
used no supplements. Physical examination revealed no
abnormalities and laboratory examination showed an
elevated methylmalonic acid (MMA) of 0.36 mmol/L.
Case B: A 66-years-old male without a relevant medical
history, was referred because of a macrocytic anemia and
fatigue. He used 4-6 glasses of wine every day. Laboratory
results showed: hemoglobin level 5.5 mmol/L, mean
corpuscular volume 109 fl, platelet count 558 x 10e9/L,
vitamin B12 907 pmol/L, ferritine 360 ug/L and MMA
0.37 mmol/L.
Case C: a 42-years-old male with an elevated vitamin B12
(> 1476 pmol/L), was referred because of jaundice. His
medical history revealed fatigue and alcoholism. Physical
examination showed, besides jaundice, cachexia and
edema. Laboratory results revealed a macrocytic anemia,
thrombocytopenia, a spontaneous INR of 2.4 and highly
elevated liver enzymes.
In all patients, vitamin B12 levels were elevated, though the
underlying causes were completely different.
Discussion: In Case A: A functional deficit of vitamin B12
was diagnosed, probably due to a decline in attachment
to transcobalamine II (a physiologic transport protein)
leading to an altered delivery to cells.Treatment with
vitamin B12 injections led to a MMA level of 0.19 umol/L.
Case B: Was diagnosed with a myelodysplastic syndrome
in which excessive production of transcobalamines led to
an elevated vitamin B12.
Case C: Was suspected of liver cirrhosis, in which the
uptake of vitamin B12 itself and its bounded form
(HC-cobalamin complex) in peripheral tissue and
hepatocytes is decreased, resulting in an elevated vitamin
B12 level.
Conclusion: These cases show that the etiology of elevated
vitamin B12 without the use of any supplements may
include not only a functional deficit, but also may be
caused by severe disease entities. It was shown that high
vitamin B12 levels may also be caused by blood disorders,
and liver diseases. Furthermore, solid tumours and inflammatory diseases are potential causes of elevated serum
vitamin B12 levels. In patients with elevated serum vitamin
B12 levels further evaluation in order to rule out severe
disease entities is warranted.
glycyrrhizin causing pseudo-hyperaldosteronism. It is less
known that chewing gum contains glycyrrhizin too. We
want to present a patient who appeared to have pseudohyperaldosteronism due to eating lots of chewing gum.
Case description: A fifty year old man, with a medical
history of hypertension and left ventricular hypertrophy,
went for a health check-up. A hypokalaemia was found
and subsequently he was referred to our hospital. His
medication consisted of perindopril 2mg once a day
and Slow-K 600mg two times a day was started recently
by his general practitioner. His dietary intake was
normal and he did not have complaints like diarrhea or
vomiting. Clinical examination showed a blood pressure of
160/90 mmHg. Serum potassium level was 2.9 mmol/L
(normal 3.5-5.1 mmol/L), urine potassium level 59 mmol/L,
serum renin level 0.25 pmol/L (normal; 0.3-7.22 pmol/L)
and serum aldosterone level 28 pmol/L (normal 110-860
pmol/L). Repeated anamnesis revealed that he took six
to ten packets of chewing gum a day and lots of throat
lozenges. Interruption of this habit normalized his blood
pressure, serum potassium, renin and aldosterone levels
and Slow-K could be stopped.
Discussion: This case illustrates that not only liquorice, but
also chewing gum en throat lozenges can cause pseudohyperaldosteronism. Due to the ingredient glycyrrhizin,
the enzyme 11-B-HSD is being inhibited, causing reduced
conversion of cortisol to cortisone. The overabundance of
cortisol leads to increased mineralocorticoid action in the
kidney, causing salt retention and therefore hypertension,
and potassium loss. To the best of our knowledge only
four similar cases have been described before. In the case
of unknown exogenous mineralocorticoid administration,
it can be useful to not only ask the patient for the use of
liquorice, but also for the use of chewing gum.
C172 Chewing gum causing pseudo-hyperaldosteronism
Introduction: The syndrome of inappropriate secretion of
antidiuretic hormone (SIADH) can have various causes,
such as neoplasms or medication. Here we report a case
of SIADH secondary to an Epstein Barr Virus infection.
Case report: A twenty five year old woman was admitted
with fever, mild dyspnea and cough. Medical history
revealed Crohn’s disease since the age of twelve. At the
time of presentation she was in complete remission with
Azathioprine 150 milligrams once a day. Last use of corticosteroids had been in 2003. Physical examination showed
C173 SIADH secondary to an acute Epstein Barr infection
L. Louter1, F. Borst2, J.T. Brouwer2
1
IJsselland Hospital, Department of Internal Medicine, Prins
Constantijnweg 2, 2906 ZC CAPELLE A/D IJSSEL, the
Netherlands, e-mail: [email protected], 2Reinier de
Graaf Gasthuis, DELFT, the Netherlands
E.H.C.C. Janssen, C. van Guldener, A.A.M. Ermens,
J.W.J. van Esser
Amphia Hospital, Department of Internal Medicine,
Molengracht 21, 4818 CK BREDA, the Netherlands, e-mail:
[email protected]
Introduction: Abundant use of liquorice can result in
hypertension and hypokalaemia due to the ingredient
123
a sub febrile temperature of 37.7°C and a blood pressure
of 110/65 mm Hg. There were no enlarged lymph nodes
or hepatosplenomegaly. Neurological examination was
normal. Laboratory results revealed: serum sodium level
126 mmol/L, serum osmolality 246 mosmol/kg, potassium
4.5 mmol/L, creatinine 47 umol/L, uric acid 0.7 mmol/L,
TSH 0.53 U/L, ESR 57 mm/hour, CRP 32 mg/dl. Peripheral
blood smear showed atypical lymphocytes. Urine sodium
was 149 mmol/L, and urine osmolality 586 mosmol/kg.
Chest X-ray was clear. Serological findings showed a primary
Epstein Barr virus infection with anti-viral capsid antigens
IgM and IgG both positive (248 U/ml and > 160 U/ml). EBV
DNA-PCR was positive (2.42x 103 geq/ml). Cytomegalovirus
and Hepatitis A, B and C were ruled out. An adrenal insufficiency was excluded by an ACTH stimulation test.
Discussion: In our case, the hyponatremia was explained
by SIADH secondary to an EBV infection. The patient
did use Azathioprine. However, she had used this for
several years, and a relationship between Azathioprine
and SIADH has never been described. The hyponatremia
was treated with a fluid restriction of 750 milliliters a day.
Serum sodium concentration normalized 8 weeks after
the first presentation. Contrary to other viruses such as
varicella zoster virus and human immunodeficiency virus,
SIADH as a consequence of an EBV infection is rare. To
our knowledge, only five cases have been described. The
mechanism behind the development of SIAHD after an
EBV infection is unknown. Previous case reports describe
it could involve stimulation of the hypothalamic-neurohypophyseal system. Acute pandysautonomia has been
suggested as an explanation in a case of SIADH secondary
to an acute cytomegalovirus infection. However, we have
no data in our case to support this hypothesis.
Conclusion: An acute EBV infection could cause SIADH
even though it is rare. The precise mechanism remains
unclear.
upon MR-imaging. Increased levels of ferritin without
iron overload, in association with (early onset) cataract are
pathognomonical for the Hereditary Hyperferritinemia
Cataract Syndrome (HHCS). Sanger sequencing of the
L-ferritin gene showed a known pathogenic mutation.
HHCS is an autosomal dominant disorder, caused by
various mutations in the L-ferritin gene located on
chromosome 19. Affected individuals show dysregulated
translation of L-ferritin that is independent of the availability of iron, which results in accumulation of L-ferrtin
in the lens epithelium. Typically, HHCS does not lead to
iron overload and hence does not require phlebotomies.
