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Summary: Background: Tinea is an infectious disease by dermatophytes, of which Trichophyton species accounts for the overwhelming majority of case. Tinea often causes itching with inflammation. In terms of pruritus by fungal infection, however, tinea has not been investigated sufficiently to date. Aim: To evaluate itch caused by Trichophyton infection and the effect of antifungal agents on the infection, by measuring scratch behaviour and profiles of inflammatory cytokines and chemokines. Methods: We used a previously established mouse model of contact hypersensitivity induced by trichophytin, a crude extract from Trichophyton mentagrophytes. Scratching behaviour was recorded using a counting device that measured an electric current induced in a coil by movement of magnets that had been inserted into the hind paws of each animal. We investigated expression of various genes in lesional skin of mice and in normal human epidermal keratinocytes. We also investigated the antipruritic effects of the corticosteroid dexamethasone (DEX) and three antifungal agents: ketoconazole (KCZ), terbinafine (TBF) and liranaftate (LNF). Results: Biphasic peaks of scratching were observed at 1 h and at 6–7 h during an observation period of 14 h after trichophytin induction. For lesional skin, RNA was extracted 24 h after trichophytin challenge, and increased expression was seen in the genes for interleukin (IL)‐17A, interferon‐γ, tumour necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐2 and Dectin‐1, whereas there was no obvious change in the genes for IL‐31 and prostaglandin (PG)E2. Furthermore, KCZ inhibited histidine decarboxylase (HDC) expression in vitro and in vivo, and inhibited scratching in the very early phase. LNF inhibited expression of thymic stromal lymphopoietin (TSLP) and IL‐8 in vitro, and TSLP, TNF‐α, IL‐1α and MIP2 in vivo, and also scratching in the early phase. TBF did not induce any significant alterations in either gene expression or scratching. DEX suppressed expression of all the chemical mediators except HDC in vitro and in vivo, and inhibited scratching. Conclusion: Antifungals can inhibit itching induced by fungal infection through different mechanisms. [ABSTRACT FROM AUTHOR]

A 42-year-old Vietnamese egg factory worker in Ishikawa prefecture, Japan, presented with itchy concentric erythema on the trunk and left calf. The lesions tested positive by direct potassium hydroxide examination, and two fungal strains were isolated. The isolates produced conidia abundantly and were morphologically indistinguishable from Trichophyton mentagrophytes/interdigitale, but were identified as Trichophyton indotineae by internal transcribed spacer sequence of ribosomal DNA. The lesions were refractory to treatment with topical luliconazole (LLCZ) cream for 4 weeks but subsided with oral itraconazole (ITCZ) 100 mg/day for 4 weeks in combination with topical lanoconazole (LCZ) cream. The lesions recurred 6 weeks after discontinuation of oral ITCZ, and an additional isolate was cultured. The minimum inhibitory concentrations of antimycotics for the isolate cultured at the first visit were: terbinafine (TBF) 0.03 μg/mL, ITCZ 0.015 μg/mL, LLCZ 0.0005 μg/mL, and LCZ 0.002 μg/mL. No TBF-resistant mutation in the amino acid sequence of squalene epoxidase, i.e., Leu 393 Ser/Phe or Phe 397 Leu, was detected in the isolate. The reason for recalcitrance in this case, despite the isolate's sensitivity to antimycotics, was unclear. Possible factors include insufficient use of the antimycotics, incomplete removal of abundantly produced conidia from the lesions, the patient's environment, and a language gap between the patient and physician hindering communication., (© 2024 Japanese Dermatological Association.)

