Behcet's disease in Iran: Analysis of 7641 cases.

Objective: To analyze Behcet's Disease (BD) in Iran, from 1975 to 2018, and compare to 35 large/small reports from other countries.Methods: Patients from all over Iran, when suspected, were sent to the BD Unit. The diagnosis was done by expert opinion. All data were recorded in the BD registry (updated in each follow-up). The data are given in percentage with 95% confidence Intervals.Results: The mean age at onset was 25.6 years. Standard deviation (SD) was 9.8. The mean disease duration was 11.7 years (SD: 8.9). Males were 55.8% (54.7-56.9), Females 44.2% (43.1-45.3), Oral Aphthosis (OA) 97.5% (97.1-97.9), genital aphthosis (GA) 64.4% (63.3-65.5), skin lesions 62.2% (61.1-63.3), ocular lesions 55.6% (54.5-56.7), Joint Manifestations 38.1% (37.0-39.2), Gastrointestinal 6.8% (6.2-7.4), Vascular 8.9% (8.3-9.5), neurological (central-peripheral) 3.9% (3.5-4.3), epididymitis 4.6% (4.1-5.1). Lab tests were positive pathergy test 50.4% (49.3-51.5), elevated ESR 51.1% (50.0-52.2), abnormal urinalysis 13.4% (12.6-14.2). The International Study Group (ISG, 1990) criteria and the International Criteria for Behcet's Disease (ICBD, 2014) had respectively a sensitivity of 76.2% (75.2-77.2) and 96.6% (96.2-97.0). The specificity was 99.3% (99.1-99.5) and 97.3% (96.9-97.7). The accuracy was 86.4% (85.8-87.0) and 96.9% (96.6-97.2).Conclusion: The most frequent manifestations were OA, GA, skin manifestations, and ocular manifestations.

Paediatric Behçet's disease in Iran: report of 204 cases.

OBJECTIVES: This study proposed to report the characteristics of paediatric Behçet's disease (PED-BD) in a cohort of patients from Iran's registry and compare them with different reports throughout the world. METHODS: From a cohort of 7504 Iranian patients with Behçet's disease those diagnosed before the age of 16 years were included in this study. Data were collected on a standard protocol comprising 105 items, including demographic features, type of presentation, and different clinical and laboratory findings. RESULTS: PED-BD was seen in 2.7% of patients. The male/female ratio was 1.02/1, and the mean age at onset was 10.5±3.4. Positive familial history was present in 9.9%. As a first manifestation, oral aphthosis was the most frequent (75%) followed by ocular lesions in 19.1%. The prevalence rates of various manifestations were as follows: oral aphthosis: 91.7%; genital ulcer: 42.2%; skin: 51.5% (pseudofolliculitis: 43.1%, erythema nodosum: 10.3%); ocular lesions: 66.2% (anterior uveitis 52%, posterior uveitis 58.3%, retinal vasculitis 39.7%); articular manifestations: 30.9%; neurological involvement: 4.9%; vascular involvement: 6.4% (venous 4.9%, arterial 2.5%); gastrointestinal manifestations: 5.9%; epididymo-orchitis: 8.7% (boys); high ESR (≥20): 50.8%; abnormal urine: 14.1%; positive pathergy test: 57%; HLA-B5/51: 48.7%. ICBD criteria have the highest sensitivity for the classification of PED-BD patients in Iran (91.7%). CONCLUSIONS: The clinical spectrum of PED-BD in Iran in this study was similar to that of other reports; however, genital ulcers, skin lesions (notably erythema nodosum), and gastrointestinal involvement were noticed to occur less frequently, while ocular lesions were more frequent and more severe compared to other reports.

Clinical features of Behcet's disease in patients without oral aphthosis.

OBJECTIVES: In current study we evaluated clinical features of Behcet's Disease (BD) in patients without oral aphthosis (NOA cases). METHODS: In a cohort of BD, patients registered during a period of 36 years were collected. We determined clinical features of BD NOA cases and compared them with patients with oral aphthosis (OA cases). The comparison was performed by chi square and Fischer's exact test. RESULTS: Among 6,821 BD patients, 175 patients (2.56%) were NOA cases. Male/Female ratio was less in NOA cases (p-value: 0.078). Mean age of disease onset was significantly higher in NOA cases (p-value: 0.001). Among NOA cases, the first manifestations comprised uveitis (70.3%), joint involvement (8.0%), retinal vasculitis (6.9%), and genital aphthosis (4.0%). During the course of disease, the prevalence of ocular lesions and positive pathergy test were significantly higher in NOA cases. Conversely genital aphthosis (OR: 0.048), mucocutaneous (OR: 0.470), joint involvement (OR: 0.478), and positive family history for BD (OR:0.138) were significantly less frequent in NOA cases. NOA cases fulfilled different criteria including International Criteria for BD (ICBD), Japan Revised, Iran, Dilsen, and Classification Tree. CONCLUSIONS: These results addressed the distinct clinical features in NOA subset of BD Including more prevalent eye involvement and positive pathergy.

