Risk factors for the development of tinea pedis and onychomycosis: Real-world evidence from a single-podiatry center, large-scale database in Japan.

Dermatomycosis, including tinea pedis and onychomycosis, is frequently encountered in routine medical care in Japan. Identifying the risk factors for tinea pedis and onychomycosis development is important to encourage hospital visits by patients who may have these diseases but who are not undergoing any treatment. This approach may lead to the prevention of disease progression and the spread of infections to others. Risk factors for onychomycosis development have been reported both in and outside of Japan. However, most of the risk factors were identified based on a multicenter, questionnaire survey study and included evidence obtained from unclear or inconsistent diagnostic criteria for tinea pedis, onychomycosis, and identified risk factors. The current study analyzed the risk factors for developing tinea pedis and onychomycosis in real-world practice in Japan using a single-center, large-scale database that included the data of patients managed with consistent diagnostic criteria at the Podiatry Center of Juntendo University Hospital. A total of 2476 patients (1012 males, 1464 females) with a mean age of 63.4 years were included. Among these patients, 337 (13.6%) had tinea pedis and 346 (14.0%) had onychomycosis. A total of 259 patients (~ 75% of each patient population) had both diseases concomitantly. Multivariate logistic regression analysis adjusted for the possible risk factors of age (per 10 years), sex, diabetes, dialysis, visual impairment, ulcer history, lower-limb ischemia (LLI), and diabetic peripheral neuropathy (DPN) revealed that advanced age, male sex, diabetes, and LLI were independent risk factors for the development of tinea pedis. In addition, DPN was an independent risk factor for developing onychomycosis. We believe that these data are useful for identifying patients who are at high risk of developing tinea pedis and onychomycosis, which may result in disease prevention and suppression in real-world clinical practice in Japan.

Effectiveness of venetoclax and azacytidine against myeloid/natural killer cell precursor acute leukemia.

Myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL) is a rare leukemia subtype that possibly originates from precursor NK cells. The disease has a poor prognosis, and information on its treatment is lacking. We herein report the first case of a 46-year-old woman with MNKPL who was refractory to two lines of acute myeloid leukemia (AML)-type intensive chemotherapy but was successfully treated with venetoclax and azacytidine (VEN/AZA). She was diagnosed with MNKPL based on the conformations of immature lymphoblastoid morphology without myeloperoxidase reactivity that showed a CD7/CD33/CD34/CD56/HLA-DR positive phenotype and extramedullary regions. The disease was refractory to induction therapy with daunorubicin and cytarabine (DNR/Ara-C) and to reinduction therapy with mitoxantrone, etoposide, and cytarabine (MEC). After two lines of induction chemotherapy, massive pericardial and pleural effusion was found, and was suspected to be extramedullary lesions. The patient developed cardiac tamponade and required pericardiocentesis. Thus, VEN/AZA was administered as third-line therapy. After two cycles of VEN/AZA, the pericardial and pleural effusion disappeared, and complete remission was achieved. The patient received post-transplant cyclophosphamide-based haploidentical transplantation and has stayed relapse-free as of her last follow-up examination 2 years after diagnosis.

A Case of Kerion Celsi due to Trichophyton tonsurans.

The patient was a 13-year-old boy who was a member of the judo club at his junior high school. Approximately 1 week prior to his presentation, he developed multiple erythematous pilaris papules on his occipital area and was treated by a local doctor. The erythematous lesions expanded to 10 × 10 cm, showing granulation with drainage and strong spontaneous pain. At this point, he visited our hospital. He was diagnosed with kerion celsi due to Trichophyton tonsurans by fungal examination. The patient was treated with terbinafine (125 mg/day) for 6 weeks, and a brush test at 6 weeks was negative. All 18 members of the judo club, including this patient, were investigated; brush tests were positive in 4 cases, and one was positive for tinea corporis alone. The patient's family members parents were both negative. When an athlete is diagnosed with ringworm, T. tonsurans infection should be considered, and testing and treatment of family members and fellow athletes should be carried out to prevent the spread of infection.

