Kerion Celsi due to Microsporum canis in an Adult Woman, Treated Successfully with Fosravuconazole.

A 64-year-old woman presented with a fist-sized, severely painful lesion with scales, crusts, pustules, erythema with subcutaneous abscess, and hair loss on the left temporal region. Direct microscopic examination revealed a large number of spores around the hair, which indicated ectothrix hair invasion, and some hyphae were also found. Histopathological examination showed significant inflammatory cell infiltration from the dermis to the subcutaneous tissues and into the hair follicles, destruction of the hair follicles with granulomatous reactions, and fungal masses along the hair within the hair follicles. Microsporum canis was identified based on morphological features via culture method and molecular biological analysis of the internal transcribed spacer region DNA sequence. The patient was diagnosed with kerion celsi caused by M. canis. For treatment of kerion celsi, we chose an oral antifungal agent, fosravuconazole (FRVCZ), which has been available since 2018 only in Japan. Clinical symptoms were cured in 12 weeks without scarring. No side effects were observed during oral administration of FRVCZ. The results of our case and several previous reports suggest that FRVCZ is effective in treating various types of dermatomycoses.

Treatment Outcome with Fosravuconazole for Onychomycosis.

Fosravuconazole L-lysine ethanolate (F-RVCZ), a ravuconazole prodrug, is a newly available agent with high expectations for efficacy in the treatment of onychomycosis. However, clinical data regarding the efficacy of F-RVCZ are limited because the drug was launched only in Japan in 2018. Therefore, we analyzed the outcome of F-RVCZ therapy in the treatment of onychomycosis at outpatient dermatology clinics in Japan. We examined data for 109 patients (68 male, 41 female) with varying clinical type, including total dystrophic onychomycosis and dermatophytoma, and a wide range of age groups, including the elderly. The complete cure rate at 12 weeks was 6.4% (7/109) and 67.9% (74/109) at the last visit (mean time to last visit: 32 ± 14.2 weeks). Mean rate of improvement in the affected nail area was 49.1 ± 23.3% at 12 weeks and 86.8 ± 22.4% at the last visit. Efficacy at 12 weeks and the last visit, respectively, was as follows: none, 4 cases and 1 case; slight, 35 cases and 4 cases; moderate, 51 cases and 21 cases; significant, 12 cases and 9 cases; complete cure, 7 cases and 74 cases. There were no serious adverse events. This retrospective survey was the first large-scale analysis of actual clinical practice outcomes and had minimal exclusions. Compared to previous reports, our results demonstrated excellent efficacy of F-RVCZ therapy in a variety of patients. Considering our results and the ease of oral administration (1 capsule/day for 12 weeks) and few adverse events, F-RVCZ therapy appears to be a useful option for the treatment of onychomycosis.

A Case of Tinea faciei Due to Nannizzia gypsea: Inflammatory Eruption on the Medial Angle of the Eyelid.

Nannizzia gypsea is a geophilic dermatophyte, previously known as Microsporum gypseum before renaming under the new taxonomy. This organism is distributed all over the world and is considered to be involved in keratin degradation in the soil. Generally, human infection involves direct contact with fertile soil. Tinea caused by geophilic dermatophytes is much rarer than that caused by anthropophilic dermatophytes. According to the latest survey in Japan, dermatophytosis due to N. gypsea accounted for only 0.4% of cases. Clinical presentations vary and may mimic other inflammatory dermatitis, leading to incorrect diagnosis and delayed treatment. According to that past report, distal parts of the upper and lower extremities were more commonly affected, followed by the trunk, face and scalp, and rarely the nail plate. A 38-year-old woman presented with an approximately 3-week history of an itchy, solitary erythematous lesion on the left medial angle of the eyelid. Direct microscopic examination of scales revealed fungal elements, and the causative agents was identified as N. gypsea by morphological and molecular biological diagnoses. The eruption improved with systemic itraconazole treatment at 100 mg/day for 8 weeks. No recurrence has been seen for a year. However, she had no history of contact with any infectious source. Herein, we report a case of tinea faciei due to N. gypsea with an uncommon site and route of infection.

