Systemic Mycoses with Cutaneous Manifestations

Systemic Mycoses: Intro - Deep Skin Invaders

• Systemic mycoses: Fungal infections originating deep within the body, capable of disseminating to skin and other organs.
• Routes: Inhalation (primary lung focus), direct inoculation.
• Host status: Crucial. Immunocompromised (↑risk, severity); Immunocompetent (endemic, often self-limiting).
• Key Types:
  • Dimorphic fungi (e.g., Histoplasma, Coccidioides)
  • Opportunistic: Yeasts (e.g., Cryptococcus), Moulds (e.g., Aspergillus)

⭐ Most systemic mycoses are acquired via inhalation of spores, leading to a primary pulmonary infection before cutaneous dissemination.

Dimorphic Mycoses - Two-Faced Terrors

Dimorphic fungi: molds in environment, yeasts in tissue ($37^\circ C$).

⭐ Paracoccidioides brasiliensis yeast cells show a characteristic 'Mariner's wheel' appearance in tissue an important diagnostic clue often tested in exams.

Opportunistic Mycoses - Vulnerable Targets

• Cryptococcosis:
  • Species: C. neoformans (AIDS), C. gattii
  • Predisposing: HIV (CD4 < 100 cells/µL), steroids, transplant
  • Skin: Umbilicated papules/nodules (molluscum-like), cellulitis, ulcers.
  • Dx: India ink (CSF), Cryptococcal antigen (CrAg) (serum/CSF)
• Systemic Candidiasis:
  • Species: C. albicans, C. tropicalis
  • Predisposing: Neutropenia, central lines, TPN, broad-spectrum antibiotics
  • Skin: Diffuse erythematous macronodules (often tender), pustules
• Invasive Aspergillosis:
  • Species: A. fumigatus, A. flavus
  • Predisposing: Prolonged neutropenia, high-dose steroids, Chronic Granulomatous Disease (CGD)
  • Skin:
    • Primary (direct inoculation): Necrotic plaques/pustules at trauma/IV sites
    • Secondary (hematogenous): Ecthyma gangrenosum-like lesions, hemorrhagic bullae
• Mucormycosis:
  • Genera: Rhizopus, Mucor, Lichtheimia
  • Predisposing: Diabetic Ketoacidosis (DKA), neutropenia, iron overload (e.g., deferoxamine therapy), burns
  • Skin: Necrotic black eschars; Rhino-orbito-cerebral (ROC) form can extend to facial skin.

⭐ Cutaneous cryptococcosis can be the first sign of disseminated disease in AIDS patients, often when CD4 count is very low.

Diagnosis & Management - Attack Plan

• Polyenes (Amphotericin B): Binds ergosterol, forms pores. Broadest spectrum. Major toxicity: Nephrotoxicity.
• Azoles (Fluconazole, Itraconazole, Voriconazole, Posaconazole): Inhibit ergosterol synthesis. Key for many mycoses. Major toxicities: Hepatotoxicity, drug interactions.

  ⭐ Voriconazole is the drug of choice for invasive aspergillosis.

• Echinocandins (Caspofungin, Micafungin): Inhibit β-(1,3)-D-glucan synthesis. For Candida, Aspergillus. Generally well-tolerated.
• Flucytosine: Converted to 5-FU, inhibits DNA/RNA synthesis. Combination therapy (e.g., cryptococcosis). Major toxicity: Myelosuppression.

High‑Yield Points - ⚡ Biggest Takeaways

• Systemic mycoses: Caused by dimorphic fungi, common in immunocompromised patients.
• Histoplasmosis: Features oral ulcers, reticuloendothelial involvement; critical in AIDS.
• Blastomycosis: Shows verrucous skin lesions, lung disease; broad-based budding yeast on microscopy.
• Coccidioidomycosis: Presents with erythema nodosum/multiforme; spherules with endospores are diagnostic.
• Paracoccidioidomycosis: Key signs are mucocutaneous lesions and "mariner's wheel" yeast.
• Sporotrichosis: Known for lymphocutaneous spread ("rose gardener's disease"); cigar-shaped yeast.
• Cryptococcosis: May cause molluscum-like skin lesions; India ink shows capsulated yeast.