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Purpose: To compare the long-term results of the patients with branch retinal vein occlusion (BRVO) secondary to Behçet's syndrome (BS) with the patients with unknown etiology., Methods: Medical records and optical coherence tomography (OCT) imaging results of the patients with BRVO secondary to BS and with unknown etiology were reviewed retrospectively between 2016 and 2018 at a single center. The anatomical location of the BRVO, involvement of the macula, application of laser photocoagulation, and intravitreal injection were evaluated., Results: Twenty-eight eyes of 23 patients with BRVO secondary to BS as the study group and 22 eyes of 19 idiopathic BRVO patients as the control group were included in the study. The mean duration of follow-up after the development of BRVO was 74.6 ± 57.4 months in the study group and 63.6 ± 59 months in the control group. The rate of bilaterality, macular involvement, and application of laser photocoagulation was not statistically significantly different between the groups. However, the frequency of injection requirement was significantly lower in the patients with BRVO secondary to BS in comparison to the control group (P= 0.009)., Conclusion: Although the treatment of BRVO is laser photocoagulation and intravitreal injection of anti-VEGF agents or dexamethasone implant, the patients with BS might respond very well to systemic immunomodulatory agents in case of BRVO. Thus, rearrangement of the immunomodulatory treatment before starting intravitreal injections should be considered in the patients with BRVO secondary to BS., Competing Interests: None

Objectives: The efficacy and safety of biosimilar infliximab (bio-IFX) was shown in randomised controlled trials and it was approved for all indications of the reference product in several countries. However, a previous case series of 3 patients with Behçet's syndrome (BS) reported disappointing results. We aimed to share our experience with bio-IFX treatment in different types of organ involvement in patients with BS., Methods: We reviewed the charts of all BS patients who were prescribed reference infliximab (ref-IFX) or bio-IFX in our BS clinic. Among the 181 BS patients who were prescribed IFX since 2003, 6 (3%) were prescribed bio-IFX due to refractory disease despite conventional immunosuppressives., Results: A total of 6 patients (mean age: 32.1±6.2, mean disease duration: 5.3±1.8 years, 5 men and 1 woman) received bio-IFX for uveitis, nervous system, vascular and joint involvement. Four of the 6 patients obtained remission and stayed in remission during the 16±6.5 months they used bio-IFX. Among the 4 patients who obtained remission, 2 were switched to ref-IFX due to unavailability of bio-IFX infusion set and did not experience adverse events or loss of efficacy. However, relapses occurred during tapering. The other 2 patients are still in remission with bio- IFX. Among the remaining 2 patients, one had to be switched to ref-IFX after the first infusion, due to a change in the reimbursement policy and the other was non-responsive., Conclusions: Our limited experience showed that bio-IFX may be a safe and effective alternative for patients with BS, refractory to conventional immunosuppressives.

Objectives: The prognosis of uveitis in Behçet's syndrome (BS) has improved over decades. Whether this is related to the use of more aggressive management strategies is not known., Methods: This is a retrospective study of BS patients who received infliximab (IFX) for refractory eye disease between 2003-2015. The patients were divided into two groups according to the date of onset of in IFX treatment as before and after 2013. We compared the two groups in terms of disease characteristics at the onset of IFX treatment and response to treatment., Results: There were 43 patients in the old and 14 patients in the new group. The duration of uveitis and previous immunosuppressive treatment before the initiation of IFX were significantly shorter in the new group compared to the old group (p=0.043 and p=0.028, respectively). The baseline visual acuity (VA) at the initiation of IFX was better in the new group, but this was only significant for the left eye. Treatment with IFX was effective in both groups in preserving VA and this was more pronounced in the new group. Attack frequency under IFX was significantly lower in the new group (p<0.001)., Conclusions: IFX seems to be initiated earlier and also in less severe cases during the course of BS uveitis than before. Despite the few numbers of patients and relatively short duration of follow-up, our results give a hint that this change has improved the outcome.

