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Demographic and clinical features of 521 Turkish patients

with Behcet’s disease

Ilknur Balta1, MD, Gulfer Akbay2, MD, Goknur Kalkan3, MD, and Meral Eksioglu2, MD

1Department of Dermatology, Ministry of

Health, Etlik Ihtisas Training and Research

Hospital, 2Department of Dermatology,

Ministry of Health, Ankara Training and

Research Hospital, Ankara, and3Department of Dermatology, School of

Medicine, Gaziosmanpasa University,

Tokat, Turkey

Correspondence

Ilknur Balta, MD

Department of Dermatology

Ministry of Health

Etlik Ihtisas Training and Research

Hospital, 06018 Etlik-Ankara

Turkey

E-mail: [email protected]

Conflicts of interest: None.

Abstract

Background The aim of this study is to reveal demographic and clinical features of

Behcet’s disease (BD) in a Turkish population.

Methods We retrospectively evaluated the clinical findings of 521 patients with BD.

Results A total of 521 patients (287 female and 234 male) were included in this study.

Onset signs: oral ulceration (72.7%) was followed by genital ulceration (3.1%), ocular

involvement (1.0%), and erythema nodosum-like lesions (ENLL) (0.2%). In 120 patients

(23%), the onset manifestation compromised more than one symptom. During follow-up, in

females and males respectively, oral ulceration was found in 100%, genital ulceration in

90.9% and in 82.5%, papulopustular lesions in 52.6% and in 71.4%, positive pathergy test

in 45.3% and in 48.7%, ENLL in 43.6% and in 31.6%, ocular involvement in 36.9% and in

58.1%, gastrointestinal involvement in 6.6% and in 5.6%, joint involvement in 4.2% and in

6.4%, vascular involvement in 1.7% and in 10.6%, neurological involvement in 0% and in

4.7% and pulmonary involvement in 0.7% and in 0.7%. Genital ulceration and ENLL were

found to be statistically higher in females than males. Papulopustular lesions and ocular,

neurological, and vascular involvement were significantly higher in males than females.

Conclusions In our study, systemic involvement was higher in males than females, as the

disease is more severe in males than females. As the only initial finding of the disease can

be genital ulceration or ocular manifestations, gynecologists, urologists, ophthalmologists,

and family practitioners must keep in mind BD as a differential diagnosis.

Introduction

Behçet’s disease (BD) is a multisystemic inflammatory dis-order with unknown etiology, which was first describedby a Turkish dermatologist, Dr. Hulusi Behçet, as a triadof the symptoms, including recurrent oral ulceration, gen-ital aphthosis, and iridocyclitis with hypopyon. In addi-tion to the classic triad of symptoms, joint, pulmonary,vascular, urogenital, gastrointestinal, and neurologicalinvolvement is also seen.1,2 Although BD occurs world-wide, it is generally regarded as being most common inthe Mediterranean countries, Middle East, and Far East.3

The highest prevalence was reported in Turkey, 80–370cases per 100,000 populations.4

BD has diverse clinical expression in various geographicalareas (e.g. gastrointestinal involvement occurs in about one-third of patients from Japan but rarely in Mediterraneancountries).4 Gender is also a factor that may influence theprevalence and expression of BD. This difference could beattributed to genetic and environmental factors.5,6

The aim of this study is to reveal the demographic andclinical features of BD in the Turkish population. The

differences in clinical manifestations between male andfemale are also analyzed.

Patients and methods

We retrospectively evaluated the clinical findings of 521

patients with BD followed up by the multidisciplinary team at

the Ministry of Health Ankara Training and Research Hospital.

The diagnostic criteria of the International Study Group of

Behçet’s Disease was used for the diagnosis of BD.

The following characteristics were recorded retrospectively in

all patients. Demographic properties were age of onset, age of

diagnosis, initial symptoms, sex, and family history. Clinical

properties included oral ulceration, genital ulceration, skin

lesions (erythema nodosum-like lesions [ENLL], papulopustular

lesions [PPL]), positive pathergy test, and ocular, joint,

neurological, gastrointestinal, cardiovascular, pulmonary, and

renal involvement. Organ involvement was considered only if

confirmed by clinical and/or laboratory assessment (e.g.

computed tomography, magnetic resonance imaging,

endoscopy, biopsy).

