Alpha-methyldopa-induced systemic vasculitis confused with Wegener's granulomatosis.

To the Editor: Alpha-methyldopa was introduced as an antihypertensive drug in 1960. Side effects of its administration have included dry mouth, fever, gastrointestinal upset, positive results on antinuclear antibody (ANA) tests and lupus erythematosus cell preparations, granulocytopenia and thrombocytopenia, positive direct Coombs’ test results, hemolytic anemia, and serious hepatic injury ( I ,2). We report a case of acute hepatic injury and systemic granulomatous disease mimicking Wegener’s granulomatosis (WG) occurring I 1 days after initiation of therapy with alpha-methyldopa for essential hypertension. The patient, a 48-year-old white man, experienced the sudden onset of migratory rnyalgias, fatigue, nightly fevers (103°F orally), and drenching night sweats. One week later, symptoms of arthritis developed-swelling and stiffness of the wrists, fingers, and knees, as well as bilateral conjunctival injection. These symptoms occurred 11 days after methyldopa (250 mg twice daily orally) was substituted for the previous regimen of hydrochlorothiazide and atenolol to improve blood pressure control; they persisted for 6 weeks after the methyldopa therapy was discontinued. For the preceding 2 years, the patient had also been taking allopurinol(lO0 mg twice daily orally) for hyperuricemia and presumed gout. In the subsequent 3 weeks, the patient experienced a 5-lb weight loss, worsening vision, frontal and occasionally bitemporal headache, and an erythematous, macular, nonpruritic rash on the trunk, which faded after 10 days. At the time of hospitalization, the methyldopa was discontinued because “adequate blood pressure control” had been achieved. Physical examination revealed the truncal rash as well as a liver span of 20 cm in the midclavicular line. Bilateral scleral and corneal ulcerations were seen. The pupils were dilated to 6 7 mm and unresponsive to light. There was anesthesia of the cornea, nasal vestibules, and labial folds. Laboratory evaluation revealed a mild anemia. Liver enzymes were elevated up to 6 times normal levels. Urinalysis and renal function test results were normal. Total hemolytic complement was profoundly decreased. Westergren erythrocyte sedimentation rate was 76 mm/hour. Results of a VDRL test, Monospot test, tests for ANA and rheumatoid factor, as well as bacterial, viral, fungal, and mycobacterial cultures of blood, bone marrow, liver, sputum, and stool were negative. Results of a chest radiograph were normal. Computed tomography of the head revealed only a mucous retention cyst in the right maxillary sinus. A temporal artery biopsy specimen was normal. A random nasal biopsy from the right medial turbinate (which healed well) revealed necrotizing granulomatous inflammation with vasculitis. Liver biopsy showed necrosis and granulomatous inflammation with widespread hepatocyte dropout (Figure 1) . The patient was diagnosed as having WG and was transferred for initiation of immunosuppressive therapy. However, it was decided instead to observe the patient before beginning this treatment, and during the next 3 Figure 1. Liver biopsy specimen from a patient with alphamethyldopa-induced systemic vascu!itis. There are wide areas of hepatocyte dropout. Focally, neutrophils are admixed with epithelioid cells (hematoxylin and eosin stained. original magnification x 250).