Systemic & Opportunistic Fungi

Dimorphic fungi: mold in the cold, yeast in the heat

The rule. Dimorphic fungi grow as molds at 25 °C in the environment and as yeasts at 37 °C in the body ("mold in the cold, yeast in the heat," or in the beast); Coccidioides is the exception, forming spherules rather than yeast in tissue. Spores are inhaled from soil in a characteristic region, and the resulting systemic mycoses form granulomas that mimic TB. Treat local or mild disease with itraconazole and serious systemic disease with amphotericin B.

Histo Hides inside macrophages; Blasto Buds Broadly; Coccidioides makes endospore-filled spherules; Paracoccidioides looks like a captain's (mariner's) wheel.

Sporothrix schenckii. A dimorphic fungus (cigar-shaped yeast in tissue) introduced into the skin by a thorn prick, hence rose gardener's disease. A local ulcer is followed by nodules ascending along the draining lymphatics. Treat with itraconazole or potassium iodide.

Opportunistic yeasts: Candida and Cryptococcus

Candida albicans. A normal commensal that forms germ tubes at 37 °C and pseudohyphae. The disease reflects the host defect:

• Oral thrush and diaper rash: white plaques that scrape off (unlike EBV hairy leukoplakia).
• Esophagitis: an AIDS-defining illness, typically at CD4 <100.
• Vulvovaginitis: diabetes, antibiotic use.
• Candidemia and endocarditis: neutropenia, central catheters, IV drug use.

Mucosal disease responds to topical azoles or nystatin, esophagitis to fluconazole, and invasive disease to an echinocandin or amphotericin B.

Cryptococcus neoformans. An encapsulated yeast with narrow-based budding, inhaled from soil and pigeon droppings, that disseminates to the meninges in AIDS (CD4 <100). Its polysaccharide capsule is the key virulence factor. India ink shows a clear halo, mucicarmine stains the capsule red, and the latex agglutination test for capsular antigen is the most sensitive test. Brain imaging may show "soap-bubble" lesions. Treat with amphotericin B plus flucytosine, then fluconazole.

Opportunistic molds: Aspergillus and Mucor

Aspergillus fumigatus. A mold (not dimorphic) with septate hyphae that branch at acute 45° angles. Its disease pattern tracks host immunity:

• Allergic bronchopulmonary aspergillosis: hypersensitivity in asthma and cystic fibrosis.
• Aspergilloma: a fungus ball growing in an old cavity, classically from TB.
• Invasive aspergillosis: angioinvasive disease in neutropenia.

A. flavus produces aflatoxin, which contaminates stored grains and peanuts and causes hepatocellular carcinoma through p53 mutation. Treat invasive disease with voriconazole.

Mucor and Rhizopus. Molds with irregular, broad, nonseptate hyphae that branch at wide (90°) angles. In ketoacidotic diabetics and neutropenic patients they cause rhinocerebral mucormycosis:

Management is urgent amphotericin B plus surgical debridement.

Pneumocystis jirovecii

Presentation. An inhaled, yeast-like fungus that causes diffuse interstitial pneumonia in AIDS once CD4 falls below 200. Expect progressive dyspnea, bilateral ground-glass opacities, elevated LDH, and hypoxemia.

Diagnosis and treatment. Methenamine silver stain of bronchoalveolar lavage fluid shows cup- or disc-shaped cysts. TMP-SMX both treats and prevents PCP, and prophylaxis starts once CD4 drops below 200. Add corticosteroids if PaO₂ <70 mm Hg or the A-a gradient >35 mm Hg.

Antifungal drugs

Selective targets. Fungal membranes use ergosterol instead of cholesterol, and fungi have a β-glucan cell wall, so most antifungals attack one of these.