International Journal of Dermatology 2014, 53, 564–569 ª 2013 The International Society of Dermatology

564

Statistical analysis

All data were assessed using the SPSS software package (SPSS

17.00, Chicago, IL, USA). Differences were defined as

statistically significant at P < 0.05. Statistical analysis was

made by Mann–Whitney U-test, chi-square test, and

independent samples t test.

Results

Of the 521 patients with BD, 287 (55.1%) were female and234 (44.9%) were male. The female/male ratio was 1.22.The mean age of disease onset was 26.20 ± 8.50 years inall patients, 26.35 ± 9.14 years in female patients, and26.01 ± 7.67 years in male patients. The mean age at diag-nosis of disease was 30.39 ± 9.01 years in all patients,30.90 ± 9.52 years in female patients, and 29.76 ±8.31 years in male patients.Family history was positive in 21.9% of all patients. It

was positive in 24.7% of female patients and 18.4% ofmale patients, without any statistically significant differ-ence. There was no statistically significant differencebetween the patients who have family history or not interms of systemic involvement.The mean ± SD duration between symptom onset and

fulfillment of diagnostic criteria was 3.44 ± 4.55 years infemale patients and 2.43 ± 3.83 years in male patients.There was a statistically significant difference(P = 0.006). The mean ± SD duration between the timepoint of fulfillment of diagnostic criteria and diagnosiswas 1.09 ± 3.62 years in female patients and1.31 ± 3.01 years in male patients, without any statisti-cally significant difference (Table 1).

Initial symptom

The frequency of onset manifestations in patients withBD is given in Table 2. Oral ulceration was the mostcommon initial symptom. Oral ulceration (72.7%) wasfollowed by genital ulceration (3.1%), ocular involve-ment (1.0%), and ENLL (0.2%). In 120 patients (23%),the onset manifestation compromised more than onesymptom.

The pulmonary system involvement ratio is statisticallyhigher for the patients who had multiple onset symptomsthan patients who had just one onset symptom, and therewere no differences between the other systemic involve-ments in each group.

Clinical findings

The most common symptom in all patients with BD wasoral ulceration (100%), followed by genital ulceration(87.1%), PPL (61.0%), positive pathergy test (47.0%),ENLL (38.2%), ocular involvement (46.4%), gastrointes-tinal involvement (6.1%), joint involvement (5.2%), vas-cular involvement (5.7%), neurological involvement(2.1%), and pulmonary involvement (0.8%). Neurologi-cal involvement was observed in 11 (2.1%) patients. Ofthese, cerebral thrombosis (two patients, 0.3%) and vas-culitic changes in brain magnetic resonance imaging (nine,1.7%) were present. Vascular involvement was found in30 (5.7%) patients, including deep vein thrombosis (16,3.6%), superficial thrombophlebitis (11, 2.1%), superiorvena cava obstruction syndrome (one, 0.1%), and arteriallesions (abdominal aortic aneurysm in a patient and rightmain carotid artery pseudoaneurysm in a patient, 0.3%).Cardiac and renal involvements were not seen.The frequencies of clinical findings in female and male

patients with BD are given in (Figures 1 and 2). The mostcommon symptom in female patients was oral ulceration(100%), followed by genital ulceration (90.9%), PPL(52.6%), positive pathergy test (45.3%), ENLL (43.6%),ocular involvement (36.9%), gastrointestinal involvement(6.6%), joint involvement (4.2%), vascular involvement(1.7%), and pulmonary involvement (0.7%). Neurologi-cal involvement was not seen. The most common symp-tom in male patients was oral ulceration (100%),followed by genital ulceration (82.5%), PPL (71.4%),

Table 1 T1 and T2 values for female and male patients

Female Male P value

T1 3.44 ± 4.55 2.43 ± 3.83 0.006a

T2 1.09 ± 3.62 1.31 ± 3.01 0.46a

T1, time interval between initial symptom and fulfillment ofdiagnostic criteria; T2, time interval between fulfillment ofcriteria and diagnosis.a, Independent samples t test.

Table 2 The frequency of onset manifestations

Onset lesions Patients %

Oral ulcer 379 72.7

Genital ulceration 16 3.1

Ocular involvement 5 1.0

ENLL 1 0.2

Simultaneous occurrence of the symptoms

Oral ulcer, genital ulceration 94 18.1

Oral ulcer, ocular involvement 10 1.9

Oral ulcer, genital ulceration, ocular involvement 8 1.5

Oral ulcer, genital ulceration, ENLL 4 0.8

Oral ulcer, genital ulceration, ENLL, ocular

involvement

2 0.4

Oral ulcer, ENLL, ocular involvement 1 0.2

Oral ulcer, ENLL 1 0.2

Total 521 100

ENLL, erythema nodosum like lesions.