Impact of the positive pathergy test on the performance of classification/diagnosis criteria for Behcet's disease.

BACKGROUND: The only diagnostic test that currently exists for Behcet's disease (BD) is the pathergy test. A positive pathergy test (PPT) is an important component of many of the 16 sets of classification/diagnosis criteria used to diagnose BD. The aim of this study was to determine the importance of a PTT in the performance of the diagnosis/classification criteria for BD. PATIENTS AND METHODS: All patients listed in the BD registry of the Rheumatology Research Center, Tehran (6,727) and 4,648 BD controls were enrolled in the study. The diagnosis was clinical when no other diagnosis could explain the patient's manifestations. The criteria were tested with and without PPT results. Sensitivity, specificity, and accuracy were calculated. RESULTS: Without PPT, all sets of criteria lost sensitivity, gained specificity, and lost accuracy, with the exception of the Cheng-Zhang criteria. The largest loss in sensitivity was for the Hubault-Hamza (35 %) and Dilsen (17.3 %) criteria; the least was for the Curth (1.9 %) and ICBD (6.5 %) criteria. The largest gain on specificity was for the Dilsen (4.7 %) and Curth (3.1 %) criteria; the least was for the Japan (0.1 %) and Japan revised (0.1 %) criteria. The greatest loss in accuracy was for the Hubault-Hamza (20.4 %) and Dilsen revised (9.3 %) criteria; the least was for the ICBD (3.6 %), while Curth gained 0.3 %. CONCLUSION: Without PPT as a criterion for the diagnosis of BD, the sensitivity and accuracy of the sets of classification/diagnosis criteria decrease, while the specificity improves.

Diagnosis of Behçet's disease: clinical characteristics, diagnostic criteria, and differential diagnoses.

BACKGROUND: The diagnosis of Behçet disease (BD) is challenging in many cases. The purpose of this study was to describe the clinical characteristics of patients at a referral BD clinic. METHODS: In a retrospective study, we collected data from patients at a national referral Behçet clinic from November 2018-August 2019. A BD diagnosis was confirmed (BD group) or ruled out (Non-BD group), and the two groups were compared for differences. RESULTS: A total of 238 patients satisfied the inclusion criteria. Forty patients (16.8%) were finally diagnosed with BD. Ocular and genital lesions were significantly more prevalent in the BD group. A positive pathergy test and HLA-B51 were also significantly more common in BD. However, oral lesions, articular involvement, and gastrointestinal manifestations were similar between groups. Also, patients with BD were significantly more likely to have multi-organ (≥2 organ systems) involvement. CONCLUSIONS: Being the first study to evaluate the clinical characteristics of patients who are visited at a referral BD clinic and are believed to have a high probability of Behçet, the results of this study are important from an epidemiological standpoint. Also, the findings of this study could be used by referral Behçet clinics, which evaluate and diagnose patients with a high pretest probability and atypical presentations of BD on a daily basis. The alternative diagnoses established in this study could be used as the list of the most common differential diagnoses for Behçet's disease.

Colchicine versus placebo in Behçet's disease: randomized, double-blind, controlled crossover trial.

The effect of colchicine was evaluated in a large cohort of Behçet's disease (BD) patients and compared to placebo. In a randomized, double-blind, controlled crossover trial, 169 patients without major organ involvement were selected consecutively. They fulfilled the International Criteria for Behçet's Disease. Patients were randomly assigned to colchicine or placebo. At 4 months, they were swapped over (colchicine to placebo, placebo to colchicine) for another 4 months. The primary outcome was the overall disease activity index, the IBDDAM. The secondary outcome was the responses of the individual symptoms. A Student's paired t test was used to evaluate results within each group, and an ANOVA to check for differences between colchicine and placebo. Analysis was performed using the "intention to treat" method. For placebo, IBDDAM worsened from 3.17 to 3.63 (t = 1.750, P = 0.08). For colchicine, IBDDAM improved from 3.35 to 2.75 (t = 4.143, P < 0.0001). Oral aphthosis, genital aphthosis, pseudofolliculitis, and erythema nodosum improved significantly with colchicine but not with placebo. According to the ANOVA, the difference in IBDDAM between colchicine and placebo was highly significant (F = 14.674, P = 0.00016). The difference between the results for males and females was not significant (F = 0.181, P = 0.67). In conclusion, colchicine, but not placebo, significantly improved the overall disease activity index. The difference between the results for colchicine and placebo was also statistically significant.

