Prevalence & Impact of COVID-19 in Systemic Sclerosis Patients and Assessment of the Demographic & Clinical Features in Cases Associated with Worse Prognosis: Results of a Single Centre Registry.

Background: Our knowledge of the COVID-19 infection impact on systemic sclerosis (SSc) is scarce. This study aimed to assess the prevalence of COVID-19 infection and to determine the predictive factors of worse outcomes and death in SSc patients. Methods: In this cohort study all patients who attended our clinic between 20th February 2020 and 20th May 2021 were followed, and those with a history of COVID-19 infection completed the questionnaire. Results of para-clinical tests were extracted from the SSc database. The outcomes were classified as: alive vs. deceased and, mild vs. worse outcomes. Descriptive statistics and binary logistic regression models were applied. Results: Of the total 192 SSc patients studied, COVID-19 affected 12.5%; 6% experienced mild disease, 7% were hospitalized and 3% died. The worse outcome was associated with: older age [95%CI: 1.00-1.08], smoking [95%CI: 2.632-33.094], diabetes [95%CI: 1.462-29.654], digital pitting scars (DPS) [95%CI: 1.589-21.409], diffusing capacity of the lungs for carbon monoxide [DLCO<70 [95%CI: 1.078-11.496], left ventricular ejection fraction (LVEF)<50% [95%CI: 1.080-38.651], systolic pulmonary artery pressure (sPAP)>40 mmHg [95%CI: 1.332-17.434], pericardial effusion (PE) [95%CI: 1.778-39.206], and tendon friction rub [95%CI: 1.091-9.387]. Death was associated with male gender [95%CI: 1.54-88.04], hypertension [95%CI: 1.093-2.155], digital ulcers (DU) [95%CI: 0.976-18.34], low forced vital capacity (FVC) [95%CI: 0.03-0.81], and joint flexion contracture (JFC) [95%CI: 1.226-84.402]. Conclusion: Risk factors for the worse outcome in COVID-19 infected SSc patients included, older age, smoking, diabetes, DPS, DLCO<70, LVEF<50%, sPAP>40 mmHg, PE, and TFR. Death was associated with the male gender, hypertension, DU, low FVC, and JFC.

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.

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.

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.

Ophthalmic findings in Behcet׳s disease: Cases without apparent ocular signs.

PURPOSE: To evaluate the fluorescein angiography and infrared autofluorescence finding in patients with confirmed Behcet׳s disease (BD) but without clinical ocular signs. METHODS: In this prospective, non-interventional case series, montage fluorescein angiography (MFA) and infrared autofluorescence imaging were performed for all patients with confirmed BD but without ocular signs in clinical examination. RESULTS: Fifty BD patients (100 eyes) without clinical ocular manifestations were investigated. In MFA, we found fluorescein angiography (FA) leakage in 22 cases (44%) in both eyes, mostly at the periphery of retina. In infrared autofluorescence, profound changes were found in 43 patients, 86 eyes (86%). Twenty-five patients, 50 eyes (50%), presented retinal vascular branching modifications, straightening, tortuosity, and shunt. CONCLUSION: MFA of retina may be useful in patients with presumed BD for early diagnosis, early treatment, and follow-up of patients.

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.

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.

Evaluation of damage index and its association with risk factors in patients with systemic lupus erythematosus.

BACKGROUND: This study aimed to determine the value of damage index in patients with systemic lupus erythematosus (SLE) and the association between damage index and disease severity, flare up numbers, disease duration, and antiphospholipid antibodies. METHODS: Eighty patients with systemic lupus erythematosus were included. The damage was measured using the SLICC (Systemic Lupus International Collaborating Clinics)/ACR damage index (SDI). The disease flare was defined by the increase in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). The disease severity surrogates were the presence of class III/IV glomerulonephritis, the presence of severe central nervous system (CNS) involvement, and cyclophosphamide administration. Analysis was performed by independent Student-t and chi-square tests via SPSS(16) software. RESULTS: There were significant association between the damage accrual and the disease severity, flare-up, and antiphospholipid antibodies (p = 0.001, p = 0.004, and p = 0.05, respectively). CONCLUSIONS: The disease severity, frequency of flares, and positive antiphospholipid antibodies are associated with damage accrual in patients with systemic lupus erythematosus.

A case of ochronosis with gout and Monckeberg arteries.

Alkaptonuria is an inborn error of amino acid metabolism. A defect in tyrosine metabolism that results in accumulation of homogentisic acid in connective tissue, especially cartilage, has long been known. Degenerative arthropathy, especially of the knee and spine, develops at a relatively early age in adults. Accumulation also occurs in heart valves, and there may be a predisposition to atherosclerosis. We describe a 72-year-old man with ochronosis, gouty arthritis of both hands, and monckeberg arteries.