Histoplasmosis

Introduction

Histoplasmosis is caused by inhalation of dust-borne microconidia of the dimorphic fungus Histoplasma capsulatum. In the United States, most disease is localized along the Ohio and Mississippi river valleys.

Clinical Presentation and Diagnosis

• In the vast majority of patients, low-inoculum exposure to H. capsulatum results in mild or asymptomatic pulmonary histoplasmosis. The course of disease is generally benign, and symptoms usually abate within a few weeks of onset. Patients exposed to a higher inoculum during a primary infection or reinfection may experience an acute, self-limited illness with flu-like pulmonary symptoms, including fever, chills, headache, myalgia, and nonproductive cough.
• Chronic pulmonary histoplasmosis generally presents as an opportunistic infection imposed on a preexisting structural abnormality, such as lesions resulting from emphysema. Patients demonstrate chronic pulmonary symptoms and apical lung lesions that progress with inflammation, calcified granulomas, and fibrosis. Progression of disease over a period of years, seen in 25% to 30% of patients, is associated with cavitation, bronchopleural fistulas, extension to the other lung, pulmonary insufficiency, and often death.
• In patients exposed to a large inoculum and in immunocompromised hosts, progressive illness, disseminated histoplasmosis, occurs. The clinical severity of the diverse forms of disseminated histoplasmosis generally parallels the degree of macrophage parasitization observed.
• Acute (infantile) disseminated histoplasmosis is seen in infants and young children and (rarely) in adults with Hodgkin disease or other lymphoproliferative disorders. It is characterized by unrelenting fever; anemia; leukopenia or thrombocytopenia; enlargement of the liver, spleen, and visceral lymph nodes; and GI symptoms, particularly nausea, vomiting, and diarrhea. Untreated disease is uniformly fatal in 1 to 2 months
• Most adults with disseminated histoplasmosis demonstrate a mild, chronic form of the disease. Untreated patients are often ill for 10 to 20 years, with long asymptomatic periods interrupted by relapses characterized by weight loss, weakness, and fatigue.
• Adult patients with acquired immunodeficiency syndrome (AIDS) demonstrate an acute form of disseminated disease that resembles the syndrome seen in infants and children. Progressive disseminated histoplasmosis can occur as the direct result of initial infection or because of reactivation of dormant foci.
• In most patients, serologic evidence remains the primary method in the diagnosis of histoplasmosis. Results obtained from complement fixation, immunodiffusion, and latex antigen agglutination antibody tests are used alone or in combination.
• In the AIDS patient with progressive disseminated histoplasmosis, the diagnosis is best established by bone marrow biopsy and culture, which yield positive cultures in 90% of patients.

Treatment

Asymptomatic or mildly ill patients and patients with sarcoid-like disease generally do not benefit from antifungal therapy. Therapy may be helpful in symptomatic patients whose conditions have not improved during the first month of infection.

Acute pulmonary histoplasmosis: Asymptomatic, mild or moderate or symptoms <4 weeks:

. Itraconazole (200 mg three times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks) is recommended for patients who continue to have symptoms for 11 months.

Symptoms >4 weeks: Itraconazole 200 mg once daily × 6–12 weeks.

• Amphotericin B dosages of 50 mg/day (up to 1 mg/kg per day) should be administered intravenously (IV) to a cumulative dose of 15 to 35 mg/kg (1 to 2 g) in patients who require hospitalization.
• Amphotericin B can be replaced with itraconazole 200 mg orally twice daily when the patient no longer requires hospitalization or IV therapy to complete a 12-week total course of induction therapy. In patients who do not require hospitalization, itraconazole therapy for 12 weeks can be used.