17.2 Dimorphic Fungi and Dermatophytes

17.2 Dimorphic Fungi and Dermatophytes

Quick Answer: Grow the suspected dimorph at 25°C (mold) and 37°C (yeast), then read tissue morphology and geography together. Histoplasma: Ohio/Mississippi, intracellular yeast, tuberculate macroconidia. Blastomyces: broad-based budding. Coccidioides: spherules in tissue, barrel arthroconidia, Southwest, lab hazard — do not make slide cultures of mature mold at BSL-2 without controls. Sporothrix: cigar bodies, rose-gardener lymphocutaneous disease. Dermatophytes (Trichophyton, Microsporum) stay mold at both temperatures and are identified by macroconidia, urease, and hair perforation.

Dimorphic fungi are the organisms that force you to think in two temperatures at once. At 25–30°C on Sabouraud or potato dextrose they look like molds. At 37°C in enriched media (brain-heart infusion with blood, or in tissue) they convert to yeast — except Coccidioides, which does not form a conventional yeast colony; its parasitic form is the spherule. Conversion can take days to weeks and is not required for a report if the mold morphology, exoantigen/DNA probe/MALDI, and clinical picture already agree, but the 25 vs 37°C principle is an M favorite.

Handle mold-form cultures of the systemic dimorphs as airborne hazards. Arthroconidia of Coccidioides and microconidia of Histoplasma have infected laboratory workers. Use a biosafety cabinet, avoid aerosolizing plates, and do not prepare slide cultures of a mature, fluffy white mold from a Southwest respiratory specimen. Tape mounts, if done at all, are performed in a BSC with respiratory protection per the laboratory's BSL-2-plus or BSL-3 procedure. When in doubt, inactivate or send the isolate to a reference laboratory rather than "just making a tease mount on the bench."

Histoplasma capsulatum

Endemic along the Ohio and Mississippi River valleys, in soil enriched by bird or bat droppings, and in caves (spelunkers). Inhalation of microconidia produces pulmonary disease that may disseminate in infants and in cell-mediated immunodeficiency (HIV, TNF inhibitors, transplant). The tissue/yeast form is a small (2–4 µm) intracellular yeast inside macrophages; Giemsa or Wright stain of bone marrow, blood buffy coat, or BAL is often faster than culture. The yeasts show narrow-based budding and a rim of unstained cell wall that can mimic a capsule — do not call them Cryptococcus. Cryptococcus is extracellular and truly encapsulated; Histoplasma is intracellular and is not India-ink positive.

The mold form (slow, often 1–4 weeks) produces tuberculate (echinulate, finger-like projections) macroconidia and small infectious microconidia. Conversion to yeast at 37°C on BHI is slow and may fail; DNA probes, MALDI after inactivation, and Histoplasma antigen on urine or serum support the ID. Antigen cross-reacts with Blastomyces — geography and morphology still matter. Blood-culture or lysis-centrifugation systems recover disseminated disease. Cave and construction exposures plus pancytopenia and marrow yeasts are the case-vignette cluster.

Blastomyces dermatitidis (B. gilchristii complex)

Overlaps the same river valleys and extends into decaying wood and wet earth of the Midwest and Southeast. After inhalation it causes pneumonia that seeds skin and bone — verrucous skin lesions that look like squamous cell carcinoma are a clinical clue. The yeast form is large (8–15 µm) with a thick double-contoured wall and broad-based budding (the bud is nearly as wide as the mother cell). That single feature separates it from Cryptococcus (narrow-based, capsule) and Histoplasma (small, intracellular). The mold form is a white to tan fluffy colony with lollipop-like round conidia on conidiophores. Conversion at 37°C yields the broad-based yeast. Do not confuse the large yeast with Coccidioides spherules, which are much larger and filled with endospores, not a single bud.

Coccidioides immitis / C. posadasii

Southwest deserts (southern California, Arizona, New Mexico, west Texas, and analogous soils in Latin America). Valley fever follows dust exposure, drought-then-rain cycles, and archaeological digs. In tissue the parasitic form is a spherule (10–80 µm) packed with endospores — not a budding yeast. When the spherule ruptures, endospores seed new spherules. The mold form, even on a routine Sabouraud plate incubated at 25°C, produces barrel-shaped arthroconidia alternating with empty disjunctor cells. Those arthroconidia are highly infectious.

