June 2006
KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Reversible Posterior Leukoencephalopathy Syndrome: A
Review with Two Illustrative Cases
Dowod Tarek, Sajid Burud
Department of Medicine, Al-Adan Hospital, Kuwait
Kuwait Medical Journal 2006, 38 (2): 94-99
ABSTRACT
Objective: To shed more light on the newly recognized
neurological disorder, reversible posterior leukoencephalopathy syndrome (RPLS).
Setting: Medical Department, Al-Adan Hospital,
Kuwait.
Materials and Methods: In two patients who were
hospitalized for acute illness, we had noted a syndrome
of altered mental functioning, seizures and motor signs
with findings indicating predominantly posterior
leukoencephalopathy on neuroimaging studies. The
findings on neuroimaging studies were characteristic of
subcortical edema without infarction and reversible.
To elucidate this syndrome, we searched the literature for
the differential diagnoses of reversible radiological
shadows on neuroimaging of the brain (CT scan and
MRI).
Results: Hinchey and colleagues reported the syndrome
of RPLS for the first time in 1996. Thereafter, the
syndrome was reported with increasing frequency both
in pediatric and adult populations.
In this study, we report two cases of RPLS due to acute
hypertensive encephalopathy. The patients were treated
with antihypertensive medications and the neurological
deficits abated completely within two weeks.
Conclusion: Essentially the diagnosis of RPLS is
retrospective; significant reversal of neuroradiological
abnormalities coupled with complete clinical recovery
suggests the diagnosis. Clinicians must be aware of this
syndrome as its recognition obviates unnecessary
diagnostic procedures. Moreover, the syndrome is
reversible with prompt treatment and has a good
outcome.
KEYWORDS: cerebral edema, hypertension, immunosuppressive therapy, leukoencephalopathy
INTRODUCTION
Reversible posterior leukoencephalopathy syndrome
(RPLS), also known as posterior reversible
encephalopathy syndrome and reversible posterior
cerebral edema, is a newly recognized neurological
disorder[1].
Hinchey et al in 1996 used this phrase for the
first time and in a retrospective study noted white
matter edema on neuroimaging studies in the
posterior temporo-parieto-occipital regions in a
variety of conditions including severe hypertension,
and they proposed the acronym RPLS to
emphasize its location and relatively reversible
nature[2].
The syndrome may occur in a host of clinical
situations (Tables 1 and 2) such as hypertensive
encephalopathy[2-6], toxemia of pregnancy[7,8], chemotherapy[9-11], immunoglobulin therapy[12,13], thrombotic
thrombocytopenic purpura[14], acute intermittent
porphyria[15], following organ transplantation[16,17],
collagen vascular disease such as systemic lupus
erythematosis, polyarteritis nodosa, Behcet’s disease
and acquired immunodeficiency syndrome[18].
As many clinicians and radiologists are not
aware of this newly recognized neurological
disorder, we decided to shed more light on its
etiopathogenesis, clinical features, differential
diagnoses, investigations, treatment and outcome.
MATERIALS AND METHODS
In two patients who were hospitalized for acute
illness, we noted a syndrome of altered mental
functioning, seizures and motor signs with
findings indicating predominantly posterior
leukoencephalopathy on neuroimaging studies.
The appearance on neuroimaging was characteristic
of subcortical edema without infarction and was
reversible (Figs. 1 and 2).
To elucidate this syndrome, we searched the
literature for the differential diagnoses of reversible
radiological shadows on neuroimaging of the brain
(CT scan and MRI).
The syndrome of RPLS was included in the
differential diagnoses of such reversible shadows.
As there was little data available on this syndrome,
we searched the literature again under the title
Address correspondence to:
Dr.Dowod Tarek, P.O.Box: 47854, Fahaheel, Kuwait. Tel.No: +965 6052897, +965 3718245, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
Fig. 1 : Non-contrast Cranial CT scan; 1a: Bilateral symmetrical posterior
parieto-occipital white matter hypodensities (arrows) on presentation.
The patient presented with an acute onset of confusion, coma, multiple
witnessed seizures, severe hypertension (blood pressure of 300/120
mmHg) and motor signs.
RPLS for more detailed information on the
syndrome. There was scant data available in the
textbooks, and therefore, our search was done mostly
in journals of all specialties and on the Internet.
RESULTS
Hinchey and colleagues, in 1996, reported the
syndrome of RPLS for the first time. Thereafter, the
syndrome was reported with increasing frequency
both in pediatric and adult populations.
In our study, we reported two cases of RPLS
secondary to acute hypertensive encephalopathy
(one in a 27-year-old male patient associated with
renal disease due to focal segmental glomerulosclerosis as proved by renal biopsy, and the other in
a 61-year-old male patient due to poor drug
compliance with antihypertensive medications).
The clinical findings included severe hypertension
(blood pressure of 300/120 mmHg) confusion,
coma, multiple witnessed generalized tonic-clonic
seizures and motor signs in the first patient, and
severe hypertension (blood pressure of 250/130
mmHg) headache, vomiting, cortical blindness and
motor signs in the second patient. The reported
motor signs included generalized weakness of
pyramidal nature grade III-IV, hypertonia,
generalized brisk deep tendon jerks, bilateral
extensor plantar response in both patients; the first
patient also had bilateral sustained ankle clonus.
Fundus examination and pupillary responses were
normal in both patients apart from grade II
hypertensive changes in the second patient. The
results of laboratory tests in the first patient showed
95
1b: Resolving hypodensities after 10 days (The neurological deficits
disappeared completely in thirteen days).
Hb of 10.3 g/dl of normocytic normochromic type,
blood urea of 16.9 mmol/l, S. creatinine of 386
umol/l, S. albumin of 19 g/l, T. protein of 4.8 g/l, T.
cholesterol of 7.2 mmol/l, 24-hour urinary protein
of 3.6 g with normal blood sugar, S. electrolytes, S.
calcium and magnesium. Renal biopsy was
subsequently done and showed focal segmental
glomerulosclerosis. Serologic tests for vasculitis,
HIV 1/2, syphilis, ecchinococcosis, toxoplasmosis,
blood film for malaria and blood cultures were
negative. The results of laboratory tests in the
second patient showed blood urea of 8.6 mmol/l, S.
creatinine of 165 umol/l with normal Hb, S.
electrolytes, S. calcium, magnesium, lipid profile
and blood sugar. CT and MRI studies showed
extensive bilateral white matter abnormalities
suggestive of edema in the posterior regions of
cerebral hemispheres (Figs. 1a and 2a). The patients
were treated with antihypertensive medications
and the neurological deficits resolved completely
within two weeks (thirteen days in the first patient
and four days in the second one). Follow-up
scanning showed resolution of abnormalities at ten
days in the first patient and two months in the
second one (Figs. 1b and 2b).
We have observed reluctance on the part of
physicians to consider the possibility of hypertensive
encephalopathy without demonstrable evidence of
end-organ damage attributable to elevated blood
pressure such as schistocytes on blood film,
evidence of retinal edema, papilledema or left
ventricular hypertrophy on ECG.
In view of the range of blood pressure values
associated with this clinical syndrome and the
evidence for factors predisposing to selective
96
Reversible Posterior Leukoencephalopathy Syndrome: A Review with Two Illustrative Cases
Fig. 2: T2-weighted axial MRI sections; 2a: Bilateral symmetrical
hyperdensities (arrows) in the occipito-parietal lobes. The patient
presented with sudden onset of severe headache, vomiting, confusion,
cortical blindness, severe hypertension (blood pressure of
250/130mmHg), and motor signs.
vulnerability of the cerebral circulation with even
modest acute elevation of blood pressure, this
position should no longer be tenable.
DISCUSSION
Etiopathogenesis:
The causes of this syndrome are diverse.
However, hypertensive encephalopathy, toxemia of
pregnancy and uremic encephalopathy are the
most common causes of RPLS [19]. The exact
etiopathogenesis of the condition is not known. It
may result from a rapid rise in blood pressure that
overcomes the brain’s normal autoregulation of
cerebral blood flow. This disturbance of homeostasis
produces dilatation of cerebral arterioles with
opening up of endothelial tight junctions and
leakage of plasma into the extracellular space
producing cerebral edema[4,5]. Clinical and radiological
parameters indicate that the occipito-parietal
vasculatures are the most vulnerable [2]. The
vulnerability of posterior circulation to the cerebral
hemisphere may be explained by a paucity of
autonomic innervations as compared to the
anterior circulation. The resulting edema is usually
vasogenic and reversible but may become cytotoxic
in some patients[20]. The frequent association of the
syndrome with precipitating factors not usually
responsible for blood pressure elevation and the
occasional occurrence of this syndrome in patients
with only modest elevation of blood pressure
suggest that some additional factor(s), either local
or systemic, may be responsible for predisposing
June 2006
2b: Resolving hyperdensities after two months (The neurological deficits
ceased completely in four days).
the cerebral circulation to the effects of acute
elevation in blood pressure. Dysfunction of
particular subtypes of endothelial cells has also
been hypothesized to result in vasospasm, bloodbrain barrier breakdown and loss of fluid from the
intravascular compartment, all of which are seen in
this syndrome. However, mechanism(s) leading to
the endothelial cell dysfunction in this syndrome
are at present unclear [21].
The pathophysiology of immunosuppression on
the development of RPLS in the absence of
hypertension is not clear but is probably related to
either a primary or secondary breakdown of the
blood-brain barrier[2]. Eichler et al reported that
widespread metabolic abnormalities consisting of
increased choline and creatine levels and mildly
reduced N-acetylaspartate occurred in the regions
with both normal and abnormal MRI appearances.
They suggested that proton MR spectroscopic
imaging might be helpful for the diagnosis and
investigations of the underlying pathophysiology
of RPLS [22].
Clinical Features:
The syndrome characteristically begins with a
subacute prodromal period of altered alertness and
activity. Lethargy and somnolence are often the first
signs noted, with slowing of mental functions and
confusion as the syndrome progresses. Increasing
headache and visual blurring may occur during
this period and frequently brings the patient to
June 2006
KUWAIT MEDICAL JOURNAL
Table 1: Causes of RPLS
97
Table 2: Immunosuppressive agents and drugs causing
RPLS
Common causes:
t Hypertensive encephalopathy
t Cyclosporine A
t Eclampsia
t Interferon alpha
t Immunosuppressive agents and cytotoxic drugs
t Intravenous immunoglobulins
t Renal failure with hypertension
Other reported causes:
t Collagen vascular disease
n Systemic lupus erythematosis (SLE)
n Polyarteritis nodosa
n Behcet’s disease
t Thrombotic thrombocytopenic purpura
t Acute intermittent porphyria
t Following organ transplantation
t Acquired immunodeficiency syndrome
medical attention. This prodromal period is
important to recognize as it provides an
opportunity to minimize morbidity by initiating
early treatment and may help to differentiate this
syndrome from other disorders. However, the
syndrome can also become manifest by acute
seizures without an obvious prodrome. A 1996
study of 15 patients in Europe and the United States
with this syndrome listed the most common clinical
features as headache, altered alertness and
behavior, seizures and abnormalities of visual
perception[2]. A review of 52 cases of RPLS in the
pediatric population confirmed these four signs
and symptoms as being the most common [23]. In the
latter study, 76% of the cases had at least three of
the four listed signs and symptoms, although their
severity varied considerably among cases.
Alteration in alertness ranged from drowsiness and
diminished spontaneity to stupor. Abnormalities of
visual perception ranging from blurred vision to
frank cortical blindness are almost always
detectable; some patients with cortical blindness
have also denial of blindness (Anton’s syndrome)[2].
Fundus examination (especially in eclampsia
and patients with renal failure) and pupillary
reflexes are often normal [18].
Deep tendon reflexes are frequently brisk and
the plantar reflex may be extensor. A few patients
may have weakness and incoordination of the
limbs[1,3]. The clinical features usually disappear
after appropriate treatment is started and the
majority of the patients recover completely[18]. The
clinical features are summarized in Table 3.
Investigations:
CSF examination is usually normal; however, it
may show mild elevation in protein. Metabolic
abnormalities in RPLS may include hypomagnesaemia,
hypocholesterolemia; both of which are present in
≥ 50% of patients with RPLS secondary to
cyclosporine A[9]. Aluminum overload and elevated
t Erythropoietin
t Cisplatin
t Tacrolimus (FK506)
t Cytarabine
drug levels are present in 50% of patients with
RPLS secondary to cyclosporine A[9].
Radiological Findings:
The findings on neuroimaging studies in RPLS
include non-enhancing white matter abnormalities
that appear as areas of low attenuation on CT scan
and appear hypo-intense on T1-weighted MRI and
hyper-intense on T2-weighted MRI (Figs. 1a and
2a). These abnormalities partially or completely
resolve on follow-up scanning, thereby suggesting
subcortical edema without infarction (Figs. 1b and
2b).
The lesions are mainly seen in posterior regions
of the cerebral hemispheres[6,20,24]. In patients with
extensive involvement, other structures such as
brainstem, basal ganglia and frontal lobes can also
be affected. The imaging abnormalities are often
symmetrical; however asymmetric involvement is
not unusual. At times, the grey matter is also
extensively affected[1,2,7].
The lesions of RPLS are best visualized with
MRI studies. However, Hinchey et al consider that
MRI is not essential for the diagnosis of RPLS; CT
scans can also be used satisfactorily for these
patients[2].
Differential Diagnosis:
The differential diagnosis of RPLS includes
various acute neurological conditions such as
stroke, cerebral venous thrombosis, encephalitis
and demyelinating disorders[18]. Radiological
distinction from top-of-the basilar syndrome with
bilateral posterior cerebral artery infarction with
cytotoxic edema is evident by sparing of the cortical
and paramedian occipital structures as well as
resolution of the lesions on follow-up imaging.
Diagnosis can be easily recognized with MRI
imaging. Acute infarction usually demonstrates
hyper-intensity on Echo-planar diffusion weighted
imaging (DWI) and T2-weighted imaging with
reduced apparent diffusion coefficient (ADC)
levels. As opposed to those findings, there is hypoor iso-intensity on DWI, hyper-intensity on fluid
attenuated inversion recovery imaging (FLAIR)
and T2-weighted imaging, and markedly elevated
98
Reversible Posterior Leukoencephalopathy Syndrome: A Review with Two Illustrative Cases
June 2006
Table 3: Clinical features of RPLS
Table 4: Differential diagnoses of RPLS
Acute to subacute onset
Vascular
t Infarction especially “Top-of-the-Basilar syndrome” with
bilateral posterior cerebral artery ischemia
t Hemorrhage
t Venous thrombosis
Infection
t Encephalitis, meningitis
Inflammatory/autoimmune Vasculitis
t Especially SLE
Neurological symptoms
n Headache
n Altered mental status / confusion / drowsiness
Visual disturbances
n Hemianopia
n Visual neglect
n Cortical blindness or Anton’s syndrome (denial of
blindness, confabulation)
Seizures
n Often precede the other symptoms
n Usually generalized, tonic-clonic in nature
n May be preceded by visual aura or hallucinations
n Single seizure infrequent, usually multiple
Systemic Signs
n Usually acute rise in blood pressure
n Hypertension may be mild, moderate or severe
depending on the patient’s usual BP
ADC levels with RPLS [25]. The differential diagnosis
is summarized in Table 4.
If the history of an acute seizure or uncontrolled
blood pressure is not obtained or is an underemphasized aspect of the clinical presentation and
not mentioned to the radiologist, an incorrect
diagnosis of gliomatosis cerebri, progressive
multifocal leukoencephalopathy, demyelinating
disease or infection may be offered on the basis of
neuroimaging. Such incorrect diagnoses may result
in invasive biopsies or inappropriate therapies[26].
So, it is recommended that when high signal
intensity is seen on MRI and there is history of
seizures or high blood pressure, a follow-up scan in
a period of 1-2 weeks will most often document
reversibility of vasogenic edema and avoid
expensive or potentially invasive work-up for other
primary cerebral disease[27].
Treatment:
The recognition of the syndrome is critical as
delay in the diagnosis or treatment can result in
permanent neurological deficits while prompt early
control of blood pressure or withdrawal of
causative drugs can reverse the syndrome [28,29].
l A 10-20% reduction in mean arterial pressure
is usually sufficient to terminate the
dysfunctional process
l Discontinue or reduce the dose of offending
drugs (e.g. cytotoxic agents)
l Treat hypomagnesemia
l Treat seizures with anti-convulsants
Prognosis:
After prompt treatment, most patients recover
completely within hours (12-24 hours) to days.
Imaging findings may persist for weeks. If the
syndrome is not treated promptly, it can lead to
posterior circulation infarction or hemorrhage [30].
The extent of combined T2 and DWI signal
abnormalities correlate with the patient outcome.
High DWI signal intensity and pseudo normalized
ADC values are associated with cerebral infarction
and may represent the earliest signs of nonreversibility as severe vasogenic edema progresses
to cytotoxic edema [31].
Patients do not require chronic anti-epileptic
treatment once imaging abnormalities have
resolved[4,32].
CONCLUSION
Early diagnosis of this syndrome is of utmost
importance as it is generally considered to be
reversible and readily treated by controlling the
patient’s blood pressure. It is also important to
distinguish this syndrome from conditions, which
require specific treatment such as immunosuppressive therapy or anticoagulation, and from
conditions in which aggressive lowering of blood
pressure may be harmful as in acute ischemic
stroke. The potential reversibility of the syndrome,
the risk of permanent neurological dysfunction, if
left untreated, and the potential for diagnostic
confusion with other serious disorders affecting the
CNS mandate that a high index of clinical suspicion
be maintained in patients presenting with
neurological symptoms associated with acute
elevation of blood pressure. Such patients should
be evaluated and treated on an emergency basis.
ACKNOWLEDGEMENT
We thank the radiology department of Al-Adan
hospital for the radiographic material provided to
us for preparing this manuscript.
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Neurol 1997; 16:145-148.
KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Smoking among Health Care Workers of the Capital
Governorate Health Region, Kuwait: Prevalence and
Attitudes
Ibrahim S Al-Eisa1, Adel M Al-Terkit2, Maged M Radwan 2, Tarek Al-Jassar3, Manal S Al-Mutar4
Primary Health Care,Capital Health Region, Kuwait
Preventive Health Department, Primary Care, Capital Health region, Kuwait
3
Al Amiri Hospital, Ministry of Health, Kuwait
4
Sawaber Health Center, Capital Health Region, Ministry of Health, Kuwait
1
2
Kuwait Medical Journal 2006, 38 (2): 100-106
ABSTRACT
Objectives: To determine the prevalence of smoking
among health care workers in the Capital Health Region
and associate it to socio-demographic characteristics, and
to study attitudes and behavior of smoking and quitting.
Subject and Methods: A cross-sectional study was
conducted during August and September 2002. All
health care workers at Ministry of Health facilities,
Capital Region, including Al-Amiri Hospital and the
health centers propagated through the Capital Region
were invited to participate using a self-administered
questionnaire. The survey collected information on
socio-demographic characteristics and on behavior and
attitudes toward smoking and quitting.
Results: Out of a total of 1,625 participants in the study,
604 were male and 1021 were female; 76.4% were
married, 47.7% were nurses and 41.1% had received a
diploma. The overall prevalence of smoking among
participants was 16.8%. The prevalence of smoking was
37.3% among males and 4.4% among females. It was
observed that the prevalence of smoking was high
among clerks (30.5%) and among those who had primary
level of education (45.5%).
The majority of males (78.7%) started smoking before the
age of 20 years while the highest percentage of females
(60.5%) started after. The majority of male smokers (74%)
attempted to stop smoking while only 50% of females
attempted to quit. 8.8% of participants were classified as
ex-smokers; they were obviously used to smoking fewer
cigarettes daily.
Conclusion: Health Care Workers have to set a good
example to others by playing a vital role at various levels
of smoking cessation. Hence, comprehensive tobacco
control laws including bans on tobacco advertising and
smoke-free public places, largeclear health warnings and
health education campaigns are needed.
KEYWORDS: Kuwait, prevalence, smoking, social factors
INTRODUCTION
Cigarette smoking is an important cause of
cancers of the lung, larynx, pharynx, nasal cavities,
nasal sinuses, esophagus, bladder, kidney, pancreas,
stomach, liver, cervix and myeloid leukemia [1].
Results of a study of ex-smokers with lung cancer
found that those who started smoking before age
20 yrs had twice as many cell mutations as those
who started after age 20[2]; stopping smoking before
middle age avoids more than 90% of the risk
attributable to smoking [3]. Smoking affects not only
the tobacco user but also non-smokers near the
smoker, such as family, friends, co-workers and
unborn children [4]. Tobacco consumption has fallen
over the past 20 years in most high-income
countries such as Britain, Canada, the United
States, Australia and most northern European
countries. In contrast, tobacco consumption increased
in low and middle-income countries by about 3.4%
per annum between 1970 and 1990[5].
Smoking is a major preventable cause of
morbidity and mortality all over the world[6]. The
prevention and treatment of tobacco addiction
have been targeted by WHO as priorities for
intervention in developing countries. It has been
estimated that, unless immediate steps are taken to
reduce smoking rates, the number of deaths due to
tobacco use will rise to 10 million per year over the
next 30-40 years, and 70% of these deaths will occur
in developing countries [7-,9]. By 1990, almost 91
countries had adopted the national anti-tobacco
legislation. Perhaps as significant as the spread of
legislation is the increased strength and effectiveness
of recently enacted statutes[10]. As governments
have faced the persistence of the tobacco epidemic,
they have banned all advertising and promotion of
Address Correspondence to:
Ibrahim Al-Eisa, RCGP, P.O. Box : 14982, Faiha Postal Code:72860, Kuwait. Tel: (965)2541428, Fax: (965)2552358, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
tobacco, have substantially raised taxes on the price
of tobacco products and have expanded restrictions
on smoking in public, workplaces and public
transport. In 1995, the national Assembly in Kuwait
approved a comprehensive legislation for tobacco
control. Before this legislation, the anti-smoking
laws consisted of the following: (i) resolution No.
981 of 1980, whereby the mayor of the municipality
of Kuwait cancelled licenses for advertisements of
tobacco products within the municipality; (ii) the
ministerial resolution No. 25 of 1980 consisting of
the particulars to be stated on cigarette packages;
and (iii) the ministerial decree No. 180 of April 1988
stating the necessity to provide for the analysis of
components of imported cigarettes[11] There have
been reports on the smoking habits of physicians
around the world[12]. Little is known about smoking
prevalence, behaviors and attitudes among health
workers. It is assumed that hospital workers are
more informed than the general population with
regard to smoking hazards and are supposed to set
an example for the rest of the community regarding
smoking habits[13]. However, smoking prevalence
among hospital workers was found to be the same
as in the general population in different studies
conducted all around the world [14,15].
The aims of our study were to determine the
prevalence of smoking among health care workers
at the Capital Health Region, to study the relationship
between the prevalence of smoking and age,
marital status, occupation and level of education,
and to study the attitude and behavior of smoking
and quitting.
SUBJECTS AND METHODS
A cross-sectional survey was conducted during
August and September 2002. All health care
workers (2,477) working at Ministry of Health
facilities, Capital Region including Al-Amiri hospital
and the health centers propagated through the
Capital Region, were invited to participate using a
self-administered questionnaire. A modified version
of the standard WHO questionnaire for surveying
smoking prevalence and behavior was used[16].
The questionnaire consisted of three parts : (1)
sociodemographic characteristics (age, sex, marital
status, level of education and nature of work), (2)
smoking behavior and attitudes (smoking status,
age at which smoking started, number of cigarettes
smoked daily, kind of smoking, reasons for
smoking and for not quitting), (3) quitting behavior
and attitudes (age of starting smoking, number of
cigarettes smoked daily, age of quitting smoking,
reasons for quitting and method used for quitting).
Respondents were classified as current smokers,
ex-smokers and never-smokers. Current smoker
were defined as those smoking at the time of survey
101
Table 1: Prevalence of smoking among health employees
by age, marital status, occupation and education
Characteristics
Male Smoking Female Smoking All Smoking
%
%
responses
%
Age (years)
18-20
6
21-25
77
26-30
162
31-35
140
36-40
122
41-45
56
46-50
26
51-60
15
Significance
NS
Marital status
Single
118
Married
477
Separated/divorced/
widowed
9
Significance
NS
Occupation
Physician
112
Nurse
197
Clerk
234
Technician
61
Significance
p < 0.001
Education
Primary
14
Intermediate
153
Secondary
118
Diploma
113
University
128
Post-graduate
78
Significance
p < 0.001
Total
604
66.7
48.1
36.4
38.6
32.8
33.9
19.2
46.7
5
163
318
295
163
51
20
6
NS
0.0
2.5
5.3
4.1
6.1
3.9
15
0.0
11
240
480
435
285
107
46
21
NS
36.4
17.1
15.8
15.2
17.5
19.6
17.4
33.3
43.2
35.6
214
765
5.1
3.3
332
1242
18.7
15.7
42
p < 0.0001
28.6
51
p <0.01
31.4
31.3
116
23.9
578
51.3
254
37.3
73
p < 0.0001
2.6
1.6
11.4
9.6
228
775
488
134
p< 0.0001
16.7
7.2
30.5
22.4
57.1
8
45.1
165
40.7
89
40.7
560
0.5
134
19.0
65
p < 0.0001
25
6.1
21.3
0.9
7.5
3.1
22
318
207
673
262
143
p< 0.0001
45.5
24.8
32.4
7.6
18.7
11.9
4.4
1625
16.8
44.4
37.3
1021
Results of П‡2 test
NS = Not Significant
and had smoked more than 100 cigarettes in their
lifetime; ex-smokers, if they had smoked more than
100 cigarettes in their lifetime but no longer
smoked; never-smokers, if they had never smoked
or had smoked fewer than 100 cigarettes in their
lifetime[17].
An Arabic version of the questionnaire as well
as an English one were pilot tested on a random
sample of 100, and the wording of some of the
questions was modified before it was formally
administered. To minimize non-response and
under-reporting, respondents were told that the
information obtained would be confidential and
used only for statistical purposes.
The descriptive statistics including frequencies,
mean and standard deviation were used to describe
the study findings; also the association between
two discrete variables was tested by the Chi-square
test and by the Z test for proportion using microstat
software program for statistical analysis. A p-value
of ≤ 0.05 was considered significant. The
102
June 2006
Smoking among Health Care Workers of the Capital Governorate Health Region, Kuwait: ....
Table 2: Distribution of current smokers by age of
starting smoking, number of cigarettes smoked per day
and kind of smoking
Characteristics
Male
(N = 225)
n
%
Female
(N = 48)
n
%
Age of starting smoking (years)
10-14
54
24.0
3
15-19
123
54.7
16
20-24
34
15.0
23
25-29
8
3.6
3
30 and above 6
2.7
3
Number of cigarette smoked/day
<10
20
8.9
19
10-20
85
37.8
20
21-30
65
28.9
5
31-40
43
19.1
2
> 40
12
5.3
2
Kind of smoking
Cigarettes 207
92.0
36
Water pipe
11
4.9
12
Other
7
3.1
0.0
All smoker Significance
(N = 273)
n
%
6.3
33.2
47.9
6.3
6.3
57
139
57
11
9
20.9
50.9
20.9
4.0
3.3
39.5
41.7
10.4
4.2
4.2
39
105
70
45
14
14.3
38.5 p < 0.0001
25.6
16.5
5.1
75.0
25.0
0. 0
243
23
7
89.0
8.4
2.5
p < 0.001
p < 0.001
Results of П‡2 test
quantification of risk was calculated by Odds Ratio
(OR) and 95% Confidence Intervals (CI) using the
EPI info program (version 6).
