What is the recommended treatment for adrenal histoplasmosis?

Treatment of Adrenal Histoplasmosis

For adrenal histoplasmosis, treatment with liposomal amphotericin B (3-5 mg/kg IV daily) for 1-2 weeks followed by itraconazole (200 mg three times daily for 3 days, then 200 mg twice daily) for at least 12 months is recommended, with some experts preferring 18-24 months due to the high risk of relapse. 1

Initial Treatment Approach

1. Induction Phase:

   • Liposomal amphotericin B (3-5 mg/kg IV daily) for 1-2 weeks 1
   • Alternative: Amphotericin B deoxycholate (0.7-1.0 mg/kg daily IV) in patients at low risk for nephrotoxicity 2

2. Maintenance Phase:

   • Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily 1
   • Duration: At least 12 months, with many experts recommending 18-24 months for adrenal histoplasmosis 2, 1

Monitoring During Treatment

• Measure itraconazole blood levels after 2 weeks of therapy to ensure adequate drug exposure 2, 1
• Monitor:
  • Daily renal function, electrolytes, CBC, and liver function tests during amphotericin B therapy 1
  • Liver enzymes before starting itraconazole and at 1,2, and 4 weeks, then every 3 months 1
  • Histoplasma antigen levels during therapy and for 12 months after completion 1
  • Continue therapy until Histoplasma antigen concentrations are <4 units in urine and serum 1

Special Considerations for Adrenal Histoplasmosis

• Adrenal insufficiency is common in adrenal histoplasmosis and requires appropriate hormone replacement 3
• Evidence suggests that cortisol insufficiency often does not normalize despite antifungal treatment 3
• Regular follow-up imaging of adrenal glands is recommended to monitor treatment response 4
• Consider adrenal biopsy after treatment to confirm clearance of infection in cases with persistent adrenal enlargement 4

Important Caveats

• Adrenal histoplasmosis has shown persistence of the organism even after standard treatment courses, with one case reporting persistence 7 years after 9 months of itraconazole therapy 4
• The mortality rate remains significant (20% in one study) despite appropriate treatment 3
• Patients should be monitored for relapse, which occurs in approximately 15% of cases 1
• Lifelong suppressive therapy with itraconazole 200 mg daily may be necessary in immunocompromised patients if immunosuppression cannot be reversed 1

Alternative Therapy

• If itraconazole is not tolerated, fluconazole 800 mg daily can be considered, though it has lower efficacy (70% response rate) 1

This treatment approach is based on the most recent guidelines from the Infectious Diseases Society of America and clinical evidence specific to adrenal histoplasmosis, which requires longer treatment duration than other forms of histoplasmosis due to the high risk of persistence and relapse.