Available online at www.sciencedirect.com
General Hospital Psychiatry 33 (2011) 604 – 611
Delusional infestation: treatment outcome with antipsychotics in
17 consecutive patients (using standardized reporting criteria)☆
Markus Huber, M.D.a,⁎, Peter Lepping, M.B, Ch.B., M.Sc.b,c , Roger Pycha, M.D.a ,
Martin Karner, M.D.d , Josef Schwitzer, M.D.e , Roland W. Freudenmann, M.D.f
a
Department of Psychiatry, General Hospital-Bruneck, Spitalstrasse 4, I-39031 Bruneck, Italy
b
Glyndŵr University, Wrexham, North Wales, UK
c
Central Wrexham Community Mental Health Team, Betsi Cadwaladr University Health Board, Wrexham Academic Unit, Wrexham LL13 7YP, Wales
d
Department of Radiology, General Hospital-Bruneck, Spitalstrasse 4, I-39031 Bruneck, Italy
e
Department of Psychiatry, General Hospital-Brixen, Dantestrasse 51, I-39042 Brixen, Italy
f
Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany
Received 8 February 2011; accepted 24 May 2011
Abstract
Objective: The multietiological nature of delusional infestation (DI) implies that therapy needs to be customized according to the various
forms of DI (primary/secondary). Usually, treatment of DI is difficult to achieve in psychiatric settings because of the patients' nonpsychiatric
concept of the illness.
Methods: We analyzed the data of all consecutive DI patients seen in the Psychiatric Outpatient Department of the General Hospital
Bruneck/Italy from 1998 to 2010, including structural brain imaging findings. Standardized reporting criteria are applied for the presentation
of the cases in a naturalistic setting.
Results: Our sample consisted of 17 patients. Notably, 15 out of these 17 patients (88%) could be engaged in an antipsychotic treatment trial.
With different, mainly second-generation antipsychotics, all but one patient profited from antipsychotics, at least after substances were
changed: 12 (71%) of the cases reached full remission, and another 2 (12%) had partial remission. The average duration of treatment was
remarkably long: 3.8 years. Eight cases were classified as secondary to a brain disorder or medical condition, four cases were classified as
secondary to psychiatric disorders and five cases fulfilled the criteria for primary DI (i.e., delusional disorder somatic type). All cases
secondary to a brain disorder/medical condition showed macroscopic brain lesions mainly in the basal ganglia.
Conclusions: Our study confirmed previous experience that an excellent clinical outcome can be achieved in unselected patients with
different DI forms provided that patients can be engaged in antipsychotic treatment. Although studies in DI are difficult to conduct,
randomized controlled trials would be desirable to evaluate specific antipsychotic medication in DI in general and in the different forms of
DI. More sophisticated investigations (single photon emission computed tomography and positron emission tomography) than structural
brain imaging (magnetic resonance imaging and computed tomography) are needed to better elucidate underlying brain dysfunction in DI.
© 2011 Elsevier Inc. All rights reserved.
Keywords: Delusional infestation; Classification; Treatment, Antipsychotics; Neuroimaging
1. Introduction
☆
Conflict of interest: P.L. has received honoraria from Ely Lilly,
AstraZeneca and Otsuka in the past 5 years.
⁎ Corresponding author. Tel.: +39 474 586340; fax: +39 474 586341.
E-mail addresses: [email protected] (M. Huber),
[email protected] (P. Lepping), [email protected]
(R. Pycha), [email protected] (M. Karner),
[email protected] (J. Schwitzer),
[email protected] (R.W. Freudenmann).
