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Darier's disease (DD) is a rare autosomal dominant genetic disorder caused by a mutation in ATP2A2, which encodes calcium (Ca2+) ATPase pumps in the endoplasmic reticulum. In this report, we present the first documented case in Japan successfully treated with apremilast. An 18‐year‐old female presented with red or brown hyperkeratotic papules and plaques on her head, neck, and chest. Histopathological examination revealed a hyperkeratotic, acanthotic epidermis, along with suprabasal acantholysis characterized by corps ronds and grains. Exome sequencing of DNA from peripheral blood mononuclear cells identified a missense mutation in ATP2A2. Based on the above results, we diagnosed her with DD despite the absence of a family history. Given the effectiveness of apremilast, a phosphodiesterase 4 inhibitor, in treating Hailey‐Hailey disease (HHD), a genetically related disorder involving ATPases in epidermal calcium channels, we opted for apremilast therapy. Eight weeks post‐initiation, significant improvement was observed in the patient's skin lesions on the head, neck, and chest. In this paper, we discuss the successful treatment of DD and HHD cases with apremilast, providing insights into its therapeutic potential, and offer a comprehensive review. [ABSTRACT FROM AUTHOR]

Alopecia totalis (AT) and alopecia universalis (AU) is known to have a poor prognosis with high relapse rate, and treatment failure is observed in most patients, regardless of the type of therapy. Although treatment and the prognosis of AT and AU have improved in recent years, old data are routinely cited in recent review papers without questioning them. The authors aimed to study the clinical characteristics and prognosis of AT and AU to update and compare the results with those of previously reported studies. The authors retrospectively reviewed patients diagnosed with AT and AU from 2006 to 2017 in a single institution. Of the 419 patients, the mean age at first episode was 22.9 years, and 24.6% had early onset (≤13 years). During follow‐up, 53.9% had more than 50% hair growth, and 19.6% of patients showed >90% hair growth. Among patients who showed >50% improvement, 36.7% had no recurrence. In early studies conducted in the 1950s and 1960s, the chance of full hair regrowth was reported to be <10%. In our study, patients with >90% improvement in AT and AU accounted for 19.6% of patients. The authors provide an update on data regarding the prognoses of AT and AU. [ABSTRACT FROM AUTHOR]

We accumulated the demographic information and analyzed the prevalence of myositis‐specific antibodies (MSAs) in a large cohort across Japan as standard testing for MSAs becomes more widely available. This retrospective, observational, cohort study analyzed the records of individuals aged 0–99 years who are tested for serum MSAs at SRL Incorporation from January 2014 to April 2020 across Japan. An enzyme‐linked immunosorbent assay testing was applied to determine the presence of anti‐aminoacyl tRNA synthetase (anti‐ARS), anti‐Mi‐2, anti‐melanoma differentiation‐associated gene 5 (anti‐MDA5), or anti‐transcriptional intermediary factor 1‐γ (anti‐TIF1γ) (Medical and Biological Laboratories). Anti‐TIF1γ antibody was detected more in male patients than female patients. In contrast, women were predominant in patients with other MSAs. More than half of the anti‐ARS or anti‐TIF1γ antibody‐positive patients were over 60 years old, although anti‐MDA5 or anti‐Mi‐2‐positive patients were mostly under <60 years old. Anti‐MDA5 antibody‐positive patients were mostly aged 40–59 years, while other MSA groups were mostly 60–79 years. Anti‐MDA5 antibody was detected most frequently in the age range of 0–29 years. Anti‐TIF1γ antibody was the second most commonly detected autoantibody in the age range of 0–19 years. Anti‐ARS antibody was the most frequently detected autoantibody after the age of 30 years, and the frequency of anti‐ARS gradually increased at more advanced ages. The second and third most detected autoantibodies were anti‐MDA5 and anti‐TIF1γ, respectively, in ages 30–79 years. We performed a nationwide >3‐year evaluation of MSA detection in a routine diagnostic setting. This paper provides clinical images concerning the relationship between four MSA types and the distribution of sex and age in a large population. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is an autoimmune blistering disease associated with anti‐BP180 and anti‐BP230 antibodies. The pathogenic action mechanism of immunoglobulin E (IgE) antibodies in BP has been studied since the 1970s, and IgE antibodies have gradually been confirmed as being important in BP; therefore, anti‐IgE therapy may be a new option for the treatment of BP. Omalizumab, as an IgE monoclonal antibody, has been increasingly used clinically to treat BP in recent years. Here, we collected 35 papers investigating omalizumab for BP treatment in a total of 83 patients, and the vast majority of patients showed varying degrees of improvement after treatment, except for a small number of patients with poor clinical outcomes. The patients were then divided into three groups according to dosing frequency and number of doses. Statistical analysis indicated that dosing frequency had little effect on clinical efficacy. While the groups with different numbers of doses were evaluated, the results concluded that clinical efficacy was affected by the number of doses, but there was no positive correlation between the number of doses and clinical efficacy. [ABSTRACT FROM AUTHOR]

In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS‐CoV‐2 is the causative pathogen of coronavirus disease 2019 (COVID‐19). Although this new COVID‐19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID‐19 can be classified into seven categories: (i) chilblain‐like skin eruption (e.g., COVID toes), (ii) urticaria‐like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID‐19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune‐mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain‐like lesions and herpes zoster after COVID‐19 mRNA vaccination have been published. Various skin diseases associated with COVID‐19 and COVID‐19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID‐19 infection, although it was initially called COVID‐toe and considered a COVID‐19‐associated cutaneous eruption. In fact, some COVID‐19‐associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID‐19‐ or COVID‐19 vaccine‐associated skin reactions need to be elucidated and verification of causal relationships is required. [ABSTRACT FROM AUTHOR]

