fungal pneumonia

**PATHOPHYSIOLOGY** - Acquired by inhalation of spores/conidia from soil, bird/bat droppings, or the environment. It is NOT person-to-person (except rare transplant or donor-derived cases). - Endemic dimorphic fungi: mold at 25°C (environment) and yeast at 37°C (body temperature). Host defense relies on cell-mediated immunity (T cells, macrophages, granuloma formation). - Opportunistic fungi: disease occurs when immunity fails. Neutropenia predisposes to Aspergillus and Mucorales. Low CD4 (<200 for PCP, <100 for Cryptococcus) predisposes to PCP and Cryptococcus.

**KEY ORGANISMS (high-yield)** 1. **Histoplasma capsulatum** - Ohio and Mississippi River valleys. Bat/bird droppings (caves, chicken coops, old buildings). - Tiny intracellular yeast within macrophages. Hilar/mediastinal lymphadenopathy, and calcified granulomas that mimic TB. - Disseminated disease: hepatosplenomegaly, pancytopenia, adrenal insufficiency, oral ulcers. - Dx: urine/serum antigen, tissue biopsy. Tx: itraconazole for mild to moderate disease; amphotericin B for severe disease. 2. **Coccidioides immitis/posadasii** - Southwestern US (San Joaquin Valley fever, "desert rheumatism"). Large spherules containing endospores. - Erythema nodosum, arthralgias. Risk factors for dissemination: Filipino and African American ethnicity, pregnancy, immunosuppression. Dissemination to skin, bone, and meninges. - Dx: serology (IgM/IgG), spherules on histology. Tx: fluconazole or itraconazole; amphotericin B for severe disease. 3. **Blastomyces dermatitidis** - Ohio/Mississippi River valleys and Great Lakes. Broad-based budding yeast ("broad-based bud"). - Pulmonary disease plus skin (verrucous ulcers) and bone (osteolytic lesions) dissemination. Can mimic cancer or TB. - Tx: itraconazole; amphotericin B for severe disease. 4. **Paracoccidioides brasiliensis** - Latin America. "Captain's wheel" (pilot wheel) yeast with multiple buds. Pulmonary disease and mucocutaneous lesions (oral/mucosal ulcers). - Tx: itraconazole. 5. **Aspergillus fumigatus** - Septate hyphae with acute-angle (45°) branching. Spectrum: - *Aspergilloma* (fungus ball in a pre-existing cavity such as old TB or sarcoid; hemoptysis). - *ABPA* (type I and III hypersensitivity; asthma or CF; central bronchiectasis, eosinophilia, high IgE). - *Invasive aspergillosis* (neutropenia; halo sign on CT; hemoptysis; angioinvasion). - Dx: galactomannan, β-D-glucan, CT, biopsy. Tx: voriconazole (first line for invasive disease); amphotericin B or echinocandins as alternatives. 6. **Mucorales (Mucor, Rhizopus)** - Broad, nonseptate, right-angle-branching hyphae. DKA and neutropenia are risk factors. - Rhinocerebral and pulmonary forms. Angioinvasion causes necrosis (black eschar). Reverse halo sign on CT. - Tx: surgical debridement plus liposomal amphotericin B. 7. **Pneumocystis jirovecii** - HIV with CD4 <200, or chronic steroids or transplant. Subacute dyspnea, dry cough, hypoxemia, and elevated LDH. - CXR/CT: bilateral diffuse interstitial ("ground-glass") infiltrates. - Dx: BAL with silver stain or immunofluorescence (cysts), β-D-glucan. - Tx: TMP-SMX; add steroids if PaO2 <70 mmHg or A-a gradient ≥35. Prophylaxis: TMP-SMX when CD4 <200. 8. **Cryptococcus neoformans** - Encapsulated yeast (India ink, mucicarmine); pigeon droppings. Pulmonary disease plus meningitis in immunocompromised patients. - Dx: cryptococcal antigen (CrAg). Tx: amphotericin B + flucytosine, then fluconazole.

**CLINICAL FEATURES** - Often indistinguishable from bacterial or TB pneumonia: fever, cough, dyspnea, chest pain, weight loss, and night sweats. Think fungal when there is a geographic or exposure history, an immunocompromised host, or failure to respond to antibiotics. - Imaging can show nodules, cavities, lymphadenopathy, miliary patterns, or infiltrates.

**DIAGNOSIS** - Culture (Sabouraud agar), KOH or silver stains (GMS), histology, antigen tests (Histoplasma urine Ag, galactomannan, CrAg), serology (Coccidioides), and β-D-glucan (elevated in many fungi but NOT Mucorales or Cryptococcus).

**TREATMENT SNAPSHOT** - Azoles (itraconazole, fluconazole, voriconazole) for mild to moderate disease. Amphotericin B for severe or disseminated disease. Echinocandins for Candida and as salvage for Aspergillus. TMP-SMX for PCP.

**BOARD PEARLS** - Histoplasma = tiny yeast in macrophages; Blastomyces = broad-based budding; Coccidioides = spherules; Aspergillus = acute-angle septate hyphae; Mucor = right-angle nonseptate hyphae. - Itraconazole is the usual treatment for the endemic mycoses; fluconazole for Coccidioides and Cryptococcus maintenance. - Amphotericin B toxicity: nephrotoxicity, hypokalemia, hypomagnesemia, infusion reactions. - Voriconazole: hepatotoxicity, visual disturbances; CYP450 inhibitor.