Retrospective Survey of Treatment Outcomes of Efinaconazole 10% Solution and Luliconazole 5% Solution for Onychomycosis in Our Facility.

Many clinicians prefer to treat onychomycosis systemically. However, systemic therapy may not be suitable for all onychomycosis patients due to drug interactions, side effects of oral medications, or comorbidities. Two topical agents (efinaconazole 10% in 2014 and luliconazole 5% in 2016) have recently been approved for treatment of onychomycosis in Japan. We investigated the efficacy of these topical agents at Teikyo University Mizonokuchi Hospital, Kanagawa, Japan. We conducted a retrospective survey among patients diagnosed with onychomycosis at our outpatient clinic and had been treated with either efinaconazole 10% solution or luliconazole 5% solution. Prior to commencement of treatment, the disease severity was evaluated using the Scoring Clinical Index for Onychomycosis (SCIO). Furthermore, the efficacies of these agents were evaluated using turbidity scoring at each visit to our outpatient clinic. Sixty-two patients (33 men, 29 women) applied efinaconazole 10% solution, and 72 patients (35 men, 37 women) applied luliconazole 5% solution. The mean SCIO scores were 18.1 and 17.4, respectively, and the mean 5-grade evaluation scores were 3.5 and 3.4, respectively. Complete cure rates were 40.3% (25/62) and 33.3% (24/72), respectively. The mean durations of treatment were 15.4 months and 11.9 months, respectively. There were no serious side effects in either treatment group. There were no significant differences between the two agents in improvement scores as assessed by the Tukey's test. Thus, efinaconazole 10% and luliconazole 5% topical solutions were effective for the treatment of onychomycosis. These topical agents may become important treatment options for this indication.

2016 Epidemiological Survey of Dermatomycoses in Japan.

We report here the results of the 2016 epidemiological survey of dermatomycosis in Japan. In total, 6,776 cases were analyzed as follows: dermatophytosis, 5,772 cases (85.2%); candidiasis, 757 cases (11.2%); Malassezia infection, 235 cases (3.5%); and other fungal infections, 11 cases (0.2%). In dermatophytosis, tinea pedis was the most frequent (3,314 cases: male, 1,705; female, 1,609), followed by tinea unguium (1,634 cases: male, 766; female, 868), tinea corporis (423 cases: male, 241; female, 182); tinea cruris (316 cases: male, 242; female, 74); tinea manuum (58 cases: male, 29; female, 29); tinea capitus, Celsus' kerion (26 cases: male, 19; female, 7); and tinea barbae (1 case: male, 1). The most frequent pathogen was Trichophyton rubrum. In candidiasis, candidal intertrigo was the most frequent (181 cases: male, 98; female, 83), followed by oral candidiasis (165 cases: male, 84; female, 81), genital candidiasis (119 cases: male, 45; female, 74), diaper candidiasis (113 cases: male, 49; female, 64), erosio interdigitalis (63 cases: male, 13; female, 50), onychomycosis (41 cases: male, 17; female, 24), onychia et paronychia (28 cases: male, 2; female, 26), and angular cheilitis (23 cases: male, 6; female, 17). Although the number of cases varied depending on the role of each cooperating medical institution in the area and on population composition, no significant differences in the frequencies of clinical types were observed.

Efficacy of long-term treatment with efinaconazole 10% solution in patients with onychomycosis, including severe cases: A multicenter, single-arm study.

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.

Secreted Hydrolytic and Haemolytic Activities of Malassezia Clinical Strains.

