Phaeohyphomycosis is a rare infectious disease caused by dematiaceous fungi. The condition commonly affects cuta- neous or subcutaneous skin layers and, less commonly, visceral organs. Although these dematiaceous fungi are generally nonpathogenic to humans, they can produce opportunistic infections in immunocompromised individuals¹. Phaeohypho- mycoses are characterized by melanin, which is responsible for the spores' dark pigmentation, and conidia, which likely function as a virulence factor².

Most phaeohyphomycosis cases are caused by Exophiala (E.) jeanselmei and Wangiella dermatitidis, although other, less-common species have been implicated³. In Korea, E. jeanselmei is the most common causative species, followed by E. dermatitidis, Dreschslera dematioidea, Phoma species, and Alternaria species⁴.

E. xenobiotica can cause phaeohyphomycosis5; however, few cases have been reported, and none from Korea. This report describes the case of an immunocompetent patient with phaeohyphomycosis caused by E. xenobiotica.

A 75-year-old female presented with an asymptomatic, erythematous, and crusted subcutaneous nodule on her left-hand dorsum (Fig. 1A, 1B). The lesion gradually enlarged over the preceding 2 years without associated tenderness or purulence. Her past medical history was significant for hypertension, atrial fibrillation, and hyperlipidemia. Further, she showed no evidence of immunosuppression. The patient was living in an urban area, did not work, and recalled no history of trauma to the affected area.

Figure 1. (A, B) An enlarged, solitary, 1.5-cm erythematous crusted nodule on the left-hand dorsum without tenderness or purulence (C) The lesion appears significantly improved after treatment.

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Histopathological findings revealed suppurative granu- lomatous infiltration of the dermis with multinucleated giant cells with lymphohistiocytic and neutrophilic elements. Septate hyphae and spores were stained with periodic acid-Schiff (PAS) in the dermis (Fig. 2). A fungal culture created from skin tissue on Sabouraud dextrose agar (SDA) showed micro- scopic olivaceous, black velvety colonies and black and septate hyphae with single-celled conidia (Fig. 3). Molecular identifi- cation through internal transcribed spacer (ITS) sequencing showed a 99% match with E. xenobiotica.

Figure 2. Histological features of the biopsy specimen taken from the cutaneous lesion (A) Incisional biopsy on the lesion shows suppurative granulomatous infil- tration in the dermis (H&E, ×40). (B) Multinucleated giant cells, lymphohistiocytes, and neutrophils (H&E, ×200) are evident. (C) Septate hyphae and spores in the dermis (PAS, ×400)

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Figure 3. (A) Fungal culture on Sabouraud dextrose agar (SDA) shows olivaceous, black-colored velvety colonies. (B) Microscopic morphology shows black, septate hyphae and single-celled conidia.

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We diagnosed the patient with phaeohyphomycosis and began a 3-week course of terbinafine rather than itraconazole due to the potential for a drug interaction with nonvitamin K antagonist oral coagulant (NOAC). With only slight im- provement with terbinafine, she continued treatment with fluconazole after tapering the NOAC. The lesion was signifi- cantly improved after 3 months (Fig. 1C), at which time treatment stopped. There have been no recurrences over the 10 months that have passed since stopping treatment.

Phaeohyphomycosis is a rare subcutaneous or systemic infection caused by dematiaceous fungi such as Bipolaris, Phialophora, Alternaria, and Exophiala¹. Melanin is respon- sible for these species' black coloration, directly involved in phaeohyphomycoses' virulence. Melanin resists oxidation by free radicals within the hosts' phagocytic cells and binds to hydrolytic enzymes within phagocytic cells and to antifungal medications⁶. These infections occur across all climates, but are more common in the tropics. It is frequently observed in immunocompromised patients, particularly patients receiving long-term glucocorticoid therapies. Many patients also report a history of trauma to the affected area⁷. Phaeohyphomycosis typically manifests as a solitary abscess or nodule on an ex- tremity. Histopathological examination and cultures are used to identify the fungal pathogen and differentiate it from sporotrichosis, chromoblastomycosis, and eumycetoma⁸.

The Exophiala genus comprises 29 species, 18 of which are infectious. The most commonly isolated genera of dematiaceous fungi that cause phaeohyphomycosis are E. jeanselmei, E. spinifera, and E. dermatitidis⁹. Typically E. species are identified morphologically and physiologically. Macroscopically, they manifest as dark olivaceous-to-black colonies; microscopically, they exhibit septate hyphae and conidiophores with numerous conidia. Recent advances in molecular tools have supplemented traditional diagnostic approaches, particularly rDNA sequencing of the ITS region. This method identifies distinct morphologically indistinguish- able strains, enabling clinicians to assess prognosis¹⁰. E. xenobiotica was initially classified as E. jeanselmei; however, newer, molecular methods revealed the novel species. E. xenobiotica is commonly found in habitats rich in monoaro- matic hydrocarbons and alkanes, such as industrial biofilter sites¹¹. Despite her denial of any work or trauma history, we suspect that a past minor trauma contributed to the infection.

E. xenobiotica is less virulent than other E. species and is frequently associated with cutaneous infections of mild-to-moderate severity10. However, there is disagreement as to the optimal treatment. A combined-modality treatment of antifungal drugs and surgery has shown promising clinical outcomes^12,13. Additionally, itraconazole and posaconazole are more effective against E. species than voriconazole or amphotericin B5.

Our case illustrates the efficacy of a combination treatment comprising terbinafine and fluconazole, but without concomi- tant surgery. A literature review revealed 7 cases of phaeo- hyphomycosis caused by E. xenobiotica (Table 1)^{5,12,13,15-17} and we know of no other case reported from Korea. Of the published cases, 6 of 8 (75%) occurred in immunocompro- mised patients; however, our patient was immunocompetent. This suggests that although E. xenobiotica infections are com- monly observed in immunocompromised patients, patients without overt immunocompromise may also be susceptible. This is the first report of phaeohyphomycosis caused by E. xenobiotica in an immunocompetent patient who was suc- cessfully treated with terbinafine and fluconazole. Considering the rarity of E. xenobiotica infections and the fact that no standard treatment exists, more reports are needed to estab- lish treatment strategies.