Antifungal Susceptibility Testing for Microsporum canis from Cats in Japan.

Control of infection caused by Microsporum canis in pet animals are important for prevention of zoonosis. Treatments for animal dermatophytosis have generally consisted of itraconazole (ITZ) and terbinafine (TRF); however, a TRF-resistant M. canis strain from a case of feline dermatophytosis has been reported. In the present study, we examined the in vitro susceptibility of clinical isolates of M. canis to new antifungal drugs, such as ravuconazole (RVZ) and luliconazole (LCZ). The results indicated that RVZ and LCZ are more effective than ITZ and TRF. Therefore, oral administration of RVZ or topical application of LCZ may serve as new treatment options.

Microsporum canis Infection in a Cat Breeder Family and an Investigation of Their Breeding Cats.

Two pediatric cases of Microsporum canis infection that occurred in a cat breeder family and the isolation of dermatophytes from their 166 breeding cats are reported. The patients were a 16-month-old girl and her 26-month-old sister who both had tinea capitis. Their family consisted of six members: the sisters, their great-grandmother, grandmother, grandfather, and mother. Except for the two sisters, the family had no history of skin lesions. The grandmother had been a cat breeder for 20 years. We tested the cats using the hairbrush technique, and 56 of the 158 cats (35%) tested were positive for M. canis. In particular, cultures performed from 4 cats developed M. canis colonies that grew densely from all spikes on the hairbrush. On the basis of observations of the cultures, cutaneous infection was suspected when five or more colonies grew on a single plate medium (9 cats), whereas growth of fewer colonies was thought to suggest saprophytic colonization on cat hair. M. canis is known to be highly transmittable among cats, but 65% of the cats investigated remained negative. It was thus considered possible to prevent further spread of infection by practicing basic infection control and improving the environment.

Sudden out-of-hospital cardiac arrest in pediatric patients in Kyushu area in Japan.

BACKGROUND: It is well-known that a neurologically favorable outcome of out-of-hospital cardiac arrest (OHCA) is associated with the presence of bystander-initiated cardiopulmonary resuscitation (bystander CPR) and use of an automated external defibrillator. However, little is known about the effect of the presence of pre-existing conditions, prior activity, and locations on the outcome of pediatric OHCA. METHODS: We analyzed the data from questionnaires about pediatric patients with OHCA aged from 3 days to 19 years in the Kyushu area in Japan between 2012 and 2016. RESULTS: A total of 594 OHCA cases were collected. The numbers of OHCA cases and the rate of 1 month survival with a favorable neurological outcome during sleeping, swimming / bathing, and exercise were 192 (1.0%), 83 (32.5%), and 44 (65.9%), respectively. When an OHCA occurred at school (n = 56), 88% of children / adolescents received bystander CPR, but when it occurred at home (n = 390), 15% received bystander CPR. Cardiovascular (n = 61), suicide (n = 61), and neurological / neuromuscular (n = 44) diseases were three major pre-existing conditions. The OHCA of cardiovascular disease was associated with exercise (24/61) and mainly occurred at school (22/61). The OHCA of neurological / neuromuscular disease was associated with swimming/bathing (15/44) and mainly occurred during bathing at home (12/44). Multivariate regression analysis showed that the presence of bystander CPR (P < 0.001) and occurrence of OHCA at school (P < 0.001) were independently predictive of a favorable outcome in pediatric OHCA. CONCLUSION: The outcome was different among pre-existing conditions, prior activity, and location of OHCA. These findings might be useful for preventing OHCA and improving the outcome of pediatric OHCA.

Guidelines for the management of dermatomycosis (2019).

The "Guidelines for the management of dermatomycosis" of the Japanese Dermatological Association were first published in Japanese in 2009 and the Guidelines Committee of the Japanese Dermatological Association revised it in 2019. The first guidelines was prepared according to the opinions of the Guidelines Committee members and it was of educational value. The revised version is composed of introductory descriptions of the disease concepts, diagnosis, medical mycology and recent advances in treatment, along with clinical questions (CQ), which is intended to help in general practice for dermatologists. The CQ are limited to those involved in therapy but include some of the recently launched antifungal agents. The level of evidence and the degree of recommendation for each item were reviewed by the committee based on clinical studies published by 2018. For rare dermatomycoses, recommendations by the committee are described in the guidelines. In this field, there are still few good quality studies on treatment. Periodic revision in line with new evidence is necessary.