High-dose intravenous steroid pulse therapy in ocular involvement of Behcet's disease: a pilot double-blind controlled study.

AIM: To evaluate the efficacy of intravenous high-dose pulses of methylprednisolone (IVPM) for treatment of ocular involvement in Behcet's disease (BD). METHOD: In a double-blind control study, we randomized BD patients with posterior uveitis (PU) and/or retinal vasculitis (RV) into two groups. They received either IVPM (1000 mg methylprednisolone) or placebo for 3 consecutive days. Both groups received combination therapy with IV cyclophosphamide, azathioprine and prednisolone for 6 months. Visual acuity (VA), Disease Activity Index (DAI) based on the inflammatory state of each section of each eye, total inflammatory (TIAI) and adjusted DAI (TADAI) for each patient were calculated. The comparisons were done by paired t- and Mann-Whitney U-test. RESULTS: Seventeen patients in each group completed the treatment. The mean VA improved from 0.5 to 0.8 (P < 0.000001) for the study and from 0.6 to 0.7 (P < 0.02) for the placebo group. The difference was significant (P = 0.01). The comparison showed no significant difference regarding DAI improvement in other items (P > 0.2): PU, 1.9 to 0.5 (P < 0.0006) versus 2.3 to 0.8 (P < 0.0002); RV: 4.0 to 1.1 (P < 0.0004) versus 3.1 to 1.1 (P < 0.0005); TIAI: 23 to 5.7 (P < 0.0002) versus 24.8 to 8.4 (P < 0.003); TADAI: 24.1 to 7.3 (P < 0.0002) versus 25.9 to 7.9 (P < 0.004). We had one flare in the study versus seven in the placebo group (P < 0.005). CONCLUSION: Adding high-dose intravenous steroid pulse therapy to conventional combination therapy for severe ocular lesions of BD may cause better improvement on VA and fewer flares during the first 6 months of treatment.

Behcet's disease: epidemiology, clinical manifestations, and diagnosis.

INTRODUCTION: Behcet's Disease (BD) is classified among vasculitides. The aim of this review was to put together different known reports in order to help the reader to better understand the disease, to avoid the frequent misdiagnosis, and to decide the best treatment. Areas covered: a) Epidemiology: BD is rare, and is seen along the Silk Road, from 20 to 420/100,000 in Turkey and 80/100,000 in Iran, to 0.64/100,000 in the UK. b) Clinical manifestations: oral aphthosis is seen in more than 95% of patients, genital aphthosis (60-90%), skin (pseudofolliculitis/erythema nodosum, 40-90%), eyes (uveitis/retinal vasculitis, 45-90%), gastrointestinal (diarrhea/hemorrhage/perforation/pain, 4-38%), vascular (venous/arterial thrombosis, aneurysm, 2.2-50%), neurological (all kinds, especially meningo-encephalitis, 2.3-38.5%), and articular (arthralgia/arthritis/ankylosing spondylitis, 11.6-93%). c) Pathergy test is positive in some patients: 8.6% (in India) to 70.7% (in China). This data was extracted from the five nationwide surveys and the largest case series from BD conference reports and a Pubmed search. Expert commentary: Diagnosis is clinical but classification/diagnosis criteria may help. The best criteria for BD is the International Criteria for Behcet's Disease (ICBD). BD is a multisystem disease progressing by attacks and remissions. Each attack may resemble the preceding or it may be different in duration, severity, and the systems involved.

Adult Behcet's disease in Iran: analysis of 6075 patients.

