Onychomycosis, fungal infection of the nail, is common but difficult to treat. Non-dermatophyte molds account for approximately 10% of onychomycosis worldwide¹, and it is hard to clinically differentiate non-dermatophyte from dermatophyte infection. Therefore, evaluations such as fungus culture, biopsy and sequencing should be performed to identify the exact strain of the fungus. One of the non-dermatophyte molds is Fusarium species, a saprophyte abundant in soil and involved mainly in decaying crops. Human infection caused by Fusarium species is distinct from local infections such as keratitis, skin infection and onychomycosis, and systemic infections². In onychomycosis, Fusarium species commonly affects toenails which have existing trauma or nail dystrophy. Fusarium solani and Fusarium oxysporum are relatively common pathogens^3,4, but Fusarium proliferatum is a rare pathogen. We report a case of a 68-year-old woman with fingernail onychomycosis caused by Fusarium proliferatum, which was diagnosed by fungus culture and sequencing.

A 68-year-old woman presented with an onychodystrophic nail lesion on the left third fingernail, which occurred after chemotherapy for advanced gastric cancer. Upon initial examination, it manifested as white- to yellow-colored patches on the left third fingernail plate, with a rough surface and subungual hyperkeratosis (Figure 1). It was accompanied by nail brittleness and whitish horizontal lines on the proximal part of the nail. A smear with 10% potassium hydroxide (KOH) and fungal culture were performed. The KOH smear showed a number of hyphae, and non-dermatophyte type mold was cultured on Sabouraud's dextrose agar plates, suggesting fungal infection. The patient started four cycles of oral itraconazole pulse therapy (200 mg bid × 7 days) and 5% topical amorolfine treatment, but the condition did not improve. A KOH smear and fungal cultures were conducted again to identify the reason for this failure. The KOH smear showed multiple long hyphae with vertical branches (Figure 2A). After incubation in Sabouraud's dextrose agar plate at 25℃ for four days, colonies started to grow. White-colored villous colonies with central brownish discoloration were formed, suggesting infection by Fusarium species (Figure 2B, C). To identify the exact strain of fungus, sequencing was performed with an internal transcribed spacer (ITS) region isolated from the colonies. This sequence was 100% identical with Fusarium proliferatum (GenBank accession number EF534188.1, Figure 3). A BLAST search showed that the most similar strain was Fusarium proliferatum. The patient was finally diagnosed as suffering from onychomycosis caused by Fusarium proliferatum. She was treated with oral fluconazole 150 mg per week, topical amorolfine 5%, and laser therapies simultaneously. Topical amorolfine 5% was applied after CO2 laser holing. The lesion had improved a year after her first visit (Figure 4), but follow-up was lost due to the patient discontinuing visits to our clinic.

Figure 1. White- to yellow-colored patches on the left third fingernail plate with rough surface and subungual hyperkeratosis

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Figure 2. (A) KOH revealed long hyphae with vertical branches. (B, C) White-colored villous colonies with central brownish discoloration were cultured on Sabouraud's dextrose agar plates.

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Figure 3. The nucleotide sequence of the internal transcribed spacer (ITS) region of the cultured fungus was 100% identical with Fusarium proliferatum (GenBank accession number EF534188.1)

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Figure 4. Improved left third fingernail plate after one year of treatment

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Onychomycosis is a fungal infection of nails caused by dermatophytes, non-dermatophytes, and yeasts. The causative agents of 90% of onychomycosis are dermatophytes such as Trichophyton rubrum and Trichophyton interdigitale, and the remaining 10% is caused by non-dermatophyte fungus such as yeast, Acremonium, Aspergillus, and Fusarium species⁵. Fusarium species accounts for about 3% of all onychomycosis⁶. Fusarium species is a harmless saprotroph and is widely distributed throughout the world. It causes a wide range of infections, from local opportunistic infections such as keratitis and onychomycosis to systemic infections in immunosuppressed patients³. Onychomycosis caused by Fusarium species mainly occurs in toenails with previous dysplasia or traumas, and infections involving the fingernail are not common. In previous case reports, onychomycosis caused by Fusarium species showed clinical features of distal and lateral subungual onychomycosis⁷. The most common pathogens among Fusarium species are Fusarium oxysporum and Fusarium solani. In a KOH smear, the hyphae vary in thickness, with branches at 45 degrees or 90 degrees, and multiseptated fusiform macroconidias are observed⁸. Fusarium species grows rapidly in Sabouraud's dextrose agar plate at room temperature and forms colonies covered with white fluffy hyphae within four to five days. Various colors such as purple, orange and green appear at the later stages, according to the species⁹.

In the case reported here, onychomycosis developed in an immunocompromised patient after chemotherapy for advanced gastric cancer. There was no evidence of any other systemic infection or local infection such as keratitis. The clinical features of the nail lesion were similar to those of distal and lateral subungual onychomycosis. However, it is noteworthy that our case occurred in the fingernail, as toenails are the main site of onychomycosis caused by Fusarium species.

As Fusarium species is ubiquitous in soil, onychomycosis cannot be diagnosed only because it is observed in nails. Diagnosis is possible if Fusarium species is cultured over time, and if dermatophyte infection is excluded¹⁰. Recently, the nucleotide sequence analysis of the ITS region of the fungus strain has been used to confirm the pathogen causing onychomycosis¹¹.

In this case, a Fusarium species were cultured in two fungus cultures. To identify the exact fungus strain, we performed nucleotide sequencing of the ITS region isolated from the fungus DNA and BLAST was performed using the DNA sequence. Fusarium proliferatum was the highest-scoring result, and the patient was finally diagnosed as having onychomycosis caused by Fusarium proliferatum.

Some previous case reports of Fusarium onychomycosis showed successful treatment with itraconazole or terbinafine⁷. However, in this case, the patient was resistant to itraconazole and the treatment was changed to fluconazole. She also received topical antifungal therapy and laser therapy, including topical amorolfine 5% applied after CO2 laser holing. After the combination therapy, her nail lesion improved. Some research has been undertaken into the effectiveness of laser therapy in treating onychomycosis, but there is no clear consensus. Further studies regarding effective antifungal therapy for Fusarium onychomycosis and the use of laser therapy in treating onychomycosis are needed.

A few cases of onychomycosis caused by Fusarium have been previously reported, of which Fusarium proliferatum accounts for a small percentage. In Korea, cases of Fusarium solani, Fusarium oxyporum and Fusarium verticilloides infections have been reported^9,12,13. There are a few cases of onychomycosis due to Fusarium proliferatum but, as far as we know, it has not yet been reported in Korea. Therefore, we report a rare case of onychomycosis occurred in the left third fingernail, caused by Fusarium proliferatum.

The patient provided written informed consent for the publication and the use of his or her images.