Trichophyton tonsurans infection in Japan: epidemiology, clinical features, diagnosis and infection control.

In this review, we summarize the status of Trichophyton tonsurans infection in Japan in terms of epidemiology, clinical features, diagnosis and infection control. Since approximately 2000, outbreaks of T. tonsurans infections among combat sports club members have been reported frequently, with the infection then spreading to their friends and family members. The most common clinical features of T. tonsurans infection are tinea corporis, which is difficult to differentiate from eczema, and tinea capitis. Tinea capitis is classified as the seborrheic form, kerion celsi form or "black dot" form, although 90% or more of patients are asymptomatic carriers. The diagnosis of symptomatic T. tonsurans infection is established by potassium hydroxide examination and fungal culture. However, because there are many asymptomatic carriers of T. tonsurans infection, tests using the hairbrush culture method are necessary. An increase in asymptomatic carriers of T. tonsurans makes assessment of the current prevalence of the infection challenging and underscores the importance of educational efforts and public awareness campaigns to prevent T. tonsurans epidemics.

[A case of secondary cutaneous cryptococcosis manifesting as rapidly enlarging skin ulcers on the dorsal surface of the hand and the left thigh].

 In April 2012 an 88-year-old woman, who was receiving oral prednisolone (15 mg/day) for the treatment of chronic inflammatory demyelinating polyneuropathy, was admitted to our hospital with suspected pneumonia. The patient was diagnosed with pulmonary cryptococcosis based on the findings from chest radiography and computed of tomographic imaging and observation of a high cryptococcal antigen titer. The general condition of the patient, including her fever, improved after initiation of an intravenous infusion of fluconazole (200 mg/day). However, the skin ulcers on all the limbs, which were present at the time enlarged since her admittance, were found to have rapidly enlarged. The patient underwent a detailed examination by a dermatologist. Skin ulcers measuring 4 × 6 cm on the dorsal surface of the left hand and understood without reporting 2 × 3 cm on the left thigh were noted, and she was diagnosed as having cutaneous cryptococcosis based on the results of skin biopsy, direct microscopic examination of pus, and mycological culture. For treatment of the skin ulcers, fluconazole was administered by intravenous infusion at 200 mg/day for 7 days. The treatment was then changed to oral itraconazole (200 mg/day). However, after 1 week, the patient exhibited a liver disorder, and the treatment was switched back to oral fluconazole (200 mg/day). After 2 months of treatment, the ulcers began to diminish. Thus, we believe that deep mycosis, including cutaneous cryptococcosis, should be considered during differential diagnosis if the patient is either elderly or undergoing corticosteroid/immunosuppressant therapy and has an ulcer.

A case of phaeohyphomycosis caused by Exophiala oligosperma successfully treated with local hyperthermia.

A 58-year-old Japanese woman who was engaged in dairy farming presented with multiple subcutaneous nodules and abscesses on the dorsum of her left hand from 5 months ago. These had been unsuccessfully treated with oral itraconazole. The patient had a history of Sjögren syndrome and diabetes mellitus, for which she had been taking oral prednisolone for 10 years. Direct microscopy of a pus sample treated with potassium hydroxide (KOH) showed brownish-red branching hyphae. In fungal culture, black colonies covered with gray-white villi were formed. Slide culture showed conidiogenesis from an annellide. The fungal strain was identified as Exophialia oligosperma by molecular biological techniques. Histopathological examination revealed abscesses and surrounding granulomatous infiltration in the dermis and subcutis, and hyphae in the granulomatous infiltration in the outer area. However, no eumycotic granules were observed. The diagnosis was phaeohyphomycosis caused by E. oligosperma. Since the previous treatment with itraconazole had not been effective, we performed daily hyperthermia using a disposable body warmer and drainage of the pus, which ceased after 3 weeks. After approximately 4 months, the skin eruptions became scarred. To the best of our knowledge, this is the second case of phaeohyphomycosis caused by E. oligosperma reported in Japan which was successfully treated with hyperthermia.

