Disseminated Histoplasmosis Following Prolonged Low-Dose Methotrexate Therapy
To the Editor: A 43-year-old woman from central Minnesota presented to her primary internist with a 4-month history of weight loss and abdominal distension and a 2-week history of fevers, sweats, weakness, and anorexia. She was receiving treatment with low-dose methotrexate (15 mg every week) for the last 5 years for rheumatoid arthritis. Splenomegaly was noted on examination. Her hemoglobin was 11.5 g/dl, leukocyte count (WBC) was 3.2 ร 10 9 /l, and platelets were 115 ร 10 9 /l. Routine liver and renal function tests were normal. Bone marrow biopsy showed normocellular marrow with normal trilineage hematopoiesis. A diagnosis of felty's syndrome was made, and treatment with prednisone, 60 mg per day, was started. Her symptoms continued to progress. She was referred to the University of Minnesota for a second opinion 2 weeks later. On examination weight loss, splenomegaly (25 cm below the costal margin), and ascites was noted. Her pancytopenia had progressed: hemoglobin, 8.2 g/dl; WBC, 1.8 ร 10 9 /l (56% neutrophils); platelets, 49 ร 10 9 /l; and reticulocyte count, 10%. Serum albumin was 2.1 g/dl, bilirubin 2.2 mg/dl, AST 81 (n โซืกโฌ 0-50 U/l), ALT 44 (n โซืกโฌ 0-50 U/l), alkaline phosphatase 117 (n โซืกโฌ 50-120 U/l), creatinine 0.9 mg/dl, and lactate dehydrogenase 1110 (n โซืกโฌ 275-645 U/l). Abdominal CT scan confirmed massive splenomegaly and ascites without hepatomegaly or adenopathy. Over the next 6 days, her hemoglobin further dropped and evidence of disseminated intravascular coagulation appeared. Bone marrow examination showed multiple granulomata and numerous intracellular yeastlike organisms within the macrophages suggestive of Histoplasma (Fig. 1).
Intravenous amphotericin B was begun, and splenectomy was performed the next day. Histopathological examination of spleen, lymph glands from the splenic hilum, and an intra-operative liver biopsy showed extensive granulomata with intracellular yeastlike inclusions. Cultures of the biopsied material yielded Histoplasma capsulalum. A test for human immunodeficiency virus (HIV) antibodies was negative. The patient received a total of 2 g of amphotericin B as an outpatient and made an uneventful recovery.