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Foundational Sciences · Microbiology

Fungi: Systemic, Opportunistic & Cutaneous

A high-yield Step 1 tour of the medically important fungi — systemic dimorphic, opportunistic, and cutaneous/subcutaneous — pairing each organism's identifying morphology and lab clues with its classic vignette buzzwords and board-tested treatment, capped by an antifungal mechanism map. Corrected from the draft: coccidioidal meningitis is treated with high-dose fluconazole (not amphotericin B), and Pneumocystis uses a cholesterol membrane (so azoles/ampho B fail, hence TMP-SMX).

15 min readHigh yield

Overview: How the Boards Group the Fungi

Board fungi fall into three buckets: systemic (endemic) dimorphic mycoses, opportunistic mycoses, and cutaneous/subcutaneous mycoses. Two structural facts drive most of the drug questions: the fungal membrane uses ergosterol (the target of amphotericin B and the azoles) and the cell wall contains β-1,3-glucan (the target of echinocandins).

Dimorphism is the recurring theme of the systemic group: "mold in the cold, yeast in the heat" — they grow as a mold at 25 °C in the environment and convert to yeast at 37 °C in tissue. Two exceptions the boards love: Coccidioides forms a tissue spherule (not a yeast), and Candida does the reverse — yeast/pseudohyphae at lower temperature but germ tubes/true hyphae at 37 °C.

Know the stains: KOH prep (skin scrapings), GMS/methenamine silver and PAS (tissue fungi), India ink and mucicarmine (Cryptococcus capsule).

