Predictive value of erythrocyte sedimentation rate and C-reactive protein in Behcet's disease activity and manifestations: a cross-sectional study.

BACKGROUND: Behcet's disease (BD) as a chronic inflammatory condition that affects the eyes, skin, central nervous system, gastrointestinal tract and vessels. According to the literature, the exact value of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in predicting active manifestations of BD remains controversial. In this study, we aim to assess and compare values of ESR and CRP between BD patients with active/inactive BD and active/inactive manifestations of the disease. Moreover, we try to determine the predictive value of ESR and CRP for disease activity. METHODS: Participants (n = 514) were drug-naïve BD patients; Based on last two visits, ESR and CRP values, disease activity, and active manifestations were recorded. The Man-Whitney U test measured the associations, and the binomial logistic regression evaluated the predictive value of ESR and CRP for active disease and each active manifestation. The sensitivity and specificity and the area under the curve (AUC) for each model were determined using receiver operating characteristic curves (ROC). Multiple regressions were run to predict BD activity score from ESR and CRP. RESULT: Patients with active oral, genital, joint and dermal manifestations had higher ESR and CRP values (Mann-Whitney U test, p < 0.05 for all). Binomial logistic regressions showed that ESR had valuable predictive value for active BD (OR = 1.09 [1.04-1.13], AUC = 0.79 [0.74-0.83], p < 0.001) and active vascular manifestations (1.03 [1.01-1.05], AUC = 0.85 [0.79-0.92], p < 0.001). CRP had good predictive value for active vascular manifestations (OR 1.98 [1.45-2.72], AUC = 0.86 [0.8-0.91], p < 0.001). The optimal value of ESR ≥ 10.5 and ESR ≥ 42.5 could predict active BD and active vascular manifestations with sensitivity, specificity = 71%, 75% and = 81%, 83% respectively. CONCLUSIONS: ESR and CRP are both associated with active BD and most manifestations of the diseases. They can be used for the prediction of active BD and active vascular manifestations in BD patients. Further studies can help to confirm the findings of the current research.

Cardiac Manifestations in Iranian Patients with Behçet's Disease.

Background: Behcet's disease (BD) is a vasculitis with multisystem and multiorgan involvement. Cardiac involvement in BD is a rare complication with a poor outcome that manifests itself in different forms. In this study, we aimed to investigate cardiac involvement in BD. Methods: This is a retrospective study based on cardiac manifestations in BD according to the data of the Behçet's Disease Unit, the Rheumatology Research Center, Tehran University of Medical Sciences, from registered patients from 1975 until June 2017. Cardiac manifestations consisted of pericarditis, myocardiopathy, myocardial infarction, stable ischemic heart disease, endomyocardial fibrosis, thrombosis, and valvular and coronary involvement. All the patients' baseline and demographic data were recorded in a designed questionnaire. The laboratory workups, imaging, and pathological tests were also performed. Results: We studied 7650 patients with BD, of whom 51% were male. In the entire study population, 47 patients manifested cardiac involvement: valvular involvement in 6.1%, myocardial infarction in 23.4%, stable ischemic heart disease in 20%, pericarditis in 21.3%, intracardiac thrombosis in 2.1%, coronary aneurysm in 2.1%, heart failure in 12.8%, and dilated cardiomyopathy in 4.3%. Conclusion: The prevalence of cardiac involvement in our patients with BD was 0.6%. A multidisciplinary approach can reduce mortality and morbidity rates. Consequently, we suggest that echocardiography and other cardiac diagnostic tests be routinely considered for early diagnosis and subsequent treatment.

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.