RESULTS
Out of 2,477 questionnaires, 1625 were completed
giving a response rate of 65.6%, while 852 (34.4%)
refused to participate. The reason for noncompliance was that they felt furnishing this type
of information would help in incriminating them,
since they worked in the Ministry of Health.
Overall, 16.8 % of the participates were classified
as current smokers, 8.8% as ex-smokers, and 74.2%
as never-smokers. Of all participants, 604 (37.2%)
were males and 1021 (62.8%) were females. Large
groups of participants (480; 29.5%) were in the age
group of 26-30 years, (242; 15.7%) were married,
(775; 47.7%) worked as nurses and (673; 41.4%) had
received a diploma (Table 1).
The overall prevalence of smoking among
workers was 16.8%. Significantly the prevalence of
smoking was higher among males (225/604 or
37.3%) than females (48/1021 or 4.4%). Smoking
among males was 12 times more than among
females (OR = 12.03, 95% CI, 8.52-17.04). The
highest prevalence of smoking among males
(66.7%) was in the youngest age group (18-20),
while the highest rate of smoking among females
(15%) was observed in the age group 46-50 with no
significant differences between sexes. For both
males and females, smoking was significantly
higher among clerks (51.3%, p < 0.001; 11.4%, p <
0.001 respectively ).
Significantly, both males (57.1%) and females
(25%) who had received a primary level of
Table 3: Characteristics and attitudes towards smoking of
current smokers
Characteristics
and attitudes
Males
n = 225
% Females
n = 48
Reasons for smoking
Relax
123
54.7
12
Relieve
boredom
117
39.1
36
Relive anger,
frustration
101
44.9
12
Concentrate
at work
88
52
1
Relieve pressure
of working hard 68
30.2
3
Mix in social
situations
61
27.1
4
Enjoy pleasant
events
56
24.9
—Get going in
the morning
29
12.9
—Boost self
confidence
9
4
—Do you want to stop smoking?
Yes
150
66.7
27
No
53
23.6
15
Uncertain
22
9.8
6
Attempts to stop smoking
Yes
167
74.2
24
No
58
25.8
24
Do you smoke in presence of your children*
Yes
95
63.3
8
No
55
36.7
30
Reasons for not quitting smoking
Lack of
willpower
146
64.9
22
People around
me smoke
83
36.9
3
Not sure how
to quit
56
24.9
17
Don’t want
to stop
50
22.2
3
I like it very
much
23
10.2
4
Stress at work
24
10.7
1
Stress at home
14
6.2
12
Fear of gaining
weight
7
3.1
5
%
Total
n = 273
%
Significance
25
125
75
153
56
p < 0.01
25
113
41.4
p < 0.05
2.1
89
32.6 p < 0.0001
6.3
71
26 p < 0.001
8.3
65
23.8
—-
56
20.5 p < 0.001
—-
29
10.6
p < 0.01
—-
9
3.3
NS
56.3
31.3
12.5
177
68
28
64.8
24.9
10.3
NS
50
50
191
82
70 p < 0.001
30
21.1
78.9
103
85
54.8 p < 0.001
45.2
45.8
168
61.5
6.3
86
31.5 p < 0.0001
35.4
73
26.7
NS
6.3
53
19.4
p < 0.05
8.3
2.1
25.0
27
25
26
9.9
NS
9.2 p < 0.05
9.5 p < 0.0001
10.4
12
4.4
45.8 p < 0.001
p < 0.01
p < 0.01
p < 0.05
Results of П‡2 test
* This question was only for 188 respondents who have children
education, smoked more than people with other
levels of education (p < 0.01 and P < 0.0001
respectively).
Females who were separated, divorced or
widowed were eleven times more likely to smoke
than those who were currently married or single
(OR = 11.84; 95% CI, 5.06-27.51 and OR = 11.07; 95%
CI, 3.95-31.42 respectively).
Also, single males were fourteen times more
likely to smoke than single females (OR = 14.05;
95%CI, 6.62-30.45). Married males were 16 times
more likely to smoke than married females (OR =
June 2006
KUWAIT MEDICAL JOURNAL
16.39; 95%CI, 10.36-26.12). However, there was no
significant difference between the male’s marital
status and prevalence of smoking .
Table 2 shows the distribution of current
smokers by the age at which they began smoking,
the number of cigarettes consumed per day and the
kind of smoking. The majority of smokers (71.8%)
started smoking regularly when younger than 20
years of age. Significantly more males (78.7%) than
females (39.5%) began to smoke regularly before
they reached the age of 20 (p < 0.001). Females were
more likely to begin smoking in the age group of
20-24 years (47.9%).
The average age at which the respondent began
smoking was about 17 years in males and 20 years
in females (p < 0.001), whereas the average
duration of smoking was 15 years for males and 12
years for females (p < 0.05).
The average daily consumption of cigarettes
was about 21, but males consumed considerably
more cigarettes than females (22 and 14 cigarettes
daily respectively; p < 0.05). On the other hand,
more than three quarters of females (81.2%)
smoked less than 20 cigarettes daily while more
than half of females (53.3%) smoked more than 20
cigarettes daily (p < 0.001)
Many current smokers were using other methods
to smoke tobacco. 25% of females, which is
significantly higher than males (4.9%) (p < 0.01)
reported that they were using a narghile (also
known as Hubble-bubble, or sheesha) which is a
traditional form of social smoking. On the other
hand, 8% of males smoked other than cigarettes.
Table 3 shows that the most common reasons for
smoking for all participants were to relieve
boredom followed by the need to feel relaxed, to
relieve anger and frustration, to concentrate at
work, to relieve pressure of working hard and to
mix in social situations.
When data were examined separately for both
sexes, using smoking to relax (54.7%; p < 0.001) was
the most common reason given by males, whereas
using smoking to relieve boredom (75% ; p < 0.01)
was the most common reason given by females.
Out of 188 smokers who had children 54.8%
reported that they smoked in the presence of their
children, but it was clear that more males than
females did this (p < 0.01).
Two thirds (64.8%) of all smokers stated that
they wanted to stop smoking and about 70% had
attempted to quit. The attempts of men (74.2%) were
significantly higher than women (50%; p < 0.01).
For all participants the most common reasons
for not quitting for current smokers were a
perceived lack of will power (61.5%), the influence
of other smokers around (31.5%) and uncertainty
about how to quit (26.7%). Reasons for not quitting
in males differed significantly from females, for
103
Table 4: Patterns of smoking and factors associated with
quitting smoking among ex-smokers
Patterns
Male
(N = 87)
n
%
Age started smoking (years)
10-14
4
15-19
28
20-24
36
25-29
15
30 and above
4
No. of cigarettes smoked/day
<10
40
10-20
32
21-30
10
31-40
1
> 40
4
Age quit smoking(years)
10-19
1
20-29
56
30-39
23
40-49
7
Reasons for quitting
Harmful effects on health 58
Scientific evidence of
smoking hazards
41
Messiness of the habit
32
Influence of spouse
family members *
29
Prohibited by religion
34
Being a bad example
to children
29
Did not really enjoy
smoking
24
To improve sense of
taste or smell
19
Advised by physician *
13
Cost of cigarette
5
Method used to quit
Just quit/stopped suddenly60
Gradually decrease
no.of cigarette
9
First switched to
low tar cigarettes
2
Set a quit date
1
Quit with a friend/relative 5
Nicotine patch/gum
14
Attend stop smoking clinic 9
Female
(N = 38)
n
%
Total
n
%
4.8
32.2
41.4
17.2
4.8
5
9
10
12
2
13.2
23.7
26.3
31.6
5.3
9 7.2
37 29.6
46 36.8
27 21.6
6 4.8
46.0
36.8
11.5
1.1
4.6
16
20
2
0.0
0.0
42.1
52.6
5.3
0.0
0.0
56
52
12
1
4
44.8
41.6
9.6
0.8
3.2
1.1
64.4
26.4
8.0
3
25
8
2
7.9
65.8
21.1
5.3
4
81
31
9
3.2
64.8
24.8
7.2
66.7
21
55.3
69
55.2
47.1
36.8
14
10
36.8
26.3
55
42
44.0
30.6
33.3
39.1
2
10
5.3
26.3
31
44
24.8
35.2
33.3
9
23.7
38
30.4
27.6
7
18.4
31
24.8
21.8
14.9
5.7
9
0.0
0.0
23.7
0.0
0.0
28
13
5
22.4
10.4
4.0
69.0
23
60.5
83
66.4
10.3
5
13.2
14
11.2
2.3
1.1
5.7
16.1
10.3
2
2
3
7
3
5.3
5.3
7.9
18.4
7.9
4
3
8
22
12
3.2
2.4
6.4
17.6
9.6
Results of П‡2 test
* p > 0.05
instance, lack of will power, neighbour pressure,
stress at home and fear of weight gain.
Table 4 shows the patterns of smoking and
factors associated with quitting smoking among exsmokers. Out of all participants, 125 (87 males, 38
females) were classified as ex-smokers. The average
age at which ex-smokers started smoking was 21
years for both males and females with no
significant difference between sex (p > 0.05).
44.8% of ex-smokers had consumed fewer
cigarettes daily (less than 10), with no significant
differences between males and females.
104
Smoking among Health Care Workers of the Capital Governorate Health Region, Kuwait: ....
Approximately two thirds of ex-smokers
(64.8%) stopped smoking between the ages of 20
and 29 years. The average age of quitting for men
was 29 and for women was 27, with no significant
difference between males and females.
The most common reasons for quitting for both
men and women were the harmful effects of
smoking on health (55.2%) followed by scientific
evidence of the hazards of smoking (44.0%) and
being prohibited by religion (35.2%). However,
males’ reasons for quitting differed significantly
from females, in terms of influence of spouse and
family members and advice given by physicians. A
majority of ex-smokers (66.4%) reported that they
just quit without any formal plan, followed by use
of nicotine chewing gum or a patch (17.6%), by
gradually decreasing the number of cigarette
smoked (11.2%) and by attending a stop smoking
clinic (9.6%).
DISCUSSION
T h e re are no published studies on the
epidemiology of smoking in Kuwait among health
care workers ( i.e., those who are supposed to
introduce health care and are in direct contact with
people receiving health care and in the first line in
facing dangers of tobacco consumption). Published
studies on the prevalence of smoking in Kuwait
have been restricted to specific groups such as
physicians, university students, married couples
and Kuwaiti adults[18]. These studies reported that
the prevalence of smoking among physicians was
18.4% as current smokers and 15.8% as former
smokers[19]. 30% of male university students were
currently smokers, whereas 11.2% were former
smokers[20]. 37% of married Kuwaiti men were
currently smokers, whereas 0.5% of married
women were reported to be smokers[21]. Moody et
al[22] reported that the prevalence of smoking among
Kuwaiti adults working in different ministries was
34.4%. Our study showed that the prevalence of
smoking among health workers at the Capital
Health Region was relatively high. However, it was
consistent with the prevalence of smoking in other
countries. Siddiqui et al [13] showed that the
prevalence of smoking among health staff in Saudi
Arabia was 19%, ex-smokers 14% and non-smokers
67%.
The prevalence of smoking among physicians in
our study was 31.3% which is less than a previous
study done by Benner et al [12], where the prevalence
was 63%. Although our prevalence was lower, it
was still too high, particularly because physicians
should set a model for their patients; we know that
British doctors are unique in their rejection of
smoking with only 10 percent now smoking[26].
In general, patterns of smoking in men and
women
differ
between
developing
and
June 2006
industrialized countries. Significantly more men
(40-60%) but fewer women (2-10%) smoke in
developing countries compared with approximately
25-30% of both men and women who smoke in
industrialized countries[23]. Women in developing
countries tend to have lower rates of smoking, start
smoking later than men, and consume fewer
cigarettes daily. Smoking is not common among
Arab women due to Arab culture and more likely
because Islamic teaching forbids smoking, considering
it both distasteful and unlawful[24]. This is consistent
with our study which showed that smoking among
males was 12 times more than among females. On
the other hand, 25% of females were regular users
of the water pipe, which indicates a new trend in
female behavior and their direction towards this
kind of smoking.
Our data showed that the highest prevalence of
smoking was in those working as clerks and the
lowest in the nurses’ group. A similar study in
Saudi Arabia reported similar results and attributed
that to the kind of work in different departments as
nicotine also had a relaxing effect and a pleasure
enhancing effect and the workers in the department
started smoking under the influence of other fellow
smokers[13].
The separated, divorced and widowed group
showed a high prevalence of smoking among males
(47%) and females (6.5%). For females, this group
was 11 times more likely to be smoking than
married or single women. The explanation of this
may be found in social structures.
Our results showed an inverse relation between
education and smoking prevalence. This is consistent
with similar study done in Kuwait which showed
that respondents with less education (only
primary) were 3.5 times more likely to smoke than
those with more education (university level)[18].
Concerning cigarette-smoking initiation for
current smokers, we found the majority of smokers
of both sex combined (71.8%) started smoking
when younger than 20 years old. This finding is
consistent with many studies which suggests that
individuals who initiate cigarette smoking habits
during childhood are at higher risk of becoming
long-term smokers than those who initiate smoking
in adolescence[28,29].
It has been reported that the highest probability
of smoking initiation was found for the age group
15-20 years[22], which is consistent with our study. A
study by Sugathan et al[20], showed that one tenth of
the students initiated smoking between ages 16 and
17 with the rate increasing and reaching 30% by age
20 and almost 50% by the age of 24.
Our study showed that to relieve boredom was
a major reason for females to smoke, but less so in
males. This can be explained by the fact that
females play a dominant role in taking care of their
June 2006
KUWAIT MEDICAL JOURNAL
family which make them face a lot of stress. On the
other hand, stress at work was a remarkably trival
reason for males to smoke since they are used to
looking after their future in the active period of
their life.
In Memon’s study[18] the percentage of current
smokers who have smoked in front of their children
was 77%; in our study it was lower but still too
high. This is an important issue concerning the
health consequences of passive smoking on
children and awareness of hazards of passive
smoking should be increased especially in our
participants because they are health care providers.
Furthermore, parents who smoke should be aware
that their children might become ill as a result of
breathing in airborne tobacco smoke. Also, the
children of smokers are more likely to take up the
habit themselves because they copy the behaviour
of adults and will perceive smoking as the norm if
they grow up in a household where adults smoke[30].
About two thirds of our current smokers (64.8%)
had wanted to stop smoking and 70% of them had
tried. This finding raises the need for strengthening
and targeting the programs directed against
smoking particularly clinics working to help
smokers stop smoking especially because we found
9.6% of ex-smokers had stopped by attending a
stop-smoking clinic. This result is consistent with
the findings of other authors who showed that an
estimated 70% of smokers (33.2 million) want to
quit, but only 2.5% (1.2 million) per year succeed in
quitting smoking permanently[31,32].
For ex-smokers, the age of starting smoking was
obviously different from current smokers. The highest
percentage of ex-smokers had started smoking later
than the age of starting for current smokers. We can
conclude that starting smoking later helps in
quitting. Ex-smokers also used to smoke fewer
cigarettes than current smokers.
About reasons for quitting smoking: in exsmokers, knowledge of the harmful effects of
smoking on health was the highest percentage with
no significant difference between the two sexes.
Siddiqui et al[13] reported that awareness regarding
the harmful effect of smoking was 96%. This
awareness regarding harmful effects may be due to
strong social and cultural consensus against
smoking. Conversely, the lowest percentages of
reasons were the cost of cigarettes and advice from
a physician (4.0%, 10.4% respectively) which raise a
big question about the role of physicians in helping
their patients to stop smoking. Many studies have
shown that the role of physicians in helping their
patients stop smoking is crucial and can have a
significant impact on helping patients to stop
smoking by giving them strong recommendations
to quit[25,26]. One recent study reported that only 15%
105
of smokers who saw a physician in the past year
were offered assistance with quitting, and only 3%
were given a follow-up appointment to address the
problem[33].
CONCLUSION
The emphasis of public health policies tends to
be strongly on curative care. Less emphasis is
placed on preventive programs, which are often
viewed as less urgent and less important because
they are less specific and are focused on groups
within the population who may still be healthy.
Although these can make a major impact on health
education and various economic strategies, these
strategies are more effective when used in
combination[34].
Cigarette smoking is an important public health
problem in Kuwait generally and in health care
workers specifically. Given that health care
providers should set a model for others, they
should receive a continuous education about
smoking hazards as well as smoking cessation
techniques to help their clients stop smoking.
Systematic interventions have been shown to
increase patient smoking cessation rates, even with
very modest expectations; 100,000 physicians using
effective intervention can produce over 3 million
new ex-smokers in the United States each year[35].
Cross-sectional studies should be conducted
regularly to monitor changes in prevalence, attitudes,
behavioral and socio-demograghic determinants of
starting, continuing and quitting smoking. Also,
effective strategies for treating tobacco addiction
should include brief advice by medical providers,
counselling, and pharmacotherapy.
ACKNOWLEDGMENT
We would like to express our thanks and
gratitude to Dr Ahmed Al-Sebeei, the director of
Capital Health Region. We are also grateful to all
health care workers at Capital Health Region who
gave us their time to answer our questionnaires.
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June 2006
KUWAIT MEDICAL JOURNAL
Original Article
Sheesha Smoking among a Sample of Future Teachers in
Kuwait
Heyam R A Mohammed1, Ian M Newman 2, Raja Tayeh3
Department of Curriculum and Instruction, Kuwait University, Kuwait
Department of Educational Psychology, University of Nebraska-Lincoln, USA
3
Department of Teaching, Learning and Teacher EducationUniversity of Nebraska-Lincoln, USA
1
2
Kuwait Medical Journal 2006, 38 (2): 107-113
ABSTRACT
Objective: To assess the prevalence of sheesha smoking
and the personal, social and environmental factors
associated with it.
Subjects and Methods: A convenience sample of 761
students (261 male, 500 female) in the teacher training
program of the Public Authority for Applied Education
and Training in Kuwait City answered a 70-question
survey regarding sheesha use. Data were analyzed using
SPSS version 10.
Results: 24.6% of males and 5.5% of the females smoked
sheesha. 49.2% of the male sheesha smokers smoked at
least one bowl a day, as did 26.9% of the female sheesha
smokers. The majority of sheesha smokers first started
smoking sheesha at age 18 or older. Almost half were
encouraged to smoke sheesha the first time by their
friends. The majority of sheesha non-smokers had
sheesha non-smokers as friends. Among the sheesha
smokers, 59.2% of females and 61.3% of males said all or
most of their friends smoked sheesha. Sheesha smokers
were more likely than sheesha non-smokers to live in a
home where there are other sheesha smokers. Half of the
males and one-third of the females who smoked sheesha
wanted to quit. The majority of sheesha smokers also
smoked cigarettes. Teachers, including female teachers,
were frequently seen smoking in their schools. As
expected, sheesha smokers had more positive attitudes
towards sheesha smoking and were less likely to believe
in its harmful effects.
Conclusions: This is the first known study of sheesha use
among college students in Kuwait. Results suggest
efforts to reduce sheesha smoking in this young
population should: 1) help young people address
pressures from peers, 2) reduce sheesha smoking at home
and school environment, 3) counteract personal beliefs
and attitudes that contribute to sheesha smoking, and 4)
reinforce beliefs about the health risks of sheesha
smoking.
KEYWORDS: attitude, behavior, belief, tobacco survey
INTRODUCTION
The water pipe, known in Arabic as nargile or
sheesha and in English as hookah, is a traditional
Arab method of smoking tobacco, especially for
men. In this article the term sheesha refers to all
types of water pipe, nargile, or hookah used for
inhaling tobacco smoke. Water pipes present an
especially attractive means of smoking tobacco.
They are frequently beautiful works of art
representing an exotic tradition and the promise of
relaxation and pleasure. They can be used by
several people at the same time contributing to
friendship and camaraderie. The mix of rolled
tobacco leaf, molasses and flavouring used to
produce jurak allows for many taste preferences.
When inhaled, the sound of the smoke bubbling
through the water adds an auditory pleasure. The
water cools the smoke allowing deep inhalation,
maximizing the opportunity to appreciate the
smoking sensation. These aesthetic and social
qualities of sheesha smoking have likely
contributed to the recent spread of sheesha use
around the world. This study assessed the
prevalence of sheesha smoking and the personal,
social and environmental factors associated with it
in a student population.
Studies of Tobacco Use in Kuwait
Data on sheesha smoking in Kuwait and other
Arab countries are limited. Cigarette smoking,
however, has been described quite extensively,
suggesting possible patterns of sheesha use.
Cigarette smoking in Kuwait is increasing,
especially among young males, and the age of
Address correspondence to:
Professor Ian Newman PhD, University of Nebraska-Lincoln, Department of Educational Psychology, P. O. Box 880345, Lincoln, NE 68588-0345
USA. Tel: 402 472 3844, Fax: 402 472 8319, E-mail: [email protected]
108
Sheesha Smoking Among a Sample of Future Teachers in Kuwait
beginning smoking is declining. Memon et al [1] and
Moody et al[2] reported that 34.4% of males and 1.9%
of females smoked cigarettes at the time of their
survey and had smoked more than 100 cigarettes in
their lifetime. Memon et al reported that 13.8% of males
and 7.7% of females began smoking cigarettes
between the ages of 10 and 14, and 56.5% of the
males and 25.6% of the females began smoking
between the ages of 15 and 19[1]. More than half of
the male cigarette smokers (57%) and 69% of the
female cigarette smokers also smoked other types
of tobacco, most often sheesha. Behbehani et al’s
2004 survey of tobacco use among Kuwait
physicians reported 18.4% smoked cigarettes and
12% smoked sheesha[3]. A 1993 study of Kuwait
physicians reported 31% smoked cigarettes [4].
Cigarette smoking was reported by 37% of married
Kuwaiti men [5] and 30% of male Kuwait university
students[6].
Tobacco Use in Other Arab Countries
In Syria, among a sample of 587 university
students, 30.9% of males and 7.4% of females were
cigarette smokers, with 24.8% of males and 5.2% of
females reporting daily smoking. The same study
reported that 62.6% of men and 29.8% of women
had tried smoking sheesha, and 25.5% of men and
4.9% of women were at least occasional sheesha
smokers. Only 7% of the men smoked sheesha
daily[7,8]. Among primary care physicians in Bahrain
26.6% were reported smokers and 18.8% were daily
smokers[9]. In Iran, 26.0% of men and 3.6% of
women were reported current cigarette smokers[10].
In Saudi Arabia, a 2004 study reported 29.8% of
male secondary school students were current
cigarette smokers and 83.7% of these smokers
started smoking at age 15 years or less[11]. Abolfotouh
et al reported cigarette smoking at 30.6% among
male Saudi college students [12].
The World Health Organization reports that
smoking prevalence among young people in Arab
countries differs greatly: 7% in Oman, 14% in Iran,
18% in Kuwait, 23% in Iraq, 25% in Saudi Arabia
and Jordan, 31% in Syria, 43% in Yemen and 53% in
Lebanon[13].
Sheesha
Many consider sheesha smoking less harmful
than cigarette smoking because they believe the
water filters out the harmful substances. Sheesha
smoke does contain less nicotine than cigarette
smoke but more carbon monoxide. Zahran, Ardawi
and Al-Fayez found higher blood carboxyhemoglobin concentration in sheesha smokes than
in cigarette smokers [14]. The World Health
Organization reported, “sheesha is lighter than
other forms of tobacco smoking, but generates a
June 2006
high level of carbon monoxide, in part from the
charcoal that keeps the jurak burning’[15]. Cigarette
smokers and sheesha smokers are more likely to
report coughs, dizziness, headaches, palpitation,
nausea, epigastric pain and heartburn than nonsmokers[16]. Both sheesha smokers and cigarette
smokers have a higher risk of developing
pulmonary diseases such as obstructive airway
disease (OAD) than non-smokers.
Many Islamic scholars recognize that smoking is
harmful and conclude that smoking is, therefore,
forbidden by the Qur’an and the Hadith[17]. The
Qur’an, however, is silent on the specific topic of
tobacco[18] and no verse in the Qur’an specifically
prohibits smoking tobacco. The Qur’an does give
guidance for distinguishing right from wrong and
commands the avoidance of wrong behavior.
Major wrongs outlined in the Qur’an include
harming oneself or others[19-21]. Medical evidence
suggests that smoking and exposing others to
second-hand smoke causes significant harm[22].
SUBJECTS
Our subjects were 761 students (261 male and
500 female) enrolled in the teacher training
program of the Public Authority for Applied
Education and Training in Kuwait City, Kuwait.
The average age for subjects was 21.0 years for
males and 20.8 years for females. The sample for
this cross-sectional study was constructed by
randomly sampling classes in the teacher training
program until 900 students were identified and
asked to voluntarily answer the questionnaire.
Students completed questionnaires in the sampled
classes.
METHOD
A questionnaire was developed to explore
sheesha smoking behavior and attitudes and beliefs
about the dangers of sheesha smoking. Questions
were based on a careful review of the available
literature and interviews and discussions with
young people in Kuwait. The initial questionnaire
was pilot tested with 30 volunteer students at the
University of Kuwait, College of Education. Revisions
to the questionnaire were based on feedback from
the College of Education students and on
discussions and review by a panel of experts in
questionnaire development. The final version of the
questionnaire contained 70 questions: 23 questions
about sheesha use were answered only by sheesha
smokers and 12 questions about beliefs regarding
sheesha were answered only by sheesha nonsmokers. All students responded to eight attitude
statements and ten belief statements. The attitude
and belief statements were answered on a fivepoint scale (1 = strongly disagree, 2 = disagree, 3 =
June 2006
KUWAIT MEDICAL JOURNAL
Table 2: Friends’ Sheesha smoking
Table 1: Demographic characteristics of the sample
Gender
Class standing
First year
Second year
Third year
Fourth year
Total
Missing
Age
17-21
22-26
27 and over
Total
Missing
Marital status
Married
Single
Divorce/widow
Total
Missing
109
n
Male
%
n
Female
%
n
Total
%
261
34.3
500
65.6
761
100.0
49
54
58
98
259
2
18.9
20.9
22.4
37.8
100.0
158
160
86
96
500
0
31.6
32.0
17.2
19.2
100.0
207
214
144
144
759
2
27.3
28.2
19.0
25.5
100.0
164
87
6
257
4
63.8
33.9
2.3
100.0
341
138
19
498
2
68.5
27.7
3.8
100.0
505
225
25
755
6
66.9
29.8
3.3
100.0
29
226
6
261
0
11.1
86.6
2.3
100.0
187
303
8
498
2
37.6
60.8
1.6
100.0
216
529
14
759
2
28.5
69.7
1.8
100.0
neither disagree nor agree, 4 = agree, and 5 =
strongly agree). The remaining questions asked
about sheesha and tobacco use and demographic
characteristics. Questions about attitudes toward
sheesha by sheesha smokers and non-smokers had
reliability coefficients of 0.98 and 0.97, respectively.
Two of the belief statements were eliminated from
the analysis because the wording of the statements
was confusing. The remaining questions about
beliefs had a reliability coefficient of 0.51, well
within the acceptable range [23].
In this study, anyone who said they smoked
sheesha and had smoked sheesha for at least one
month was classified as a sheesha smoker. Those
who had not smoked sheesha or said they had quit
were classified as sheesha non-smokers.
RESULTS
Seven hundred sixty-one (84.5%) students
returned usable questionnaires for analysis. The
sample is described in Table 1.
Sheesha use and age of onset
Twenty-four percent (24.6%) of males and 5.5%
of females were sheesha smokers. The males were
more likely to smoke at least one bowl a day
(49.2%) than females (26.9%). Of the male sheesha
smokers, 15.5% reported their first use was before
the age of 14 years, as did 4.0% of the females.