C175 Hyperammonemia due to very late-onset Ornithine
Carbamyoltransferase deficiency
A. van de Logt, M. Janssen
Radboud University Medical Centre, Department of Nephrology,
Geert Grooteplein-Zuid 10, 6525 GA NIJMEGEGEN, the
Netherlands, e-mail: [email protected]
Case: A 59-year old woman, with a medical history of
mental retardation after perinatal asphyxia, diabetes
mellitus type II, cerebrovascular accident and myelodysplastic syndrome was referred to our hospital because of
coma due to hyperammonemia after she was treated for a
fracture of the pelvis. The ammonia level was 280 umol/L.
Laboratory investigation showed normal liver enzymes,
albumin and coagulation factors. She was treated with a
high caloric/Low protein diet, lactitol, infusion of citrulline
and sodium benzoate. She became fully conscious at an
ammonia level of 100 umol/L. Acquired disorders as
explanation for the hyperammonemia were excluded: liver
failure, portosystemic shunt, infection with urease positive
bacteria, urinoma and bacterial overgrowth. Metabolic
investigations showed an elevated glutamine and alanine,
suspect for OTC deficiency. Citrulline was normal. Orotic
acid could not be demonstrated in urine. DNA investigations for OTC deficiency are being performed at this
moment.
Discussion: This is one of the first patients in literature
in who the diagnosis of OTC deficiency is made at this
age. She had no medical history of coma, but she was
mentally retarded. This was always considered due to
perinatal asphyxia. She had one son and didn’t have
problems during pregnancy or delivery. OTC deficiency,
the most common urea cycle defect, is a X-linked
disorder. Especially the phenotype in females cannot
be predicted because of random X-inactivation of the
X-chromosome. A part of them becomes symptomatic
later in life and symptom onset coincides with a precipitating factor such as infection, surgery, physiological
stress, excess protein intake or a trauma as in this case.
C174 A 43-year-old female with an increased level of
ferritin
D.M. Cohn, S. van Wissen
Onze Lieve Vrouwe Gasthuis, Department of Internal Medicine,
Postbus 95500, 1090 HM AMSTERDAM, the Netherlands,
e-mail: [email protected]
A 43-year-old Caucasian female attended our outpatient
clinic because of an increased ferritin level (1432 ug/L), as
recently determined by her general physician. She reported
bilateral cataracts since the age of 3 and lens replacements
at the age of 15. Futhermore, there were six first-degree
and eight second-degree family members who had been
diagnosed with early onset cataract. The iron level was
not increased (11 ug/L) and iron overload was excluded
124
carefully revising the patient’s history it seemed that our
patient had received lysine acetylsalicylate (LAS) intravenously in the ambulance. Salicylate was found highly
concentrated in the first blood sample (> 800 mg/L) and it
turned out that the first blood sample was taken from the
intravenous catheter. As LAS carries no electric charge
and has to be metabolised to salicylate in the liver, no high
anion gap was found, which is usually seen in salicylate
intoxication. A few months thereafter, another patient
presented with chest pain in which similar lab results were
found. Salicylate was highly elevated in the blood sample
which was also taken from the intravenous catheter.
Conclusion: High-osmolality gap hypertonic hyponatremia has a broad differential diagnosis. In some cases
it can be very hard to find the causative agent. As we have
demonstrated, preanalytical errors should be considered.
In our case the hypertonic hyopnatremia was caused by
blood taken from the intravenous catheter that was used
for salicylate infusion, resulting in a diluted blood sample.
The diagnosis of OTC deficiency is confirmed when
plasma amino acid analysis reveals elevated glutamine
and alanine levels and decreased citrulline level, and
orotic acid is found in the urine. The diagnosis can be
confirmed by molecular genetic studies. The therapeutic
principles for management of OTC deficiency include
minimizing endogenous ammonia production, protein
catabolism, and nitrogen intake; administration of urea
cycle substrates that are lacking as a consequence of the
enzymatic defect; and administration of compounds that
facilitate the removal of ammonia through alternative
pathways. Since OTC deficiency and diabetes have
different dietary implications the treatment of this patient
challenging.
Conclusion: Hyperammonemia due to urea cycle disorders
can occur at any age. It is important for the internist to
consider a metabolic disorder at every age.
C176 Unexplained hypertonic hyponatremia? Consider a
salicylate effect
C177 Rat poison: A rat with an unexpectedly long tail
N. Zelis, M.T.M. Raijmakers, G.J.M. Mostard
Atrium Medical Centre, Department of Internal Medicine,
Henri Dunantstraat 5, 6419 PC HEERLEN, the Netherlands,
e-mail: [email protected]
M.J.W. van den Berg1, C. Kramers2
1
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6800 TA ARNHEM, the Netherlands,
e-mail: [email protected], 2Radboud University
Medical Centre, NIJMEGEN, the Netherlands
Introduction: Most patients presenting with hyponatremia
have a low or normal plasma osmolality. Hypertonic
hyponatremia is seen in patients with hyperglycemia or
high osmolality gap often caused by high ethanol concentrations. When the ethanol concentration is low, it may be
hard to find the source for the elevated osmolality gap.
Case: A 43-year old female presented to the emergency
department with acute onset of pain in the epigastric
region. She has a history of M. Crohn and epigastric
discomfort for which she takes omeprazole. In the
emergency department the pain has resolved and she
feels fine. On physical examination blood pressure was
134/77 mmHg, pulse rate was 93 bpm, saturation was 99%
breathing ambient air and there was no fever. Laboratory
tests revealed a hypertonic hyponatremia (sodium concentration of 123 mmol/L with an osmolality of 340 mOsm/
kg). Other laboratory results showed decreased levels of
bicarbonate (16 mmol/L), potassium (3.4 mmol/L and
albumin (34.1 g/L). Glucose level was normal (4.8 mmol/L)
and no ethanol was present. We calculated the osmolality
and anion gap and found these to be elevated (86.5 mOsm/
kg) and normal (8 mmol/L), respectively. Urine analysis
showed a sodium concentration of 34 mmol/L with an
osmolarity of 200 mOsm/kg in the absence of ketones.
Because these results did not correlate with the clinical
presentation of our patient we analysed another blood
sample in which all laboratory tests were normal. After
Introduction: Long acting vitamin K antagonists (superwarfarins) are used as rat poison. Some of these have a very
long half-life (up to 12 days). Difethalione is a superwarfarin with a relatively short half-life (48 hours).
We present a case of a severe intoxication with difethialone, a second generation coumarin derivate, which
unexpectedly had an extremely long half-life.
Case: A 33 year old woman with a medical history of
anorexia nervosa presented at the emergency room after
deliberately ingesting 100 to 200 grams of Rodilon
(0.0025% difethialone) a day, for 10 consecutive days. The
total dose was 1.6 kilograms Rodilon (40 mg difethalione).
Blood tests revealed a PT of > 90 seconds, INR > 12. She
had no signs of hemorrhage. In the literature the reported
half-life of difethalione is 48 hours, so it was estimated that
the patient should be treated for approximately 15 days. In
addition the literature advices 20-40 mg vitamin K daily.
Our patient needed 80 mg vitamin K daily to normalize
coagulation tests. In addition, after 30 days of treatment
clotting times were still prolonged and vitamin K therapy
remained necessary. The patient remained admitted at the
closed psychiatry ward because of persisting suicide wish.
After 85 days of treatment she refused the vitamin K and
her INR immediately rose to 11.7 (PT > 90sec). Only after
a treatment of 150 days it was possible to stop vitamin K.
125
Both the heparin induced platelet activation assay and
heparin ELISA were positive, confirming the clinical
diagnosis of HIT.
