Antineutrophil cytoplasmic antibody (ANCA) in connective tissue diseases

Background: Antineutrophil cytoplasmic antibody (ANCA) test is frequently used in the diagnostic evaluation of systemic vasculitides, especially Wegener's granulomatosis (WG). The test becomes positive in some other diseases like systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, infectious diseases and drug-induced conditions. Indirect im-munofluorescence (IIF) and enzyme linked immunosorbent assay (ELISA) are different techniques to detect ANCA. This study was planned to evaluate the frequency of positive ANCA in connective tissue diseases and the control group. Patients and methods: The study group was made up of patients with rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, polymyositis, systemic sclerosis, and those with various vasculitic syndromes. We used the serum of couples that were undergoing pre-marital screening tests as our control group. Both IIF and ELISA techniques were performed on the two groups. Results: Positive test result was detected in none of the 171 individuals in the control group. However, among 152 patients of the study group, 24 were positive for p-ANCA, one was positive for c-ANCA, 5 were positive for anti-PR3, and 7 were positive for anti-MPO. There was only one c-ANCA positive test result among the anti-PR3 positive cases. This case had a high titer of anti-PR3. We did not find any association between anti-MPO by ELISA and p-ANCA pattern in IIF, instead the association between antinuclear antibodies and p-ANCA positivity was statistically significant c-ANCA and anti-PR3 tests were most frequently positive in WG patients. Anti-MPO was more frequently positive in patients with systemic lupus erythematosus, dermatomyositis, and polymyositis. Conclusion: Our data showed that neither p-ANCA nor anti-MPO is specific for the diagnosis of vasculitis and it seems that c-ANCA, though specific for vasculitis, it is not sensitive for the detection of low-to-moderate antibody titres. This alongwith the problem regarding the correlation of p-ANCA and anti-MPO underlines the necessity of using both methods (IIF and ELISA) in the search for antineurophil cytoplasmic antibodies

Combination therapy with pulse cyclophosphamide plus corticosteroids improves renal outcome in patients with lupus nephritis

Background: The prognosis of SLE is influenced by the onset of glomerulonephritis. Clinical trials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management of lupus nephritis for preserving renal function. Objective: The purpose of this study is to define the outcome of renal function with bolus pulses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical trial, to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: 1) Induction with bolus methylprednisolone and cyclophosphamide. 2) Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3) Tapering with reduction of prednisolone by 10 each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4) Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms, urine protein excretion falling below 0.3 gr/dL or by at least 50, RBC cast disappearance, C3, C4, Hb, and ESR return to normal limits. Results: Twenty-three patients with lupus nephritis completed our therapeutic protocol. Renal biopsy was performed in 22 cases and indicated type IV in 20 patients (95.2), and type V in 2 patients. After an average of 4+1.95 months 22 patients achieved remission (95.65) and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant statistical differences were achieved between creatinine, proteinuria, hematuria, leukocyturia, urinary cast, C3, C4, ESR, and Hb before and after therapy (p<0.05). Plasma creatinine fell from 1.44+0.95 mg/dL to 0.97+0.78 (p<0.004). Proteinuria fell from 1879.78+1854.46 to 408.34+572.92 mg/24h (p<0.001). Thirteen episode of relapses were treated again with repeated cycles of cyclophosphamide and all remitted again. Conclusion: Intensive immunosuppression with steroid and cyclophosphamide provides excellent results with an acceptable rate of complications in the treatment of lupus nephritis

Screening for amyloid deposition by subcutaneous fat tissue aspiration technique in rheumatoid arthritic patients and investigating its clinical significance in Iran

Aim: This study examined the frequency of secondary amyloidosis in Iranian patients with rheumatoid arthritis (RA) in order to determine its clinical significance. Methods: A total of 220 RA patients (167 female, 53 male), with minimum disease duration of 5 years, were included in this prospective study over a period of about 2 years. Abdominal subcutaneous fat-pad aspiration (ASFA) method was used in obtaining specimens from all subjects. All of the specimens were examined for apple-green birefringence under polarized light microscope. Amyloid deposits were graded from 1+ to 3+. Clinical, radiological, and laboratory characteristics of the patients were assessed and recorded. Results: Amyloid deposition was detected in 11 (5) of the fat smears stained with Congo red stain. All of the samples had minimal (1+) amyloid deposits. In this study, amyloid-positive cases showed clinically significant symptoms; six of the patients (55) presented with proteinuria, and seven other cases (64) presented with severe constipation. Conclusion: Abdominal fat amyloid deposition was found to be uncommon in adult Iranian RA patients. In up to half of the patients the deposits were subclinical. A longer follow-up and larger multicentric collaborative study is needed to determine the significance of subclinical amyloid deposits. © 2007 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd

Prevalence of amyloid deposition in long standing rheumatoid arthritis in Iranian patients by abdominal subcutaneous fat biopsy and assessment of clinical and laboratory characteristics