INTRODUCTION: This is an analysis of adult Behcet's disease (BD) in Iran, from the Iran Registry of 7187 BD patients, gathered from 1975 to 2014, among which 6075 were adults (84.5%). PATIENTS: Patients were seen by a multidisciplinary team of experts. The diagnosis was by expert opinion, not by any specific classification/diagnosis criteria. However, 96.8% of them were classified by the International Criteria for Behcet's Disease (ICBD). Adult BDs were patients who had their first manifestation at the age of 16 or later. RESULTS: Males constituted 56% (male/female ratio 1.3/1). The mean age at onset was 28.3 ± 8.7, mean duration 10.8 ± 8.2, and mean follow-up 5.0 ± 6.3. Oral aphthosis was seen in 97.5%, genital aphthosis 65.7%, skin manifestations 64.6% (pseudofolliculitis 53.2%, erythema nodosum 23.9%), ocular manifestations 58.1% (anterior uveitis 41.1%, posterior uveitis 45%, retinal vasculitis 33.6%, cataract 24.4%), joint manifestations 39.4% (arthralgia 18.9%, monoarthritis 9.1%, oligoarthritis 17.8%, ankyloing spondylitis 2%), gastrointestinal manifestations 7% (gastroduodenitis 2.3%, peptic ulcer 1.2%, diarrhea 2.1%, rectorrhagia 1.0%, abdominal pain-nausea 1.8%), neurological manifestations 10.6% (central 3.7%, peripheral 0.3%, headache 7.6%), vessel involvement (large vessel 1.7% with large vein thrombosis 1.1% and arterial involvement 0.7%, phlebitis 6.6%, superficial phlebitis 2.3%), epididymitis 4.6%, pulmonary manifestations 1% and cardiac manifestations 0.6%. Positive pathergy test was seen in 52.3%, human leukocyte antigen (HLA)-B5 in 54%, HLA-B51 in 48.9%, and high erythrocyte sedimentation rate in 52.8% of patients. By International Study Group (ISG) criteria 77.9% were classified, compared to ICBD revised criteria with 96.9%. The specificity of ISG was 99.2% and ICBD 97.2%. CONCLUSION: Results are near the nationwide surveys from Japan, China, Korea and Germany.

Validation of the revised International Criteria for Behcet's Disease (ICBD) in Iran.

The first internationally agreed criteria for Behcet's disease were the International Study Group (ISG) criteria. It had very high specificity, but lacked good sensitivity, missing an important subset of patients. The International Criteria for Behcet's Disease (ICBD) were created in 2006 to overcome this lack of sensitivity. It was revised in 2010. The objective of this study was to evaluate the performance of the revised International Criteria for Behcet's Disease (rICBD) in Iran. In this study, the ISG and ICBD were evaluated and compared to the rICBD. All patients from the Behcet's Disease Registry (7,011) and controls (5,226), up to March 2013, entered the study. The diagnosis was clinical, by expert opinion. Sensitivity, specificity, and accuracy were calculated for ISG, ICBD, and rICBD. A 95% confidence interval (95%CI) was calculated for percentages. For ISG, the sensitivity was 77.5% (95%CI = 76.5-78.5). It was 98.3% for ICBD (95%CI = 98.0-98.6) and 96.8% for rICBD (95%CI = 96.4-97.2). Specificity was 99.2% (95%CI = 99.0-99.4) for ISG, 96.2% for ICBD (95%CI = 95.7-96.7), and 97.2% for rICBD (95%CI = 96.8-97.6). Accuracy was 86.7% (95%CI = 86.1-87.3) for ISG, 97.4% for ICBD (95%CI = 97.1-97.7), and 97.0% for rICBD (95%CI = 96.7-97.3). In Iranian patients, ICBD has 20.8% and rICBD 19.3% higher sensitivity than ISG. Although the specificity was lower than ISG by 3% for ICBD and 2% for rICBD, the accuracy was higher respectively by 10.7 and 10.3%. ICBD has by far better performance than ISG. The difference was even more prominent in Iranian patients than for the ICBD cohort of patients and controls.

The saga of diagnostic/classification criteria in Behcet's disease.