A CT-scan performed a month after admission showed
normal adrenals. Hemorrhage of the adrenals, without
necrosis, is therefore probably more likely in this case.
Discussion: Adrenal hemorrhage and hemorrhagic
necrosis are rare complications of heparin-induced trombocytopenia (HIT), occuring in about 3 to 5% of HIT
cases. The pathogenesis is adrenal vein trombosis, with
secondary hemorrhage and infarction. Typical complaints
are abdominal or flank pain. Acute adrenal insufficiency
is a dangerous complication of extensive bilateral adrenal
hemorrhage and may even be fatal if unrecognized.
Conclusion: Pain in the back and both flanks can be caused
by adrenal hemorrhage due to heparin-induced thrombocytopenia. This diagnosis should be considered in patients
recently started on heparin.
Several Difethialone levels were determined during her
treatment which revealed a half-life of approximately 40
days. There were no indications of saturating kinetics.
Discussion: The reported half-life for difethialone of 48
hours did not apply for this patient. We considered the
possibility that she kept intoxicating herself with difethialone, but deemed this very unlikely. The metabolic route
of difethalione is unknown and possibly our patient has a
metabolic defect. Because of the high difethialone serum
levels, the patient also needed a very high dose (80 mg
daily) of vitamin K, with vitamin K serum levels which
were 35x the upper limit of normal to maintain a normal
clotting time.
Conclusion: In the literature difethalione is known as a
superwarfarin with a relatively short half-life (48 hours).
Unexpectedly in our patient half-life appeared to be
extremely prolonged. Clinicians should be aware of
extremely prolonged half-life of difethalione in individual
patients and the very high dose of vitamin K that might be
needed to reach and maintain normal clotting times.
C179 An elderly patient presenting with elevated lactate
levels, cardiac ischemia and edema
C178 Adrenal hemorrhage due to heparin-induced
thrombocytopenia
S.H.M. Robben, C.E.M. de Mooij, A.H.E. Herbers
Jeroen Bosch Hospital, Department of Internal Medicine,
Postbus 90153, 5200 ME ’S-HERTOGENBOSCH, the
Netherlands, e-mail: [email protected]
G.L.G. Haverkamp, V.J. Mathot, A.M. Lagaay,
B.J. Borgstein, A. Griffioen-Keijzer, G.H. Wattel-Louis
Spaarne Hospital, Department of Internal Medicine,
Spaarnepoort 1, 2134 TM HOOFDDORP, the Netherlands,
e-mail: [email protected]
Case report: An 85 year old patient was referred to our
emergency department because of recurrent falls and
behavior change. On presentation, he complained of
nausea and mild abdominal pain. Physical examination
showed an ill-groomed, tachypnoeic, oliguric and
hypothermic man. He had a cardiac murmur, crepitated
slightly over his lungs and had tenderness in his lower
abdomen, without guarding. Further, he suffered marked
edema of the upper and lower extremities. Laboratory tests
showed a macrocytic anemia (Hb 5.9 mmol/L, MCV 109
fl, folic acid 2.5 pmol/L), elevated creatinin (134 umol/L),
elevated liver tests (bilirubin 35 umol/L, ASAT 80 u/L,
ALAT 32 u/L, LD 608 u/L, AF 157 U/L, gGT 63 U/L),
elevated cardiac enzymes (CK 644 U/L, trop I 0.80 ug/L)
and a spontaneous INR of 1.5. Blood gas analysis demonstrated a combined respiratory alkalosis and metabolic
acidosis with a significantly elevated lactate (13,3 mmol/L).
A CT-thorax/abdomen was made, which showed pleural
effusion, but no signs of intestinal ischemia. The ECG
showed low voltage complexes, a prolonged PR interval,
and slight ST-depression. Based upon the patient’s
neglected appearance, the elevated lactate, edema and
the oliguria, wet beriberi was suspected. Therefore, we
started treatment with thiamine (250 mg 1dd1 i.m.) and
furosemide. As sepsis with multi organ failure could not
be ruled out, antibiotics were started as well. Upon this
Case: A 59-year-old man, without any important medical
history, presented to our emergency department with
acute pain in the back and flanks. He was started on
coumarin and heparin since a week because of deep
venous thrombosis.
Physical examination showed besides an obvious pain
in both flanks, no abnormalities. Urine screening and
laboratory results were normal, except slightly elevated
transaminases. A CT-scan was performed which excluded
acute pathology, such as pulmonary embolism or aortic
dissection. However, the CT-scan showed bilaterally
slightly enlarged adrenals with induration and stranding
in the surrounding fat tissue.
Our patient remained substantially painfull during
admission and developed a thrombocytopenia. A suspicion
arose of heparin-induced thrombocytopenia (HIT). The
patients complaints and the abnormalities seen on CT-scan
could be explained due to secondary adrenal hemorrhage,
possibly with necrosis.
The heparin was discontinued, while continuing coumarin
and the patient’s complaints improved significantly. Also
an increase in platelet count was observed. The synacthen
test showed no abnormalities.
126
and was admitted to the ICU for observation where 100%
O2 was supplied. After 12 hours the methemoglobin level
decreased to 1.2% and the patient was discharged in good
clinical condition.
Discussion: In methemoglobin, a different form
of hemoglobin, the ferrous (Fe2+) irons of heme are
oxidized to the ferric (Fe3+) state, which are unable to
bind oxygen. Furthermore, the affinity for oxygen in
remaining Fe2+ hemes in the Hb-molecule is increased,
resulting in a left shift of the oxygen dissociation curve
and a subsequent acute impairment in oxygen delivery to
tissues. Methemoglobinemia can be congenital, but most
cases are acquired, caused by increased methemoglobin
formation by exogenous agents, such as topical anesthetic
agents, dapsone, chloroquine or nitrites. Alkyl nitrites
(amyl, butyl, and isobutyl nitrites), are inhaled as a recreational drug (‘poppers’) and cause smooth muscle relaxation
and dilation of cerebral blood vessels leading to a pleasant
rush. Symptoms of methemoglobinemia include headache,
fatigue, dyspnea, and lethargy. Higher methemoglobin
levels (> 30%) can lead to respiratory depression, altered
consciousness, shock, seizures, and eventually death.
Conclusion: Cyanosis can be caused by methemoglobinemia, which is most often an acute acquired
condition caused by exogenous agents and is potentially
life-threatening.
treatment, the patient’s lactate gradually normalized and
the edema decreased. After two weeks he was discharged
to a nursing home for further rehabilitation. Additional
history through his informal caregiver revealed that the
patient rarely drank alcohol, but lived on a very limited
diet consisting of bread and meat or seafood. He did not
eat vegetables.
Discussion: Wet beriberi, a disease caused by thiamine
deficiency, is rarely encountered in developed countries.
It is most commonly seen in alcoholics, but as this case
shows should also be suspected in severely neglected
patients. Its fulminant form, Shoshin beriberi, is
characterized by circulatory shock, oliguria, peripheral
cyanosis and lactic acidosis. Therefore, it can be difficult
to distinguish from sepsis with multi organ failure,
especially as thiamine levels are not readily available.
Unfortunately, we did not measure thiamine levels before
starting suppletion.
Conclusion: Wet beriberi is a rare condition, especially in
non-alcoholics. However, it should always be considered in
severely neglected patients presenting with elevated lactate
levels, oliguria and edema, as treatment with thiamine can
rapidly improve their clinical condition.
C180 Pop ‘till you drop
M.A. Sleddering, J.W. van ’t Wout, E.D. Beishuizen
Bronovo Hospital, Department of Internal Medicine,
Bronovolaan 5, 2597 AX DEN HAAG, the Netherlands,
e-mail: [email protected]
C181 A young man with multiple lymphomas and icterus,
a malignant disease?