We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10 -8 ) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10 -15 ). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

Purpose: Ophthalmic involvement may lead to permanent vision loss in 25% of cases in patients with BD and it is a main concern in the literature. Although several studies have been investigated, the etiology and the cause of the disease and attacks are not yet known. This study aimed to investigate the correlation between visual impairment and personal characteristics and social circumstances in patients with BD., Materials and Methods: A total of 153 patients with BD and age-and gender-matched 26 healthy control subjects completed the self-report Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and State and Trait Anxiety Inventory (STAI-S and STAI-T). We classified the study participants into three groups with respect to severity of eye involvement and one control group. Each group was compared with the other two study groups and control group., Results: According to TCI, we revealed that there was a trend in BD patients with eye involvement + poor prognosis having less disorderliness traits than BD patients with eye involvement + good prognosis (p = 0.016). The BD patients with eye involvement + poor prognosis had significantly lower attachment scores than BD patients with eye involvement + good prognosis (p = 0.005) and healthy controls (p = 0.005). The BD with eye involvement + poor prognosis had lower empathy scores than healthy controls (p = 0.002). In the way of average TCI parameters, only SD was statistically significant. In terms of subdimensions of TCI parameters, RD 3, SD 3, SD 5 , and C 2 were shown to be statistically significant among some of the groups., Conclusion: BD patients with eye involvement were demonstrated to be more extravagant and socially disinterested. It may reflect that severe visual loss caused BD patients to be more systematic, depressive, self-contained, and exhausted. Considering psychological aspects of BD and its visual manifestations may contribute to helping these patients more effectively.

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Purpose: Our aim was the evaluation of retinal nerve fiber layer (RNFL) and central macular thickness (CMT) in patients with Neuro-Behcet's disease (NBD) and to compare the results with healthy control subjects., Methods: We recruited 50 eyes of 25 patients with NBD and 42 eyes of 21 age-matched healthy control subjects. Patients and control subjects underwent a thorough ophthalmic examination, including retinal nerve fiber layer and macular thickness measurements by optical coherence tomography., Results: No significant difference was found between groups for age, sex, intra-ocular pressure and central corneal thickness measurements. The average RNFL in patients with NBD was significantly lower than that of healthy controls (86.92 ± 18.36 μm vs. 99.74 ± 8.73 μm; p = 0.00). There was significant thinning of the RNFL in three of four quadrants of the peripapillary area, superior (107.22 ± 30.91 μm vs. 125.57 ± 20.97 μm; p = 0.00), inferior (110.36 ± 25.57 μm vs. 132.19 ± 12.71 μm; p = 0.00) and nasal (68.84 ± 18.47 μm vs. 74.98 ± 11.42 μm; p = 0.05), in patients with NBD. Average CMT was significantly lower in NBD patients than in control subjects (244.06 ± 26.25 μm vs. 261.69 ± 25.71 μm; p = 0.00)., Conclusions: There are significant differences in average RNFL and CMT between the two groups. RNFL and CMT thicknesses are reduced in patients with NBD compared with the healthy controls.

Unlabelled: Abstract Purpose: To evaluate agreement and estimate sensitivity and specificity of uveitis specialists' interpretation of ocular photographs in diagnosing Behçet uveitis., Methods: Fourteen Turkish uveitis specialists, masked to demographic and clinical features of patients, independently labeled ocular photographs (29 Behçet/30 other diagnoses) as "Behçet uveitis" or "non-Behçet." Level of agreement was evaluated using kappa statistics. Photographs were categorized based on ocular signs captured and performance of observers., Results: Exact agreement with the correct diagnosis was 56-81%. Seven reviewers correctly labeled more than 70% of photographs. Interobserver agreement among those 7 reviewers revealed moderate (κ = 0.41-0.60) or substantial (κ = 0.61-0.80) agreement in 76% of pairs. Smooth layered hypopyon, superficial retinal infiltrate with retinal hemorrhages, and branch retinal vein occlusion with vitreous haze were correctly recognized as Behçet uveitis by majority of reviewers., Conclusions: There are ocular signs of Behçet disease that can be considered diagnostic even in the absence of any other clinical information.