Malassezia yeasts are opportunistic pathogens associated with a number of skin diseases in animals and humans. The free fatty acids released through these organisms' lipase and phospholipase activities trigger inflammation in the host; thus, these lipase and phospholipase activities are widely recognised as some of the most important factors in Malassezia pathogenesis. In this study, we sought to investigate and examine the relationship between these secreted hydrolytic activities and haemolytic activity in newly isolated Malassezia clinical strains. This characterisation was expected to elucidate pathogenicity of this fungus. We isolated 35 clinical strains of Malassezia spp.; the most frequently isolated species were M. sympodialis and M. furfur. Next, we analysed the hydrolytic activities of all of these clinical isolates; all of these strains (except for one M. dermatis isolate) showed detectable lipase and phospholipase activities against 4-nitrophenyl palmitate and L-α-phosphatidylcholine, dipalmitoyl, respectively. Most of the M. globosa isolates showed higher lipase activities than isolates of other Malassezia species. In terms of phospholipase activity, no significant difference was observed among species of Malassezia, although one isolate of M. globosa showed considerably higher phospholipase activity than the others. All tested strains also exhibited haemolytic activity, both as determined using 5% (v/v) sheep blood agar (halo assay) and by quantitative assay. Although all tested strains showed detectable haemolytic activity, we did not observe an apparent correlation between the secreted lipase and phospholipase activities and haemolytic activity. We infer that the haemolytic activities of Malassezia spp. are mediated by non-enzymatic factor(s) that are present in the secreted samples.

Epidemiological survey of onychomycosis pathogens in Japan by real-time PCR.

In Japan, an epidemiological survey of onychomycosis pathogens was performed using culture methods; however, the positive culture rate was 40% or less. As part of an epidemiological survey of dermatomycoses in Japan, we overcame this low positive rate by employing a real-time polymerase chain reaction (PCR) assay that allowed rapid and accurate detection and identification. In 2011, nail specimens were collected from patients at nine institutes in various prefectures in Japan and diagnosed as onychomycosis. For the detection and identification of the main pathogens causing onychomycosis, we performed real-time PCR using specific TaqMan® MGB probes and primer sets. Of the 496 onychomycosis samples, real-time PCR detected 382 cases (77.0%) caused by Trichophyton rubrum; 74 cases (15.0%) caused by Trichophyton interdigitale; and eight cases (1.6%) caused by Candida albicans. The real-time PCR positive rate was 96.2%. The most frequent pathogen was T. rubrum throughout life, with the number of patients affected peaking in the range of 60 to 69 years of age and no significant differences in the composition of causative pathogens by sex. We were able to detect and identify pathogens from almost all specimens and succeeded in analyzing the pathogens involved in onychomycosis cases in Japan. These data confirmed that our real-time PCR method was effective for detecting and identifying the main fungal pathogens from onychomycosis specimens.

[National Trends in the Distribution of Candida Species Causing Candidemia in Japan from 2003 to 2014].

The Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative Candida species. Data from 2003 to 2014 were collected from 10 Japanese university hospitals. A total of 328,318 blood cultures were included. The prevalence of fungi in all cultures and in positive cultures were 0.58±0.09% and 4.46±0.66%, respectively. Among the results that were positive for Candida species (N=1,921), Candida albicans was the most common species (39.5%) and was followed by Candida parapsilosis (23.3%), Candida glabrata (13.2%), Candida tropicalis (7.1%), Candida krusei (3.2%), and others (13.7%). During the last 6 years, the frequency of C. albicans has significantly decreased in Japan, while that of C. glabrata has increased. Additional surveys are needed to continuously monitor the trends in the distribution of candidemia.

A Case of Tinea Corporis due to Trichophyton tonsurans that Manifested as Impetigo.

A 41-year-old man visited our dermatology clinic because an eruption, which was resistant to steroid ointment treatment, had appeared on his right forearm. An oval, soybean-sized erythematous infiltrated lesion with scales and crusts was located in the central part of the extensor surface of the right forearm and showed partial erosion with attached yellow crusts. The lesion had an impetigo-like appearance. Fungal elements were confirmed from the scales by KOH examination and the fungus was identified as Trichophyton tonsurans by fungal culture and molecular method. Clinical features of T. tonsurans infection vary, wherein some patients have strong inflammatory manifestations, while others remain as asymptomatic carriers. Especially at the early stage of the infection, diagnosis is difficult because it is often misdiagnosed as eczema. We report a case of T. tonsurans infection that had impetigo-like appearance. We also studied the mechanism of the disease.

Treatment Outcomes for Malassezia Folliculitis in theDermatology Department of a University Hospital in Japan.

