Dermatoscopic and Mucoscopic Features of Lesions in Patients with Behcet's Disease.

OBJECTIVE: Behcet's disease (BD), as a vasculitis, can affect small and large vessels. As dermatoscopy has been shown to improve the accuracy in diagnosis of various skin lesions especially vascular patterns, we set this study to find if there is any characteristic pattern in the dermatoscopy of Behcet's mucocutaneous lesions. METHODS: This prospective cross-sectional observational study designed to evaluate dermatoscopic features of Behcet's mucocutaneous lesions. Fifty six consecutive patients presenting at the outpatient clinic of the BD Research Unit were included. If present, for each patient one oral, one skin and one genital lesion were evaluated by dermatoscopy. When indicated, pathergy test was performed according to a standard protocol and the results were evaluated by dermatoscopy. RESULTS: A total of 40 oral, 8 genital, 14 skin lesions and 14 pathergy tests were evaluated by dermatoscopy. While vascular component was the most prominent feature in oral aphthae, this component was less prominent in genital lesions. Dot vessels were the most common form of vessels in both oral and skin lesions. All the oral lesions were characterized by a central white structureless area. Skin lesions were characterized by a red structureless background. In pathergy tests, negative pricks showed absence of specific features while positive pricks were characterized by a structureless background in pink, purple or red. No obvious vascular component was detected in any of the pricks. CONCLUSION: It seems that these findings have no specific clues for the diagnosis of BD, but our study is the first study in this field and the findings may give way to further investigations.

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.

The association of pathergy reaction and active clinical presentations of Behçet's disease.

OBJECTIVES: The pathergy skin test is a hypersensitivity reaction to a prick skin trauma caused by a pin or a needle, which is considered as a specific presentation in Behçet's disease (BD) and the precise mechanism of this test is not well elucidated. This study was designed to evaluate the association of pathergy reaction (PR) with the active clinical manifestations of BD patients, to assess the clinical importance of PR. MATERIALS AND METHODS: This was a cohort study on 1675 BD patients who fulfilled the entry criteria based on the International Criteria for Behçet's Disease (ICBD) from 1975 to 2011. The patients were divided into two groups; the pathergy positive group included 841 patients (50.2%) and the pathergy negative group 834 patients (49.8%). The active mucocutaneous and systemic disease manifestations were analyzed according to the presence of the PR. The odds ratio and 95% confidence interval (95% CI) were calculated for each item. RESULTS: In this study, 841 patients (50.2%) had a positive pathergy test. Patient's mean age and mean disease duration were similar in the two groups (pathergy positive and pathergy negative patients). There was no association between positive pathergy test and age of patients, or disease duration. The PR was associated with male gender (p = 0.013), oral aphthosis (p < 0.001), pseudofolliculitis (p < 0.001), anterior uveitis (p = 0.001) and posterior uveitis (p = 0.028). CONCLUSIONS: The presence of PR was associated with male gender, as well as some of mucocutaneous manifestations and uveitis in adult patients. There was no association with retinitis and vascular involvements. PR isn't associated with the severity of the disease.

Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility.

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-1ß 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.

Prospective study of articular manifestations in Behçet's disease: five-year report.

AIM: To evaluate different aspects of articular involvements (prevalence, types, relation to extra-articular manifestations, etc.) in Iranian patients with Behcet's disease (BD). METHODS: In a prospective study, all patients with BD attending an outpatient BD clinic were enrolled. The type of articular involvements (peripheral or axial), involved joints, duration of attacks and their relation to extra-articular manifestations, human leukocyte antigen (HLA)-B5 and HLA-B27 were evaluated. Data analysis was done by using descriptive statistical indices such as mean and confidence interval. The comparisons were done by chi-square test. RESULTS: In a 5-year period, 2312 patients were recruited. Musculoskeletal manifestations were recorded in 430 patients (190 without previous history of these involvements). The remaining 1882 patients showed no musculoskeletal involvements, of which 753 had past histories of musculoskeletal manifestations. The 5-year incidence rate was 18.6%, and the prevalence rate was 51.2%. History of previous musculoskeletal involvements has no effect in its new development (P = 0.2). Arthritis was the most common type of involvement (289/430, 67%). The most frequent pattern was monoarthritis (191/289, 66%), and the most frequent involved joints were knees (147/289, 50.9%). The arthritic attacks were unilateral in 82.4% of cases. Ankylosing spondylitis was seen in 44/430 (10.2%). There was no association between HLA-B5 or HLA-B27 and any type of musculoskeletal involvements (P > 0.5). Pseudofolliculitis was the only extra-articular manifestation related to arthritic attacks (P = 0.046). CONCLUSION: Musculoskeletal involvement is a common manifestation of BD seen in more than half of patients. Acute knee monoarthritis was the most common pattern of articular involvement in BD.