There are 17 sets of diagnosis/classification criteria for Behcet's disease: Curth (1946), Hewitt (1969), Mason (1971), Japan (1972), Hubault (1974), O'Duffy (1974), Cheng (1980), Dilsen (1986), Japan revised criteria (1988), International Study Group on Behcet's disease (ISG criteria, 1990), Iran traditional criteria (1993), Iran Classification Tree (1993), Dilsen revised criteria (2000), Korea Criteria (2003), International Criteria for Behcet's Disease (ICBD, 2006) and the revised ICBD (2010). This review is intended to show how to use them and show their performance in patients from different parts of the world. The major sets of patients (patient numbers, control numbers, year) on which the criteria were tested are: ISG set (886/97/1990), Iran (2069/1540/1993), Asia and Pacific League of Associations for Rheumatology (APLAR: 216/145/1998), Russia (105/233/2000), USA (50/NA/2000 [NA: not available]), India (50/NA/2004), Singapore (37/NA/2004), China (98/NA/2004), Korea (1454/NA/2004), Iran (4900/2020/2004), ICBD (2556/1163/2006), Germany (86/38/2008), China (322/118/2008), Iran (6128/3400/2010) and Iran (7011/5226/2013). For the following criteria sets (O'Duffy, Dilsen, Japan revised, ISG, Korea, ICBD, revised ICBD), the sensitivity in ISG cohort was 82/95/93/91/NA/NA/NA%, in APLAR 62.5/75/73/72/NA/NA/NA%, in Russia 91/92/92/86/NA/NA/NA%, USA 88/85/82/76/NA/NA/NA%, ICBD 83/87/88/82/90/96/96%, China 64/71/66/65/85/87/NA% and in Iran (2013) 69.5/81/86/77.5/86/98/97%. Specificity in ISG was 83/79/89/96/NA/NA/NA%, in APLAR 98/96/99/99/NA/NA/NA%, in Russia 88/91/92/100/NA/NA/NA%, ICBD 95/91/92/96/93/89/91%, China 97.5/95/98/99/97/94/NA% and in Iran (2013) 99/95/98/99/98/96/97%. Accuracy in ISG was 82.5/87/91/93.5/NA/NA/NA%, in APLAR 80/85/86/86/NA/NA/NA%, in Russia 89.5/92/92/93/NA/NA/NA%, ICBD 87/88/89/87/91/94/94.5%, China 72/78/74/74/88/89/NA% and in Iran (2013) 82/87/91/87/91/97/97%. ISG criteria has very good specificity, but lacks good sensitivity and accuracy. In contrast, ICBD has much better sensitivity, a little less specificity and better accuracy.

Combination of pulse cyclophosphamide and azathioprine in ocular manifestations of Behcet's disease: longitudinal study of up to 10 years.

AIM: Ocular lesions of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Retinal vasculitis is the most aggressive lesion of ocular manifestations and predicts a worse systemic outcome. We present here the outcome with a combination of pulse cyclophosphamide, azathioprine and prednisolone, on long-term usage, up to 10 years, on 295 patients (18 493 eye-months of follow-up). METHODS: Cyclophosphamide was used as a 1-g monthly pulse for 6 months and then every 2-3 months as necessary. Azathioprine was used at 2-3 mg/kg daily. Prednisolone was initiated at 0.5 mg/kg daily. Upon the suppression of the inflammatory reaction, prednisolone was tapered gradually. Patients fulfilled the International Criteria Behcet's Disease (ICBD) and had active posterior uveitis (PU) and/or retinal vasculitis (RV). Visual acuity (VA), PU, RV and TADAI (Total Adjusted Disease Activity Index) were calculated. RESULTS: Overall results: mean VA improved from 3.5 to 4.3 (P < 0.0001), 44% of eyes improved (95% CI = 40-50). Mean PU improved from 2.1 to 0.8 (P < 0.0001), 73% of eyes improved (95% CI = 69-78). Mean RV improved from 3.0 to 1.4 P < 0.0001), 70% of eyes improved (95% CI = 65-74). Mean TADAI improved from 29 to 18 (P < 0.0001), 72% of patients improved (95% CI = 66-77). The details of the longitudinal studies are given in the main article. CONCLUSION: All parameters significantly improved. VA improvement was the least, mainly due to cataracts. This combination is the best treatment choice for retinal vasculitis before opting for biologic agents.

Mesenchymal stem cell therapy unable to rescue the vision from advanced Behcet's disease retinal vasculitis: report of three patients.