Objective: To test the hypothesis that colchicine use during early disease decreases immunosuppressive use in Behçet syndrome (BS) in the long term., Methods: Patients with BS who participated in a double-blind, placebo-controlled trial of colchicine 16.6±1.1 years ago were evaluated for immunosuppressive use during the posttrial period., Results: We could contact 90/116 patients; 28 (31%) received immunosuppressives during the posttrial period, 14 being from the colchicine arm. Posttrial colchicine use and cumulative duration were similar between patients who received immunosuppressives and those who did not., Conclusion: Continuous use of colchicine, even when initiated at an early disease stage, does not seem to decrease the use of immunosuppressives in the long term.

Individuals with Behçet's disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behçet's disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behçet's disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 × 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 × 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease.

Purpose: To analyze the referral patterns and clinical features of uveitis in tertiary eye care centers in Turkey., Methods: Uveitis services of eight university clinics collected data on uveitis patients who presented during 2004. Data were collected on a form including a questionnaire on socio-demographic and clinical features which were documented at presentation., Results: A total of 761 patients (1187 eyes) with a mean age of 35.5 years were included in the study. Male to female ratio was 1.04:1. The majority of patients (89.6%) were from an urban population, 53% were referrals and 43% had had uveitis for more than one year. The most common type of uveitis was anterior uveitis (52.5%) followed by panuveitis (28.1%), posterior uveitis (12.7%) and intermediate uveitis (6.7%). In 56.8% of patients an etiological classification was established. The most common etiology was Behcet's disease (32.1%), followed by Fuchs' heterochromic iridocyclitis (5.1%) and ocular toxoplasmosis (4.7%). Among 48 pediatric patients uveitis associated with juvenile idiopathic arthritis and ocular toxoplasmosis both having equal frequencies (12.5%) were the most common diagnosis. These were followed by Behcet's disease with juvenile-onset (10.4%). At the time of presentation, 6.25% of the patients were legally blind (having visual acuity less than 0.1 in the better seeing eye)., Conclusion: Compared to the uveitis series reported from other countries, Behcet uveitis was the leading cause of uveitis in this series. Uveitis associated with juvenile idiopathic arthritis and ocular toxoplasmosis were the most common cause of uveitis in childhood. On the other hand, entities like acquired immunodeficiency syndrome-related uveitis, presumed ocular histoplasmosis and Birdshot retinochoroidopathy were rare.

Objective: Crohn's disease (CD) and ulcerative colitis (UC) share common clinical features with Behçet's syndrome (BS). We surveyed UC and CD patients for pathergy phenomenon and features of BS with the aim of determining how much overlap is present between these 2 entities in a setting where BS is relatively common, the frequency of pathergy positivity in inflammatory bowel disease (IBD) patients and evaluating how International Study Group (ISG) criteria perform in differentiating IBD from BS., Methods: This study was conducted among patients with CD and UC attending the gastroenterology outpatient clinic of a university hospital which is also a referral center for BS. Consecutive CD and UC patients were screened for BS using ISG criteria. Pathergy test was performed and evaluated by 2 independent observers in a masked manner., Results: Ninety-three patients with CD and 130 with UC were surveyed. None of the CD patients fulfilled ISG criteria for BS while 2 of 130 UC patients did. Twenty CD patients had oral ulcers while 4 reported having genital ulcers but no scars could be observed. Twenty-two CD patients had papulopustular lesions, 2 had nodular lesions, 3 had arthritis and none had uveitis. Thirty-two UC patients had oral ulcers, none had genital ulcers, 23 had papulopustular lesions, 3 had nodular lesions, 2 had arthritis and 2 had uveitis. Pathergy test was positive according to at least one of the observers in 10/93 CD and 8/130 UC patients and according to both observers in 4/130 UC patients., Conclusion: Despite similarities between the clinical features of CD and UC with BS, coexistence is uncommon. ISG criteria perform well in differentiating these diseases. About 8% of IBD patients show the pathergy phenomenon.