Pemphigus is a group of blistering disorders characterized by the formation of intraepithelial blisters in skin and mucous membranes induced by the binding of circulating autoantibodies to intercellular adhesion molecules. The pathogenesis is complex and not fully understood; however, genetic predisposition and various triggers are widely accepted as key factors in pemphigus development. A few cases of new‐onset pemphigus following coronavirus disease 2019 (COVID‐19) vaccination have already been published. The present paper reports a total of two cases of pemphigus foliaceous and three cases of pemphigus vulgaris that occurred following vaccinations against COVID‐19, with anamnestic, clinical, and diagnostic data collection suggesting assumptions over a possible causal correlation. [ABSTRACT FROM AUTHOR]

While many patients with psoriasis are candidates for topical agents, long‐term treatment effects are unclear. This systematic review evaluated global findings from clinical trials and real‐world studies of topical calcipotriol and the two‐compound formulation of calcipotriol and betamethasone dipropionate for mild‐to‐moderate plaque psoriasis (including scalp psoriasis). PubMed, Embase and MEDLINE were searched for relevant English‐language publications along with Chinese, Japanese, Korean and Latin American publication databases. Identified articles were screened by title and abstract against predefined inclusion/exclusion criteria. A narrative synthesis of key efficacy and safety findings from the full papers of selected publications was developed. Thirty‐seven relevant papers were identified (25 English, 11 Chinese and one Japanese‐language study) including 28 randomized controlled trials. While there was significant heterogeneity in study length, treatment intensity and clinical measures, following a critical review of the published data combined with expert opinion, the following clinical practice recommendations were agreed in order to assist healthcare providers: in adults, long‐term treatment with calcipotriol/betamethasone dipropionate is well tolerated and efficacious for up to 1 year on an 'as needed' basis, and for up to 16 weeks on a fixed‐treatment regimen. Calcipotriol is also well tolerated and efficacious when used long term (up to 52 weeks) 'as needed' and for up to 20 weeks on a fixed‐treatment regimen. Used on an 'as needed' basis for up to 1 year, the safety and efficacy profile of fixed‐dose combination calcipotriol/betamethasone dipropionate is more favorable than calcipotriol alone; regular consultation between patients and their dermatologist/primary care physician is required to review psoriasis symptoms and adjust treatment accordingly; a specific treatment goal should be agreed on initiation of topical agent(s) to determine when long‐term treatment can begin or if a regimen change is warranted; and application frequency during the continued treatment phase should consider the patients' treatment expectations and goals. [ABSTRACT FROM AUTHOR]

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety and systematizing treatment, employing evidence‐based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQ) were decided based on the important clinical issues. For document retrieval, key words for published work searches were set for each CQ, and work published from 1980 to the end of September 2014 was searched in PubMed, Cochrane Library and Japana Centra Revuo Medicina databases. The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System technique. A total of 33 CQ were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence‐based guidelines for the management of vascular anomalies. [ABSTRACT FROM AUTHOR]

In this paper, we report the case of a 71‐year‐old man with an 8‐year history of melanonychia on the right little finger, who referred to our hospital because the color of pigmented area had gradually darkened and the width had expanded. Physical examination revealed longitudinal melanonychia with brown color (4 mm in width). Dermoscopic examination revealed multiple white round clods and splinter hemorrhages. No micro‐Hutchinson sign was observed. We performed a punch biopsy (diameter 3 mm) of the nail matrix for diagnosis. Histopathological examination revealed irregular acanthosis of epithelium of the nail bed and distal matrix, which consisted of basaloid cells without nuclear atypia. Several zones exhibited cell whorls reminiscent of squamous eddies. The whorls were composed of large pink cells arranged in an onion peel‐like fashion. The basaloid cells tested negative for human papillomavirus in situ hybridization and p16 staining. The morphology of white round clods (milia‐like cysts in metaphoric term) observed in dermoscopic analysis corresponded to squamous eddies in histopathology. Considering these features, ungual seborrheic keratosis (SK) with longitudinal melanonychia was diagnosed, which is an atypical site for SK. We suggest that the dermoscopic finding of milia‐like cysts may be useful for the diagnosis of ungual SK. [ABSTRACT FROM AUTHOR]

Cutaneous angiosarcoma (CAS) is a rare malignant tumor with a poor prognosis for which neither basic research on molecular pathomechanisms nor clinical prospective studies have progressed. A retrospective study of 28 CAS cases reported that chemoradiotherapy with taxanes was superior to conventional surgery. Since that time, chemoradiotherapy with paclitaxel (PTX + RT) has become a standard treatment. In this paper, we retrospectively investigate 21 cases of CAS that had been treated in the Department of Dermatology at Hokkaido University Hospital. Patients initially treated with PTX + RT followed by maintenance taxane chemotherapy showed better prognosis in overall survival (OS) and progression‐free survival (PFS) (median OS, 28 months; median PFS, 12 months) compared to others (median OS, 10 months; median PFS, 5 months) (OS and PFS: p < 0.05, log–rank test). Our results are consistent with those of a previous study that suggested that PTX + RT followed by maintenance taxane chemotherapy is a better therapeutic option than other interventions, including surgery. [ABSTRACT FROM AUTHOR]

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Palmoplantar pustulosis is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. Palmoplantar pustulosis has many similar aspects to psoriasis, either plaque and pustular type, namely familial occurrence between palmoplantar pustulosis and psoriasis, the appearance of the Köbner phenomenon, joint involvement, and nail involvement. Pustular psoriasis is classified into generalized and localized types, and there are a number of papers regarding palmoplantar pustulosis as an acral variant of localized pustular psoriasis. Many Japanese dermatologists consider palmoplantar pustulosis to be a distinct entity from pustular psoriasis, and the coexistence of palmoplantar pustulosis and psoriasis is rare. However, outside Japan, palmoplantar pustulosis is often considered to be palmoplantar psoriasis or palmoplantar pustular psoriasis, and extra‐palmoplantar lesions are also considered to be psoriasis. The purpose of the current review is to compare the similarities and differences between palmoplantar pustulosis and generalized/localized pustular psoriasis. Japanese patients with palmoplantar pustulosis have a close relationship with focal infection, and the associated bone–joint manifestation exclusively involves the anterior chest wall. Furthermore, pediatric occurrence of palmoplantar pustulosis is extremely rare, and difference of genetic background between palmoplantar pustulosis and psoriasis has also been reported. Treatment of focal infection often results in dramatic effects on both cutaneous lesions and joint pain of palmoplantar pustulosis. Those findings suggest that palmoplantar pustulosis should be separately considered from either palmoplantar psoriasis or palmoplantar pustular psoriasis. The clinicopathological features and therapeutic approach of both diseases are discussed. [ABSTRACT FROM AUTHOR]

