Cardiac Sarcoidosis which Occurred four Years after Successful Treatment of Cutaneous Sarcoidosis with Minocycline.

A 67-year-old woman was admitted to our hospital because of a complete right bundle branch block. She had been treated with minocycline for skin sarcoidosis and her symptoms had ameliorated four years previously. Gallium scintigraphy revealed an abnormal uptake in the heart but not in the skin or lungs. She was diagnosed with cardiac sarcoidosis, although an endomyocardial biopsy could not detect any sarcoid lesions. Immunohistochemical staining for Cutibacterium acnes was positive for granulomas of the skin lesions which had been previously biopsied. One year after starting the administration of steroids, her condition improved.

Exacerbating factors and disease burden in patients with atopic dermatitis.

The number of patients with atopic dermatitis is on the rise worldwide, and Japan is no exception. According to recent estimates of the percentage of patients with atopic dermatitis in Japan by age, the majority of patients are between 20 and 44 years old. Because the peak age of onset of atopic dermatitis is during infancy, many patients may experience prolonged symptoms from infancy to adulthood. A prolonged clinical course also increases the burden of atopic dermatitis on affected patients. Decreased productivity due to work disruptions, reduced daily activity, higher direct medical costs, fatigue, and daytime sleepiness due to sleep disturbances are typical burdens on patients with atopic dermatitis. In order to reduce these burdens, it is necessary to shorten its clinical course and achieve long-term control without relying on medications, possibly by using avoidance or coping measures of aggravating factors. Typical aggravating factors of atopic dermatitis include irritant dermatitis, food allergy in children, sweating, and psychological stress in adults. Food allergy places a heavy burden on the quality of life of affected patients and their families. The effectiveness of educational interventions for sweating and psychological stress is unclear. We must also evaluate the economic burden and cost-effectiveness of interventions on the patient as aggravating factors to be addressed.

Chronological evaluation of treatment effect for tinea unguium with efinaconazole: Possibility of an early estimation of treatment effects.

The topical antifungal efinaconazole was applied to 27 nails (17 patients), and the treatment effects were monitored over a stipulated period (after 3, 6, and 12 months). Fourteen nails were observed for 18 months. Effects of the treatment were determined on the basis of the improvement rate of the turbidity ratio compared with that before treatment. After 12 months, five nails were cured and marked improvement was noted, whereas moderate and marked improvements were noted in 11 and six nails, respectively. The cured patients exhibited a significantly better improvement rate at 6 months (68.8%) than the other groups. Only 10.6% improvement was observed at the same point in time for the mild improvement group. Thus, in cases where the improvement rate after 6 months of treatment was 10% or less, it was judged that oral treatment should be considered. Furthermore, of the nails monitored for 18 months, those that exhibited further growth in improvement rates at 12 months was 51.6%, suggesting that an improvement rate of 50% at 12 months after starting treatment could be used as an indicator to determine switching to oral treatment.

Clinical effectiveness of efinaconazole 10% solution for treatment of onychomycosis with longitudinal spikes.

Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs.

Factors associated with the development of oral allergy syndrome: A retrospective questionnaire survey of Japanese university students.

BACKGROUND: Oral allergy syndrome (OAS) is an IgE-mediated food allergy. Ingestion of causative antigens leads to the development of local symptoms such as numbness of the oral mucosa in most cases and anaphylaxis in a few cases. The prevalence of OAS including in healthy people has not been investigated. Thus, we conducted a questionnaire survey of Japanese university students. METHODS: We conducted a cross-sectional study of 2688 first-year students using a questionnaire survey in marksheet format and examined the epidemiological characteristics of OAS. RESULTS: Only 2.7% of students were aware of the term "oral allergy syndrome". A total of 143 (5.3%) students had OAS. There were significant associations between OAS and other allergic diseases including allergic rhinitis (AR) (OR: 3.8, 95% CI: 2.7-5.5), atopic dermatitis (AD) (OR: 4.6, 95%CI: 3.3-6.6), and bronchial asthma (BA) (OR: 3.0, 95%CI: 2.0-4.5). The onset age of OAS showed bimodal peaks at 0 and 10 years, and the latter peak coincided with the peak onset age of AR. CONCLUSIONS: Awareness of OAS was low in our study, which will make it difficult to treat properly and prevent its development. This survey confirmed the association between OAS and other allergic diseases, especially AR, which suggests that OAS is involved in the allergic march. A novel finding was that sensitization to antigens for OAS occurred around the same time as sensitization to antigens for AR. These results will help medical professionals diagnose OAS and develop lifestyle guidelines to prevent OAS-related symptoms such as anaphylaxis.