Aim: The aim of this report was to provide a detailed description of the clinical features of Vogt-Koyanagi-Harada (VKH) disease in Turkish patients., Methods: We retrospectively analyzed 45 patients diagnosed with VKH disease at seven referral centers in Turkey. A standard data acquisition form was used for the analysis of demographic and clinical features., Results: The study cohort consisted of 45 patients (32 female, 13 male) who had a mean age at presentation of 31 years. Seven patients (15%) were aged 16 years or younger. Nineteen (42%) patients presented in the acute or subacute stage and 26 (58%) in the chronic stage. According to the revised diagnostic criteria, nine (20%) patients had the complete form of the disease, 23 (51%) had the incomplete form, and 13 (29%) had probable VKH disease. All patients had bilateral ocular involvement. Sunset-glow fundus was observed in 89% of the patients, pigment clumping in 73%, nummular depigmented scars in 71%, cataract in 53%, optic atrophy in 31%, glaucoma in 29%, subretinal fibrosis in 22%, choroidal neovascular membranes in 7%, and phthisis in 4%. All patients who presented at the acute uveitic stage received systemic corticosteroid therapy. Immunosuppressive treatment was employed in 30 (66%) patients, which was initiated at the acute uveitic stage in ten (22%) patients. Final visual acuity was better than 0.5 in 59% of the patients' eyes, between 0.1 and 0.5 in 21%, and less than 0.1 in 20%., Conclusions: VKH disease is rare in Turkey. We conclude that the majority of patients with VKH in Turkey do not have the complete form of the disease. Based on our results, most patients with VKH seem to be late referrals. Ocular complications were common among these patients.

Objective: To determine the effect of the tumor necrosis factor-alpha blocker etanercept on the pathergy and monosodium urate (MSU) status and on the mucocutaneous and articular manifestations of patients with Behçet's disease (BD)., Methods: Forty male patients with BD, all with positive pathergy and MSU tests and mucocutaneous disease and/or arthritis, were randomized (20 patients to each study arm) to receive either etanercept 25 mg twice a week or placebo for 4 weeks. The pathergy and MSU responses and the frequencies of mucocutaneous and articular manifestations were compared between the 2 groups., Results: There were no decreases in the pathergy and MSU responses in the etanercept group compared to the placebo group at any time. The mean numbers of oral ulcers, nodular lesions, and papulopustular lesions were less in the etanercept group compared to the placebo group at all weekly evaluations, except for the second week for papulopustular lesions. The probability of being free of oral ulcers and nodular lesions was also significantly higher in the former group (log-rank chi-square = 9.83, p = 0.0017; log-rank chi-square = 14.17, p = 0.0002, respectively)., Conclusion: Etanercept did not affect the pathergy reaction and the cutaneous response to MSU crystals. However, the drug was effective in suppressing most of the mucocutaneous manifestations of BD.

This study was conducted to determine the frequency of antinuclear antibodies (ANA) positivity and uveitis in our newly diagnosed juvenile idiopathic arthritis (JIA) patients classified according to International League Against Rheumatology (ILAR) classification criteria. Ninety-two girls and 106 boys, totally 198 children were enrolled in the study. of them 36 (18.2 percent) were found to be ANA positive. Chronic anterior uveitis was detected in 20 (10.1 percent) patients. ANA positivity was determined in 4 of the systemic JIA patients, in whom no uveitis had been detected. Twenty-five of 37 patients with oligoarticular JIA were ANA positive, in 10 of them uveitis was also diagnosed. ANA were positive in 3 of 34 patients with RF positive polyarticulat JIA, only one patient had positive ANA, and another one had uveitis. Nine patients were extended JIA and in none of them, ANA positivity or uveitis were present. Of 43 patients classified as enthesitis related arthritis (ERA), uveitis was diagnosed in 6 and there was no evidence of ANA positivity, but one had uveitis. We conclude that the incidence of ANA positivity and uveitis is low in Turkish children with JIA.

