Ali D. Askari

Steroid myopathy in connective tissue disease

In eight women with polymyositis (three patients), systemic lupus erythematosus (SLE) (three patients), rheumatoid arthritis (one patient) and shoulder-hand syndrome (one patient), weakness developed during high dose prednisone therapy. These women were studied using serial functional and manual muscle tests, determination of serum glutamic oxaloacetic transminase (SGOT), creatine phosphokinase (CPK) and serum aldolase levels, and urinary excretion of creatine. Insidious onset of weakness was characteristic. Myalgias were seen in five patients and unusual sudden weakness in two. Weakness was always most severe in the pelvic girdle muscles; there was a lesser involvement of shoulder girdle and distal muscles. Serum muscle enzyme levels were normal in all cases, but urinary creatine excretion was invariably increased and proved to be the most sensitive laboratory indicator for clinical diagnosis and for monitoring patient improvement. Serial urinary creatine excretion and serum enzyme studies were of value in differenting steroid myopathy from a flare of myositis in patients with connective tissue disease. Diagnosis and effective management were achieved by the use of readily available laboratory and clinical procedures without resorting to muscle biopsy.

Control of periodontal infection reduces the severity of active rheumatoid arthritis

Objective:To determine if eliminating periodontal infection and gingival inflammation affects the severity of active rheumatoid arthritis (RA) in patients with chronic inflammatory periodontal disease. Methods:Twenty-nine subjects with confirmed diagnosis of RA and mild-to-moderate chronic periodontitis of at least 3 years’ duration were enrolled in the study. The activity of RA was assessed using the disease activity score test (DAS28). Seventeen subjects completing the study received periodontal treatment consisting of scaling/root planing and oral hygiene instruction; 12 subjects completing the study received no treatment. Participants continued their usual disease-modifying medications for RA without any changes in DMARD therapy during the study period. RA measurements, and periodontal indices were recorded at baseline and at 8 weeks for each participant. Mann-Whitney U and χ2 tests were used to test for significant differences in the severity of RA in the periodontally treated group compared with the untreated groups. Results:Ten of 17 subjects (58.8%) in the treated group and 2 of 12 subjects (16.7%) in the untreated group showed improvement in RA scores. There was a statistically significant difference in DAS28 (4.3 ± 1.6 vs. 5.1 ± 1.2) and erythrocyte sedimentation rate (31.4 ± 24.3 vs. 42.7 ± 22) between the treatment and the control groups. Conclusion:Control of periodontal infection and gingival inflammation by scaling/root planing and plaque control in subjects with periodontal disease may reduce the severity of RA. This notion is supported by reported subjective improvement in treated patients.

Pulmonary Hypertension and Systemic Lupus Erythematosus

A combination of systemic lupus erythematosus (SLE) and fatal pulmonary hypertension occurred in a patient who, to our knowledge, had the highest pulmonary artery pressure (120/65 mm Hg) reported without any clinical or autopsy findings of pulmonary interstitial disease or vasculitis. The gradual development of pulmonary hypertension over years is a rare complication in patients with SLE.

Cardiac abnormalities in polymyositis/dermatomyositis.

P OLYMYOSITIS and dermatomyositis are inflammatory disorders of skeletal muscle that are clinically characterized by weakness in the pelvic and pectoral girdle muscles.’ The primary histologic findings are degeneration and regeneration of muscle fibers, a predominantly mononuclear cell inflammatory infiltrate, and at times, fibrosis. Extraskeletal muscle manifestations, such as skin rash occurring in dermatomyositis, Raynaud phenomenon, arthritis,2 and pulmonary complications,’ are documented in these disorders. Cardiac involvement, first described by Oppenheim in 1899,4 was previously thought to be infrequent. In fact earlier reports either did not address the cardiac involvement or considered it a rare occurrence in these disorders.‘,” In recent years, however, there has been an increasing number of reports on cardiac abnormalities in adult polymyositis and dermatomyositis.7m2’ Categorically, these abnormalities have included electrocardiographic changes, cardiac arrhythmias, congestive heart failure, coronary artery disease, and myocarditis (Table 1). The electrocardiogram usually has been abnormal. The most frequently noted changes have been nonspecific ST-T changes, varying degrees of atrioventricular block (including bundle branch block), right and left axis deviation, and left atria1 complex abnormalities. Of particular interest are documented cases of complete

Behçet's disease and treatment with colchicine

A case of Behçets disease characterized by anterior uveitis, arthritis, oral, genital, and cutaneous lesions, as well as gastrointestinal involvement, all documented over a 10-month period, is presented. Less commonly appreciated complications, such as pyoderma gangrenosum, hidradenitis suppurativa, perianal fistula, and persisting leukocytosis, were among striking clinical features of the patients history. Remission of cutaneous lesions and no recurrence of ocular or gastrointestinal manifestations occurred with 0.6 mg oral colchicine twice daily in a period of 5 weeks.