A 10 yr old spayed female ragdoll cat presented with sudden onset of sneezing, nasal discharge, and stertor. There was no improvement in clinical signs despite treatment with antibiotics, feline interferon, and nebulization. A computed tomography (CT) scan revealed findings consistent with chronic rhinitis, and a tissue biopsy obtained by rhinoscopy led to a histopathologic diagnosis of sinonasal aspergillosis. Polymerase chain reaction amplification identified the causative agent as Aspergillus udagawae. Oral itraconazole therapy was initiated. However, the cat's clinical signs progressed to include left exophthalmos, nictitating membrane protrusion, and lacrimation. A second CT scan revealed a soft-tissue attenuating structure extending into the left retrobulbar space, confirming progression to sino-orbital aspergillosis (SOA). The oral medication was changed to posaconazole and continued for 5 mo, resulting in resolution of the clinical signs. The cat has remained asymptomatic over 24 mo since initial diagnosis. This case represents the first successful treatment of feline SOA caused by A udagawae infection with posaconazole. A udagawae is the second most common cause of SOA and is known to be intractable because of its low susceptibility to antifungal agents and poor response to topical clotrimazole. Posaconazole may be a valuable treatment option for SOA caused by A udagawae., (© 2024 by American Animal Hospital Association.)

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA in situ hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA in situ hybridization can be a potent tool for detecting the spread of VZV infection in the skin., (© 2024 Japanese Dermatological Association.)

Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its similarity to nail malignant melanoma, particularly with respect to the clinical manifestation of black nail streaks. While skin biopsy is usually employed for diagnosis, it is an invasive procedure. We report the case of a 52-year-old healthy Japanese male with a pigmented streak on the nail of the fourth finger of his right hand, which had extended from the central to the lateral nail fold within 4 months. Dermoscopic examination revealed a dark-brown pigmented band with splinter microhemorrhage. Clinically, nail Bowen's disease was suspected. The lesion was excised in strips under local anesthesia. Histopathological examination revealed hyperkeratosis, parakeratosis, papillomatosis, and dyskeratotic cells with atypical nuclei irregularly arranged. Immunohistochemistry using anti-HPV L1 antibody detected HPV-positive cells in the upper epidermis and stratum corneum of the nail matrix. Mucosal high-risk HPV type 58 DNA was detected from brush cytology of the keratotic surface prior to surgery, which was confirmed in formalin-fixed, paraffin-embedded excised samples using polymerase chain reaction (PCR) and subsequent direct DNA sequencing. Our case highlights HPV type 58 as a potential causative agent of nail Bowen's disease and shows that brush cytology of the surface material prior to excision may be a useful and less invasive way for mucosal high-risk HPV detection. PCR analysis of the nail surface could serve as a supplementary diagnostic tool for nail Bowen's disease., (© 2024 Japanese Dermatological Association.)

An 85-year-old woman with no history of herpes zoster (HZ) presented with a primary lesion of erythema and blistering on her left thigh and a secondary similar lesion on her right chest which had appeared at 4 and 3 days before presentation, respectively. Tzanck smears for both lesions were positive, revealing multinucleated giant cells. Immunochromatography to detect varicella-zoster virus (VZV) antigen (DermaQuick®VZV) showed positive on the left thigh at initial onset but negative on the right chest at subsequent onset. The latter repeatedly tested negative for VZV by DermaQuick®VZV. A skin biopsy of the subsequent onset area revealed giant cells, and inclusion bodies were observed in the epidermis. Immunohistochemical staining with anti-VZV antibody and polymerase chain reaction to detect VZV DNA were positive. The patient was diagnosed with HZ duplex bilateralis and treated with acyclovir. The right thoracic region of the posterior part of the lesion became negative for DermaQuick®VZV. It is thought that expression of viral antigens was suppressed in the right thoracic region, i.e., the late-onset area., (© 2023 Japanese Dermatological Association.)

Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of onychomycosis caused by Fusarium spp., it is characterized by drug sensitivity and other characteristics. Here, we report what may be the first case of onychomycosis caused by Fusarium lactis. We analyzed the mycology and characterized previously reported cases of onychomycosis caused by Fusarium spp. A 73-year-old otherwise healthy woman presented with discoloration and thickening of her right thumbnail with paronychia. Direct microscopy revealed unevenly swollen hyphae, and a Grocott-stained nail specimen showed septate hyphae. Based on the morphological features and gene analysis of fungus isolated from the nail, we diagnosed onychomycosis caused by F. lactis belonging to Fusarium fujikuroi species complex. Partial nail removal and topical application of 1% luliconazole solution resolved the condition in 6 months. Minimum inhibitory concentrations for isolated F. lactis showed high sensitivity to luliconazole but not itraconazole or terbinafine. The isolated F. lactis was temperature-sensitive. A search of the literature revealed 57 cases of onychomycosis caused by Fusarium spp. with delineated clinical characteristics. Since those cases were investigated using morphological and/or molecular methods, we analyzed them by species complex as well as species. Onychomycosis caused by Fusarium spp. is predominantly found on the big toe, with Fusarium solani species complex and Fusarium oxysporum species complex accounting for over 70% of cases. Infection of only one digit with paronychia is a characteristic clinical manifestation of onychomycosis caused by Fusarium spp. Since there has been an increase in instances of molecular determination of Fusarium spp., it is deemed necessary to clarify its clinical and fungal nature. Due to its characteristic drug sensitivity and temperature-sensitive nature, new treatments are expected to be developed., (© 2023 Japanese Dermatological Association.)