L. Nieuwenhuizen, R.J. van Alphen
Twee Steden Hospital, Department of Internal Medicine, Dr.
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected]
Case report: A 54-year old man, with an unremarkable
medical history, was seen in the Emergency Department
because of chest discomfort. He reported recurrent short
periods of an unpleasant feeling in the chest since several
hours, without chest pain or dyspnea. At presentation we
saw a pale looking man with blue lips. Pulse oximetry
showed an oxygen saturation of 92% breathing ambient
air with a respiratory rate of 20/min. Blood pressure was
116/77 mmHg with a pulse of 90/min. Further physical
examination was unremarkable. Laboratory test showed
no abnormalities. ECG and X-ray of the chest were normal.
Capillary blood gas analysis showed a pH of 7.39, pCO2 of
5.1 kPa, HCO3- of 23 mmol/L and a methemoglobin level
of 17.6% (reference range: 0.4-1.2%). The medical history
was taken again, but the patient denied any intoxications
and only reported the use of mouthwash and color-rinse
shampoo. After extensive questioning he eventually stated
that during the day, as a lawyer, he was on a bust with
the police at a warehouse were illegal chemicals used for
the fabrication of poppers were found, and he might have
inhaled some chemicals. The patient was diagnosed with
methemoglobinemia caused by the inhalation of poppers
Case report: A 28-year old man, with recent history
of diarrhoea, rectal bleeding loss and rectal ulcer on
colonoscopy, was referred with abdominal discomfort,
weight loss, red skin rash, night sweats, decreased appetite
and icterus. There was no history of tropical trips, no
unsafe sexual contacts or any familiar diseases. His
pregnant wife had no symptoms.
Physical examination showed icteric sclerae, little red
raised spots all over the body, multiple lymphomas
inguinal and hepatic enlargement. Laboratory findings
included total bilirubin 139 mmol/L, conjugated bilirubin
138 mmol/L, alkaline phosphatase 439 U/L, GGT 254
U/L, ASAT 85 U/L, ALAT 178 U/L, LDH 167 U/L. An
abdominal ultrasound showed a pathologic mass in the
amount of the hepatic hilus. After which a CT-scan was
performed under suspicion of a malignant lymphoma.
Biopsy was performed of inguinal lymphoma. At this time
patients situation deteriorated with worsening of icterus,
127
liver enzymes and skin rash. A skin biopsy and serologic
tests for hepatitis, CMV, EBV, HIV, syphilis and parvovirus
were performed. Results showed acute hepatic B infection,
positive syphilis serology and a skin biopsy positive for
syphilis. The pathologist reviewed rectal ulcer biopsy,
which showed an ulcus durum, suiting a Treponema
pallidum infection. With this diagnosis a new history was
taken. Then, finally, patient told us he have had unsecure
sexual contacts with men.
Conclusion: this case report illustrates an example of
infectious disease mistaken for malignant disease which
caused additional anxiety and insecurity at hospital
admission. The case highlights the importance of a
properly conducted history and also the relevance of
repeating this because of unsuspected disease course. It is
also important to realise that Treponema pallidum is not
routinely investigated in colorectal ulcer biopsies.
all pregnancies. It is characterized by itching and elevated
serum bile acid concentrations. Most women also have
elevated total bile concentrations and other cholestatic
laboratory findings may be present. Serum aminotransferases can be highly elevated therefore viral hepatitis
should be considered. Elevation of alkaline phosphatase is
normal in pregnancy due to placental alkaline phosphatase.
GGT levels are mostly normal or slightly elevated, which
is in contrast with other cholestatic conditions. We
experienced difficulties in making the correct diagnosis
because of the high serum aminotransferases and only
slightly elevated total bilirubin levels. Eventually the serum
bile acid concentration confirmed the diagnosis.
Conclusion: During pregnancy, liver tests may be physiologically altered. The laboratory values in intrahepatic
cholestasis of pregnancy differ from the usual findings
in cholestasis.Furthermore, diagnostic and therapeutic
decisions may have consequences for both mother and
fetus. This all together makes the diagnoses of liver disease
in pregnancy challenging and we hope we will be invited to
present a diagnostic protocol and treatment schedule which
would have helped us certainly in this case.
C182 A pink cloud changing into green discomfort
I. Maijers, H.H. van Ojik
Twee Steden Hospital, Department of Internal Medicine, Dr
Deelenlaan 5, 5042 AD TILBURG, the Netherlands, e-mail:
[email protected]
C183 Old anticoagulants and old kidneys
Introduction: We describe a patient with severe itching
during pregnancy. Diagnosis of elevated liver tests is
challenging and needs more attention.
Case report: A 22-year old gravida1 para0 was seen by the
gynaecologist at 31 weeks of gestation with progressive
itching since five days. Her medical history consists of
asthma and pityriasis versicolor. Further history-taking
and physical examination showed no abnormalities. She
used no medication or alcohol. The CTG showed normal
variability. Laboratory investigations revealed abnormal liver
tests (elevated ALAT, ASAT, alkaline phosphatase and total
bilirubin, GGT was normal). We were consulted for analysis
of the elevated liver tests without signs of pre-eclampsia.
An ultrasound of the abdomen was normal. Extensive
serological tests were negative. At 32 weeks the liver tests
worsened. The itching caused sleep disturbances and
mood problems. Finally the bile acid concentration turned
out to be elevated. The final diagnosis was intrahepatic
cholestasis of pregnancy. Ursochol treatment was started
and the bile acid concentration decreased. At > 35 weeks
a healthy daughter was born after a spontaneous delivery.
After a short increase both the liver tests and the bile acid
nearly normalized in the 11 following days. The ursochol
was reduced and discontinued 1.5 months after delivery. The
itching decreased and eventually disappeared. Five months
after delivery the liver tests remain slightly elevated.
Discussion: Intrahepatic cholestasis of pregnancy occurs
mainly in the third trimester of pregnancy, in 0.3-5.6% of
R.M. Nijmeijer, M.P. Kooistra, V. Mattijssen
Rijnstate Hospital, Department of Internal Medicine,
Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, e-mail:
[email protected]
Introduction: There is much ado about the risks and
benefits of the new oral anticoagulant drugs. However,
care should be taken as well when prescribing traditional
anticoagulant drugs, specially in elderly with renal failure.
Case presentation: Case A. An 85-year-old men (65 kg,
eGFR MDRD 30 ml/min/1.73m2) with cardiovascular
disease used acenocoumarol for atrial fibrillation.
He underwent endovascular treatment because of an
ischemic foot. After this, acenocoumarol was restarted in
combination with nadroparin 5700 IE (0.6 ml) twice daily
sc. until INR would be adequate. After using both anticoagulants for seven days, he was readmitted because of
falling, confusion and multiple haematomas. Haemoglobin
concentration had decreased from 6.9 to 4.3 mmol/L,
plasma creatinine increased from 186 to 428 mmol/L. A
CT-scan showed large haematomas in the psoas and medial
gluteal muscles.
Case B. An 80-year-old woman (90 kg, eGFR 44 ml/
min/1.73m2) used acenocoumarol for atrial fibrillation.
She underwent an ERCP procedure with stent placement
(under ‘bridging’ with low molecular weight heparin,
LMWH) because of a carcinoma of the pancreas. After
this, acenocoumarol was restarted and nadroparin 7600
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IE (0.8 ml) twice daily s.c. was continued temporarily.
Three days after dismissal, she was readmitted because
of a collapse. At that moment, she used LMWH for fifteen
days. Haemoglobin concentration had decreased from 7.1
tot 5.2 mmol/L. A CT-scan showed a large haematoma of
the rectus muscle with active bleeding. Also, an acute on
chronic renal failure (serum creatinine 124 mmol/L, eGFR
36 ml/min/1.73m2) had developed due to both hypotension
and compression of the urinary tract by the haematoma.