Another 30 percent of the males and 12.0% of the
females reported their first use of sheesha between
ages 14 and 17 years. The majority of the sheesha
smokers (63.9%) did not begin until they were 18
years or older (54.5% of males and 84.0% of
Sheesha Sheesha
Smokers Non-smokers
n
%
n
%
How many of your
close friends smoke sheesha?
MALES
All of them
10
Most of them
28
A few of them
19
None/I don’t know
5
Total
62
FEMALES
All of them
4
Most of them
12
A few of them
6
None/I don’t know
5
Total
27
Total
n
%
16.2
45.1
30.6
8.1
100.0
10
39
25
119
193
5.2
20.2
13.0
61.6
100.0
20
8.0
67 26.2
44 17.3
124 48.5
256 100.0
14.8
44.4
22.2
18.6
100.0
3
25
76
354
458
0.6
5.4
17.0
77.0
100.0
7
1.4
37
6.8
82 17.2
359 74.6
485 100.0
Males: П‡2 = 55.03, df=3, p<0.05; Females: П‡2 = 98.59, df=3, p<0.05; Missing: 5
males and 15 females did not answer this question.
females). Almost half of the sheesha smokers were
first encouraged to smoke by their friends (47.6%).
Sheesha Use and Cigarette Smoking
This study uses the U.S. Center for Disease
definition of a cigarette smoker: A cigarette smoker
is someone who smoked cigarettes and had
smoked cigarettes for at least one month[24]. Thirtynine percent (38.8%) of males and 7.9% of females
were cigarette smokers. Of the male sheesha
smokers, 71.4% were also cigarette smokers and of
the female sheesha smokers 63.0% were also
cigarette smokers. Among the sheesha nonsmokers 28.1% of the males and 4.6% of the females
smoked cigarettes.
Social and Environmental Factors
Considerable research suggests that social
factors, such as the behavior and expectations of
other people, and environmental factors, such as
the availability of sheesha, rules and regulations
about sheesha sale and use, penalties for breaking
rules, and public attitudes toward sheesha have a
significant effect on the behavior of young
people[25]. Changes in the social environment of
Kuwait have possibly encouraged sheesha smoking
and need to be considered in interpreting these
results.
Sheesha in the home
Almost all of these sheesha smokers (96.4%)
smoked in their homes. Forty-three percent (42.8%)
of the male sheesha smokers and 74.1% of the
female sheesha smokers reported two or more
other sheesha smokers living in their home. Of the
sheesha non-smokers, 41.5% of the males and 46.7%
Sheesha Smoking Among a Sample of Future Teachers in Kuwait
110
Table 3: Friends’ attitudes toward Sheesha Smoking
Sheesha
Smokers
n
%
Sheesha
Non-smokers
n
%
Table 4: Beliefs about Sheesha
%
Among your friends, how accepted would you say that sheesha
smoking is?
MALES
Very accepted
Accepted
Neither accepted
nor unaccepted
Unaccepted
Very unaccepted
Total
FEMALES
Very accepted
Accepted
Neither accepted
nor unaccepted
Unaccepted
Very unaccepted
Total
Sheesha
SheeshaSmokers Non-smokers
M
SD
M
SD
Total
n
June 2006
10
21
15.8
33.4
9
39
5.2
20.2
20
60
7.8
23.5
7
18
7
63
11.1
28.6
11.1
100.0
25
38
81
193
12.9
19.7
42.0
100.0
32
56
88
256
12.5
21.8
34.4
100.0
8
11
29.6
40.8
4
35
0.8
7.7
12
46
2.5
9.6
3
5
0
27
11.1
18.5
.0
100.0
39
93
286
457
8.5
20.4
62.6
100.0
42
98
286
484
8.6
20.2
59.1
100.0
Males: П‡2 = 26.18, df=4, p<0.05; Females: П‡2=131.5, df=4, p<0.05; Missing: 5
males and 16 females did not answer this question.
of the females lived in homes where nobody else
smoked sheesha. Only 16.1% of the male sheesha
non-smokers and 20.2% of the female sheesha nonsmokers lived in homes with two or more sheesha
smokers. More than half (59.7%), of the male
sheesha smokers indicated that smoking was not
allowed in any part of their homes, whereas 33.3%
of the female smokers indicated smoking was not
allowed in any part of their home.
Friends’ behaviour and attitudes
Friends’ behaviors and attitudes have been
shown in a large number of studies to be a
particularly powerful force in shaping someone’s
behavior[26-28]. Table 2 shows that sheesha smokers
were significantly more likely to have sheesha
smokers as friends: 61.3% of the male sheesha
smokers and 59.2% of the female sheesha smokers
said all or most of their friends smoked sheesha.
Sheesha non-smokers were significantly more
likely to have friends who were sheesha nonsmokers or to not know the sheesha smoking status
of their friends. Peer pressure (wanting to be like
your friends) depends upon knowing your friends’
behavior; therefore, it was appropriate to combine
friends whose sheesha smoking status was
unknown and friends who were sheesha nonsmokers because neither group would be known by
their friends as sheesha smokers.
Friends’ attitudes toward sheesha smoking were
also related to sheesha smoking (Table 3). About
half (49.2%) of the male sheesha smokers and 70.4%
MALES
Inhaling smoke from a parents’ sheesha
harms the health of babies and children
Sheesha smoking is associated with
decreased oxygen in the blood
Sharing a sheesha mouthpiece can lead to
transmission of infection/disease
Smoking sheesha daily for a period of time
might cause mouth ulcers
Smoking sheesha is associated
with lung cancer
Smoking sheesha is associated with diseases
such as heart disease and high BP
Sheesha contains more carbon
monoxide compared to cigarettes
FEMALES
Inhaling smoke from a parents’ sheesha
harms the health of babies and children
Sheesha smoking is associated with
decreased oxygen in the blood
Sharing a sheesha mouthpiece can lead to
transmission of infection/disease
Smoking sheesha daily for a period of
time might cause mouth ulcers
Smoking sheesha is associated
with lung cancer
Smoking sheesha is associated with diseases
such as heart disease and high BP
Sheesha contains more carbon monoxide
compared to cigarettes
t
3.83 1.432
4.24 1.248 2.217*
3.38 1.136
3.79 1.049 2.546*
3.41 1.291
4.01
3.18 1.222
3.75 1.036 3.628*
3.67 1.107
4.10 1.086 2.764*
3.61 1.150
4.06 1.098 2.738*
3.14 1.060
3.64 1.051 3.239*
4.07 1.141
4.54
.971 2.385*
3.67
1.00
4.03
.892 2.047*
3.74 1.163
4.36
.832 2.666*
3.56
.934
4.10
.835 3.251*
3.81
.921
4.34
.845 3.126*
4.04
.706
4.38
.800 2.429*
3.42
.809
3.72
.900 1.668*
.957 3.354*
Scale: 1 = strongly disagree, 2 = disagree, 3 = neither disagree nor agree,
4 = agree, 5 = strongly agree. *p < 0.05 after Levine’s post test with Welch’s
adjustment[29,30], BP= blood pressure
of the female sheesha smokers reported that
sheesha smoking was either accepted or very much
accepted by their friends. Among the sheesha nonsmokers, 61.7% of the males and 83.0% of the
females reported that sheesha smoking was either
unaccepted or very much unaccepted by their
friends. Both males and females tended to have
friends whose behavior and attitudes reflected their
own behaviors, but for females there was a
tendency for homogeneity of friendship groups to
be more pronounced.
Teacher behavior
Almost all the males (93.4%) and almost half of
the females (44.6%) had observed their teachers
smoking cigarettes inside their schools.
Quitting
Among the current sheesha smokers 50.8% of
the males and 33.3% of the females had tried to quit
and 58.7% of the males and 26.0% of the females
said they would like to quit. Of those who had tried
June 2006
KUWAIT MEDICAL JOURNAL
to quit in the past, 59.4% of the males and 33.3% of
the females said they would still like to quit.
Attitudes and Beliefs about the Dangers of
Sheesha Smoking
An independent t-test indicated a statistically
significant difference in the attitudes of sheesha
smokers and sheesha non-smokers. As expected,
across both genders, sheesha smokers had more
positive attitudes towards sheesha smoking than
sheesha non-smokers (t =3.776, p < 0.001 for males
and 3.153, p = 0.002 for females).
Similarly, an independent t test indicated that
both male and female sheesha non-smokers were
more likely to believe in the statements about the
danger of sheesha smoking than were sheesha
smokers (t = 3.767, p < 0.001 for males and t =3.792,
p < 0.001 for females).
Because the belief scale had not previously been
validated, each item was examined individually
using a non-parametric t test and Levine’s post test
with Welch’s adjustment[29,30]. Results indicated that
all seven items showed significant differences
between sheesha smokers and sheesha nonsmokers for males and six of the seven items
showed significance for females (Table 4).
DISCUSSION
This is the first known study of sheesha
smoking among future teachers in Kuwait.
Therefore, it is not possible to compare these
findings with other Kuwait studies. A comparison
of these Kuwait findings for sheesha smoking with
survey data on cigarette smoking gives some
perspective to the results. In Kuwait, among the
adult population 34% of the males and 2% of the
females reported smoking cigarettes[1,2]. In this
sample of students, 38.8% of the males and 7.9% of
the females reported smoking cigarettes, and 24.6%
of the males and 5.5% of the females reported
sheesha smoking. These results indicate that more
college females smoke cigarettes than females in
the general population[1,2]. Comparable data for
sheesha smoking is not available. Whether or not
this represents an increase in smoking among
younger Kuwaiti females is not clear. It does
suggest the need for public health workers to
carefully monitor cigarette and sheesha smoking
rates among males and females and to consider the
need for specific tobacco education programs for
females.
Data from Saudi Arabia and Syria allow
comparison of sheesha use by male college
students. Sheesha smoking among male college
students in Kuwait (24.6%) is comparable to the
27.3% found for male college students in Saudi
Arabia and the 25.5% found for males in the general
111
population in Syria [8,12].
The male sheesha smoking rate of 24.6% in this
Kuwait sample of students is lower than the 34% of
the total male population that smokes cigarettes as
reported by Memon et al and Moody et al[1,2], but still
suggests that sheesha smoking is a significant
public health issue.
The apparent popularity of sheesha smoking is
difficult to explain. The widespread attention
focused on the dangers of cigarette smoking and
increasing efforts to discourage cigarette smoking
might unintentionally encourage sheesha smoking,
since sheesha smoking is viewed as a less
dangerous alternative. Anti-smoking messages are
often specific to cigarettes. Some cigarette packs
carry warning labels about the dangers of smoking
to health. Because sheesha pipes are frequently
prepared by someone other than the smoker, any
printed health warnings are rarely seen by the
smoker. Increasing attention to Arab identity
possibly contributes to an increase in sheesha
smoking. Sheesha has traditionally been a unique
middle-east practice, associated with socializing,
relaxing, the company of friends and the esthetics
associated with the beauty of the water pipes
themselves. As sheesha gains popularity
throughout the world, it may also increase sheesha
use in the countries where it has long been a
tradition. Similarly, the increasing emancipation of
women may encourage sheesha smoking among
women.
The acceptance of sheesha smoking in a variety
of social settings may be influencing young
people’s intentions to use sheesha. During
Ramadan, for example, sheesha smoking is a
common practice when families and friends gather
to break the fast. Because this is an especially
important social event, the messages received by
young people watching this adult behavior may
impact a young person’s behavior in the future. For
example, if a young person views sheesha smoking
as an adult behavior, he or she may imitate the
behavior as a means to becoming “more adult.” The
strong association of the sheesha behavior of those
students with the finding that most sheesha
smoking occurred at home (96.4%) and the finding
that 74.1% of the female sheesha smokers were
from homes with two or more other sheesha
smokers again reflects a clear message of
acceptance, even for females.
A majority of the students in this sample have
seen their teachers smoking cigarettes (though not
sheesha). This is another environmental factor that
may affect young people’s attitude regarding
smoking in general. Teachers are typically admired
by young people and this adds to the impression
that society apparently accepts smoking.
112
Sheesha Smoking Among a Sample of Future Teachers in Kuwait
One of the most potent environmental forces is
the influence of friends (peer pressure)[26-28]. These
results, like results from practically all other studies
of smoking behavior, confirm the influence of
friends. These data show that the sheesha nonsmokers have sheesha non-smokers as their friends
and that smokers have sheesha smokers as friends.
The finding that the friendship patterns of female
sheesha smokers and non-smokers were more
homogeneous than for males suggests that sheesha
smoking by females is not as accepted in society - a
condition that public health workers should
reinforce. This finding and the finding that a
majority of female sheesha users came from homes
with two or more other sheesha smokers suggested
there is a family acceptance of a behavior that is not
yet publicly accepted. Understanding the dynamics
of friendship patterns (both male and female) has
been a focus of western social scientists for some
time, but friendship patterns have not been studied
as extensively among Middle Eastern youth. It is
not possible, therefore, to assume that friendship
patterns in the Middle East are the same as
friendship patterns among western young people.
There is a need for studies on this topic, if effective
programs to discourage smoking among young
people are to be developed.
Other environmental factors such as the
examples set by parents and teachers and available
entertainment opportunities in the community are
often overlooked in understanding young people’s
behavior. The leisure patterns of young males, such
as spending time with their friends going around
the community together, watching TV, playing cards
and drinking tea, provides many opportunities for
smoking cigarettes and sheesha. Cafes and
restaurants provide places where it is easy for
young men to smoke sheesha. The females’
environment is more restricted. Young females are
encouraged to stay at home and spend time with
their friends in the house. Consequently female
sheesha smokers come from homes where sheesha
smoking is accepted and they choose friends who
are also sheesha smokers.
As evidence of the health related dangers of
sheesha smoking accumulates, it is important for
health workers to carefully measure the extent of
sheesha smoking and its associated motivations.
Understanding the motivations to smoke sheesha
will be critical for the development of educational
initiatives to discourage this behavior. Because
sheesha smoking is a long-standing traditional
behavior, its reduction will present challenges as
complicated, if not more complicated, than the
challenges of decreasing cigarette smoking.
The finding that sheesha smoking and cigarette
smoking tend to occur together in the same
June 2006
segments of the population suggests these two
behaviors may be dealt with together when
formulating public health strategies to reduce or
prevent smoking. But we do not understand
whether these two behaviors (sheesha smoking and
cigarette smoking) are motivated by the same
factors and whether the two behaviors would be
responsive to similar educational interventions.
Sheesha smokers who do not smoke cigarettes may
have quite different motives for smoking than
sheesha smokers who also smoke cigarettes.
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Moody PM, al-Bustan A, al-Shatti A. Cigarette smoking
habits among Kuwait University male students pre-and
post-invasion periods: 1990-1993. Journal of the Kuwait
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Bachir ME, Fouad MF, and Ward KD. Characteristics of
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in Syria. Prev Med 2004; 39:330-336.
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Rastam S, Eissenberg T, Ward KD. Prevalance and
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Hamadeh RR. Smoking habits of primary health care
physicians in Bahrain. J R Soc Health 1999; 119:36-39.
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Mediterranean Publication, Report # 23; 2001.
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concentration in smokers of sheesha and cigarette in Saudi
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16. Zahran FM, Ardawi SM, Attallah AA. Hazard of smoking
sheesha in Saudi Arabia. Riyadh, Directorate of Scientific
Research, King Abdul College of Science and Technology,
1988.
17. Strauch S. The evil of smoking [downloadable file 8KB]. AlAin, UAE: Zayed Centre for New Muslims. Available at
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18. Gabb S. Smoking and its enemies: a short history of 500
years of the use of and the prohibition of tobacco
(brochure). London: The Freedom Organization for the
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20. Qur’an (Surah al-Baqarah 2:195).
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Michigan: Al-QuГ•ran was-Sunnah Society of North
America, 1996. Available at http://www.qss.org/articles/
smoking.html. Retrieved November 24, 2004.
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KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Pretransplant Antitubercular Therapy - How Long?
Amitava Mukherjee, Antony Devasia, Lionel Gnanaraj, Ninan Chacko, Nitin Kekre, Ganesh Gopalakrishnan
Department of Urology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
Kuwait Medical Journal 2006, 38 (2): 114-117
ABSTRACT
Objective: To define a safe duration of antitubercular
therapy in patients on dialysis awaiting a kidney
transplant. Patients with chronic renal failure are more
prone to develop tuberculosis than the general
population. Continuing dialysis till completion of
antitubercular therapy (ATT) has its problems both in
terms of morbidity and finances. Since most patients in
developing countries have to pay for their dialysis, it is
important to define a safe duration of ATT prior to renal
transplantation which balances the risk of flare up of
tuberculosis with the problems of prolonged dialysis.
Design: Retrospective.
Setting: Department of Urology, Christian Medical
College, Vellore, Tamil Nadu, India.
Materials and methods: Records of 1360 patients who
had received renal allograft at our hospital were
reviewed retrospectively. Patients who were found to
have tuberculosis prior to transplantation and received
therapy according to our hospital protocol were assessed
for the duration of pre transplant ATT and their outcome
after transplantation.
Results: Out of 96 patients who received ATT starting at
a mean of 122 В± 82 days before transplant, only one
developed tuberculosis in the post transplant period. Of
the 96 patients, a subgroup of 23 patients had received an
allograft between six to eight weeks after initiating ATT,
while the rest were transplanted at varying periods after
that. At a mean follow up of 29 months post transplant,
none of these 23 patients developed recurrence of
tuberculosis. This compares favorably with a 13.3%
incidence of post transplant tuberculosis among those
patients who did not have the disease preoperatively.
Conclusion: Renal transplantation after 6-8 weeks of ATT
is probably associated with a minimal risk of flare up of
the disease in the post transplant period.
KEYWORDS: allograft, ESRD, Mycobacterium, renal transplant, tuberculosis
INTRODUCTION
Tuberculosis (TB) is a common disease in India.
It is estimated that at least 50% of the Indian
population above the age of 20 years is infected
with the tubercle bacillus and remains at risk of the
disease[1]. The prevalence of tuberculosis in the
urban population in India is 1.3%[2]. Compared to
the general population, the risk of tuberculosis in
India, in patients undergoing dialysis, is reported
to be as much as 13 times higher[3]. Reports from the
US put the relative incidence at 10 -15 folds[4,5] while
in Turkey it is reported to be between 24 and 273
times[6,7]. With increasing number of end-stage renal
disease (ESRD) patients undergoing renal transplantation, the problem of balancing the risk of flare-up
of the disease in the post transplantation period
and the risk and expense of maintaining these
patients on dialysis assumes greater significance.
We attempted to review the outcome of management
of these patients at our hospital and identify a
reasonably safe period after starting ATT when
renal transplantation could be performed.
MATERIALS AND METHODS
We reviewed the records of 1360 patients for
whom adequate information was available and
who had undergone renal transplantation at our
centre between 1985 and 2001. Patients who had
tuberculosis prior to renal transplantation and
received ATT in the peritransplant period were
included in the study. The predominant location of
tubercular involvement and the duration of
antitubercular therapy prior to renal transplantation
were studied. We also looked at the posttransplantation period for possible recurrence or
reinfection with the tubercular bacillus.
Patients suspected of having tubercular lung
involvement were assessed by chest X-ray, sputum
acid fast bacillus (AFB), gastric juice AFB or
bronchoalveolar lavage specimen for AFB smear
and culture. Tissue diagnosis was obtained from
accessible lymph nodes, pleura or from the
pericardium in patients requiring an open
pericardiostomy for effusion with tamponade.
Pleural or pericardial fluid was also stained and
Address correspondence to:
Dr. G. Gopalakrishnan MS, MCh, Professor and Head, Dept. of Urology -II, Christian Medical College and Hospital, Vellore-632 004, Tamil
Nadu, India. Tel: +91-416-2222102 (Ext: 2111), Fax: +91-416-2232035, 2232105, E-Mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
115
Table 1: Distribution of site of pre transplant tuberculosis (n
= 96)
Table 2: Distribution of findings in patients with PUO (n
= 34)
Site of infection
n
%
Site of infection
PUO
Lymph node
Pulmonary
Pleural effusion
Positive gastric juice AFB
TB Spine
Abdominal tuberculosis
Genitourinary tuberculosis
Miscellaneous
Total
29
26
19
6
6
3
3
2
2
96
30.2
27.0
19.8
6.3
6.3
3.1
3.1
2.1
2.1
100
cultured for AFB. Patients suspected to have
disseminated disease or those without localizing
signs underwent bone marrow aspiration for AFB
smear and culture. Patients with suspicious lymph
nodes in areas difficult to access, those with pyrexia
of unknown origin or those with lymphocytic
exudative collections negative for AFB on smear,
were assessed by their response to a therapeutic
trial of anti tubercular drugs, while awaiting
culture reports. A positive therapeutic response is
usually seen by about two weeks in the form of
resolution of fever, weight gain, improvement in
appetite and a feeling of general well being.
Serological tests and PCR were not routinely
performed for the diagnosis of tuberculosis in these
patients.
All patients received 18 months of antitubercular
therapy beginning with rifampicin (10 mg/kg/d),
isoniazid (INH - 5 mg/kg/d), ethambutol (25
mg/kg/d) and pyrazinamide (35 mg/kg/d). Doses
of drugs were modified according to the renal
function. Ethambutol and pyrazinamide require
50% dose reduction in ESRD while INH is given at
150-200 mg per day in adults. Five days prior to
transplantation rifampicin was substituted with
ofloxacin (400 mg in adults) at the time when
cyclosporine is started. Ofloxacin was continued
for nine months while pyrazinamide was stopped
after three months. Isoniazid and ethambutol were
continued for 18 months after which all patients
were put on lifelong secondary INH prophylaxis at
a dose of 300 mg per day. We follow this intensive
ATT regimen since another study from our
institution showed a very high incidence of
primary single and multi-drug resistant
tuberculosis in our population[8]. In patients with
atypical mycobacterial infection, treatment was
initiated with amikacin and clarithromycin in
addition to other drugs, according to sensitivity
reports. Patients with ESRD were considered for
renal transplantation after six weeks of ATT, if no
other contraindication was noted.
n
%
PUO only
20
PUO with
Pleural effusion
5
CXR suggestive
3
Pericardial effusion
1
Ultrasound / CT / CXR diagnosis of
Mass at Porta hepatis
1
Para aortic lymph nodes
2
Para tracheal lymph nodes
1
Mediastinal lymph nodes
1
58.8
Total
100
34
14.8
8.8
2.9
2.9
5.9
2.9
2.9
Patients received prednisolone and azathioprine
(2 mg/kg/d) immunosuppression until 1989 and
thereafter cyclosporine (8 mg/kg/d in two divided
doses) with prednisolone (20 mg/d) and azathioprine
was used. Before 1989 prednisolone was started at
a dose of 80 mg per day when used as part of two
drug regimen and gradually tapered. Those with an
uncomplicated course were given the option of
withdrawal of cyclosporine at one year. Monoclonal
antibody (OKT3) was used for the treatment of
recurrent or refractory rejection from 1994.
Mycophenolate mofetil and rapamycin have been
used in a few patients during drug trials, as rescue
therapy for cyclosporine toxicity and for recurrent
rejections.
All patients were followed up in-centre three
times a week for the first two months, twice a week
for the next two months and once weekly for the
subsequent two months. Thereafter they were seen
at nine and twelve months and whenever required.
RESULTS
Out of 1360 patients studied, 112 had developed
tuberculosis prior to transplantation. Of them 16
had completed antitubercular therapy prior to
transplantation. Thus 96 patients could be evaluated
in the peritransplant period and formed our study
group. These patients were diagnosed to have TB at
varying periods after the diagnosis of CRF. Thus
patients required renal replacement therapy after
varying periods of ATT. The common indications
for starting antitubercular therapy in these patients
are shown in Table 1. Forty three patients were
already on dialysis at the time of diagnosis of
tuberculosis. Of the 34 patients started on ATT for
pyrexia of unknown origin (PUO), 20 (58.8%) had
fever only, while the rest had other featur es
suggestive of tuberculosis in addition to fever
(Table 2). Two patients were diagnosed as having
atypical mycobacterial infection.
116
Pretransplant Antitubercular Therapy - How Long?
Out of the 96 patients who were on ATT in the
peritransplant period 11 (11.45%) patients expired
due to various causes while still on ATT. Fourteen
(14.58%) patients were lost to follow up before
completing ATT. Seven (7.29%) patients were still
on ATT at the time when this study was undertaken.
Patients underwent renal transplantation at a
median of 90 days after the initiation of ATT (range
27 - 420 days). The mean duration was 122.25 В±
82.49 days. The time between diagnosis of
tuberculosis and the development of ESRD, other
co-morbidities, donor preparation and financial
constrains influenced the time when renal
transplantation could be performed. This resulted
in the wide range of time between initiating ATT
and performing the transplantation. These patients
were followed up for a mean of 36.79 В± 34.65
months (range 2 - 216 months). Twenty three
patients received an allograft between six to eight
weeks of initiation of antitubercular therapy. These
patients had a mean follow up of 29 months (range
7 - 120 months). Of these 23 patients, 19 had
microbiologically or pathologically confirmed
tuberculosis. Eight had sputum positive for AFB,
three grew AFB from pleural fluid and two from
gastric aspirate, and five had a histologically
positive lymph node while one patient had pleural
biopsy suggestive of tuberculosis. Of the four
patients with PUO in this group, two had only
fever while two had PUO with pleural effusion.
The only patient who developed recurrence of
tuberculosis in the post transplant period developed
combined tubercular and cryptococcal meningitis
three years after renal transplantation . His primary
disease was tuberculosis of the spine and he
received an allograft nine months after initiation of
antitubercular therapy.
Out of 96 patients, 19 (20%) had expired at the
time when this study was undertaken. Except the
above mentioned patient who expired due to
combined tubercular and cryptococcal meningitis,
the other deaths were unrelated to tuberculosis.
DISCUSSION
The prevalence of tuberculosis in patients with
ESRD on hemodialysis is 13.6%[9]. The prevalence of
tuberculosis in CRF patients awaiting renal
transplant at our centre was 8.45%. Inability to
make a definitive microbiological or tissue
diagnosis of tuberculosis is common [10]. This
problem is more in endemic areas and in children
where antitubercular therapy is often started on the
basis of clinical, biochemical and radiological
features[11,12] or scoring systems [13] to assist in
diagnosis. Such patients are also diagnosed by
response to a therapeutic trial of ATT[12]. A definite
diagnosis of tuberculosis was made in 78 of the 112
June 2006
patients (70%) in our study. Patients on hemodialysis
are known to have a higher incidence of
predominant or exclusive extrapulmonary disease.
It is reported to constitute between 40[4] to 92% [15] of
the total cases. In our study 41 of the 78 patients
(52.5%) in whom tuberculosis could be localized,
had extra pulmonary involvement. Lymph node
was the commonest extra pulmonary site
constituting 39.7% (31/78) of the proven
presentations. About 30% of our patients presented
with pyrexia of unknown origin, 41% of whom had
other clinical or radiological features suggestive of
tuberculosis. In these patients, when a detailed
workup failed to identify any cause, response to a
therapeutic trial of ATT confirmed the diagnosis.
The ideal duration of antitubercular therapy
before renal transplantation is not defined. Most
centers offer therapy with two or three drugs
usually rifampicin, INH and ethambutol for about
12 to 24 months. We prefer to stop rifampicin since
the dose requirement of cyclosporine is known to
go up by atleast two times[16], significantly increasing
the cost of treatment. Some studies have
demonstrated unpredictable variation in blood
levels of cyclosporine and a higher rate of acute
rejection when both these drugs were used together.
