Dermatophyte antigen kit: A useful diagnostic tool for onychomycosis.

A dermatophyte antigen kit (DQT) was released in Japan as an in vitro diagnostic tool to identify tinea unguium in June 2022. From July 2022 to February 2023, we examined 75 potassium hydroxide (KOH)-negative patients (male, n = 23; female, n = 52; mean ± SD age, 63.6 ± 13.9 years) and determined the accuracy in confirming the fungal element with ZoomBlue™ staining at 400× magnification. The DQT results were classified into three categories. DQT-positive onychomycosis was detected in 27 patients with tinea unguium and two with non-dermatophyte onychomycosis. Fungal cultures were positive in 14 (51.8%) patients (Trichophyton rubrum [n = 11], T. interdigitale [n = 1], Fusarium solani [n = 1], and Talaromyces muroii [n = 1]). DQT-negative onychomycosis included ten patients with cured tinea unguium and 3 with Candida onychomycosis. Twenty-three patients had DQT-negative mimics for onychomycosis (onychauxis [n = 11], traumatic onycholysis [n = 8], yellow nail syndrome [n = 5], pincer nail deformity [n = 3], brittle nail syndrome [n = 2], contact dermatitis [n = 2], lichen planus [n = 1] and psoriasis [n = 1]). Because sparse, atrophic and/or fragmented mycelia are invisible in direct microscopy with potassium hydroxide (KOH) at 100× magnification, DQT was beneficial for diagnosing onychomycosis.

Empiric antifungal therapy in patients with cutaneous and subcutaneous phaeohyphomycosis.

We encountered two cases of phaeohyphomycosis caused by Exophiala jeanselmei and E. oligosperma that were treated with fosravuconazole and terbinafine, respectively. Our cases were successfully treated with empiric therapy before the pathogen's species or antifungal sensitivity had been determined. We summarized 32 cases of cutaneous and subcutaneous phaeohyphomycosis caused by Exophiala species in Japan. The patients received antifungals, including itraconazole, terbinafine, voriconazole, and fosravuconazole, and the treatment success rates of these monotherapies were 77% (17/22), 67% (8/12), 100% (5/5), and 50% (1/2), respectively. Although the broad-spectrum azole antifungal itraconazole is the first choice for treatment, terbinafine at 125 mg/day might exert the same efficacy. Fosravuconazole is a novel broad-spectrum azole and a moderate inhibitor of Cyp3A4 that causes fewer drug interactions than itraconazole and voriconazole, indicating a promising drug for this disease.

Genomic landscape of circulating tumour DNA in metastatic extramammary Paget's disease.

Although cancer personalized profiling by deep sequencing (CAPP-Seq) of cell-free DNA (cfDNA) has gained attention, the clinical utility of circulating tumour DNA (ctDNA) in extramammary Paget's disease (EMPD) has not been investigated. In this study, genomic alterations in the cfDNA and tumour tissue DNA were investigated in seven patients with metastatic EMPD. CAPP-Seq revealed mutations in 18 genes, 11 of which have not yet been reported in EMPD. The variant allele frequency of some of the mutated genes reflected the disease course in patients with EMPD. In one patient, the mutation was detected even though imaging findings revealed no metastasis. In another patient with triple EMPD (genital area and both axilla), cfDNA sequencing detected the mutation in a rib metastatic lesion, which was also detected in both axilla lesions but not the genital region. Investigations of the ctDNA may be useful towards the elucidation of clonal evolution in EMPD.

Topical efinaconazole: A sequential combination therapy with oral terbinafine for refractory tinea unguium.

Efinaconazole is a topical antifungal drug approved in Japan for tinea unguium. Although topical treatments generally have low cure rates with a prolonged therapy period, a Cochrane review confirmed that high-quality evidence supports the effectiveness of efinaconazole for the complete cure of tinea unguium. Combination therapy is a way to improve the cure rate of onychomycosis. In this study, topical efinaconazole was administrated to 12 patients who had been treated with oral terbinafine (125 mg daily) for more than 20 weeks with little expected effect. Because terbinafine accumulates for a long time in the nail, treatment immediately followed by other drugs can be considered sequential combination therapy. During terbinafine monotherapy, the percentage involvement decreased from 53.5% to 44.0% after 37.4 weeks and the effective and cure rates were 16.7% and 0%, respectively. During sequential topical efinaconazole therapy combined with lasting terbinafine in the nail, the percentage involvement decreased from 44.0% to 18.7% after 28.4 weeks, and the effective and cure rates were 66.7% and 16.7%, respectively. The improvement rate per month of combination therapy (12.6%) was higher than that with monotherapy (2.1%) (p = 0.002). There were no serious side-effects. This sequential combination therapy with efinaconazole was effective in poor terbinafine responders, making it a promising regimen for improving the cure rate of tinea unguium.