OBJECTIVE: Retinal vasculitis (RV) is the most aggressive lesion of ocular manifestations of Behcet's disease, seen in 32.1% of patients. Although visual acuity (VA) improves with early and aggressive treatment, in the long run it is seen in only 48% of patients. Mesenchymal stem cell (MSC) transplantation (MSCT) can theoretically reverse the RV process. PATIENTS AND METHODS: Three patients with advanced RV and very low VA were selected. Eyes selected for MSCT were legally blind (no useful vision) with severe retinal damage due to vasculitis, resistant to combinations of monthly pulse-cyclophosphamide (1000 mg) + azathioprine 2-3 mg/kg/day + prednisolone 0.5 mg/kg/day. After patient signed written consent, 30 mL of bone marrow were taken and cultured for MSC growth. After having enough MSCs in culture (4-5 weeks) and taking into consideration all safety measures, cells were injected in one eye of each patient (approximately 1.8 million MSCs). VA was measured. Disease Activity Index (DAI) was calculated for anterior uveitis (AU), posterior uveitis (PU) and RV. RESULTS: Visual acuity was light perception (LP) for two patients and finger count (FC) for the third. Follow-up at 1, 6 and 12 months were respectively LP/LP/FC at 0.5 m, no-light perception (NLP)/LP/LP, NLP/LP/NLP. DISCUSSION: Results showed a total failure of the procedure, essentially due to the late and advanced state of vasculitis. However, the autoimmune/inflammatory reaction was greatly controlled by the procedure. CONCLUSION: Earlier cases have to be selected for further trials.

Methotrexate in ocular manifestations of Behcet's disease: a longitudinal study up to 15 years.

BACKGROUND: Ocular manifestations of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Methotrexate is the least toxic, used mainly for posterior uveitis. We present here the outcome of eye lesions with methotrexate and prednisolone, in a longitudinal study of up to 15 years, on 682 patients (5447 eye-years of follow-up). PATIENTS AND METHODS: Methotrexate was started at 7.5-15 mg/week. Prednisolone was added at 0.5 mg/kg/daily, then adjusted as needed. INCLUSION CRITERIA: (i) fulfilling the International Criteria for Behcet's Disease; and (ii) having active posterior uveitis (PU). Visual acuity (VA) was calculated on a scale of 10. Activity indexes were calculated for PU and retinal vasculitis (RV) for each eye. Total Inflammatory Activity Index (TIAI) demonstrating the inflammatory index of both eyes of the patient, and Total Adjusted Disease Activity Index (TADAI) showing both TIAI + VA were also calculated. RESULTS: Overall results: the mean VA improvement was 0.4 (P < 001), PU 1.2 (P < 0.001) and RV 0.6 (P < 0.001). VA improved in 46.5%, PU in 75.4%, and RV in 53.7% of eyes. TIAI improved in 74% of patients and TADAI in 69.4%. VA was aggravated in 37.2%, PU in 11.1%, and RV in 30.3% of eyes. TIAI was aggravated in 17.4% and TADAI in 21.6% of the patients. The remaining kept their baseline values. CONCLUSION: All parameters improved, PU better than RV. Improvement of VA was the least, mainly due to secondary cataracts.

Behcet's disease: is there a gender influence on clinical manifestations?

AIM: In Behcet's disease (BD), it is customary to believe that men are more affected than women, major organs are more involved in men, and they have worse outcomes. The male-to-female ratio is reported from 5.37 to 1 (Egypt), to 0.38 to 1 (US). If in the majority of reports BD was seen more frequently in men, in some others it was more frequent in women. The aim of this study was to examine a large cohort of patients, in whom manifestations were gender related, and to examine the strength of associations and their clinical relevance. PATIENTS AND METHODS: All patients of the BD registry, Rheumatology Research Center, Tehran University of Medical Sciences, entered the study (6702 patients). The percentage of 95 items was calculated in both genders (with their 95% confidence intervals), and were compared together by the chi-squared test. Odds ratio (OR) and relative risk (RR) were also calculated. RESULTS: Forty-three out of 95 items were gender-related (29 for males, 14 for females) with a statistically significant difference by chi-squared. Significant OR (confidence interval not reaching 1) was found for 79 items. However, clinically significant OR (2 or more for men and 0.5 or less for women) showed an association only with 16 items; five with females and 11 with males. The most important was vascular involvement. CONCLUSION: No strong association (OR of 2 or more) was found between the male gender and major organ involvement, except for vascular lesions.

Diagnostic value of pathergy test in Behcet's disease according to the change of incidence over the time.