Discussion: These two cases draw attention to the risks
of LMWH in (elderly) patients with decreased kidney
function. In both cases, nadroparin dose was adjusted to
body weight, but not to kidney function. LMWH dosage
should be lowered by 25-33% in patients with a creatinine
clearance between 30 and 50 ml/min. Below 30 ml/min,
therapeutic LMWH should not be started. Both patients
were over 70 years of age. In this age group, the MDRD
eGFR formula is not validated, and may overestimate the
actual GFR.
Conclusion: In patients with chronic renal failure, LMWH
treatment may be dangerous, especially in the frail and
elderly. In these patients, when coumarins are started, we
may consider treatment with unfractionated heparin until
INR is adequate.
Toxicology screening was negative for alcohol and salicylic
acid. Lactate was 3.2 mmol/L and beta-hydroxybutyric acid
was strongly elevated and later proved to be 5846 umol/L.
This high aniongap and osmolgap metabolic acidosis
in absence of a blood alcohol level, was interpreted as a
diabetic ketoacidosis in the context of a diabetes de novo
and insulin therapy was started. Nevertheless hyperglycemia was rather mild and a new onset type 1 diabetes is
rarely seen at this age.
She was admitted to the ICU for monitoring and treatment.
Glucose levels dropped quickly and acidosis recovered
within 24 hours. There was a high need for potassium.
Insulin infusion was rapidly tapered and eventually
discontinued without reemerging acidosis. Blood glucose
levels remained normal. Later on she admitted prior use of
alcohol. She had drunken so much that she became ill and
was forced to stop drinking a few days before admission.
This explains her negative alcohol blood level at admission.
A final diagnosis of alcoholic ketoacidosis was established.
Key points: In a patient with a history of alcohol abuse,
presenting with a high anion- and osmolgap metabolic
acidosis, alcoholic ketoacidosis should be considered
despite a negative blood alcohol level. In fact, in most
cases described, alcohol at admission is not detectable. A
modest increased plasma glucose can be seen in up to 10%
of patients with alcoholic ketoacidosis.
C184 Not a ‘sweet’ cause of ketoacidosis
I.J.A. de Bruin, B.J.J.W. Schouwenberg, C.J. Tack
Radboud University Medical Centre, Department of Internal
Medicine, Geert Grooteplein 8, 6525 GA NIJMEGEN, the
Netherlands, e-mail: [email protected]
C185 A rare case of syndrome of inappropriate antidiuretic hormone secretion as first manifestation of
rheumatoid arthritis
W. Plattel, L.J.M. de Heide
Medical Centre Leeuwarden, Department of Internal
Medicine, LEEUWARDEN, the Netherlands, e-mail:
[email protected]
Introduction: The most common cause of ketoacidosis is
diabetic ketoacidosis although other causes are possible.
We present a case of ketoacidosis with an alternative cause.
Case: A 51-year-old woman of Russian descent, presented to
our emergency department with tachypnea and confusion.
She had a medical history of depression, auto-intoxications
and alcohol abuse. Although she normally speaks Dutch,
she now mainly spoke Russian which rendered it difficult
to obtain a proper history. She denied taking an overdose of
drugs or alcohol. She had no history of diabetes. At physical
examination she was tachypnoeic (40/min.), her heart
rate was 100 bpm, blood pressure and temperature were
normal. Cardiac and pulmonary evaluation revealed no
abnormalities. Laboratory examination showed a partially
compensated high aniongap metabolic acidosis (pH 7.22,
pO2 17.1 kPa, pCO2 1.1 kPa, bicarbonate 3.4 mmol/L,
base excess -21.5 mmol/L). Blood glucose at admission
17.3 mmol/L, decreased sodium, potassium and chloride
levels (126 mmol/L, 3.3 mmol/L and 86 mmol/L), elevated
creatinin level of 177 umol/L, liver enzymes were elevated.
Besides the elevated anion gap there was an osmolgap.
A 76 year old women was referred to our outpatient clinic
because of a persistent hyponatremia. She had a history
of mitral valve insufficiency and mild sensory polyneuropathy. Three years before, a diagnosis of Sjögren’s
syndrome was made based on hypergammaglobulinemia,
positive SS-A antibodies and dry eyes but no further investigation was performed because symptoms spontaneously
resolved. She did not use medication that could cause
hyponatremia except for amitriptyline for her sensory
neuropathy. There were no sicca symptoms or gait disturbances. Physical examination did not show signs of volume
depletion or edema. There were no clinical or biochemical
signs of liver cirrhosis, renal failure, adrenal insufficiency or hypothyroidism. Laboratory evaluation revealed
a hyponatremia of 126 mEq/L and a low plasma osmolality
of 267 mosm/kg. Urine analysis showed high osmolality
(471 mosm/kg) and a high sodium concentration
129
(75 mEq/L) consistent with the diagnosis of syndrome of
inappropriate antidiuretic hormone secretion (SIADH).
After cessation of amitriptyline hyponatremia did not
resolve. Subsequent analyses for neurologic, infectious,
malignant or pulmonary causes of SIADH were negative
and SIADH without apparent etiology was concluded. Fluid
restriction alone was insufficient but the addition of the
vasopressin 2 receptor antagonist tolvaptan resulted in near
normalization of sodium concentration.
Six months later, she developed a polyarthritis of her handand knee joints. Serologic evaluation showed high levels
of rheumatoid factor and anti cyclic citrullinated peptide
antibody consistent with the diagnosis of rheumatoid
arthritis. Therapy with methotrexate was initiated on
which symptoms gradually improved. Together with
improvement of rheumatic symptoms hyponatremia also
gradually recovered after which tolvaptan treatment could
be discontinued. The SIADH was concluded to be the first
sign of her developing rheumatoid arthritis.
SIADH is a disorder of fluid balance which results from
the excessive release of antidiuretic hormone leading to
hyponatremia. There are many systemic diseases and
drugs associated with SIADH but the association with
rheumatoid arthritis is not very well established. Only
a few cases describing SIADH as a rare complication
of rheumatoid arthritis exist in literature. In our case
resolution of SIADH with control of the disease supports
the role of active inflammation as a causative factor. An
additional role for her Sjögrens syndrome can not be ruled
out although no signs or symptoms were present at time
of diagnosis of SIADH or during follow-up.
In conclusion, we describe a patient with SIADH as a first
manifestation of rheumatoid arthritis.
III, myocardial infarction, cerebrovascular accident,
diabetes, severe osteoporosis and rheumatoid arthritis.
This bed-ridden patient, who had been constipated for
several days, was administered a rectal sodium-phosphate
enema after which the patient did not produce any feces.
Prior to the administration of the enema electrolytes were
within the normal range. Subsequent blood tests, however,
revealed an increase of serum phosphate from 1.3 mmol/L
to 4.85 mmol/L and a calcium decrease from 2.21 mmol/L
to 1.58 mmol/L (ionized 0.92 mmol/L). 25-OH vitamin D
was 126 nmol/L and parathormone 14 pmol/L. Phosphate
and calcium normalized within 3 days after hydration and
calcium administration. No clinical symptoms of hypocalcaemia were observed.
Discussion: A medline search using the terms
(Hypocalcemia OR Hypocalcaemia OR Calcium) AND
(Enema OR Laxative OR Clyster) identified a review and
several case reports describing a total of 58 patients.
Patients’ risk increasing characteristics described in
these studies were chronic renal failure, diseases altering
intestinal motility, elderly and children. Complications
included renal failure, tetany, multi-organ failure, coma,
respiratory failure and death.
