What are the treatment guidelines for histoplasmosis?

Histoplasmosis Treatment Guidelines

Treatment of histoplasmosis should be based on disease severity, with liposomal amphotericin B for severe disease followed by itraconazole, while itraconazole alone is appropriate for mild to moderate disease. 1

Treatment Approach by Disease Severity

Severe/Moderately Severe Acute Pulmonary Histoplasmosis

• First-line therapy: Lipid formulation of amphotericin B (3.0-5.0 mg/kg daily IV) for 1-2 weeks 2, 1
  • Liposomal amphotericin B is preferred due to higher response rates and lower mortality 2
  • Alternative: Amphotericin B deoxycholate (0.7-1.0 mg/kg daily) for patients at low risk for nephrotoxicity 2, 3
• Follow-up therapy: Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for a total of 12 weeks 2, 1
• Adjunctive therapy: Methylprednisolone (0.5-1.0 mg/kg daily IV) during first 1-2 weeks for patients with respiratory complications, including hypoxemia 2

Mild to Moderate Acute Pulmonary Histoplasmosis

• Symptoms <4 weeks: Treatment usually unnecessary 2
• Symptoms ≥4 weeks: Itraconazole 200 mg once or twice daily for 6-12 weeks 2

Chronic Cavitary Pulmonary Histoplasmosis

• Itraconazole 200 mg once or twice daily for at least 12 months (some prefer 18-24 months due to relapse risk) 2, 1
• Monitor blood levels of itraconazole after 2 weeks to ensure adequate drug exposure (target >1 μg/mL) 2, 1

Progressive Disseminated Histoplasmosis

• Severe disease: Lipid formulation of amphotericin B (3.0-5.0 mg/kg daily) for 1-2 weeks, followed by itraconazole 2, 1
• Mild to moderate disease: Itraconazole 200 mg twice daily for 6-18 months 1, 4
• Immunocompromised patients: Lifelong suppressive therapy with itraconazole 200 mg daily if immunosuppression cannot be reversed 1, 5

Special Clinical Manifestations

Pericarditis

• Mild cases: Nonsteroidal anti-inflammatory therapy 2
• Severe cases: Prednisone (0.5-1.0 mg/kg daily, maximum 80 mg daily) in tapering doses over 1-2 weeks 2
• With hemodynamic compromise: Pericardial fluid removal indicated 2
• If corticosteroids used: Add itraconazole (200 mg once or twice daily for 6-12 weeks) 2

Mediastinal Lymphadenitis

• Usually: Treatment unnecessary 2
• With symptoms warranting corticosteroids: Prednisone (0.5-1.0 mg/kg daily) in tapering doses over 1-2 weeks plus itraconazole 2
• Symptoms ≥4 weeks: Itraconazole (200 mg once or twice daily for 6-12 weeks) 2

Mediastinal Granuloma

• Asymptomatic: No treatment needed 2
• Symptomatic: Itraconazole (200 mg once or twice daily for 6-12 weeks) 2
• Surgery may be required to relieve obstruction 2

Mediastinal Fibrosis

• Antifungal treatment not recommended (ineffective) 2

Monitoring During Treatment

• Itraconazole levels: Check after 2 weeks of therapy (target >1 μg/mL) 1
• Liver enzymes: Monitor before therapy and at 1,2, and 4 weeks, then every 3 months 1
• Antigen levels: Monitor during therapy and for 12 months after completion 1
• Drug interactions: Itraconazole has numerous drug interactions; avoid antacids, H2 blockers, and proton pump inhibitors 1
• Administration: Take itraconazole capsules with food or cola drinks to enhance absorption 1

Important Considerations

• Relapse occurs in approximately 15% of cases, particularly in immunocompromised patients 1
• Most immunocompetent patients with acute pulmonary histoplasmosis recover without therapy 1, 6
• Amphotericin B should not be used to treat noninvasive fungal infections 3
• Never exceed total daily dose of 1.5 mg/kg of amphotericin B due to risk of fatal cardiac or cardiopulmonary arrest 3
• Fluconazole (200-800 mg daily) may be considered for patients who fail or cannot tolerate itraconazole, but has lower efficacy (70% response rate) 2, 1

By following these evidence-based guidelines, clinicians can optimize outcomes for patients with histoplasmosis while minimizing treatment-related complications.