ABSTRACT
Objectives: To study the
types and frequency of mucocutaneous and systemic manifestations of Behcet's
disease among Jordanian patients.
Methods: A retrospective analysis of 107 patients diagnosed clinically to have
Behcet's disease between January 2004 and December 2007 at King Hussein
Medical Center
was conducted. All Patients fulfilled
the International Study Group Criteria for the diagnosis of Behcet's disease.
Simple statistical analysis was used.
Results: Eighty-two
patients were males and 25 were females, the age range was between 16 and 65
year, 52 (48%) patients’ age ranged between 20-29 year, 104 (97%) patients had
oral ulceration, 93 (87%) patients had genital ulcers, 99 (92%) patients had
skin manifestation were acneiform eruption was the most common finding of skin
manifestation, eye involvement was recorded in 34 (32%) patients (17 patients
had bilateral uveitis, five had unilateral uveitis, 13 had retinal vasculitis
and five were blind, two of whom had unilateral blindness). Arthritis was seen
in 64 patients, vascular lesions in 39 patients, and neurological manifestations
were seen in 22 patients. Pathergy test was positive in 36 patients. HLA-B51 was
positive in 48 patients and negative in 26 patients, while undetermined in 33
patients.
Conclusion: Mucocutaneous manifestations of the disease are common
in Jordanian patients. They are similar
to other countries in the region in many aspects of diverse manifestations, age
of onset and chronicity. Male predominance was noted in this series of cases. Superficial
thrombophlebitis was common and morbidity was higher. Intracranial hypertension
was more prevalent in patients with neurological manifestations.
Key words: Behcet's disease, cutaneous and systemic manifestations,
epidemiology
JRMS
June 2010; 17(2): 19-22
Introduction
Behcet's disease (BD) was
named in 1937 after the Turkish dermatologist Hulusi Behcet, who first
described the triple-symptom complex of recurrent oral aphthous ulcers, genital
ulcers, and uveitis. Behcet's disease is a multisystem disease with
unpredictable course and almost all organs of the body can be affected concomitantly
or consecutively.(1) Behcet's
disease is a multisystem polysymptomatic disease including involvement of the
mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary,
urologic, central nervous system, joints, and blood vessels. Behcet's disease
is most prevalent in the Mediterranean region (Middle East).
The type and frequency of cutaneous manifestation of Behcet's disease is
variable and diverse with unpredictable exacerbation and remission.
The cause of Behcet's disease is not known. However,
immunogenetics, immune regulation, vascular abnormalities, or bacterial and
viral infection may have a role in its development. There is genetic background
with a high prevalence of the disease among people of the Mediterranean, the Middle
East, China and Japan.
There are occasional familial cases and association with HLA types particularly
with HLA-B5 (Bw51 split).(2)
The typical course of Behcet's disease is one of
periodic remissions and exacerbations. Over time, the disease typically becomes
less severe; but few serious consequences may develop. Current therapies are
often somewhat effective, yet frequently complicated by undesirable side
effects.
Methods
A retrospective simple statistical analysis of 107 patients diagnosed clinically at King Hussein Medical Center to have Behcet's disease between January 2004 and December 2007 was conducted to define the cutaneous manifestation and other systemic involvement. Patients fulfilled the International Study Group (ISG) criteria for the diagnosis of Behcet's disease (Table I), and analysis of skin lesions was performed by dermatologist
Results
The 107 patients who were diagnosed with Behcet's
disease fit the International Study Group (ISG) criteria, 82 of those were
males and 25 were females. Their age ranged between 16 and 65 years. Fifty-two
(48%) of the patients’ age ranged between 20-29 years and one patient was above
50 years old (Table II). One hundred and
four (97%) patients had oral ulcers, 93 (87%) had genital ulcers, and 99 (92%) had
skin involvement. Acneiform eruption was the most common finding (Table III).
Eye involvement was seen in 34 (32%) patients, 17 of whom had bilateral
uveitis, five had unilateral uveitis, 13 retinal vasculitis and three were
blind in both eyes and two were blind in one eye. Arthritis was seen in 64
patients.
Vascular lesions were found in 39 patients, 10 of whom had gastrointestinal symptoms of
gastritis and esophageal varices. Thrombophlebitis
was found in 12 patients, nine had deep vein thrombosis, pulmonary symptoms due
to aneurysm or emboli occurred in eight patients. Thrombosis in either superior or inferior vena
cava was seen in eight patients. Neurological
manifestations were seen in 22 patients, the most common symptom being headache
(10 patients) due to increased intracranial pressure. Two patients had meningoencephalitis, three
patients had cerebral infarction, three had seizures, and two had peripheral
neuropathy. Pathergy test was positive in 36 patients out of 83 (43%) patient
tested and 33% of all cases. HLA-B51 allele was positive in 48 patients, negative
in 26 patients and undetermined in 33 patients.
Discussion
The cause of Behcet's disease is unknown and there is
no specific test to diagnose the disease.