Rifampicin is known to increase the clearance of
corticosteroids two fold[17] and that of cyclosporine
about two to five-folds [18-20] by its effect on
cytochrome P-450. Not much is written in the
literature regarding the ideal duration of anti
tubercular therapy prior to renal transplant.
Malhotra et al in their study of tuberculosis and
renal transplant have mentioned performing renal
transplantation in 11 patients three to six months
after initiation of ATT[3]. They continued the
medication for two years and observed one
recurrence. In another study, four out of eight
patients received an allograft in less than six
months after starting ATT. They observed no
recurrence[9].
In India, the cost of maintaining a patient on
dialysis with erythropoietin therapy would be
about Rs. 30,000/- (US$ 600) per month. The mean
per capita monthly income of a salaried citizen of
this country is Rs. 17,188/- (US $ 350) [21]. Since most
patients have to pay for their transplants by
themselves, it is important to define a shorter, but
safe duration of ATT that prevents recurrence of TB
in this population, allowing earlier transplantation.
While cost certainly is a cause for concern, the
much higher mortality in patients awaiting renal
transplant is also a reason for attempting surgery
earlier. Even in developed countries, mortality rates
from sepsis are one to several hundred fold higher
in dialysis patients as compared to the general
population[22]. Renal transplant recipients have
June 2006
KUWAIT MEDICAL JOURNAL
sepsis associated mortality rates approximately 20
folds higher than those of the general population
but 15 folds lower than those of dialysis patients.
We believe that with the protocol of therapy
mentioned earlier, it is safe to perform renal
transplantation after six weeks of initiation of
antitubercular therapy. Even in established ESRD
patients however, donor preparation, economic
considerations and other comorbidities in the
recipient at that time influence our ability to do so.
In the study population, 23 of the 96 patients
(23.95%) could actually receive an allograft
between six to eight weeks. At a mean follow up of
29 months, none of these 23 patients developed
recurrence of the disease. We know that about 58%
cases of post transplant tuberculosis manifest
within the first year after transplant[23]. Thus a mean
follow up of 29 months in these 23 patients appears
adequate to demonstrate the safety of performing a
renal transplant after six weeks of ATT. Among the
entire group of 96 patients, at a mean follow up of
36.79 months, only one patient developed a
recurrence of tuberculosis in the post transplant
period. They had received a mean of 122.25 days of
ATT prior to transplantation. Of the 19 patients
who expired in the post transplant period only one
(5.3%) did so of tuberculosis. In another study from
our hospital, which looked at post transplant
tuberculosis in the period 1986 -1999[24], 166 of 1251
(13.3%) renal transplant recipients developed
tuberculosis in the post transplant period. These
patients had no evidence of tuberculosis prior to
transplant. Out of 53 patients who expired; 17 (32%)
were due to post transplant tuberculosis. This
particular study, which looked at the same patient
population and over a period almost equal to our
study, provides data on the population which could
serve as a control in our study. A comparison of
these two studies suggests a reduction in risk of
post transplant tuberculosis from 13.3% to about
1% and reduction in the risk of death due to
tuberculosis from about 10% to 1%. Thus it appears
that using the treatment protocol mentioned above
and also using secondary INH prophylaxis, renal
transplantation can be performed safely within six
to eight weeks of initiation of antitubercular
therapy with very little risk of flare up of the
disease or of its recurrence in the post transplant
period . To the best of our knowledge, this study
has evaluated the largest number of patients
reported till date on the necessary duration of
pretransplant antitubercular therapy.
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incidence of tuberculosis among renal transplant recipients
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KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Factors Underlying Bottle-feeding Practice in Kuwait (2001)
Hamdiya AS Al-Fadli1, Layla Al-Jasem2, Abdul Hameed A Al-Jady1, Gamal M Masoud 3
Department of Primary Health Care, Ministry of Health, Kuwait
Health Education Department, Ministry of Health, Kuwait and Department of Community Medicine, Kuwait University,
Kuwait
3
Department of Community Medicine, Alexandria University, Egypt
1
2
Kuwait Medical Journal 2006, 38 (2): 118-121
ABSTRACT
Objective: To explore the factors underlying the practice
of bottle-feeding among mothers with children less than
two years old in Ahmadi region, Kuwait in the year 2001.
Method: A descriptive study was carried out in Ahmadi
governorate. Data was collected from 361 mothers whose
babies were less than two years old and bottle fed. The
interviewed mothers were selected from labor rooms and
the post-natal ward in Adan hospital and from preventive
health centers in Ahmadi governorate.
Results: The rate of bottle-feeding practices in Ahmadi
region was found to be high among Kuwaiti mothers and
those with high family income. The rate of bottle-feeding
practice increases among mothers with infants older than
four months due to early weaning. The main reasons for
bottle-feeding practice were insufficient breast milk, the
need to go back to work and using contraceptive pills.
Also pediatricians (child health doctor) were found to be
the main persons prescribing infant formula for mothers.
Conclusion: The rate of bottle-feeding practice in
Ahmadi region increases among Kuwaiti mothers who
have high family income and who reported that they
have insufficient milk. Health education programs to
promote breast-feeding are necessary for mothers and
health care providers.
KEYWORDS: bottle-feeding, infant feeding, maternal factors
INTRODUCTION
Breast-feeding is the natural, physiological way
of feeding infants and young children[1]. Human
milk is the natural milk made especially for human
infants, while most formulas made from cow’s milk
or soya beans are only superficially similar. Advertising
which states otherwise is misleading. Breast milk is
the only food the baby needs until at least four
months of age and most babies do very well on
breast milk alone for six months or more[2,3]. There is
no advantage of adding other sorts of foods or milk
to breast milk before 4-6 months, except under
unusual or extraordinary circumstances[3,4]. Despite
increasing medical research showing the benefits of
breast feeding for both mothers and babies[5-9],
many women opt to bottle-feed their infants
occasionally or routinely. Bottle-feeding is associated
with many medical risks: cow-milk allergy and
intolerance[10], increased risk of respiratory and gastro
intestinal diseases[11-14], high incidence of otitis
media[15] and oral malocclusion and dental
caries[16,17].
Many studies were carried out in different parts
of the world to investigate factors influencing the
infant feeding practice[18-21]. Maternal factors
associated with bottle-feeding practice were:
younger age[19,22], employment and using estrogen
containing oral contraceptive pills[18-20]. Other reported
factors were embarrassment [23], availability of
supplementary formula[19], early introduction of
food and water [24] and negative attitudes of doctors
and nurses[25]. Most studies were conducted to
identify feeding practices of young children in
Kuwait[21,26-30]. In 2001, the rate of breast-feeding in
Ahmadi governorate was 60.8% among infants
below four months of age. 22.6% of them had
mixed feeding (breast fed and bottle fed)[30]. This
study was conducted to explore the factors
underlying bottle feeding practice in Kuwait
among mothers with children less than two years
old in Ahmadi region in the year of 2001.
MATERIAL AND METHODS
Study Population:
Data was collected from 361 mothers with
infants less than two years old and bottle-fed at
Adan hospital and the Primary Health Care Center.
This study is part of a larger study with 1200
mothers in Ahmadi Governorate concerning breast
and bottle feeding conducted between September
2000 and February 2001. The interviewed mothers
were selected from labor rooms and the post-natal
ward in Adan hospital. Others were those attending
Address correspondence to:
Dr. Hamdiya A.S. Al-Fadli, Ahmadi Health Region, P.O.Box 1778, Sabah al-Salem, Kuwait. Tel: 3940595 - 9076558, Fax: 3940594 - 3839792,
E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
Table 1: Distribution of infant bottle feeding according to
background characteristic, in Ahmadi region, Kuwait
Total Sample
N=1200
n
%
Mother’s age (years)
< 20
90
20 to < 30
626
30 to < 40
443
≥ 40
41
Mother’s education
Not educated
57
Primary and
intermediate school
387
Secondary and university 756
Family income (KD)
< 400
361
> 400 to 600
444
> 600
395
Birth order
1
241
2-3
476
4-5
315
6+
168
Nationality
K
848
NK
352
Sex of the baby
Male
640
Female
560
Age of the baby
< 4 months
602
>4-2Y
598
Total
1200
Bottle-fed Significance
N=361
n
%
7.5
52.2
36.9
3.4
25
198
126
12
27.78
31.63
28.44
29.27
4.8
11
19.30
П‡ 2=3.870
32.3
63
124
226
32.04
29.89
p=0.144
30.1
37.0
32.9
75
133
153
20.78
29.95
38.73
20.1
39.7
26.3
14.0
60
144
101
56
24.90
30.25
32.06
33.33
П‡2=4.520
p=0.210
70.7
29.3
286
75
33.73
21.31
П‡21=18.242
p=0.000*
53.3
46.7
199
162
31.09
28.93
П‡21=0.666
p=0.415
50.2
49.8
100
261
361
16.61
43.65
30.08
П‡21=104.240
p=0.000*
П‡23=1.519
p=0.678
2
П‡23=28.927
p=0.000*
* Significant
Preventive Health Centers for vaccinating their
children. Selection of subjects was done systematically
by interviewing every third mother. A consent for
participation was obtained verbally. The interviews
were carried out by a well-trained group of nurses.
Only 1% of the mothers refused to be interviewed.
The Study Tools:
The World Health Organization (WHO)
indicators for assessing infant feeding practice were
used[31]. A bottle-fed child is one who receives fluids
or semisolid food from a bottle with a teat. The
questionnaire included questions on socioeconomic characteristics of infants (age, sex,
mother’s age, education and family income). The
method of feeding practice (breast fed or bottle fed)
and some characteristics of bottle feeding practice
(first feed, type of feed, who prescribed the feed
and, lastly, answers to open questions about the
reason for choosing bottle feeding practice) were
also recorded. A one-month pilot study on 50
subjects preceded the actual work. During the pilot
study, questionnaire and interviewing teams were
assessed and modified accordingly.
119
Table 2: Distribution of bottle-fed children according to
the type of milk
Type of Milk
Fresh milk
Powder milk
Baby formula
Special formula
Total
n
%
13
52
214
82
361
8.6
14.4
59.3
22.7
100
Analysis:
Statistical analysis was done using the SPSS
program. Descriptive analyses included frequencies
and percentages. Associations between categorical
variables were tested by the chi-square test. All
tests were assessed at the 5% level of significance.
RESULTS
Sample Characteristics:
Table 1 shows the distribution of infant bottlefeeding according to background characteristics.
The results showed that half (52%) of the mothers
in the sample were in the age group of 20 to less
than 30 years. More than two thirds (71%) of the
mothers were Kuwaiti and a little more than a third
(37%) of the sample reported to have family income
ranging from 400 to 600 Kuwaiti Dinars (KD) per
month (KD 1 = US $3.30). Bottle-feeding was found
to be significantly associated with the mother’s
nationality and family income. One third (34%) of
Kuwaiti mothers practiced bottle-feeding as
compared to one fifth (21%) non-Kuwaitis. Also,
over two thirds (68%) of mothers with family
income over 400 KD practiced bottle-feeding. In
addition, the results showed that 44% of mothers
with children older than four months practiced
bottle-feeding.
Table 2 shows the distribution of bottle-feeding
practice according to the type of milk. Baby formula
is the common milk used (59 %) followed by special
formula, which is mainly prescribed by pediatricians
in polyclinics or by pediatricians in the hospital.
Table 3 shows that almost half of the infants
(39%) in the study were prescribed bottle-feeding
by a pediatrician (child health doctor) in a hospital,
and one third (29%) of the infants were bottle-fed
by the mother’s choice.
Table 4 shows that insufficient milk was the
most common reason cited (44%). The second
reason was the need to go back to work (24%).
Other reasons given for bottle-feeding were
maternal disease (10%) and the use of oral
contraceptive pills (10%).
DISCUSSION
The study results showed a higher rate of bottlefeeding practice among Kuwaiti mothers than non-
120
Factors Underlying Bottle Feeding Practice in Kuwait (2001)
Table 3: Distribution of bottle-fed children according to
the person who prescribed the milk
Bottle-feeding Practice
Yes (N=361)
n
%
Physician in Polyclinic
Pediatrician in Hospital
Nurse in Polyclinic
Nurse in Hospital
Family member
Herself
Total
64
140
1
2
49
105
361
17.73
38.78
0.28
0.55
13.57
29.09
100
Kuwaiti. These findings support previous research[3238]
which shows infant feeding choices can differ by
ethnicity. Baisch et al found that adult white women
practiced breast-feeding more than adult black
women[38]. Similar to other studies [21,30], mothers
from high-income families were more likely to
practice bottle-feeding. Such results could be
explained by the fact that Kuwaiti women have
gone through fast westernization in their lifestyle,
especially in the ways of using modern technology,
due to the oil revenue. However, they did not catch
up to recent western civilization in relation to a
healthy lifestyle including breast-feeding[30]. Many
studies[39] showed that women practiced less breastfeeding after the baby reached four months of age
for reasons such as early weaning. Similarly the
rate of bottle-feeding increased with the increase in
child age. The reason is that almost all mothers
began solid foods before the infant was four
months old and discontinued breast-feeding. These
observations highlight ignorance about basic infant
feeding practices among the mothers. Health
education programs should therefore focus on
encouraging mothers to exclusively breast-feed
their babies up to the age of six months. The finding
of this study showed that physicians were the ones
who commonly prescribed infant formula. Health
care providers were cited as sources of encouragement
of bottle-feeding and discouragement for breastfeeding in other studies[25,34]. The negative attitude of
the pediatricians towards breast-feeding could be
explained by the fact that many schools of medicine
failed to include breast-feeding in their curricula.
Also, many health professionals are exposed to
advertisement for infant formula. Pediatricians are
required to have an educational program to
promote breast-feeding among mothers[38]. Similar
to other studies[22,26,34,39], the main reasons for bottlefeeding in this study were insufficient milk and the
need to go back to work. Many Kuwaiti women
believe that they do not have sufficient milk for
their babies, especially in the first week after labor.
This can be explained by the lack of awareness
among these women about the oxytocin reflex
June 2006
Table 4: Reasons given by mothers regarding the choice
of bottle-feeding practice
Causes
Insufficient Milk
Going to work
Affect her body image
Body gets fat with bottle feed
Infant’s disease
Maternal disease
Oral contraceptive pills
Total
Bottle-feeding (N=361)
n
%
157
85
18
7
24
35
35
361
43.49
23.55
4.97
1.94
6.65
9.70
9.70
100
mechanism that increases milk production due to
the infant continuously sucking on the breast[1]. In
addition, working mothers believe that separation
from their infants for a long period of time is an
obstacle for breast-feeding. Educating mothers
about the breast feeding mechanism, milk
production and showing them how to squeeze their
breast milk should be the main focus for health
education programs for pregnant women. This will
encourage breast-feeding and reduce bottle-feeding
with the support of baby-friendly hospital initiative
such as that started in Ahmadi Region in 1992. The
need for lactation consultants to advice mothers in
the immediate postpartum period to encourage
breast-feeding is recommended.
LIMITATION OF STUDY
Limiting the study to Ahmadi Governorate will
affect generalization of the study results to all
women in Kuwait. Also, recall bias affects the
accuracy of the results. The study design (crosssectional) will not explain a causal relationship
between any of the factors involved in the study.
Despite the fact that our sample was chosen
systematically, a high proportion of the mothers
had university education. Thus further research is
needed to confirm the findings of this study.
CONCLUSION
The results of this study showed that the
mothers in Ahmadi region practiced bottle-feeding
due to their lack of experience and lack of
awareness on the breast milk production
mechanism. At the same time, pediatricians’
prescription of infant formula and mothers’
misconceptions about breast-feeding was an
important reason for bottle-feeding. Therefore,
health education programs focusing on promoting
breast-feeding are recommended. Such programs
should provide accurate information to correct
misconception about breast-feeding among young
mothers and health care providers.
June 2006
KUWAIT MEDICAL JOURNAL
ACKNOWLEDGMENTS
We would like to express our thanks to Dr Zam
Zam Al-Mousa, MOH, Mrs. Fawzia Al-Awadi, the
Regional Director and Head Nurse in Ahmadi
Health Region, Dr. Abdelazeez Algendy, Mr George
Varghese, MOH and Mr. Wayne Cox for making
this work possible.
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KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Hepatitis C Virus Infection in Non-Hodgkin’s Lymphoma
Patients: Virological Evaluation
Hanaa M Alam El-Din, Samah A Loutfy
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt
Kuwait Medical Journal 2006, 38 (2): 122-127
ABSTRACT
Background: Viral hepatitis is a common and important
problem in immunocompromised cancer patients. The
present study was conducted to investigate changes in
some virological parameters as a consequence of
Hepatitis C Virus (HCV) infection in non Hodgkin’s
lymphoma patients (NHL).
Setting: The Pediatric Service of the National Cancer
Institute, Cairo University, Egypt.
Subjects: The study included 40 NHL patients: 20 antiHCV antibody positive (Gr. I) and 20 anti-HCV antibody
negative (Gr. II). In addition, forty non-cancer controls
(NCCs) were included: 20 of them were anti-HCV
antibody positive (Gr. III) and 20 anti-HCV antibody
negative (Gr. IV).
Methods: Virological studies included detection of HCV
antibody (Ab) of both types (IgG and IgM) by ELISA. In
addition, Line Immunoassay for HCV by LIAtest as well
as RT-PCR to detect HCV viremia were done.
Results: Eleven out of the twenty (55%) NHL patients
from Gr. I had HCV antibody index value of ≥ 6 in
comparison to 8/20 (40%) only in their non-cancer
controls. No difference was observed between the
positivity of anti-HCV IgM Ab in NHL patients from Gr.
I and their non-cancer controls in Gr. III; eleven out of 20
(55%) were positive for anti-HCV IgM Ab in both Gr. I
and Gr. III. As regards confirmatory HCV-Ab patterns
(LIA), nineteen out of 20 (95%) NHLpatients of Gr. I were
LIApositive in comparison to 18 out of 20 (90%) NCCs of
Gr. III. Further analysis showed that reactivity to both
core and nonstructural regions combined was more
frequent in NHLpatients (18/19, 95%) than in their noncancer controls (12/18, 67%). HCV viremia was
displayed by RT-PCR in 18 out of 20 (90%) NHLpatients
of Gr. I in comparison to 12 out of the 20 (60%) NCCs of
Gr. III.
Conclusion: From all the above virological findings two
main inferences could be drawn: (1) HCV leads a mild
course of infection in NCCs as evidenced by normal ALT
level in all but 20% (4/20) of subjects, and hence a mild
hepatocellular injury, and (2) In the immunocompromised
NHL patients the virus leads a potentially more aggressive
course as evidenced by higher percentage of positive
HCV RNA in blood, higher HCV-Ab titer and higher
incidence of reactivity to both core and NS regions(s)
KEY WORDS: adults, Egypt, hepatitis C virus, non Hodgkin’s lymphoma
INTRODUCTION
Non Hodgkins lymphoma (NHL) comprises
75% of all lymphoma cases presented at the
National Cancer Institute (NCI), Cairo University,
and about 6% of all cancers in Egypt with a mean
age of 40 years and male predominance with sex
ratio of 1.9:1 [1].
Several studies have reported a high prevalence
of Hepatitis C Virus (HCV) infection in patients
with lymphoproliferative disorders including
NHL. In an early study by Ferri et al[2] HCV related
markers were detected in 34% of their NHL
patients and this prevalence was particularly
significant when compared with HCV seropositivity
in Hodgkin’s disease and healthy controls. The
high prevalence of anti-HCV Ab was also noticed
among Egyptian NHL patients: 40% were reported
positive by Attia et al [3] and 70% by Hashem et al [4].
HCV infection can be responsible, for instance, for
the lymphoproliferation underlying mixed
cryoglobulinemia and its evolution to malignant Bcell lymphoma[5-7].
Since the false-positive reactions of current
HCV ELISA tests have frequently been observed, it
is advisable to confirm reactive samples by other
assay systems [8]. Such confirmatory assays must be
based on different viral antigens. Specific testing
identifying distinctive antibodies can also provide
additional information during the analysis,
monitoring, and follow up of patients. The LIA
HCV-Ab III is now widely used to confirm the
reactivity of the ELISA HCV Ab result. Anti-HCV
antibody reactivity does not necessarily correlate
with the presence of an infectious virus. To
discriminate between ongoing and resolved
Address correspondence to:
Hanaa M Alam El-Din, M.Sc., Ph.D. Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Fom El-Khaig,
Cairo 11796, Egypt. Tel and Fax: + 202 3644-720, E-mail : [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
Table 1: Age and sex distribution of NHL patients and
their non-cancer controls
Group
NHL:
Gr. I
Gr. II
NCC:
Gr. III
Gr. IV
No. of
Cases
M
Sex
F
Age (Y)
Range
Mean
20
20
9
11
11
9
20-78
17-71
45.1
41.1
20
20
11
18
9
2
18-50
20-45
33.1
31.0
NHL: Non Hodgkin’s lymphoma
NCC: Non-cancer controls
Gr. I: NHLpatients anti-HCV Ab positive
Gr. II: NHLpatients anti-HCV Ab negative
Gr. III: Non-cancer controls anti-HCV Ab positive
Gr. IV: Non-cancer controls anti-HCV Ab negative
infection detection of HCV RNA by RT-PCR is
presently the method of choice.
Our aim was to study the viral profile of HCV
infection in a group of Egyptian NHL patients.
MATERIAL AND METHODS
Patients: This study was conducted on a total of 40
patients with NHL divided into 20 anti-HCV
antibody positive (Gr. I) and 20 anti-HCV antibody
negative (Gr. II). All patients were presented before
treatment to the Medical Oncology Department of
the National Cancer Institute, Cairo University,
during the period of March 1996 to June 1997. Forty
non-cancer control subjects were also included in
this study, out of which 20 were anti-HCV AB
positive (Gr. III) and 20 were anti-HCV AB negative
(Gr. IV).
All patients and their controls were subjected to
a full history, clinical examination in addition to a
battery of investigations including liver function
tests (ALT,AST, prothrombin time, bilirubin, and
albumin).
Virological investigation: 10 ml venous blood was
withdrawn from each subject under study and
processed as follows:
Sera were separated from 7 ml of coagulated
blood and kept at -20 ВєC in aliquots until examined.
Anti-HCV IgG AB: This was done using Enzyme
Linked Immunosorbent Assay (ELISA) kit
provided by Sorin Biomedica, (Sallugia, Italy).
Anti-HCV IgM AB: All sera of patients and
controls found to be positive for anti HCV-Ab by
ELISA were tested for IgM anti-HCV using kit
provided by ABBOTT Laboratories (Chicago,
Illinois).
Line Immunoassay for HCV: This was done for
positive HCV-Ab by ELISA using 3rd generation
123
Table 2: Pathological grades of NHL patients
Group
Gr. I
Gr. II
No. of
Cases
20
16
NHLpathological grades
Grade 1 (%) Grade 2 (%) Grade 3 (%)
2 (10)
4 (25)
13 (65)
10 (63)
5 (25)
2 (12)
Gr. I: NHLpatients anti- HCV Ab positive.
Gr. II: NHLpatients anti-HCV Ab negative.
LIA(INNO-LIAHCV AB III) kit (INNOGENETICS,
Zwijndrecht, Belgium). INNO-LIA HCV Ab III
assay: In this third generation sandwich-type line
immunoassay, HCV antigens derived from the core
region, the E2/NS1, the NS3 helicase, and NS4A,
NS4B and MS5A regions are incorporated as
discrete lines on a nylon strip with plastic backing.
In addition, four control lines are coated on each
strip: antistreptavidine, three positive control
(antihuman Ig), one positive control (human IgG),
and the В± cutoff line ( human IgG). A diluted test
sample is incubated in a trough together with the
LIA III strip. If present in the sample, HCV
antibodies will bind to the HCV antigen lines on the
strip. Subsequently, an affinity-purified alkaline
phosphatase-labeled goat antihuman IgG (H+L)
conjugate is added and reacts with specific HCV
antigen/antibody complexes, if previously formed.
Incubation with enzyme substrate produces a
chestnut-like color, the intensity of which is
proportionate to the amount of HCV-specific
antibody captured from the sample
RT- PCR for HCV: Viremia was detected by RTPCR using three steps:
a) Nucleic acid extraction: Total RNA was
extracted from 100 Вµl serum by silica method
previously described by Boom et al[9].
b) Synthesis of c-DNA was performed using
superscript reverse transcriptase Enzyme (GibcoBRL-Gaithersburg, MD). The cDNA samples were
amplified by polymerase chain reaction using
published primers chosen from the highly
conserved 5’ noncoding region nucleotide sequence
of the HCV genome according to Attia et al[10].
c) Upon completion of the amplification
reaction, 10 Вµl of PCR product was analyzed by gel
electrophoresis through 2% agarose gel in TrisAcetate-EDTA buffer (pH 8.0) stained with
ethidium bromide.
Statistical analysis: SPSS (statistical package for
social sciences) was used for analyzing the data.
Chi square test was used for comparison of
independent proportions. Non-parametric T test
was used for two independent groups. p value was
significant at < 0.05 level.
124
Hepatitis C Virus Infection in Non-Hodgkin’s Lymphoma Patients: Virological Evaluation
Table 3: IgM HCV-Ab, LIA HCV, serum HCV RNA and
Index values of HCV ELISA in HCV-total Ab positive
NHLpatients and their non-cancer controls
Variable
No. of cases with different indices
NHL(%)
NCC (%)
Index values of HCV EIA:
≤ 3@
> 3-6
≥ 6
IgM + ve
LIA+ ve
PCR + ve
1/20 (5)
8/20 (40)
11/20 (55)
11/20 (55)
19/20 (95)
18/20 (90)
4/20 (20)
8/20 (40)
8/20 (40)
11/20 (55)
18/20 (90)
12/20 (60)
NHL: Non Hodgkin’s lymphoma
NCC: Non-cancer controls
@ Index values = O.D. sample/ cut-off
RESULTS
Age and sex distribution in all study groups are
summarized in Table 1. Pathological grades of NHL
patients are shown in Table 2. Out of the 20 NHL
patients from Gr. I, 11 (55%) had HCV antibody
index values of ≥ 6 in comparison to 8/20 (40%) only
in the non-cancer controls (Gr. III), whereas 1/20 (5%)
only of the former group (Gr. I) had an index value
≤ 3 compared to 4/20 (20%) in the latter (Table 3).
No difference was however, observed between
the positivity of anti-HCV IgM Ab in NHL patients
of Gr. I and their non-cancer controls of Gr. III:
eleven out of 20 (55%) were positive for anti-HCV
IgM Ab in both Gr. I and Gr. III.
As regards confirmatory HCV-Ab patterns, 19
out of the 20 (95%) NHL patients of Gr. I were LIA
positive in comparison to 18 out of the 20 (90%)
NCCs of Gr. III. As regards reactivity to different
HCV core regions (C1+2 and C3+4) and the
nonstructural regions (1, 3, 4, and 5) in LIApositive
NHL patients and non-cancer controls: Reactivity
to both core and nonstructural regions combined
was more frequent in NHL patients 18/19 (95%)
than in their non-cancer controls (12/18, 67%), but
this difference is not statistically significant (p =
0.07), whereas reactivity to the core regions alone
was more frequently seen in the non-cancer group
(4/18, 22.2%) than in the NHL patients (1/19, 5%)
but again, the difference is not statistically
significant (p = 0.08).
Evidence of viremia was studied in relation to
reactivities of ELISA anti-HCV IgG and IgM and
LIA anti-HCV antibodies in subjects of Gr. I and Gr. III.