This study was conducted to investigate therapeutic value of a soluble tumor necrosis factor-alpha (TNF-alpha) receptor, etanercept, in a rat model of endotoxin-induced uveitis (EIU). Forty-two inbred male Lewis rats were divided into seven equal groups. 200 microg of Escherichia coli 055:B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Groups 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received subcutaneous etanercept 24 hr prior to LPS injection at a dose of 0.4 mg kg(-1). Group 1 rats were used as controls. Eight, 24, and 48 hr after treatment clinical uveitis scores (miosis, iris hyperemia, and hypopyon) were assessed by a masked observer and the rats were euthanized. Neutrophil leukocytes, CD8+, CD4+, and CD45RO+ cells in the anterior uveal tissue were counted either after hematoxylin-eosin or monoclonal antibody staining. TNF-alpha levels were also measured in the aqueous humor samples by an ELISA method. Etanercept treatment significantly improved clinical uveitis scores at all examination points compared to the LPS injected animals. The improvement was almost complete expect for the miosis score, since no significant difference was detected between the controls and LPS + Etanercept treated animals at all examination points. Cell counts were also at significantly lower levels in LPS + Etanercept treated animals at all examination points, except for CD8+ and CD45RO+ cell counts at 24 hr examination point. There was no significant difference between the controls and LPS + Etanercept treated animals at all examination points as with CD4+ and CD45RO+ cell counts at 48 hr. Our data showed that etanercept had a definite effect on the treatment of EIU. Further studies should clarify its efficacy on clinical uveitis conditions.

We surveyed the 20-year outcome of a cohort of patients with Behçet syndrome with emphasis on both mortality and morbidity. During 1999 and 2000, we collected outcome information on 387/428 (90.4%) of a cohort of patients (262 male, 125 female) who had registered in a dedicated outpatient clinic between July 1977 and December 1983. In 245/345 (71.0%) patients, outcome information was based on a formal hospital reevaluation, and in the remaining patients, on detailed telephone interviews. Forty-two patients (9.8%) (39 male, 3 female) had died, mainly due to major vessel disease and neurologic involvement. Mortality, as measured by standardized mortality ratios (SMR), was specifically increased among young males, among whom morbidity was also the highest. However, the SMR tended to decrease significantly with the passage of time. The same was also true for all mucocutaneous and articular manifestations. Both the onset of eye disease and its greatest damage were also usually within the first few years of disease onset. These suggest that the "disease burden" of Behçet syndrome is usually confined to the early years of its course, and in many patients the syndrome "burns out." However, central nervous system involvement and major vessel disease are exceptions. They can have their onset late (5-10 yr) during the disease course. As reflected in the mortality figures, the disease was less severe among the females for almost each disease manifestation. There were no female patients with arterial aneurysms. Severely impaired vision did not always mean an eventual loss of useful vision, and those patients with a late onset of eye disease had a better visual prognosis.

Background: Eye involvement is the main cause of morbidity in Behçet's syndrome. The efficacy of the combined use of azathioprine and interferon alfa in treating this condition has not been studied., Methods: Ten male BD patients with retinal involvement but no irreversible structural changes were treated with azathioprine 2.5 mg/kg/day and IFN alpha 2b three times weekly for 24 weeks in an open trial. At week 24, IFN alpha was stopped and the patients continued to use azathioprine or received other immunosuppressives as indicated. Clinical response was assessed by visual acuity changes of either eye under the combination treatment and during the follow-up after stopping interferon., Results: As compared to the study entry, the mean visual acuities of either eye increased significantly at the end of the combination treatment (right eye 5.8 +/- 1.26 vs. 8.3 1.14; P = 0.043; left eye 6.3 1.15 SEM vs. 9.1 +/- 0.9 SEM; P = 0.027). The improvement in visual acuity persisted in the nine patients who were followed for 7.2 +/- 1.6 SEM months after stopping interferon. Reversible hematologic toxicity, mostly in the form of leukopenia, was detected in six patients during the combination treatment., Conclusions: The combination of IFN alpha and azathioprine appears to be effective for eye involvement of BD. However, the frequent occurrence of myelosuppression mandates close monitoring.