Retrospective cohort study on combination therapy with the histamine H2-receptor antagonist lafutidine for antihistamine-resistant chronic urticaria.

We conducted a retrospective cohort study evaluating the efficacy and usefulness of the addition of lafutidine, a novel histamine H2-receptor antagonist, in treatment of patients with idiopathic chronic urticaria whose disease was not well controlled with histamine H1-receptor antagonists. Based on the assessment of global improvement, moderate or better improvement was achieved in 39 of 46 patients (85%) after 1-3 weeks of additional administration of lafutidine and 35 patients (76%) after 3 months. No incidence of drug-related adverse reactions was reported in any patient. Lafutidine was rated as useful or better in 34 patients (74%) after 3 months of treatment. The usefulness of the drug was not affected by differences in background factors, such as disease duration, previous treatment duration and the number of concomitant H1-receptor antagonists. Lafutidine appears to be a promising addition to histamine H1-receptor antagonist therapy for the treatment of chronic urticaria resistant to treatment with H1-receptor antagonists alone.

The results of Trichophyton tonsurans screening examinations and infection management in University Judo Federation of Tokyo athletes over a 4-year period.

BACKGROUND: T. tonsurans infection is spreading among combat sport athletes in Japan, and preventive measures are necessary. METHODS: A questionnaire survey and hairbrush-culture tests were conducted over a 4-year period on university judo athletes from about 50 university teams affiliated with the University Judo Federation of Tokyo. Culture-positive individuals were given specific treatment recommendations based on culture results and were advised to seek treatment at a medical clinic. Culture-positive individuals were re-tested at 3 months post-treatment. RESULTS: Approximately 65% of participants reported a history of T. tonsurans infection. The incidence of hairbrush culture-positive individuals overall gradually decreased from 11.3% (academic year 2008) to 5.4% (2011). Each year the incoming freshmen had the highest infection rate of the four academic classes. Beginning in 2009 the infection rates decreased sharply among those who had participated in the survey the previous year, and the decreases continued the following year (s) until graduation. Among culture-positive individuals, the incidence of asymptomatic carriers increased each year, from 86% in 2008 to 98% in 2011. The culture-negative conversion rate was 86% overall for those undergoing treatment. CONCLUSION: Preventive measures against T. tonsurans infection in the University Judo Federation of Tokyo were successful in increasing awareness of the disease, lowering the incidence of infection, and detecting asymptomatic carriers who require treatment.

[The present state of Trichophyton tonsurans infection in Japan and measures to combat it].

More than 10 years have passed since Trichophyton tonsurans infection first began to increase in Japan. Initially the infection was confined to high school and university students participating in combat sports clubs, but it has now spread among the athletes' family members and friends. In a recent survey, 10% of Judo athletes tested positive for Trichophyton tonsurans; most were asymptomatic carriers. T.tonsurans infection usually causes tinea corporis or tinea capitis, but lesions can occur on other sites, causing tinea unguim, tinea manus, etc . The course of infection is usually only mildly symptomatic, and individuals with long-term infection can become asymptomatic carriers. It is likely that many individuals are unaware that they have Trichophyton tonsurans infection. The number of individuals infected with clear without repeating is difficult to assess due to the complexity of the fungal culture process. Diagnosis is made by direct examination in KOH and culture, and treatment consists of topical and / or oral antifungals. Prevention of Trichophyton tonsurans infection through increased awareness of the disease and careful hygiene is important.

Screening examination and treatment of Trichophyton tonsurans infection in judo athletes affiliated with the University Judo Federation of Tokyo.

