Phaeohyphomycosis

Microbiology and Pathogenesis

Common Causative Organisms

More than 100 species of dematiaceous fungi have been reported to cause phaeohyphomycosis. The most frequent include:

• Exophiala jeanselmei and Exophiala dermatitidis: the leading causes of the subcutaneous fungal cyst (phaeohyphomycotic cyst).
• Alternaria spp. (particularly Alternaria alternata): typically cause skin lesions in organ transplant recipients or patients on long-term corticosteroids.
• Curvularia spp., Bipolaris spp. and Cladophialophora bantiana (a strongly neurotropic species that can cause brain abscesses).

How the Fungus Enters the Skin and Forms a Cyst

• Traumatic inoculation: spores from soil, plants and decaying vegetation are introduced through a wood splinter, thorn prick or skin scratch.
• Formation of a subcutaneous cyst: in people with normal immunity, macrophages and neutrophils are recruited to wall off the infection. The body then lays down a fibrous capsule that completely encloses the fungus, producing a phaeohyphomycotic cyst filled with brown-yellow necrotic pus and fragments of pigmented hyphae.
• Immune evasion through melanin: melanin in the fungal cell wall shields the organism from the reactive oxygen species (ROS) released by neutrophils, allowing it to persist in the tissue.

Main Clinical Forms

• Superficial phaeohyphomycosis: the infection stays within the stratum corneum or the hair shaft. Classic examples are tinea nigra (caused by Hortaea werneckii, producing painless dark patches on the palms or soles) and black piedra (caused by Piedraia hortae, producing hard black nodules stuck to the hair shaft).
• Subcutaneous phaeohyphomycosis – the form most often seen in dermatology clinics. It mainly affects the limbs (forearms, hands, lower legs, feet). The lesion is a well-defined, mobile cyst or nodule under the skin; it is painless at first but may later become mildly tender or rupture and drain grayish-brown pus.
• Locally invasive cutaneous form: usually seen in immunocompromised patients (transplant recipients, people on anti-rejection drugs, or patients with lupus). Lesions take the form of indurated plaques, chronic ulcers or spreading necrotic growths that progress quickly and are easily mistaken for an acute bacterial infection.
• Disseminated and systemic form: the fungus spreads through the bloodstream to the lungs, heart or central nervous system (for example, brain abscess caused by C. bantiana). This form is very dangerous and carries a high mortality rate.

Comparing the Three Dematiaceous Fungal Infections

Our Diagnostic Workup at Haute-Derma

Direct Microscopy:

• Pus is aspirated from the subcutaneous cyst, or scale is scraped from the edge of the lesion, and treated with 10%–20% KOH.
• Microscopy shows light- to dark-brown hyphal fragments with clear septa, 2–6 µm in diameter; some segments may be distorted or swollen into yeast-like forms.

Skin Biopsy and Histopathology:

• H&E stain: a subcutaneous cyst with a thick fibrous wall and a central area of suppurative necrosis containing many neutrophils, macrophages and multinucleated giant cells. Naturally brown hyphae are scattered through the necrotic center.
• Fontana-Masson stain (specific): a silver-based stain that highlights the melanin in the hyphal walls. It is especially useful when the fungus is so lightly pigmented that it is hard to see on routine H&E.
• PAS / GMS stains: clearly outline the hyphal walls and branching pattern.

Fungal Culture and Species Identification:

• The specimen is cultured on Sabouraud dextrose agar (SDA) at 25°C and 37°C.
• Dematiaceous molds grow as olive-green, gray-black or velvety black colonies. The species is then identified by examining spore morphology under the microscope or by PCR/sequencing (Exophiala, Alternaria, etc.).

Our Multimodal Treatment Approach at Haute-Derma

Complete Surgical Excision of the Cyst – The Gold Standard

For a localized subcutaneous lesion (phaeohyphomycotic cyst), removing the entire cyst together with its fibrous capsule is the most definitive treatment.

• Technique: the incision follows the natural skin creases, and the cyst is carefully dissected out intact (rupture would spill spore-laden pus into the surrounding tissue and seed a recurrence). The surgical field is then irrigated with an antiseptic solution.

Systemic Antifungal Therapy

Used before or after surgery, or on its own when the lesions are too extensive to operate on:

• Itraconazole:
  • Dose: 200–400 mg/day, taken right after a high-fat meal.
  • Duration: 2–6 months, depending on clinical response and how completely the lesions clear.
• Voriconazole / posaconazole: reserved for severe invasive or deep infections, or for strains resistant to itraconazole (voriconazole 200 mg twice daily).
• Amphotericin B (liposomal formulation): the required regimen for disseminated phaeohyphomycosis or internal organ involvement in immunocompromised patients.