ª 2013 The International Society of Dermatology International Journal of Dermatology 2014, 53, 564–569

Balta et al. Clinical features of patients with Behçet’s disease Report 565

ocular involvement (58.1%), positive pathergy test(48.7%), ENLL (31.6%), vascular involvement (10.6%),joint involvement (6.4%), gastrointestinal involvement(5.6%), neurological involvement (4.7%), and pulmonaryinvolvement (0.7%). There was no statistically significantdifference between females and males in terms of clinicalfindings except genital ulceration, ENLL, PPL, ocular,neurological, and vascular involvement. Genital ulcera-tion and ENLL were found to be statistically higher infemales than in males (P = 0.005, P = 0.006,respectively). PPL, ocular, neurological, and vascularinvolvement were statistically higher in males than infemales (P > 0.001, P > 0.001, P > 0.001, P> 0.001,respectively).

Discussion

We studied the clinical characteristics of a Turkish popu-lation with BD and compared the pattern of disease withstudies from other countries (Table 3).Within sex ratios, female predominance is seen in the

United States, Korea, and Brazil, whereas male predomi-nance is seen in most other countries (Asia, Middle East,and the Mediterranean). Although male predominancewas formerly reported in Turkey, the male to female ratiohas decreased in the last 20 years and currently reachedan equal rate.7,8 In contrast to the literature, in our study,the female to male ratio is 1.22, and female predomi-nance has drawn attention in our study.The mean age of onset ranges from the mid- to late 20s

to the fourth decade.9 In our study, the mean age of dis-ease onset was 26.2 years. In the study by Gurler et al.,10

mean age was 25.6 years at the time of disease onset,which is similar to our results.In the study by Alpsoy et al.,11 the duration between

symptom onset and fulfillment of diagnostic criteria wascalculated to be longer in female patients than in malepatients, which is similar to our study. This result pointsto a faster course of disease in males. In this study,between two groups, no statistically significant differencewas seen in terms of duration between the time point offulfillment of diagnostic criteria and diagnosis. It may beconsidered that there is no significant difference betweenthe two groups for diagnostic delay. This can beexplained by increased consciousness about BD in societyand in physicians about dealing with cases.In studies by Gurler et al.10 and Alpsoy et al.,11 family

history was positive in 7.3% and 11.6%, respectively. Inour study, family history (21.9%) was higher in the litera-ture. Furthermore, family history was higher in femalepatients (24.7%) than in male patients (18.4%). Therewas no statistically significant difference between patientswho have family history or not in terms of systemicinvolvement.Oral ulceration is the most constant symptom of BD,

which was seen in nearly every patient. It was seen in100% of patients in Turkey, 97% in Iran,12 98%in Japan,13 98% in Korea,14 100% in China,4 and 100%in Singapore.15

The prevalence of genital ulceration among our patientswas 87%, which is comparable with that reported inSaudi Arabia16 and Jordan.17 However, in Iran,12 Singa-pore,15 and China,4 a lower prevalence was noticed.Skin lesions were reported in 70% of our patients. The

most frequent skin lesions are PPL and ENLL. The leastcommon lesions are subcutaneous nodule, erythema, pur-pura, pyoderma gangrenosum-like lesions, and Sweet syn-drome-like lesions.18 PPL and ENLL were reported in 61

Figure 2 The frequencies of systemic involvement of patients,both female and male. ART, articular involvement; CVS,cardiovascular involvement (P < 0.001); EYE, ocularinvolvement (P < 0.001); GIS, gastrointestinal involvement;NEURO, neurological involvement (P < 0.001); PUL,pulmonary involvement

Figure 1 The frequencies of mucocutaneous lesions ofpatients, both female and male. ENLL, erythema nodosum-like lesions (P = 0.006); GU, genital ulceration (P = 0.005);OTHER, other cutaneous lesions; OU, oral ulceration; PPL,papulopustular lesions (P < 0.001); PT, pathergy test


Report Clinical features of patients with Behçet’s disease Balta et al.566

and 38% of our patients, respectively. In only one of ourpatients, Sweet syndrome-like lesions were present. Ourresults are in line with reports from China4 and Greece.19