(1) In anti-HCV Ab positive cases: Eighteen
cases out of the 20 (90%) anti-HCV Ab positive
cases of Gr. I were positive for HCV RNA by RTPCR compared to only 12 (60%) out of 20 in Gr. III.
Marked correlation between viremia and the
index value ≥ 6 was observed where 6/8 cases
(75%) were RNA positive by RT-PCR. However,
only 1/4 (25%) with an index value < 3 was positive
for RT-PCR (p < 0.05).
June 2006
(2) ELISAanti-HCV IgM Ab positive cases: HCV
viremia was detected in 10/11 (91%) of the IgM
positives and in 8/9 (89%) of the IgM negatives of
Gr. I, whereas it was found in 8/11 (73%), and in
4/9 (44%) of the IgM positives and IgM negatives
of Gr. III respectively.
(3) In LIA HCV-antibody positive cases: 17 out
of the 19 (89%) LIA positive NHL patients of Gr. I
were positive for HCV RNA as compared to 12 out
of 18 (67%) in their normal controls from Gr. III. So,
in Gr. III, individuals reactive to nonstructural
region(s) were seldom RNA-negative, whereas
those non-reactive to nonstructural region(s) were
seldom RNA-positive. The two individuals nonreactive to the core region were RNA-positive.
In conclusion, there was no significant
correlation between viremia and any of the above
antibody markers.
Regarding liver function tests, in group I, ALT
was high in 12/20 (60%), high INR in 10/20 (50%)
and high bilirubin and low serum albumin in 8/20
(40%) cases. In group II, high ALT was found in
10/20 (50%), low serum albumin, and high INR in
8/20 (40%), while 6/20 (30%) had high total
bilirubin. In group III (NCC), ALT was normal in
16/20 (80%), total bilirubin and serum albumin
were normal in 18/20 (90%), while INR was normal
in all patients in this group. This difference between
group III and I was statistically significant (p <
0.05).
DISCUSSION
The higher HCV Ab titers in cancer patients of
Gr. I, indicated by higher indices than in NCCs of
Gr. III, might be due in part to enhanced viral
replication in the immunocompromised cancer
patients. Association between HCV antibody titer
and viremia was also reported by others[11-13]. In our
study, 6/8 (75%) cases with high HCV antibody
index value of ≥ 6 were associated with viremia.
Apparently, in most cases the humoral response
directed at multiple determinants involving most
of the viral antigens cannot control infection[14].
Antiviral antibodies are present in almost all
patients with chronic hepatitis C but do not seem to
be virus neutralizing, probably due to the high
mutational rate of viral envelope proteins[15].
Similarly, our results show that HCV specific
antibody titers had no apparent protection against
the viral infection, Although high index value ≥ 6
of ELISA anti-HCV Ab was noticed in 11/20 (55%)
and 8/20 (40%) cases, yet HCV PCR was positive in
10 out of the 11 (91%) and 6 out of the 8 (75%)
patients in Gr. I and Gr. III respectively. HCVantibody reactivity to both LIA nonstructural and
core regions combined was scored in 30 out of the
40 (75%) subjects of Gr. I and Gr. III collectively, of
June 2006
KUWAIT MEDICAL JOURNAL
which 27 out of 30 (90%) were HCV RNApositive.
LIA positivity was in the order of 95% and 90%
in Gr. I and Gr. III respectively. The high percentage
of reactivity in the immunoblot assay among ELISA
anti-HCV positive cases was in agreement with
other findings reported elsewhere: 98% in Japan[16],
94% in Italy[17], 97% in France[18] and 82 to 94% in
Egypt[19, 3 ,20].
As regards reactivity to HCV LIA core (C1+2
and C3+4) and nonstructural (1, 2, 4, and 5) regions,
the present results showed that 25/30 (83%)
subjects reactive to both regions combined were
viremic, whereas 2/5 (40%) with single reactivity
(core positive and NS negative) were viremic. They
showed that the probability of presence of viremia
in a blood donor with complete profile in the
supplemental assay (core positive and nonstructural
positive) was much higher (82%) than that (10%) in
an anti-HCV positive donor with single reactivity
(i.e., core positive and nonstructural negative)[21].
Similarly, it was reported by Dow and associates
(1996), that their reactives to 3 and 4 bands in RIBA3 were found to have 74 to 84% HCV PCR positivity,
whereas this percentage falls dramatically among
those reactive to 2 bands only (34%). Also, Berger
et al (1996) stated that PCR positive samples
showed an average range of 2.5 reactive proteins on
immunoblot, whereas with the HCV-RNA-negative
samples, only 0.9 bands or proteins were reactive[13].
In an attempt to evaluate the relation between
HCV replication and antibody responses toward
specific HCV proteins in our series, we compared
those reactive and those non-reactive to
nonstructural region(s) in relation to HCV viremia.
It was found that out of 14 reactive to NS region(s)
in the NCCs of Gr. III, 11 (79%) were HCV RNApositive. In a study by Zanella et al in 1995[23] it was
shown that reactivity to E2/NS1 identified by LIA
III was present in the vast majority of HCV RNA positive subjects. Also, Shimotohno and Feinstone
(1997)[24] stated that the association between
antibody against HCV NS4A protein and HCV
RNAwas significant.
In our results, three out of the four (75%) who
were reactive to core region(s) but non-reactive to
any of the NS regions were PCR negative.
Yatsuhashi, et al in 1993 [25] showed that all six who
were positive for HCV core region but not NS were
all negative for HCV-RNA, and stated that this
might indicate successful viral elimination.
Antibodies against non-structural proteins therefore,
correlate with viral replication, while core-specific
antibodies can be found in both continued and past
infection and absence of viremia.
In the present study, anti-HCV IgM antibody
positivity in 11/20 (55%) of our chronically infected
patients of Gr. I and Gr. III (none of whom had
125
apparent disease and all but two, had normal ALT)
agrees with similar records reported and
documented by others; Anti-HCV IgM antibodies
were detected in 50 to 90% of patients with chronic
hepatitis C[26-29]. The positivity of anti-HCV IgM
antibodies in acute hepatitis C did not vary
significantly from those in chronically infected
patients; 50% positivity were reported in The
Netherlands[30], 64% in Spain[31], 82% in Italy[32] and
87% in Abbott Laboratories, USA [33].
Detection of anti-HCV IgM antibodies appears
therefore, to be of limited value to diagnose early
HCV infection[34,35]. An association however, may
exist between anti-HCV IgM antibody positivity
and viremia. It has been reported that 76% and up
to 100% of anti-HCV IgM antibody positive
individuals are simultaneously HCV RNA
positive[36,27,37,38]. On the other hand, negative IgM
anti-HCV does not exclude detectable HCV RNA.
Martinelli et al (1994)[29] reported that 10/12 (83%)
of anti-HCV IgM antibody negative subjects were
positive for HCV RNA. In our series, viremia was
apparently not associated with the state of viremia
in the immunocompromized cancer patients of Gr.
I, where viremia was detected in 10/11 (91%) of
IgM antibody-positives and in 8/9 (89%) of the
negatives for IgM patients; yet an association was
observed between IgM positivity and viremia in the
NCC group (Gr. III), where 8/11 (73%) and 4/9
(44%) were viremic in the IgM positive and IgM
negative subjects of Gr. III respectively.
The higher percentage of viremia (18/20, 90%)
among the immunocompromised NHL patients
than among non-cancer controls (12/20 60%) was
discussed before, where it can be depicted that
immunosuppression is associated with enhanced
viral replication in agreement with previous
records. Viremia was detected in 84% of anti-HCV
antibody-positive B-cell lymphoma patients[7]. It
was also shown by Ghany et al (1996)[39] that
immunosuppressed renal transplant recipients
with chronic HCV infection had significantly
higher HCV RNA levels when compared to
immunocompetent controls. Watson et al (1996)[40]
showed that patients with variable immunodeficiencies
acutely infected with HCV, also had significantly
higher hepatitis C virus RNA titers on presentation
than immunocompetent patients. Sheiner et al
(1995)[41] postulated that clinical recurrence of
hepatitis C after rejection of liver transplantation is
associated with augmented immunosuppresion
and hepatitis C virus replication.
In immunocompetent apparently healthy HCVinfected subjects, HCV viremia was less detected
than in the immunocompromised patients. The
RNA positivity of 60% in the non-cancer Gr. III
agrees with that reported by others, where HCV
126
Hepatitis C Virus Infection in Non-Hodgkin’s Lymphoma Patients: Virological Evaluation
viremia ranged from 41 to 68% in anti-HCV
antibody-positive blood donors with persistently
normal ALT level[42,43,11,44]. However, higher percentage
of viremia (85 to 97%) was reported in anti-HCV
antibody positive patients with chronic hepatitis[29, 27].
None of the anti-HCV negative NHL patients of
Gr. II and their non-cancer controls of Gr. IV was
viremic.
HCV leads a mild course of infection in NCCs as
evidenced by normal ALT level, normal total
bilirubin, normal serum albumin and INR in most
of the patients (80%).
In conclusion, it seems that in the
immunocompromised NHL patients, the virus
leads a potentially more aggressive course as
evidenced by higher percentage of positive HCV
RNA detected in blood, higher HCV-Ab titer, and
higher incidence of reactivity to both core and NS
region(s) combined in HCV LIAtest.
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KUWAIT MEDICAL JOURNAL
June 2006
Original Article
Profile of Vitiligo in Farwaniya Region in Kuwait
Nawaf Al-Mutairi, Ashok K Sharma
Department of Dermatology, Farwaniya Hospital, Kuwait
Kuwait Medical Journal 2006, 38 (2): 128-131
ABSTRACT
Background: Vitiligo is common worldwide. However,
there are few studies available on pattern and
epidemiology of vitiligo from the Gulf countries,
including Kuwait.
Objective: To determine the clinical patterns of Vitiligo,
the associated socio-demographic factors and its
associated disorders among patients attending
dermatology outpatient department of Farwaniya
hospital in the central region of Kuwait.
Materials and methods: All patients presenting with
signs and symptoms suggestive of vitiligo seen over a
period of one-year (from July 2003 to June 2004) at the
out-patient clinics in the Dermatology Department of
Farwaniya Hospital and two affiliated dermatology
clinics in Kuwait were included in the study. Sociodemographic details about age, sex, marital status,
education, occupation, and nationality were recorded on
a proforma. A detailed clinical history pertaining to the
presenting complaint and clinical examination findings
were noted on the same proforma. Relevant available
investigations were carried out in all the patients
depending on their signs and symptoms to determine
any associated disorders with vitiligo .
Results: Four hundred and forty-eight adult patients, 76
adolescents and 88 children with vitiligo were studied.
Males constituted 257 (42%) patients and females 355
(58%) of the total number of patients. Duration of disease
at the time of presentation ranged from two weeks to 12
years. The lower limb was the initial site of onset of
vitiligo in majority (32.19%) of the patients, followed by
the upper limbs, head and neck, trunk and mucosae in
decreasing order of frequency. The commonest clinical
pattern observed was vitiligo vulgaris followed by focal,
acrofacial, mucosal, segmental and universal types.
Lesions showing leukotrichia were observed in 144
(23.53%) patients and koebnerization was observed in
141 (23%) patients. Seven child patients with halo nevi
were seen. Associated abnormalities included atopic
dermatitis (49 patients), alopecia areata (21 patients),
psoriasis (2 patients), diabetes mellitus (9 patients) and 13
patients showed anti-thyroid antibodies. A positive
family history was obtained in 8.98% of the patients.
Conclusion: Vitiligo vulgaris is the most common
clinical-type skin disorder observed in Kuwait. There
were associated disorders/abnormalities in some
patients such as atopic dermatitis, alopecia areata,
psoriasis, and diabetes mellitus. Keeping in view the
observation of anti-thyroid antibodies in some of these
patients we suggest that patients having these antibodies
should be followed up for the possible development of
clinical thyroid dysfunction.
KEY WORDS: associated disorders, clinical profile, vitiligo
INTRODUCTION
Vitiligo is an acquired, pigmentary disorder of
the skin and hair characterized by well-circumscribed,
asymptomatic white cutaneous macules devoid of
identifiable melanocytes. It affects 0.1 - 4% of the
population worldwide[1]. Vitiligo occurs in all races,
affects both sexes, and can develop at any age.
Vitiligo is a common depigmentation disorder
of the skin. The destruction of melanocytes is the
cause of depigmented maculae that clinically
represent the disease vitiligo[2,3]. The premise that
vitiligo, or a susceptibility to the disease, is
inherited is based on the fact that familial
aggregation is often seen. Theories concerning the
cause of vitiligo have concentrated on three different
mechanisms: autoimmune, autocytotoxic, and neural.
The disorder has been reported in association with
several endocrinopathies and other disorders of
autoimmune nature[4].
MATERIALS AND METHODS
Farwaniya Hospital is a secondary care hospital
serving a sizeable population of Kuwait. This was a
prospective study and the data were collected
between July 2003 and June 2004. All new patients
with vitiligo were included in this study. The
diagnosis was made by experienced dermatologists
and was essentially clinical.
A complete history regarding age, family
history, site of onset, duration, and past treatment
was taken. A thorough clinical examination was
done, and the site and pattern of the lesions were
Address correspondence to:
Dr. Nawaf Al-Mutairi , P.O. Box 280, Farwaniya, Kuwait. Tel: (965) 9370203, Fax: (965) 4808167, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
129
Table 1: Number of patients with positive family history
Type of patients
Children
Adolescents
Adults
Total
Fig. 1: Age at onset of vitiligo
noted as was the activity of the disease as
evidenced by the appearance of new lesions and
increase in the size of existing lesions over the past
six months. The cases were classified into six
groups according to the standard working
classification of clinical types of vitiligo[5]. Presence
of leukotrichia, Koebner phenomenon, and halo
nevi were noted. Screening was also done for
autoimmune and endocrine disorders by history
and clinical examination; these disorders included
thyroid disease, diabetes mellitus, pernicious
anemia, Addison’s disease, connective tissue
diseases and alopecia areata. Investigations
including hemoglobin level, total and differential
leukocyte counts, erythrocyte sedimentation rate,
peripheral smear, blood sugar level, T3, T4, TSH,
anti-thyroid antibodies (antithyroglobulin and
antimicrosomal antibodies) and fluorescent
antinuclear antibodies were done for all patients.
RESULTS
Out of 37, 246 new patients examined, 612 new
patients were diagnosed as having vitiligo (1.64%).
Out of these, there were 448 adults (>18 years), and
164 children and adolescents.
The total number of males with vitiligo was 257
(42%) and the total number of females with the
disease was 355 (58%) as shown in Fig. 1. The
duration of the disease at the time of presentation
ranged from 15 days to two years.
According to the age of onset, patients were
divided into three groups: children (≤ 12 years),
adolescents (13-18 years), and adults (> 18 years) as
shown in Fig. 1.
The number of patients with active disease
(appearance of new lesions or increase of the size of
existing lesions within six months) was 489
(79.90%). Koebner phenomenon was found in 141
patients (23%) of the total vitiligo patients and 123
(87%) of them had active disease.
Number
24
16
76
116
The number of patients with positive family
history was 116 (18.95%). These are summarized in
Table 1.
The site of onset of vitiligo lesions in patients is
shown in Table 2. The most common site of onset
was lower limbs followed by, upper limbs, head
and neck, trunk, genitalia and mucosae. Halo nevi
were seen in seven patients; all of them were
children and had non-segmental vitiligo. Lesions of
vitiligo showing leukotrichia of the overlying hair
in hair bearing areas were observed in 144 (23.53%)
patients.
The distribution of vitiligo in patients is shown
in Table 3. The distribution pattern of lesions which
denotes the clinical types of vitiligo is shown in
Table 4. Vitiligo vulgaris (generalized vitiligo)
showing scattered circumscribed macular depigmented
lesions was the most common type, followed by
focal, acrofacial, mucosal, segmental, and universal
types. All cases with mucosal vitiligo were girls,
having involvement of the genital mucosa. Out of
the 26 cases with segmental vitiligo, 15 cases had
vitiligo involving the face.
Patients with vitiligo having other associated
conditions are summarized in Table 5. Thirteen
patients had anti-thyroid antibodies but none of
these patients had clinical evidence of thyroid
disease. Insulin dependent diabetes mellitus was
seen in nine patients. Alopecia areata was seen in 21
patients and atopic dermatitis was observed in 49
patients.
No patient complained of deafness. Ocular
examination failed to reveal any abnormality in any
of the patients.
DISCUSSION
Many studies indicate that vitiligo is mostly
acquired early in life. However, our study shows
that a sizeable number of patients (448 out of 612
new patients) have their onset of vitiligo after the
age of 18.
Female preponderance was observed in our
study. Kovacs[5] also referred to a preponderance of
females among patients with vitiligo. However, he
also pointed out that this observation is not
statistically significant. In a study on Indian
patients, Handa and Kaur stated that 54.5% of cases
were men [6]. Alkhateeb et al in a recent study from
Profile of Vitiligo in Farwaniya Region in Kuwait
130
Table 2: Site of onset of vitiligo
Site of onset
Head and neck
Trunk
Lower limbs
Upper limbs
Mucosa & genitalia
Total
Number of cases
110
100
197
157
48
612
June 2006
Table 3: Distribution of vitiligo in patients
Percentage
17.97
16.35
32.19
25.65
7.84
100
USA have noted that the frequency of vitiligo
appeared approximately equal in males and
females [7]. We feel that the observed female
preponderance in our cases is presumably for two
reasons; first, the higher cosmetic concern among
female patients and the relatively more time they
have for long-term therapy allowing them to seek
active treatment more often; and second, males
being bread earners in contemporary society, must
work all day long throughout the year and this
makes them relatively unconcerned or so busy to
consult for the treatment of vitiligo
In our study children constitute 14.4% of the
total number of vitiligo patients, which is
comparatively less than that was reported in other
studies. Nanda et al highlighted the spectrum of
cutaneous diseases seen in children in Kuwait and
they pointed out that the incidence of vitiligo
showed a steady increase from 0.4% in infants to
1% in preschool children, 2.1% among primary
school children and 3.5% in preadolescents [8].
Hann et al reported that family history was
present in 13% of their patients[9]. In a study from
India by Handa and Kaur, 11.5% of patients had a
family history of vitiligo[6]. In our study, a positive
family history was present in 18.95% of the
patients. We believe that genetic factors are playing
a role in this part of the world as there is a high
incidence of consanguineous marriage here.
The lower limbs were found to be the site
initially developing depigmentation in the majority
of our patients, followed by upper limbs, head and
neck, trunk and the mucosae. Handa and Kaur[6]
reported that sites of onset were the face, trunk, and
legs in descending order of frequency. The exact
significance of this observation is difficult to
appreciate. However, we feel that trauma prone
sites like the lower legs and the hands may develop
vitiligo lesions more easily in genetically
predisposed persons and may be the sites of onset
of disease more often.
Generalized vitiligo (vitiligo vulgaris), characterized
by multiple, bilateral, symmetrical lesions
involving upper and lower limbs and trunk, was
the most commonly seen clinical type in our
patients. This was followed by focal vitiligo,
acrofacial vitiligo, mucosal vitiligo, segmental
Distribution
Number of cases
Exposed areas
Unexposed areas
Exposed & unexposed areas
Total
484
119
9
612
Percentage
79.1
19.5
1.47
100
vitiligo and universal vitiligo types. Hann et al
broadly classified their patients as having
segmental or non-segmental vitiligo and observed
non-segmental vitiligo in 79.5% of their patients[9].
Kovacs also reported that generalized vitiligo is the
commonest presentation[5]. Handa and Kaur reported
that vitiligo vulgaris was the commonest type seen
followed by focal vitiligo and segmental vitiligo[6].
However, with the present state of our knowledge
it is difficult to comprehend the mechanisms and
determinants underlying varying clinical patterns
of vitiligo seen in different patients.
Many lesions in hair bearing areas show
leukotrichia of the overlying hair and such lesions
were seen in 144 (23.53%) of our patients.
Leukotrichia was seen in 43.5% of South Korean
patients[9] and in 11.5% of Indian patients [6].
Koebnerization was observed in 23% of our
patients. Others have reported it in 21%[9] and in
5%[6] of their patients respectively.
Halo nevi were seen in seven patients; all had
non-segmental vitiligo and were children. None of
the adult patients showed halo nevi. This constituted
7.95% of the studied children. Halo nevi were seen
in only 2.5% of the children in the study from
Korea[10] while Handa et al[11] observed halo nevi in
4.4% of the children. However, our observation is
consistent with the observation of Cho et al[10] in that
all patients with halo nevi had non-segmental
vitiligo. We believe that halo nevi co-existing with
vitiligo lesions are not commonly seen in adultonset vitiligo.
Association of vitiligo with other diseases/
abnormalities has also been a subject of great
interest. We also observed an association of vitiligo
with cutaneous diseases like atopic dermatitis (49
patients), alopecia areata (6 patients), psoriasis (2
patients), and, with systemic disorders like diabetes
mellitus (9 patients). Anti-thyroid antibodies were
detected in 13 patients (all asymptomatic for
thyroid dysfunction). Handa and Kaur[6] observed
atopic/nummular eczema in 1.4%, alopecia areata
in 0.4%, bronchial asthma in 0.7%, diabetes mellitus
in 0.6% and thyroid disease in 0.5% of their
patients. We feel that the significant number of
atopic dermatitis patients having vitiligo in our
study merely expresses the high prevalence of
atopic dermatitis observed in the general
population in Kuwait[8]. We should mention here an
June 2006
KUWAIT MEDICAL JOURNAL
Table 4: Agewise percentage of the pattern of
distribution of vitiligo lesions
≤ 12 years = 88 patients
Number of
Percentage
cases
Vulgaris
Focal
Acrofacial
Universalis
Segmental
Mucosal
Total
42
23
12
1
7
3
88
47.73
26.14
13.64
1.14
7.95
3.40
100
> 12 years = 524 patients
Number of
Percentage
cases
152
135
138
24
19
56
524
29.00
25.76
26.34
4.58
3.63
10.69
100
interesting study where the frequency of atopy was
found to be significantly higher in patients with
vitiligo[12]. Kovacs also stated that patients with
vitiligo have an increased risk of developing
autoimmune diseases[5]. He also noted that autoantibodies against different organ systems can be
present in vitiligo patients without clinical
correlation. A landmark study, including children
as well as adults, was reported in 1994[4], which
discussed whether the association of other diseases
with vitiligo is co-existence or a true association.
This study could not confirm a higher prevalence
for thyroid diseases or any other autoimmune
disease for childhood vitiligo. They did not find a
higher prevalence of auto-antibodies in their series;
however, they concluded that as a developing
group, vitiligo patients are at higher risk of
developing thyroid disease with impaired function;
association with other diseases is a random event.
Alkhateeb et al have stated that the frequency of
six autoimmune disorders is significantly elevated
in vitiligo probands and their first-degree relatives;
vitiligo itself, autoimmune thyroid disease, pernicious
anemia, Addison’s disease, systemic lupus
erythematosus, and probably inflammatory bowel
disease[7]. A recent article [13] has reported the
presence of thyromegaly, antithyroid antibodies
and thyroid dysfunction in a significant number of
children and adolescents with vitiligo. We believe
that the issue is not settled yet. Discrepancy among
various studies stresses on the need for more
thorough studies on this aspect.
Our study did not show any of our patients
having clinically apparent deafness or any ocular
abnormality. Auditory disability and ocular
involvement in vitiligo patients has attracted
attention, because it is known that the inner ear
contains melanocytes and also the pigment
epithelium of the retina and the choroid are rich in
melanocytes[14,15]. Since vitiligo affects all active
melanocytes, auditory and ocular problems can
result in patients with vitiligo[5].
131
Table 5: Association of vitiligo with other diseases
Associated disease
Thyroid antibodies
Diabetes mellitus
Alopecia Areata
Atopic dermatitis
Psoriasis
Number of cases
13
9
21
49
2
Percentage
2.12
1.47
3.4
8
0.33
In conclusion, a clinico-epidemiologic study of
vitiligo in Kuwait shows that generalized vitiligo is
the commonest clinical-type observed. There were
associated disorders/abnormalities in some patients.
Keeping in view the observation of anti-thyroid
antibodies in some of these patients, we suggest
that patients having these antibodies should be
followed up for the possible development of
clinical thyroid dysfunction.
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Bolognia JL, Pawelek JM. Biology of hypopigmentation. J
Am Acad Dermatol 1988; 19:217-255.
Moscher DB. Vitiligo: etiology, pathogenesis, diagnosis and
treatment. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al,
editors. Dermatology in General Medicine, 4th edn. New
York: McGraw-Hill; 1993, p 923-933.
Ortonne JP, Moscher DB, Fitzpatrick TB. Hypomelanotic
Disorders in Vitiligo and other hypomelanoses of Hair and
Skin. New York: Plenum; 1983, p 129-310.
Schallreuter KU, Lemke R, Brandt O, Schwartz R,
Westhofen M, Montz R, et al. Vitiligo and other diseases:
Coexistence or True association? Dermatology 1994;
188:269-275.
Kovacs SO. Vitiligo. J Am Acad Dermatol 1998; 38:647-666.
Handa S, Kaur I: Vitiligo: clinical findings in 1436 patients,
J Dermatol 1999; 26:653-657.
Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA:
Epidemiology of vitiligo and associated autoimmune
diseases in Caucasian probands and their families, Pigment
Cell Res 2003; 16:208-214.
Nanda A, Al-Hasawi F, Alsaleh QA. A prospective survey
of pediatric dermatology clinic patients in Kuwait: an
analysis of 10,000 cases. Pediatr Dermatol 1999; 16:6-11.
Hann SK, Chun WH, Park YK: Clinical characteristics of
progressive vitiligo. Int J Dermatol 1997; 36:353-355.
Cho S, Kang HC, Hahm JH. Characteristics of vitiligo in
Korean Children. Pediatr Dermatol 2000; 17:189-193.
Handa S, Dogra S. Epidemiology of childhood vitiligo: a
study of 625 patients from north India. Pediatr Dermatol
2003; 20:207-210.
Perfetti L, Cespa M, Nume A, Orecchia G. Prevalence of
atopy in vitiligo. A preliminary report. Dermatologica 1991;
182:218-220.
Kurtev A, Dourmishev AL. Thyroid function and
autoimmunity in children and adolescents with vitiligo. J
Eur Acad Dermatol Venerol 2004; 18:99-117.
Wolff D. Melanin in the inner ear. Arch Otolaryngol 1931;
14:195-211.
Albert D, Wagoner M, Pruett R, Nordlund JJ, Lerner AB.
Vitiligo and disorders of the retinal pigment epithelium. Br
J Ophthalmol 1983; 67:153-156.
KUWAIT MEDICAL JOURNAL
June 2006
Case Report
Bone Involvement in Hodgkin’s Disease at Presentation: A
Series of Three Case Reports with a Brief Review
Farhat Aziz Khan, Shad Salim Akhtar, Muhammad Kamil Sheikh
Department of Medical Oncology, King Fahd Specialist Hospital, Buraidah, Al-Qassim, Saudi Arabia
Kuwait Medical Journal 2006, 38 (2): 132-135
ABSTRACT
Most patients with Hodgkin’s lymphoma present with
progressive painless lymphadenopathy. Very few patients
have presented with bony involvement at the time of
diagnosis. We report on three cases of Hodgkin’s
lymphoma who presented with signs and symptoms of
bone involvement in addition to other clinical features of
the disease. On staging workup, all the three patients
were found to have bony lesions at the time of diagnosis,
confirmed by imaging studies. All patients were treated
with chemotherapy and radiotherapy directed at their
bony lesions.
