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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]

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]

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]

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]

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]

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]

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence‐based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG. [ABSTRACT FROM AUTHOR]

Generalized bullous fixed drug eruption (GBFDE) is a rare type of life‐threatening severe cutaneous adverse reaction that is considered a medical emergency because of its potential lethality. Currently, only a few cases of bullous adverse reactions have been reported after coronavirus disease 2019 (COVID‐19) vaccination. We describe a patient with distinct clinical, histopathological, and immunological findings that are consistent with severe GBFDE, after Pfizer messenger RNA COVID‐19 vaccination. An 83‐year‐old man presented with a fever and well‐demarcated multiple erythematous patches that occurred only 4 h after receiving the first dose of COVID‐19 Pfizer vaccination. Over the next few days, the patches became generalized and turned into blisters covering approximately 30% of the body surface. The patient was started on intravenous methylprednisolone and oral cyclosporine. There were no additional blistering lesions after 10 days of treatment, prompting a gradual dose reduction. Our case suggests that a stepwise vaccination adhering to the standard dosing schedule should be warranted with close monitoring for possible significant side effects. [ABSTRACT FROM AUTHOR]

Nevus sebaceous (NS) is a congenital hamartoma associated with an increased risk of secondary neoplasms in approximately 10%–20% of patients. However, additional genomic alterations underlying tumorigenesis in NS lesions have not been clarified. We performed whole‐exome sequencing of archived tumor tissues (n = 8; six basal cell carcinomas and two trichoepitheliomas) and matched germline tissues (n = 7) with from seven patients with secondary tumors arising from NS. We also analyzed NS lesions without secondary tumors (n = 8). Somatic mutations and copy number alterations (CNAs) were analyzed. We identified a median of 129 somatic mutations (corresponding to 2.6/Mb in target regions, range 26–336) for eight tumors, while a median of 118 somatic mutations (2.3/Mb, range 1–196) for eight NS lesions. Known RAS hotspot mutations were found in seven of the eight tumors (six for HRAS p.G13R and one for HRAS p.Q61R) and in six of the eight NS lesions (four for HRAS p.G13R, one for KRAS p.G12C, and one KRAS p.G12D). Except RAS mutations, several putative driver mutations were detected in tumors: TP53 p.F134L/p.R213*, MYCN p.P59L, OR2Z1 p.P167S, PTPN14 p.Q768*, and SMO p.W535L. As for CNAs, two tumors harbored copy‐loss in regions encompassing PTCH1 gene. However, eight NS lesions did not harbor both putative driver mutations and CNAs. In conclusion, our study revealed that secondary tumors arising from NS harbor known RAS hotspot mutations and additional genomic alterations, including putative driver mutations and PTCH1 copy‐loss. These results could help to define the high‐risk group for tumor development in patients with NS and provide evidence for prophylactic resection. [ABSTRACT FROM AUTHOR]

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]

Infantile hemangiomas (IH) are benign vascular tumors that are common in infancy. They vary in growth, size, location, and depth, and although most lesions are relatively small, approximately one fifth of patients have multiple lesions. Risk factors for IH include female sex, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history, but the mechanism that causes multiple lesions is unclear. We hypothesized that blood cytokines are involved as a cause of multiple IHs, and tried to prove this using sera and membrane arrays from patients with single and multiple IHs. Serum samples were obtained from five patients with multiple lesions and four patients with a single lesion, none of which had received any treatment. Serum levels of 20 cytokines were measured using human angiogenesis antibody membrane array. Four of the 20 cytokines (bFGF, IFN‐γ, IGF‐I, and TGF‐β1) were higher in the patients with multiple lesions than in those with single lesion, with statistically significant difference (p < 0.05). Notably, signal for IFN‐γ was evident in all cases with multiple IHs, but was absent in cases with single IH. Although not significant, there was mild correlation between IFN‐γ and IGF‐I (r = 0.64, p = 0.065), and between IGF‐I and TGF‐β1 (r = 0.63, p = 0.066). bFGF levels were strongly and significantly correlated with the number of lesions (r = 0.88, p = 0.0020). In conclusion, blood cytokines could act as a cause of multiple IHs. This is a pilot study with a small cohort, so further large‐scale studies are necessary. [ABSTRACT FROM AUTHOR]