Conclusion: Our case demonstrates that even rectally
administered phosphate may cause a hyperphosphatemia
in a potentially toxic range. Considering the amount
of enemas prescribed, the percentage of patients with
severe complications is limited, however, potentially lifethreatening. Enemas containing phosphate should be
administered with caution – particularly to the elderly or
children – and not to patients with chronic renal failure
and impaired intestinal motility. If the enema is not
cleared within 5-10 minutes, the serum levels of calcium
and phosphate should be determined.
C186 Severe hypocalcaemia after a rectal sodiumphosphate enema. Patients at risk for a phosphate
enema intoxication
C187 Abdominal silicosis causing small bowel volvulus
D.P. Boer, L. Makkus, E.F.H. van Bommel
Albert Schweitzer Hospital, Rietveld-erf 15, 3315 DA
DORDRECHT, the Netherlands, e-mail: [email protected]
N.F. Schroten, M. Feenstra-Harthoorn, M.C. Weijmer
St Lucas Andreas Hospital, Department of Internal
Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the
Netherlands, e-mail: [email protected]
We report a case of a 65 year old man presenting with
a small bowel volvulus caused by enlarged abdominal
lymph nodes due to silicosis. Although rare abdominal
silicosis is described in post mortem studies, for as far as
we know this is the first case of abdominal silicosis proven
by life. Abdominal silicosis is most likely explained by
the presence of a lymph system from the thorax to retroperitoneal lymph nodes. Silicosis should not been forgotten
as a possible cause of enlarged lymph nodes especially
in patient with a history of exposure to dust and silica.
Pathology shows double breaking material in affected
lymph nodes.
Introduction: Millions of enemas are administered in and
outside hospitals worldwide and are generally considered
harmless. However, even a simple enema may cause life
threatening side effects in certain patients.
Case: We present a case of a 75-year old woman that
developed severe hypocalcaemia and hyperphosphataemia
following a single rectal sodium-phosphate enema. The
patient was admitted because of severe back pain caused
by progression of osteoporotic vertebral fractures. Her
medical history included chronic kidney disease stage
130
C188 Tetraplegia after laparoscopic cholecystectomy
described in PRES. The abnormalities in PRES are mostly
reversible when therapy is promptly started.
Conclusion: Our case shows the importance of appropriate
family history taking in patients with a non-specific
clinical presentation. Although AIP is relatively rare,
physicians should be aware of this condition, for delay
in treatment may result in slower response and possible
neurological sequelae.
J.W.M. Nin, F.J.H. Magdelijns, F. Laugs, A.A. Postma,
E.M.E. Bouwmans
Maastricht University Medical Centre, Department of Internal
Medicine, P. Debyelaan 25, 6229 HX MAASTRICHT, the
Netherlands, e-mail: [email protected]
Case: A 54-year-old woman with a medical history of
depression visited the emergency department (ED) on two
consecutive days with abdominal pain. The abdominal
ultrasound showed bile sludge without evidence for choledocholithiasis. She was admitted with biliary colic and
underwent a laparoscopic cholecystectomy. The surgical
specimen showed neither signs of cholelithiasis nor
inflammation. Ten days after the cholecystectomy she
visited the ED with abdominal pain. She was admitted for
observation and developed tetraplegia within three days.
A CT-scan showed a post-cholecystectomy biloma. A brain
MRI showed bilateral patchy white matter hyperintensities in the posterior territory as well as in the frontal and
parietal regions suggesting posterior reversible encephalopathy syndrome (PRES). At that time patient’s partner
revealed that two of patient’s siblings were diagnosed with
acute intermittent porphyria (AIP). Urine portion analyses
showed elevated uroporphorin and coproporphyrin.
Porphobilinogen (PBG) analysis was not possible during
the weekend. Treatment for an AIP attack was started,
i.e. heme arginate, carbohydrate loading and analgesics.
A second AIP attack with neurologic deterioration and
abdominal pain was initiated due to experienced stress.
This time, PBG in a urine portion was elevated. Treatment
was restarted and within days she improved and could
move her limbs again. Genetic analysis did not show the
mutation found in patient’s siblings, which could suggest
a de novo mutation. Two months after initial presentation,
the radiological diagnosis PRES was confirmed by showing
recovery of the occipital white matter lesions, while some
residual abnormalities in the frontal and parietal regions
were still present.
Discussion: The porphyrias are a group of mainly inherited
metabolic diseases that result from partial deficiency
of individual enzymes in the heme synthesis pathway
and accumulation of pathway intermediates. The most
common variant is AIP characterized by episodic, lifethreatening neurovisceral attacks, but symptoms may be
non-specific and include abdominal pain, constipation,
vomiting, and neuropathic symptoms. During acute
attacks, urinary PBG is virtually always increased and is
not in any other medical condition. Reversible MR abnormalities in porphyria attacks are documented. The hyperintense lesions can be reversible and are similar to those
C189 Tear-drops without sadness
Y.H.M. Krul-Poel, M. Westerman, F. Stam
Medical Centre Alkmaar, Department of Internal Medicine,
Wilhelminalaan 12, 1815 JD ALKMAAR, the Netherlands,
e-mail: [email protected]
Introduction: Dacrocytes (a ‘tear-drop cells’) are usually
interpreted as characteristic for the presence of myelofibrosis. We describe a women with a severe anemia with
dacrocytes found in the peripheral blood smear caused by
a severe vitamin B12 (cobalamin) deficiency.
Case report: A 56-year old women was referred to the
emergency room with progressive fatigue, loss of appetite
and 5 kg of weight loss. Her medical history mentioned an
auto-immune hypothyroidism for which she was treated
with levothyroxin. Physical examination demonstrated
a pale women without lymfadenopathy or hepatosplenomegaly. Laboratory testing showed the following abnormalities: hemoglobin 4.3 mmol/L, mean corpuscular volume
117.5 fl, reticulocytes 0.028 x 1012/L, thrombocytes 70 x
109/L and leucocytes 3.2 x 109/L. Lactate dehydrogenase
was raised to 3400 U/L. Her thyroid function was normal
with a thyroid stimulating hormone level of 1.2 m U/L. The
peripheral blood smear demonstrated hypersegmentation,
strong anisocytosis and several dacrocytes. Despite the
strong association between dacrocytes and myelofibrosis,
the thought of an vitamin B12 deficiency raised, based on
pre-existing auto-immune disease, the strongly elevated
mean cell volume and hypersegmentation. Her vitamin
B12 concentration was indeed strongly decreased: 36
pmol/L (normal value 135-675 pmol/L). Treatment with
intramuscular hydroxycobolamin injections was initiated.
Six weeks later she had no complaints anymore with
normalisation of her hemoglobin and peripheral blood
smear.
Conclusion: This case demonstrates that dacrocytes are not
pathognomic for myelofibrosis and that they can be seen in
a severe vitamin B12 deficiency.
131
C190 What you see is what you get. How erythrocyte form
points to specific mutations in congenital hemolysis
due to membrane abnormalities
imply that the morphology of the red cells has been investigated. A systematic approach combined with cross talk
to clinical chemists at their benches and progress in DNA
technology comes to help the clinicians at the bedside. A
“simple” bloodsmear is a basic test in elucidating the cause
of hemolytic anemia.
R. Bijleveld, M.J.M. Diekman
Deventer Hospital, Department of Internal Medicine, Nico
Bolkesteinlaan 75, 7416 SE DEVENTER, the Netherlands,
e-mail: [email protected]
C191 High Anion Gap Metabolic Acidosis due
to 5-Oxyproline; to treat or not to treat with
N-acetylcysteine?
A 20-year old Caucasion female presented with jaundice.
Her previous history mentioned an episode of hemolytic
anemia three years earlier due to parvo B19 infection.