KEYWORDS: bony lesions, Hodgkin’s lymphoma, painless lymphadenopathy
INTRODUCTION
The most common presentation in Hodgkin’s
disease is progressive painless lymphadenopathy.
Although bone involvement is frequent during the
course of disease, an onset with bone involvement
and its symptoms is extremely rare. We present
here three cases of Hodgkin’s disease, one male and
two female, diagnosed at King Fahd Specialist
Hospital, Al-Qassim, Saudi Arabia, over a period of
three years. All the three patients were young and
presented with signs and symptoms of bone
involvement in addition to other clinical features of
Hodgkin’s lymphoma. Two patients presented with
backache and one with pain in the left hand and left
arm. Diagnosis was confirmed histopathologically
in all patients. On staging workup, all the three
patients were found to have bony involvement at
the time of diagnosis confirmed by imaging studies.
Diagnosed as stage IVB disease, all of them received
treatment in the form of chemotherapy and
radiotherapy directed at their bony lesions.
Case - 1
A 19-year-old female presented with a four
week history of backache, irregular fever and
weakness. During this period, she also noticed
small multiple swellings on both sides of her neck
and lost some weight as well. Her back pain was
moderately intense without any radiation or motor
power weakness. There was no history of any
urinary, respiratory or gastrointestinal manifestations.
Also, she did not give history of any definitive
treatment. On examination, she was ill-looking,
pale and febrile. Multiple bilateral cervical and
right axillary lymph nodes were palpable. Her back
examination revealed a spinal gibbous and tenderness
over lower dorsal and lumbar spines. Abdominal
examination showed mild hepatospleno-megaly and
rest of the systemic examination was normal.
Laboratory investigations revealed an Hb of 7
gm/dl and a high LDH level. Rest of the parameters
was normal. Her chest X-ray (CXR) showed bilateral
hilar and paratracheal lymphadenopathy and an Xray of the dorsolumbar spine showed a compression
fracture of L1 vertebra (Fig. 1). A CT scan of the
neck, chest and abdomen showed bilateral
pretracheal, paratracheal, subcarinal and right hilar
nodes. Multiple para-aortic and inter-aortocaval
lymph nodes were also seen. The liver and spleen
were normal. A MRI of the spine confirmed a
wedge shaped compression fracture of L1 vertebra
with bone destruction. Post contrast MRI showed
an adjacent para-spinal enhanced soft tissue
invasion and prevertebral lymph node mass at the
level of L1 without epidural invasion or cord
involvement; there was also post contrast
enhancement in the bodies of T9, T12, L2 and L5
vertebrae (Fig. 2). Radioactive isotope bone scan
suggested increased uptake in L1, L4 and L5 and
bilateral greater trochanters. Bone marrow aspiration
and biopsy did not confirm any marrow
infiltration. Fine needle aspiration of cervical
lymph node suggested Hodgkin’s disease which
was subsequently confirmed by biopsy. Diagnosed
as stage IVB Hodgkin’s disease, she was treated
with chemotherapy (ABVD x 6) and simultaneous
Address correspondence to:
Dr. Farhat Aziz Khan, Advanced Medical And Dental Institute, Universiti Sains Malaysia Suite 141, Eureka Complex, 11800 USM, Penang,
Malayasia. Tel:04-6532738/017-4691636, Fax:04-6532734, E-mail:[email protected]
June 2006
KUWAIT MEDICAL JOURNAL
133
Fig. 2: Spinal MRI showing a wedge shaped compression fracture of L1,
post contrast enhancement in the bodies of T9, T12, L1, L2 and L5
vertebrae. There is no epidural invasion or cord compression. Also
shown, is the spinal gibbous.
Fig. 1: X-Ray of Lumbar spine (lateral view) showing compression
fracture of L1 vertebrae
radiotherapy to her spine. The patient was
discharged after her first cycle of chemotherapy
and advised to follow up for further treatment.
Case - 2
A 28-year-old Saudi male patient was admitted
with history of backache, shortness of breath,
generalized weakness and loss of weight for one
month. He also noticed bilateral multiple swellings
in his neck and there was associated history of
night sweats and occasional low-grade fever. On
examination, he was dyspneic at rest and had
bilateral lymphadenopathy in supraclavicular,
jugulodigastric, subclavicular and axillary regions.
The nodes were rubbery and the biggest one over
left jugulodigastric region was 5 cm x 2 cm in
diameter. Chest examination revealed diminished
breath sounds over left hemithorax with stony dull
note on percussion suggestive of pleural effusion.
Cardiovascular and nervous system examination
was normal. Abdominal examination showed
hepatosplenomegaly. Musculoskeletal examination
revealed tenderness over the lumbar area.
Fig.3: CT scan of abdomen showing retroperitoneal, paraaortic
lymphadenopathy with infiltration of right psoas area and right border of
second lumbar vertebrae
Investigations revealed a WBC count of 28,000 x
109/L with 91% neutrophils and 3.3% lymphocytes.
Hemoglobin was 11.2 gm/dl and the platelet count
was normal. Serum chemistry was unremarkable
except for low total proteins (40.6 gm/l). Lymph
node biopsy revealed the diagnosis of a grade-II
nodular sclerosis type of classical Hodgkin’s
lymphoma. Bone marrow aspiration did not reveal
any bone marrow infiltration. His CT scan brain,
neck, chest, abdomen and pelvis showed bilateral
cervical lymphadenopathy, massive left-sided
pleural effusion with collapse of left lung and
evidence of re t roperitoneal and para-aortic
lymphadenopathy with hypodense necrotic mass
infiltrating in the region of the right psoas muscle,
2nd and 3rd lumbar vertebrae and medial aspect of
the right kidney (Fig. 3 and 4). Diagnosed as StageIVB Hodgkin’s disease, he was started on
chemotherapy (ABVD) and simultaneous radiation
therapy to his spine. After receiving his first cycle of
chemotherapy the patient was asymptomatic and
was discharged with advice to follow up for further
chemotherapy.
134
Bone Involvement in Hodgkin’s Disease at Presentation: A Series of Three Case Reports with a .....
June 2006
Fig. 4: Reconstructed CT scan image showing destroyed lumbar vertebral
body
Fig. 5: X-ray left hand showing spongiosclerosis with periosteal
apposition of 2 nd and 3rd metacarpal bones
Fig. 6: Periosteal apposition of postero-lateral and medial aspect of
middle 3rd of left femur
Case - 3
A 16-year-old young girl presented with a
complaint of pain, mainly in left hand and left arm
and a fever of two week duration. There was no
history of any visible swelling, weight loss or
sweating. On physical examination, she was
looking well with stable vital signs. She had left
supraclavicular lymphadenopathy. A musculoskeletal
system examination revealed an inflammatory
swelling over the dorsum of her left hand and
tenderness of the left arm below elbow joint and left
mid thigh. Other systemic examination was
unremarkable.
CBC and chemistry was normal. A CXR revealed
haziness over left apex (left paratracheal
lymphadenopathy). Abdominal USG was normal
and CT scan chest, neck and abdomen showed left
cervical and paratracheal lymphadenopathy. Limb
X-rays revealed multiple sclerotic bony lesions viz., (i) spongiosclerosis with periosteal apposition
affecting 2 nd and 3 rd metacarpal bones of the left
hand (Fig. 5), (ii) periosteal apposition of middle
third of right radius with focal spongiosclerosis,
and (iii) periosteal apposition of the postero-lateral
and medial aspects of the middle 3rd of left femur
(Fig. 6). Excisional biopsy of the left cervical lymph
node was done and histopathology was suggestive
of Hodgkin’s disease, nodular sclerosis. Diagnosed
as stage IVB with bone involvement, this patient
was started treatment on chemotherapy (ABVD x 6
cycles) and after completing full treatment the
patient was in complete remission.
June 2006
KUWAIT MEDICAL JOURNAL
DISCUSSION
Hodgkin’s disease usually presents with nodal
and visceral enlargement. Bone involvement in
Hodgkin’s disease at the time of presentation is
extremely rare[1,2]. Less than 20 such cases have been
reported in the literature. Kaplan et al[3] reported
only four out of 334 cases of Hodgkin’s disease to
have
radiologically demonstrable skeletal
involvement at the time of initial diagnosis. Gross et
al[4] reported two cases of primary Hodgkin’s
disease of the bone. Gall and Mallory [5] did not find
a single case with initial bone involvement out of
229 cases of Hodgkin’s disease studied by them.
Most of the cases with bone involvement at initial
presentation have been adolescents and few adults,
which is comparable with our case reports.
Osseous involvement in Hodgkin’s disease
occurs through hematogenous spread or direct
spread from a contiguous involved lymph node.
The presenting complaints of bone involvement are
usually insidious onset of pain with associated
weight loss and malaise. Radiologic evaluation
reveals osteosclerosis alone, osteolysis alone or a
combination of two. Osteolytic lesions are poorly
defined and are associated with periostitis in
approximately one third of cases[6]. Technicium 99
bone scan may disclose other clinically unapparent
sites of bone involvement. The common sites are
spine, pelvis, ribs, femur and sternum[7].
For isolated bone lesions radiotherapy is quite
effective and long-term disease-free survival in
such patients has been reported[8]. Patients with
pelvic or spinal bone involvement are unlikely to
135
survive for long because their response to cytotoxic
therapies is relatively poor[9]. In the present series,
treatment consisted of chemotherapy (ABVD x 6
cycles) and radiation therapy directed at the bony
lesions.
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Bonnadonna C, Weirmik PH, Santoro A. Clinical treatment
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Kaplan HS. Hodgkin’s Disease, 2nd ed. Cambridge:
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Gross SB, Robertson Jr. WW, Large BJ, Bunin NJ,
Drummond DS. Primary Hodgkin’s disease of bone. A
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Gall AE, Mallory TB. Management of lymphoma. Am J
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117-131.
KUWAIT MEDICAL JOURNAL
June 2006
Case Report
Unusual Presentation of a Common Disease: Disseminated
Tuberculosis Presenting as Osteomyelitis
Ajay Gupta, Moncy Jacob Oommen, Jayant Amritlal Budhdev
Department of Internal Medicine, Khoula Hospital, Oman
Kuwait Medical Journal 2006, 38 (2): 136-137
ABSTRACT
Tubercular osteomyelitis is an uncommon form of
skeletal tuberculosis. We report one such case associated
with disseminated tuberculosis and treated with antitubercular medication.
KEY WORDS: anti-tubercular treatment, disseminated tuberculosis, osteomyelitis
INTRODUCTION
Tubercular osteomyelitis of the digits or
Dactylitis is a rare variant of skeletal tuberculosis,
spinal form being the most common. We report a
case, which presented as dactylitis but the
etiological diagnosis was suggested by the
concomitant presence of tuberculosis elsewhere in
the body.
CASE REPORT
A 20-year-old lady was admitted to the plastic
surgery ward of Khoula Hospital with complaints
of pain and swelling proximal to base of the left
thumb, of one and a half month’s duration. On
examination, she had features of an abscess on the
dorsal aspect of the first metacarpal. The radiograph
showed features of osteomyelitis (Fig. 1). A
diagnosis of abscess with osteomyelitis of the 1st
metacarpal was made. As the patient gave a history
of respiratory infection, a chest X-ray was taken.
The medical team was called for further evaluation
as the chest radiograph showed abnormal
shadows.
On detailed medical history, she admitted
having cough of six-week duration with low-grade
fever and significant weight loss. Her general
examination revealed a thinly built lady with pallor
and a solitary, 2 cm diameter, mobile non-tender
lymph node in the right cervical area. Rest of her
general and systemic examination was unremarkable.
Her combined blood count was normal; erythrocyte
sedimentation rate was 57 mm in first hour and rest
of the routine biochemistry was normal. Her
hepatitis B and HIV serology were non-reactive.
Mantoux test was negative. Her chest radiograph
showed a pattern of small nodular opacities all
over the lung fields (Fig. 2).This raised the
suspicion of miliary tuberculosis and prompted
further confirmation of the aetiology. Aspirate from
the abscess over the thumb showed acid fast bacilli
(AFB) on Ziehl Neelsen (ZN) staining. Sputum
examination as well as fine needle aspirate from
cervical lymph node also came positive for AFB on
ZN staining. Ultrasonography examination of the
abdomen revealed para-aortic lymph nodes.
A final diagnosis of tuberculous osteomyelitis of
the 1st metacarpal giving rise to a cold abscess, with
disseminated tuberculosis leading to pulmonary and
lymph node involvement was made. She was given
splint immobilisation for the first metacarpal. The
patient was started on a four drug regimen
(isoniazid + rifampicn + pyrazinamide + ethambutol
for the first two months followed by isoniazid +
rifampin for a total of nine months) as per DOT
guidelines. She was doing better with healing of
the abscess (without any surgery) and gain in
weight. Both the sputum and aspirated pus from
the metacarpal grew Mycobacterium tuberculosis
sensitive to all four drugs. She was admitted to the
general surgery ward after two months for excision
of the same cervical lymph node. Biopsy showed
fibro-collagenous tissue with granulomas composed
of epithelioid cells suggestive of granulomatous
lesions most likely due to tuberculosis. She continued
with just her anti-tubercular therapy and had
complete recovery from her chest condition, lymph
node and dactylitis. There were no further
complications either from the drugs or from the
musculoskeletal system. She was discharged from
follow up after nine months of therapy.
Address correspondence to:
Dr Ajay Gupta, 1/54 Robert Street, Jesmond NSW 2299, Australia. Tel: 00610755281253, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
137
Fig. 1: X-ray Hand showing typical lytic areas in the first metacarpal with
subperiosteal new bone formation
Fig. 2: X-ray Chest showing small nodular opacities all over the chest,
suggesting disseminated pulmonary tuberculosis
DISCUSSION
Approximately, 30 million people worldwide
are affected by tuberculosis. Out of this, about 1 to
3% have skeletal involvement[1]. Tuberculous
osteomyelitis comprises 2 to 3% of all cases of skeletal
tuberculosis[2].In bone and joint disease, pathogenesis
is related to reactivation of hematogenous foci or to
spread from adjacent paravertebral lymph nodes.
Late activation of Ghon focus does not usually lead
to hemato-genous spread. This was probably primary
pulmonary tuberculous infection leading to
disseminated bone infection. It commonly presents
as pain and swelling with abscess with or without
sinus formation. A small focal area of osteomyelitis
located eccentrically with little or no surrounding
reactive bone is characteristic (unless secondary
infection supervenes) and the presence of local
osteopenia helps in the diagnosis of tuberculosis[3].
In some cases, especially the small bones of hands
and feet, the affected bone may show subperiosteal
new bone formation, referred to as “spina ventosa”
type of tuberculous osteomyelitis (Fig. 1). The variable
clinical and radiological picture may mimic chronic
pyogenic osteomyelitis, Brodie’s abscess, tumor or
granulomatous lesion[4]
On routine investigation, around 20% of such
patients have associated pulmonary tuberculosis[5].
We have not come across any literature showing
concomitant presence of tuberculous osteomyelitis,
cervical lymphadenopathy and active disseminated
pulmonary tuberculosis (Fig. 2). A high ESR and
negative Mantoux test (which is seen with disseminated
tuberculosis) also go in favour of tuberculosis. Lack
of familiarity and awareness of tuberculous
osteomyelitis may lead to delays in diagnosis.
Positive proof of the disease can be obtained by
specifically asking for ZN staining of the material
obtained on aspiration or by showing tubercular
involvement of other systems in histopathology
specimens.
CONCLUSION
Tubercular osteomyelitis is a rare clinical entity.
Looking for any evidence of tuberculosis elsewhere
may help in formulating a correct diagnosis. We
have reviewed our experience in the hope of
stimulating a high index of suspicion for early
diagnosis.
ACKNOWLEDGEMENT
The authors would like to thank Dr C Thomas,
Head and other members of the plastic surgery
department for their valuable support in
completing this case report.
REFERENCES
1.
2.
3.
4.
5.
Tuli SM. Tuberculosis of skeletal system. 2nd Ed. New
Delhi: Jaypee Brothers Medical publishers; 1997.
Martini M, Boudjeman A, Hannachi MR: Tuberculous
osteomyelitis. A review of 125 cases. Int Orthop 1986;
10:202-207.
Rajeev Vohra, Harinder S. Kang, et al. Tuberculous
osteomyelitis. J of Bone and Joint Surgery 1997; 79:562-566.
Rasool MN, Govender S, Naidoo KS. Cystic tuberculosis of
bone in children. J Bone and Joint Surgery 1994; 76:113-117.
Griffith JF, Kumta SM, Leung PC. Imaging of
musculoskeletal tuberculosis: A new look at old disease.
Clin Orthop 2002; 398:32-39.
KUWAIT MEDICAL JOURNAL
June 2006
Case Report
3C Syndrome (Cranio-Cerebello-Cardiac Dysplasia) or
Ritscher-Schinzel Syndrome: A Rare Case Report with
Review of Literature
Adnan El-Kishawi, Sakeer V Thrikovil, Amrit L Soni
Department of Pediatrics, Farwaniya hospital, Kuwait
Kuwait Medical Journal 2006, 38 (2): 138-140
ABSTRACT
A very rare case of 3C (cranio-cerebello-cardiac)
syndrome is reported for the first time in an Arab infant
from Kuwait. The diagnostic features and differential
diagnosis is discussed. We support the autosomal recessive
inheritance of this condition due to consanguinity
between the parents. Need of antenatal diagnosis and
genetic counseling is highlighted for this prognostically
poor condition.
KEYWORDS: autosomal recessive, consanguinity, 3C syndrome
INTRODUCTION
Ritscher-Schinzel or cranio-cerebello-cardiac
(3C) syndrome is a very rare condition and so far
only 30 cases are reported all over the world,
mostly from North America and Europe[1, 2]. We are
reporting a typical case for the first time from a
Saudi family living in Kuwait.
CASE REPORT
A baby girl was born to a 31-year-old para 5,
Saudi mother at 37 weeks of gestation by normal
delivery. The father was 40 years old and a distant
cousin of mother. All four siblings (two brothers
and two sisters) were healthy. Family history was
not remarkable. The pregnancy was uneventful.
Birth weight was 2.1 kg (10th centile); head
circumference was 34 cm (90th centile) and length
was 44 cm (3rd centile). Apgar scores were six and
nine at one and five minutes.
Many dysmorphic features were noted after
birth and they were as follows: cleft palate, low set
abnormal ears, depressed nasal bridge, hypertelorism,
prominent occiput, micrognathia, anteverted nostrils,
long philtrum, overriding of fingers, rocker bottom
feet, hypoplasia of the middle and distal phalanges
of the 5 th finger, large anterior fontanelle (4 x 4 cm)
and anal atresia with recto-vaginal fistula (Figs. 1,2
and 3). The baby had respiratory distress and a
significant cardiac murmur at birth, diagnosed as
patent ductus arteriosus (PDA) with multiple
ventricular septal defects (VSD’s) by echocardiography.
She was ventilated, given anti-failure treatment and
subsequently operated by pulmonary artery
banding for VSD and PDA ligation by midline
sternotomy (Fig. 1).
CT scan of the head showed Dandy Walker
malformation, corpus callosum agenesis and large
retro-cerebellar cyst (Fig. 4). Abdominal ultrasound
revealed bilateral hydronephrosis with a normal
sized bladder. Skeletal survey, eye examination,
fundoscopy and karyotyping were normal. The
baby is now three and a half month old with failure
to thrive (Weight : 2.3 kg, Length : 46 cm, Head
Circumference : 34 cm; all below the 3rd centile),
severe psychomotor retardation and mild hypotonia.
She is tube-fed and oxygen dependent for bronchopulmonary dysplasia.
DISCUSSION
Ritscher et al (1987) described two sisters with
congenital heart malformation, cerebellar anomalies
and craniofacial anomalies[3]. In 1989, Verloes et al
reported a third case, a female with VSD, enlarged
fourth ventricle and cisterna magna; and proposed
the name Ritscher-Schinzel syndrome [4].
Ritscher-Schinzel syndrome, also known as 3C
(cranio-cerebello-cardiac) syndrome is a rare
autosomal recessive syndrome characterized by
craniofacial, cerebellar and cardiac anomalies.
Cardiac anomalies include VSD, ASD, PDA,
Tetralogy of Fallot, double outlet right ventricle;
hypoplastic left heart syndrome, aortic stenosis,
pulmonary stenosis and other valvular anomalies.
Central nervous system anomalies include DandyWalker malformation, cerebellar hypoplasia, and
enlargement of cisterna magna. Craniofacial
abnormalities are cleft palate, ocular coloboma,
prominent occiput, low set ears, hypertelorism,
Address correspondence to:
Dr. Adnan El-Kishawi, P.O Box 1786, Salmiya - 22018, Kuwait. Tel: 5733008, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
139
Fig. 2: Showing prominent occiput, low set abnormal ears and anteverted
nostril
Fig. 3: Showing anal atresia and rectovaginal fistula
Fig. 1: Showing hypertelorism, anteverted nostril, overriding fingers and
scar of cardiac surgery
down slanting palpebral fissures, depressed nasal
bridge and micrognathia. These features may occur
in isolation or as a part of many syndromes[5]. Other
rare malformations noted in less than 10% of
patients are absent ribs, adrenal hypoplasia, anal
atresia, congenital glaucoma, cutis aplasia,
hemangioma, hemi vertebrae, hypospadias, hypoplasia
of nail, nipple or penis, inguinal hernia, malrotation
of gut, polydactyly, renal malformation, single
umbilical artery, growth hormone deficiency and
immunodeficiency[6-13]. Recently, a case with
heterochromia of iris has been reported [2].
The proposed minimum criteria for diagnosis of
this syndrome are the presence of cardiac
malformation other than isolated patent ductus
arteriosus, cerebellar malformation, and cleft palate
or ocular coloboma or four of the following seven
findings: prominent forehead, prominent occiput,
hypertelorism, down-slanting palpebral fissures,
low-set ears, depressed nasal bridge, and
micrognathia[5].
There are no studies on incidence and prevalence.
The syndrome seems to be pan ethnic: 18 cases were
Caucasian, two African-American, three Canadian
Native Americans, three Pakistanis and four of
unspecified race and ethnicity. The gender ratio of
10 males to 18 females is not significantly different
from expected 1:1 for an autosomal recessive
inheritance, which is supported by reports of four
sets of affected siblings born to unaffected parents
and of affected children born to consanguinous
parents[15]. Our case is from an Arab family and this
was not reported earlier. We also support autosomal
recessive etiology as both parents are related[1].
Karyotyping was normal in all reported cases, as
also in our case.
Several syndromes should be considered in the
differential diagnosis of patients with suspected 3C
syndrome[5]. Joubert syndrome involves cerebellar
vermis hypoplasia, ataxia, hyperpnoea, abnormal
eye movements and occasionally cleft lip and
palate. Patients with Joubert syndrome may have
heart malformation. Ellis-Van Crevald syndrome
can involve alveolar ridge anomalies, heart defects
and occasionally Dandy-Walker malformation.
Dandy-Walker malformation has been described
along with craniofacial and congenital heart defects
in the Brachmann-de Lange syndrome. The latter
two syndromes however, have other distinctive
extra cranial anomalies, which distinguish them
from the Ritscher-Schinzel syndrome[5].
140
3C Syndrome (Cranio-Cerebello-Cardiac Dysplasia) or Ritscher-Schinzel Syndrom
June 2006
consanguinity in parents with or without positive
family history, the antenatal diagnosis of 3C
syndrome is very likely; and the option of
therapeutic abortion may be discussed with parents
in view of the poor prognosis of this condition. We
therfore advocate an early antenatal diagnosis of
the 3C syndrome.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
Fig. 4: CT scan of brain showing Dandy Walker malformation and
retrocerebellar cyst
Most of the cases die before the age of six years,
but one case is reported to have survived upto the
age of 21 years. All cases were invariably retarded
physically and mentally [14].
Because the diagnosis of an autosomal recessive
syndrome implies a 25% risk of recurrence of
Ritscher-Schinzel syndrome in siblings of affected
children, an accurate diagnosis is important for
genetic counselling. Use of the proposed diagnostic
criteria will enable more accurate diagnosis and
more reliable counselling of affected families[5]. A
prenatal sonogram done in second trimester can
easily diagnose the cardinal features of 3C
syndrome viz., Dandy-Walker malformation or its
variants like posterior cranial fossa cyst or aplasia /
hypoplasia of cerebellar vermis, congenital heart
disease and intrauterine growth retardation[5]. If
these features are found in association with
8.
9.
10.
11.
12.
13.
14.
15.
Orstavik KH, Bechensteen AG, Fugelseth D, Orderud W.
Sibs with Ritscher-Schinzel (3C) syndrome and anal
malformations. Am J Med Genet 1998; 75:300-303.
Hatzidaki E, Manoura A, Korakaki E, Germanakis J,
Karabekios S, Giannakopoulou C. Ritscher-Schinzel or 3C
syndrome, with heterochromatic iris. Pediatr Int 2003;
45:574-576.
Ritscher D, Schinzel A, Boltshauser E, Briner J, Arbenz U,
Sigg P. Dandy-Walker (like) malformation, atrio-ventricular
septal defect and a similar pattern of minor anomalies in 2
sisters: a new syndrome? Am J Med Genet 1987; 26:481-491.
Verloes A, Dresse MF, Jovanovic M, Dodinval P, Geubelle
F. 3C syndrome: third occurrence of cranio-cer ebellocardiac dysplasia (Ritscher-Schinzel syndrome). Clin Genet
1989; 35:205-208.
Leonardi ML, Pai GS, Wilkes B, Lebel RR . Ritscher-Schinzel
cranio-cerebello-cardiac (3C) syndrome: report of four new
cases and review. Am J Med Genet 2001; 102:237-242.
Lurie IW, Ferencz C. �Shifted’ threshold may explain
diversity of cardiovascular malformations in multiple
congenital abnormalities syndromes: 3C (Ritscher-Schinzel)
syndrome as an example. Am J Med Genet 1996; 66:72-74.
Digilio MC, Marino B, Giannotti A, Mingarelli R,
Dallapiccola B. Atrioventricular canal and 3C (craniocerebello-cardiac) syndrome (Letter). Am J Med Genet 1995;
58:97-98.
Fraser FC. Liability, thresholds, malformations, and
syndromes (Editorial). Am J Med Genet 1996; 66:75-76.
Gurrieri F, Neri G. An additional patient with the 3C
syndrome. Clin Genet 1992; 41:263-265.
Hoo JJ, Kreiter M, Halverson N, Perszyk A. 3C (craniocerebello-cardiac) syndrome: a recently delineated and
easily recognizable congenital malformation syndrome. Am
J Med Genet 1999; 52:66-69.
Kosaki K, Curry CJ, Roeder E, Jone KL. Ritscher-Schinzel
(3C) syndrome: documentation of the phenotype. Am J
Med Genet 1997; 68:421- 427.
Lauener R, Seger R, Jorg W, Halle F, Aeppli R, Schinzel A.
Immunodeficiency associated with Dandy-Walker-like
malformation, congenital heart defect, and craniofacial
abnormalities (Letter). Am J Med Genet 1989; 33:280-281.
Saraiva JM, Gama E, Moreira PM, Sequeira JF. First report
of glaucoma as a feature of the 3C syndrome. Clin
Dysmorph 1995; 4:156-160.
Zankl A, Gungor T, Schinzel A. Cranio-cerebello-cardiac
(3C) syndrome: follow-up study of the original patient. Am
J Med Genet 2003; 118:55-59.