Objective: Colchicine is a widely used treatment for Behçet's syndrome, even though in a previous 6-month controlled study, it was shown to be effective only in controlling erythema nodosum and arthralgias. We reassessed the effect of colchicine in Behçet's syndrome in a study conducted among a larger group of patients for 2 years., Methods: We randomized 116 patients with Behçet's syndrome (60 male/56 female), who had active mucocutaneous disease without eye or major organ involvement, to receive either placebo or colchicine (1-2 mg/day, adjusted to body weight) in a double-blind trial for 2 years. The primary outcome measure was the sustained absence of any lesions during treatment (complete response). The secondary outcome measure was the difference in the number of mucocutaneous lesions or arthritic joints between the active drug and placebo arms. Women and men were analyzed separately., Results: Eighty-four patients (72%; 45 male, 39 female) completed the 24-month study. Kaplan-Meier analyses showed significantly more complete responses in the colchicine treatment group in terms of reduced occurrence of genital ulcers (P = 0.004), erythema nodosum (P = 0.004), and arthritis (P = 0.033) among the women, and reduced occurrence of arthritis (P = 0.012) among the men. The mean numbers of genital ulcers (P = 0.001), erythema nodosum lesions (P = 0.002), and arthritic joints (P = 0.014) among the women were less in the colchicine group, and the mean number of arthritic joints (P = 0.026) among the men was less in the colchicine group. Adverse effects were similar in both groups., Conclusion: Colchicine may be useful for treating some of the manifestations of Behçet's syndrome, especially among women. This might be a reflection of less severe disease among the women.

Objective: Patients with ulcerative colitis (UC) and Crohn's disease (CD) were not represented in the diseased controls group that had been utilised in the development of the International Study Group (ISG) criteria for the diagnosis of Behçet's syndrome (BS). Having similar features, both of these conditions can pose problems in the differential diagnosis of BS. Moreover, there has been a recent awareness of coexistence of BS and familial Mediterranean fever (FMF). The aim of this study was to reassess the performance of ISG criteria among patients with BS and other rheumatological conditions, specifically including those with CD, UC, and FMF., Methods: 302 consecutive patients with BS and 438 patients with other rheumatological conditions were surveyed for the presence or absence of the features of BS by means of a standard form which had been prepared according to ISG criteria. All control patients with a history of oral ulcer had a pathergy test and an eye examination by an experienced ophthalmologist with a slit lamp. The sensitivity and specificity of the ISG criteria were calculated., Results: Seven of 302 patients with BS (2%) did not fulfill the ISG criteria while 5 of 438 controls (1%) fulfilled the ISG criteria., Conclusion: In this study ISG criteria performed well in correctly classifying BS. Further specificity studies might be considered in CD.

Immune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behçet's disease and posterior uveitis (BD-posterior uveitis; n = 33) in comparison with non-Behçet anterior uveitis (AU, n = 14), Behçet's patients without uveitis (BD, n = 15) and healthy controls (HC, n = 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2.8 +/- 1.3) than those with AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.1 +/- 0.4) and HC (SI 1.1 +/- 0.6) for B27PD (P < 0.0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3.3 +/- 1.6) than AU (SI 1.5 +/- 0.4), BD without uveitis (SI 1.2 +/- 0.3) and HC (SI 1.1 +/- 0.6) (P < 0. 0001). A significant correlation between the responses to PDSAg and B27PD (r = 0.56, P < 0.001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.

Behçet's syndrome (BS), originally described as a triad of oral aphthae, genital ulcerations and uveitis, is a systemic vasculitis that is prevalent in the Middle east, Far East and in the Mediterranean basin. It is characterized by a heightened state of inflammation although the main drive that initiates and sustains this is not yet elucidated. Suppression of this inflammatory state constitutes the major goal of treatment and therapy is tailored according to the specific manifestations observed. We now have considerable more insight on drug management of BS compared to 20 years ago. Particularly, within the recent past we have learned to use more rationally the agents that were already available to us. This is especially true for azathioprine, cyclosporin A, thalidomide and colchicine. Promising data are also being collected with alpha-interferon. With these agents, significant progress has been achieved in the management of uveitis and mucocutaneous symptoms but treatment issues related to thrombotic problems, major vessel involvement and neurological disease have not yet been resolved.