As a result, the clinical criteria of ISG are used for diagnosis. These criteria identify the most common features of Behcet's disease
throughout the world. Aphthous stomatitis is one of the major criteria and the
first symptom of Behcet's disease. Differences in disease manifestations in various
geographical regions affect the disease severity.(3) Behçet's disease is endemic among populations clustered
along the historic Silk Road, which extended from Eastern Asia to the
Mediterranean basin.(4) and Turkey has the highest
prevalence of the disease. Behcet's
disease is common between the second and fourth decades of life, but can be
develop at any age with more severe picture of disease in males and younger age
of onset.(5) Prepubertal
onset is rare, as is elderly onset (>50 years).(6)
Our patients’ age range is consistent with these
findings where 89 (83%) patients were between 20-40 years. The male to female
ratio was 3.28:1 which is similar to many previous studies.(6,7,8)
However, new studies reveal roughly
equal incidence in both sexes, with male predominance still persisting in Arab
countries,(9) while in an American study the female to male
ratios was 1.9:1.(3)
Cutaneous lesions were common and recurrent and these
include: erythema nodosum like lesions, acneiform eruptions and
thrombophlebitis.(10) The acneiform eruptions and
papulopustular lesions usually run normal course and are cleared smoothly. The
erythema nodosum was seen in 26 patients and had similar course as non Behcet's
associated erythema nodosum. Interestingly Forty-seven patients (47%)
had more than one type of skin lesion which is higher than that seen in similar
studies where the percentage of patients who had more than one lesion was 21%.(11) Five of our patients had superficial or deep thrombophlebitis;
one of them had severe superficial thrombophlebitis with widespread post
inflammatory hyperpigmentation.
Table I. The ISG criteria for Behcet’s disease (17)
|
Major criteria (need 1)
|
Recurrent oral ulceration
|
Minor aphthous, major
aphthous, or herpetiformis ulceration observed by physician or patient that
recurred at least three times over a 12-month period
|
|
Minor criteria (need 2)
|
Recurrent genital
ulceration
|
Aphthous
ulceration/scarring observed by physician or patient
|
|
Eye lesions
|
Anterior or posterior
uveitis or cells in vitreous on slit lamp examination; or retinal vasculitis
observed by ophthalmologist
|
|
Skin lesions
|
Erythema nodosum observed
by physician or patient, pseudofolliculitis or papulopustular lesions; or acneiform
nodules observed by the physician in a post adolescent patient who is not
receiving corticosteroid treatment
|
|
Positive Pathergy test
|
As interpreted by
physician at 24 to 48 hours
|
|
Table II. Age distributions of patients
|
Age range
|
No of patients
|
% of patients
|
|
10-19
|
12
|
11
|
|
20-29
|
52
|
48
|
|
30-39
|
37
|
35
|
|
40-49
|
5
|
5
|
|
50-59
|
0
|
0
|
|
60-69
|
1
|
1
|
|
Table III. Cutaneous manifestations of Behcet’s
disease
|
Skin manifestations
|
No of patients
|
% of patients
|
|
Acneiform eruption
|
53
|
50
|
|
Erythema nodosum
|
26
|
25
|
|
Psuedofolliculitis
|
13
|
12
|
|
Papulo pustulosis
|
12
|
12
|
|
|
Table IV. The different manifestations of Behcet’s disease
|
Clinical feature
|
Number of patients
|
%
|
|
Oral ulceration
|
104
|
97
|
|
Genital ulceration
|
93
|
88
|
|
Skin manifestations
|
99
|
92
|
|
Eye involvement
|
34
|
32
|
|
Arthritis
|
64
|
60
|
|
Neurological manifestations
|
22
|
20
|
|
Vascular lesions
|
39
|
36
|
|
Pathergy
|
36
|
33
|
|
One patient developed unilateral eye blindness four
years after onset of Behcet's disease followed by blindness of other eye after
20 years. Twenty two patients had neurological manifestations, ten of them had
headache at presentation due increased intracranial pressure, three developed meningoencephalitis
presenting with headache and fever, three patients developed cerebral infarcts,
three had seizures and two presented with peripheral neuropathy.
A higher rate of positivity
of Pathergy test (84-98%) was found more frequently in Mediterranean areas, compared
to the Far East (40-70%), or Western countries.
Our results were positive for 36 out of 107 cases (33%) and 43% of the 83
tested patients which is comparable to studies around our region. A positive Pathergy
test is characterized by the formation of a pustule greater than 2mm at the
site of injury within 24 hours.(12,13)
The earliest mucocutaneous
lesions were the oral ulcers which ranged from multiple small painful to less
frequent herpetiform ulcers. They preceded other systemic involvement by an average of 4.8 years
which was less than that seen in other comparative studies.(14,15)
but this is comparable with the study done in our region by Al-aboosi and
colleagues.(16) Patients
usually presented with oral aphthae (minor >major > herpetiform), which
may be the only manifestation of disease for six to seven years before any
major manifestation is apparent. Gastrointestinal involvement affects 3-16% of
patients with Behcet's disease. Areas affected often
include the esophagus and ileocecal area with symptoms included abdominal pain,
bloating, and GI bleeding. Complications often result from deep ulceration of
intestinal sections.
Arthritis in most
of our patients was non erosive symmetrical arthropathy with most of the symptoms
at the time of acute attacks of mouth ulceration. HLA-B51 is significantly
associated with Behcet's disease in Japan,
Korea, Turkey, and France. Our results were similar to
those in neighboring countries and higher than an American study.(3)
Many systemic diseases with mucocutaneous
manifestations may have similar presentation like Behcet's disease including
bollous diseases, connective tissue diseases, erythema nodosum and sweet
syndrome; the differentiation made based on the clinical criteria of
international study group.
Many patients with Behcet's
disease go into complete remission with the passage of time. No standard therapy for Behcet's disease is
present. Treatment options according to severity of symptoms where: topical
measures for cutaneous manifestations and systemic corticosteroids and
immunosuppressant medications for severe systemic involvements.
Conclusions
Mucocutaneous
manifestations of Behcet’s disease in our study sample were similar in many
aspects to studies from around the world, but differ in persistence of male
preponderance, prolonged morbidity of cutaneous manifestations, and higher
percentage of increased intracranial pressure in patients who presented with
headache.
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