Drug-induced syndrome is very rare; only one case has been reported [1]. We describe another case.

A 69-year-old woman was admitted with upper gastrointestinal bleeding. Her current medications included labetolol, amlodipine, warfarin, dypyridamole, and ramipril. Ramipril therapy had been introduced about 3 weeks before admission. Results of physical examination were normal except for skin bruises. The leukocyte count was 9800 cells/mm³, the hemoglobin level was 10.7 g/dL, and the platelet count was 3000 cells/mm³ (14% eosinophils and no platelet clumping or schistocytes). Prothrombin time, activated partial thromboplastin time, fibrinogen level, and fibrinogen degradation product level were all normal. The serum creatinine level was 0.9 mg/dL, the lactate dehydrogenase level was 924 IU/L, and no protein was present in the urine. Results of direct and indirect Coombs tests were positive. Bone marrow biopsy showed erythroid, eosinophilic, and megakaryocytic hyperplasia. The patient was positive for antinuclear antibody (titer, 1:5120), negative for anti-DNA antibody, positive for antihistone antibody, and negative for HIV antibody. The C3 level was normal, and the C4 level was less than 15 mg/dL.

In view of the life-threatening gastrointestinal bleeding, we initiated aggressive immunosuppressive therapy with a high-dose steroid and infusion of immunoglobulin, 1 g/kg of body weight, for 2 consecutive days. Four days later, the platelet count continued to be less than 5000 cells/mm³. We therefore added cyclosporine and discontinued ramipril therapy. Ten days later, the platelet count began to increase gradually. Steroid and cyclosporine therapy were successfully discontinued 2 months later, at which point the blood counts were normal.

Systemic lupus erythematosus was unlikely in this patient because of the lack of diagnostic criteria and negativity for anti-DNA antibody. Antihistone antibodies are more commonly seen in drug-induced autoimmune diseases [2-5]. We believe that this patient had drug-induced Evans syndrome because of the hypereosinophilia at presentation, positivity for antihistone antibodies, and the prompt improvement of hematologic indices after discontinuation of ramipril therapy. This case underscores the usefulness of antihistone antibodies in supporting the diagnosis of drug-induced autoimmune reactions. The early recognition of this condition and the prompt discontinuation of therapy with the drug can be life-saving.