Warts, caused by human papillomavirus (HPV) infection, have various clinical presentations, making them difficult to differentiate from clavus, callus, and sometimes, squamous cell carcinoma. Although skin biopsies are the gold standard, a less-invasive method of examining these lesions is desired. Ninety patients with warts and related diseases, such as clavus and callus, were recruited to explore new differentiation methods using the surface of the warts. DNA was extracted from three types of specimens in each case: surface swab, shaved hyperkeratotic scale, and post-shaved surface swab. Total DNA was successfully extracted from these three specimens and was sufficient for subsequent HPV DNA detection. We analyzed samples for the HPV type and HPV viral load using polymerase chain reaction (PCR). Fifty-five cases were PCR-positive, and HPV1a, 2a, 4, 27, 57, and 65 were detected. The amount of HPV1a DNA produced was significantly greater than that of other HPV types. Regarding the correlation between the clinical diagnosis and HPV detection, the positive agreement rate was 90.9%, the negative agreement rate was 40.0%, and the overall agreement rate was 71.1%. Ten of the 21 cases clinically diagnosed as plantar warts were PCR-negative, especially in elderly patients. This suggests that it is difficult to distinguish plantar warts from clavus and callus in clinical practice. Although the amount of HPV DNA in the removed keratinization scale was highest for all HPV types, HPV detection by swabbing before and after shaving is also useful for follow-up as well as for differential diagnosis., (© 2023 Japanese Dermatological Association.)

Exophiala species cause chromoblastomycosis, mycetoma, and phaeohyphomycosis, which are occasionally fatally in immunocompromised patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provides rapid and accurate examination of isolated bacteria and some fungal isolates, but the preparation method for filamentous fungi is complicated. In this study, 31 clinical isolates of Exophiala spp. in Japan were identified by MALDI-TOF MS with a library enriched by adding data. To simplify the sample preparation method, two modified methods were compared with the standard method for filamentous fungi. The agar cultivation sample preparation method reduced the time required for liquid culture and was considered suitable for clinical use. In 30 of 31 clinical isolates of Exophiala spp., the species identified by MALDI-TOF MS with the highest score matched the species identified by sequencing the internal transcribed spacer region. Exophiala dermatitidis, E. lecanii-corni, and E. oligosperma were identified above the genus level, while E. jeanselmei and E. xenobiotica were often not identified at the species level. The identification scores tended to be lower for less-registered strains in the in-house library. It is suggested that library enrichment and the modified preparation method may facilitate early diagnosis of rare fungal infections by Exophiala spp. in clinical laboratories using MALDI-TOF MS., (© 2023 Japanese Dermatological Association.)

Microsporum canis, a major causative agent of zoonotic dermatophytosis, has become prevalent in Japan. Molecular epidemiological surveys using multilocus microsatellite typing (MLMT), a sensitive genotyping tool for fungi, have been conducted to reveal intraspecies polymorphisms of M. canis.The present study utilized MLMT optimized for Japanese strains of M. canis to analyze epidemic trends of fungal infection. Six individual loci were targeted; namely, MS1, 2, 4, 5, 6, and 7. Analysis of data from 1974 through 2022 identified 416 strains, which were sorted into 60 genotypes by MLMT.The major genotypes showed changes in dominance during this period-changes that may reflect historical increases and decreases in the numbers of patients infected with M. canis patients. The main origins of infection included animal breeders and pet stores, as well as stray cat communities. Forty-nine episodes of familial outbreaks and cohabitant animal infections were recorded, and genotypes responsible for each episode were determined. MLMT analysis is not only a robust tool to understand population structures, but likely the most suitable method for tracking M. canis infections.

