Endemic Mycoses: Histoplasmosis, Blastomycosis & Coccidioidomycosis
Where the patient has been decides which fungus is growing in the lung
Overview: dimorphic fungi and exposure
Thermal dimorphism. Histoplasma, Blastomyces, and Coccidioides grow as molds in soil and shed spores that are inhaled when the soil is disturbed. At body temperature they convert to yeasts (Histoplasma, Blastomyces) or spherules (Coccidioides). Most infections are silent or a self-limited pneumonia contained by granulomas; chronic, severe, or disseminated disease clusters in the immunocompromised and after heavy exposure. Because these infections imitate bacterial pneumonia, TB, sarcoidosis, and lung cancer, travel, hobbies, and occupation are the decisive history.
| Feature | Histoplasmosis | Blastomycosis | Coccidioidomycosis |
|---|---|---|---|
| Region | Ohio and Mississippi River valleys | Great Lakes, Ohio and Mississippi basins | Arizona, California Central Valley, desert Southwest |
| Exposure | Bird and bat droppings, caves, demolition | Moist soil, rotting wood near waterways | Desert dust, construction, dust storms |
| Lung | Hilar adenopathy; calcified granulomas | Mass-like consolidation mimicking cancer | Valley fever; nodules, thin-walled cavities |
| Beyond the lung | Marrow, liver, spleen, adrenals, oral ulcers | Verrucous skin, lytic bone, prostate | Skin, bone, meninges |
| Tissue form | Tiny (2–4 μm) yeasts in macrophages | Large broad-based budding yeasts | Spherules with endospores |
| Key test | Urine/serum antigen | Microscopy and culture | Serology with complement-fixation titer |
| Oral drug | Itraconazole | Itraconazole | Fluconazole |
Who gets treated. Mild acute histoplasmosis or coccidioidomycosis in a healthy host usually resolves on its own. Treat moderate–severe, prolonged, chronic cavitary, or disseminated disease and every immunocompromised patient; most experts treat all blastomycosis because it can progress or disseminate. Liposomal amphotericin B is used for severe, CNS, or life-threatening disease and in early pregnancy, followed by an azole.
Itraconazole capsules need food and gastric acid for absorption (the solution is taken fasting), serum levels should be checked, and it is a negative inotrope and CYP3A4 inhibitor. Echinocandins do not treat the endemic mycoses.
Histoplasmosis
Acute infection. Histoplasma capsulatum thrives in soil enriched by bird and bat droppings: caves, chicken coops, and old buildings under demolition in the Ohio and Mississippi River valleys. Most infections are silent or a flu-like pneumonia with hilar or mediastinal adenopathy and patchy infiltrates, sometimes with erythema nodosum and arthralgias, healing into calcified granulomas in the lung and spleen. A heavy inoculum, such as clearing a bat-filled attic, causes diffuse nodular pneumonia with hypoxemia even in healthy people.
Mediastinal and chronic complications. Calcified nodes can erode into airways (broncholithiasis). Fibrosing mediastinitis, a rare exuberant fibrotic reaction, encases the SVC, pulmonary vessels, or airways, producing SVC syndrome or hemoptysis, and does not respond to antifungals. Chronic cavitary histoplasmosis in smokers with emphysema mimics reactivation TB, with upper-lobe cavities and weight loss, and needs 12–24 months of itraconazole.
Disseminated disease. AIDS (CD4 <150), TNF-α inhibitors, transplantation, and infancy allow spread through macrophages: fever, weight loss, hepatosplenomegaly, lymphadenopathy, pancytopenia from marrow infiltration, oral or GI ulcers, skin lesions, adrenal insufficiency, and sometimes septic shock. LDH and ferritin are often strikingly high.