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe hereditary skin disease, caused by mutations in the COL7A1. However, whether non‐invasive prenatal testing (NIPT) can be used for this monogenic genodermatosis remains unknown. Accordingly, we conducted a study in which one couple at high risk of having a fetus with RDEB were recruited and tested by haplotyping‐based NIPT. Next‐generation sequencing‐based multi‐gene panel testing was carried out in this couple and their first child as proband who was affected with RDEB. We deduced parental haplotypes via single nucleotide polymorphism (SNP)‐based haplotype linkage analysis. Then the maternal plasma cell‐free DNA was also sequenced to determine the fetal haplotypes using a parental haplotype‐assisted hidden Markov model (HMM) analysis. Results show that the fetus was only a heterozygous mutation carrier in COL7A1 and the identical results were obtained after birth. These results demonstrate that haplotyping‐based NIPT is a feasible method for NIPT of RDEB. [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative condition. Skin biopsies taken from the lower leg were reported to be a standard diagnostic procedure for NIID; however, no studies have addressed the optimal skin biopsy locations. We retrospectively analyzed 12 cases in which skin biopsies were performed for diagnosing NIID. We collected clinical information including age, sex, skin biopsy site, the presence of nuclear inclusion bodies, the results of p62 immunostaining, the final diagnosis from the department of neurology, and the presence of abnormal GGC repeats in the NOTCH2NLC gene. Four of the 12 cases had a final diagnosis of NIID. One of the four cases was biopsied from the lower leg, whereas the other three cases were biopsied from the abdomen or thigh. Biopsy specimens of the four definite NIID cases revealed the average rates of nuclear inclusion body‐positive cells in adipocytes, sweat gland cells, and fibroblasts to be 13.2%, 10.3%, and 6.3%, respectively. GGC repeat abnormalities in the NOTCH2NLC gene were observed in two of the four cases. The present study indicates that sites with ample subcutaneous fat tissue could be promising for diagnostic skin biopsies for NIID. [ABSTRACT FROM AUTHOR]

Darier's disease (DD) is a rare autosomal dominantly inherited disorder. DD patients usually present with widespread keratotic eruptions with itching in the seborrheic regions that are exacerbated by various factors, including heat, sweat, and physical trauma. The SARS‐CoV‐2 (COVID‐19) pandemic has stirred confusion among the medical community, including dermatologists, as this infection has been implicated in various skin conditions. Only a handful of reports have documented DD associated with COVID‐19. Here, we report a 30‐year‐old male with Darier's disease whose symptoms were exacerbated following both COVID‐19 vaccination and COVID‐19 infection. The patient had noticed slight eruptions 7 years prior, but was not particularly concerned. After COVID‐19 vaccination and infection, he had erythematous maculopapular lesions in large areas of the trunk and extremities. The previously reported pathogenic variant c.2255_2257del (p.(Ile752_Tyr753delinsAsn)) in ATP2A2 was detected in the present patient. Oral etretinate greatly improved his DD manifestations. As far as we know, the present patient is the first genetically confirmed DD case who showed both COVID‐19 infection‐ and vaccination‐related DD exacerbations independently. We think that the further accumulation of DD cases exacerbated by COVID‐19 infection/vaccination is needed to clarify the mechanisms of DD aggravation. [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)‐6, IL‐7, IL‐12, IL‐21, IL‐22, IL‐23, interferon (IFN)‐α, and IFN‐γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK‐signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque‐type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board‐certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association. [ABSTRACT FROM AUTHOR]

Cutaneous manifestations in coronavirus disease 2019 (COVID‐19) patients may possess prognostic value for identifying potentially severe cases. This systematic review investigated whether dermatological features are associated with COVID‐19 outcomes in elderly patients. Literature retrieval was conducted on May 11, 2022, from databases, hand‐searching, and tracing citations. Following selection against eligibility criteria, the remaining records were evaluated utilizing the National Heart, Lung, and Blood Institute Study Quality Assessment Tool or Newcastle–Ottawa Scale. The pooled individual data were subsequently analyzed using the Cochran–Mantel–Haenszel test to calculate the odds ratio (ORs) and confidence intervals (CIs) for the severity and mortality of each skin lesion type. We incorporated 70 articles, including 180 and 117 entries, with information regarding disease severity and mortality. Further analysis revealed that vascular type was the skin lesion most frequently noticed in confirmed COVID‐19 elderly patients (46.2%) and was associated with an increased risk of developing advanced disease (OR 7.32, 95% CI 3.39–15.81) and the ensuing termination (OR 5.73, 95% CI 2.46–13.36). The converse phenomenon was observed in maculopapular type (severity OR 0.27, 95% CI 0.14–0.52; mortality OR 0.10, 95% CI 0.03–0.36). In conclusion, skin manifestations may predict COVID‐19 severity and mortality in the senior group. [ABSTRACT FROM AUTHOR]