In Japan, Trichophyton tonsurans infection has become an increasing problem among combat sports participants. We investigated the prevalence of T. tonsurans infection in athletes affiliated to judo clubs in the 21 First Division universities that were registered with the University Judo Federation of Tokyo in 2008. Study procedures performed by the subjects included (i) completion of a questionnaire concerning lifestyle, risk factors for tinea corporis and medical history; (ii) scrubbing the scalp with a circular hairbrush to obtain samples for fungal culture; (iii) anti-fungal treatment as recommended by a dermatologist, based on the number of fungal colonies isolated from the hairbrush; and (iv) repeat testing using the hairbrush method 3 months after treatment recommendations were received. Of 902 study subjects, 102 (11.3%) yielded positive hairbrush culture results. Of these, 14 individuals (13.7%) had tinea corporis; the remainder were asymptomatic. Conversion to negative fungal culture was observed in 85 of 96 culture-positive individuals who performed the second hairbrush culture test following treatment. Control of T. tonsurans infection among judo athletes could be achieved by educating athletes, trainers and coaches in judo clubs concerning detection, prevention, and treatment of T. tonsurans infection.

[Role of cytokine secretion of human keratinocytes in dermatophytosis].

The clinical presentation of dermatophytosis depends on species of the infecting fungus. The infections caused by the anthropophilic species tend to be chronic and intractable, and the resultant inflammation is minimal. On the other hand, the infections caused by the geophilic and zoophilic species tend to be self-healing, and the resultant inflammation is more severe. We investigated the role of cytokine secretion of human keratinocyte during dermatophyte infections: Arthroderma benhamiae, a zoophilic dermatophyte, and Trichophyton tonsurans, an anthropophilic dermatophyte. The results demonstrate that keratinocytes secrete a broad spectrum of cytokines including proinflammatory cytokines, chemokines, and immunomodulatory cytokines in response to A. benhamiae infection, whereas T.tonsurans infection stimulates the production of only a limited number of cytokines. Such differential cytokine secretion of the keratinocytes in response to infection by dermatophyte species may reflect the distinct inflammatory responses in the skin.

[Dermatophytosis: a summary of dermatomycosis as a proposal for future revision of the guidelines].

In preparing guidelines for dermatomycosis (tinea, trichophytia, dermatophytosis), we have primarily summarized the disease types and treatments as described in 4 textbooks used in Japan and abroad. We present our classification draft based on these following descriptions. In Japan, any dermatophytosis other than favus or tinea imbricata is considered to be tinea, while outside Japan, favus and tinea imbricata are also classified as tinea. Tinea capitis is classified together with trichophytia superficialis capillitii and kerion celsi, in a group that tends to include asymptomatic carriers. Most textbooks generally classify trichophytia profunda of the glabrous skin and granuloma trichophyticum as subtypes of tinea corporis. Tinea faciei can easily be misdiagnosed, but in many cases can be distinguished from tinea corporis by its specific clinical picture. Tinea unguium is regarded as one type of onychomycosis. We present a summary of dermatomycosis treatment as a proposal for future revision of the guidelines. One of the problems in the treatment of tinea capitis is that the safety of itraconazole (ITZ) and terbinafine hydrochloride (TBF) in children has not been established. Severity criteria for concomitant use of oral medications in the treatment of tinea pedis remains to should be established. Although many clinical studies concerning tinea unguium have been published, 3 of the 4 textbooks we consulted clearly stated that most of those studies were conducted by pharmaceutical companies. Further studies on the etiology and disease severity of tinea unguium are needed.

Dewetting self-assembly of nanoparticles into hexagonal array of nanorings.

Nanoparticles self-assembled into ring-shaped aggregates that were arranged in a two-dimensional (2D) hexagonal pattern. This hierarchic pattern was prepared by casting a toluene solution composed of polystyrene (PS) and Ag nanoparticles (NP). Dewetting of the thin composite layer induced the mesoscopic hexagonal array of PS-NP droplets. Within each dried droplet (dot), Ag nanoparticles self-assembled into a spot- or a ring-shaped 2D superlattice alternatively depending on the size of the dot, which was controlled by the molecular weight of PS.