Lab hazard (tested). A mature white mold from a Southwest sputum is Coccidioides until proven otherwise. Do not make slide cultures of mature mold at BSL-2 without the laboratory's additional controls. Do not sniff plates. Seal plates, work in a BSC, and confirm with a DNA probe, MALDI after kill, or a reference laboratory. Conversion in vitro to spherules requires special conditions and is not a routine bench test; diagnosis rests on spherules in tissue or wet prep, arthroconidia in a controlled mount, antigen/serology, and molecular methods. C. immitis (California) and C. posadasii (elsewhere) are clinically similar for M purposes.

Sporothrix schenckii complex

Rose-gardener disease: a thorn, sphagnum moss, or timber puncture inoculates the mold, which then spreads as lymphocutaneous nodules along draining lymphatics (sporotrichoid spread). Pulmonary and disseminated disease occur in alcohol use disorder and immunodeficiency. The yeast form is a small, elongated cigar body (2–6 µm); yeasts can be scarce in tissue, so culture is more sensitive than histology. The mold at 25°C is beige and later dark; daisy-like (flowerette) clusters of conidia form at the tips of conidiophores. Convert at 37°C on blood-enriched media to confirm dimorphism. Unlike the pulmonary dimorphs, Sporothrix is a classic skin-and-lymph organism first.

Temperature conversion is the conceptual glue: mold at 25°C, yeast at 37°C. If a white mold does not convert and produces arthroconidia from the Southwest, you are still looking at Coccidioides, not a failed Blastomyces conversion. If small yeasts are inside macrophages, think Histoplasma, not Candida. If the yeast bud is broad-based, think Blastomyces, not Cryptococcus.

Dermatophytes: Trichophyton and Microsporum

Dermatophytes are keratinophilic molds that infect hair, skin, and nails (tinea capitis, corporis, pedis, cruris, unguium). They are not dimorphic — they grow as molds at 25°C and do not become yeasts at 37°C. Incubate skin, hair, and nail specimens on dermatophyte media (DTM, mycobiotic/cycloheximide-containing Sabouraud) at 25–30°C for up to 2–4 weeks. Cycloheximide suppresses many contaminant molds and Candida; do not use cycloheximide as the only plate if you also need Candida or a systemic dimorph from the same lesion.

Macroconidia vs microconidia is the first split:

• Microsporum: numerous rough, thick-walled, spindle-shaped macroconidia. M. canis (zoophilic, cats/dogs; ectothrix tinea capitis; often fluoresces green on Wood lamp) has tapered macroconidia with more than six septa. M. gypseum (geophilic) has shorter, thinner-walled macroconidia with fewer septa. Microconidia are few.
• Trichophyton: many microconidia, few smooth thin-walled pencil-shaped macroconidia. T. rubrum (most common skin and nail isolate) has tear-shaped microconidia along hyphae, a wine-red reverse on cornmeal or PDA, urease negative, and in vitro hair perforation negative. T. mentagrophytes complex has grape-like microconidia, spiral hyphae, urease positive, and hair perforation positive. T. tonsurans (endothrix tinea capitis in the United States) has balloon or matchstick microconidia and often needs thiamine. T. verrucosum (cattle) likes 37°C and thiamine/inositol.

Epidermophyton floccosum is the third classic genus (smooth club-shaped macroconidia in clusters, no microconidia, skin and nails, not hair). Know it exists so you do not force every dermatophyte into Trichophyton or Microsporum, but the outline items you were given emphasize those two genera.

Urease and in vitro hair perforation are the pair used to separate T. mentagrophytes (both positive) from T. rubrum (both negative). In vivo hair invasion is a different concept: ectothrix spores coat the outside of the hair (Microsporum, some Trichophyton); endothrix spores fill the hair shaft (T. tonsurans, T. violaceum) and the hair breaks at the scalp ("black-dot" tinea capitis). Wood-lamp fluorescence supports M. canis but does not rule out T. tonsurans, which does not fluoresce.

Disease-state language: tinea corporis is ringworm of glabrous skin; tinea capitis is scalp hair; tinea unguium is nail (onychomycosis may also be Candida or a mold — KOH plus culture, not morphology of the nail alone). A skin scraping that shows spaghetti and meatballs is Malassezia, not a dermatophyte. A lymphocutaneous chain after a rose thorn is Sporothrix, not tinea. Keep those three algorithms separate.