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.

IL10 low-frequency variants in Behçet's disease patients.

AIM: To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. METHODS: To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). RESULTS: Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3' untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. CONCLUSION: This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions.

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.

Brief report: association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behçet's disease in Iranians.

OBJECTIVE: To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behçet's disease (BD). METHODS: We tested 14 single-nucleotide polymorphisms (SNPs) in 13 genomic loci (excluding the major histocompatibility complex [MHC], IL10, and IL23R-IL12RB2, which have already been associated with BD in Iranians) for allelic and genotypic associations with BD in 973 patients and 828 controls from Iran and performed meta-analyses of the significantly associated markers. RESULTS: Six SNPs (in decreasing order of significance, rs7616215 located 38 kb downstream of CCR1, rs2617170 [p.Asn104Ser] in KLRC4, rs17810546 in IL12A-AS1, rs7574070 in STAT4, and rs10050860 [p.Asp575Asn] and rs13154629 in ERAP1) were nominally associated with BD in both allelic association tests (5.05 × 10(-9) ≤ Pallele ≤ 7.55 × 10(-3) ) and sex-adjusted genotypic association tests (6.01 × 10(-9) ≤ adjusted P value ≤ 1.30 × 10(-2) ). For all 6 SNPs tested by meta-analysis (Pmeta ), the association with BD was strengthened, because the direction and magnitude of association were similar across populations (e.g., for rs7574070, odds ratio [OR] for A allele 1.29 [95% confidence interval (95% CI) 1.21-1.37], Pmeta = 2.34 × 10(-16) ; for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], Pmeta = 1.54 × 10(-19) ; for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], Pmeta = 6.34 × 10(-11) ; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], Pmeta = 2.75 × 10(-14) ; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], Pmeta = 3.57 × 10(-10) ). CONCLUSION: This study reinforces the notion that CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 are bona fide susceptibility genes for BD, in addition to the MHC, IL10, and IL23R-IL12RB2 loci. Future genetic and functional studies are now warranted to uncover the roles of these genes in the pathogenesis of BD.

Characterization of the major histocompatibility complex locus association with Behçet's disease in Iran.

INTRODUCTION: The aim of this study was to characterize the association of human leukocyte antigen (HLA) B alleles and major histocompatibility complex (MHC) single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) in an Iranian dataset. METHODS: The association of three SNPs in the MHC region previously identified as the most associated in high-density genotyping studies was tested in a case-control study on 973 BD patients and 825 controls from Iran, and the association of HLA-B alleles was tested in a subset of 681 patients and 414 controls. RESULTS: We found that HLA-B*51 (P = 4.11 × 10(-41), OR [95% CI] = 4.63[3.66-5.85]) and B*15 confer risk for BD (P = 2.83 × 10(-2), OR [95% CI] = 1.75[1.08-2.84]) in Iranian, and in B*51 negative individuals, only the B*15 allele is significantly associated with BD (P = 2.51 × 10(-3), OR [95% CI] = 2.40[1.37-4.20]). rs76546355, formerly known as rs116799036, located between HLA-B and MICA (MHC class I polypeptide-related sequence A), demonstrated the same level of association with BD as HLA-B*51 (P adj = 1.78 × 10(-46), OR [95% CI] = 5.46[4.21-7.09], and P adj = 8.34 × 10(-48), OR [95% CI] = 5.44[4.20-7.05], respectively) in the HLA-B allelotyped subset, while rs2848713 was less associated (P adj = 7.14 × 10(-35), OR [95% CI] = 3.73[2.97-4.69]) and rs9260997 was not associated (P adj = 1.00 × 10(-1)). Additionally, we found that B*51 genotype-phenotype correlations do not survive Bonferroni correction, while carriers of the rs76546355 risk allele predominate in BD cases with genital ulcers, positive pathergy test and positive BD family history (2.31 × 10(-4) ≤ P ≤ 1.59 × 10(-3)). CONCLUSIONS: We found that the HLA-B*51 allele and the rs76546355/rs116799036 MHC SNP are independent genetic risk factors for BD in Iranian, and that positivity for the rs76546355/rs116799036 risk allele, but not for B*51, does correlate with specific demographic characteristics or clinical manifestations in BD patients.

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.

Non-corticosteroid risk factors of symptomatic avascular necrosis of bone in systemic lupus erythematosus: A retrospective case-control study.

