This study presents the first case of
Fusarium proliferatum-induced lip ulcer in an immunocompetent state which was an unusual manifestation of a rare infection. Another point that makes our case very impressive was its susceptibility to itraconazole and subsequent successful treatment without recurrence of infection with oral itraconazole. Sometimes chronic mucocutaneous ulceration represents an underlying clinical problem and diagnostic challenge affecting the quality of life. Opportunistic fungal infections of the skin are becoming more prevalent with the increased use of single and multi-agent immunosuppressive medications [
7]. Known risk factors for these infections include severe illness and debility, hematopoietic malignancy, diabetes mellitus, hematopoietic or solid-organ transplantation, long term or massive doses of antibiotics, long-term of parenteral nutrition, drug addiction, human immunodeficiency virus (HIV) and use of immunosuppressants [
3]. The clinical manifestations of
Fusarium infections depend on the route of infection and the host immune system condition. The genus
Fusarium is an opportunistic fungus with a worldwide distribution that has been associated with various infections such as keratitis, fungus ball, paranasal sinusitis, and abscesses caused by plant thorns [
8]. The most common mucocutaneous manifestations of the infection are umbilicated or necrotic papules, pustules, abscesses, cellulitis, and subcutaneous nodules. While in immunocompetent hosts, onychomycosis and keratitis are the most common forms [
9]. Localized skin lesions in immunosuppressed patients should be considered as they may be a sign of disseminated and life-threatening fusariosis. Nevertheless, little is known about
Fusarium cutaneous infections in healthy people. In immunocompetent conditions, cutaneous infections by
Fusarium are characterized by preceding skin breakdown, localized involvement, slow pace of progression, and acceptable response to therapy [
9]. In localized deep fungal mucocutaneous infections, especially in immunocompetent patients, a history of direct trauma is an important clue for infection. The patient we reported here had no well‐defined and classical risk factors for opportunistic infection. Also, she had no remarkable history of trauma, cosmetic tattoo, or burning on her lips. The diagnosis of
Fusarium infection is established by detecting fungal elements in tissue. This can be performed by conventional microbiological methods or molecular techniques. In the present case, the diagnosis of
Fusarium species was carried out by direct visualization of fungal hyaline hyphae in scrapings and positive culture, leading to administration of the antifungal susceptibility testing and molecular identification. Since the microscopic and macroscopic features of the
Fusarium species are frequently variable in subculture scenes [
10], species identification becomes challenging by traditional tests. However, in the majority of clinical cases, the identification performed by phenotypic methods [
11], the species remains unidentified. The ITS sequence was applied to identify the current isolate. Although elongation factor (
TEF1) has been widely used for species identification in the genus
Fusarium, application of the nuclear ribosomal ITS sequence should be worthy of placing most strains within the relevant complex. This region will not be able to discriminate among individual species within the complex [
12] (one of the limitations of the present study). Still, it is reliable for confirming the phenotypic diagnosis. Patients with localized infection usually need surgical debridement and topical antifungal drugs [
3]. The routine antifungal susceptibility pattern of
Fusarium species reveals the resistance to most antifungals; however, various species may have different susceptibility patterns [
13]. In general,
Fusarium isolates exhibit quite high MIC values for ketoconazole, flucytosine, fluconazole, miconazole, posaconazole, and itraconazole, and low MICs of natamycin, econazole and amphotericin B [
14]. In contrast to the report of Nucci
et al. [
3] that all
Fusarium strains were resistant to itraconazole, the current isolate was susceptible to itraconazole (MIC: 0.032 mg/mL). Some experts have suggested combination therapy with the justification that since most
Fusarium species exhibit high MICs for voriconazole, it would be trusty to start treatment with amphotericin B and an azole (generally voriconazole) [
15].
Fusarium species show a large variability of resistance to antifungals. For example,
F. dimerum is commonly susceptible to itraconazole and voriconazole, whereas
F. oxysporum is more susceptible to terbinafine than other antifungal agents [
16]. All
Fusarium species are resistant to fluconazole; nevertheless, susceptibility to posaconazole is variable [
17,
18]. This is an important point in clinical practice when selecting empiric antifungal therapy in patients with clinical suspicion of localized opportunistic fungal infections and unusual presentation; uncommon species also should be considered for initiating antifungal therapy.