0163-8343/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.genhosppsych.2011.05.013
Delusional infestation (DI), also known as delusional
parasitosis, is a psychotic syndrome characterized by a
sufferer's strong, mostly delusional belief (delusion) and/or
aberrant perception to be infested with parasites or various
other pathogens against all medical evidence [1]. The chief
characteristic is the patients' firm conviction to harbor
pathogens that are crawling, biting, stinging, leaving marks
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
or building nests on, in or underneath their skin, around or
inside body openings, in the stomach or bowels, or in the
sufferer's immediate environment. There are two principle
explanatory hypotheses of DI [2,3]: (a) a specific, possibly
hallucinatory perception (such as itching) leads to a
secondary development of delusions about the origin of the
perception (sensorialist approach) or (b) a primary change in
the brain causes delusions that are then reinforced by
particular perceptions (cognitive approach).
Patients with DI usually have a prolonged illness history.
Sometimes, they damage their skin by attempting to “dig out
the pathogens” and use various dubious remedies or even
pesticides on their skin. Patients with DI frequently exhibit
the so-called specimen sign [1] (formerly known as matchbox
sign). This means that they provide specimen of the alleged
offending organisms to the physician that at examination only
consist of skin scrapings or other samples of dust, lint, hair,
fibers or scabs rather than evidence of true infestation [4–6].
The disorder is usually classified according to its assumed
etiological nature (pathogenesis). Primary DI is a monodelusional disorder with no detectable etiological condition [i.e.,
meeting the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
criteria for delusional disorder somatic type or the International Classification of Diseases, 10th Revision criteria for
persistent delusional disorder]. By contrast, secondary DI
forms are classified as a result of a detectable etiological
condition such as a brain disorder or a general medical illness
that affects brain function, but also frequently occur on the
basis of a preexisting psychiatric disorder or as a substanceinduced psychotic disorder (including prescribed substances)
[1,7,8]. The assumed multietiological nature of DI implies
that therapy needs to be customized according to the various
forms of DI [1,9]. All primary and secondary cases require
antipsychotic treatment unless stopping the triggering cause
leads to an immediate cessation of DI symptoms.
The only available structural cranial magnetic resonance
imaging (cMRI) study in DI reported that four of five patients
from the subgroup of secondary DI (total sample N=9) had
structural brain lesions in the striatum, predominantly the
putamen [10]. This study first pointed to the putamen as a
potential key structure in DI and gave rise to the model of a
disturbed fronto-striato-thalamo-cortical network to mediate
symptoms of DI [1]. Disturbed functioning of the putamen
and associated brain areas of the somatic/dorsal striatothalamo-cortical loop (abnormal body perception) is thought
to cause somatic delusions and tactile misperceptions, while
frontal dysfunction is hypothesized to be responsible for the
maintenance of the rigid, false belief to be infested (disturbed
judgment). An experimental neuroimaging study in two
model patients with secondary DI found preliminary
evidence of the involvement of these brain structures using
six imaging techniques [11]. The involvement of the
dopaminergic putamen, i.e., dorsal striatum, and the efficacy
of D2-dopamine antagonists (antipsychotics) indicate dopaminergic dysfunction in DI. Evidence from DI in intoxication
605
with substances influencing the dopamine transporter (DAT)
(e.g., cocaine, amphetamines, bupropion) further supports
this observation. Our proposed DAT hypothesis in DI
provides supporting evidence that increased levels of
extracellular dopamine are likely to be the result of decreased
DAT functioning in the basal ganglia (striatum) [12].
Comprehensive reviews have shown that conclusive
evidence on both etiology and treatment is missing for
both primary DI and secondary DI as shown in a number of
recent systematic reviews, although low-level evidence
suggesting the efficacy of dopaminergic antipsychotics
does exist for both primary and secondary DI [1,9,13,14].
Controlled clinical trials with adequate sample sizes are
absent for all forms of DI and for both first- and secondgeneration antipsychotics. Low-level evidence from case
series and open studies, however, supports the efficacy of
antipsychotics. The main obstacle to conducting better
studies on the use of antipsychotics in DI is the patients'
reluctance and inability to give consent to any trial
particularly with antipsychotics based on the patients' false
somatic or infective disease model [15]. In view of the
difficulties to organize a randomized controlled trial,
standardized criteria for reporting cases and outcome have
been proposed and successfully used [9,13,14]. In this paper,
using these reporting criteria, we present 17 consecutive DI
cases that add to our limited knowledge on the use of
antipsychotics in the different forms of classified DI. To our
knowledge, this is the first naturalistic and unselected sample
of DI patients that was effectively treated in a psychiatric
setting (only exception reported from India [16]).
