Methyldopa-induced connective tissue disorder.

Several drugs are known to cause a lupus-type syndrome.1 Methyldopa causes positive anti-nuclear antibody reactions, but only two previously reported cases of a methyldopa-induced lupus-type syndrome have been described.23 We report a case of this syndrome which failed to resolve fully on withdrawal of the drug, and which has features of a mixed connective tissue disorder (MCTD). CASE HISTORY A 78-year-old woman presented in March 1985 with myalgia, arthralgia, loss of energy and postural dizziness. Drug therapy prior to admission was methyldopa 500 mg three times daily and cyclopenthiazide 500 pg daily, which she had taken for four years for 'hypertension', and naftidrofuryl oxalate 100 mg three times daily. On examination she had severe postural hypotension (supine blood pressure 140/80 mmHg, erect 80/40 mmHg), generalised muscle tenderness, marked leg oedema and ascites. The ESR was 106 mm/hour, Hb 11.7 g/dl, WCC 13.1 x 109/1 (eosinophils 2.22 x 109/1), urea and electrolytes normal, total protein 49 g/l, alkaline phosphatase 62 u/I, aspartate transaminase 28 u/I, alanine transaminase 13 u/l and gammaglutamyltransferase 5 u/l. Plasma protein electrophoresis showed generalised hypergammaglobulinaemia. Serum creatinine was 123 pmol/l, creatinine clearance 30 ml/min, urinary protein output 0.14 g/24 hours. Serum C3 and C4 complement levels were normal. Anti-nuclear antibodies (ANA) were present, titre 1: 320 (IgG class, diffuse pattern) but antibodies to double-stranded DNA and to ribonucleoprotein were negative. The chest X-ray showed a moderate right-sided pleural effusion. All her drugs were stopped and, at review one month later, her postural hypotension had resolved. The ESR was 30 mm/hour, the WCC 10.9 x 109/1 (eosinophils 0.26 x 109/1) and the total serum protein had risen to 63 g/l. The pleural effusion had resolved radiologically and the ascites had cleared. At this review, she had severe Raynaud's phenomenon and complained of 'taut, tight skin' on hands and feet. There was a violaceous rash on the extensor surfaces of elbows and knees and around the eyes suggestive of dermatomyositis. There were discrete telangiectatic areas over the hands, and the skin appeared