At that time laboratory investigation revealed no signs
of hemoglobinopathy, no enzyme deficiencies and a
normal amount of spectrin and normal expression of
Band 3 protein. One year later a second hemolytic episode
occurred due to an EBV infection. Five days before consultation she became acutely ill with nausea, vomiting and
diarrhea when travelling in Spain. Symptoms abated
spontaneously but she became jaundiced. On examination
she was not acutely ill but icteric with normal vital signs
and without hepato-splenomegaly. Results of laboratory
investigations pointed to hemolysis as the cause of the
jaundice. A presumptive diagnosis of mild infectious
enterocolitis with concomitant hemolysis was made. After
a wait and see policy she recovered.
G6PD deficiency which might have been missed (in the
first) episode due to a normal enzyme content in young
erythrocytes, was excluded by retesting three months
later. Decreased levels of haptoglobin persisted as a sign
of a mild degree of chronic compensated hemolysis. The
bloodsmear showing abnormal erythrocyte morphology
with poikilocytosis and stomatocytes and decreased
osmotic resistance and abnormal osmotic erythrocyte
deformability found on ektacytometry pointed towards
a vulnerable erythrocyte membrane. Molecular DNA
analysis revealed compound heterozygoty for a-spectrin
(SPTA 1 gene) and band 3 (SLC4A1 gene) mutation
The deformability of the erythrocyte is due to its specific
cell membrane structure. Transmembrane proteins
anchor an intracellular cytoskeleton which can contract by
interaction of actin/myosin molecules. The cytoskeleton
takes the form of a heaxagonal filamentous meshwork
of various proteins, notably spectrin. Derangements in
each component of the cytoskeleton can lead to characteristic shapes of the erythrocyte. In general heterozygous
carriers of a mutation have a normal phenotype, because
the abnormal allele is sufficiently compensated by the
wild-type allele. Homozygotic mutations in proteins which
are involved in the vertical movement cause spherocytosis,
while mutations in proteins which are involved in the
horizontal interaction cause elliptocytosis.
Although a laboratory analysis report mentions results
of a (leukocyte) blood cell “differentiation” this does not
A.J.J.M. Cloin
Maastricht University Medical Centre, Department of Internal
Medicine, Postbus 5800, 6202 AZ MAASTRICHT, the
Netherlands, e-mail: [email protected]
Introduction: We present the case of a 59-year-old man
with High Anion Gap Metabolic Acidosis (HAGMA) due
to 5-Oxyproline which we treated with N-acetylcysteine
and measured the acidosis levels and 5-oxyprolinuria for
12 hours. 5-oxyproline is a relatively rare cause of High
Anion Gap Metabolic Acidosis. 5-oxyproline is a metabolite
in the gamma-glutamyl cycle of wich glutathione is the
endproduct. Several risk-factors have been identified as
a possible cause for high 5-oxyproline levels. Treatment
of this potentially deadly condition is supportive care and
removal of risk-factors. N-acetylceisteine administration is
also recommended in several publications. In our patient
with HAGMA due to high 5-oxyproline levels we administered N-acetylceisteine in controled condicions on the
ICU and measured the levels of acidosis, 5-oxyprolinuria
for 12 hours.
Case: At consultation for the orthopedic surgeon for a
patient who “wasn’t doing well” showed us a 59-year-old
man with heavy Kussmaul-breathing. Relevant medical
history was stomachband and pancreaticobiliary deviation
according to Scopinaro. He was initialy admitted for a
total hip prothesis, complicated by prothesis infection.
Arterial bloodgas showed evident metabolic acidosis
(pH 7.21, pCO2 1.2 kPA, pO2 25.6 kPA, bicarbonate
3.6 mmol/L, BE -21.9, Sat 95%). A high aniongap (24.5
corrected for hypoalbuminemia). And normal osmolgap
(0.8) were calculated. We concluded this patient was
suffering from HAGMA. All other possible causes for
metabolic acidosis were ruled out and 5-Oxyproline levels
in a urine sample was 5.6 mmol/mmol creatinine. More
than 5000 fold of normal urinelevels. We identified
several riskfactors: malnutricion after Scopinaro surgery,
treatment with flucloxacilline, renal failure and high dose
paracetamol use. Because of risk of exhaustion the patient
was transferred to the ICU.
5-oxyproline is a metabolite of a normaly secondary
pathway in the gamma-glutamyl cycle. In certain
132
conditions 5-oxyproline acumulates and causes an acidosis.
The rationale behing supplementing N-acetylcysteine is
that gluthationlevels would rise and thereby gluthatione
regains the negative feedback on gamma-glutamyl
cysteinesynthetase. We suspected N-acetylceisteine
suppletion might worsen the acidosis by augmenting the
5-0xyproline production. In controlled ICU conditions we
measured the acidosislevels and 5-oxyprolinuria levels
for 12 hours while supplementing. The acidosis cleared
slowly and 5-oxyprolinuria decreased in this timeframe.
Hereby we present a case in which it seemed not harmful
to supplement N-acetylcysteine in HAGMA due to high
5-oxyproline levels.
hemochromatosis and schistosoma were negative. Further
histologic analysis of a liverbiopsy, bone marrow biopsy
and even biopsy of the spleen were all unremarkable.
PET-CT scan showed no evidence for lymphoma, nor
signs of primary splenic disease. We concluded that our
patient most likely suffered from non-cirrhotic portal
hypertension, and initiated diuretic treatment. However,
the ascites was resistent to therapy and numerous paracentesis were performed. Despite the signs of portal hypertension, initially detected by abdominal ultrasound,
invasive measurement of the hepatic venous pressure
gradient could not confirm this diagnosis. Because
the patient’s clinical condition rapidly deteriorated, we
decided to proceed to a splenectomy. After an uncomplicated procedure, the spleen’s histology showed a splenic
marginal zone lymphoma. Treatment with rituximab was
initiated and the patient’s clinical condition improved
significantly. The development of ascites decreased
slowly. Lymphatic system invasion by lymphoma cells was
suggested as a possible cause for the recurrent ascites.
Conclusion: The differential diagnosis of ascites and
splenomegaly is extensive and sometimes only splenectomy
will reveal the diagnosis
C192 Exploring the cause of ascites: still the usual
suspects?
A.M. Siegel, S. Anten, A. Iglesias del Sol
Rijnland Hospital, Department of Internal Medicine, Simon
Smitweg 1, 2353 GA LEIDERDORP, the Netherlands, e-mail:
[email protected]
Introduction: Splenomegaly and ascites are associated
with a wide variety of diseases. It may cause a diagnostic
challenge when standard tools seem insufficient.
Case: A 78- year old man presented at our outpatient
department with asymptomatic splenomegaly. Further
physical examination was unremarkable, except for a
palpable spleen. Extensive laboratory testing revealed mild
thrombocytopenia and an elevated lactate dehydrogenase
(LDH). Abdominal ultrasound showed a pathologically
enlarged spleen and increased blood flow in the portal
vein, indicating portal hypertension. Additional laboratory
testing showed no signs of viral infection nor auto-immune
disease. During one-year of follow up no progression of the
enlargement was seen, making lymphoma unlikely. Patient
was discharged from follow-up.
Two years later, our patient returned with fatigue and
progressive abdominal distention. This time, laboratory
testing revealed a normocytic anemia, lymfopenia, thrombocytopenia, and an increase in LDH and cholestatic liver
enzymes. Abdominal ultrasound revealed progressive
splenomegaly and a small amount free abdominal fluid.
An additional CT scan showed splenomegaly, and ascites,
but no signs of hepatic cirrhosis or portal or splenic vein
thrombosis and no lymphadenopathy. Analysis of the
ascites was performed and gave evidence for a transudate
origin, testing for tuberculosis was negative. Additional
laboratory analysis showed a high reticulocyte count and
positive Coombs, suggesting auto immune hemolysis,
likely associated with lymphoma. Furthermore, cell type
specific marker typing of peripheral blood was performed,
but no abnormalities where found. Additional tests for
133
INDEX
FIRST AUTHOR
Achterbergh
R.
