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• Histoplasmosis Return to Top

• 1. Acute pulmonary histoplasmosis:

• 1.1 Moderate severe or severe

• Preferred regimen: Lipid formulation of amphotericin B (3.0–5.0 mg/kg daily intravenously for 1–2 weeks) followed by itraconazole (200 mg 3 times daily for 3 days and then 200 mg twice daily, for a total of 12 weeks) is recommended.
• Preferred regimen (2): The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily intravenously) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity (A-III)
• Preferred regimen (3): Methylprednisolone (0.5–1.0 mg/kg daily intravenously) during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress (B-III).
• Note (1): In severe cases, cases accompanied by respiratory insufficiency, or hypoxemia, anecdotal reports [49] suggest that corticosteroid therapy may hasten recovery
• Note (2): The pulmonary infiltrates should be resolved on the chest radiograph before antifungal therapy is stopped.

• 1.2 Mild to Moderate:

• Treatment is usually unnecessary
• Patients who continue to have symptoms for >1 month: Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks)
• Note (1): Antifungal treatment is unnecessary in patients with mild symptoms caused by acute pulmonary histoplasmosis

• 2. Chronic Cavitary Pulmonary Histoplasmosis:

• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for at least 1 year) is recommended
• Note (1): Blood levels of itraconazole should be obtained after the patient has been receiving this agent for at least 2 weeks to ensure adequate drug exposure
• Note (2): Patients with underlying emphysema often develop progressive pulmonary disease, which is characterized by cavities with surrounding inflammation, after infection with Hysotplasma capsulatum

• 3. Pericarditis:

• 3.2 Mild cases

• Preferred regimen: Nonsteroidal anti-inflammatory therapy

• 3.3 Patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy:

• Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)

• 3.4 If corticosteroids are administered

• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)
• Note: Pericardial fluid removal is indicated for patients with hemodynamic compromise
• Note: Pericarditis occurs as a complication of inflammation in adjacent mediastinal lymph nodes in patients with acute pulmonary histoplasmosis.

• 4. Rheumatologic Syndromes

• 4.1 Mild cases:

• Preferred regimen: Nonsteroidal anti-inflammatory therapy

• 4.2 Severe cases:

• Preferred regimen: Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)

• 4.3Corticosteroids administration:

• Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)
• Note: If corticosteroids are used, concurrent itraconazole treatment is recommended to reduce the risk of progressive infection
• Note (2): Bone or joint involvement is very rare in progressive disseminated histoplasmosis, but it should not be overlooked.

• 5. Mediastinal Lymphadenitis

• 5.1 Treatment is usually unnecessary (if asympthomatic)**
• 5.2 Patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for >1 month

• Itraconazole (200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks)

• 5.3 Severe cases with obstruction or compression of contiguous structures

• Preferred regimen: Prednisone (0.5–1.0 mg/kg daily [maximum, 80 mg daily] in tapering doses over 1–2 weeks)
• Note: Antifungal treatment is unnecessary in most patients with symptoms due to mediastinal lymphadenitis
• Note (2): Itraconazole is recommended for 6–12 weeks to reduce the risk of progressive disseminated disease caused by corticosteroid-induced immunosuppression in patients who are given corticosteroids and in patients whose symptoms last longer than 1 month.

• 6. Mediastinal Granuloma

• 6.1 Treatment is usually unnecessary **
• 6.2 Symptomatic cases
• Preferred regimen: Itraconazole (200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks)

• Note: Itraconazole is appropriate for symptomatic cases, but there are no controlled trials to prove its efficacy.
• Note (2): There is no evidence that mediastinal granuloma evolves into mediastinal fibrosis. Thus, treatment with either surgery or itraconazole should not be used to prevent the development of mediastinal fibrosis

• 7. Mediastinal Fibrosis

• 7.1 Antifungal treatment is not recommended**
• 7.2 If clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma No differentiate from mediastinal fibrosis and granuloma ***
• Preferred regimen: Itraconazole (200 mg once or twice daily for 12 weeks)

• Note: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
• Note (2): Mediastinal fibrosis is characterized by invasive fibrosis that encases mediastinal or hilar nodes and that is defined by occlusion of central vessels and airways

• 8. Broncholithiasis

• 8.1 Antifungal treatment is not recommended **
• Note: Bronchoscopic or surgical removal of the broncholith is recommended

• 9. Pulmonary Nodules (Histoplasmomas)

• Antifungal treatment is not recommended**
• Note: Lung parenchymal sites of infection may contract and then persist indefinitely as lung nodules or histoplasmomas.... (what about this large comment)

• 10. Progressive Disseminated Histoplasmosis

• 10.1 Moderately severe to severe disease

• Preferred regimen: Liposomal amphotericin B (3.0 mg/kg daily) is recommended for 1–2 weeks, followed by oral itraconazole (200 mg 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months)
• Note: Substitution of another lipid formulation at a dosage of 5.0 mg/kg daily may be preferred in some patients because of cost or tolerability
• Note (2): The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity
• 10.2 Immunosupressed patients
• Lifelong suppressive therapy with itraconazole (200 mg daily)
• 10.3 Mild to moderate disease
• Itraconazole (200 mg 3 times daily for 3 days and then twice daily for at least 12 months)
• Note: Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy
• Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
• Note (3): Antigen levels should be measured during therapy and for 12 months after therapy is ended to monitor for relapse (B-III). Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.

• • • evidence summary...

• 10.Prophylaxis Recommended for Immunosuppressed Patients

• Preferred regimen: Itraconazole (200 mg daily) in patients with HIV infection with CD4 cell counts <150 cells/mm3 in specific areas of endemicity where the incidence of histoplasmosis is >10 cases per 100 patient-years

::::* Note: Prophylaxis with itraconazole (200 mg daily) may be appropriate in specific circumstances in other immunosuppressed patients

• • • evidence summary...

• 11.Treatment for Central nervous system Histoplasmosis

• Preferred regimen: Liposomal amphotericin B (5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks) followed by itraconazole (200 mg 2 or 3 times daily) for at least 1 year and until resolution of CSF abnormalities, including Histoplasma antigen levels.
• Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure

• • • evidence summary...

• 12.Histoplasmosis in Pregnancy

• Preferred regimen: Lipid formulation amphotericin B (3.0–5.0 mg/kg daily for 4–6 weeks) is recommended
• Prefered regimen low risk for nephrotoxicity: The deoxycholate formulation of amphotericin B (0.7–1.0 mg/kg daily) is an alternative to a lipid formulation
• Note: If the newborn shows evidence for infection, treatment is recommended with amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks)
• Note (2): Unique issues in pregnancy include the risk of teratogenic complications of azole therapy [93] and of transplacental transmission of H. capsulatum to the fetus

• 13.Histoplasmosis in Children

• Note: Treatment indications and regimens are similar to those for adults, except that amphotericin B deoxycholate (1.0 mg/kg daily) is usually well tolerated, and the lipid preparations are not preferred
• Itraconazole dosage: 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation

Histoplasmosis in Children?

  Acute Pulmonary Histoplasmosis

  Progressive Disseminated Histoplasmosis

Progressive Disseminated Histoplasmosis???

• Note (2):