Impact of daily wearing of fabric gloves on the management of hand eczema: A pilot study in health-care workers.

Hand eczema is a major occupational disease, especially in medical workers, reducing their quality of life (QOL) and work productivity. Daily wearing of fabric gloves to prevent loss of moisture and lipids from the surface of the hands has been regarded as good in the management of hand eczema. However, limited evidence is available regarding the efficacy of moisturizing care with daily gloves on hand eczema. This pilot study was performed to evaluate the efficacy of moisturizing intervention with daily wearing of fabric gloves on skin barrier function, disease severity, and microbiome in health-care workers with hand eczema. Study 1: Nurses in the neonatal intensive care unit or growing care unit with and without hand eczema were recruited in the study. Subjects were instructed to apply moisturizer and wear two types of fabric gloves, common cotton gloves and moisturizing fabric gloves containing malate, for 4 weeks. Study 2: Physicians and health-care workers were recruited and instructed to wear a cotton glove on one hand at nighttime for 4 weeks. Disease severity, skin barrier function, QOL, and hand microbiome (Study 1) were evaluated. Study 1 found that daily wearing of both types of fabric gloves accompanied by use of topical moisturizers reduced the severity of hand eczema without changing the variation of microbiome. Study 2 found no apparent change between wearing and not wearing cotton gloves. In summary, topical moisturizer is of fundamental importance, and concomitant use of fabric gloves may merely enhance the efficacy of moisturizer in the management of hand eczema.

Tinea Capitis Caused by Microsporum audouninii: A Report of Two Cases from Côte D'Ivoire, West Africa.

We report here two cases of tinea capitis caused by Microsporum (M.) audouinii in Côte d'Ivoire, West Africa. The patients were a three-year-old boy and a six-year-old girl who presented with scaly patches on the scalp. The causative fungus was isolated using an adhesive tape-sampling method and cultured on Sabouraud dextrose agar plates. It was identified as M. audouinii both by its macroscopic and microscopic features, confirmed by DNA sequencing. These are the first documented cases of M. audouinii infections confirmed with DNA sequencing to be reported from Côte d'Ivoire. The practicality of the tape-sampling method makes it possible to carry out epidemiological surveys evaluating the distribution of these dermatophytic infections in remote, resource-limited settings.

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.

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol.

BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

Subcutaneous phaeohyphomycosis due to Exophiala jeanselmei following renal transplantation: A case report with a published work review of phaeohyphomycosis in Japan.

We describe a case of cutaneous phaeohyphomycosis following renal transplantation and include a review of the previously published Japanese cases. A 40-year-old Japanese woman taking immunosuppressants following renal transplantation 6 years prior presented to our hospital with a subcutaneous lesion on her right leg. Skin biopsy revealed an abscess, and culture confirmed Exophiala jeanselmei to be the causative agent. Treatment with itraconazole combined with surgical drainage was effective, and the lesion disappeared after 15 months. Upon review of 128 Japanese phaeohyphomycosis cases, it was found that more than 80% of the cases occurred in patients aged more than 60 years, and most cases involved underlying diseases associated with immunodeficiency. E. jeanselmei was the most common etiologic fungus. Recently, however, the Exophiala species has been reclassified based on molecular identification, and cases due to E. jeanselmei decreased with the concomitant increase of cases due to Exophiala oligosperma and Exophiala xenobiotica. In approximately half of the cases, lesions were treated by surgical removal, with or without concomitant antifungal drugs. Itraconazole was the antifungal agent most frequently used. In many cases, the disease course was reported as either healing or improving. There was no difference in either treatment or prognosis based on the etiologic species of fungus.