Systemic (Endemic) Dimorphic Mycoses
  • All are dimorphic — mold in soil (25 °C), yeast in tissue (37 °C); except Coccidioides, which forms a tissue spherule packed with endospores.
  • Histoplasma capsulatum — Mississippi/Ohio River valleys; bird & bat droppings (caves/spelunking, chicken coops); tiny yeast inside macrophages; can mimic TB (granulomas, cavitary lung disease).
  • Blastomyces dermatitidis — Great Lakes/eastern US; broad-based budding yeast about the same size as the parent cell; pneumonia + verrucous/ulcerated skin lesions and bone involvement.
  • Coccidioides immitis/posadasii — Southwestern US (San Joaquin Valley, Arizona), "Valley fever"; inhaled arthroconidia (dust storms, earthquakes, digs); associated erythema nodosum, erythema multiforme, arthralgia ("desert rheumatism").
  • Paracoccidioides brasiliensis — rural Latin America; "captain's-wheel" (mariner's-wheel) multiple-budding yeast.
  • Treatment: mild/localized → itraconazole (Coccidioides → fluconazole); severe/disseminated → amphotericin B (liposomal), then step-down azole. Board pitfall: coccidioidal meningitis is treated with high-dose fluconazole (often lifelong), NOT amphotericin B.
Photomicrograph of a Coccidioides immitis spherule filled with endospores in tissue
Coccidioides tissue form: a spherule packed with endospores — the classic 'Valley fever' morphology (not a yeast). · Wikimedia Commons — Wikimedia Commons — Public domain, via Wikimedia Commons
Opportunistic Mycoses (the ICU/AIDS Killers)
  • Candida albicans — germ tubes at 37 °C, pseudohyphae + budding yeast; thrush/esophagitis (AIDS CD4 <100, inhaled steroids), vulvovaginitis (diabetes, antibiotics), diaper rash, candidemia/endocarditis (neutropenia, central lines, IV drug use). Tx: mucocutaneous → nystatin/azole; systemic → echinocandin (caspofungin) or amphotericin B.
  • Aspergillus fumigatus — septate hyphae, acute-angle (45°) branching; a monomorphic mold. Syndromes: ABPA (asthma/CF), aspergilloma ("fungus ball" in an old TB cavity), angioinvasive/invasive aspergillosis (neutropenia). Aflatoxin (A. flavus, moldy grain/peanuts) → hepatocellular carcinoma (p53 mutation). Tx: voriconazole.
  • Cryptococcus neoformans — heavily encapsulated, narrow-based budding yeast; pigeon droppings; India ink halo, mucicarmine-red capsule, latex agglutination for capsular antigen (CrAg); meningoencephalitis in AIDS (CD4 <100), "soap-bubble" brain lesions. Tx: amphotericin B + flucytosine, then fluconazole.
  • Mucor/Rhizopus (mucormycosis) — broad, nonseptate (aseptate) hyphae, wide/right-angle (90°) branching; DKA diabetics and neutropenics; rhinocerebral disease, black necrotic eschar on palate/turbinates, frontal-lobe abscess. Tx: amphotericin B + surgical debridement (+ correct the DKA).
  • Pneumocystis jirovecii — PCP, diffuse interstitial pneumonia in AIDS CD4 <200; bilateral "ground-glass" infiltrates, elevated LDH; disc/cup-shaped cysts on GMS silver stain of BAL. Its membrane uses cholesterol, not ergosterol → azoles/amphotericin B are ineffective. Tx/prophylaxis: TMP-SMX (start prophylaxis at CD4 <200); add steroids if PaO₂ <70 mmHg or A–a gradient >35.
India ink preparation showing Cryptococcus neoformans yeast surrounded by clear capsular halos
India ink prep of Cryptococcus neoformans: narrow-based budding yeast with wide clear polysaccharide capsules. · Wikimedia Commons — Photo Credit: Content Providers(s): CDC/Dr. Leanor Haley — Public domain, via Wikimedia Commons
Cutaneous & Subcutaneous Mycoses
  • Malassezia furfur → tinea (pityriasis) versicolor; hypo-/hyperpigmented scaly patches on the trunk (worse in hot, humid weather); "spaghetti-and-meatballs" appearance (short hyphae + round spores) on KOH. Tx: topical selenium sulfide or topical azole (ketoconazole).
  • Dermatophytes — Trichophyton, Microsporum, *Epidermophyton* → tinea (ringworm): corporis, pedis, cruris, capitis, unguium (onychomycosis); pruritic scaly ring with central clearing; KOH shows branching septate hyphae; some Microsporum fluoresce under a Wood's lamp (Trichophyton does not). Tx: topical azole/terbinafine; oral terbinafine or griseofulvin for capitis/onychomycosis (topicals don't reach the hair follicle or nail bed).
  • Sporothrix schenckii → "rose gardener's disease"; thorn-prick / sphagnum-moss inoculation; cigar-shaped budding yeast in tissue; local ulcer with nodules ascending along lymphatics (nodular/ascending lymphangitis). Tx: itraconazole (or potassium iodide, KI).
Buzzword Vignette Bank → Organism → Treatment
  • Spelunker/cave explorer in Ohio, fever + cough; biopsy shows oval yeast inside macrophages → Histoplasma capsulatum → itraconazole (ampho B if severe).
  • Arizona worker after a dust storm, cough + erythema nodosum; tissue spherules full of endospores → Coccidioides → fluconazole (ampho B if severe/disseminated; meningitis → high-dose fluconazole).
  • Wisconsin man, pneumonia + a wart-like (verrucous) skin ulcer; broad-based budding yeast → Blastomyces dermatitidis → itraconazole.
  • AIDS, CD4 40, headache + neck stiffness; CSF India ink shows encapsulated yeast / cryptococcal antigen positive → Cryptococcus neoformans → amphotericin B + flucytosine, then fluconazole.
  • DKA diabetic, black eschar on the palate + facial pain; biopsy broad nonseptate hyphae, right-angle branching → Mucor/Rhizopus → amphotericin B + surgical debridement.
  • Neutropenic leukemic, hemoptysis + halo-sign lung nodule; septate acute-angle hyphae → Aspergillus fumigatus → voriconazole.
  • AIDS, CD4 150, dyspnea with a near-clear exam but bilateral ground-glass infiltrates and high LDH; silver-stain cysts in BAL → Pneumocystis jirovecii → TMP-SMX (+ steroids if hypoxic).
  • Gardener pricked by a thorn, then a chain of nodules ascending up the arm → Sporothrix schenckii → itraconazole (or KI).
  • Young adult, hypopigmented scaly trunk patches after summer; KOH "spaghetti and meatballs" → Malassezia furfur → topical selenium sulfide.
GMS silver stain of angioinvasive aspergillosis showing septate hyphae branching at acute angles
GMS silver stain of invasive Aspergillus: septate hyphae with uniform acute-angle (about 45°) branching. · Wikimedia Commons — Yale Rosen from USA — CC BY-SA 2.0, via Wikimedia Commons
Micro Classics (Real Ones Only)
  • "Mold in the cold, yeast in the heat" — every systemic dimorphic fungus (mold 25 °C ↔ yeast 37 °C).
  • Broad-Based Blastomyces — Blasto = broad-based budding.
  • Aspergillus = Acute Angles (both start with A), septate; Mucor/Rhizopus = wide/right angles, nonseptate.
  • India ink + "soap-bubble" brain lesions = Cryptococcus.
  • "Spaghetti and meatballs" = Malassezia (tinea versicolor).
  • "Captain's wheel" = Paracoccidioides.
  • aFLAtoxin from A. flavus → Liver (hepatocellular carcinoma) — think moldy peanuts/grain.

