Aspirin-induced hepatic dysfunction in a patient with adult rheumatoid arthritis

A patient with classical rheumatoid arthritis receiving high doses of aspirin developed significant elevation of serum glutamic oxaloacetic transaminase. This patient had recently been on phenylbutazone and an initial liver biopsy, at the time of elevation of the transaminase revealed nonspecific mild fatty infiltration of the liver compatible with the pathology seen with rheumatoid disease. Because of the severity and activity of her rheumatoid arthritis, and thus the need to know whether aspirin was the etiologic factor in liver dysfunction, the patient was challenged with aspirin. SGOT elevation occurred after a 4-6 day lag period, which promptly remitted when salicylates were discontinued. A liver biopsy at this time revealed evidence for degeneration, regeneration, and mild focal mononuclear infiltration. Although previous reports note salicylate-related hepatocellular dysfunction in patients with systemic lupus erythematosus and juvenile rheumatoid arthritis, these data clearly demonstrate the relationship of ASA to liver dysfunction in a patient with adult onset rheumatoid arthritis. This histologic picture as well as the clinical course of this patient's hepatic abnormality suggest a toxic rather than hypersensitivity etiology for this syndrome.     

The use of exhaled carbon monoxide for the diagnosis of carbon monoxide poisoning. A case report

Antigliadin antibodies (AGA) mark celiac disease, but AGA are also encountered in IgA-nephritis, psoriasis, sickle-cell anemia, hepatic disorders, juvenile rheumatoid arthritis, autoimmune thyroidism and in persons who occupationally contact great amounts of wheat. AGA IgA and/or IgG were registered in 19 of 60 subjects (51 adults and 9 children) with various immunomediated diseases without symptoms of celiac disease: in 4 cases of chronic active hepatitis, in 2 of 4 cases of chronic persistent hepatitis, in 4 of 16 cases of rheumatoid arthritis, in 3 of 19 cases of IgA-deficiency, in 1 of 8 cases of SLE, in 2 cases of postvaccine reaction, in all the single cases of juvenile rheumatoid arthritis, focal scleroderma, macroglobulinemia. IgA only occurred in in 6 patients, IgG- in 6 patients, both IgA and IgG in 7 patients. The most pronounced positive reaction to AGA was recorded in 8-year-old girl with juvenile rheumatoid arthritis. The emergence of AGA in immunomediated diseases may be attributed to the response to food protein in pathological conditions and is often unrelated closely with celiac disease.     

Antibiotic therapy for rheumatoid arthritis. Scientific and anecdotal appraisals

Minocycline is arguably the most interesting new drug for rheumatoid arthritis since the development of methotrexate. Tetracycline compounds have long been used by rheumatologists who were considered mavericks by their peers, and recent controlled studies have demonstrated their antirheumatic activity. The reason that minocycline works is unclear, and their niche in the treatment of rheumatoid arthritis remains to be established. Nonetheless, it is clear that some patients with rheumatoid arthritis respond favorably to this form of treatment.     

Diagnosis and treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic, inflammatory, connective-tissue disease that has well-defined clinical and laboratory characteristics. The management of rheumatoid arthritis requires an aggressive multidisciplinary treatment combining both pharmacologic and nonpharmacologic measures. Using this approach, most patients with rheumatoid arthritis can maintain their functional capacity while having their pain and suffering relieved.     

Do minocycline and other tetracyclines have a place in rheumatology?

Tetracyclines are a family of antimicrobials with activity against a broad range of organisms including those that develop intracellularly. Links have been reported between some infections and some inflammatory joint diseases, with the most notable example involving mycoplasmas and rheumatoid arthritis. Reactive arthritides are known to be triggered by organisms found in the gastrointestinal or genitourinary tract, and antigenic material from these organisms has recently been demonstrated in synovial tissue from patients with reactive arthritis. These facts led to the hypothesis that tetracyclines may be useful in rheumatoid arthritis and reactive arthritis. Two controlled studies found that minocycline benefited rheumatoid arthritis patients when it was given either as an adjunct to another second-line treatment or as the only slow-acting drug. Lymecycline has been found to expedite recovery from reactive arthritis due to Chlamydia trachomatis, and tetracycline to decrease the incidence of reactive arthritis due to sexually-transmitted diseases. The safety profiles of these treatments were acceptable in all available studies but require further investigation during long-term administration. The benefits may be related to the immunomodulating effects of tetracyclines and/or to their ability to inhibit metalloproteases such as collagenases. Whether tetracycline therapy influences the course of radiologic lesions in rheumatoid arthritis remains unknown. However, minocycline therapy has given sufficient proof of its efficacy to make it an attractive alternative in rheumatoid arthritis.     