Pathergy test (PT) is used for the diagnosis of Behcet's disease (BD). It is a criterion in many classification/diagnosis criteria. PT is mainly seen in BD but can be seen in other conditions too. PT has been reported with high frequency from most countries along the Silk Road. The sensitivity of pathergy phenomenon (PP) is declining over the time. The aim of this study was to look for the diagnostic value of PT in the past and at the present time. The BD registry (Rheumatology Research Center, Tehran University of Medical Sciences) has the data of 6,607 BD and 4,292 control patients. Patients and controls were divided in four groups of 1,650 BD and 1,073 controls. Sensitivity, specificity, positive and negative predictive value (PPV-NPV), positive and negative likelihood ratio (PLR-NLR), diagnostic odds ratio (DOR), and Youden's index (YI) were calculated for each group. The first and the fourth quartiles were compared. Sensitivity of PT decreased from 64.2% (first quartile) to 35.8% (fourth quartile). Specificity improved from 86.6% to 98.4%. PPV improved from 82.7% to 95.7%. NPV decreased from 82.7% to 60.5%. PLR improved from 4.8 to 22.4, while NLR deteriorated from 0.41 to 0.65. DOR improved from 11.6 to 34.3. Yuden's index worsened from 0.5 to 0.34. Although sensitivity of PP decreased, the increase of specificity is a plus value for diagnosis. As a result, PPV, PLR, and DOR improved, while NPR, NLR, and YI deteriorated. Although the pathergy test lost its sensitivity during the past 35 years, it has not lost its value as a diagnostic test, improving many of its characteristics. In a practical view, the chances of getting a positive test have decreased over the time. However, a positive test is rather the synonym of Behcet's disease, with a probability of 98.4%.

Gender influence on ocular manifestations and their outcome in Behcet's Disease. A long-term follow-up of up to 20 years.

It is of general belief that males are prone to more frequent, more severe manifestations, and less favorable outcome. We evaluated this hypothesis in ophthalmological manifestations (OM) of Behcet's Disease (BD). Visual acuity (VA), anterior uveitis, posterior uveitis (PU), and retinal vasculitis (RV) were checked, according to Ben Ezra, in 1,515 patients with eye lesions. The data at baseline and last visit were compared. Male/female ratio was 1.2 in the BD registry (6,500 patients) and 1.51 for OM patients (Chi(2) = 98.962, p < 0.0001). The patients-year-follow-up was 4,987. All parameters improved significantly from the baseline. Mean VA improved from 4.87 to 5.35 for males (p < 0.0001) and from 5.20 to 5.74 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.60). The mean improvement for males/females was statistically non-significant (p = 0.58). Percent improvement of eyes for males/females was 47.1%/48.8% (p = 0.41). Mean PU improved from 1.83 to 0.71 for males (p < 0.0001) and from 1.66 to 0.49 for females (p < 0.0001). Difference between males/females at baseline was significant (p = 0.01). The mean improvement for males/females was statistically non-significant (p = 0.45). Percent improvement of eyes for males/females was 75.4%/81.0% (p = 0.004). Mean RV improved from 2.05 to 1.16 for males (p < 0.0001) and from 1.97 to 0.99 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.42). The mean improvement for males/females was statistically non-significant (p = 0.47). Percent improvement of eyes for males/females was 62%/64.4% (p = 0.33). Male gender is more prone to ocular manifestations. The severity of lesions at baseline was the same for VA and RV. For PU, the difference was statistically significant, but was not clinically relevant. The therapeutic outcome (mean improvement and percent of improved eyes) was the same for all parameters.

How to deal with Behcet's disease in daily practice.

INTRODUCTION: Behcet's Disease (BD) is classified as a vasculitis, and progresses via attacks and remissions. BD is mainly seen around the Silk Road. The picture varies in different reports. For clinical descriptions, the data from the international cohort of patients (27 countries), will be used. CLINICAL MANIFESTATIONS: Mucous membrane manifestations were oral aphthosis seen in 98.1%, and genital aphthosis in 76.9% of patients. Skin manifestations were seen in 71.9% (pseudofolliculitis in 53.6% and erythema nodosum in 33.6%). Ocular manifestations were seen in 53.7% (anterior uveitis 38.8%, posterior uveitis 36.9%, retinal vasculitis 23.5%). Joint manifestations were seen in 50.5% (arthralgia, monoarthritis, oligo/polyarthritis, ankylosing spondylitis). Neurological manifestations were seen in 15.5% of patients (central 11.5%, peripheral 4.4%). Gastrointestinal manifestations were seen in 6.3% of patients. Vascular involvement was seen in 18.2% of patients and arterial involvement in 3% (thrombosis, aneurysm, pulse weakness). Deep vein thrombosis was seen in 8%, large vein thrombosis in 6.5%, and superficial phlebitis in 5.8%. Orchitis and epididymitis were seen in 7.2%. Pathergy test was positive in 49.3% and HLA-B51 in 49.1% of patients. DIAGNOSIS: Diagnosis is based on clinical manifestations. The International Criteria for Behcet's Disease (ICBD) may be helpful. TREATMENT: The first line treatment is colchicine (1 mg daily) for mucocutaneous manifestations, non-steroidal anti-inflammatory drugs for joint manifestations, anticoagulation for vascular thrombosis, and cytotoxic drugs for ocular and brain manifestations. If incomplete response or resistance occurs, therapeutic escalation is worthwhile. CONCLUSION: Behcet's disease is a systemic disease characterized by mucocutaneous, ocular, vascular and neurologic manifestations, progressing by attacks and remissions.