Diagnosis. Urine and serum Histoplasma antigen are the most sensitive rapid tests in disseminated and heavy acute infection; the antigen cross-reacts with Blastomyces. Fungal blood cultures and marrow or tissue biopsy showing tiny yeasts inside macrophages confirm it. Serology (complement fixation, immunodiffusion) is useful in subacute and chronic disease but often falsely negative in immunosuppression.
- Severe or disseminatedLiposomal amphotericin B for 1–2 weeks; stop TNF inhibitors and assess adrenal function.
- Step downItraconazole to complete 12 weeks for severe acute pulmonary disease, or at least 12 months for disseminated disease.
- HIVStart ART and continue itraconazole until CD4 recovers (>150) with suppressed viral load.
- Mild–moderateItraconazole alone; symptoms beyond 4 weeks usually warrant 6–12 weeks.
Blastomycosis
Exposure and lung disease. Blastomyces dermatitidis lives in moist soil and decaying wood near rivers and lakes in the Great Lakes region and the Ohio and Mississippi basins, infecting hunters, canoeists, outdoor workers, and their dogs; illness in a hunting dog can herald human cases from the same exposure. Lung disease ranges from acute pneumonia to a chronic mass-like consolidation that mimics lung cancer or TB, and it can progress to ARDS.
Dissemination. Blastomycosis often spreads even in healthy hosts. Skin is the most common extrapulmonary site, with verrucous, crusted plaques with heaped-up borders or ulcers that mimic squamous cell carcinoma. Bone follows (lytic lesions of vertebrae, ribs, and long bones), then the genitourinary tract (prostatitis, epididymo-orchitis), and less often the CNS.
Diagnosis and treatment. Sputum, skin scrapings, or tissue show large (8–15 μm) yeasts with a thick, double-contoured wall and a single broad-based bud; culture confirms. Antibody tests perform poorly and antigen tests cross-react with Histoplasma. Mild–moderate disease is treated with itraconazole for 6–12 months; severe or CNS disease starts with liposomal amphotericin B, then an azole.
Narrow-based budding suggests Cryptococcus; multiple buds in a ship's-wheel pattern suggest Paracoccidioides from Latin America.
Coccidioidomycosis
Valley fever. Coccidioides lives in desert soil in Arizona and California's San Joaquin (Central) Valley, as well as New Mexico, west Texas, and northern Mexico; construction, dust storms, earthquakes, and archaeological digs release arthroconidia. Symptoms follow exposure by 1–3 weeks. Valley fever brings fever, cough, pleuritic pain, prolonged fatigue, erythema nodosum, arthralgias, and eosinophilia, and it can leave pulmonary nodules that mimic cancer or thin-walled cavities that may rupture into the pleura. Erythema nodosum reflects strong cellular immunity and a lower dissemination risk.
Dissemination. Risk rises sharply with Filipino or Black ancestry, pregnancy (especially the third trimester and postpartum), and immunosuppression (HIV with low CD4, transplantation, TNF inhibitors, high-dose steroids). Targets are skin (verrucous plaques, abscesses), bones and joints (vertebral osteomyelitis), and meninges, where chronic basilar meningitis causes headache, confusion, and hydrocephalus.
Diagnosis. Screen with EIA IgM and IgG and confirm with immunodiffusion. The complement-fixation IgG titer is quantitative: high (≥1:16) or rising titers signal extensive or disseminated disease, and falling titers track response. Complement-fixing antibody in CSF diagnoses meningitis. Tissue shows large spherules (20–100 μm) packed with endospores, and cultures are a serious laboratory hazard, so the lab must be warned.
Treatment. Uncomplicated valley fever in a healthy host can be observed with serial clinical and radiographic follow-up. Fluconazole (or itraconazole) is given for severe or prolonged symptoms, high titers, risk factors, or dissemination; amphotericin B is used for severe, rapidly progressive disease.
Azoles are teratogenic in the first trimester, so amphotericin B treats coccidioidomycosis in early pregnancy. Coccidioidal meningitis needs high-dose fluconazole for life, because most patients relapse when it stops.