Geographical variations in ocular and extra-ocular manifestations in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is a rare vasculitis that results in multi-organ inflammatory disease. At-risk populations are most prevalent in the Middle East and East Asia. Clinical data on BD in Western countries, especially in the United States, are scarce. We have compared clinical patterning of BD vasculitis in two geographically defined patient cohorts in the Western United States and Iran. METHODS: Comparative analysis of a retrospective cohort of 56 patients with BD evaluated at Stanford University Hospital between 2000 and 2016 and a cohort of 163 patients from the BD Registry at Tehran University of Medical Sciences. Clinical, demographic, laboratory, and treatment data were available. Comparisons were performed using descriptive statistics, Student's t-test, and χ2-test. RESULTS: The Stanford patients with BD were significantly younger at disease onset, had a higher proportion of females, and had longer disease duration than Iranian patients with BD. Genital ulcers, skin, joint, neurological, vascular, cardiopulmonary manifestations were all significantly more common in the Stanford cohort and 38% of Stanford patients had four or more organ systems involved compared with approximately 10% of Iranian patients. In contrast, Stanford patients had fewer ocular lesions (Stanford 21.4% vs. Iran 53.4% p<0.05), with the biggest difference seen for retinal vasculitis. CONCLUSION: Patients with BD from the Western US have a more severe disease course when compared to Iranian patients with BD, as demonstrated by earlier onset and a higher rate of multi-organ involvement. The high risk of Iranian patients with BD developing vasculitis of ocular structures suggests distinct pathomechanisms driving ocular versus extra-ocular BD.

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.

Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis.

Epigenetics refers to a set of regulatory mechanisms that affect gene expression, while the original sequence of the DNA remains unchanged. Because the advance of noncoding RNAs (ncRNAs), the role of microRNAs (miRNAs) has been gradually highlighted in the regulation of numerous cellular processes. A bulk of studies has identified that ncRNAs might be divided into several subtypes. On the one hand, investigations have disclosed the role of these molecules in normal physiological conditions of the cells. On the other hand, there is sufficient evidence that ncRNAs participate in the pathogenesis of diseases. Through this review article, we attempted to gain a comprehensive understanding of the role of ncRNAs, long ncRNAs, miRNAs, and other subtypes in pathogenesis, diagnosis, and treatment of rheumatoid arthritis (RA). Research demonstrated aberrant expression of several miRNAs in various cell and tissue types of patients with RA in comparison to the healthy individuals as well as in animal studies. Furthermore, plausible molecular mechanisms of alterations in ncRNAs expression has been discussed in causing the disease state. These alterations seem promising to be used as biomarkers in RA diagnosis. Alternately, they might be targeted by drugs to interrupt inflammation and other disease complications to treat patients with RA.

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 effects of team-based learning on learning outcomes in a course of rheumatology.

INTRODUCTION: We evaluated the effects of implementing Team-Based Learning (TBL) on student engagement, accountability, satisfaction, and preference for lecture or team-based learning. Moreover, we assessed the effect of TBL on knowledge retention and application over time through short answer questions based on clinical scenarios addressing history taking and diagnosis skills in medical students. METHODS: The study was conducted in a quasi-experimental design. The study population were all of the third-year medical students (n = 84) participating in a course of rheumatology in Shariati Hospital, which is a teaching hospital affiliated to Tehran University of Medical Sciences. We compared TBL with the conventional lecture-based method. The assessments were performed after implementation of TBL by the Classroom Engagement Survey (CES) and Team-Based Learning Student Assessment Instrument (TBL-SAI). The assessment for application of knowledge was conducted in 3 time-points through short answer questions on rheumatic diseases. The comparison of results was made by Student's t-test and repeated-measures analysis of variance (RM-ANOVA) using SPSS software, version 16. RESULTS: The CES scores indicated a high level of engagement in TBL (Mean±SD=26.7±3.70, p=0.0001) but not in the lecture-based sessions (Mean±SD=23.80±4.35, p=0.09). The total mean score (SD) for TBL-SAI was 159.68 (14.14) for TBL sessions indicating a favorable outcome (p=0.0001). The student scores obtained from the short answer questions showed that over time the students' scores had declined significantly less for the TBL sessions in comparison to the lecture-based sessions, F (2, 166) = 4.624, p=0.011. CONCLUSION: The results indicated higher student engagement, satisfaction and long term learning by TBL.

Macrophages from Behcet's Disease Patients Express Decreased Level of Aryl Hydrocarbon Receptor (AHR) mRNA.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.