2. Methods
2.1. Patient recruitment
In the following, we report all consecutive cases of DI
seen in the Psychiatric Outpatient Department of the General
Hospital Bruneck/Italy between 1998 and 2010. The hospital
has a catchment area of 70 000 habitants with around 1800
psychiatric patients (in- and outpatients) yearly. Two of the
17 cases were referred from outside the catchment area. All
diagnoses were made according to DSM-IV-TR based on a
detailed clinical history and supporting clinical findings. In
order to further determine the DI classification, all cases were
assigned to one of the proposed types of DI (primary or
secondary) according to their assumed etiological nature.
The data for all patients were collected according to the
criteria for the presentation of DI cases set out by our group
[13,14]. They include gender, age, age at symptom onset
(AAO), duration of illness (DOI), duration of treatment
(DOT), onset of effect (OOE), time of maximum effect
(TME), treatment (antipsychotic substance with dosage),
outcome and effect evaluation (no effect, partial remission or
full remission), treatment setting and DI classification. All
DI patients were clinically assessed by the same psychiatrist
(M.H.) and screened for cognitive impairment using the Mini
606
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
Mental State Examination [17]. We also noted every
patient's handedness (writing hand). Furthermore, all DI
patients were examined for structural brain abnormalities by
means of cMRI or cranial computed tomography (cCT) in
cases where MRI was difficult to perform for medical or
logistical reasons. The respective case reports with additional
information (ages of patients with first presentation of DI to a
psychiatrist, sociodemographic characteristics, delusional
content, medical history with additional diseases and
medications, as well as the detailed specifications of the
performed cMRI/cCT images) are reported as an online
supplement. All data were presented in a descriptive and
comparative way. Data from case 1 to case 9, in parts already
published in our early DI cMRI study [10], were added. All
patients gave their written informed consent to the
publication of personal and clinical information.
3. Results
A total of 17 patients with DI, 10 women (59%) and 7
men (41%), were seen in the study period from 1998 to 2010.
Table 1
Summaries of 17 consecutive DI cases using standardized reporting criteria
Case
Sex
Age
AAO
1
F
79
73
2
F
86
3
M
4
DOI,
years
DOT,
years
OOE,
weeks
TME,
weeks
Treatment outcome and effect evaluation
Last follow-up (Oct/Nov 2010)
TS
DI form classification
3.9
2.8
1
2
HAL 1–3 mg/d (Aug 05 to Jun 08) ++
since then without neuroleptics in ++ (Oct 10)
P
D
73
13.1
74
8.3
0
2
1
2
0
3
5
20
F
75
35
40.3
0.2
0.1
2
1
5
3
5
M
82
71
11.3
5.0
1
3
OLZ 5 mg/d/ARI 5 mg/d (Jan 07 to Aug 07) nr? nc
RIS 2 mg/d (Sep 07 to May 08) but ESE and nc ++
HAL 0,5-1mg/d (Oct-08 to Oct-10) +
OLZ 10 mg/d (Jul 00 to Feb 10) ++ (in the
first three treatment years intermittent combined