Limited data are available on the predisposing factors to fractures and falls of patients with psoriatic arthritis (PsA). Our study intended to explore the differences between PsA patients and controls, concerning bone mineral density (BMD), the 10‐year fracture risk, the number of prevalent fractures, the frequency of falls and to investigate the association of the same factors with PsA disease characteristics within the PsA group. Medical reports of 61 PsA patients and 69 consecutive, age‐matched controls were analyzed, physical examination and bone mineral density (BMD, and T‐score) were performed, and the 10‐year fracture risk was calculated. The results were subjected to statistical analysis. Femoral neck BMD, as well as vertebral and femoral neck T‐scores were lower, the odds ratio (OR) for low BMD and the 10‐year risk of hip fracture was higher (p = 0.0029; 0.0002, p < 0.0001, OR = 21,9, p = 0.014) in the PsA group. The PsA patients were more predisposed to prevalent fractures, including peripheral fractures, and vertebral fractures as well as falls (OR 3.42; 2.26; 13.33; 3.95, respectively), compared to controls. Within the PsA group (beyond the age) scalp psoriasis and late‐onset psoriasis, were significantly associated with a greater number of prevalent fractures (p = 0.0049; 0.029), while the number of falls per year correlated with late‐onset psoriasis and the flexural psoriasis (p = 0.007; 0.023). Our results suggest that PsA is an independent risk factor for reduced bone density and falls hence to related bone fractures. Patients with late‐onset psoriasis are more likely to suffer falls and related fractures, especially if their disease is characterized by the involvement of the hairy scalp and body folds. [ABSTRACT FROM AUTHOR]

Although endotoxin concentration in the environment is negatively associated with atopic dermatitis (AD) onset in early childhood, the association between endotoxin concentration in the environment and eczema resolution in children with preexisting eczema is unclear. The aim of this study was to evaluate the association between endotoxin concentration in house dust and eczema persistence in young children. The authors used data from children participating in JECS (Japan Environment and Children's Study). In children who had AD or AD‐like lesions at the age of 1 year, the authors investigated the association between the prevalence of eczema at the age of 3 years and endotoxin concentration (categorized by quartiles) in the dust on children's mattresses at the ages of 1.5 and 3 years. This study included 605 children. Eczema was significantly less prevalent among children whose mattresses were in the second and third quartiles of endotoxin concentration when they were 18 months old than among children whose mattresses were in the first quartile (adjusted odds ratio, 0.57 [95% confidence interval, 0.35‐0.93] and adjusted odds ratio, 0.49 [95% confidence interval, 0.29–0.83], respectively). Moreover, of the children with eczema at age 3 years, those whose mattresses had endotoxin concentrations in the first quartile had significantly worse sleep disturbance caused by itchy rash (>1 time per week) than did those whose mattresses were in the third and fourth quartiles (20.0% vs 3.3% and 3.7%, both p values < 0.01). The findings indicate that low endotoxin exposure is associated with a higher prevalence of persistent eczema during early childhood. [ABSTRACT FROM AUTHOR]

Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare genodermatosis characterized by a classic triad of follicular ichthyosis, alopecia, and photophobia. We report a Chinese patient displaying features of IFAP triad along with painful palmoplantar keratoderma, recurrent infections, periorificial keratotic plaques, nail dystrophy, and pachyonychia. Whole‐exome sequencing revealed an intronic variant (NM_015884.3: exon7:c.970+5G>A) in the gene MBTPS2. Sanger sequencing confirmed that the variant segerated with phenotype in the family. Sequencing of cDNAs derived from the patient indicated the variant introduced a new splice donor site, leading to partial skipping of exon 7 (r.951_970del). An in vitro mini‐gene assay also revealed abnormal splicing of exon 7. This study presents a case complicated with X‐linked IFAP syndrome and Olmsted syndrome, and highlights the significance of using validation assays to identify the pathogenicity of intronic variants in MBTPS2. [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]

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]

Intra‐ and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer‐based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non‐ to minimally‐invasive alternative to percutaneous injection. [ABSTRACT FROM AUTHOR]