Marles SL , Chodirker BN, Greenberg CR, Chudley AE.
Evidence for Ritscher-Schinzel syndrome in Canadian
native Indians. Am J Med Genet 1995; 56:343-350.
June 2006
KUWAIT MEDICAL JOURNAL
Case Report
Successful Treatment of Pyogenic Granuloma Complicating
Motility Peg Hydroxyapatite Orbital Implant using Topical
Steroids Alone - A Case Report
Jamal H Behbehani, Ramnata B Paramasivam, Anil K Uboweja
Department of Ophthalmology, Al-Adan Hospital, Kuwait
Kuwait Medical Journal 2006, 38 (2): 141-143
ABSTRACT
Pyogenic granuloma is a known complication of
motility peg hydroxyapatite orbital implants.
Treatment options including invasive surgical
procedures and topical applications of mitomycin
C have been reported in the literature. We present a
case of pyogenic granuloma involving the base of
motility peg hydroxyapatite orbital implant, that
was successfully treated using topical steroids
alone.
KEYWORDS: hydroxyapatite, peg, pyogenic granuloma
INTRODUCTION
Pyogenic granuloma (PG ) is a hemangioma of
granulation tissue[1]. Hartzell first used the term
granuloma pyogenicum in 1904[2]. PG may involve
many areas pertinent to the ocular and adnexal
structures including eyelids, palpebral and bulbar
conjunctiva, limbus, cornea, socket, motility peg
implant, and along surgical incisions[3,4]. It may
occur following infection[5] mechanical irritation [3,6],
and trauma including surgery[3]. It may also present
in the conjunctiva without any preceding incident[2,7].
PG may present as sessile or pedunculated growth
ranging from few millimeters to greater than 3 cm
in diameter[2,8]. Its rate of growth is often fast and its
surface may show superficial ulcerations[2,8]. It
easily bleeds after trauma due to its vascularity.
Clinically and histopathologically, PG may resemble
Kaposi’s sarcoma, a malignant condition common
in patients with AIDS. It may be mistaken for rare
benign conditions including intravascular papillary
endothelial hyperplasia and angiolymphoid
hyperplasia with eosinophilia (ALHE). A chronic
lesion may thicken and resemble capillary
hemangioma or may shrink into a fibrous nodule [2].
The standard treatment for PG is simple
excision combined with or without cautery to the
base of the lesion[7]. We present a case of PG
involving the base of motility peg hydroxyapatite
(HA) orbital implant which was treated successfully
using topical steroids alone.
Case Description
A 49-year-old woman had an uneventful right
eye evisceration and a primary HA orbital implant.
Eleven months later, drilling and motility peg
placement was performed without complications.
Prosthesis was coupled to the peg six weeks later.
Post-operatively, the patient remained satisfied and
comfortable for a period of 23 months when she
started to complain of mucoid discharge that
persisted for two months. The patient lately
complained of difficulty in placing the prosthesis.
On examination, the patient was not wearing
the ocular prosthesis and was keeping it in its pack.
A pinkish circular mass measuring 16 mm in
diameter centered on the motility peg was seen
(Fig. 1). The mass was a thick, vascularized
granulation tissue that was partly covering the peg
head. The peg was not displaced. The surrounding
conjunctiva looked normal with no signs of
infection. The ocular prosthesis appear ed
adequately polished and free from any damage or
deposits.
Culture swabs taken from the mass lesion, the
conjunctiva and the mucoid discharge showed no
growth. Because the patient was reluctant to go for
surgery, it was decided to treat the PG
conservatively. The patient was treated with topical
prednisolone acetate 1% eye drops four times daily.
The patient reported significant improvement in
her symptoms with noticeable reduction of the
mucoid discharge a week after starting the treatment.
Address Correspondence to:
Dr. Jamal H. Behbehani, MBBCh. FRCSC, Head, Department of Ophthalmology, Al-Adan Hospital, P.O. Box 46969, Fahaheel, Postal Code:
64020, Kuwait. Tel: (965) 394-0600 Ext. 5660 - 5661, Fax: (965) 394-1707, E-Mail: [email protected]
142
Successful Treatment of Pyogenic Granuloma Complicating Motility Peg Hydroxyapatite ...
Fig. 1: Pyogenic granuloma mass pre-treatment
Fig. 3: Total resolution of pyogenic granuloma after six weeks of
treatment
Examination after two weeks showed a dramatic
regression in the size of the PG (Fig. 2). The same
treatment was continued for a period of four weeks
and was gradually tapered over the next two weeks
and then stopped. Both the PG and the mucoid
discharge totally resolved after six weeks of
initiating the treatment (Fig. 3). The patient was
eventually able to wear her ocular prosthesis
normally. She was followed for a period of 14
months with no signs of recurrence.
DISCUSSION
The complication rates of peg related HAorbital
implants are numerous, and range from 37.5 to
48.0%[9,10]. They include discharge, conjunctival
edema, PG, peg falling out, poor transfer of
movement, clicking, conjunctiva overgrowing peg,
poor-fitting sleeve, exposure of sleeve shaft, angled
peg drilling, exposure of HA implant around peg
hole, off-center peg drilling, popping peg, excess
peg movement, and implant infection[9].
PG as a complication of motility peg HA orbital
implants has been reported by Jordan et al to be the
second commonest complication, and by Lin et al as
the third commonest complication. Its frequency
June 2006
Fig. 2: Pyogenic granuloma mass two weeks post treatment
ranges from 16.7 to 30.6%[9,10]. It can occur with both
peg systems (i.e. peg alone and peg with sleeve). It
may occur within the peg hole or around the peg
hole[9]. Microscopically, the lesion contains granulation
tissue with prominent radiating capillaries that
spread from the base of the lesion toward the
surface. Its cellular component consists predominantly
of proliferating fibroblasts and endothelial cells as
well as mononuclear cells particularly lymphocytes,
plasma cells, and scattered polymorphs [1].
Apart from surgical excision, other treatment
modalities include topical applications of
mitomycin C[11], argon blue laser[9], combination of
carbon dioxide laser and topical steroids[12] and
topical steroids alone[13]. Although topical steroids
as a primary regimen in the treatment of PG
complicating motility peg HA orbital implant was
mentioned in the literature, its efficacy has not been
previously demonstrated in detail. Only two
reports have mentioned successful use of topical
steroids in the treatment of PG complicating
motility peg HAorbital implants. In one report, two
cases were treated using a combination of carbon
dioxide laser and topical steroids[12]. In the second
report, four cases were treated by excision or
topical steroids [13]. Additional details including the
name of steroid, the concentration, the frequency of
instillation, and the total duration of treatment
were not mentioned. The mechanism of steroid
action in ocular inflammation is well known. They
inhibit phospholipase A2, resulting in inhibition of
arachidonic acid degradation and subsequent
synthesis of prostaglandins and leukotrienes by
cyclooxygenase and lipooxygenase pathways.
Steroids suppress the proliferation of fibroblasts,
constrict blood vessels, and inhibit vascular
permeability and thereby minimize the leakage of
fluids, proteins and inflammatory cells in to the
target site [2]. Based on such properties, and due to
its safety as well as the patient’s reluctance to
undergo any surgical procedures, we initiated
June 2006
KUWAIT MEDICAL JOURNAL
topical steroid therapy. Both the patient’s
symptoms and the PG mass resolved within a
period of six weeks without untoward
complications. No recurrence was noted during a
follow up period of 14 months duration.
6.
REFERENCES
8.
1.
9.
2.
3.
4.
5.
Font RL: Cystic lesions: Eyelids and lacrimal drainage
system, In: Spencer WH, editor. Ophthalmic Pathology, An
Atlas and Textbook, Vol. 3. Philadelphia: WB Saunders;
1985; 2242
Albert and Jakobiec’s Principles and practice of
ophthalmology, WB Saunders, 1995; 282, 1014, 1720, 2110.
Liszauer AD, Brownstein S, Codere F. Pyogenic granuloma
on a dermis fat graft in acquired anophthalmic orbits. Am J
Ophthalmol 1987; 104:641-644.
Ferry A. Pyogenic granulomas of the eye and ocular
adnexa: A study of 100 cases. Trans Am Ophthalmol Soc
1989; 87:327.
Jordan DR, Brownstein S, Jolly SS. Abscessed hydroxyapatite orbital implants. A report of two cases.
Ophthalmology 1996; 103:1784-1787.
7.
10.
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12.
13.
143
Yoon-Duck Kim, Robert A. Goldberg, Norman Shoer,
Kenneth D. Steinsapir. Management of exposed
hydroxyapatite orbital implants. Ophthalmology 1994;
101:1709-1715.
Jakobiec FA. Corneal tumors, In: Kaufman H, Barron B,
McDonald M, et al, editors. The Cornea. New York:
Churchill Livingstone; 1998; 600-601
Lucas DR: The eyelids, In: Greer’s Ocular Pathology, 4th ed.
Boston: Blackwell Scientific; 1989; 97
Jordan DR, Chans Stanley, Mawn Louise, et al.
Complications associated with pegging hydroxyapatite
orbital implants. Ophthalmology 1999; 106:505-512.
Lin CJ, Liao SL, Jou JR, Kao SC, Hou PK, Chen MS:
Complications of motility peg placement for porous
hydroxyapatite orbital implants. Br J Ophthalmol 2002;
86:394-396.
Greer D, Popp JC : The use of mitomycin C for the treatment
of pyogenic socket granulation tissue associated with
motility pegs. J Ophthal Prosth 1996; 1:25-28.
Dutton JJ. Coralline hydroxyapatite as an ocular implant.
Ophthalmology 1991; 98:370-377.
Kalreider S, Newman S. Prevention and management of
complications associated with HA implant. Ophth Plast
and Recons Surg 1996; 12:18-31.
KUWAIT MEDICAL JOURNAL
June 2006
Case Report
Gitelman’s Syndrome: A Separate Disorder or a Variant of
Bartter’s Syndrome
Rasha Kamel Ghaddar, Fatma MAAbu Tiban
Department of Medicine, Amiri Hospital, Kuwait
Kuwait Medical Journal 2006, 38 (2): 144-146
ABSTRACT
Gitelman’s Syndrome (GS) is described as a separate
entity of potassium (K) loosing nephropathy that has to
be distinguished from Bartter’s Syndrome (BS). We
present a case report followed by a short review of
patients with chronic hypokalemia and the
differentiating features of these two K - loosing
nephropathies.
Key words: Bartter’s syndrome, chronic hypokalemia, Gitelman’s syndrome
INTRODUCTION
Hypokalemia, defined as serum potassium (SK)
< 3.6 mmol/l, is found in over 20% of hospitalized
patients. It is the most common electro l y t e
abnormality encountered in clinical practice.
However, when it comes to chronic hypokalemia,
its occurrence is infrequent but it presents a clinical
challenge in finding the cause[1]. It is well established
that the term familial BS includes a variety of
tubular transport disorders. The classical BS is
referred to as hypokalaemic alkalosis with
normocalciuria or hypercalciuria; while GS is
referred to as hypokalaemic alkalosis with
hypomagnesemia and hypocalciuria. We report a
case of GS and review the differential work up of
these two syndromes.
CASE REPORT
Mr FT, a 52-year-old Indian male patient was
admitted to the medical ward in Amiri Hospital to
investigate an accidental discovery of confirmed
hypokalemia on routine blood collection, after he
presented to the medical casualty with fever and
follicular tonsillitis. He had adequate dietary
intake, was on no drugs and had no other positive
symptoms. His past medical and family history
was unremarkable. Physical examination was
normal apart from congested tonsils. Basic
investigations showed normal renal function tests
with SK of 2.5 mmol/l. He had mild elevated S.
calcium of 2.6 mmol/l [normal range (nr) 2.2 - 2.65]
and low S. magnesium (SMg) 0.3 mmol/l(nr 0.8 1.2). Arterial blood gases (ABG) showed mild
metabolic alkalosis with pH of 7.5, normal pO2 and
pCO2 with S. bicarbonate of 32 mmol/l (nr 21 - 28).
Other investigations like electrocardiogram, chest
X-ray, complete blood count and liver function tests
were normal.
He was treated with high doses (> 180 mmol/d)
of i.v. potassium chloride. However, this could not
correct his hypokalemia. Once hypomagnesaemia
was noticed and corrected first, by i.v. Mg sulfate
for three days, his S.K returned to normal on much
lower doses.
Further investigations were as follow: ultrasound
of the kidneys and suprarenals was normal; 24hour
urine for metabolic screen showed the following:
K - 27 mmol/d (nr 20-100), Mg 8.96 mmol/d (nr
3.0 - 5.0), Calcium 1.3 mmol/d (nr 2.5 - 8), aldosterone
197.7 pmol/l (nr 111 - 863) - ambulatory, S-rennin 92
ng/ml/hr (nr 7 - 76).
This patient was labeled as GS. He was
discharged later on oral slow K, 1200 mg three
times/day and oral Mg oxide 500-mg twice/day
with SK of 3.8 mmol/l and S. Mg of 0.79/l.
DISCUSSION
Hypokalemia is classified as mild (3.0 - 3.5
mmol/l) usually asymptomatic; moderate (2.5 - 3.0
mmol/l) with non-specific symptoms; and severe
(below 2.5 mmol/l) where it can cause ascending
paralysis and muscle necrosis. In patients with
underlying cardiac disease, cardiac arrhythmias are
more common even with mild hypokalemia[2].
Chronic hypokalemia is less likely to induce
symptoms, as rapidity of decrease in SK is very
much correlated with induction of symptoms[2].
Hypokalemia is almost the result of K depletion
Address correspondence to:
Dr. Rasha Kamel Ghaddar,Medical Specialist, Department of Medicine, Amiri Hospital, Kuwait. P.O. Box 5254, Code No. 32083, Hawally,
Kuwait. Telephone: 2549094 Pager: 9358849, E-mail: [email protected]
June 2006
KUWAIT MEDICAL JOURNAL
induced by abnormal losses in urine or stool.
Uncommonly, it can be attributed to redistribution
of K between extracellular and intracellular spaces.
Inadequate intake is another possible cause[2,3].
Hypomagnesaemia, induced either by dietary
restriction or abnormal losses, reduces the
intracellular K concentration or leads to renal K
wasting. Mg depletion often co-exists with K
depletion as a result of drugs or disease process
(e.g., diarrhea) making it difficult to asses whether
it is an independent effect. However, the ability to
correct K deficiency is impaired when the S. Mg is
below 0.5 mmol/l. Repletion of Mg improves the
co-existent K deficit [2,4].
The first step in management of hypokalemia is
to review the patient, his drug and dietary record.
In surreptitious vomiting, hypochloremia, low
urine chloride and mild renal impairment are
supportive. High urine chloride is indicative of
diuretic abuse; while high stool weight and low
urine sodium indicate laxative abuse. If urine K is
> 20.0 mmol/l, it usually points to a renal cause.
ABG is also useful in the diagnostic work up. The
finding of metabolic alkalosis can exclude renal
tubular acidosis and laxative abuse[3].
When none of the usual causes apply and when
urine K is high, then BS is often suspected. GS
should also be considered although there are only a
few reports in the literature.
Bartter’s first description of his syndrome was
in 1962; it is characterized by hypokalaemic
metabolic alkalosis, hyperprostaglandin production,
hyperrenninemia, secondary hyperaldosteronism
with juxta-glomerular hyperplasia and normal
blood pressure[5]. It is associated with high urinary
prostaglandin levels. It has an autosomal recessive
mode of inheritance but sporadic cases have been
reported[5,6].
Recent advances in the field of molecular
genetics have demonstrated that there are four
genetically distinct abnormalities, which result
from mutations in renal electrolyte transporters and
channels.
Neonatal Bartter syndrome affects neonates and
is characterized by polyhydramnios, premature
delivery, severe electrolyte derangement, growth
retardation, and hypercalciuria leading to
nephrocalcinosis. It may be caused by a mutation in
the gene encoding the Na-K-2Cl cotransporter.
Classic Bartter syndrome is due to a mutation in the
gene encoding the chloride channel, and typically
presents in infancy or early childhood with failure
to thrive. Nephrocalcinosis is typically absent
despite hypercalciuria. The hypocalciuric,
hypomagnesaemic variant of Bartter syndrome
(Gitelman syndrome), presents in early adulthood
with predominantly musculoskeletal symptoms
145
and is due to mutations in the gene encoding the
Na-Cl cotransporter[7].
GS was first described in 1971 in three patients.
Several reports came after. These patients are
unlikely to present with symptoms except for
tetany or muscle weakness. Histopathology usually
shows minimal changes of the juxta-glomerular
apparatus[5]. GS has been noted to have an
autosomal mode of inheritance [1].
GS represents the clinical manifestations of
inactivating mutations in the gene encoding for the
thiazide sensitive sodium chloride cotransporter in
the distal convoluted tubule. Thus, the biochemical
characteristics resemble those seen with thiazide
d i u retics: hypokalemia, hypomagnesaemia,
h y p o c a l c i u r i a , metabolic alkalosis and blood
pressure in the low normal range. Until the genetic
background was clarified in 1996, GS was often
mistaken for BS, which is now attributed to defects
in the ion transportation system in the thick
ascending limb of Henle’s loop[8].
A further distinguishing feature was the
demonstration of hypercalciuria in patients with BS
while those with GS had abnormally low urinary
calcium excretion [5]. Hypomagnesaemia, usually of
a mild degree, is a major feature of GS but it is also
present in one fifth of patients with BS[4].
BS is an abnormality of chloride transport in the
thick ascending limb of the loop of Henle which
leads to loss of calcium and sodium, activation of
the rennin angiotensin aldosterone system and loss
of K. It resembles a state produced by furosemide.
In contrast, GS resembles a state produced by a
thiazide diuretic. Most probably the defect is in the
distal cortical convoluted tubule. The renal Mg
wasting in GS remains to be explained[4,5].
In BS, prostaglandin production is almost a
constant feature and many features of BS can be
improved by the use of cyclo-oxygenase inhibitors.
This has not been demonstrated in GS[1]. Even
though our understanding of these disorders has
been greatly advanced by these discoveries, the
pathophysiology remains to be completely defined.
In conclusion, this case report presents a
classical case of GS. The patient had all the definite
criteria including hypokalaemic metabolic alkalosis,
hypomagnesemia, and increased Mg excretion in
the urine, hypocalciuria, and high rennin level with
no evidence of hyperaldo-steronism. His age group
combined with normal physical examination
further establishes the diagnosis.
REFERENCES
1.
2.
C Luchy MTA, A Bettinelli, S Iseln. Normal
Prostaglandinuria E2 in Gitelman’s syndrome. Am J Kidney
Dis 1995; 25:824-828.
F John Gennari. Hypokalemia. NEJM 1998; 339:451-457.
146
3.
4.
5.
Gitelman’s Syndrome: A Separate Disorder or a Variant of Bartter’s Syndrome
U Gladziwa, R Schwarz, AH Gitter. Chronic hypokalemia
of adults: Gitelman’s Syndrome is frequent but classical
Bartter’s Syndrome is rare. Nephrol Dial Transplant 1995;
10:1607-1613.
Gary A Quamme. Renal magnesium handling: New
insights in understanding old problems. Kidney
International 1997; 52:1180-1195.
DA Mc Credie. Variants of Bartter’s Syndrome. Ped
Nephrol 1996; 10:419-421.
6.
7.
8.
June 2006
GH Malik, J Alwakeel, S Almohaya. Bartter’s Syndrome in
two successive Generations of a Saudi Family. Am J
Nephrol 1997; 17:459-498.
Shaer AJ. Inherited Primary renal tubular hypokalemic
alkalosis: review of Bartter’s syndrome and Gitelman’s
syndrome. Am J Med Sci 2001; 322:316-332.
Hansen KW, Mosekilde L. Gitelman’s syndrome, an
overlooked disease with chronic hypokalemia and
hypomagnesaemia in adults. Ugeskr Laeger 2003; 165:11231127.
June 2006
KUWAIT MEDICAL JOURNAL
Case Report
Factor XIII Deficiency in a Kuwaiti Child: Typical
Presentation with Delayed Diagnosis
Ibrahim Abdel Monsif Al-Sharkawy1, Kadankandy C Aboobacker 2, Mona H Bourhama 2
Department of Pediatrics, Al-Sabah Hospital, Kuwait
Pediatric Hematology Unit, NBK Children Department, Al-Sabah Hospital, Kuwait
1
2
Kuwait Medical Journal 2006, 38 (2): 147-148
ABSTRACT
Congenital factor XIII deficiency is a rare bleeding
disorder, presenting usually during the neonatal period.
We report here a case of a child with bleeding tendency
due to congenital factor XIII deficiency. Though he had a
typical presentation, the diagnosis was delayed due to
lack of a high index of suspicion. The patient was treated
successfully with cryoprecipitate and is doing well on
cryoprecipitate prophylaxis. This is indeed, the first case
report of this disorder from Kuwait.
KEYWORDS: bleeding disorder, congenital Factor XIII deficiency, cryoprecipitate
INTRODUCTION
Factor XIII deficiency is a rare bleeding disorder
occurring in approximately, one in two million
persons[1]. The main function of factor XIII is to
convert the loose fibrin polymer into a firm, highly
organized and cross-linked structure having
increased tensile strength, firmly anchored to the
site of the wound with an in-built resistance to
fibrinolysis[2]. The half life of factor XIII is long (1114 days) [2]. Clinical features include delayed
bleeding in the form of umbilical cord bleeding,
delayed cord separation, significant bleeding
following circumcision and trauma, poor wound
healing and an unusually high incidence (25-30%)
of intracranial hemorrhage[1,3]. The bleeding in this
disorder characteristically occurs 12-36 hours posttrauma. Factor XIII deficiency is inherited as an
autosomal recessive trait and is commonly due to
absence of the Factor XIII-A subunit protein in the
plasma[4]. Antenatal exclusion diagnosis can be
undertaken in subsequent pregnancy[4]. We report a
case of factor XIII deficiency in a male child who
developed recurrent delayed bleeding and went
undiagnosed upto the age of one year seven
months. To the best of our knowledge, he is the first
case of factor XIII deficiency reported from
Kuwait.
CASE REPORT
This one year and seven months old Kuwaiti
boy was admitted to our hospital with persistent
bleeding from a cut wound on the tongue and
bruise over the right groin following a fall in the
swimming pool five days ago. In the surgical
department, stitches were taken on the tongue to
stop the bleeding and he was sent home. He had
recurrence of bleeding at home and hence he was
brought to the pediatric department and was
admitted.
He was born in a private hospital at 36-week
gestation by caesarean section being small for date
with a birth weight of 1.76 kg. The parents are
second degree cousins and of Iranian ancestry. He
is the first child in the family. There was no family
history of bleeding disorders. He was well until the
age of 12 days when after separation of umbilical
cord, he started to bleed from the umbilical stump.
He was taken to a private hospital where he
received vitamin K but with no response. He was
then taken to special baby care unit in a regional
hospital where he was found to be pale and anemic
together with normal coagulation profile and
biochemical screening. He was given vitamin K
and blood transfusion. He improved and was
discharged home two days later.
At 14 months of age, he had small cut in the chin
following trauma requiring stitches but continued
to ooze blood from the wound for two weeks. He
had a history of gum bleeding during teething. At
the age of 18 months, he was admitted to the
surgical department with swelling in the scalp and
vomiting for five days after banging his head on
the wall in a fit of anger. The scalp swelling started
one day after trauma and progressively became
larger. He was investigated with a CT scan of the
head which showed diffuse sub-aponeurotic
hemorrhage, more on the left side without any
intracranial hemorrhage (Fig. 1). His CBC showed a
Hb of 80 gm/l and the coagulation profile
(platelets, PT, PTT) was normal. He was given
Address correspondence to:
Dr. Kadankandy C. Aboobacker, FRCP, DCH, P.O. Box 43470, Hawally, 32049, Kuwait. Tel: 4835826, Fax: 4835826, E-mail:
[email protected]
148
Factor XIII Deficiency in a Kuwaiti Child: Typical Presentation with Delayed Diagnosis
Fig. 1: Computerized tomography of the head showing diffuse bilateral
sub-aponeurotic hemorrhage without any intracranial bleeding
blood and was seen by a pediatrician who advised
further evaluation in our pediatric department to
rule out coagulation disorder. But parents could
bring the child to our department only one month
later when he started to bleed from a cut wound on
the tongue together with a bruise on the right groin
following trauma in the swimming pool.
On admission, the child was conscious, alert,
and active with bleeding from cut wound on the
tongue, multiple bruises over the lower limbs, and
bruises and hematoma in the right groin. His height
and weight were on 25th centile. No organomegaly
was noticed and he was not circumcised.
Investigations showed: Hb 108 gm/l, MCV 69 fl,
WBC 8.2 x 109/l with normal differential count,
platelets 431 x 109/l. Biochemical screen was
normal. Bleeding time, PT, INR and APTT were
normal.
In view of the history of recurrent delayed
bleeding tendency since birth together with normal
coagulation profile, congenital factor XIII deficiency
was suspected and was confirmed by positive
fibrin clot solubility in 5M urea and “1%
monochloracetic acid” and very low factor XIII in
the blood (Factor XIII level < 12.5%, N = 70-140). He
was treated with cryoprecipitate successfully and was
discharged home on cryoprecipitate prophylaxis every
three weeks. He had a successful circumcision
under cryoprecipitate cover without any problem
at the age of two years and three months. He
remains well on two units of cryoprecipitate
prophylaxis every three weeks and is developing
normally with no further bleeding diathesis
third hospital admission. We attribute this to many
factors : First, in factor XIII deficiency primary
coagulation study is normal; second, factor XIII
deficiency is a rare bleeding disorder and needs
high index of suspicion[5] and lastly the transfusion
of blood, plasma and other blood products before
collecting investigations can be especially
problematic in the interpretation of coagulation
tests[1]. The clinical features and investigation
results in factor XIII deficiency had been reviewed
in recent publications[2,3,5,6]. Our patient had indeed
the typical presentation. He presented in the
neonatal period with delayed cord separation
followed by umbilical stump bleeding not
responding to vitamin K injection but to blood
transfusion. He then continued to have recurrent
delayed bleeding tendency following teething and
traumas. Bleeding tendency in factor XIII
deficiency can be spontaneous, post surgery or post
trauma, even a minor injury [3]. Contrary to
hemophilia, joint bleeding is rare[3]. Good history is
very important to reach a proper diagnosis.
Delayed bleeding tendency with normal
coagulation profile is very suspicious of factor XIII
deficiency. The diagnosis then is to be confirmed by
clot solubility test and factor XIII assay. Whole
blood, fresh frozen plasma, stored plasma and
cryoprecipitate have all been used successfully in
the treatment of factor XIII deficiency and are
adequate sources of factor XIII[2]. Plasma-derived
pasteurized factor XIII concentrate under the name
of Fibrogammin P is now available. Recombinant
factor XIII is now being tested in experimental
animals[2]. Our case was indeed treated successfully
with cryoprecipitate at the time of bleeding and is
now doing well under regular cryoprecipitate
prophylaxis every three weeks without any
bleeding problem and with normal growth and
development. Because of long half life of factor XIII,
three weekly prophylaxis is quite adequate.
REFERENCES
1.
2.
3.
4.
5.
DISCUSSION
Despite a high index of suspicion for a bleeding
disorder in this case, the diagnosis was not made
until the age of one year and seven months on his
June 2006
6.
Richard S Neman, Mehrdad Jalili, Bradley J Kolls. Factor
XIII deficiency mistaken for battered child syndrome. Am J
Hematol 2002; 71:328-330.
Anwar R, Miloszewski KJ. Factor XIII deficiency, Review.
