What is the recommended treatment for histoplasmosis?

Treatment of Histoplasmosis

The treatment of histoplasmosis should be tailored based on disease severity, with lipid formulation of amphotericin B (3.0-5.0 mg/kg daily IV) or amphotericin B deoxycholate (0.7-1.0 mg/kg daily) for 1-2 weeks as initial therapy for severe disease, followed by itraconazole (200 mg twice daily) to complete 12 weeks of treatment, while mild-to-moderate disease can be treated with itraconazole alone. 1

Treatment Based on Disease Severity

Severe or Moderately Severe Disease

• Lipid formulation of amphotericin B (3.0-5.0 mg/kg daily IV) or amphotericin B deoxycholate (0.7-1.0 mg/kg daily) for 1-2 weeks as initial therapy 1
• Liposomal amphotericin B has demonstrated higher response rates (88% vs 64%) and lower mortality (2% vs 13%) compared to amphotericin B deoxycholate in patients with AIDS and progressive disseminated histoplasmosis 2, 1
• After clinical improvement, transition to itraconazole 200 mg twice daily to complete a total of 12 weeks of treatment 1
• Methylprednisolone (0.5-1.0 mg/kg daily IV) during the first 1-2 weeks may be beneficial for patients who develop respiratory complications, hypoxemia, or significant respiratory distress 2, 1

Mild to Moderate Disease

• Itraconazole 200 mg once or twice daily for 6-12 weeks is the preferred treatment 2, 1
• For patients with symptoms lasting less than 4 weeks, treatment may be unnecessary as the condition is often self-limited 2, 1
• Voriconazole should be avoided as it has been associated with increased mortality in the first 42 days compared to itraconazole (HR 4.30,95% CI 1.3-13.9) 3

Specific Clinical Presentations

Chronic Cavitary Pulmonary Histoplasmosis

• Itraconazole 200 mg once or twice daily for at least 12 months 1
• Blood levels of itraconazole should be monitored after at least 2 weeks of therapy to ensure adequate drug exposure 2, 1
• Relapse occurs in approximately 15% of cases, requiring careful follow-up 1

Pericarditis

• Nonsteroidal anti-inflammatory therapy is recommended in mild cases 2
• Prednisone (0.5–1.0 mg/kg daily, maximum 80 mg daily) in tapering doses over 1–2 weeks for patients with hemodynamic compromise 2
• Pericardial fluid removal is indicated for patients with hemodynamic compromise 2
• Itraconazole (200 mg 3 times daily for 3 days, then once or twice daily for 6–12 weeks) if corticosteroids are administered 2

Mediastinal Lymphadenitis

• Treatment is usually unnecessary for uncomplicated cases 2
• Itraconazole (200 mg 3 times daily for 3 days, then 200 mg once or twice daily for 6–12 weeks) for patients requiring corticosteroids or with symptoms persisting >1 month 2
• Prednisone (0.5–1.0 mg/kg daily, maximum 80 mg daily) in tapering doses for severe cases with obstruction or compression of contiguous structures 2

Monitoring and Follow-up

• Hepatic enzyme levels should be measured before starting azole therapy and at 1,2, and 4 weeks, then every 3 months during treatment 1
• Itraconazole blood levels should be monitored in cases of suspected treatment failure, concerns about absorption, drug interactions, or when adjusting dosage 1
• Chest radiographs should show resolution of pulmonary infiltrates before antifungal therapy is discontinued 2

Common Pitfalls and Caveats

• Itraconazole capsules require high gastric acidity for absorption and should be taken with food or a cola drink 1
• Patients receiving antacids, H2 blockers, or proton pump inhibitors should not use itraconazole capsules due to decreased absorption 1
• Treatment is not indicated for asymptomatic patients with healed histoplasmosis manifestations such as pulmonary nodules, mediastinal lymphadenopathy, or calcified splenic lesions 2, 1
• Presumed ocular histoplasmosis syndrome does not respond to antifungal therapy 2, 1
• For patients on TNF-α blocker therapy who develop histoplasmosis, the immunosuppressive therapy should be discontinued initially and may be safely resumed after at least 12 months of antifungal treatment 4