Topical or systemic antifungal therapy was administered to patients diagnosed with Malassezia folliculitis during the 5-year period between March 2007 and October 2013. The diagnosis of Malassezia folliculitis was established on the basis of characteristic clinical features and direct microscopic findings (10 or more yeast-like fungi per follicle). Treatment consisted of topical application of 2% ketoconazole cream or 100 mg oral itraconazole based on symptom severity and patients' preferences. Treatment was given until papules flattened, and flat papules were examined to determine whether the patient's clinical condition had "improved" and the treatment had been "effective". The subjects were 44 patients (35 men, 9 women), with a mean disease period of 25±15 days. In regard to the lesion site, the frontal portion of the chest was the most common, accounting for 60% of all patients. The mean period required for improvement was 27±16 days in 37 patients receiving the topical antifungal agent and 14±4 days in the 7 patients receiving the systemic antifungal agent. The results were "improved" and the treatment was "effective" in all patients. Neither treatment resulted in any adverse reactions. Although administration of oral agents has been recommended for the treatment of Malassezia folliculitis, this study revealed that beneficial results are safely obtained with topical antifungal therapy alone, similar to those of systemic antifungal agents.

[2011 Epidemiological Survey of Dermatomycoses in Japan].

An epidemiological survey of dermatomycoses and their causative fungus flora in Japan for 2011 was conducted in accordance with methods and criteria of the past four surveys. The survey covered a total number of 36,052 outpatients who visited 12 dermatological clinics throughout Japan. The results were as follows. 1）Dermatophytosis was the most prevalent cutaneous fungal infection (2,980 cases) seen in these clinics, followed by candidiasis (378 cases) and then Malassezia infections (152 cases). 2）Among dermatophytoses, tinea pedis was the most frequent (1,930 cases : male, 980 ; female, 950), then in decreasing order, tinea unguium (780 cases : male, 409 ; female, 371), tinea corporis (203 cases : male, 132 ; female, 71), tinea cruris (112 cases : male, 86 ; female, 26), tinea manuum (43 cases : male, 25 ; female, 18), and tinea capitis including kerion (16 cases : male, 13 ; female, 3). 3）Tinea pedis and tinea unguium were seen to increase in the summer season and occur mostly among the aged population. Compared to the last survey, by clinical form, there was a marked decrease in dermatophytosis patients. 4）As the causative dermatophyte species, Trichophyton rubrum was the most frequently isolated at about 80 % among all dermatophyte infections excluding tinea capitis. T. mentagrophytes was about 10 %. Microsporum canis was isolated in five cases. M. gypseum was isolated in three cases, and Epidermophyton floccosum was isolated in only one case. T. tonsurans was isolated in 13 cases. 5）Cutaneous candidiasis was seen in 378 cases (305, male ; 537, female). Intertrigo (298 cases) was the most frequent clinical form, followed by diaporcandidiasis (79 cases), erosion interdigitalis (62 cases), genital candidiasis (46 cases). 6）Tinea versicolor was seen in 97 cases. Malassezia folliculitis was isolated in 55 cases.

[2006 Epidemiological survey of dermatomycoses in Japan].

An epidemiological survey of dermatomycoses and the causative fungus flora of dermatomycoses in Japan for 2006 was made on a total number of 63,029 outpatients who visited 16 dermatological clinics throughout Japan. The results were as follows. 1) Dermatophytosis was the most prevalent cutaneus fungal infection (7,582 cases) seen in these clinics, followed by candidiasis (842 cases) and then Malassezia infections (283 cases). 2) Among dermatophytoses, tinea pedis was the most frequent (4,779 cases : male 2,358, female 2,241), then in decreasing order, tinea unguium (2,582 cases : male 1,376, female 1,206), tinea corporis (564 cases : male 341, female 223), tinea cruris (309 cases : male 254, female 57), tinea manuum (145 cases : male 92, female 53), and tinea capitis including kerion (17 cases : male 12, female 5). 3) Tinea pedis and tinea unguium are seen to increase in the summer season, among the aged population. When compared to the last survey 2002 by clinical form, t. unguium patients increased 459 cases. 4) As the causative dermatophyte species, Trichophyton rubrum was the most frequently isolated among all dermatophyte infections except tinea capitis. Microsporum canis was slightly increased. M.gypseum and Epidermophyton floccosum are small number. T.tonsurans was increased up to 37 cases. 5) Cutaneous candidiasis was seen in 842 cases (305 male, 537 female). Intertrigo (298 cases) was the most frequent clinical form, followed by erosion interdigitalis (136 cases), oral candidiasis (135 cases), onychia et paronychia (108 cases), genital and diaper candidiasis in total (88 cases). 6) Tinea versicolor was seen in 175 cases. Malassezia folliculitis were collected 108 cases, 63 cases are reported from one clinic.