Br J Haematol 1999; 107:468-484.
Rudolf Egbring, Arno Kroniger, Rainer Seitz. Factor XIII
deficiency: Pathogenic mechanisms and clinical significance.
Thromb Haemost 1996; 22:419-425.
Caroline J Killick, Carol J Barton, Shazia Aslam, et al.
Prenatal diagnosis in Factor XIII deficiency. Arch Dis Child
1999; 80:F238-239.
Fahad Z Al-Sharif, Mahmoud D Aljurf, Abdulkarim M AlMomen, et al. Clinical and laboratory features of congenital
factor XIII deficiency. Saudi Med J 2002; 23:552-554.
Anwar R, Minford A, Gallivan L, et al. Delayed umbilical
bleeding-a presenting feature for factor XIII deficiency.
Pediatrics 2002; 109: E32.
June 2006
KUWAIT MEDICAL JOURNAL
Selected Abstracts of Articles Published
Elsewhere by Authors in Kuwait
Kuwait Medical Journal 2006, 38 (2): 149-152
Selected Abstracts of Articles Published Elsewhere by Authors in
Kuwait
Two-trocar Laparoscopic Varicocelectomy: Cost-reduction Surgical Technique
Al-Hunayan A, Abdulhalim H, Kehinde EO, El-Barky E, Al-Awadi K, Al-Ateeqi A
Division of Urology, Department of Surgery, Mubarak Teaching Hospital, Kuwait University Faculty of Medicine,
Safat, Kuwait. E-mail: [email protected]
Urology 2006; 67:461-465
Objectives: To describe the technique of two-trocar laparoscopic varicocelectomy and compare it
with the standard three-trocar laparoscopic technique in terms of effectiveness, morbidity, and
cosmesis.
Methods: Two matched groups of patients with left varicocele were recruited. Each group included
30 patients. One group underwent three-trocar and the other two-trocar lapar oscopic
varicocelectomy. The results of the two approaches were compared.
Results: No significant differences were found in terms of mean hospital stay or morbidity between
the two-trocar and three-trocar techniques. A significant difference was found in the operative time
and proportion of patients needing postoperative parenteral narcotic analgesia in favor of the twotrocar technique. In both approaches, the previously infertile patients had a significant improvement
in sperm count and motility (P <0.05). Cosmetically, the trocar wound scars were aesthetically
superior using the two-trocar technique.
Conclusions: No significant difference was found between two-trocar and three-trocar laparoscopic
varicocelectomy in terms of effectiveness and morbidity. The cost of an extra 5-mm disposable trocar
in the three-trocar technique and the improved cosmesis after the two-trocar technique have made
us prefer the latter technique.
Prostate Cancer Risk: The Significance of Differences in Age
Related Changes in Serum Conjugated and Unconjugated Steroid
Hormone Concentrations Between Arab and Caucasian Men
Kehinde EO, Akanji AO, Memon A, Bashir AA, Daar AS, Al-Awadi KA, Fatinikun T
Faculty of Medicine, Department of Surgery, Kuwait University, P.O. Box 24923, 13110, Safat, Kuwait.
E-mail: [email protected].
Int Urol Nephrol 2006; 38:33-44
Introduction: Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000
men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone
metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab
and Caucasian populations, to determine if these can provide a rational explanation for differences
in incidence of prostate cancer between the two populations.
Patients/Method: Venous blood samples were obtained from 329 unselected apparently healthy
indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from
similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The
150
June 2006
samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex
hormone binding globulin (SHBG), free androgen index (FAI); adrenal C(19)-steroids,
dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using
Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in
Arab men were compared with those reported for similarly aged Chinese, German and White USA
men. Results: In all four ethnic groups, median TT and FAI declined with age, while SHBG increased
with age. However, the mean TT and SHBG was significantly lower (p<0.01) and the FAI
significantly higher in Arab men (p<0.01) compared to German men only in 21-30 years age group.
In the other age groups the levels of TT and SHBG were higher in the Germans but the differences
were not statistically significant. In all the racial groups serum levels of DHEAS and ADT reached a
peak by about 20 years of life, and then declined progressively. The mean DHEAS in American
Caucasians aged 20-29 years was 11.4 mumol/l compared to 6.22 mumol/l in the Arabs (p<0.001).
The mean DHEAS in USA Caucasians aged 70-79 years was 2.5 mumol/l compared to 1.8 mumol/l
(p<0.03) in the Arabs. There was no significant difference in mean serum levels of DHEAS between
German and USA men. Similarly, there was no significant difference in the level of the hormones
between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum
TT, SHBG and DHEAS compared to those without the disease. Conclusions: The mean TT and SHBG
was significantly lower in Arab men compared to Caucasian men especially in early adulthood.
Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT
especially in early adulthood compared to Arab men. These observations of low circulating
androgens and their adrenal precursors in Arab men may partially account for the decreased risk for
prostate cancer among Arab men.
Relationship between Serum Prostate Specific Antigen and the
Pattern of Inflammation in Both Benign and Malignant Prostatic
Disease in Middle Eastern Men
Anim JT, Kehinde EO, Prasad A, Sheikh M, Mojiminiyi OA, Ali Y, Al-Awadi K
Department of Pathology, Faculty of Medicine, Kuwait University and Mubarak Al-Kabeer Hospital, Kuwait.
Int Urol Nephrol 2006; 38:27-32
To determine the effect of prostatitis on serum prostate specific antigen in the diagnosis of prostate
cancer in Middle Eastern men, H&E-stained sections of all consecutive prostate specimens were
reviewed for diagnosis (malignant or benign) and pattern of inflammation. Inflammation was
categorized into acute, active chronic and chronic inactive and graded semi-quantitatively according
to previously published criteria. Results were correlated with serum PSA obtained from patients’
records. Of 513 prostate specimens reviewed; 435 (84.8%) were benign and 78 (15.2%) were
malignant. Chronic inactive prostatitis was present in 259 (204 benign, 55 malignant) and active
chronic prostatitis in 221 (204 benign, 17 malignant). Acute prostatitis alone was not observed and
prostatitis was absent in 33 (27 benign, 6 malignant). There was no significant difference in the
prevalence of inactive chronic prostatitis between benign and malignant specimens (p < 0.071), but
active chronic prostatitis was more prevalent in benign specimens (p < 0.001). Increasing serum PSA
was observed for increasing grades of both inactive and active chronic prostatitis in both benign and
malignant disease. Prostate cancer showed higher serum PSAlevels than benign, at different cut-off
points (4 ng/ml = p < 0.0001; 8 ng/ml = p < 0.0001; 12 ng/ml = p < 0.0001). However, significant
numbers of patients with benign prostate biopsies presented with PSA above 12 ng/ml (82/260 =
32%). We conclude that active chronic prostatitis is common in Middle Eastern men with benign
prostatic disease and a significant number of these present with very high PSAlevels, some over 300
ng/ml.
June 2006
KUWAIT MEDICAL JOURNAL
151
Determination of the Prevalence of Lymphatic Filariasis among Migrant
Workers in Kuwait by Detecting Circulating Filarial Antigen
Iqbal J, Sher A
Department of Microbiology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
E-mail: [email protected]
J Med Microbiol 2006; 55:401-405
The main objective of this study was to determine the prevalence of filarial infection among migrant
workers in Kuwait. The study was conducted from April 2000 to November 2003. A total of 1050
migrant workers (>90 % from the Indian subcontinent) from filarial endemic countries and 260
individuals residing in Kuwait as controls (50 healthy Kuwaiti blood donors, 50 microfilarianegative individuals from endemic areas and 160 patients with other parasitic infections) were
screened for filarial infection. All specimens were tested for microfilaraemia by microscopy of
nucleopore-filtered blood (NFB) and detection of circulating filarial antigen (CFA) by an
immunochromatographic test (ICT) and the TropBio assay. The overall prevalence of filarial
antigenaemia was 18.3 % (192 individuals) using the ICT and 20.3 % (213 individuals) using the
TropBio assay. Thirty-two cases (3 %) of Wuchereria bancrofti were detected by microscopy and the
mean microfilaria count in these cases was 816 microfilariae ml(-1). CFA was detected only in two of
the 260 control subjects. Statistical analysis to calculate the sensitivity, specificity and prevalence of
infection was carried out using maximum-likelihood statistical methods. The overall sensitivity and
specificity of the ICT and TropBio assay to detect CFA were comparable. Compared with NFB
microscopy, the sensitivity of the ICT was 93.8 % and specificity ranged from 84 to 100 %. The
sensitivity and specificity of the TropBio assay were 90.1 and 100 %, respectively. However, the ICT
failed to detect CFA in two cases with a microfilarial load of <20 microfilariae ml(-1). In conclusion,
the prevalence of filarial infection among the migrant workers in Kuwait was 18.3 % as determined
by the ICT.
Molecular and Clinical Evaluation of Primary Congenital Glaucoma
in Kuwait
Alfadhli S, Behbehani A, Elshafey A, Abdelmoaty S, Al-Awadi S
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, PO Box 31470
Sulaibekhat, Kuwait. E-mail: [email protected]
Am J Ophthalmol 2006; 141:512-526
PURPOSE: To report the spectrum of the CYP1B1 mutation in Kuwaiti patients with primary
congenital glaucoma (PCG). DESIGN: Clinical diagnosis of PCG and laboratory based experimental
study. METHODS: Polymerase chain reaction-restriction polymorphism length fragment (PCRRPLF) and direct sequencing of exon 2 and the coding region of exon 3 of CYP1B1 gene were the
methods used for screening 17 PCG patients, their families, and 105 health individuals from the
same ethnicity. RESULTS: Four different mutations were detected in CYP1B1 in 70.6% of the
screened patients. The most common one (47%) was homozygote Gly61Glu mutation, previously
described in Saudi Arabia, Turkey, and Morocco; all patients were products of consanguineous
marriages. The second common mutation was a novel missense (Ala388Thr) mutation found in three
patients (17.6%) as compound heterozygote with Arg368His in one patient, and with Gly61Glu in
another one while the second mutation in third patient was not detected in the CYP1B1 gene. One
patient (5.8%) was homozygote for Cyt280X mutation previously reported in only one Japanese
family. In addition to these mutations, a novel Val422Gly polymorphic site was found in three of the
PCG patients and in 18 of the 210 tested chromosomes of healthy volunteers. CONCLUSIONS: The
CYP1B1 mutation spectrum of Kuwaiti PCG patients is similar to that detected in the neighboring
countries. No clear genotype-phenotype correlation detected in patients showed different types of
CYP1B1 mutation.
152
June 2006
Body Mass Index of Kuwaiti Children Aged 3-9 Years: Reference
Percentiles and Curves
Al-Isa AN, Thalib L
Department of Community Medicine and Behavioural Sciences, Faculty of Medicine, University of Kuwait, P.O. Box
24923, Safat, Code 13110, Kuwait. E-mail: [email protected]
J R Soc Health 2006; 126:41-46
AIM: The suitability of using the standards for body mass index (BMI), produced in the U.S. by the
National Center for Health Statistics, for assessing overweight and obesity among children in
Kuwait and other Arabian Gulf countries has not been examined. These standards were obtained
from better-nourished and genetically different populations to those found in Kuwait and in other
Gulf region countries. The purpose of this study was to develop BMI reference percentiles and
curves appropriate for children aged 3-9 in these countries. METHOD: Attempts were made to
include all healthy Kuwaiti kindergarten and elementary education children in this study The total
sample was 113,013, comprising 55,053 males and 57,960 females. The children were measured for
weight and height from which the BMI was calculated. Appropriate polynomial regression
smoothing techniques were used to obtain the best-fitting percentile curves. RESULTS: At percentiles
< or =25th, the BMI of boys exceeded that of girls. At the 50th percentile, boys’ BMI was mostly
higher than or equal to that of the girls except at age nine where it was lower At the 75th percentile,
the BMI of both genders was similar, with exceptions at age six and nine years. At the 85th and 95th
percentiles, girls’ BMI was consistently higher than males. At the lowest percentile, the BMI of US
children was higher than Kuwaiti, Saudi (starting at six) and Iranian children. The BMI of Kuwaiti
children at higher percentiles was higher than that of Saudi, Iranian (except at age < four years) and
US children. CONCLUSION: BMI curves for Kuwaiti children follow almost the same pattern as
their US counterparts but with noticeable variations especially at the lower and higher percentiles.
This study may reflect that western standards may not be directly applicable to assess the level of
BMI in Kuwait and possibly in the neighbouring Gulf countries, since they may overestimate the
levels of overweight, obesity and underweight.
Incidence of Acute Myocardial Infarction during Islamic Holiday
Seasons
Zubaid M, Thalib L, Suresh CG.
Department of Medicine, Faculty of Medicine, Kuwait University, PO Box 24923, 13110, Safat, Kuwait.
E-mail: [email protected].
Eur J Epidemiol 2006; 21:191-195
Some weather and holiday seasons are associated with increased incidence of acute myocardial
infarction (AMI). We studied the influence of one such season, Islamic holiday season of “Eid AlFitr”, on the incidence of AMI in a Muslim country. This was carried out by examining the
admissions to the coronary care unit of a large hospital over six consecutive years (from 1997 to
2003), encompassing six consecutive holiday seasons in Kuwait. We compared the admission rates
during three time intervals in each of those 6 years; the Eid holiday season, the 2 months before and
the 2 months after. A total of 964 AMI admissions occurred, with a mean age of 55 years. When the
admission rates were compared, the Islamic holiday seasons were associated with a significant
increase in AMI admission rate (45 cases vs. 31 cases, p < 0.01). This increase occurred mainly on the
second day of the 4-day holiday season. This finding was confirmed using Locally Weighted Smooth
Regression (LOESS) regression models with different smoothing levels. Our finding might have
potential implications for preventive health campaigns in Muslim countries.
KUWAIT MEDICAL JOURNAL
June 2006
WHO-Facts Sheet
1. Improved Formula for Oral Rehydration Salts to Save Children’s Lives
2. New Tuberculosis Therapy Offers Potential Shorter Treatment
3. Blinding Trachoma: Progress towards Global Elimination by 2020
4. Investment in Cleaner Household Energy Yields Major Health and Economic Benefits
Compiled and edited by
Babichan K Chandy
Kuwait Medical Journal 2006, 38 (2): 160-163
1. IMPROVED FORMULA FOR ORAL
REHYDRATION SALTS TO SAVE
CHILDREN’S LIVES
Improved formula means better treatment for
life-threatening diarrhoeal dehydration
The World Health Organization (WHO) and
UNICEF announced a new formula for the
manufacture of Oral Rehydration Salts (ORS). The
new formula will better combat acute diarrhoeal
disease and advance the Millennium Development
Goal of reducing child mortality by two-thirds
before 2015.
Diarrhoea is currently the second leading cause
of child deaths and kills 1.9 million young children
every year, mostly from dehydration.
The latest improved ORS formula contains less
glucose and sodium (245 mOsm/l compared with
the previous 311 mOsm/l). The lower concentration
of the new formula allows for quicker absorption of
fluids, reducing the need for intravenous fluids
and making it easier to treat children with acute
non-cholera diarrhoea without hospitalization.
ORS use is the simplest, most effective and
cheapest way to keep children alive during severe
episodes of diarrhoea. The ORS solution is absorbed
in the small intestine, thus replacing the water and
electrolytes lost. WHO provides the only updated
international quality specifications for this formula
and UNICEF is a leading supplier of ORS to poor
countries. WHO and UNICEF have jointly issued
guidance for the production of the new ORS.
WHO and UNICEF recommend that countries
manufacture and use the new ORS in place of the
previous formula. WHO and UNICEF will help
national authorities develop manufacturing guidelines
and procedures for the new formula. Establishing
the local production of ORS will be a key step to
ensure countries can meet their own needs in
controlling diarrhoeal disease.
According to UNICEF and WHO, oral
rehydration therapy should be combined with
guidance on appropriate feeding practices.
Provision of zinc supplements (20 mg of zinc per
day for 10 to 14 days) and continued breastfeeding
during acute episodes of diarrhoea protect against
dehydration and reduces protein and calorie
consumption to have the greatest impact on
reducing diarrhoea and malnutrition in children.
For further information please contact: Daniela
Bagozzi, Communications Officer, WHO, Tel: (+41 22)
791 4544, mobile: (+41) 79 475 5490, e-mail:
[email protected]
2. NEW TUBERCULOSIS THERAPY OFFERS
POTENTIAL SHORTER TREATMENT
Phase III Trials Results
Clinical results on a new combination treatment
that could dramatically shorten the length of
tuberculosis (TB) treatment were presented at the
45th Annual Interscience Conference on Antimicrobial
Agents and Chemotherapy in Washington, D.C in
December 2005.
The phase II trial results of a gatifloxacincontaining regimen are demonstrating good
potential. The regimen is significantly more potent
than the currently recommended six-month
regimen of isoniazid, rifampicin, pyrazinamide and
ethambutol, and suggests that when gatifloxacin is
used instead of ethambutol, the standard six-month
regimen may be shortened to four months.
“We are working to bring together public and
private partners to speed development for this new
treatment,” says Dr. Robert Ridley, Director of the
World Health Organization-based Special Programme
Address correspondence to: Office of the Spokesperson, WHO, Geneva. Tel.: (+41 22) 791 2599; Fax (+41 22) 791 4858; Email: [email protected]; Web
site: http://www.who.int/
June 2006
KUWAIT MEDICAL JOURNAL
for Research and Training in Tropical Diseases
(TDR). This is the most advanced shorter TB
treatment regimen presently in development, and
could be available to the public by the end of 2009
if positive results continue.
Finding options to shorten the length of
treatment has been declared a public health priority
by the Stop TB partnership. “The gatifloxacin fixeddose combination responds to the new WHO Stop
TB Strategy’s call for new tools, in particular, new
regimens that can significantly shorten the current
six-month treatment time,” said Dr. Mario
Raviglione, Director of WHO’s Stop TB.
One-third of the world’s population is infected
with Mycobacterium tuberculosis, the causative agent
of TB, with approximately eight million people
developing the active form of the disease every
year. The HIV/AIDS pandemic has dramatically
increased the incidence of this disease. A shorter TB
regime will also help improve treatment adherence
and preventing the development of multidrugresistant TB.
The phase II trial was conducted by the South
African Medical Research Council in Durban,
South Africa, in patients with newly diagnosed
pulmonary tuberculosis with and without HIV coinfection. It was designed to measure the antituberculosis activity of the treatment in the first two
months of therapy when compared to standard
WHO recommended treatment and two other
similar regimens which contained either ofloxacin
or moxifloxacin. Treatment with either the
gatifloxacin or moxifloxacin containing regimen
was shown to be significantly more active than
either the standard regimen or the ofloxacin
containing regimen after two months of treatment.
A multi-centre Phase III clinical trial is planned
to definitely assess whether the four month
gatifloxacin containing regimen is equivalent to the
current standard six month short course regimen.
Study sites are in Benin, Guinea, Kenya, Senegal
and South Africa. Arnd Hoeveler, of the European
Commission (EC), says, “The clinical trial sites are
the result of an EC funded Consortium of ten
European and African institutions (the OFLOTUB
Consortium) that are in the process of finalizing the
terms of a proposed collaboration with the WHO to
develop a new short course treatment regimen. We
are delighted to contribute to this effort.”
The research is planned to continue as part of an
international collaboration which is being
developed between the World Health Organization
-based Special Programme for Research and
Training in Tropical Diseases (TDR), the European
Commission (EU), the OFLOTUB Consortium that
is coordinated by the French Institut de Recherche
161
pour le DГ©velopement (IRD), and Lupin
Pharmaceuticals, Ltd. “The IRD is extremely proud
to have significantly contributed to the foundation
of this collaborative effort,” says Jean Fran≤ois
Girard, chairman of IRD.
For further information please contact: Jamie Guth,
TDR, Communications Manager, Tel.: +41 22 791
1538. Mobile: +41 79 441 2289, email: [email protected]
3. BLINDING TRACHOMA: PROGRESS
TOWARDS GLOBAL ELIMINATION BY 2020
Several countries are on track to eliminate the
infectious eye disease, blinding trachoma, the
World Health Organization (WHO) announced
today. This progress results from efforts to achieve
the global goal set by the World Health Assembly in
1998 to eliminate this disabling disease by the year
2020.
The estimated number of people affected by
trachoma has fallen from 360 million people in 1985
to approximately 80 million people today. This is
the result of a concerted effort by the WHO Alliance
for the Global Elimination of Blinding Trachoma
(GET 2020) combined with socioeconomic
development in endemic countries. Trachoma
affects the poorest and most remote rural areas of
56 countries in Africa, Asia, Central and South
America, Australia and the Middle East.
At today’s 10th meeting of GET 2020, held at
WHO Headquarters in Geneva, the Islamic
Republic of Iran, Mexico, Morocco and Oman have
reported successfully implementing their national
strategies of interventions necessary for eliminating
trachoma, based on the WHO-recommended SAFE
strategy. The WHO SAFE strategy emphasizes
comprehensive public health action and stands for
lid surgery (S), antibiotics to treat the infection (A),
facial cleanliness (F); and environmental changes
(E). If implemented comprehensively, the SAFE
strategy could prevent virtually all cases of
blindness.
“This is very encouraging progress,” said Dr
LEE Jong-wook, WHO Director-General. “If
countries continue at this rate, the global goal to
eliminate blinding trachoma as a public health
problem by 2020 can be achieved.”
WHO is currently developing the specific
epidemiological assessment criteria to determine
when countries have fully eliminated blinding
trachoma. The criteria are expected to be finalized
by the end of 2006, at which time WHO will be able
to evaluate the effectiveness of national strategies
and provide country-by-country certification that
the disease has been eliminated.
162
WHO-Facts Sheet
Blinding trachoma
Trachoma originates from an eye infection that
is spread from person to person, is frequently
passed from child to child and from child to mother
within the family, especially in environmental
conditions of water shortages, flies, and crowded
households. Through the discharge from an
infected person’s eyes, trachoma is passed on by
hands, on clothing, or by flies that land on the
person’s face. Infections often begin during infancy
or childhood and become chronic. If left untreated,
these infections eventually cause the eyelid to turn
inward which in turn causes the eye lashes to rub
on the eyeball, resulting in intense pain and
scarring of the front of the eye. This ultimately
leads to irreversible blindness, typically beginning
between ages 30-40 and often resulting in
deepening poverty for individuals and their
families. Women are blinded two to three times
more often than men, probably due to their close
contact with affected children.
The alliance for the global elimination of
blinding trachoma
Launched under WHO’s leadership in 1997, the
Alliance for the Global Elimination of Blinding
Trachoma by the Year 2020 (GET2020) is a
partnership formed
to
support country
implementation of the SAFE strategy. The Alliance
is led by WHO and is open to members from all
sectors - public, nongovernmental and commercial
willing to work with governments to implement
the SAFE strategy. Alliance members include
WHO, national governments, nongovernmental
organizations research institutions, foundations,
and the pharmaceutical industry.
Pzifer International Inc and its Foundation have
been key partners in the fight against trachoma. It
has already donated 37 million doses of
azithromycin and has committed to provide 100
million additional doses by 2008.Azithromycin is a
long-acting antibiotic used as one component of the
SAFE strategy.
For more information please contact: Ms Alexandra
Munro, Communications Officer, Tel; +41 22 791
5053, Mobile: +41 79 754 7763 Email:
[email protected]
Dr Silvio P. Mariotti, Medical Officer, Tel: +41 22
791 3491, Mobile: +41 79 217 3452 Email:
[email protected]
June 2006
4. INVESTMENT IN CLEANER HOUSEHOLD
ENERGY YIELDS MAJOR HEALTH AND
ECONOMIC BENEFITS
New report calls attention to health threat from
indoor air pollution
Every day for the next 10 years, 485 000 people
would need to gain access to cleaner fuels in order
to halve by 2015 the population relying on solid
fuels. A new report from the World Health
Organization, Fuel for Life: Household Energy and
Health, demonstrates that investing in cleaner
household fuels can yield a seven-fold economic
benefit in health and productivity gains..
Cooking with wood, dung, coal and other solid
fuels on open fires or simple stoves is a daily reality
for more than half of the world’s population. This
leads to high levels of indoor air pollution, a major
risk factor for pneumonia among children and
chronic respiratory disease among adults. Globally,
pneumonia remains the single most important
child killer and is responsible for two million
deaths a year.
Every year, the killer in the kitchen is
responsible for 1.5 million deaths. Sub-Saharan
Africa and South East Asia are particularly affected,
with 396 000 and 483 000 annual deaths,
respectively. Indoor air pollution also disproportionately affects women and children. In 2002,
cooking with solid fuels was responsible for nearly
800 000 deaths among children and more than 500
000 deaths among women.
The good news is that effective solutions are
available. Liquefied petroleum gas, biogas and
other cleaner fuels represent the healthiest
alternative. Switching from a traditional stove to an
improved stove substantially reduces indoor
smoke.
“Making cleaner fuels and improved stoves
available to millions of poor people in developing
countries will reduce child mortality and improve
women’s health,” said Dr LEE Jong-wook, WHO
Director-General. “In addition to the health gains,
household energy programmes can help lift
families out of poverty and accelerate development
progress.”
On an average, 100 million more homes using
liquefied petroleum gas, biogas or modern fuels for
cooking would lead to 473 million fewer women,
children and men exposed to harmful indoor air
pollution, and 282 thousand fewer deaths from
respiratory diseases per year.
The economic case for adopting practical
solutions on a large scale is just as strong as the
humanitarian case. For as little as six dollars,
June 2006
KUWAIT MEDICAL JOURNAL
families can install better ventilated and fuel
efficient stoves. A total cost of 13 billion dollars per
year to halve the number of people worldwide
cooking with solid fuels by 2015 shows a payback
of 91 billion dollars per year, highlights the report.
Making improved stoves available to half of those
still burning biomass fuels and coal on traditional
stoves would save USD 34 billion in fuel
expenditure every year, and generate an economic
return of USD 105 billion every year over a 10 year
period.
The majority of these costs are borne at the
household level which is also where the majority of
the benefits occur. Nevertheless, donor investments
are required upfront for designing appropriate
technologies, setting up local businesses, and
putting micro-credit systems in place. Developing
energy infrastructure in this way would not only
mean less illness and death but also less time spent
ill, collecting fuel and cooking. With more time
available, children would do better at school, while
their mothers could engage in childcare, agriculture
or other income-generating activities as a way to
break the vicious cycle of poverty.
“It is a travesty that 1.5 million lives a year many of those of children whose lives have not
even started - are snuffed out every year because of
needless exposure to indoor smoke. We have
163
simple, affordable solutions; let us ensure that they
reach the people who can benefit from - and live by
- using them,” said Dr Maria Neira, WHO’s
Director for Public Health and Environment.
Some low-income countries with enormous
financial constraints are already responding to the
challenge, and programmes are operating
effectively and producing results. The same
commitment needs to be replicated worldwide.
The problem of indoor air pollution has been
around since the Stone Age, yet international
development agendas fail to recognize that missing
out on clean energy equals missing out on life.
Today’s report provides an overview of the global
situation on indoor air pollution, and calls for
vigorous action to close the household energy gap
by developing energy infrastructure to meet basic
household needs in a healthy, safe and sustainable
way.
For further information, please contact:New York:
Ms. Celinda Verano, Information Officer, WHO Office,
New York. Tel: + (212) 963-6000; Fax: +(212)-2232920, Email: [email protected] OR Mr Gregory Hartl,
Communications Advisor, Sustainable Development
and Healthy Environments, World Health
Organization, Geneva. Tel. (+4122) 791 4458; email
[email protected].

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