Epidemiological survey of 42 403 dermatophytosis cases examined at Nagasaki University Hospital from 1966 to 2015.

The causative species of a total of 42 403 dermatophytosis cases that occurred during 1966-2015 were surveyed. The most prevalent clinical type was tinea pedis, followed by tinea unguium, corporis, cruris, manus, faciei and capitis. The prevalence of tinea faciei and capitis has increased since the late 1990s and the late 2000s, respectively. The most prevalent dermatophyte species was Trichophyton rubrum, followed by Trichophyton mentagrophytes (the majority of the isolates were Trichophyton interdigitale in the latest nomenclature). These dermatophytes were detected in over 80% of the isolates identified in tinea pedis, unguium, cruris and manus cases. Recently, Microsporum canis and Trichophyton tonsurans have been increasingly identified. The frequency of M. canis isolated from tinea corporis, faciei and capitis cases started to rise in the early 1990s. T. tonsurans was first identified in Nagasaki in 2003. T. rubrum was the most commonly isolated pathogen in tinea faciei and corporis cases. However, the proportion of cases attributed to it has decreased since the early 1990s, whereas M. canis and T. tonsurans are being increasingly isolated since the early 2000s. In tinea capitis cases, the proportion of each pathogen isolated has changed dramatically. M. canis was first identified in the late 1970s, with an increasing prevalence up to the early 1990s. In contrast, the prevalence of T. tonsurans has increased since the early 2000s. In the 2010s, the most common fungus causing tinea capitis was T. tonsurans, followed by M. canis and T. rubrum.

Genome analysis of myelodysplastic syndromes among atomic bomb survivors in Nagasaki.

Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure.

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.

A Case of Cutaneous Fusariosis of the Scrotum as a Complication of Acute Myeloid Leukemia.

Fusarium, a hyphomyocetous fungus, is often isolated from the environment as a laboratory contaminant, but is also known as a pathogen causing keratomycosis, onychomycosis, and opportunistic infection of the skin and viscera. We report a 67-year-old man with localized cutaneous fusariosis of the scrotum, as a complication of acute myeloid leukemia (AML) under chemotherapy. An induration of 25 mm in diameter, which was covered by necrosis and black crust and with pain upon pressure, was found on the scrotum. Direct microscopic examination of the necrosis showed numerous fungal elements. Culture on Sabouraud dextrose agar with cycloheximide yielded a floccose, grayish white colony. Microscopically, crescent-shaped macroconidia and oval microconidia were abundant. The fungus was identified using gene analysis as Fusarium falciforme of the Fusarium solani species complex. The lesion was treated by voriconazole (total dose: 66,180 mg) and was reduced to 15 mm in diameter. Other metastatic lesions did not appear. After 4 months from the first visit to our department, the patient died of AML. It is believed that the treatment in the early stage of infection prevented further extension of the lesion. During examination of necrotic lesions occurring on the skin of patients with hematological malignancies, it is important to include mycological examination for opportunistic fungal infections, such as aspergillosis or fusariosis, which are easily overlooked by routine culture methods using conventional media with cycloheximide. This paper summarizes cases of cutaneous fusariosis in Japan.

Concurrent subcutaneous candidal abscesses and pulmonary cryptococcosis in a patient with diabetes mellitus and a history of corticosteroid therapy.

A 50-year-old man with a history of long-term corticosteroid treatment following adrenalectomy for Cushing's syndrome and uncontrolled diabetes mellitus was admitted for an examination of an abnormal thoracic shadow. Cryptococcal serum antigens were positive, and the histopathology of a lung biopsy showed encapsulated yeast resembling Cryptococcus neoformans. On admission, the serum ß-D-glucan level was approximately twice the cutoff value, several nodules were observed on both legs and magnetic resonance imaging revealed subcutaneous abscesses. Candida albicans was identified from needle aspirates, and the patient was successfully treated with fluconazole and flucytosine. We herein report the first case of concurrent C. albicans skin abscesses and pulmonary cryptococcosis.