Pulmonary histoplasmosis is the most common endemic systemic mycosis in North America, caused by Histoplasma capsulatum var. capsulatum (or H. capsulatum var. duboisii in Africa, predominantly cutaneous and bone disease). Histoplasma is a thermally dimorphic fungus existing as mold (mycelial form) in soil at ambient temperature and yeast form at 37°C in tissue. The fungus thrives in soil enriched with nitrogen from bird droppings (especially starlings, blackbirds, chickens) and bat guano in caves.
Endemic regions include the Ohio and Mississippi River valleys in the United States (highest endemicity), parts of Central and South America (Mexico, Brazil, Venezuela), the Caribbean, parts of Africa, India, and Southeast Asia. Outbreaks occur after disturbance of contaminated soil (cave exploration, demolition, excavation, chicken coop cleaning). Microconidia are inhaled, deposited in alveoli, and converted to yeast form, ingested by macrophages where they multiply intracellularly. Infection ranges from asymptomatic (95% with low-inoculum exposure) to severe disease.
Clinical syndromes include: (1) acute pulmonary histoplasmosis — flu-like illness with fever, chills, headache, dry cough, chest discomfort 2-3 weeks after high-inoculum exposure, with hilar/mediastinal adenopathy and patchy infiltrates; (2) chronic cavitary pulmonary histoplasmosis — in patients with structural lung disease (COPD, emphysema), mimicking tuberculosis with apical cavitary disease, weight loss, hemoptysis; (3) histoplasmoma — solitary pulmonary nodule with concentric calcification; (4) mediastinal granuloma — caseating necrosis of mediastinal nodes with potential to develop fibrosing mediastinitis (rare but devastating, with vascular and airway compression); (5) progressive disseminated histoplasmosis (PDH) — in immunocompromised hosts (HIV with CD4 less than 150, solid organ or stem cell transplant, biologic agents like TNF-alpha inhibitors, congenital immunodeficiency) with fever, weight loss, hepatosplenomegaly, pancytopenia, oral ulcers, adrenal involvement, CNS disease (10-25%); rapidly fatal without treatment. Diagnosis: urine Histoplasma antigen (highest sensitivity in PDH, over 90%), serum antigen, complement fixation and immunodiffusion serology, fungal culture (slow, weeks), histopathology with GMS or PAS staining showing intracellular yeasts in macrophages. Treatment: itraconazole 200 mg twice daily for mild-moderate disease; liposomal amphotericin B 3 mg/kg/day for severe disease, switched to itraconazole maintenance for total 12 months (PDH) or 12-24 months (chronic cavitary). HIV patients with CD4 less than 150 require lifelong secondary prophylaxis with itraconazole.