Psoriasis has a strong impact on patients' lives and is closely linked to psychiatric disorders such as depression, anxiety and substance‐related disorders, especially dependence on alcohol and nicotine. The aim of our study was to systematically assess the psychiatric comorbidity and possible associations between psychological factors, disease severity and dermatology‐related quality of life in psoriatic patients from a high‐need university hospital dermatology department. Consecutive psoriatic patients (new and permanent patients) at the Department of Dermatology, University Hospital Essen, Germany, were asked to fill out a paper‐based questionnaire. In the first part of the questionnaire, baseline demographics, pre‐existing mental disorders and data on substance abuse were collected. In the second part of the questionnaire, mental and physical health was explored using different validated self‐rating tests. The current Psoriasis Area and Severity Index (PASI) was documented by a dermatologist. Patients with signs of mental disorders were offered an appointment with a board‐certified psychiatrist. Between August 2016 and February 2019, 228 consecutive psoriatic patients (138 men [60.5%], 90 women [39.5%]; mean age, 48.3 years [standard deviation, 13.6; range, 18–80]) participated in the study. Approximately 50% of the patients had evidence of suffering from mental health problems, mostly depression and anxiety, as well as alcohol dependence. Patients with a PASI of 3 or more showed a statistically significant reduced Dermatology Life Quality Index (DLQI) and a significantly impaired psychological as well as physical quality of life. DLQI correlated with all psychological test results. The data indicate a significant psychological burden in a tertiary psoriatic population. Our findings underscore the importance of screening psoriatic patients for psychiatric disorders, with a focus on depression, anxiety as well as alcohol and nicotine dependence, in a multidimensional approach involving psychiatrists and psychologists. [ABSTRACT FROM AUTHOR]

Hypotrichosis simplex (HS) is a rare form of hereditary alopecia caused by a variety of genetic mutations. Currently, only four studies regarding LSS‐related HS have been reported. In this study, we try to make a definite diagnosis in two unrelated Chinese families with three pediatric patients clinically suspected of HS. Whole‐exome sequencing (WES) was performed for these two families to reveal the pathogenic mutation. WES revealed two different compound heterozygous mutations in LSS in two probands that confirmed the diagnosis, including three novel mutations. In this paper, we describe a new accompanying phenotype of teeth dysplasia in a HS patient. Moreover, we provide a review of all reported LSS mutation‐related patients and infer some potential genotype–phenotype correlations for the first time. [ABSTRACT FROM AUTHOR]

The association of psoriasis with thyroid dysfunction has been investigated. However, it remains unclear; some papers indicate it, and others do not. In this study, we evaluate the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA), generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP), and the association of thyroid dysfunction with inflammation. Data on 201 psoriatic patients visiting our hospital from January 2014 to November 2017 (159 men and 42 women; 74 PsV, 42 PsA, 38 GPP and 47 EP) were retrospectively analyzed. Thirty‐three percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with EP (60% EP, 42% GPP, 19% PsA, 19% PsV). The prevalence of thyroid dysfunction decreased significantly when patients switched from EP to PsV or PsA (58% vs 17%; median, 20.5; range, 4–65 months). Most of the patients with thyroid dysfunction had low thyroxine syndrome (serum levels of free thyroxine are low, but serum thyroid‐stimulating hormone level is normal). Patients with thyroid dysfunction demonstrated significantly higher CD3+ and CD4+ T‐cell absolute count levels than those without thyroid dysfunction. Meanwhile, patients with thyroid dysfunction demonstrated lower immunoglobulin (Ig)A and IgM levels than those without thyroid dysfunction. Finally, patients with thyroid dysfunction demonstrated higher elevated serum C‐reactive protein levels than those without dysfunction in total, although there were no statistical differences. Our data indicate that thyroid dysfunction in patients with psoriasis may be associated with inflammation caused by psoriasis. [ABSTRACT FROM AUTHOR]

There is no current published work on the sun‐protection practices of bone marrow transplant recipients. The burden of post‐transplant skin malignancy is a growing public health concern. This paper evaluates the compliance of bone marrow transplant recipients with advice about sun protection through a cross‐sectional observational study involving participants completing a questionnaire regarding sun protection. Whilst most bone marrow transplant patients recalled receiving education (94%) and understood why they required additional precautions (84%), half did not practice adequate photoprotection. Future research should explore barriers to non‐compliance with sun‐protection measures in bone marrow transplant patients so additional interventions can be more targeted within this population. [ABSTRACT FROM AUTHOR]

Terminal osseous dysplasia with pigmentary defects (TODPD) is an extremely rare X‐linked dominant syndrome characterized by pigmentary skin defects, cutaneous digital fibromas and skeletal anomalies. Recent studies have identified that TODPD is caused by a unique variant, c.5217G>A (p.Val1724_Thr1739del), in the FLNA gene, which could in turn lead to the elastic fiber abnormality in TODPD. We herein present a rare case of TODPD in a Chinese girl due to an FLNA c.5217G>A heterozygous mutation, but the skin lesion biopsy showed that the elastic fibers were within normal limits in the dermis. A published work review of TODPD with the FLNA mutation from various origins is also included in this paper. To the best of our knowledge, this is the first report on TODPD with the FLNA mutation in China. [ABSTRACT FROM AUTHOR]

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid‐stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C‐reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = −0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis. [ABSTRACT FROM AUTHOR]

