Treatment of Histoplasmosis Caused by Histoplasma capsulatum
For histoplasmosis treatment, liposomal amphotericin B (3.0 mg/kg daily) is recommended for 1-2 weeks for moderately severe to severe disease, followed by oral itraconazole (200 mg three times daily for 3 days, then 200 mg twice daily) for a total of at least 12 months, while mild-to-moderate disease can be treated with itraconazole alone for 12 months. 1
Treatment Algorithm Based on Disease Severity
Severe Disease
- Initial therapy: Liposomal amphotericin B 3.0 mg/kg daily IV for 1-2 weeks 1
- Follow-up therapy: Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for a total of at least 12 months 1
- Adjunctive therapy: Consider methylprednisolone 0.5-1.0 mg/kg daily IV for 1-2 weeks in patients with respiratory complications 3
Mild-to-Moderate Disease
- Primary therapy: Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for at least 12 months 1
- Alternative: For symptoms persisting >4 weeks but not severe enough for amphotericin B, itraconazole 200 mg once or twice daily for 6-12 weeks 1
Special Considerations
Immunocompromised Patients
- Lifelong suppressive therapy with itraconazole 200 mg daily may be required if immunosuppression cannot be reversed 1
- In HIV/AIDS patients, antiretroviral therapy should not be withheld due to concerns about immune reconstitution inflammatory syndrome 1
- For patients on TNF-α blockers, discontinuation of immunosuppression during treatment is recommended 4
Monitoring During Treatment
- Blood levels of itraconazole should be obtained to ensure adequate drug exposure (target >1 μg/mL) 1, 3
- Antigen levels should be measured during therapy and for 12 months after therapy ends to monitor for relapse 1, 3
- Liver enzymes should be monitored before therapy and at 1,2, and 4 weeks, then every 3 months due to risk of hepatotoxicity 3
Disease-Specific Considerations
Chronic Pulmonary Histoplasmosis
- Itraconazole 200 mg once or twice daily for at least 12 months 1
- Relapse occurs in approximately 15% of cases 1
Pericarditis
- Nonsteroidal anti-inflammatory agents for mild cases 1
- For moderate-severe cases: Prednisone 0.5-1.0 mg/kg daily in tapering doses over 1-2 weeks plus itraconazole 200 mg once or twice daily for 6-12 weeks 1
Mediastinal Lymphadenitis
- Mild symptoms <4 weeks: No treatment needed 1
- Symptoms warranting corticosteroids: Prednisone 0.5-1.0 mg/kg daily in tapering doses over 1-2 weeks plus itraconazole 200 mg once or twice daily for 6-12 weeks 1
- Symptoms ≥4 weeks: Itraconazole 200 mg once or twice daily for 6-12 weeks 1
Common Pitfalls and Caveats
Unnecessary treatment: Most immunocompetent patients with acute pulmonary histoplasmosis recover without therapy within a few weeks 1, 3
Drug interactions: Itraconazole has numerous drug interactions that can affect efficacy 3
- Requires gastric acidity for absorption
- Should be taken with food or cola drinks
- Avoid antacids, H2 blockers, and proton pump inhibitors
Renal impairment: In patients with severe disease and renal impairment, continue liposomal amphotericin B rather than switching to azoles prematurely, as the poor prognosis justifies using the most effective therapy 1
Resumption of immunosuppressive therapy: For patients on TNF-α blockers, resumption appears safe after appropriate antifungal therapy for at least 12 months 4
Histoplasmomas: Antifungal agents have no effect on histoplasmomas (pulmonary nodules) and there is no evidence that these contain viable organisms 1
The treatment approach to histoplasmosis should be guided by disease severity, patient immune status, and specific organ involvement, with careful monitoring of drug levels and treatment response to ensure optimal outcomes and prevent relapse.