Agterhuis
D.E.
Alidjan
F.M.F.
Altenburg
S.
Awater
S.P.J.
Baan
J.
Bakker
J.L.
Beers
E.J.
Beijers
A.J.R.
Beijers
A.J.M.
Berg
M.J.W.
Bergeijk
S.J.C.
Berrevoets
M.A.H.
Besseling
R.
Bie
S.
Bijleveld
R.
Bilt
F.E.
Blazevic
A.
Blokken
K.C.C.
Boer
S.E.
Boer
S.A.
Boer
D.P.
Boersma
H.E.
Boink
G.J.J.
Bolhuis
K.
Bons
E.
Boreen
M.C.
Borm
F.J.
Bos
S.
Both
L.
Breedijk
A.
Breugom
A.J.
Breukelen-van der StoepD.F.
Brouns
A.J.W.M.
Brouns
S.H.A.
Brouwers
F.P.J.
Bruin
I.J.A.
Buitenwerf
E.
Burg
L.M.
Bussel
B.C.T.
Calf
A.H.
Carels
R.A.
Caris
M.G.
Carpaij
N.
Claushuis
T.A.M.
Cloin
A.J.J.M.
Cohn
D.M.
Crane
R.F.
Dickinson
M.G.
Dijk
M.
Dongen
C.M.P.
Douma
J.A.J.
Dresselaars
H.F.
Dreyer
G.J.
ABSTRACT NR
van
van den
van
de
van der
de
de
van
van
de
van der
van
van
van
FIRST AUTHOR
C170
C139, C090
C082
C054
C132
C020
O29
O14
C144
C062
C177
C038
O20, C098
C048
C112
C190
O37
C158
C005
C035
C014
C187
C008
C072
C086
C094
C088
C108
C130
O08, C044
C037
C060
O39, C155
C080
O23, O24, C145
C137
C184
C125
C026
C071
C100
C151
C115
C114
C113
C191
C006, C174
C046
C136
C120
C050
O25
O02
C169
Driessen
Drijvers
Eising
Elderman
Es
Exter
Feijter
Geerts
Geerts
Gieteling
Gil
Gisolf
Glas
Guillen
Gulpen
Hakkers
Hal
Halteren
Hamoen
Hassing
Haverkamp
Hazebroek
Hazenberg
Hellemons
Hemmelder
Holm
Hotho
Huang
Huijben
Hulle
Indhirajanti
Janssen
Janssen
Kamps
Kempen
Kiers
Kleinjan
Kloeze
Knevel
Koek
Koning Gans
Kooiman
Kornalijnslijper-Altena
Kort
Kortbeek
Koster
Kouijzer
Kremers
Krol
Krul-Poel
Ladenius
Lagro
Lahdidioui
Langeveld
134
ABSTRACT NR
C.M.L.
J.M.
J.
J.H.
M.J.
P.L.
J.M.
P.A.F.
J.W.H.J.
E.
L.
E.H.
N.A.
S.S.G.
A.J.W.
C.S.
T.W.
H.K.
E.C.
R.J.
G.L.G.
M.R.
I.T.
M.E.
M.H.
P.W.
D.M.
L.
A.M.T.
T.
S.
E.H.C.C.
J.J.B.
M.J.A.
J.A.L.
H.D.
A.
E.
R.
W.N.H.
J.M.
J.K.
R.
J.M.L.
D.
T.D.
I.J.E.
M.N.T.
R.
Y.H.M.
M.
J.
A.
T.J.C.
van
den
de
de
van
van
van der
van
de
de
C058
C133
C089
O31
C107
O36
C045
C022
C111
C103
C121
C095
O30
C004
C027
C123
C097
C033
C011
C091
C178
O16
C019
C102
C085
O33
C142
C159
C061
C075
O07
C030, C172
O10, C150
C143
C031
O22
C052
C116
C041
C163
C096
O27
C025
O19, O26
C168
C153
O18
C171
C087
C189
C157
C165, C166
C055
C093
FIRST AUTHOR
Lap
Laurenssen
Leenen
Levin
Liesting
Logt
Louter
Maijers
Malgo
Markhorst
Meijden
Melsen
Michels
Moek
Moeniralam
Morelli
Newsum
Nieuwenhuizen
Nijmeijer
Nin
Noeverman
Oei
Oever
Oldenburg-Ligtenberg
Pelkmans
Pelt-Sprangers
Pijpers
Plattel
Poel
Raaijmakers
Radersma
Robben
Rood
Roosmalen
Roukema
Sampimon
Santbergen
Scholtes
Schop
Schouten
Schroten
Seijger
Siegel
Sikkens
Sjouke
Slavenburg
Sleddering
Slegers
Smid
Smit
Smit
Smits
Smulders
Soomers
Spil
Stenvers
Tijmensen
Timmer-Bonte
ABSTRACT NR
C.J.G.
N.C.W.
C.H.M.
M.D.
C.
A.
L.
I.
F.
J.G.M.
W.A.G.
W.G.
W.M.
K.L.
H.S.
F.
A.M.
L.
R.M.
J.W.M.
M.J.
R.L.
J.
P.C.
L.G.
J.M.
E.
W.
M.W.M.
S.
M.
S.H.M.
I.M.
S.
W.
D.E.
B.
B.M.J.
A.
V.L.
N.F.
C.G.W.
A.M.
E.C.M.
B.
S.
M.A.
C.A.D.
B.E.
S.
P.M.
M.
Y.M.
V.L.M.N.
W.E.
D.J.
J.E.
J.N.H.
van de
van der
ten
van
van der
van
van
FIRST AUTHOR
C081
O06
O05
O15, C146
C056, C057
C175
C034, C156, C173
C182
O09
C001
C065
C012
O28, C126, C127
C010
C147
C124
C066
C181
C092, C183
C188
C007, C154
C164
C161
C016
O01
C064
O21
C024, C185
C018
C105
C109
C179
C135
C003
C069
C140
C040
C028, C029, C063
C021, C023
C070
C186
C167
C192
O11
O38
C149
C180
O17
O34
C078
C053
C013, C032
C073
C131
C104
C051
O12, C099
C059
Timmermans
Tjwa
Twist
Ursinus
Valk
Veenstra
Veer
Veldhuijzen
Vellinga
Ven
Vergragt
Visschers
Vlasveld
Vleut
Vos
Vos
Vreeswijk
Vries
Vries
Vrijmoeth
Walpot
Weijer
Wetter
Wiebers
Wieringen
Wijngaart
Wijsman
Wit
Witmer
Wlazlo
Woittiez
Zegers
Zelis
Zondag
Zuur
Zwaag
135
ABSTRACT NR
S.A.M.E.G
D.J.T.H.
D.J.L.
J.
H.
T.C.
T.
N.M.H.
A.
A.L.M.
J.
M.J.A.
I.N.
R.E.
N.S.
F.E.
S.J.M.
H.
M.A.
T.
J.M.J.B.
B.A.M.
M.R.
S.
S.D.
H.
C.A.
H.M.
J.L.
N.
L.R.
I.H.A.
N.
W.
A.T.
J.
van
van der
van der
van de
de
de
de
van
van der
de
C141
C043
O03, C079
C083, C134
C117
C101
C160
C129
C118
C074
O04
C122
C002
C106
C036
C049
C119
C138
C017, C076
C039
C077, C148
C068, C152
C047
O13
C128
C067
O35
O40
C110
C015
C009
C042
C176
C084
O32
C162