The association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD remains elusive. A systematic review and meta‐analysis were conducted to assess the association between AA and AITD focusing on the prevalence of thyroid antibodies, thyroid diseases and serological thyroid dysfunctions, respectively. Data collection was performed in October 2018 by searching for articles in two electronic databases: Medline and Embase. Case–control, cohort and cross‐sectional studies were included. Meta‐analysis of studies eligible for quantitative synthesis was performed to estimate pooled odds ratios of thyroid antibodies; thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (TG‐Ab), diagnosed thyroid diseases and serological thyroid dysfunctions. Four hundred and eighty nine research papers were identified and 17 studies with 262 581 patients and 1 302 655 control subjects were included for quantitative synthesis. AA was significantly associated with both TPO‐Ab and TG‐Ab. In comparison, there was no significant association between AA and diagnosed hypothyroidism or hyperthyroidism and serological hypothyroidism or hyperthyroidism. In conclusion, AA is significantly associated with the existence of thyroid antibodies rather than with clinical or laboratory thyroid abnormality. Lack of long‐term follow‐up data is a limitation of the existing published work. Our findings do not support routine screening of thyroid diseases for asymptomatic AA patients but highlight the potential future risk of AITD particularly in severe and refractory AA. [ABSTRACT FROM AUTHOR]

This study aimed to determine the prevalence of vitamin D insufficiency among Thai dermatologists compared with the general working‐age population in Bangkok. A cross‐sectional study was conducted in healthy Thai physicians who had at least 1 years' experience in dermatology practise and a subsample of the general Thai population from the Fourth National Health Survey. Serum 25‐hydroxyvitamin D (25[OH]D), a combination of 25(OH)D2 and 25(OH)D3, levels in both groups were measured using liquid chromatography coupled with mass spectrometry. The majority of dermatologists were of Fitzpatrick skin type III (n = 61, 61.3%) or IV (n = 32, 33.3%). The mean serum 25(OH)D and 25(OH)D3 levels were 18.9 and 18.2 ng/mL, respectively, whereas the corresponding levels in the general population were 26.5 and 25.8 ng/mL. None of the dermatologist had serum 25(OH)D sufficiency (>30 ng/mL), 38 (38.78%) had vitamin D insufficiency (20–30 ng/mL) and 60 (61.22%) had vitamin D deficiency (<20 ng/mL). The frequency of vitamin D deficiency in dermatologists was significantly higher than in the general population (61.2% vs 19.2%, P < 0.001). Ninety percent of dermatologists used sunscreen daily and spent time mostly indoors. Dermatologists used physical sun‐protection more than half of the time when outdoors, for example, a book or paper as a sunshade (70.3%), an umbrella (48.4%), a long‐sleeved shirt (20.4%) or a hat (9.7%). In conclusion, dermatologists showed a remarkably high prevalence of vitamin D deficiency which may be due to inadequate exposure to sunlight, regular use of sunscreen and practicing various sun‐protection activities. [ABSTRACT FROM AUTHOR]

The aim of the present study was to review the effectiveness of psychological and/or educational interventions for reducing psoriasis severity and improving psychological and quality of life ( QOL) outcomes in psoriasis. Sixteen papers met the inclusion criteria. Overall, the effectiveness of the existing interventions from this narrative synthesis is positive, especially in psychological and QOL outcomes. Of the 16 included studies, only five were randomized controlled trials ( RCTs). The strength of the evidence to support the effectiveness of the existing interventions was limited due to methodological weakness in the included studies. The review concludes that further research is needed to examine the effectiveness of psychological and/or educational interventions for individuals with psoriasis, including a greater number of RCTs in order to increase the methodological validity of intervention studies. Also, future research needs to be conducted to establish which interventions are most effective for specific sub-populations who may best profit from psycho-educational interventions. [ABSTRACT FROM AUTHOR]

H syndrome is a rare autosomal recessive disorder with characteristic dermatological findings consisting of hyperpigmentation and hypertrichosis patches mainly located on the inner thighs and multisystemic involvement including hepatosplenomegaly, hearing loss, heart abnormalities and hypogonadism. The aim of this study was to conduct a clinical and genetic investigation in five unrelated Tunisian patients with suspected H syndrome. Hence, genetic analysis of the SLC29A3 gene was performed for four patients with a clinical diagnosis of H syndrome. We identified a novel frame-shift mutation in the SLC29A3 gene in a female patient with a severe clinical presentation. Furthermore, we report two mutations previously described, the p.R363Q mutation in a male patient and the p.P324L mutation in two patients of different age and sex. This paper extends the mutation spectrum of H syndrome by reporting a novel frame-shift mutation, the p.S15Pfs*86 in exon 2 of SLC29A3 gene and emphasizes the relevance of genetic testing for its considerable implications in early diagnosis and clinical management. [ABSTRACT FROM AUTHOR]

Abstract: The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor‐α inhibitors; infliximab and adalimumab, one anti‐interleukin (IL)‐12/23p40 antibody; ustekinumab, and IL‐17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti‐IL‐17A antibodies. Brodalumab is an anti‐IL17RA antibody. In this review, we pick up topics which have drawn attention regarding the safety of biologics and discuss them with recent published work. [ABSTRACT FROM AUTHOR]

Dermoscopy is a widely used technique whose role in the clinical (and preoperative) diagnosis of melanocytic and non-melanocytic skin lesions has been well established in recent years. The aim of this paper is to clarify the correlations between the 'local' dermoscopic findings in melanoma and the underlying histology, in order to help clinicians in routine practice. [ABSTRACT FROM AUTHOR]