Behçet's syndrome (BS) is a systemic vasculitis of unknown etiology. There are several reasons for doubting a primary autoimmune pathogenesis of this condition. Recent information suggests evidence for genetic anticipation. Although there is heightened inflammatory activity, as exemplified by the pathergy reaction, wound healing in BS is normal. BS also runs a more stormy course in adults and in the young. However, the amount of androgen receptors in scrotal skin have not found to be increased. Another unsolved problem is the nature of acne-like lesions and how they differ from acne vulgaris (AV). Only lesions in "non-acne" areas were compared between the two conditions, and no differences were detected. Mortality is increased in BS, especially among males. Azathioprine proved to be effective in disease control after 8 years of follow-up. We have also recently finished a 24 week controlled trial of two doses of thalidomide, 100 mg and 300 mg per day. Both doses were superior to placebo, with no real differences in efficacy, in controlling the oral and genital ulcers.

Background: Because there is an increased inflammatory response to trauma, particularly of the skin, in patients with Behçet's syndrome (BS), an alteration in wound healing in BS is expected. The aim of this study was to investigate the healing features of punch biopsy wounds in BS and acne vulgaris (AV) patients used as controls., Method: Full-thickness skin punch biopsies (4 mm) were taken from the hairless sites of the non-dominant forearms in 20 BS and 20 AV patients. Each patient was examined on days 1, 2, 3, 4, 5, 8, and 10, and the biopsy wound area and induration were marked on sterile glass slides. Other inflammatory changes, such as suppuration and pain, were also recorded. No antiseptic solutions or ointment, except saline, were used., Results: The wound area healed similarly in both groups (p > 0.05). Thirteen (65%) BS patients had erythematous haloes around the wound on the first day. The number of patients presenting inflammatory changes reached 18 (90%) on the second day in the BS group. The area of erythema around the wound in BS patients was significantly greater than that in AV patients (5; 25%). It gradually decreased day by day. Purulent changes were observed in four BS patients on day 1, and induration around the biopsy wound in six patients on day 2. Only one patient with AV had suppuration, which appeared on the second day, while no AV patient displayed induration., Conclusion: Biopsy-induced trauma may cause increased inflammation in BS, but wound healing is not altered.

Objective: To assess the effect of azathioprine (AZA) treatment on long-term prognosis in Behçet's syndrome., Methods: Patients (all male) who took part in a double-blind, placebo-controlled trial of AZA a mean +/- SD of 94 +/- 10 months previously were reevaluated., Results: The emergence of blindness (log rank chi2 = 5.6, P = 0.02) and a 2-line drop in the visual acuity of the right eye (log rank chi2 = 5.9, P = 0.015) occurred significantly more frequently among the patients originally allocated to the placebo group compared with patients who originally received AZA, despite posttrial treatment for patients in both groups when needed. There was also a trend toward more frequent occurrence of extraocular complications in the placebo group. The beneficial effect of AZA was especially pronounced among patients who had eye involvement of short duration prior to their entry into the trial., Conclusion: Early treatment with AZA tends to favorably affect the long-term prognosis of Behçet's syndrome.

We surveyed the 10-yr mortality among 152 Behçet's syndrome (BS) patients who had registered at a BS out-patient clinic and compared it to the expected mortality in the general population. Information on mortality was available in 79% of the study group, among whom six patients (all males) had died. The observed mortality of two patients in the 15-24 yr age bracket was significantly above that expected in the general population. BS is a cause of increased mortality in the young male patients