Arthritis of hemochromatosis: Clinical spectrum, relation to histocompatibility antigens, and effectiveness of early phlebotomy☆

Five patients who presented with arthritis as the sole manifestation of hereditary hemochromatosis and 51 family members were studied. Studies included clinical evaluation for the presence of arthritis and hemochromatosis, roentgenography of hands, knees, and pelvis, serum iron and serum ferritin measurements, complete HLA typing for 50 of the A and B loci, and, when indicated, liver biopsy. Arthritis occurred in 45 percent of persons with hemochromatosis. Although typical involvement of second and third metacarpophalangeal joints was observed in all five patients and some family members, two with typical arthritis did not have characteristic radiographic changes, two had constitutional symptoms without arthropathy, and one had unilateral hand changes. A specific HLA haplotype (A2/B17 in Family 1 and A29/B15 in Family 2) correlated with hereditary hemochromatosis but not with the arthropathy. Phlebotomy alleviated the early constitutional symptoms but did not help advanced arthritis. Anti-inflammatory drugs, intraarticular injections of glucocorticoids, and resection osteotomies of metacarpal heads were other treatment modalities.

Evidence for heterogeneity in hereditary hemochromatosis: Evaluation of 174 persons in nine families

Hereditary hemochromatosis is an autosomal recessive disease in which the gene is linked to the HLA system. Investigation of nine unrelated probands and their family members has revealed distinct groups based on biochemical and clinical manifestations of the disease. Four different types of disease expression were identified: Group I--classic hereditary hemochromatosis with elevated transferrin saturation, serum ferritin levels, and liver iron content; Group II--severe iron overload, accelerated disease manifesting at an early age; Group III--elevated total body iron stores, normal transferrin saturation and serum ferritin levels; Group IV--markedly elevated findings on serum biochemical tests, e.g., transferrin saturation, serum ferritin levels, with minimal elevation in total body iron stores. This evidence for several clearly distinguishable modes of expression in different families suggests that more than one genetic lesion in iron metabolism may be responsible for iron overload in hereditary hemochromatosis. This genetic heterogeneity may be helpful in delineating the fundamental abnormalities in iron metabolism in this group of disorders.

Identification of oral bacterial DNA in synovial fluid of patients with arthritis with native and failed prosthetic joints.

ObjectiveWe examined the presence of bacterial DNA in synovial fluids of native or clinically aseptically failed prosthetic joints from patients having periodontal disease and arthritis to determine whether there is bacterial spread from the oral cavity to the joints. MethodsA total of 36 subjects were enrolled in the study. Among these, 11 were diagnosed with rheumatoid arthritis (RA) and 25 were diagnosed with osteoarthritis (OA). Eight patients with OA and 1 patient with RA had failed prostheses. Synovial fluid was aspirated from the affected hip or knee joint. Pooled subgingival plaque samples were collected, followed by clinical periodontal examination. Bacterial DNA was extracted from the collected synovial fluid and dental plaque samples were followed by polymerase chain reactions and DNA sequence analysis of the 16S-23S rRNA genes. ResultsOf the 36 patients, bacterial DNA was detected in the synovial fluid samples from 5 patients (13.9%): 2 with RA (1 native and 1 failed prosthetic joints) and 3 with OA (1 native and 2 failed prosthetic joints). Of these 5 patients, 2 were diagnosed with periodontitis and had identical bacterial clones (Fusobacterium nucleatum and Serratia proteamaculans, respectively) detected in both the synovial fluid and the dental plaque samples. Fusobacterium nucleatum was the most prevalent, detected in 4 of the 5 positive samples. No cultures were done and no patients were treated with antibiotics or developed clinical infection. ConclusionsThe present findings of bacterial DNA in the synovial fluid suggest the possibility of organisms translocating from the periodontal tissue to the synovium. We suggest that patients with arthritis or failed prosthetic joints be examined for the presence of periodontal diseases and be treated accordingly.

Arthropathy, hypouricemia and normal serum iron studies in hereditary hemochromatosis

A patient manifesting the arthropathy of hemochromatosis without abnormal serum iron studies is described. Hemochromatosis was confirmed by liver biopsy. This case serves to emphasize the diagnostic value of the characteristic arthropathy of hemochromatosis. Our observations in this patient support the hypothesis that the pathogenesis of hereditary hemochromatosis differs from that of acquired iron overload states. The concurrent presence of hypouricemia is explored in this patient and in 18 other patients with hereditary hemochromatosis. Men with hereditary hemochromatosis were found to have lower serum uric acid levels than expected. In our patient, a renal defect in tubular reabsorption of uric acid appears responsible for hypouricemia. The apparent association of hemochromatosis and hypouricemia deserves further investigation.

The Biological and Clinical Activity of Anti-Malarial Drugs In Autoimmune Disorders

Chloroquine and hydroxychloroquine are 4-aminoquinoline compounds commonly employed as anti-malarial drugs. Chloroquine and its synthetic analogue, hydroxychloroquine also belong to the disease-modifying anti-rheumatic drug class because these drugs are immunosuppressive. The immunosuppressive activity of chloroquine and hydroxychloroquine is likely to account for their capacity to reduce T-cell and B-cell hyperactivity as well as pro-inflammatory cytokine gene expression. This review evaluated experimental and clinical trials results as well as clinical response data relative to the use of chloroquine and/or hydroxychloroquine as first-line medical therapies in systemic lupus erythematosus, rheumatoid arthritis, primary Sjogrens syndrome, the anti-phospholipid syndrome and in the treatment of sarcoidosis. A primary outcomes measure in these clinical trials was the extent to which chloroquine and/or hydroxychloroquine reduced disease progression or exacerbations and/or the use and dosage of corticosteroids. The relative efficacy of chloroquine and hydroxychloroquine in modifying the clinical course of these autoimmune disorders is balanced against evidence that these drugs induce adverse effects which may reduce their use and effectiveness in the therapy of autoimmune disorders.