Trichophyton tonsurans infection has been prevalent among individuals involved in contact sports in Japan since about 2000. The present review focuses on its diagnosis, molecular epidemiology, drug susceptibility, and infection control. The most commonly observed lesions of T. tonsurans, an anthropogenic dermatophyte, are tinea corporis and tinea capitis. However, the presence of asymptomatic carriers must be considered for infection control. Genotypic epidemiology using restriction fragment length polymorphisms (RFLP) in the non-transcribed spacer (NTS) region of the ribosomal RNA gene showed a lack of diversity of genotypes, and only the NTS I genotype is detected at present. In regard to drug susceptibility, terbinafine drug resistance has not been found to be associated with the RFLP genotypes, and it is assumed that there are no terbinafine-resistant strains in Japan. T. tonsurans coexisted with other fungi and bacteria in the scalp of asymptomatic carriers without affecting species diversity. T. tonsurans is an anthropogenic dermatophyte and may be difficult for the human immune system to eliminate. During an infection outbreak, screening of infection and treatment including asymptomatic carriers are essential to eradicate the infection.

Multilocus microsatellite typing was performed on 124 strains of Microsporum canis, which is the most prevalent causative fungus of zoonotic dermatophytosis, isolated in Japan between 1974 and 1981. The strains had been enclosed in glass ampoules by freeze dried process. Genotypes were detected by capillary electrophoresis targeted on six microsatellite regions, and 19 genotypes were found among these 124 strains. The most frequent genotype, which had been reported as genotype L in a previous study, comprised 56 of the 124 strains (45.2%), although genotype L was reported to comprise only six of 165 strains (3.6%) isolated between 2010 and 2017. A decrease in the prevalence of genotype L may have led to the retreat of M. canis infection in 1996 to 2006. On the other hand, genotype A, the second most predominant genotype in the aforementioned studies of strains isolated between 2010 and 2017, comprised just four of 124 strains (3.2%) in the present study. Thus, these studies reveal that prevalences of some major genotypes have changed over the last 40 years. Genotype consistency of strains was proven in all of 12 familial cases, each of which was infected with a single genotype. We emphasize the importance of fungal culture collection for further studies with new techniques in the future., (© 2022 Japanese Dermatological Association.)

Trichophyton tonsurans is the most prevalent fungus which causes dermatophytosis among contact sports players in Japan. We previously surveyed the epidemic of T. tonsurans in Japan from early 2000, and determined the genotypes of isolates by analysis of restriction enzyme fragment length polymorphisms in the non-transcription spacer (NTS) region of ribosomal RNA gene, which enabled discrimination of eight genotypes, namely NTS I to NTS VIII. In the present study, we performed genotyping of T. tonsurans isolated between 2016 and 2020, and investigated the trend of the epidemic and resistance of the pathogen to antibiotic terbinafine (TBF). Regardless of which contact sport they played, the genotype of all 123 strains of T. tonsurans isolated from athletes was NTS I. Genotypes NTS II and III, which were isolated in considerable numbers mainly from wrestlers between 2000 and 2015, were conspicuously absent. TBF susceptibility was screened in 237 T. tonsurans strains isolated between 2000 and 2020 with 28 of these further assessed for minimum inhibitory concentration of TBF and squalene epoxidase gene sequences. None of the strains showed TBF resistance. TBF may still be effective to control the epidemic of T. tonsurans., (© 2022 Japanese Dermatological Association.)