Contact allergy to gold and gold therapy in patients with rheumatoid arthritis

Patients with rheumatoid arthritis were investigated for contact allergy to gold in connection with treatment with gold preparations. There were 57 patients with rheumatoid arthritis previously treated with gold, with or without cutaneous side-effects, as well as 20 patients intended for such treatment; all were exposed to patch and intradermal tests with gold sodium thiosulfate, gold sodium thiomalate and auranofin. Contact allergy to gold was demonstrated in 8 out of 77 patients (10.4%). In the retrospective material, gold allergy was found in 1.8%, in the prospective material in 35.0%. Contact allergy to gold is very frequent among patients with rheumatoid arthritis before gold therapy. In order to avoid early hypersensitivity reactions skin tests should be carried out before gold therapy is instituted.     

Rheumatologic view of the rheumatoid foot

Rheumatoid arthritis is a common systemic disease that affects between 0.3% and 1.5% of the general population worldwide. In 1988, it was estimated by the National Arthritis Foundation that there were 4 to 6 million cases of rheumatoid arthritis in the United States. There is general agreement that the feet are a major source of pain and disability at some point in the course of the illness. The frequency of involvement of the feet among 1000 patients with rheumatoid arthritis studied by Vainio was 91% in females and 85% in males. The clinical features and pathogenesis of the rheumatoid foot and an approach to initial nonsurgical treatment will be discussed.     

Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents

Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.     

Methotrexate hepatotoxicity

Hepatoxicity is a major adverse reaction that can occur during methotrexate treatment of the rheumatic diseases. The pathologic lesions are nonspecific and the pathogenesis is poorly understood. Early studies in psoriasis clearly established a relationship between hepatic injury and several risk factors, particularly alcohol use. Methotrexate hepatoxicity occurs less frequently in rheumatoid arthritis than previously reported in psoriasis patients. Consequently, the American College of Rheumatology guidelines for methotrexate monitoring do not recommend baseline and surveillance liver biopsies in low-risk patients. These guidelines seem to be useful and cost-effective.     

Familial occurrence of two patients with malignant rheumatoid arthritis

In Japan, patients with rheumatoid arthritis associated with severe extra-articular manifestations due to vasculitis are diagnosed as having malignant rheumatoid arthritis. We report the occurrence of two cases of malignant rheumatoid arthritis in a Japanese family. Both patients, a father and son, expressed HLA-DR4 (Dw15), and were infected with Epstein-Barr virus. Moreover, the father developed malignant rheumatoid arthritis during reactivation of the Epstein-Barr virus. An unaffected male family member with the same HLA haplotypes was not infected by the virus. The possible role of the virus infection in the pathogenesis of malignant rheumatoid arthritis in a genetically susceptible family is discussed.     

Fullerene lipids: synthesis of dialkyl 1,2-[6,6]-methano-[60]-fullerene dicarboxylate derivatives

OBJECTIVE: To determine the prevalence of chronic arthritis with special reference to rheumatoid arthritis. METHOD: A cross-sectional study was performed during the years 1990 and 1991 in a randomly selected sample of the urban population of Belgrade. RESULTS: Out of 2184 participants, > or = 20 yr old, surveyed by questionnaire, 756 (34.6%) reported peripheral joint complaints. Of those with complaints, 621 (82.1%) agreed to undergo detailed examination. Arthritis was diagnosed in four men (one had rheumatoid arthritis and three had spondylarthropathy with peripheral arthritis) and 11 women (three had rheumatoid arthritis, one had B27-positive polyarthritis and seven had undifferentiated chronic arthritis). The prevalence of chronic arthritis in the adult population was 0.69% (0.35% for men and 1.05% for women). The prevalence for rheumatoid arthritis was 0.18% (0.09% for men and 0.29% for women). Re-examination of 15 individuals with chronic arthritis 3 yr later showed changes in diagnosis only in those patients who at baseline examination had undifferentiated chronic arthritis. CONCLUSION: According to the results obtained, the urban population of Belgrade is among populations with a low prevalence of rheumatoid arthritis.     

Diagnosis of early rheumatoid polyarthritis

The diagnosis of rheumatoid arthritis is mainly based on the clinical findings showing in typical cases a bilateral symmetrical polysynovitis predominantly on the small hand and feet joints, without any other extra-rheumatological feature. Even this clinical presentation is very suggestive of the diagnosis, other diagnoses of diseases life and or function threatening (septic arthritis, viral arthritis, arthritis related to hemopathy, systemic vasculitis ...) have to be systematically evocated. The interest of an early diagnosis of rheumatoid arthritis is to facilitate the treatment and the monitoring of the patients since such treatment seems to be more efficient when initiated at an early stage of the disease.     

