Histoplasmosis is a systemic dimorphic fungal infection caused by Histoplasma capsulatum, the most common endemic mycosis in North America. It is highly endemic in the Ohio and Mississippi River valleys of the United States, with global distribution including Caribbean, Central and South America, parts of Africa (Histoplasma capsulatum var. duboisii in Africa with predominantly cutaneous and bone manifestations), Asia, and Australia. Transmission occurs by inhalation of microconidia from soil enriched with bird (especially starlings, blackbirds, chickens) or bat (caves, attics) guano. Activities causing exposure include cave exploration (spelunking), demolition of bird-roosted buildings, chicken coop cleaning, gardening, and construction. Once inhaled, microconidia germinate in alveoli, are phagocytosed by macrophages, transform to yeast form, and disseminate hematogenously; cell-mediated immunity controls infection in immunocompetent hosts.
Clinical spectrum: asymptomatic infection (>90% of those exposed in endemic areas, only positive serology or healed calcified granulomas on chest X-ray); acute pulmonary histoplasmosis (flu-like syndrome with fever, cough, chest pain, fatigue, hilar/mediastinal lymphadenopathy, rheumatologic features—erythema nodosum, arthralgia—after heavy inoculum); chronic cavitary pulmonary histoplasmosis (mimics tuberculosis in patients with underlying COPD; progressive cough, weight loss, hemoptysis, upper-lobe cavitary infiltrates); progressive disseminated histoplasmosis (life-threatening in HIV/AIDS with CD4 <150, transplant recipients, infants, elderly; presents with fever, hepatosplenomegaly, mucocutaneous lesions, pancytopenia, adrenal insufficiency, GI involvement, CNS involvement; AIDS-defining illness); CNS histoplasmosis (chronic meningitis, focal lesions, mass-effect histoplasmoma); mediastinal complications (mediastinal lymphadenitis, fibrosing mediastinitis—delayed inflammatory response causing SVC obstruction, pulmonary artery compression); pericarditis; ocular histoplasmosis syndrome (presumed, with peripheral atrophic chorioretinal scars and macular choroidal neovascularization).
Diagnosis: Histoplasma urine antigen (high sensitivity 90% in disseminated disease, 75% in acute pulmonary, lower in chronic forms; cross-reacts with blastomycosis and other endemic mycoses); serum antigen (similar or slightly lower yield); CSF antigen for CNS disease; serologies (complement fixation titer ≥1:32 or fourfold rise; immunodiffusion H and M bands); fungal culture (gold standard but slow, 2-6 weeks); histopathology with GMS/PAS stains showing intracellular yeasts in macrophages; Histoplasma PCR (research/specialized labs). Treatment per IDSA guidelines: mild-moderate acute pulmonary (often self-limited; if persistent >4 weeks, itraconazole 200 mg three times daily for 3 days then twice daily for 6-12 weeks); moderately severe-severe pulmonary or chronic cavitary—itraconazole 12 months (chronic cavitary 18-24 months); progressive disseminated—liposomal amphotericin B 3-5 mg/kg/day for 1-2 weeks then itraconazole 200 mg twice daily for at least 12 months (lifelong suppression in HIV until CD4 >150); CNS—liposomal amphotericin B 5 mg/kg/day for 4-6 weeks then itraconazole at least 12 months. Itraconazole levels should be monitored (target trough >1 µg/mL); newer azoles (posaconazole, isavuconazole, voriconazole) for refractory cases.