Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.

Primary cutaneous mycotic cysts are uncommon dermal or subcutaneous fungal lesions. The most commonly implicated organisms are species within a heterogeneous group of pigmented fungi called dematiaceous fungi. Mycotic cysts usually present as solitary lesions and can be caused by traumatic introduction of fungal elements by foreign bodies or present as a cutaneous manifestation of systemic fungal infections, especially in immunocompromised patients. We present a case of a 63-year-old immunocompetent male who developed a non-erythematous solitary nodule after doing yardwork. Histopathologically, a benign-appearing epidermal inclusion cyst was apparent containing a splinter with keratinous granular debris and no indication of inflammatory host reaction. However, abundant non-pigmented hyphae were visualized after a periodic acid-Schiff stain was performed. This case offers an interesting histopathological view of a non-pigmented mycotic cyst contained within an epidermal inclusion cyst with a true epithelial lining. It also raises the question of whether mycotic cysts caused by non-pigmented fungi are rare or simply under-diagnosed because of their deceptively benign initial appearance. Even in the absence of an inflammatory or granulomatous host response, we recommend investigating for fungal elements in lesions where a splinter or other foreign body material is present in order to avoid misdiagnosis.