Multilocus microsatellite typing (MLMT) was performed on 93 strains of Microsporum canis (M. canis) isolated between 2012 and 2017 from 75 cats, 8 dogs, and 10 pet owners. These strains were derived from 2 major reservoirs: commercial breeding facilities and pet shops (PS), and stray cats and pet cats that went outdoors and came in contact with stray cats (Outdoor). Six microsatellite markers were used for genotyping. These 93 strains included 22 genotypes; 11 had been previously detected in Japan while the other 11 were new. Strains belonging to the previously reported genotypes, P and A, were distributed widely throughout Japan. Genotype P was the most frequent, accounting for 37 (39.8%) of the 93 strains. Most were derived from Outdoor sources. Genotype A was the second most frequent (11 of 93 strains, 11.8%). Most of the genotype A strains were derived from the PS reservoir. All new genotypes were detected in isolates from cats. Many of these were derived from the Outdoor reservoir. Consistency of infection was observed in 18 of the 19 familial cases. These findings indicate that genotypes differ in strains derived from PS and Outdoor reservoirs. MLMT genotyping is useful for tracking the routes of spread and transmission of M. canis in Japan.

Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) had been used for molecular identification of Sporothrix spp., which is the causative fungi of sporotrichosis and the most prevalent deep-seated dermatomycosis. Also, mtDNA-RFLP had been used to investigate the molecular epidemiology of sporotrichosis. While the current standard for molecular diagnosis is performed by sequence analysis of the calmodulin gene (CAL), correspondence between the results from CAL and mtDNA is of diagnostic and epidemiological interest. Here, we investigated the correspondence between CAL and mtDNA used for molecular identification of Sporothrix globosa and S. schenckii, which are two major species. We also investigated and propose molecular markers suitable to describe the epidemiology of S. globosa, which is considered as a species with few intraspecific polymorphisms. Eighty-seven strains morphologically identified as S. schenckii sensu lato were investigated. They were identified as group A (17 types, 17 strains) or B (14 types, 70 strains) by mtDNA-RFLP. Partial sequences of CAL, internal transcribed spacer, and spacer between atp9 and cox2 genes of mtDNA of these strains were determined. All group A strains corresponded to S. schenckii, and group B to S. globosa. The sequences of the amplicons targeted on the spacer region in mtDNA of S. globosa ranged 510-515 bp in length and exhibited 10 molecular variations, whereas CAL indicated seven molecular variations. In conclusion, most of the S. schenckii sensu lato strains isolated from Japanese sporotrichosis patients were confirmed as S. globosa, because group B, which comprised the majority of strains, matched perfectly with S. globosa by the CAL sequencing study. We proposed sequence variations in the spacer between atp9 and cox2 genes of mtDNA as a suitable molecular epidemiological marker for S. globosa., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Neoscytalidium dimidiatum is a common fungus that causes non-dermatophyte dermatomycosis in tropical regions, but there have been no reports of infection with N. dimidiatum in Japan. Here, we report the first isolation of N. dimidiatum from human dermatomycosis in Japan. A 62-year-old healthy Japanese male had been treated with oral terbinafine for tinea pedis diagnosed from a microscopic examination in 2003 with a lesion that was intractable. In 2020, re-identification by sequencing the internal transcribed spacer regions and the D1/D2 domain of the large-subunit (LSU) ribosomal RNA gene revealed that the pathogen was N. dimidiatum. Antifungal susceptibility tests showed that the minimum inhibitory concentration of the drug luliconazole (LLCZ) against the pathogen was 0.00049 µg/mL. The patient's lesions were cured by topical LLCZ. The clinical course and drug susceptibility suggest that LLCZ is a suitable first-line drug for treatment.

We report the case of a 77-year-old woman who had been diagnosed with psoriasis vulgaris at another hospital at age 33 and treated with various therapies since then. At 61 years old, she was diagnosed with psoriatic arthritis with phalangitis, swelling of both hands, and sacroiliac arthritis, and was treated with oral immunotherapy. At age 76, treatment with a humanized monoclonal antibody to interleukin-17A (ixekizumab) was started due to increased pain associated with her hand inflammation. After ten months of this treatment, she visited our hospital with the complaint of tongue pain and white fungi on the tongue surface. Direct KOH examination of the fungi showed pseudomycelia and spores, and fungal culture (CHROMagar ® Candida) showed green and dark green wet colonies. Sequencing of the D1D2 region of ribosomal RNA gene of the nuclear DNA of fungi from the colony identified Candida dubliniensis. She was treated with amphotericin B gargle (Fungizone ® syrup) for two weeks, and the lesion improved. Since then, the patient has been treated with ixekizumab with no recurrence of oral candidiasis.