However, Korea,14 Japan,13 and Tunisia5 had more fre-quent skin manifestations.The pathergy reaction is considered highly sensitive and

specific for BD in patients from Turkey and Japan yet isfrequently negative in patients from Western countries.4

In our patients, the prevalence was 47%. It was 41% inJapan,13 51% in Germany,20 and 50% in Italy.21 Thereason for this discrepancy remains unknown, althoughthe pathergy test gives more positive results in active thanin the remission period.22 The sharpness, type, sterility,and size of the needle is used to test, and number of pricksmay also be responsible for the discrepancy. In contrastto a higher positive rate of pathergy test, in the males inour study, Wang et al.4 (China) and Bang et al.14 (Korea)reported a higher positive rate of pathergy test in females.Ocular involvement is an important cause of morbidity

in BD.3 Ocular involvement had high variability of preva-lence (14–85%) depending on diagnostic criteria and eth-nic populations.4,12–16 In our study, it was seen in 46%of all patients.Joint involvement is not rare.18 It was seen in 37% of

patients in Iran,12 38% in Korea,14 and 54% in Japan.13

In our study, the joint involvement (5%) in Turkey wassignificantly less frequent than in other countries. Thepatients that have active arthritis (edema, erythema) orarthralgia at presentation were regarded as having jointinvolvement. As the history of arthralgia may be seenwith many diseases, it was not considered as a sign ofjoint involvement alone.

Neuro-Behçet is a rare and important manifestation ofBD because of its severe morbidity and occasional mortal-ity.18 Neuro-Behçet was seen in 3.7% in Iran,12 4.6% inKorea,14 and 12.7% in Japan.13 Neuro-Behçet in Turkey(2.1%) was less frequent than in other countries as ourstudy consisted mainly of patients with BD attending der-matology departments. Therefore, it can be consideredthat this study includes a rather milder spectrum of thedisease.The gastrointestinal involvement of BD is characterized

by single or multiple deep penetrating ulcers, mostly inthe terminal ileum, ileocecal region, and colon.4 The inci-dence of these manifestations (6%) in Turkey was slightlylower than that in Iran12 (7%), Korea14 (7%), andGreece19 (7%). However, gastrointestinal involvementwas very high (23.8%) in Japan.13

Vascular involvement was in 5% of cases in Turkey,8% in Iran,12 8% in China,4 6% in Japan,13 29% inIsrael,23 36% in Tunisia,5 40% in Saudi Arabia,16 and57% in Egypt.3 Deep vein thrombosis is the main fea-ture,18 which was seen in 3% of patients in Turkey, 33%in Tunisia,5 and 41% in Egypt.3 Superficial thrombophle-bitis was observed in 2% of patients in Turkey, 19% inChina,4 and 15% in Egypt.3 Arterial lesions were foundin 0.3% of patients in Turkey, 11% in Egypt,3 and 10%in Tunisia.5

Pulmonary manifestations are rare and were the leadingcause of death in BD.18 The prevalence of pulmonaryinvolvement among our patients was 0.8%, which iscomparable with that reported in Iran12 (0.9%); however,in China4 (4.1%), a higher prevalence was noticed. Inour study, cardiac and renal involvement were not seen.

Table 3 Frequency of clinical features in different ethnic groups (%)

No OU GU Skin Oph Joint CNS GI Vasc Pathergy

Turkey 521 100 87.1 70.2 46.4 5.2 2.1 6.1 5.7 47.0

Iran12 6500 97.3 64.6 64.9 56.8 37.4 3.7 7.4 8.3 52.5

Korea14 1527 98.8 83.2 84.3 50.9 38.4 4.6 7.3 1.8 NR

Japan13 2014 98.3 76.3 88.8 77.4 54.4 12.7 23.8 6.6 41.75

China4 170 100 63.5 68.2 14.1 37.1 4.1 10.0 8.8 63.5

Singapore15 37 100 64.9 48.6 35.1 43.2 40.5 5.4 5.4 NR

Egypt3 63 100 96.8 55.5 47.6 36.5 34.9 19.0 57.1 44.4

Tunisia5 260 100 83.1 78.8 48.5 38.8 24.2 1.5 36.1 62.4

Saudi Arabia16 119 100 87 57 85 37 44 4 40 17.5

Germany20 196 99 74.5 75.5 58.9 59 12.8 5.8 25.1 51.8

Greece19 82 100 82.1 73.1 76.8 59.7 19.5 7.3 10.9 42.6

Italy21 137 99.3 62.8 81.8 60.6 43.1 17.5 NR 30.7 50.8

Jordan17 150 100 85 90 46 53 28 19 29 55

Israel23 59 100 68 86 49 83 15 NR 29 46

CNS, central nervous system involvement; GI, gastrointestinal involvement; GU, genital ulceration; Joint, joint involvement;No, number of cases; NR, non-recordable; Oph, ophthalmic involvement; OU, oral ulceration; Pathergy, pathergy test; Skin,skin lesions; Vasc, vascular involvement.