Master Comparison Table

OrganismKey lab / morphology featureDisease & buzzwordTreatment
Histoplasma capsulatumYeast inside macrophages; bird/bat droppings; MS–OH valleysPulmonary (TB mimic), disseminatedItraconazole; ampho B if severe
Blastomyces dermatitidisBroad-based budding yeast; Great Lakes/eastern USPneumonia + verrucous skin/boneItraconazole; ampho B if severe
CoccidioidesSpherule with endospores; SW US arthroconidiaValley fever + erythema nodosumFluconazole; ampho B if severe; meningitis → high-dose fluconazole
ParacoccidioidesCaptain's-wheel budding; Latin AmericaPulmonary + oral/facial lesionsItraconazole; ampho B if severe
Candida albicansGerm tubes/pseudohyphaeThrush, esophagitis, vaginitis, candidemiaAzole/nystatin; echinocandin (systemic)
Aspergillus fumigatusSeptate, acute-angle hyphaeABPA, aspergilloma, invasiveVoriconazole
Cryptococcus neoformansEncapsulated, narrow-based yeast; India ink, mucicarmineAIDS meningitis, soap-bubble lesionsAmpho B + flucytosine → fluconazole
Mucor / RhizopusNonseptate, wide-angle hyphaeRhinocerebral (DKA), black escharAmpho B + debridement
Pneumocystis jiroveciiCysts on GMS; CD4 <200; cholesterol membranePCP, ground-glass, high LDHTMP-SMX (± steroids)
Malassezia furfurSpaghetti & meatballs on KOHTinea versicolor, pigment changeSelenium sulfide / topical azole
DermatophytesSeptate hyphae on KOH; Wood's lampTinea/ringworm, onychomycosisTopical azole/terbinafine; oral for capitis/nails
Sporothrix schenckiiCigar-shaped yeast; rose thornAscending nodular lymphangitisItraconazole / KI
Antifungal Quick Map (Mechanism → Use)
  • Amphotericin B — binds ergosterol and forms membrane pores; the "big gun" for severe systemic mycoses; nephrotoxic with K⁺/Mg²⁺ wasting and infusion fever/rigors (supplement electrolytes).
  • Nystatin — same mechanism but too toxic IV → topical / "swish-and-swallow" for oral–esophageal and cutaneous Candida.
  • Azoles (fluconazole, itraconazole, voriconazole, posaconazole/isavuconazole) — inhibit ergosterol synthesis (14-α-demethylase, a CYP450); fluconazole = cryptococcal maintenance, Candida & coccidioidal meningitis, voriconazole = Aspergillus, posaconazole/isavuconazole = Mucor (salvage/step-down); note P450 inhibition (drug interactions).
  • Echinocandins (caspofungin, micafungin, anidulafungin) — inhibit β-1,3-glucan synthase (cell wall); first-line invasive Candida, salvage Aspergillus.
  • Terbinafine — inhibits squalene epoxidase; oral drug of choice for onychomycosis/dermatophytes.
  • Griseofulvin — disrupts microtubules, deposits in keratin; tinea capitis; induces P450.
  • Flucytosine (5-FC) — converted to 5-FU, blocks fungal DNA/RNA synthesis; paired with amphotericin B for cryptococcal meningitis (watch bone-marrow suppression).

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