with HAL 2–4 mg) ' died in Mar 09
RIS 1–2 mg/d (Aug 99 to Sep 99 with ESE +
Since then, psychiatric treatment refused till Sep 10
ARI 10 mg/d (since Oct 10 to Nov 10) +
AMS 150–200 mg/d (since Oct 05 to Oct 10) ++
P
S
'83
0.7
0.8
2.0
8.0
6
F
78
73
3.6
3.1
2
9
7
M
76
71
5.4
8
F
54
45
8.4
0.2
3.0
8.3
0
2
4
0
4
12
9
M
77
72
4.8
3.2
4
8
10
F
87
72
15.5
11
M
76
69
7.7
12
F
60
54
6.8
0.1
0.5
0.1
1.8
0.3
0.1
0.1
6.8
0
1
0
4
0
0
1
0
0
2
0
8
0
0
2
0
13
F
84
83
1.2
14
M
77
72
5.4
0.6
0.5
0.8
1
1
1
3
2
2
RIS 1–2 mg/d (Nov 06 to Feb 08) since then ++
intermittent without neuroleptics in ++ (Oct 10)
HAL 2–4 mg/d (Jun/Jul 95) since then nc (95–02) nc
RIS 2–4 mg/d (Jan 03 to Jun 03) but ESE then nc ++
ARI 15 mg/d (Oct/Nov 08) and ESE nr
OUE 75–600 mg/d (Dec 08 to Oct 10) ++
AMS 200–400 mg/d (Jul 09 to Oct 09) nr? nc
RIS 1–3 mg/d (Nov 09) but nc/nr to Sep 10 nr? nc
QUE 200–400 mg/d (since Oct 10) (+) nc
OUE, RIS, OLZ, ARI, CLO, HAL, ZIP, AMS nr
(May 04 to Nov 10 in different combinations and doses)
RIS 2–4 mg/d (Oct 09 to Apr 10) but weight gain ++
ZIP 80 mg/d (May 10 to Oct 10) ++
RIS 2 mg/d (Mar 10 to Oct 10) ++
Secondary to BD/MC
systemic hypertension
cerebral arteriosclerosis
Secondary to BD/MC
systemic hypertension
cerebral arteriosclerosis
Secondary to BD/MC
systemic hypertension
cerebral arteriosclerosis
Secondary to BD/MC
hyperthyroidism
left temp. meningioma
Secondary to BD/MC
deafness/blindness
Secondary to PC
major depression
Secondary to PC
major depression
Secondary to PC
cyclothymia
Primary form
15
M
76
71
5.3
4.6
1
3
QUE 200–300 mg/d (Feb 06 to Nov 10) ++
16
F
81
77
4.1
3.5
1
2
HAL 1–2 mg/d (Aug 06 to Nov 10) ++
17
F
63
48
14.6
(8)
(1)
(2)
HAL 5–10 mg/d (Mar 96 to Jul 04) (+) nc
Since 2004 psychiatric attendance and treatment refused
AMS 50–100 mg/d (Feb 06 to Feb 09) but ESE ++
since then, without neuroleptics in ++ (Oct 10)
SUL 200 mg/d (Jul 07 to Aug 07) nc? nr
RIS 2 mg/d (since Sep 07 to Nov 10) ++
RIS 2–4 mg/d (Apr 01 to Oct 10) ++
P
G
P
D
P
G
P
D
P
P
D
P
D
P
D
Secondary to BD/MC
presbycusis/deafness
cerebral arteriosclerosis
P
D
Primary form
P
Primary-form
P
Secondary to BD/MC
cerebrovascular insufficiency
Primary-form
P
N
P
N
P
D
P
D
Primary form
Secondary to BD/MC
multiple ischemic insults
Secondary to PC
paranoid schizophrenia
Legend and abbreviations: case (case number); sex (F/female; M/male); age (age in 2010); AAO (age at symptom onset); DOI (duration of illness in years); DOT
(duration of treatment in years); OOE (onset of effect in weeks); TME (time of maximum effect in weeks); AMS (amisulpride); ARI (aripiprazole); CLO
(clozapine); HAL (haloperidol); OLZ (olanzapine); RIS (risperidone), SUL (sulpiride); OUE (quetiapine); ZIP (ziprasidone); ++ (full remission/no bugs, no
pruritus, no skin problems); + (partial remission); nr (no response/effect); nc (noncompliance); ESE (extrapyramidal side effects); TS (treatment setting: P/
psychiatrist, D/dermatologist, S/surgery, G/general practitioner, N/neurologist); BD/MC (brain disorder/medical condition); PC (psychiatric condition).
