Exophiala dermatitidis is typically considered a human
opportunistic pathogen, as those affected by
E. dermatitidis often have underlying health conditions. An exception to this is the neurotropic clinical presentation, which is typically found in young and otherwise healthy individuals. While over 100 fungal species can cause
phaeohyphomycosis,
E. dermatitidis is one of the two fungi most frequently implicated, along with another
Exophiala species,
E. jeanselmei.
Exophiala dermatitidis is considered to be one of the most pathogenic fungi in the genus
Exophiala, and is highly deadly, with a fatality rate of over 40%. The high fatality rate is primarily due to an ability to form systemic and neurotropic infections, which represent approximately half of reported
E. dermatitidis cases.
Local and superficial infections Exophiala dermatitidis forms cutaneous and subcutaneous phaeohyphomycosis, which most commonly affect the face and neck. Indeed, the fungus was originally isolated from the skin of a patient with lesions on their cheek, neck, and ear. Cells isolated from cutaneous infections are often spherical, and may form toruloid or moniliform chains.
Exophiala dermatitidis has been implicated various superficial infections including
onychomycosis,
otitis externa, and eye infections causing
keratitis. In Europe
E. dermatitidis tends to be associated with cystic fibrosis, and is frequently found to have colonized the lungs of CF patients. In one study,
E. dermatitidis could be isolated from 6.2% of cystic fibrosis patients using erythritol-chloramphenicol agar culture dishes.
Exophiala dermatitidis has also been reported as the etiological agent of lung infections causing pneumonia.
Systemic infections Exophiala dermatitidis forms neurotrophic infections, and is the black yeast that most commonly causes life-threatening phaeohyphomycosis. Conditions that might predispose people towards an invasive opportunistic infection include
diabetes mellitus,
lymphocytic leukemia,
bronchiectasis,
rheumatoid arthritis, and
catheterization. Systemic infections are often reported to be without cutaneous or subcutaneous involvement. Systemic
E. dermatitidis infections can include cerebral metastases. The fatality rate for such infections is reported to be over 90%. Central nervous system phaeohyphomycosis is rare, and for unknown reasons primarily arise in East Asia, despite a
cosmopolitan distribution of the fungus. Within East Asian populations, young and otherwise healthy people have developed cerebral infections. Lung infections in European CF patients and neurotropic mycosis in East Asia are caused by
E. dermatitidis strains that are genetically similar, and host factors such as immunological differences may be responsible for the different infection patterns.
Exophiala dermatitidis occurs at very high frequency in both Asian and European saunas, and absence of neurotrophic mycosis in Europe isn't explained by reduced exposure to the fungus. In 2002 a small outbreak of systemic
E. dermatitidis infection occurred in North Carolina hospitals, involving five women who received
steroid injections for pain management. In one of women the infection wasn't evident until 152 days after injection of the contaminated solution. Isolates from these patients were found by the
FDA to be susceptible to all of
voriconazole,
itraconazole, and
amphotericin B. In one patient the infection caused
sacroiliitis, while the remaining four developed
meningitis. Meningitis eventually caused death in one patient, while voriconazole was successful in treating infection in the four other patients. The outbreak was traced back to a single
compounding pharmacy, which was found by the FDA to have inadequately controlled for sterility of its products.
Immune response Exophiala dermatitidis typically causes a
non-specific and
granulomatous inflammatory response.
Lymphocytes,
histiocytes,
multinucleated giant cells and
neutrophils are recruited. The host responses are highly variable, often include
cyst formation, and vary from weak reaction to an intense inflammatory response that results in tissue
necrosis. As with other
black yeasts that cause phaeohyphomycosis,
melanin appears to have defensive purpose, and helps protect
E. dermatitidis from death within human
neutrophils. Pathogenic strains of
E. dermatitidis contain five times more melanin than
saprophytic E. dermatitidis, while melanin deficient mutants of pathogenic strains have dramatically reduced virulence.
Treatment A diagnosis of
E. dermatitidis infection of the CNS can only be reliably achieved following biopsy. For systemic infections there are few treatment options, and
E. dermatitidis is described as "notoriously resistant" to antifungal drugs. During the North Carolina outbreak, treatment with voriconazole was effective in four out of the five patients, and all of voriconazole, itraconazole, and amphotericin B were found to be effective
in vitro. Terbinafine has also been found to be effective
in vitro, and combinations of antifungal drugs can have a synergistic effect against
E. dermatitidis. A 2012 article found that of reported cases, 44% of patients responded to amphotericin B treatment, 50% responded to voriconazole treatment, and 71.4% responded to itraconazole therapy. For small and local infections surgery may be an option. As
E. dermatitidis infections are believed to be caused by traumatic implantation of the fungus, surgeons must be exceedingly careful to not re-introduce infection during operation. Despite the high heat tolerance of
E. dermatitidis, heat treatment of cutaneous lesions have been effective. == References ==