OBJECTIVE: Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE). Corticosteroid therapy has been underlined as a main risk factor for osteonecrosis. However, AVN development in patients who have never received corticosteroid and the absence of AVN in the majority of the patients, who received corticosteroid, propose a role for non-corticosteroid risk factors in AVN development. METHODS: This case-control study included two subsets: oral corticosteroid (66 AVN and 248 non-AVN patients) and pulse-therapy subset (39 AVN and 312 non-AVN patients) who have attended our Lupus clinic from 1979 to 2009. Patients received similar cumulative dose corticosteroid, equal maximum dose and 1-year maximum dose of corticosteroid. The demographic data (including sex, age of disease onset, age at the diagnosis of AVN), organs involvement, SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage index (SLICC/ACR-DI), number of disease flare ups were compared between two subsets. RESULTS: The mean age of SLE onset was younger (P value = 0.04) in the AVN patients. In oral corticosteroid subset, malar rash (P value < 0.001) and oral ulcer (P value = 0.003) were seen more frequently in non-AVN patients, whereas psychosis (P value = 0.03) was significantly more prevalent AVN subset in oral corticosteroid subset. In corticosteroid pulse subset, no significant difference in clinical features was noted. CONCLUSION: In oral corticosteroid subset, younger age of disease onset and psychosis were significantly associated with AVN, whereas malar rash and oral ulcer showed negative association AVN.

FUT2: filling the gap between genes and environment in Behçet's disease?

OBJECTIVES: To identify new susceptibility loci for Behçet's disease (BD), we performed a genome-wide association study (GWAS) using DNA pooling. METHODS: Two replicate pools of 292 Iranian BD cases and of 294 age- and sex-matched controls were allelotyped in quadruplicate on the Affymetrix Genome-Wide Human SNP Array 6.0. Of the 51 top markers, 47 were technically validated through individually genotyping. Replication of validated single nucleotide polymorphisms (SNPs) was performed in an independent Iranian dataset (684 cases and 532 controls). RESULTS: In addition to the well-established HLA-B locus, rs7528842 in a gene desert on chromosome 1p21.2, and rs632111 at the 3'UTR of FUT2 were associated in both the discovery and replication datasets (individually and in combination). However, only the FUT2 SNP was associated in a previous GWAS for BD in Turkish people. Fine-mapping of FUT2 in the full Iranian dataset showed additional associations in five coding SNPs (2.97E-06

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.

Iron deficiency state in resistant oral aphthosis of Behcet's disease.

AIM: This study was designed to evaluate iron deficiency as a predisposing factor for resistant oral aphthosis in patients with Behcet's disease (BD). METHODS: In a case control study 220 consecutive BD patients with oral aphthosis were enrolled. All patients had been treated for at least 3 months. They were divided into two groups according to their treatment response (75 patients in the Case and 145 in the Control group). Demographic and clinical characteristics of the disease, serum iron, total iron binding capacity and serum ferritin were determined in each patient. We used independent t-test and Mann-Whitney U-test to compare the quantitative variables and chi-square test for qualitative variables. Odds ratio (OR) and confidence interval at 95% (95% CI) were calculated for each item. RESULTS: There was no significant difference between the two groups in demographics or clinical characteristics of the disease. We found iron deficiency in 72 patients (32.7%, 95% CI: 6.2), higher in the Case group than Control (39.2% vs. 30.1%; P = 0.17). Despite the higher frequency of iron deficiency in men (26.8% vs. 14.5%), the difference was not statistically significant (P = 0.09). Multivariate logistic regression analysis showed that none of the iron deficiency or sex variables could predict the development of resistant oral aphthosis. The OR for iron deficiency was 1.52 (95% CI: 0.81-2.86) and for male sex was 1.04 (95% CI: 0.56-1.91). CONCLUSION: Despite the higher frequency of iron deficiency in BD patients with resistant oral aphthosis, we were not able to attribute this resistance to this deficiency.

Genital aphthosis in Behçet's disease: is it associated with less eye involvement?

