• Clinical science

General mycology

Summary

Mycoses are infections caused by fungi. They may be caused by dermatophytes (e.g., Trichophyton), yeast (e.g., Candida), or molds (e.g., Aspergillus). In immunocompetent individuals, mycoses usually result in local infection, which can be treated with local antifungals. Fungal infections may cause systemic infection in immunocompromised individuals (e.g., HIV-positive individuals, bone marrow transplant recipients), potentially leading to meningitis or severe sepsis.

Basics of mycology

Structure and characteristics of fungi

Fungi are not considered plants and are nonphotosynthetic. They extract energy (e.g., sugar and proteins) from living or dead organic matter.

Azoles target the synthesis of ergosterol, the principal sterol in fungal cell membranes. They inhibit the synthesis of ergosterol from lanosterol by interfering with 14α-demethylase (cytochrome P-450 enzyme).

Substances synthesized by fungi

Detection of fungal infections

  • Clinical features and microscopy → evaluation of fungal morphology
  • Additional characterization via:
    • Culture
    • Antigen detection (e.g., capsule components in serum)
    • Antibody detection plays a minor role.

Candida, Aspergillus, and Cryptococcus are opportunistic fungal pathogens with low inherent virulence. They commonly cause systemic mycoses in immunocompromised hosts but do not normally affect healthy hosts.

Fungi overview

Opportunistic fungal infections

Mycosis Etiology Clinical features Diagnosis Treatment
Aspergillosis
Candidiasis
Cryptococcosis
  • LP:
  • Latex agglutination test: detects capsular antigen (very specific)
Pneumocystis pneumonia
  • Chest x-ray or CT: diffuse, bilateral ground-glass opacities
  • Bronchoalveolar lavage or lung biopsy (if sputum is negative): silver stain and immunofluorescence show disc-shaped yeasts
  • High-dose TMP-SMX (treatment and prophylaxis) or dapsone +/- pyrimethamine
  • Prednisone (moderate to severe hypoxemia)
  • Prophylaxis: CD4 < 200 cells/mm3

Mucormycosis

  • Pathogen: zygomycetes Mucor and Rhizopus
  • Risk factors: diabetic and immunocompromised patients
  • Patients with chronic sinus infection lasting for more than 3 months are predisposed to mucormycosis.
  • Head CT: sinusitis with orbital and intracranial involvement
  • Tissue biopsy (confirmatory): wide-angled branching of broad nonseptate hyphae

Cutaneous fungal infections

Mycosis Etiology Clinical features Diagnosis Treatment
Dermatophytes
Tinea versicolor (pityriasis versicolor)
  • Small, hyperpigmented or hypopigmented macules on chest and back; may coalesce to form patches
  • Best initial: KOH showing short hyphae and spores that have a “spaghetti and meatballs” appearance

Systemic fungal infections

Mycosis Etiology Clinical features Diagnosis Treatment
Histoplasmosis
  • Chest x-ray: diffuse nodular densities, focal infiltrate or cavity, or lymphadenopathy
  • Best initial: positive urine and serum polysaccharide antigen test
  • Silver stain of biopsy or bronchoalveolar lavage showing macrophages filled with dimorphic fungus with septate hyphae
  • Culture (blood, sputum, bone marrow, lymph node, liver)
  • Liver biopsy: demonstrates disseminated disease with the presence of fungal organisms in the yeast-stage of development.
Coccidioidomycosis (valley fever)
  • Serology: increased IgM (increases within 2 weeks of infection and disappears after 2 months); increased IgG at 1–3 months
  • Chest x-ray: normal or infiltrates/lymphadenopathy/pleural effusion
  • KOH or culture (sputum, wound exudate, joint effusion) showing large spherules containing endospores
Paracoccidioidomycosis
  • Infected patients often asymptomatic
  • Acute pneumonia
  • Painful nasal, pharyngeal, and laryngeal mucosal ulcerations
  • Lymphadenopathy (usually cervical)
  • Can disseminate → extrapulmonary manifestations (including verrucous skin lesions)
  • KOH/calcofluor staining on smears or silver/PAS-staining on tissue biopsy: budding yeast with “captain's wheel” formation
  • Cultures have a low sensitivity.

Blastomycosis

  • Pneumonia
  • Extrapulmonary: can disseminate to the skin (verrucous lesions and granulomatous nodules) and bones
  • KOH or culture (confirmatory) of sputum, urine, or body fluids showing:
    • yeast form (at body temperature or > 37°C): broad-based buds
    • Mold form (at room temperature): circular fungal cells with filamentous hyphae

Other fungal infections

Sporotrichosis (Rose gardener disease)

  • Etiology
    • Pathogen: Sporothrix schenckii
    • Risk factor: traumatic injury to the skin while gardening (e.g., thorn prick)
  • Clinical features
  • Diagnostics
    • Fungal culture; (sputum, pus, biopsy tissue) showing dimorphic, cigar-shaped yeast
    • Septate hyphae, rosette-like clusters of conidia at the tips of the conidiophores
  • Treatment

References:[1]

Dermatophytes

  • Pathogenicity
  • Morphology
    • Form hyphae and mycelium
    • After penetration into the skin, concentric propagation may occur around the entry site.
Important pathogens Characteristics Diseases Treatment

Trichophyton species

  • Occurs worldwide
  • Partial yellow-green fluorescence under Wood lamp

Epidermophyton species

  • Occurs worldwide
  • No typical fluorescence under Wood lamp

Microsporum species

  • Occurs worldwide
  • Partial blue-green fluorescence under Wood lamp

Yeasts

Important pathogens Characteristics Diseases Treatment

Candida species

Cryptococcus neoformans

  • Humans are infected via contaminated dust particles.
  • Possesses a capsule, which can be visualized using India Ink

Malassezia furfur

  • Yellow-orange fluorescence under Wood lamp
  • Particularly present in the infundibulum of the hair follicle

Molds

  • Pathogenicity
  • Morphology
    • Formation of monomorphic septate hyphae that branch at 45° and mycelium
    • Mold can infest food products and acquire a fuzzy appearance that is macroscopically visible.
Important pathogens Characteristics Diseases Treatment

Aspergillus fumigatus

  • Ubiquitous occurrence
  • Some species produce aflatoxins

  • 1. Bradsher RW. Mycology, Pathogenesis, and Epidemiology of Blastomycosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/mycology-pathogenesis-and-epidemiology-of-blastomycosis. Last updated July 26, 2017. Accessed November 16, 2018.
  • Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Philadelphia, PA: Elsevier Saunders; 2014.
  • Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017.
  • Brooks G, Carroll KC, Butel J, Morse S, Mietzner TA. Jawetz Melnick & Adelbergs Medical Microbiology. New York, NY: McGraw Hill Professional; 2012.
last updated 05/06/2019
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