Behcet's disease: from East to West.

Behcet's disease (BD) is classified among vasculitides. There are actually five nationwide surveys of BD: Iran, Japan, China, Korea, and Germany. Among case series, four are on more than 200 cases (Turkey, Morocco, Tunisia, and UK). BD was classically seen around the Silk Route. Now, it is seen everywhere. The male to female ratios were, respectively (in nationwide surveys), 1.19, 0.98, 1.34, 0.63, and 1.40 to 1. The mean age at onset was 26.2, 35.7, 33.8, 29, and 26 years. Major manifestations were seen, respectively, in nationwide surveys: mucous membrane (oral aphthosis in 97%, 98%, 98%, 99%, and 98%; genital aphthosis in 65%, 73%, 76%, 83%, and 64%); skin manifestations (pseudo-folliculitis in 57%, N/A, 31%, N/A, and 62%; erythema nodosum in 22%, N/A, 38%, N/A, and 42%; ocular manifestations in 55%, 69%, 35%, 51%, and 53%). Minor manifestations were seen, respectively, in nationwide surveys: joint manifestations in 33%, 57%, 30%, 38%, and 53%; neurological manifestations in 9%, 11%, 6.5%, 4.6%, and 11%; gastrointestinal manifestations in 7%, 15.5%, 9%, 7.3%, and 12%; vascular involvement in 8.9%, 8.9%, 7.7%, 1.8%, and 13%; pulmonary manifestations in 0.3%, N/A, 2.2%, N/A, and 3.6%; cardiac manifestations in 0.5%, N/A, 4%, N/A, and 3.2%. Laboratory tests are not useful except the pathergy test, which was positive in 54%, 44%, N/A, 40%, and 34% of cases. ESR was normal in many patients. Diagnosis is based upon clinical manifestations. The International Criteria for Behcet's Disease (ICBD, 2006) may be of help, having a sensitivity of 98.2% and a specificity of 95.6% in Iranian patients.

Validation of the International Criteria for Behçet's disease (ICBD) in Iran.

AIM: To evaluate the performance of the new International Criteria for Behçet's Disease (ICBD) in Iran. The ICBD was created in 2006 to replace the International Study Group (ISG) criteria (created in 1990). In this study, 14 existing diagnosis/classification criteria (Curth, Hewitt, Mason and Barnes, Japan original, Hubault and Hamza, O'Duffy, Cheng and Zhang, Dilsen, Japan revised, International Study Group, Iran traditional, Iran Classification Tree, revised Dilsen, Korea), were evaluated and compared to ICBD by calculating their sensitivity, specificity and accuracy. METHODS: All patients from the Behçet's Disease registry (6128) and controls (3400), up to January 2008, entered the study. The diagnosis was clinical and not by any of the above-mentioned criteria. Sensitivity, specificity, accuracy (percent agreement), and 95% confidence interval were calculated. The performance of ICBD and ISG were compared by the McNemar test. RESULTS: The sensitivity was 98.2% for ICBD and 78.1% for ISG (P < 0.0001). The specificity was 95.6% for ICBD and 98.4% for ISG (P < 0.0001). The accuracy was 97.3% for ICBD and 85.5% for ISG (P < 0.0001). DISCUSSION: In Iranian patients, ICBD has 20.1% higher sensitivity and 11.8% higher accuracy than ISG, while the specificity was only 2.8% lower. ICBD was better optimized than ISG (difference between sensitivity and specificity 2.6% vs 20.3%). CONCLUSION: ICBD has by far better performance than ISG in Iran. The difference is even more prominent in Iranian patients than in the cohort of the international patients upon whom the criteria were created.