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
The standardized reporting criteria of our DI case series (case
1 to 17) are summarized in Table 1. The patients' ages in
2010 ranged from 54 to 87 years (mean 76.1: women 74.7;
men 78.1). The patients' AAOs ranged from 35 to 83 years
(mean 66.6: women 63.3; men 71.4). The average DOI was
9.3 years (total: 159.7; max: 40.3; min: 1.2). The average
DOT was 3.8 years (total: 65.2; max: 8.3; min: 0.3). Eight
patients were classified as secondary to a brain disorder or a
medical condition, four patients were classified as DI cases
secondary to another psychiatric condition and five cases
fulfilled criteria for primary DI (i.e., delusional disorder
somatic type).
Notably, 15 out of the 17 patients seen (88%) could be
engaged in an antipsychotic treatment trial, i.e., only two
patients refused antipsychotic treatment immediately or
within the further course of treatment. Of these 15 cases,
only a single case did not respond to antipsychotics, 12 cases
(71%) reached full remission and another 2 cases (12%)
showed partial remission. Not every patient, however,
responded to the first antipsychotic used; three patients
responded only after changes of the antipsychotic. Details
about the various antipsychotics used and results achieved
are presented in Table 2.
All cases from the secondary-organic form of DI had
macroscopic brain lesions mainly in the basal ganglia,
whereas all other cases did not show basal ganglia or
subcortical gray matter lesions. The cMRI/cCT findings are
summarized in Table 3. All patients were right handed. No
patient fulfilled criteria for severe dementia or had clinical
signs of dementia, as measured by the Mini Mental State
Examination. In the study period from 1998 to 2010 (13
years), the average frequency of DI patients was 1.3 per year
(max: 4; min: 0). This is equivalent to 0.72 DI patient per
thousand psychiatric referrals (in- and outpatients).
This excellent overall clinical outcome in our presented
DI case series was achieved with relatively small doses of the
different antipsychotics used (the exact doses used are listed
607
in Table 1 and the average doses in Table 2). In our series,
remission was mainly achieved with second-generation
antipsychotics in collaboration with the referrer, mostly a
dermatologist (Table 1). The OOE was observed within 1 to
2 weeks already (max: after 4 weeks). The TME was
observed within 5 to 6 weeks (min: after 2 weeks; max: after
20 weeks) (Table 1). The average duration of 3.8 treatment
years was remarkably long (Table 2).
As summarized in Table 3, all eight cases classified as DI
secondary to a brain disorder/medical condition showed
macroscopic brain lesions in the performed cMRI/cCT
images. All showed marked brain lesions in the basal
ganglia, mainly in the striatum (putamen, caudate nucleus).
In addition, four of the same cases showed severe
generalized brain atrophy.
All four cases secondary to another psychiatric condition
and all five primary DI cases did not show macroscopic
basal ganglia or subcortical gray matter lesions. None of the
cases secondary to another psychiatric condition and only
one primary DI case (case 14) showed severe generalized
brain atrophy.
4. Discussion
This paper summarizes the treatment outcome in a series
of N=17 consecutive DI cases seen in a psychiatric outpatient
setting using standardized reporting criteria (Table 1). Age
and sex distribution, AAO, DOI, clinical features, comorbidities and pathways to psychiatric care were consistent
with previously published data, showing that our sample was
representative [18,19]. A female preponderance was present,
but in contrast to early studies, females were on average
younger than males, and in the cases with AAOs greater than
50 years of age, we found a female to male ratio of 1:1
[16,18]. The sociodemographic characteristics and the
delusional content of our cases were typical for DI. All
Table 2
Treatment findings (antipsychotics) in 17 consecutive DI cases
Treatment
Risperidone
Amisulpride
Quetiapine
Haloperidol
Olanzapine
Ziprasidone
Aripiprazole
Clozapine
Sulpiride
Total
Last follow-up
Full remissions
a
7
2b
2
2
1
1
0
0
0
15
12
Partial remissions
c
1
0
0
1
0
0
1
0
0
3
2
Nonresponders
Noncompliance
DOT, years
AD mg/ day
Frequency of use
1
1
1
1
1
1
2c
1
1
10
1d
1
1
1
2
1
0
1
0
0
7
2
18.36
9.25
7.35
17.25
9.19
1.35
1.40
0.85
0.20
65.2
3.8e
2.2
180
300
2.7
7.5
80
8.7
375
200
10
4
4
6
3
2
4
1
1
Legend and abbreviations: DOT (duration of treatment); AD (average doses).