The frequency of onset manifestations in patients withBD is given in Table 2. Oral ulceration was the mostcommon initial symptom. Oral ulceration (72.7%) wasfollowed by genital ulceration (3.1%), ocular involvement(1.0%), and ENLL (0.2%). In 120 patients (23%), theonset manifestation comprised more than one symptom.In a study by Alpsoy et al.,11 in 79 patients (12%), theonset manifestation comprised more than one symptom.The frequency of onset manifestations in the Turkish pop-ulation was compared in Table 4. From this table, muco-cutaneous lesions and ocular involvement are the mostcommon onset lesions in the Turkish population. Thecomparison of onset signs between the Turkish popula-tion and those of the Chinese population is presented inTable 5. Ocular, joint, and gastrointestinal involvementsin the Chinese population were more common onsetsymptoms compared with the Turkish population.The pulmonary system involvement ratio is statistically

higher in patients who had multiple onset symptoms thanpatients who had just one onset symptom, and there wereno differences between other systemic involvements ineach group. Three of four patients with pulmonaryinvolvement had multiple onset symptoms. This result isthought to be related to the small number of patientswith pulmonary involvement.There was no statistically significant difference between

females and males in terms of clinical findings except gen-ital ulceration, ENLL, PPL, and ocular, neurological, andcardiovascular involvement. Only genital ulceration andENLL were more frequent in females in our study. Onthe other hand, PPL, and ocular, neurological, and car-diovascular involvement were more frequent in males.

Genital ulceration was reported more frequently in malesin the literature.6,11,24 However, in the study by Tursenet al.,7 genital ulceration and ENLL were reported morefrequently in females, which was similar to our results. Incontrast to our study, in the study by Vaiopoulos et al.,6

genital ulceration and ENLL were higher in males. In theliterature, systemic involvement was reported more fre-quently in males.7,11,24 In accordance with the literature,PPL, and ocular, neurological, and cardiovascularinvolvement were found to be significantly higher inmales than females in our study. This result may confirmthe increased morbidity of the disease among men.

Conclusions

In our study, systemic involvement was higher in malesthan females, as the disease is more severe in males thanfemales. If pulmonary system involvement is undervalued,it can be considered that there are no clinical severity andcourse differences between the patients who had multipleonset symptoms than patients who had just one onsetsymptom. Even though BD is a multisystemic disease,dermatologists may play a major role in the early diagno-sis and follow-up because oral and genital ulcerations areseen in 94% of the patients. As the only initial finding ofthe disease can be genital ulceration or ocular manifesta-tions, gynecologists, urologists, ophthalmologists, andfamily practitioners must keep BD in mind as a differen-tial diagnosis.

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Table 4 Comparison of onset manifestations in the Turkishpopulation

Our study

(%)

Alpsoy

et al.11 (%)

Oral ulceration 72.7 88.7

Genital ulceration 3.1 14.2

Skin lesions 0.2 5.7

Ocular involvement 1.0 4.2

Simultaneous occurrence of the symptoms

Oral ulcer, genital ulceration 18.1 9.8

Oral ulcer, ocular involvement 1.9 2.2

Oral ulcer, genital ulceration, ocular

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Oral ulcer, genital ulceration, ENLL,

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0.4 –

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ENLL, Erythema nodosum like lesions.

Table 5 Comparison of onset sign between Turkishpopulation and Chinese population

Our

study

China4 (Wang

et al.)

Gurler

et al.10Alpsoy

et al.11

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Genital ulceration 3.1 8.2 7.4 14.2

Skin lesions 0.2 18.2 4.8 5.7

Ocular involvement 1.0 4.1 0.5 4.2

Joint involvement – 2.4 0.5 –

Gastrointestinal

involvement

– 1.8 – –

Thrombophlebitis – 0.6 0.5 –


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