Progressive disseminated histoplasmosis; favorable response to ketoconazole

Four patients with disseminated histoplasmosis, two of whom had late relapses after previous therapy with amphotericin B, were treated with ketoconazole 200 to 400 mg daily for 1 year. All patients improved markedly during therapy, with resolution of symptoms decreasing liver and spleen size, and weight gain; resolution of oral ulcers occurred in the two patients in whom they were present. Decrease in serum alkaline phosphatase levels correlated well with clinical improvement. One patient who was much improved while receiving ketoconazole continued to harbor Histoplasma capsulatum in an abdominal aortic aneurysm, which became symptomatic 4 months after cessation of the drug. He underwent aneurysmectomy, and H. capsulatum isolated from the resected aneurysm was susceptible in vitro to ketoconazole. No significant adverse reactions to the drug were noted despite prolonged therapy. Our results indicate that ketoconazole may have a role in the therapy of disseminated histoplasmosis in adults.