Behçet's disease (BD) is a multisystem disease classified among the vasculitides with various clinical features. Genital aphthosis (GA) is one of the major manifestations of BD. The aim of this study was to evaluate the characteristics of BD patients with GA. A cross-sectional sample of BD patients registered in 37 years was selected. We determined clinical and laboratory features of BD patients with GA (GA cases) and compared them with the patients who never developed GA (non-GA cases). The comparisons were performed by the chi-square test and logistic regression analysis. Odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the precision of ORs. Among 6,935 BD patients, 4,489 cases (64.7 %) were ascribed to GA cases. Male to female ratio (1.11:1.00 vs. 1.48:1.00 OR 0.753, P value <0.001) and mean age of disease onset (OR = 0.9, P value <0.001) were lower in GA subset. In GA cases, oral aphthosis (OA) was a more common onset manifestation (OR 2.250, P value <0.001), while uveitis (OR 0.140, P value <0.001) and retinal vasculitis (OR 0.077, P value <0.001) were less common at the disease onset. In the whole course of disease, eye involvement was less common in GA cases (OR 0.215, P value <0.001). On the contrary, OA (OR 19.698, P value <0.001), skin (OR 1.762, P value <0.001), joint (OR 1.257, P value = 0.001), gastrointestinal (OR 1.302, P value = 0.009), neurological (OR 1.624, P value <0.001) and vascular involvements (OR 1.362, P value <0.001), epididymitis (OR 1.596, P value <0.001), positive pathergy test (OR 1.209, P value <0.001) and positive familial history of OA (OR 1.325, P value <0.001) were more common in GA subset. This study showed that GA subset of BD is associated with less eye involvement but higher rates of other BD manifestations.

Clinical and immunological pattern of systemic lupus erythematosus in men in a cohort of 2355 patients.

AIM: To investigate the impact of gender on expression of systemic lupus erythematosus (SLE) in a cohort of 2355 SLE patients as one of the largest series of cases among the present reports. METHOD: In this retrospective study we used medical records of all patients (239 male and 2116 female) of the SLE registry of Rheumatology Research Center (RRC), Tehran University of Medical science (TUMS), Iran. Both clinical and paraclinical manifestations of SLE patients have been registered in this database since 1976 and updated during their follow-up. Chi-square test was used to compare the clinical and paraclinical manifestations in men and women at disease onset and during the disease course. We used logistic regression to compute odds ratios with 95% confidence intervals. A P-value < 0.05 was considered as statistically significant. RESULTS: Mean age at disease onset was 25 ± 11.8 and 24.5 ± 10.3 years in men and women, respectively (P = 0.48). Comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of mucocutaneous (43.5% vs. 33.7%, P = 0.005) and a lower prevalence of musculoskeletal symptoms (44% vs. 54.7%, P = 0.003) as the initial manifestation. During the disease course, discoid rash (25.9% vs. 13%, P = 0.000) and type IV lupus nephritis (23.4% vs. 18.1%, P = 0.03) were significantly more common, whereas arthritis (61.1% vs. 71.7%, P = 0.01) and leukopenia (28.5% vs. 35.8%, P = 0.024) were significantly less common in men. CONCLUSION: This study reveals gender influence on some manifestations of SLE. Considering sex differences is recommended in diagnostic and therapeutic features of the disease.

The relationship between plasma homocysteine level and HLA-B51 in patients with Behcet's disease: a case-control study.

BACKGROUND: Various coagulation disorders have been reported to explain hypercoagulability state in Behcet's disease (BD). A possible negative association between human leukocyte antigen (HLA)-B51 and increased homocysteine level has been suggested in a previous report from Iranian patients with BD. The aim of this study was to find any possible relationship between plasma homocysteine levels and HLA-B51. METHODS: In a case-control study, BD patients (fulfilling the new International Criteria for BD) and controls (who had similar clinical symptoms but BD was clinically excluded in them) were included. Mean plasma homocysteine levels measured by enzyme-linked immunosorbent assay in HLA-B51 positive and negative individuals both in patients and controls were compared by t-test, Mann-Whitney test and analysis of variance (F-test). RESULTS: Ninety-six BD patients and 152 controls were recruited. There was no significant difference between HLA-B51 positive and negative individuals either in the mean plasma homocysteine levels (13.59 ± 9.03 vs. 12.95 ± 4.98 µmol/L, P = 0.514), or in the prevalence of hyperhomocysteinemia (17% vs. 21.4%, P = 0.504). This was true both for BD and control groups. In HLA-B51 positive and negative BD patients, mean plasma homocysteine levels were 14.29 ± 12.02 and 12.62 ± 4.79 µmol/L, respectively (P = 0.33), and the prevalence of hyperhomocysteinemia was 20.8% versus 19.5% (P = 0.55). In the control group, the mean plasma homocysteine levels in HLA-B51 positive and negative individuals were 12.85 ± 4.28 and 13.14 ± 5.10 µmol/L, respectively (P = 0.794), and the prevalence of hyperhomocysteinemia was 13% versus 22.1% (P = 0.23). The difference was non-significant regarding sex (P > 0.71) and disease activity (P > 0.31). CONCLUSION: In contrast to our previous report, we found no relationship between plasma homocysteine levels and HLA-B51 in this study, either in BD or in the control group.

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.