Phaeohyphomycosis: causes, symptoms, diagnosis, and treatment

Phaeohyphomycosis, also known as phaeosporotrichosis, is a subcutaneous or systemic infection caused by dematiaceous fungi, with brown septate hyphae.


Causes

The pathogens are dematiaceous fungi, such as Exophiala, Phialophora, Alternaria, Cladosporium, Cercospora, Curvularia, Phoma, Helminthosporium, Drechslera, Bipolaris, and Exserohilum. These fungi are conditioned pathogens.


Signs and Symptoms

Patients are mostly outdoor workers.

Superficial cutaneous phaeohyphomycosis is manifested by superficial ulcers, ecchymosis, brownish black spots, or verrucous hyperplasia. Subjective symptoms are pruritus or mild pain, but sometimes subjective symptoms are absent.

Figure 1 phaeohyphomycosis on the face

Corneal infection is characterized by ulcers, photophobia, tearing, and visual impairment. Lacrimal gland infection is manifested by obstruction of lacrimal duct, pyorrhea, and local granuloma.

Nasal sinus infection is manifested by nasal obstruction or facial pain, and sometimes exophthalmos. Symptoms of allergic rhinitis are present.

Subcutaneous phaeohyphomycosis is often manifested by solitary, deep, few centimeters in size, subcutaneous or muscular abscesses or cysts, and the entire chest can be involved. Skin lesions are brownish red or grayish black, with infiltration, with rough surface, generally without rupture. Thin pus in the subcutaneous tissue and exudate in the cysts can be seen in biopsy. If the cyst wall is incompletely excised, sinus tracts may form, leading to protracted duration.

Systemic phaeohyphomycosis results from cutaneous or subcutaneous dissemination to the lymph nodes, lungs, brain, and gallbladder. Skin lesions may be absent. Cerebral phaeohyphomycosis presents with acute onset and poor prognosis.


Histopathology

The lesions are confined to the dermis and subcutaneous tissue, and the epidermis is rarely involved. Solitary lesion is usually surrounded by large amounts of gelatinous connective tissue. The central, cystic liquefaction, containing pus or exudate, is surrounded by wide granuloma. There are a large number of giant cells, epithelioid cells, neutrophils, and occasionally eosinophils. Brown septate hyphae are easy to be found in the central necrosis and the edges of granuloma. The hyphae are different sized, branched or unbranched, 2 - 6μm in diameter. Dense septa and contractions in some hyphae can be seen. Sometimes 25μm or larger in diameter, thick-walled, swollen, bubble-like cells can be seen, resembling chlamydospores. Occasionally, the hyphae are disorganized.

Brown hyphae can be seen in HE stain, and generally no special stain is required.

Visceral lesions, including brain infections, are mixed suppurative granulomatous reactions with abscess formation. Abscesses are solitary or multiple, up to 5cm in diameter. The central area is composed of neutrophils and fragments of necrotic cells, and is surrounded by multinucleated giant cells, epithelioid cells, plasma cells, and lymphocytes. Brown hyphae are more common in pus and can also be found in giant cells on the wall of granuloma. The hyphae are scattered or piled, brown, septate, beaded.


Diagnosis

On the basis of clinical findings, fungal microscopy, and histopathology, the disease can be diagnosed. Masson-Fontana stain and KOH examination can assist in the diagnosis.


Treatment

Subcutaneous nodules can be cured with surgical excision. Although voriconazole and posaconazole have been used widely and good therapeutic effects are present, itraconazole is with excellent antifungal activity in most clinical practices. The duration of treatment varies from 6 weeks to > 12 months. Amphotericin B is often ineffective.

Brain abscesses and disseminated infections are often treated with antifungal combination therapy, such as 2 - 3 medications with at least an azole, but clinical effects are usually poor.