Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris.

BACKGROUND: The classic treatment for pemphigus vulgaris is prednisolone. Immunosuppressive drugs can be used in association. OBJECTIVE: To compare the efficacy of Azathioprine in reducing the Disease Activity Index (DAI). PATIENTS AND METHODS: A double blind randomized controlled study was conducted on 56 new patients, assigned to two therapeutic groups: (i) prednisolone plus placebo; (ii) prednisolone plus Azathioprine. Patients were checked regularly for 1 year. 'Complete remission' was defined as healing of all lesions after 12 months, and prednisolone <7.5 mg daily, (DAI ≤ 1). Analysis was done by 'Intention To Treat' (ITT) and 'Treatment Completed Analysis' (TCA). RESULTS: Both groups were similar in age, gender, disease duration, and DAI. Primary endpoint: By ITT and TCA, the mean DAI improved in both groups with no significant difference between them. The difference became significant for the last trimester (3 months; ITT: P = 0.033, TCA: P = 0.045). Secondary endpoint: The total steroid dose decreased significantly in both groups, with no significant difference between them, except for the last trimester (ITT: P = 0.011, TCA: P = 0.035). The mean daily steroid dose decreased gradually in both groups becoming statistically significant in favour of azathioprine, in the last trimester, especially at 12th months (ITT: P = 0.002, TCA: P = 0.005). Complete remission was significant at 12 months only for TCA (AZA/Control: 53.6%/39.9%, P = 0.043). LIMITATIONS: Sample size was rather small to demonstrate all differences. Other limitations include the choice of primary and secondary endpoints and the unavailability to measure thiopurine methyltransferase activity. CONCLUSION: Azathioprine helps to reduce prednisolone dose in long-run.

Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory disease characterized by oral aphthous ulcers, genital ulcers, uveitis and skin lesions. Etiology and pathogenesis of BD are not fully elucidated, but the association with human leukocyte antigen (HLA)-B51 or B*5101 has been repeatedly reported. Previous studies have shown that there are few sequence variations in the protein-coding region of B51, while there is a report on many variations in the 5'-flanking region and intron. In this study, HLA-B*5101 gene from 37 individuals including Japanese, Turkish, Jordanian and Iranian patients and healthy controls were fully sequenced to further clarify the B*5101 gene in association with BD. We found that all the patients and healthy controls carried B*510101 with no variation in the 5'-flanking region, exon and intron. However, seven polymorphisms were found in the 3'-flanking region. These polymorphisms composed of six haplotypes that were shared and stretched over the ethnic groups, suggesting that the susceptibility to BD was conferred by the B*510101 itself and not by any genes in linkage disequilibrium with B*510101. In addition, phylogenetic analyses of B*510101 showed that the 3'-flanking sequences followed an evolutional divergence differently from that of the other regions, implying that a unifying selection might operate to conserve B*510101.

Hypophosphatemic osteomalacia in von Recklinghausen neurofibromatosis.

Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement.

Histocompatibility antigens (HLA) in rheumatic diseases in Iran.

One hundred and sixty-six patients with different forms of rheumatic diseases were tissue typed for 26 antigens of the A and B locus of the HLA system, using a modified KN cytotoxicity test. Among 25 patients with confirmed ankylosing spondylitis, 23 had HLA B27 (92 per cent), compared to 2.5 per cent in the normal controls. This confirms the strong association of HLA B27 with ankylosing spondylitis. Eight patients had doubtful AS, five of whom were positive for B27. In 21 patients with mechanical disorders of the spine no B27 was found. Thirty-six patients with osteoarthrosis of the knee joints did not show any significant relationship with any HLA antigens. Twenty-one patients with systemic lupus erythematosus showed an increase of HLA B13 and B17.

Multiple Imputation to Deal with Missing Clinical Data in Rheumatologic Surveys: an Application in the WHO-ILAR COPCORD Study in Iran.

BACKGROUND: The aim of the article is demonstrating an application of multiple imputation (MI) for handling missing clinical data in the setting of rheumatologic surveys using data derived from 10291 people participating in the first phase of the Community Oriented Program for Control of Rheumatic Disorders (COPCORD) in Iran. METHODS: Five data subsets were produced from the original data set. Certain demographics were selected as complete variables. In each subset, we created a univariate pattern of missingness for knee osteoarthritis status as the outcome variable (disease) using different mechanisms and percentages. The crude disease proportion and its standard error were estimated separately for each complete data set to be used as true (baseline) values for percent bias calculation. The parameters of interest were also estimated for each incomplete data subset using two approaches to deal with missing data including complete case analysis (CCA) and MI with various imputation numbers. The two approaches were compared using appropriate analysis of variance. RESULTS: With CCA, percent bias associated with missing data was 8.67 (95% CI: 7.81-9.53) for the proportion and 13.67 (95% CI: 12.60-14.74) for the standard error. However, they were 6.42 (95% CI: 5.56-7.29) and 10.04 (95% CI: 8.97-11.11), respectively using the MI method (M=15). Percent bias in estimating disease proportion and its standard error was significantly lower in missing data analysis using MI compared with CCA (P< 0.05). CONCLUSION: To estimate the prevalence of rheumatic disorders such as knee osteoarthritis, applying MI using available demographics is superior to CCA.