BACKGROUND: The study was aimed at determining the prevalence of secondary amyloidosis in a group of Iranian patients with Rheumatoid Arthritis (RA), and the assessment of its correlation with the clinical and laboratory findings and data. METHOD: A total number of 220 patients (167 female and 53 male) with a minimum five-year history of RA were selected. Congo red staining method was used for staining the specimens obtained by abdominal subcutaneous fat biopsy (ASFB) method. All of the specimens were examined for apple-green birefringence under polarized light microscope. Clinical and laboratory characteristics of the patients were assessed. Chi-square test and unpaired student's t-test were run for intergroup comparisons. RESULTS: Amyloid deposition test yielded positive results in 15 out of the 220 cases (6.8%) examined by the ASFB technique. Thirteen patients were found to have minimal amyloid deposits. Of all the clinically significant cases, 8 (53%) presented with proteinuria, and 7 cases (46.6%) had severe constipation. CONCLUSION: The prevalence of fat amyloid deposits in Iranian patients with RA is low. In up to half of the study group the deposits were subclinical. Follow up studies are required to determine whether this subclinical amyloidosis can develop into full-blown clinically significant amyloidosis

Needle muscle biopsy using pleural biopsy needle for diagnosis of inflammatory muscle diseases

Background: Inflammatory myopathies are a complex heterogeneous group of disorders in the field of rheumatology. Muscle biopsy is the cornerstone of differential diagnosis. Objective: The aim of this study was to compare the diagnostic yield of needle muscle biopsy using large bore pleural biopsy needle with conventional open surgical biopsy. Methods: Needle muscle biopsy (NMB) using large bore pleural biopsy needle and conventional open surgical biopsy of muscles were carried out on all of the 32 patients referred to Hazrat-rasool Hospital in 18 months period with suspected inflammatory myopathies. Results: The pathologic reports were similar in 27 out of 32 patients. 4 samples were reported normal by both methods. One technical problem occurred in needle biopsy and one vasculitis case was misinterpreted as inflammatory myopathy. However, results were significantly different in respect to disadvantages by the two methods (p=0.021). Conclusion: Needle muscle biopsy with large bore pleural biopsy needle can be used as an early diagnostic tool for evaluating patients with suspected inflammatory myopathies

Ollier's disease with symmetric bony deformities

This report describes a 33-year-old man who presented with short stature, multiple bony swellings in hands and deformities in extremities. He was evaluated with radiography to determine pattern of bone and joint involvement. X-rays showed multiple enchondromas in hands, forearms, arms, thighs, legs and feet. The vertebral column was not affected. © 2006 Asia Pacific League of Associations for Rheumatology

COMBINATION THERAPY WITH PULSE CYCLOPHOSPHAMIDE PLUS CORTICOSTEROIDS IMPROVES RENAL OUTCOME IN PATIENTS WITH LUPUS NEPHRITIS

Background: The prognosis of SLE is influenced by the onset of glomerulonephritis. Clinical trials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management of lupus nephritis for preserving renal function. Objective: The purpose of this study is to define the outcome of renal function with bolus pulses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical trial, to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: 1) Induction with bolus methylprednisolone and cyclophosphamide. 2) Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3) Tapering with reduction of prednisolone by 10% each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4) Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms, urine protein excretion falling below 0.3 gr/ dL or by at least 50%, RBC cast disappearance, C3, C4, Hb, and ESR return to normal limits. Results: Twenty-three patients with lupus nephritis completed our therapeutic protocol. Renal biopsy was performed in 22 cases and indicated type IV in 20 patients (95.2%), and type V in 2 patients. After an average of 4+1.95 months 22 patients achieved remission (95.65%) and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant statistical differences were achieved between creatinine, proteinuria, hematuria, leukocyturia, urinary cast, C3, C4, ESR, and Hb before and after therapy (p<0.05). Plasma creatinine fell from 1.44+0.95 mg/dL to 0.97+0.78 (p<0.004). Proteinuria fell from 1879.78+1854.46 to 408.34+572.92 mg/24h (p<0.001). Thirteen episode of relapses were treated again with repeated cycles of cyclophosphamide and all remitted again. Conclusion: Intensive immunosuppression with steroid and cyclophosphamide provides excellent results with an acceptable rate of complications in the treatment of lupus nephritis

Global epidemiology of gout: prevalence, incidence and risk factors

Gout is a crystal-deposition disease that results from chronic elevation of uric acid levels above the saturation point for monosodium urate (MSU) crystal formation. Initial presentation is mainly severely painful episodes of peripheral joint synovitis (acute self-limiting 'attacks') but joint damage and deformity, chronic usage-related pain and subcutaneous tophus deposition can eventually develop. The global burden of gout is substantial and seems to be increasing in many parts of the world over the past 50 years. However, methodological differences impair the comparison of gout epidemiology between countries. In this comprehensive Review, data from epidemiological studies from diverse regions of the world are synthesized to depict the geographic variation in gout prevalence and incidence. Key advances in the understanding of factors associated with increased risk of gout are also summarized. The collected data indicate that the distribution of gout is uneven across the globe, with prevalence being highest in Pacific countries. Developed countries tend to have a higher burden of gout than developing countries, and seem to have increasing prevalence and incidence of the disease. Some ethnic groups are particularly susceptible to gout, supporting the importance of genetic predisposition. Socioeconomic and dietary factors, as well as comorbidities and medications that can influence uric acid levels and/or facilitate MSU crystal formation, are also important in determining the risk of developing clinically evident gout