A decrease in the ceramide content of the stratum corneum is known to cause dry and barrier‐disrupted skin. In this literature review, the clinical usefulness of preparations containing natural or synthetic ceramides for water retention and barrier functions was evaluated. The PubMed, Cochrane Library, and Igaku Chuo Zasshi databases were searched using keywords such as "ceramide", "skincare products", "barrier + hydration + moisture + skin", and "randomized trial". All database searches were conducted in February 2019. Forty‐one reports were selected based on the following criterion: comparative control studies that evaluated the effects of ceramide‐containing formulations based on statistical evidence. Among the 41 reports, 12 were selected using the patient, intervention, comparison, and outcome approach. These 12 reports showed that external ceramide‐containing preparations can improve dry skin and barrier function in patients with atopic dermatitis. However, a double‐blinded comparative study with a large sample size is warranted for appropriate clinical use. [ABSTRACT FROM AUTHOR]

Locoregional cutaneous metastases of melanoma (LCMM) represent a therapeutic challenge. Many treatment options are available with varying results. The combination of cryotherapy and imiquimod, two treatments with a possible synergistic effect, has not yet been described for treating this disease. In this paper, we aimed to show the response of LCMM to cryotherapy combined with topical imiquimod 5%. A retrospective review of 20 patients diagnosed with LCMM and treated with cryotherapy combined with topical imiquimod 5% between November 2000 and May 2014 at three institutions was performed. The locoregional cutaneous response was evaluated. After a mean of five sessions, 13 patients (65%) responded to treatment, eight (40%) of these completely and five (25%) partially. Systemic disease progressed in 16 (80%) patients. Cryotherapy followed by topical imiquimod 5% is simple to apply, has minimal adverse effects and provides response rates similar to other, more complex treatment options. [ABSTRACT FROM AUTHOR]

Skin cancer is among the 10 most common cancers. Recent research revealed the superiority of artificial intelligence (AI) over dermatologists to diagnose skin cancer from predesignated and cropped images. However, there remain several uncertainties for AI in diagnosing skin cancers, including lack of testing for consistency, lack of pathological proof or ambiguous comparisons. Hence, to develop a reliable, feasible and user‐friendly platform to facilitate the automatic diagnostic algorithm is important. The aim of this study was to build a light‐weight skin cancer classification model based on deep learning methods for aiding first‐line medical care. The developed model can be deployed on cloud platforms as well as mobile devices for remote diagnostic applications. We reviewed the medical records and clinical images of patients who received a histological diagnosis of basal cell carcinoma, squamous cell carcinoma, melanoma, seborrheic keratosis and melanocytic nevus in 2006–2017 in the Department of Dermatology in Kaohsiung Chang Gung Memorial Hospital (KCGMH). We used the deep learning models to identify skin cancers and benign skin tumors in the manner of binary classification and multi‐class classification in the KCGMH and HAM10000 datasets to construct a skin cancer classification model. The accuracy reached 89.5% for the binary classifications (benign vs malignant) in the KCGMH dataset; the accuracy was 85.8% in the HAM10000 dataset in seven‐class classification and 72.1% in the KCGMH dataset in five‐class classification. Our results demonstrate that our skin cancer classification model based on deep learning methods is a highly promising aid for the clinical diagnosis and early identification of skin cancers and benign tumors. [ABSTRACT FROM AUTHOR]

mi RNA is a family of small non-coding RNA that consists of 22 nucleotides on average. mi RNA are implicated in various cellular activities such as cell proliferation or migration via the modulation of gene expression, and also are linked to the pathogenesis of human diseases. This paper reviews recent research progress about the contribution of mi RNA to the pathogenesis of various skin diseases, and possible application of mi RNA as the disease markers in each disease. For example, downregulated miR-424-5p in psoriatic skin causes the overexpression of MEK1 and cyclin E1 in psoriatic keratinocytes, resulting in the keratinocyte overgrowth and hyperproliferation seen in the disease. Although there was no significant difference in the serum miR-424-5p levels between psoriasis patients and healthy controls, serum miR-1266-5p levels were significantly upregulated in psoriasis patients, and showed weak and inverse correlation with disease activity. Furthermore, combination of serum levels of miR-146a-5p and -203a-3p was more reliable to distinguish psoriasis patients and normal subjects, than each mi RNA alone. Hair shaft miR-424-5p levels were significantly higher in psoriasis patients than normal subjects, while hair root miR-19a-3p levels in psoriasis patients were inversely correlated with the duration between symptom onset and the first visit to the hospital. Future researches of mi RNA will enable the advances of their clinical applications including the clarification of pathogenesis, disease markers and novel treatments. [ABSTRACT FROM AUTHOR]

Tosufloxacin tosilate, a member of the naphthyridine group, was developed in Japan and became commercially available in 1990. We experienced a 69-year-old male who developed thrombocytopenic purpura due to tosufloxacin tosilate. The diagnosis was made when similar symptoms (petechiae and thrombocytopenia) were induced by inadvertent challenge with tosufloxacin tosilate. In this paper, we report the first case of tosufloxacin tosilate-induced thrombocytopenic purpura and present a brief published work review. [ABSTRACT FROM AUTHOR]

Smartphones have become essential devices in modern society. The coverage rate of smartphones in 2017 in Japan was 75% according to the Ministry of Internal Affairs and Communications. The iPhone is one of the most well‐known smartphone brands. According to the manufacturer of iPhones (Apple), more than 200 million iPhones had been sold worldwide by 2017. These devices are often charged at night‐time, especially while being used in bed. There are only three reports of smartphone charger‐induced skin damage. We present two new cases of skin ulcers induced by an iPhone charger. The iPhone's "lightning cable" has electrodes outside, and we found that this can present a higher risk of causing a skin injury compared with other types of phone chargers. We also investigated the mechanism of the skin ulcers caused by the iPhone charger. The results indicated that these ulcers were chemical burns rather than an electrical injury or heat‐induced burn. [ABSTRACT FROM AUTHOR]

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs, such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment, have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In these revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (© 2024 Japanese Dermatological Association.)