Inflammation and bone metabolism in rheumatoid arthritis. Pathogenetic viewpoints and therapeutic possibilities

BACKGROUND: Systemic osteoporosis is a common and pathogenetically heterogenous complication in rheumatoid arthritis. Various factors such as disease activity, dosage and duration of glucocorticoid treatment and immobilization are involved in pathogenesis of osteoporosis in rheumatoid arthritis. INFLAMMATION AND BONE METABOLISM: Proinflammatory cytokines secreted by immunocompetent cells have a role in the regulation of the activity of osteoblasts and osteoclasts. The effects of these proinflammatory cytokines include the inhibition of bone formation and an increase in bone resorption. Interleukin-6 and nitric oxide induced in osteoblasts by proinflammatory cytokines are likely to be important mediators between these cytokines and the function of osteoblasts and osteoclasts. Furthermore, disease activity dependent changes in the secretion of glucocorticoids and in vitamin D metabolism may be involved in the pathogenesis of osteoporosis in this disease. Alteration of bone remodeling associated with immobilization is an important factor of systemic bone loss in rheumatoid arthritis. CONCLUSION: The inflammatory process in rheumatoid arthritis may cause penarticular and systemic bone loss by various cytokine and hormone mediated mechanisms. Concluding from these pathogenetic mechanisms, bisphosphonates and active vitamin D metabolites are likely to be effective therapeutic options in osteoporosis associated with rheumatoid arthritis.     

Rheumatoid arthritis improved by treatment with levamisole and L-histidine

A case of classical rheumatoid arthritis of 12 years' duration, was treated during an exacerbation with levamisole and remission was induced. The findings support the postulate that depressed cell-mediated immunity to an unknown antigen is the primary immunity defect in rheumatoid arthritis, and that the defence mechanism stimulant levamisole is an effective treatment, at least in some cases. The lack of toxicity of the drug is noted, but in this case the blood aspirin level rose while the patient was taking levamisole with an unaltered dose of aspirin. There was some depression of the neutrophil count after five months which responded to a reduced dosage.     

Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthritis

We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis. His symptoms began at the age of 44 with pain of the hand joints, shoulders, hips, and knees and a positive rheumatoid factor. Four years later, he required replacement of both hips due to severe hip arthritis. Abnormalities in liver function were noted early on, but they were attributed to infection with the hepatitis C virus, detected serologically and by polymerase chain reaction amplification in the blood. The correct diagnosis was delayed until a decision to use methotrexate as treatment for his arthritis led to a liver biopsy, which revealed increased iron deposition consistent with hemochromatosis, confirmed by genetic testing, which revealed that the patient was homozygous for the C282Y mutation of the HLA-H gene.     

The use of Neoral in rheumatoid arthritis

Neoral (a microemulsion-based formulation) is an immunomodulator that possesses a more predictable and improved absorption than the conventional oral formulation (Sandimmun). The increased bioavailability of Neoral could result in improved efficacy. The pharmacokinetics of cyclosporin and efficacy of cyclosporin in rheumatoid arthritis are reviewed in this article. Current guidelines for the use of Neoral in the treatment of rheumatoid arthritis patients are outlined.     

Cyclosporin A--effects and side effects in the treatment of rheumatoid and psoriatic arthritis (author's transl)

The treatment of rheumatoid arthritis and psoriatic arthritis with cyclosporin A is described. Cyslosporin A is a new selective immunosuppressant which acts primarily on the T lymphocytes. It has already been shown to be effective in preventing rejection following kidney transplantation as well as in preventing graft-versus-host disease. In rheumatoid and psoriatic arthritis, however, its effect was not satisfactory, although rather different in the two conditions; overall only about one third of the patients showed any marked improvement. By contrast, and for reasons which are as yet unexplained, it had a beneficial effect on the cutaneous symptoms of psoriasis. Cyclosporin A had little effect on immune parameters. Side effects--mainly kidney toxicity, gastro-intestinal reactions and hirsutism--were common but reversible. On present evidence its principal indication among rheumatological diseases would seem to be as a treatment for severe, intractable psoriatic arthritis.     

Rheumatoid nodules of the larynx

A 67-year-old woman with rheumatoid arthritis was hospitalized because of dysphagia and severe nodulosis. Over a two-year period the patient had been treated with methotrexate. A computed tomography (CT) scan of the neck showed a 2 x 2 cm large tumour behind the top left lateral thyroid cartilage. A biopsy taken during direct laryngoscopy showed it was a rheumatic nodule. Treatment with colchicine reduced the patient's dysphagia. As methotrexate is used increasingly in the treatment of rheumatoid arthritis and as this particular drug causes rheumatic nodules in five to 10 per cent of the patients, it must be foreseen that the incidence of nodules in the upper airways will increase.     

Immunoglobulin E-rheumatoid factor in the serum of patients with rheumatoid arthritis, asthma, and other diseases

A solid-phase radioimmunoassay was developed to detect immunoglobulin (Ig)E antibodies that bound to human IgG. IgE-rheumatoid factor activity was found in the serum of 18 of 20 patients with seropositive rheumatoid arthritis, 1 of 4 patients with seronegative rheumatoid arthritis, 3 of 32 patients with seronegative rheumatoid arthritis, 3 of 32 patients with asthma, and in 1 patient with hypocomplementemic vasculitis and iodide sensitivity. Immunopathologic implications of IgE-rheumatoid factor are discussed.