Extrapulmonary Histoplasmosis

Mechanism and Risk Factors

Histoplasma can cause masses and lesions outside the lungs, particularly in immunocompromised patients through hematogenous dissemination, affecting multiple organ systems including the gastrointestinal tract, adrenal glands, liver, spleen, bone marrow, and central nervous system 1, 2, 3
Hematogenous dissemination from the lungs to other tissues occurs in virtually all infected individuals during the first 2 weeks of infection before specific immunity develops 1
Progressive dissemination occurs primarily in those with underlying immunosuppressive disorders or those at the extremes of age 1, 2
Progressive dissemination occurs primarily in patients with CD4+ counts <150 cells/µL, organ transplant recipients, and those at extremes of age 1, 3

Gastrointestinal disease typically manifests with diarrhea, fever, abdominal pain, and weight loss 3
CNS histoplasmosis typically presents with fever, headache, and if brain involvement is present, seizures, focal neurological deficits, and changes in mental status 3
For CNS disease, CSF testing shows 70-90% sensitivity for antibody and 40-70% sensitivity for antigen 4
Skin, bone, and genitourinary tract can be affected 5
Lymphadenopathy is common in disseminated disease 3

Histoplasma antigen detection in urine has 95% sensitivity and serum has 85% sensitivity for disseminated histoplasmosis in AIDS patients 3
In severe disseminated histoplasmosis, peripheral blood smears can show organisms engulfed by white blood cells 3
Sensitivity of antibody testing drops dramatically in immunocompromised patients: only 18% in organ transplant recipients and 45% in HIV/AIDS patients 4

Disseminated histoplasmosis requires antifungal treatment regardless of symptom severity 1, 2
Amphotericin B (0.7 mg/kg/day) is indicated for severe manifestations, followed by itraconazole for maintenance therapy 2
Mortality in histoplasmosis is estimated at 5% in children and 8% in adults, making rapid diagnosis essential 4