Publication

Abstract : Histoplasmosis is a systemic mycosis which has a worldwide distribution. In India disseminated histoplasmosis has been reported from various parts of the country [1, 2]. Humans are infected by inhalation of microconidia and mycelial fragments of H. capsulatum [3]. Disease manifestation can vary from completely asymptomatic, self limited infection in immunocompetent individuals to highly fatal progressive disseminated histoplasmosis in patients receiving immunosuppresive agents, infected with HIV, or in extremes of age [4, 5]. Cell mediated immunity is critical for the control of proliferation and dissemination of histoplasma. Though common in immunocompromised patients, disseminated histoplasmosis has rarely been reported in patients with aplastic anemia. We report here a case of very severe aplastic anemia who developed disseminated histoplasmosis in the form of hepatic involvement, which proved fatal due to lack of cell mediated immunity. A 4-years-old boy, who had been diagnosed as a case of very severe aplastic anemia 2 months ago, was admitted with febrile neutropenia. He had pulse rate 130/min, respiratory rate 24/min and temperature of 38.5 C. Chest examination revealed bilateral crepitations, and abdominal examination revealed tender liver palpable 3 cm below right costal margin. Hemogram showed hemoglobin 8.2 g/dl, total leukocyte count 0.18 9 109/l, absolute neutrophil count 0.03 9 109/l, platelet count 25 9 109/l and prothrombin time 14 s (control 13 s). His total bilirubin was 1.1 mg/dl and alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were 62/58/840 IU/l, respectively. Lactate dehydrogenase was 640 U/l (normal value: 100–240 U/l). He was started on empirical antibiotics for febrile neutropenia. Blood and urine cultures were sterile. Chest X-ray showed bilateral pneumonitis. Thoraco-abdominal computed tomography (CT) revealed bilateral lower lobe consolidations and two well circumscribed large focal lesions in the liver (measuring 4 9 4 cm and 4 9 5 cm, respectively)(Fig. 1). Ultrasound guided liver biopsy showed Histoplasma capsulatum (Fig. 2). Considering disseminated histoplasmosis, the patient was started on liposomal amphotericin B 3 mg/kg/day alongwith injection Granulocyte-Colony Stimulating Factor (G-CSF, 5 mg/kg/day) and supportive treatment with blood and platelet transfusions. Voriconazole (6 mg/kg/day for 1 day followed by 4 mg/kg/day) was added on day 7 of liposomal amphotericin B as he continued to have high grade fever. G-CSF was stopped as there was no response after 7 days. Follow-up CT scan of chest and abdomen after 30 days showed partial resolution of pneumonitis and 60% reduction in liver lesions (Fig. 3). Inspite of radiological regression in lesions, the patient continued to have high grade fever and succumbed to febrile neutropenia on day 40.