Pheohyphomycosis is a rare fungal infection caused by more than 100 species of dematiaceous or pigmented fungi with melanin-containing cell walls. The most common species include Exophiala, Wangiella, and Phialophora. These organisms are found in moist environments, such as decaying vegetation, wood, and soil. The disease exhibits increased prevalence and severity in immunocompromised patients. Infection can occur via traumatic inoculation to the skin or inhalation. A deficiency of CARD9 (caspase recruitment domain-containing protein 9) has been associated with phaeohyphomycosis.

Pheohyphomycosis causes a wide spectrum of clinical presentations. The organisms may be inoculated into the skin or subcutaneous layer after minor trauma. In immunocompetent persons, a solitary skin-colored or erythematous nodule that may resemble a cyst is seen. In immunosuppressed individuals, nodules may be ulcerated, necrotic, or crusted, and these may enlarge progressively. The most common locations are the feet, fingers, knees, toes, ankles, legs, and forearms.

Pheohyphomycosis can be life-threatening when it spreads to the central nervous system, usually after inhalation, by causing brain abscess, meningitis, encephalitis, myelitis, or arachnoiditis. Immunocompromised hosts are at increased risk for a life-threatening disseminated infection after primary inoculation or inhalation and therefore should be treated aggressively.

Other clinical presentations include keratitis, sinusitis, pulmonary disease, or endocarditis.