We describe three patients with RA who developed cirrhosis while taking low dose methotrexate (MTX). This report includes a review of the risk factors for cirrhosis occurring in association with MTX. Two of these patients were part of a prospective study to quantify changes in pericellular and total collagen in 76 patients with RA receiving low dose pulse MTX, giving a point prevalence of cirrhosis of 2.63%.
To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study.
Four cases of pancytopenia related to low-dose weekly pulse methotrexate therapy for rheumatoid arthritis are described. All patients were aged above 60 years and had renal impairment. In every case marrow recovery followed withdrawal of methotrexate. However, one patient developed pneumonitis and died. Cholangitis, respiratory infection and increase in methotrexate dose were precipitating factors. Pharmacokinetic data indicated prolonged tissue drug exposure in two cases studied; dose-related toxicity was further supported by successful resumption of methotrexate in reduced dosage in two cases. It is possible that methotrexate dose should be modified during intercurrent illness in patients older than 60 years who have renal impairment.
The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression.
Aortic root abnormalities including cusp thickening, subvalvular stenosis, and mild aortic root dilatation are the most common cardiac complications in patients with long standing ankylosing spondylitis (AS). Twenty-three patients with definite idiopathic AS (New York Criteria 1966) and twenty-two matched controls were studied with M-mode echocardiography. Only one of the AS patients had clinical aortic incompetence. Six of the AS patients had mildly dilated aortic roots (normal less than 3.7 cm) with a mean diameter of 3.9 cm (range 3.8 to 4.00 cm). None of the twenty-two controls matched for age, sex and blood pressure had dilated aortic roots, with a mean diameter of 3.3 cm (range 2.9 to 3.6 cm). No correlation existed between aortic dilatation and severity of disease estimated by acute phase proteins--caerulo plasmin, alpha 1-antitrypsin, alpha 1 acid glycoprotein, ferritin and C Reactive protein. Contrary to a previous report, mild aortic root dilatation occurs in long standing cases of AS. Although it is a non-specific finding, it does not appear to be related to age or blood pressure and may therefore be the forerunner of aortic incompetence.
Forty patients with arthritis (26 rheumatoid and 14 osteoarthrosis) entered a five-week double-blind crossover trial of diclofenac and ibuprofen. Four patients failed to complete the 10-week trial. There was no statistically significant difference in parameters of disease activity for the rheumatoid arthritis patients, but patients with osteoarthrosis fared significantly better on diclofenac. There was a low incidence of side effects on both regimens.