a
Antipsychotic discontinued three times because of side effects.
b
Antipsychotic discontinued once because of side effects; however, the patient remained in full remission.
c
Antipsychotic discontinued once because of side effects.
d
Only one case not responded to all the applied antipsychotic treatment attempts (nonresponder).
e
Average DOT.
608
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
Table 3
Cranial MRI and cCT findings in 17 consecutive DI cases
Case
DI secondary to
1
2
3
4
5
10 °
13
16 °
DI secondary to
6
7
8
17 °
Primary DI
9
11
12
14
15
Basal ganglia and subcortical gray
matter lesions
Subcortical white matter lesions
Cortical lesions
Left
Left
Right
Left
Right
CS
CS
CS
CE
n.a.
–
CI, CS
–
CS, CE
CS
CS
–
n.a.
CE
CE, CI, CS
–
–
–
–
T/F
n.a.
–
–
–
–
–
–
–
n.a.
–
–
–
+
+++
+++
−
+++
+++
++
−
–
CS, PVS
–
–
–
CS, PVS
–
–
–
–
–
–
–
–
–
–
+
+
−
−
–
–
–
CS
CS
–
–
–
CS
CS
–
T/F
–
–
–
–
T
–
–
–
+
+
+
+++
++
Right
brain disorder/medical condition
Pu
Nc, CL
Pu, Nc
Pu
Pu, Nc, Th, P
Nc
Pu, Nc
Pu
n.a.
n.a.
–
Pu, Nc
–
Nc
–
Pu, Nc
psychiatric disorder
–
–
–
–
–
–
–
–
–
––
–
–
–
–
–
–
–
–
Cerebral
atrophy
Legend and abbreviations: case (case number); Pu (putamen); Nc (nucleus caudatus); Th (thalamus); P (pons); CL (claustrum); CS (centrum semiovale); CE
(capsula externa); CI (capsula interna); PVS (periventricular space); T/F (temporal/frontal); n.a. (not analyzable); − (without pathological findings); + (slight), ++
(moderate); +++ (severe).
°
Examined by means of cCT.
patients were convinced that they are infested by parasites or
other pathogens on or inside the skin without evidence of
dermatological pathology. At the last follow-up (Oct/Nov
2010), 15 of the 17 DI patients (case 17 refused the followup and case 3 died in March 2009) were still doing well with
their antipsychotic treatment for years (follow-up times). Our
treatment findings (71% full remissions/12% partial remissions) confirmed the good clinical outcome with
antipsychotics in DI if patients can be engaged in a
meaningful antipsychotic treatment (Table 2).
4.1. Treatment
Successful treatments of DI with second-generation
antipsychotics have been reported in many case series [20–
24]. Comprehensive reviews of the clinical efficacy of
antipsychotics in the treatment of both primary and
secondary DI are provided elsewhere [13,14]. The overall
evidence suggests that DI seems to respond favorably to
most antipsychotics. This has been replicated in our case
series with relatively long treatment durations (Table 2). Ten
of the 12 full remissions were achieved with secondgeneration antipsychotics (risperidone, amisulpride, quetiapine, olanzapine and ziprasidone) and two with haloperidol.