Objective: To test the efficacy of systemic interferon alpha 2b (IFN alpha 2b) treatment in the mucocutaneous and joint symptoms of Behçet's syndrome., Methods: The 48-week open, self-controlled trial was conducted in 3 phases. After the pretreatment phase of 16 weeks, 20 patients (8 men, 12 women; mean age 37 +/- 7 years SD) were treated with IFN-alpha 2b at a dose of 5 million units 3 times a week for 6 weeks followed by 5 million units once a week for 10 weeks. The subsequent 16 weeks not taking the medication was the posttreatment phase., Results: Treatment with IFN-alpha 2b significantly reduced the mean number of arthritis attacks (F = 3.48; p < 0.05), their mean duration (F = 3.77; p < 0.05), and the mean erythrocyte sedimentation rate (F = 6.66; p < 0.001). The mean number of mucocutaneous lesions also showed a decrease, but this was not statistically significant. Except for the duration of arthritis, the mean number and frequency of all symptoms tended to return to pretreatment levels in the posttreatment phase., Conclusion: This pilot study shows that systemic IFN may be effective in the treatment of arthritis of Behçet's syndrome.

Pulmonary arterial involvement is an important complication of Behçet's syndrome (BS). Among 2179 patients with BS, 24 (1.1%) were diagnosed as having pulmonary arterial aneurysms (PAAs). Haemoptysis was the presenting symptom in all but one. All were male. The mean age at the time of the diagnosis of PAA was 30 +/- 11 S.D. yr (range 17-59 yr). Their mean disease duration was 5 +/- 4 yr (range 3 months-16 yr). There was a high prevalence of thrombophlebitis (21/24, 88%). Histopathological examination showed pulmonary vasculitis involving all layers of pulmonary arteries and veins. Twelve patients (50%) died after a mean of 9.5 +/- 11 S.D. months (range 1-36 months) after the onset of haemoptysis. The mean duration of follow-up of the remaining 12 patients was 25.5 +/- 24 S.D. months (range 1-78 months). The treatment consisted mainly of pulsed or oral cyclophosphamide alone or with prednisolone. As is true with other severe manifestations of Behçet's syndrome, PAAs are more common among males. They are associated with a prevalence of thrombophlebitis and there is high mortality despite treatment.

Cytotoxic agents have long been used in Behçet's syndrome, especially for eye involvement, but their effectiveness has been uncertain. We conducted a two-year randomized, placebo-controlled, double-blind trial of azathioprine (2.5 mg per kilogram of body weight per day) in Turkish men with Behçet's syndrome without eye disease (group 1; n = 25) or with eye disease (group 2; n = 48). Corticosteroid treatment remained available to all the patients. All six patients withdrawn from the study because of severe eye disease were receiving placebo (P less than 0.001). Azathioprine was superior to placebo in the prevention of new eye disease in group 1 (1 vs. 8 patients; P less than 0.01) and in group 2 among the 14 patients who at entry had disease in only one eye (P less than 0.001). There were fewer episodes of hypopyon uveitis (1 vs. 15; P less than 0.001) among the group 2 patients who took azathioprine. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis. There were no serious side effects attributable to azathioprine. We conclude that azathioprine is effective in controlling the progression of Behçet's syndrome, especially its most serious manifestation, eye disease.

It has been suggested that certain tissue types are associated with different clinical manifestations of Behçet's disease in Japan and England. Regional differences in the associations between HLA antigens and Behçet's disease have been established. We tissue type 119 patients with Behçet's disease in Istanbul and attempted to correlate various clinical manifestations with HLA antigens. The frequency of only one tissue antigen, HLA-B5, was found to be increased in these series. HLA-B5 was present in 94 of 119 patients (77%) compared to 89 of 268 controls (33%), P less than 0.0001, ARR = 6.79. Age of onset, sex, incidences of ocular disease, arthritis, thrombophlebitis and erythema nodosum did not show any positive or negative associations with any of the alleles tested.

We conducted a field survey to establish the prevalence of Behçet's syndrome among all the inhabitants aged 10 years or older in a village in northern Turkey. The prevalence of Behçet's syndrome was 19/5,131. There were 13 females and 6 males. None had eye involvement. Pathergy test was positive in 6/18 (33%) and 5/19 carried HLA-B5 (26%), suggesting that the previously established association of HLA-B5 in Behçet's syndrome is mainly true for hospital based populations. Moreover, the pathergy test was less commonly positive in milder disease.