We describe a case of recalcitrant phaeohyphomycosis caused by Exophiala lecanii-corni, which was previously reported as Exophiala jeanselmei, infection. A 63-year-old Japanese woman presented with a 15-year history of multiple pruritic erythematous patches and plaques on the face. Histopathological examination and fungal culture revealed phaeohyphomycosis by E. jeanselmei. The attempted treatments included 6 g/day 5-flucytosine (5-FC), 100 mg/day itraconazole (ITCZ), and local hyperthermia. 5-FC was effective initially, but the patient deteriorated after discontinuation. Subsequently, she was referred to our hospital. Histopathological examination showed granuloma with multinucleated giant cells with infiltrating fungal hyphae in the dermis. The causative fungus was finally identified as E. lecanii-corni by ribosomal RNA gene analysis. The patient improved after receiving 200 mg/day ITCZ orally for 15 months with local hyperthermia. In the present case, we confirmed the identification of E. lecanii-corni as the causative agent by molecular methods. We also emphasize the importance of combination therapy with antimycotic agents and local hyperthermia in phaeohyphomycosis.

Background: Ribosomal DNA (rDNA) reportedly has multiple copies in the fungal genome. The internal transcribed spacer (ITS) region in rDNA is useful for investigating relationships between close taxonomic relatives. Thus, ITS has been widely used as a target gene in medical mycology for the detection of pathogenic fungi and identification of fungal species. However, the rDNA copy number in a genome of Trichophyton interdigitale, the pathogen causing dermatophytosis, currently remains unknown., Objective: Clarification of the rDNA copy number in a genome of T. interdigitale., Methods: rDNA copy numbers in 64 clinical isolates of T. interdigitale were examined using quantitative real-time PCR (qPCR) with the absolute quantitative method targeting TruMDR2, a single-copy control gene and the ITS region in rDNA., Results: The copy numbers of the rDNA subunit varied among the 64 strains tested, from 24 to 116 copies per genome. The average rDNA copy number ± standard deviation was 59 ± 16. No correlations were observed between the rDNA copy number and colony colour, colony morphology or molecular type of the non-transcribed spacer region in rDNA. Experiments on rDNA copy numbers obtained from independent colonies of each strain in single-spore cultures revealed that the copy number was homogeneous within each strain., Conclusion: This is the first study to estimate copy numbers of the rDNA subunit in a genome of T. interdigitale. The rDNA copy number of T. interdigitale varied among the strains tested and was homogeneous within each strain., (© 2020 Wiley-VCH GmbH.)

Trichophyton tonsurans is a major causative fungus of human dermatophytosis, which has been isolated from contact sport players in Japan. The microbiome in the scalp of judoists with or without T. tonsurans infection was analyzed to investigate the correlation between T. tonsurans infection and microbiome profile. Among 30 members of the same judo team in a high school, samples were collected by scrubbing their scalp with shampoo hairbrushes; then, DNA was extracted directly from the obtained scales. Twenty-seven datasets were subjects for microbiome analysis and T. tonsurans was detected in six members (no T. tonsurans-positive participants had scalp lesions). Regarding the fungal microbiome, Cyphellophora were more abundant in the T. tonsurans-positive group (TP) than T. tonsurans-negative group (TN) (P < 0.05). Regarding the Malassezia microbiome, Malassezia caprae were more abundant in TP than TN (P < 0.01). Regarding the bacterial microbiome, Lactococcus, Actinobacillus, Beijerinckiaceae and Xanthomonas were more abundant in TP than TN (P < 0.05). Also, the Shannon diversity index revealed no significant diversity between TP and TN, and 3-D principal coordinate analysis revealed no clear separation between TP and TN. There was practically no difference in microbiome between TP and TN, indicating that T. tonsurans could colonize humans regardless of their original microbiome. T. tonsurans coexisted with other fungi and bacteria without affecting species diversity in asymptomatic carriers. To our knowledge, this is the first investigation of the correlation between T. tonsurans infection and microbiome profile., (© 2020 Japanese Dermatological Association.)