Itch, also known as pruritus, is one of the most prevalent symptoms observed in dermatological practices. Itch frequently arises from primary pruritic dermatoses, although it may also manifest in the absence of a primary pruritic skin rash. The latter itchy condition is referred to as "cutaneous pruritus" in the Japanese guidelines published in 2020. Cutaneous pruritus can be classified into two categories based on its distribution: localized cutaneous pruritus and generalized cutaneous pruritus. Localized cutaneous pruritus is indicative of a neuropathic cause, whereas generalized cutaneous pruritus suggests underlying systemic disease(s), drug-induced itch, psychogenic itch (also known as functional itch disorder), or chronic pruritus of unknown origin (CPUO). Systemic diseases associated with cutaneous pruritus include disorders of iron metabolism, chronic kidney disease, chronic liver disease (especially cholestasis), endocrine/metabolic diseases, hematological disorders, and malignant solid tumors. CPUO is a term used to describe chronic itch that is often generalized and for which no underlying cause can be identified despite a comprehensive and careful diagnostic workup. A variety of treatment approaches are available for cutaneous pruritus, including device-based physical therapies (such as phototherapy) and medications that act on the itch-perception processing pathway from the skin, peripheral sensory nerves, the spinal cord, to the brain. This review presents an overview of the current knowledge regarding cutaneous pruritus, from its underlying pathophysiologic mechanisms to the diagnostic procedures and treatment approaches that are currently available., (© 2024 Japanese Dermatological Association.)

A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase ( ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma ( ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL limited to the skin and reviews the medical published work. [ABSTRACT FROM AUTHOR]

An infant skin disease with clusters of nodules in the diaper contact area was reported as granuloma gluteale infantum. Recently, the number of elderly patients with this condition has increased, and it has been reported as diaper-area granuloma of the aged. These lesions are presumably caused by irritation from feces and urine. We observed similar cutaneous symptoms in six elderly patients, five of whom revealed clusters of nodules arranged in a circular pattern in the gluteal region presenting a peculiar clinical picture. They were all bedridden and wore cloth diapers. We speculate that wearing a cloth diaper seems to be a major factor behind this condition. Another factor was sitting during the day. A subject had lesions with nodules on the scrotum. The distribution of nodules appeared to be related to the body position and vigorous movement of the patient. In all cases, topical steroid therapies were not effective. They were all positive for bacteriuria. Chronic urinary tract infection further irritates the skin. It is necessary to reduce urine contact and keep the lesion clean. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis ( PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles of middle-aged women. PPP frequently develops or exacerbates following focal infections, such as tonsillitis, odontogenic infection and sinusitis, either with or without arthralgia and/or extra-palmoplantar lesions. Pustulotic arthro-osteitis ( PAO) is a joint comorbidity of PPP, most often affecting the anterior chest wall. PAO is sometimes regarded as the same entity as synovitis, acne, pustulosis, hyperostosis and osteitis ( SAPHO) syndrome, and may be a subtype or incomplete type of SAPHO syndrome; however, there are several differences. In Japanese patients, PPP with PAO is frequently seen, whereas SAPHO syndrome in the true meaning is rare. A difference of incidence depending on race suggests that different genetic backgrounds may be responsible for susceptibility to these disorders. Bacterial infection, especially Propionibacterium acnes, is suggested to play an important role in the pathogenesis of SAPHO syndrome. P. acnes is responsible for acne, however, bacterium is unassociated with PPP skin lesions which are characterized by sterile pustules. On the other hand, PAO is frequently triggered by focal infection, and treatment of focal infection results in dramatic effects on the release of joint pain. This paper reviews current insights into the clinicopathophysiology of PAO, and discusses its possible mechanisms in comparison with SAPHO syndrome. [ABSTRACT FROM AUTHOR]

We investigated the optimum application for evaluating skin irritation response by using samples of irritants commonly used as additives in cosmetics and other common household products. We studied 47 volunteers (16 men and 31 women). We selected three types of surfactant, one moisturizer, one anti-infective agent and one oil solution. Using Finn chambers on Scanpor tape, we performed the patch test. A total of 0.015 mL of each sample was applied to the Finn chamber. For liquids, circular filter paper was soaked in 0.015 mL of the sample. Samples were placed on the upper back of participants, and closed for 4, 24 or 48 h. A patch application time of 24 h is sufficient to detect primary skin irritation from irritants in cosmetics and other common household products. In addition, we found that skin irritation reactions were strongest at 24 h after patch removal and that the reaction tended to be weaker at 48 h after patch removal. Patch testing to evaluate irritants should be performed by means of a 24-h patch test with a follow-up reading at 24 h after patch removal. An application time of 24 h places less of a burden on patients than a 48-h patch test. [ABSTRACT FROM AUTHOR]

Endometriosis is a condition in which endometrium or endometrium-like tissue grows in areas other than the endometrium and is often found within the pelvis such as in the uterus or ovary, but occasionally develops ectopically in the skin. In this paper, we report a case of cutaneous endometriosis in the umbilical region found in a 37-year-old woman with no history of pregnancy. The lesion was a brown, firm and elastic nodule, 9 mm × 7 mm in size, and caused bleeding as well as pain which increased during menstruation. Histopathological findings revealed that there were small and large glandular cavity structures in the dermis and the edematous interstitium around it. On immunohistochemical staining for estrogen and progesterone receptors, the cellular nuclei of glandular cavity walls were mainly found to be positive for both, and cells in the edematous interstitium around the glandular cavity were positive for CD10. Consequently, we diagnosed this case as cutaneous endometriosis in the umbilical region. CD10 was initially described as a tumor-specific antigen found in acute lymphoblastic leukemia. Recently, the usefulness of CD10 in diagnosing endometriosis in addition to various types of lymphoma or blood cancer has been confirmed, and in our case it also proved to be as useful as estrogen receptor or progesterone receptor in the definitive diagnosis of endometriosis. [ABSTRACT FROM AUTHOR]

