Coccidioidomycosis
Coccidioidomycosis, also known as Valley fever or Posadas-Wernicke disease, is a chronic systemic fungal infection caused by two dimorphic fungi that live in the soil of semi-arid regions: Coccidioides immitis and Coccidioides posadasii. Their arthroconidia are carried in desert dust; once inhaled, they transform into large spherules packed with endospores.
Infection starts in the lungs, but in about 1%–5% of cases (particularly in immunocompromised people, pregnant women and those with a genetic susceptibility), the fungus spreads through the bloodstream to the rest of the body. In disseminated disease, the skin is the most common site outside the lungs. At Haute-Derma, recognizing spherules in skin tissue is central to making an accurate diagnosis and starting systemic treatment promptly.
Dimorphic Microbiology and the Spherule Life Cycle
A Temperature-Dependent Two-Phase Life Cycle
- Environmental phase (25°C, dry soil): The fungus grows as hyphae that fragment into countless small barrel-shaped arthroconidia (2–5 µm). These are very light, easily lifted by desert dust storms and inhaled deep into the alveoli.
- Parasitic phase in tissue (37°C): Unlike other dimorphic fungi, inhaled arthroconidia do not become ordinary yeasts. Instead they swell into spherules 20–100 µm across with a thick double wall.
- Release of endospores: Inside the spherule, free cell division produces hundreds of small endospores (2–5 µm). When a mature spherule ruptures, these are released into the surrounding tissue and each one grows into a new spherule, fueling a vigorous suppurative, necrotizing granulomatous reaction.
How the Fungus Reaches the Skin
The fungus travels from the lungs to the skin through the blood and lymphatics. In the dermis and subcutis, endospores provoke a dual inflammatory response: a neutrophilic infiltrate when spherules rupture, and a granulomatous reaction of macrophages and giant cells while new spherules are forming.
Clinical Forms in the Skin
Reactive (non-infectious) skin lesions: These appear in 10%–50% of patients during the acute phase of primary lung infection and are considered a sign of a good immune response:
- Erythema nodosum: Tender red nodules on the front of the shins.
- Erythema multiforme: Target-shaped lesions on the trunk and limbs.
- Note: These lesions are completely sterile (they contain no fungus) and represent a hypersensitivity reaction.
Disseminated Cutaneous Form
This occurs when the fungus multiplies directly in the skin:
- Verrucous plaques: Rough, warty plaques with a thick, cracked center and a violaceous border dotted with small pustules (very similar to blastomycosis).
- Nodules and cold subcutaneous abscesses: Nodules soften, then rupture to form sinus tracts draining pus full of endospores.
- Necrotic ulcers: Chronic ulcers with firm, raised edges and a base of bright red granulation tissue.
Primary cutaneous coccidioidomycosis (very rare): Caused by a penetrating injury that drives soil spores directly into the skin. It presents as a chancre-like lesion with lymphangitis and swelling of the regional lymph nodes (a sporotrichoid pattern).
Differential Diagnosis of Dimorphic Deep Fungal Infections of the Skin
| Coccidioidomycosis (Coccidioides) | Blastomycosis (B. dermatitidis) | Histoplasmosis (H. capsulatum) |
|---|---|---|
| Large spherules (20–100 µm) filled with endospores | Large yeasts (8–15 µm) with broad-based budding | Small yeasts (2–4 µm) inside macrophages |
| Dry desert soil (USA, Mexico, South America) | Moist soil and rotting wood near rivers and streams | Soil contaminated with bird or bat droppings, caves |
| Erythema nodosum (sterile) OR verrucous plaques/nodules/abscesses | Verrucous plaques with a violaceous border of microabscesses | Umbilicated papules, oral mucosal ulcers |
| EXTREMELY HAZARDOUS (BSL-3) | High risk (BSL-3) | Moderate risk |
| Fluconazole / itraconazole | Itraconazole | Itraconazole |
Our Diagnostic Workup at Haute-Derma
Direct Microscopy
- Technique: Pus aspirated from an abscess or a swab from the base of a skin ulcer is treated with 10%–20% KOH and stained with Calcofluor White fluorescent dye.
- Characteristic finding: Round spherules 20–100 µm in diameter with very thick walls, filled with small endospores 2–5 µm across (or collapsed, ruptured spherules releasing their endospores).
Skin Biopsy:
- Dermal findings: Mixed suppurative and necrotizing granulomatous inflammation.
- PAS and GMS stains: The walls of spherules and endospores stain sharply black or deep red, revealing both intact spherules and empty ruptured shells.
Serology and Biosafety Warning for Culture:
- Serology: IgM/IgG antibodies are detected by immunodiffusion or complement fixation (CF). A CF titer above 1:16 suggests disseminated systemic infection.
- CULTURE SAFETY WARNING: In culture, Coccidioides grows as a mold and produces vast numbers of arthroconidia that easily become airborne. Opening a culture plate improperly can cause serious infection in laboratory staff, so cultures must be handled in a biosafety level 3 (BSL-3) facility.
Treatment Protocols at Haute-Derma
Mild-to-Moderate Cutaneous Dissemination
- Fluconazole (first choice):
- Dose: 400–800 mg once daily by mouth. Fluconazole is well absorbed and penetrates tissues very well.
- Itraconazole (alternative):
- Dose: 200 mg twice daily after meals. Often more effective for bone involvement and verrucous skin lesions.
- Duration: At least 12 months (possibly several years or lifelong in immunocompromised patients).
Severe Disease or Central Nervous System Involvement
- Induction phase: Intravenous liposomal amphotericin B (3–5 mg/kg/day) until there is clear clinical improvement.
- Maintenance phase: Switch to long-term oral fluconazole 800 mg/day.