Cutaneous cryptococcosis is classified as localized cutaneous cryptococcosis and cutaneous manifestations of disseminated cryptococcosis. The former presents as lesions, confined to isolated parts of the skin, which are neither systemically disseminated nor associated with cryptococcal fungemia or antigenemia. The latter presents as lesions through dissemination of Cryptococcus from visceral organs such as the lungs, with most cases being immunosuppressed hosts. We report the case of an immunocompetent elderly long-term pigeon fancier who presented with disseminated cutaneous cryptococcosis caused by Cryptococcus neoformans. Although the patient had been at risk of inhaling the pathogen by keeping pigeons for many years, and had been treated with topical steroids for a localized nodular lesion, the cause of development of multiple skin lesions could not be determined. The patient paradoxically showed no pulmonary or central nervous system symptoms, fungemia or glucuronoxylomannan antigenemia. Treatment with oral itraconazole 200 mg/day was not effective, but combination therapy of 5-fluorocytosine 200 mg/kg per day and fluconazole 100 mg/day resolved the disease., (© 2020 Japanese Dermatological Association.)

The viability of pathogenic fungi in the scale was investigated during topical administration of 1% luliconazole (LLCZ). Thirteen tinea pedis patients found to be positive on KOH examination were assessed by mycological examinations and quantitative real-time polymerase chain reaction (PCR) targeted internal transcribed spacer (ITS) in ribosomal RNA gene at the initial visit and after 2 and 4 weeks of treatment. Assays showed that the average copy number of ITS DNA had significantly decreased to 22.9% at 2 weeks and 4.8% at 4 weeks compared with the initial visit. LLCZ topical treatment could defeat almost pathogenic dermatophytes in the scales within 4 weeks., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

We report a case of kerion celsi due to Trichophyton tonsurans. An 18-year-old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β-defensin 2 (HBD-2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)-17A generally induces HBD-2 production by epidermal keratinocytes, we also immunohistochemically investigated IL-17A expression. Unexpectedly, many IL-17A-bearing cells were found around destructed hair follicles, indicating that IL-17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL-17A-upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL-17A may cause tissue damage and resultant scar., (© 2019 Japanese Dermatological Association.)

Favus is a type of dermatophytosis known to produce yellow scutula around hair follicles. Most cases of this disease worldwide are infections of Trichophyton schoenleinii. Favus has rarely been reported in Japan throughout the last four decades, and T. schoenleinii has not been clinically isolated in any case during the period. Here, we report a case of favus of vellus hair observed in a 63-year-old Japanese woman. Fungal culture showed negative; however, we detected fungal elements in the crust and hair bulbs by Grocott staining. Pathogenic fungi were identified as T. schoenleinii by polymerase chain reaction-based DNA sequencing, targeting the internal transcribed spacer regions of the rRNA gene using the formalin-fixed, paraffin-embedded tissue sample. She was successfully treated with p.o. administration of terbinafine and topical application of luliconazole cream., (© 2019 Japanese Dermatological Association.)

In a 2012-2014 epidemiological study of feline and canine dermatophytoses in Japan, we investigated the prevalence of fungi among 296 cats and 170 dogs treated at a veterinary clinic and 51 cats and dogs at an animal shelter at Fukui City in Japan. Microsporum canis was isolated from only one cat out of the 517 animals. Also, from 2012 to 2017, we analyzed isolates from 76 cats and 15 dogs with dermatophytoses at 14 veterinary clinics across 10 prefectures in Honshu and Shikoku. M. canis was the cause for 85 of the cases and Microsporum gypseum for the other six. M. canis infection routes in cats are thought to include stray cats as well as breeding facilities and pet shops, whereas for dogs, only breeding facilities and pet shops. Tinea was found in 18.7% (14/75) of the owners of these animals. We showed that microsatellite genotyping is useful for molecular epidemiological investigations such as determination of infection routes of M. canis.