Moreover, we replicated our previous finding of a fast onset
of action in DI when antipsychotics are given, even in
relatively small doses (Table 2) [14]. The OOE was observed
within 1 to 2 weeks and the TME within 5 to 6 weeks. This
confirms that second-generation antipsychotics are a good
choice in the treatment of DI. Previous meta-analyses from
our group have shown that changing medication can be a
successful strategy if there is no response to the first
antipsychotic used [13,14]. We have seen this in our sample
as well, with several patients responding well after changes
to medication due to nonresponse or side effects.
Traditionally, first-generation antipsychotics, especially
pimozide and haloperidol, have been used to treat DI based
on their potent D2-dopamine receptor blocking properties
[25–27]. A special feature of pimozide is its antiopioidergic
activity and a hypothesized resulting antipruritic effect, as
well as its greater affinity to block serotonergic receptors
compared to other first-generation antipsychotics [28,29].
This and its long elimination half-life may explain why
pimozide became the treatment of choice in DI before the era
of second-generation antipsychotics. Among the latter,
risperidone has a higher potency for blocking 5HT2serotonin receptors than D2-dopamine receptors [30–32].
Olanzapine also has a strong antiserotonergic activity. Based
on research models that correlate effects of hallucinogens
such as LSD with 5HT2 binding affinity, the serotonin
system has been shown to contribute to psychosis [33,34].
Risperidone was the most frequently used antipsychotic drug
in the presented DI case series, but we cannot draw any
conclusion about the clinical superiority of any specific
antipsychotic drug in DI due to the size of our sample.
Although the best treatment options in DI are centered on
antipsychotic medications, the clinical management of DI
should involve a multidisciplinary approach including both
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
dermatologists and psychiatrists with a special interest in
these patients, as shown in our study. We hypothesize
various reasons why we are able to engage all consecutive
patients and achieve compliance in most of them, which is in
clear contrast to all other naturalistic studies reported so far
and clinical experience with DI patients:
1. We involved the relatives of patients from the
beginning of treatment, and it was often a relative
who ensured regular follow-up.
2. We stayed in telephone contact with patients and
their families, which may have improved the
building of trust.
3. Bruneck is in the German-speaking part of Italy, and
while we obviously explained the rationale for the use
of antipsychotics beyond normal licensing as well as
their side effects to patients in their mother tongue,
many patients were unable to fully understand the
Italian information leaflets they received, leading to
less opportunity to ponder on whether or not to take a
drug used for schizophrenia.
4. The belief in doctors among the rural population we
serve is still rather high, with relatively little
stigmatization of psychiatric services.
5. The principle investigator (M.H.) always met
patients at the hospital door when they arrived for
MRI or cCT scans and stayed with them until the
scan was performed.
4.2. Pathophysiology and classification
It became clear that the diagnostic differentiation
(classification) between primary and secondary DI is all
but easy. The classification procedure shows the general
problem of defining when a condition is secondary to
another, or when a concomitant disease is considered as a
comorbid condition rather than an etiological condition [7–
9,35]. We classified those cases as secondary to brain
disorders/medical conditions that showed the onset of the
clinical DI manifestation within 6 months of the onset of the
assumed etiological medical cause. In the DI cases
associated with another psychiatric condition, there had to
be a timely connection between the onset of the clinical DI
manifestation and an acute exacerbation of the psychiatric
illness of no less than 3 months to qualify as an etiological
cause. All other cases were classified as primary DI with
additional diseases considered as comorbid. However, there
is a wide overlap of brain lesions with normal aging and
other reasons for brain changes. Cases associated with drug
involvement were not present in our sample.
All cases secondary to medical etiologies showed
macroscopic brain lesions mainly in the striatum, whereas
all other cases did not have any pathological striatal
findings in the cMRI/cCT scans (Table 3). Although there
is little published evidence for specific brain regions
involved in DI, the majority of the reported lesions have
been found in subcortical and temporoparietal brain
609
structures, mostly after tumors, stroke or other cerebrovascular and neurological events [8,22,36–42]. We previously
hypothesized these areas to be involved in the etiology of
DI [10,12]. In line with these reports, six of our eight cases
secondary to a brain disorder/medical condition were
classified as etiologically associated with cerebrovascular
pathologies, inducing lesions in the striatum. All the cases
had lesions in the areas of the brain that are highly
associated with dopaminergic pathways, which may explain
the efficacy of dopaminergic antipsychotics.