Amelanotic vulvar melanoma is a rare type of malignant melanoma. This paper describes a case of an asymptomatic ulcerated nodule 20 mm in size. The tumor cells from the nodular lesion showed positive staining immunohistochemically for Melan-A, but negative staining with HMB-45. The cells showed negative reactivity to S-100 except in one region. The melanoma cells in the epidermis were detected in one of the specimens from the excised tumor nodule. The cells in the epidermis showed positive staining for Melan-A and S-100 and partial staining with HMB-45. The tumor was diagnosed as malignant melanoma of the vulva and immunohistochemically shown to have intratumor histological heterogeneity. This case suggests the importance of viewing non-pigmented nodules on the vulva of elderly females as potentially malignant melanoma, and that a combination of immunohistochemical stains may be useful for recognizing the stage of the melanosomes in the melanoma cells. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle‐wasting disease. Notably, several extramuscular manifestations and complications of advanced DMD, including skin disorders, are known. However, hyperhidrosis and its treatment have not been well‐described in association with advanced DMD, therefore we aimed to confirm the efficacy of 5% sofpironium bromide gel in treating secondary hyperhidrosis in patients with advanced DMD. We retrospectively reviewed patients with advanced DMD who underwent treatment with 5% sofpironium bromide gel. All patients were evaluated using the hyperhidrosis disease severity scale (HDSS) score and by measuring the gravimetric weight of palmar and/or plantar sweat. Three patients with advanced DMD were treated and the patients were aged 28, 31, and 32 years, respectively. Their HDSS scores showed a decreasing tendency within 5 weeks after treatment. In addition, all patients had a decreased gravimetric weight of palmar and/or plantar sweat, and the mean decrease rate of palmar sweat at 7 weeks after treatment was 53.7%. One patient had skin dryness on both soles, but no serious adverse events were observed. Treatment using 5% sofpironium bromide gel showed beneficial efficacy against palmoplantar hyperhidrosis in patients with advanced DMD. These findings warrant further investigation in future studies. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a group of inherited blistering disorders that primarily affect the skin and mucous membranes of the digestive tract, which can lead to poor nutritional status. Dietary supplements and nutritional support methods, such as nasogastric tubes and gastrostomy, have been employed to improve the nutritional status of patients with EB; however, few foods are suitable for enjoyable eating with family and friends. Here, we introduce a nutritionally balanced, melt‐in‐the‐mouth chocolate called andew, which was specifically designed for patients with EB. The andew chocolate is nutritionally superior and melts more easily than traditional chocolates, thus it is suitable for patients with EB, who are prone to oral erosions. Patients responded more favorably to the taste and texture of andew than to those of other dietary supplements. Not only does andew provide nutritional benefits, but it also promotes enjoyable eating with family members and friends, which could positively impact patients' mental health. [ABSTRACT FROM AUTHOR]

The long‐term safety and efficacy of 52‐week application of oxybutynin hydrochloride 20% lotion (20% OL) for the treatment of primary palmar hyperhidrosis (PPHH) in Japanese patients aged ≥12 years were evaluated in an open‐label extension (OLE) of a 4‐week, randomized, double‐blind (DB) study. The OLE included 114 patients who completed the DB study and wished to continue treatment and 12 new patients. In the safety analysis population (125 patients), the incidence of adverse events (AEs) and adverse drug reactions (ADRs) was 79.2% and 36.0%, respectively. Serious AEs were observed in two patients but were considered unrelated to the investigational drug. The incidence of AEs that led to study discontinuation was 1.6%. The incidence of application site AEs and ADRs was 35.2% and 26.4%, respectively. The severity of most events was mild. The incidence of anticholinergic AEs related to dry mouth was 3.2% for thirst and 0.8% for dry throat. The long‐term efficacy of 20% OL was confirmed by a long‐lasting reduction in sweat volume and improvement in the Hyperhidrosis Disease Severity Scale and Dermatology Life Quality Index. This study has several limitations: First the results may include some bias because most of the participants were from the prior DB study; second, the results may not be generalizable because only a few participants were in the age group most susceptible to PPHH (i.e., < 15 years old); and third, the study did not obtain safety information from treatment for more than 52 weeks, so this information must be collected in clinical practice in the future. No reduced therapeutic effect was observed in patients with PPHH in this study after 52‐week application of 20% OL. Also, few patients experienced serious AEs or AEs that led to study treatment discontinuation. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic relapsing, inflammatory skin disorder associated with skin barrier dysfunction, the prevalence of which has increased dramatically in developing countries. In this article, we propose a treatment algorithm for patients with mild-to-moderate and severe atopic dermatitis flares in daily clinical practice. An international panel of 15 dermatology and allergy experts from eight countries was formed to develop a practical algorithm for the treatment of patients with atopic dermatitis, with a particular focus on topical therapies. In cases of mild-to-moderate atopic dermatitis involving sensitive skin areas, the topical calcineurin inhibitor pimecrolimus should be applied twice daily at the first signs of atopic dermatitis. For other body locations, patients should apply a topical calcineurin inhibitor, either pimecrolimus or tacrolimus, twice daily at the first signs of atopic dermatitis, such as pruritus, or twice weekly in previously affected skin areas. Emollients should be used regularly. Patients experiencing acute atopic dermatitis flares in sensitive skin areas should apply a topical corticosteroid twice daily or alternate once-daily topical corticosteroid/topical calcineurin inhibitor until symptoms improve. Following improvement, topical corticosteroid therapy should be discontinued and patients switched to a topical calcineurin inhibitor. Maintenance therapy should include the use of pimecrolimus once daily for sensitive areas and tacrolimus for other body locations. This treatment algorithm can help guide clinical decision-making in the treatment of atopic dermatitis., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Granulomatous mastitis (GM) is a rare chronic inflammatory breast disease that can be mistaken for a variety of inflammatory and neoplastic disorders of the breast. Erythema nodosum (EN) is a common panniculitis, and is often associated with a variety of diseases, yet coexistence of EN and GM is very rare. In this paper, we present a young Japanese woman with EN associated with GM probably due to Corynebacterium infection. Both lesions of EN and GM were successfully treated with oral minocycline and surgical drainage. To the best of our knowledge, this is the first case of EN associated with GM due to Corynebacterium infection in the English-language published work. [ABSTRACT FROM AUTHOR]