Primary cutaneous aspergillosis is a rare, life-threatening fungal infection in premature infants. We report a case of primary cutaneous aspergillosis caused by Aspergillus tamarii in an extremely low birthweight infant. The infant was delivered by cesarean section with complications from an intrauterine infection, brain intraventricular hemorrhage, tension pneumothorax and cardiac tamponade. On the 12th day of life, he developed erythematous maceration with erosion on his back. Septate hyphae were detected on two occasions from specimens of the skin lesion. The manifestations of the colony and slide culture showed the characteristics of A. tamarii. The nucleotide sequences of internal transcribed spacer regions of the ribosomal RNA gene, partial sequences of β-tubulin and calmodulin gene were compatible with those of A. tamarii. Of the known Aspergillus species, Aspergillus fumigatus and Aspergillus flavus have been reported in previous studies as the major causative agents in primary cutaneous aspergillosis, whereas human infection by A. tamarii is rare. We consider that A. tamarii is important as an unusual opportunistic human pathogen among premature infants., (© 2018 Japanese Dermatological Association.)

This report describes a 77-year-old man with cutaneous mycosis caused by Scedosporium dehoogii while taking oral betamethasone and tacrolimus for the treatment of rheumatoid arthritis. At examination in our clinic, the patient had multiple cystic lesions and nodules with slight tenderness, varying in size up to 4 cm, on his left knee and shin. He had not noticed any traumatic injury at the site of the lesions. Fungal cultures of samples taken from the abscesses, scales, and crusts of the lesions yielded white, later grayish brown, fluffy surfaced colonies. Partial sequencing of the β-tubulin gene confirmed the species of the isolate. The patient was initially treated with oral voriconazole and local hyperthermia, but experienced hepatic injury 2 weeks later. His treatment was changed to itraconazole (ITC) and local hyperthermia, followed by a combination of ITC and terbinafine. The patient recovered completely during the 12-month course of treatment.

Trichophyton tonsurans, a major pathogen causing tinea capitis and tinea corporis, has been isolated from contact sports-players in Japan. The molecular types of 208 strains isolated between 2011 and 2015 were determined to understand the contemporary Japanese epidemic. Of these, 142 were isolated from practitioners of judo, 28 from wrestlers, 7 from sumo wrestlers, and 31 from individuals with unknown backgrounds. Based on length polymorphisms of the non-transcribed spacer (NTS) region of the ribosomal RNA gene, these 208 strains were divided into 3 subtypes: NTS I (204; 98.1%), II (3; 1.4%), and III (1; 0.5%). Single nucleotide polymorphisms (SNPs) and deletion/insertion profiles in the NTS region, length polymorphisms of the alkaline protease 1 gene, and a SNP in the carboxypeptidase Y gene were identified in 50 NTS I strains isolated between 2011 and 2015, and in 10 strains isolated before 2005. All 60 strains were classified as the same molecular type, with a profile identical to that of type Ib, a major type in the United States of America. These results indicate that NTS I strains isolated in Japan are clonal and independent of the type of sports activity.

A mycological survey on feet was performed in a nursing home with a geriatric hospital to ascertain the prevalence of tinea lesions. Of 100 subjects, comprising 62 in the nursing home and 38 in the geriatric wing, 70 were diagnosed with tinea pedis, tinea unguium (onychomycosis) or both of which 54 had onychomycosis alone, nine tinea pedis alone and seven had co-existing onychomycosis and tinea pedis. The most common clinical type of onychomycosis was distal lateral subungual onychomycosis (DLSO) at 30 cases, followed by superficial white onychomycosis (SWO) at 23 cases. Fifteen strains of Trichophyton (T.) interdigitale isolated from 23 SWO patients comprised six molecular types (D2II, nine cases; C2II, two cases; four other types, one case of each), based on the non-transcribed spacer region (NTS) of the ribosomal DNA. The pathogen of three other SWO cases was identified as T. rubrum. Direct physical contact between the subjects was unlikely because they were bedridden most of the time. Nine T. interdigitale strains were isolated from a bathtub used by patients on the floor with a high incidence of SWO alone, and all nine strains were D2II type, which suggests nosocomial infection. Consequently, the hospital infection control policy committee was consulted, bathing arrangements were changed, and nursing staff were educated about onychomycosis., (© 2017 Blackwell Verlag GmbH.)