[Malassezia related diseases].

Genusmalassezia are now divided to fourteen species. Different species will start or aggravate different skin diseases. In the seborrheic dermatitis, M.restricta will play an important role, in the atopic dermatitis, M.globosa and/or M.restricta are major cutaneous microflora. The availability of new tools such as genomic and proteomic analyses has begun to provide a new insight into the pathogenetic mechanisms involved.

[Strategy for educating senior dermatological residents in mycology].

To improve the ability of dermatologists to diagnose cutaneous mycoses, we have proposed a list of the minimum mycological knowledge and skills required by senior residents of dermatology. The list includes ability to select the most appropriate sampling method, knowledge of the basic method of potassium hydroxide (KOH) examination and skill in performing fungal cultures and identifying the most prevalent fungal species isolated from skin lesions. It is not possible for the Japanese Society of Medical Mycology to train every senior resident directly, and it is difficult for them to acquire sufficient expertise independently. Consequently, training and advice given by instructors in residents' home institutes is essential. A project of an advanced course for instructors, who are in charge of educating senior residents in their own institute, may be possible. Therefore, we have proposed here a list for instructors of the knowledge and skills required to educate senior residents. Employing this list should realize improved skill in dermatologists.

[Malassezia infections].

Although Malassezia yeasts are a part of the normal microflora, under certain conditions they can cause superficial skin infection Pityriasis versicolor, Malassezia folliculitis. Lipophilic yeasts are being considered as major opportunistic pathogens for a very long time. Most of the yeasts show an absolute requirement for long fatty acid chains and specific procedures are required for their isolation, conservation and identification. To date, the genus is composed of one non lipid-dependent species M. pachydermatis and lipid-dependent species M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta, M. slooffiae, M. dermatis, M. yamatoensis, M. japonica, M. nana, M. caprae, M. equina, M. cuniculi.

[Study on the usefulness of rinse containing miconazole nitrate for treatment of dandruff--a double-blind, comparative study].

A double-blind, comparative study was performed on the usefulness of rinse containing miconazole nitrate(COFRM)compared to rinse without the reagent for the treatment of dandruff, when together with shampoo containing miconazole nitrate (COF). This study showed that both COFR and COFRM had about 80% utility. On the other hand, though it was not significant, enhanced improvement of itching by COFRM compared to COFR was detected 2 weeks after start of the examination. These results suggest that by mixing the miconazole nitrate with not only the shampoo but also rinse, the reagent more certainly remained on the scalp so that proliferation of the Malassezia was disturbed. Therefore, the effectiveness could clearly be more practically felt at the early stage. Collectively, these results indicate that COFRM was a useful rinse that allowed the effect to actually be felt in the short-term when used together with COF and contributed to the compliance improvement.

[A case of nail candidiasis with severe deformities treated with oral fluconazole].

We report a case of nail candidiasis with severe deformities. The patient was a 71-year-old woman who initially consulted our department on April 5, 2006. She had diabetes, chronic rheumatoid arthritis and multiple liver metastasis of unknown origin. She had taken prednisolone for treatment of chronic rheumatoid arthritis for a long period. The initial examination demonstrated deformation of 1/3 of the inner part of the nail plate in both the third and fourth fingers, with apparent hyperkeratosis under the deformed nail plates. KOH-prepared direct microscopy revealed the presence of numerous spores and pseudohyphae. Numerous fungal elements were detected by Grocott staining and PAS staining. Candida albicans was isolated and identified by cultivation on the ATG agar and PCR-RFLP. Fluconazole (100 mg/day) was administered from April 8, 2006. After 14 weeks of treatment her clinical findings had improved, however she died of multiple organ failure on July 25, 2006.