Hidradenoma papilliferum ( HP) is a benign adnexal neoplasm which preferentially develops in the anogenital region of women. Although the origin of HP was previously thought to be an apocrine sweat gland, recent studies have suggested that it may derive from the anogenital mammary-like gland ( MLG). In this paper, we present a 43-year-old Japanese woman with hidradenoma papilliferum of the vulva. The lesion developed 7 years prior to her visit, and clinically appeared as a skin-colored cystic nodule. Histopathological examination revealed that the neoplasm was formed by the tubular structures consisting of two types of pleomorphic cells, columnar cells in the luminal layer and cuboidal cells in the basal layer. Further, the surgical specimen contained a wide, divergent, lobular ductal structure located in the vicinity of the neoplastic lesion, which was consistent with MLG. [ABSTRACT FROM AUTHOR]

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)‐4 and IL‐13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL‐31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti‐IL‐4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti‐IL‐31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti‐IL‐13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board‐certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

Hyperhidrosis is a chronic skin condition characterized by excessive sweating. It poses a burden on affected people, reducing their quality of life and productivity. We undertook a targeted literature review (TLR) to gather current evidence on the epidemiology as well as the human and economic burden posed on patients with hyperhidrosis. Searches were performed in Medline database (access via OVID interface) and ICHUSHI database. Articles published between January 2000 and September 2020 that analyzed at least 50 patients were included. Sixty‐four publications were identified and 38 publications covering a unique domain were selected to inform this TLR. The incidence of hyperhidrosis ranged from 0.13% in the UK to 0.28% in the USA, with a higher rate in females. The prevalence of hyperhidrosis varied from 2.8%–4.8% in the US general population to 18.40% in Chinese inpatients, while the prevalence of axillary hyperhidrosis varied from 1.4% in the US general population to 5.75% in Japanese employees/students. Due to excessive sweating, hyperhidrosis was reported to be a moderate‐to‐extreme limitation at work for the US patients, with 33.5% feeling unhappy. Patients' satisfaction was high post‐treatment. Considerable costs were related to the treatment with botulinum toxin and surgery. Hospital stays for surgery lasted from 10 h to 3 days. The percentage of patients who sought a medical consultation varied from 6.3% for Japanese patients with primary focal hyperhidrosis to 51% for the US general population with any type of hyperhidrosis. There is limited evidence of the hyperhidrosis burden, particularly among Japanese patients; however, the burden was high and limited patients' daily functioning. Future actions should include implementation of educational programs to raise awareness of the condition, conduct of larger studies, and generation of more evidence. Understanding the nature of hyperhidrosis and the burden it poses is of utmost importance. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is elevated inflammation, aberrant cytokine expression, and subsequent fibrosis. Interleukin‐11 (IL‐11) is a recently described profibrotic cytokine that can mediate fibrosis in the heart, lungs, and skin and is upregulated by transforming Growth Factor‐β (TGF‐β1). The objective of this study was to quantify the serum levels of IL‐11 in early diffuse SSc patients. Also, if IL‐11 could regulate the alarmin IL‐33 in dermal fibroblasts was quantified. Early diffuse SSc patient sera was isolated and IL‐11 was quantified by specific commercial ELISA compared to healthy control (n = 17). Healthy dermal fibroblasts were cultured in vitro and then serum starved and incubated with or without recombinant IL‐11. At specific early and late time points the supernatant was quantified for the alarmin IL‐33 by specific ELISA. In early diffuse SSc patients it was demonstrated that they have elevated IL‐11 in their sera. In a subgroup of SSc patients with interstitial lung disease (ILD) this elevation was particularly pronounced compared to those devoid of fibrotic lung disease. In vitro incubation of healthy dermal fibroblasts led to a significant induction of IL‐33 cytokine release into the cell media. IL‐11 is a profibrotic cytokine that is elevated in early diffuse SSc and is particularly elevated in those with ILD. This suggests that IL‐11 could be a possible biomarker of ILD in SSc. It was also found that IL‐11 led to release of the cytokine alarmin IL‐33 in fibroblasts at earlier time points but not late time points, suggesting early stimulation elicits an inflammatory response in the local microenvironment but prolonged stimulation leads to fibrosis. [ABSTRACT FROM AUTHOR]

Hypertrophic scars and keloids are fibroproliferative disorders caused by abnormal wound healing. Their exact cause has not been found, but abnormalities during the wound healing process including inflammatory, immune, genetic, and other factors are thought to predispose an individual to excessive scarring. In the present study, we performed transcriptome analysis of established keloid cell lines (KEL FIB), focusing on gene expression analysis and fusion gene detection for the first time. For gene expression analysis, fragments per kilobase per million map read values were calculated, which were validated by real‐time PCR and immunohistochemistry. Fusion genes were predicted by transcriptome sequence, and validated by Sanger sequence and G‐banding. As a result, GPM6A was shown in the expression analysis to be upregulated in KEL FIB compared with normal fibroblasts. The GPM6A upregulation in KEL FIB was confirmed by real‐time PCR, and GPM6A messenger ribonucleic acid expression was consistently significantly elevated in the tissues of hypertrophic scar and keloid compared to normal skin. Immunohistochemistry also revealed that the number of fibroblast‐like spindle‐shaped cells positive for GPM6A was significantly increased in keloidal tissues. GPM6A inhibition by small interfering ribonucleic acid significantly reduced the number of KEL FIB. On the other hand, although we hypothesized that fusion genes are involved in the pathogenesis of keloids, the transcriptome analysis could not prove the presence of fusion genes in KEL FIB. Taken together, GPM6A upregulation may have an inducible effect on cell proliferation in keloidal fibroblasts. GPM6A can be a novel therapeutic target in hypertrophic scars and keloids. The inflammatory nature may be more prominent in the pathogenesis of keloids, rather than being skin tumors, as proposed by Ogawa et al. Future studies using several cell lines will be required. [ABSTRACT FROM AUTHOR]