The present study focuses on clinical issues in the
antipsychotic treatment of different forms of DI in unselected
patients and does not aim at confirming or dismissing basal
ganglia involvement in the pathophysiology of DI. However,
the cMRI/cCT findings suggest organic brain disease
damaging basal ganglia to be associated with all DI cases
secondary to a medical condition. The cases without
structural imaging findings may require functional investigations to show brain dysfunction, e.g., in the striatum as
described in our proposed DAT hypothesis in DI [12], as
MRI findings are not able to show more subtle changes to
DAT density or DAT dysfunction or other dopaminergic
pathway lesions. Supporting this, there are some interesting
case reports using single photon emission computed
tomography demonstrating involvement of the somatic/
dorsal striato-thalamo-cortical loop (abnormal body perception) in DI [43,44]. Our as yet only positron emission
tomography study in DI showed altered presynaptic (DAT)
and postsynaptic (D2) dopaminergic neurotransmission in
the striatum in a single DI case. [11]. It is, of course, also
conceivable that primary DI and secondary DI due to
psychiatric disorders are somewhat different etiological
entities to secondary DI due to medical disorders, thus
explaining macroscopic lesions only in the latter group.
However, the efficacy of antidopaminergic and antiserotonergic medication indirectly indicates a dopamine and
serotonin pathway involvement in all cases of DI.
In view of current etiologic DI hypotheses, basal ganglia
lesions may support the so-called sensorialist approach as
proposed by Berrios (1985) in cases of DI secondary to brain
disorders or medical conditions that affect the peripheral or
central sensory–somatic system, reflecting a primary
abnormal visuotactile sensation or hallucination with a
secondary delusional elaboration that arises in response to
abnormal sensory perceptions [2,3]. It is conceivable that DI
arises from strategically placed brain lesions causing damage
to neuroanatomical pathways (e.g., putamen) and/or neurotransmitter systems (e.g., DAT) responsible for an adequate
visuotactile perception. However, it is also possible that both
the sensorialist approach (chronic tactile hallucinosis) and
the cognitive approach (delusion first, which then leads to
abnormal sensations) contribute in different patients, suggesting that DI is not a homogenous entity [7]. The so-called
cognitive approach much better explains primary monothematic delusional disorders such as primary DI. Therefore, an
accurate DI diagnosis and classification are likely to be
610
M. Huber et al. / General Hospital Psychiatry 33 (2011) 604–611
important steps in advancing research into the etiology on
DI. It may increase our understanding of the underlying
functional neurochemical and structural neuroanatomical
substrates. This could potentially lead to better and more
adequately directed pharmacological treatment.
The present DI case series is limited by the small number
of subjects. Unfortunately, the imaging findings could not be
compared to an age-matched group of healthy controls. Its
strength lies in the examination of consecutive, rather than
highly selected, patients. Because of the small sample size,
further statistical analysis or analyses of subgroups were not
reasonable. All these limit the generalization of our data, but
represent an advance on highly selected case reports or case
series with selected patients. Further neuroimaging studies,
specifically looking at dopaminergic pathways and including
pre- and postsynaptic imaging, in larger samples and
randomized controlled trials to evaluate antipsychotic
medication in DI are needed to expand the preliminary
knowledge obtained from this case study.
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
Acknowledgments
We thank all our patients for their understanding and
willingness to participate in this study. All authors of this
case study have no financial conflicts of interest relevant to
this manuscript, and no funding was received for this project.
[19]
[20]
[21]
Appendix A. Supplementary data
[22]
Supplementary data to this article can be found online at
doi:10.1016/j.genhosppsych.2011.05.013.
[23]
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