Vitiligo is a skin depigmentation disorder. GATA3 expression is downregulated in vitiligo patients, and its role and regulatory mechanism in vitiligo are unclear. GATA3 and HMGB1 levels were detected by qRT‐PCR in peripheral blood cells of vitiligo patients and healthy controls, as well as H2O2‐treated PIG1 cells. Their expression correlation was assessed by Pearson analysis. qRT‐PCR, MTT assay, Ki67 immunostaining, flow cytometry, ELISA and Western blot were applied to determine GATA3 expression, cell survival, cell proliferation, cell apoptosis, melanin contents, and melanin‐related protein expressions. The cellular distributions of HMGB1 and its deacetylation levels were detected by Western blot. The binding of GATA3 to SIRT3 promoter and effects on SIRT3 expression and HMGB1 deacetylation was determined by dual‐luciferase assay, ChIP assay, and Western blot. GATA3 was decreased, and HMGB1 was increased in vitiligo. Pearson correlation assay showed that they were negatively correlated. H2O2 significantly inhibited cell survival, proliferation, melanin secretion, and melanin‐related protein expressions but remarkably increased cell apoptosis. GATA3 overexpression could distinctly reverse the effects of H2O2 through decreasing HMGB1 expression and retained HMGB1 in nuclear due to the decreased HMGB1 acetylation. GATA3 bound to the SIRT3 and subsequently decreased H2O2‐induced HMGB1 acetylation. Overexpressing HMGB1 or knockdown of SIRT3 could reverse the effects of GATA3 overexpression. GATA3 inhibited H2O2‐induced injury in PIG1 cells and enhanced melanin secretion by SIRT3‐regulated HMGB1 deacetylation, which might provide new evidence to treat vitiligo. [ABSTRACT FROM AUTHOR]

More than 200 types of human papillomavirus (HPV) have been reported to date and have been associated with various dermatological diseases. Among dermatological diseases, viral verrucae are the most commonly reported to be associated with HPV. Epidermodysplasia verruciformis (EV) consists of three types: typical EV is an autosomal recessive genetic disorder with TMC6/TMC8 gene mutations, atypical EV develops due to various gene mutations that cause immunodeficiency, and acquired EV develops due to acquired immunodeficiency. Generalized verrucosis differs from EV in that it involves numerous verrucous nodules (mainly on the limbs), histopathologically no blue cells as seen in EV, and infection with cutaneous α‐HPVs as well as β‐HPVs. HPV‐induced skin malignancies include squamous cell carcinoma (SCC) caused by β‐HPV (especially HPV types 5 and 8) in EV patients, organ transplant recipients, and healthy individuals, and SCC of the vulva and nail unit caused by mucosal high‐risk HPV infection. Carcinogenesis of β‐HPV is associated with sunlight. Mucosal high‐risk HPV‐associated carcinomas may also be sexually transmitted. We focused on Bowen's disease of the nail, which has been the subject of our research for a long time and has recently come to the fore in the field of dermatology. [ABSTRACT FROM AUTHOR]

Herpes zoster is a disease caused by reactivation of the varicella‐zoster virus that has been latently infecting the body and is more common among the elderly. In Japan, the incidence of herpes zoster has been increasing steadily and is expected to increase further in the future. In 2016, the varicella vaccine was expanded to include prevention of herpes zoster, and a new subunit vaccine was also launched in 2020. In recent years, anti‐herpesvirus drugs with novel pharmacological effects have also been introduced, and the environment surrounding the treatment of herpes zoster is entering a new era. [ABSTRACT FROM AUTHOR]

The genomic landscape of Bowen's disease (BD), with multiple manifestations, has not yet been determined. This study aimed to investigate the genomic alterations in multiple BD. We performed whole‐exome sequencing of BD lesions (n = 9) and matched germlines collected from three patients with multiple (≥3) BD to detect somatic and germline mutations. We found a median of 64 somatic mutations in each sample (range 20–267). UV‐signature mutations accounted for 64.9% (median, range 26.0%–82.1%) of point mutations. Putative driver mutations were found in five BDs (RB1 p.R445*, ARID2 p.R274*, TP53 p.Y163D/p.Y205D/p.R342*, KMT2C p.R4549C) but not in the other four lesions. Somatic mutations were not shared between multiple BD lesions collected from the same patient, indicating a different clonal origin. We also found no known pathogenic germline mutations in cancer‐related genes. The mutational signature analysis revealed that UV signatures (SBS7a/7b) and age‐related signatures (SBS1/5) were the main active signatures. Copy number alterations (CNAs) were found in two BDs: one with extensive CNA regions (21.7% of the genome), including driver genes (PIK3CA/SOX2/TP63 and MYC gain, and CDKN2A loss), and the other with 1q gain. Our study revealed that multiple BD lesions harbor distinct genomic landscapes, suggesting that they have different risks of malignant progression. [ABSTRACT FROM AUTHOR]

Hyperhidrosis significantly reduces patients' quality of life, with many reporting feeling highly anxious. However, the relationship between hyperhidrosis and anxiety induced by sweating has not been examined in detail. The current study examined the relationship between: (1) the presence of hyperhidrosis symptoms, (2) hyperhidrosis severity, and (3) the sites of the most sweating and anxiety induced by sweating. A cross‐sectional web‐based survey was conducted among university students, and 1080 consenting participants (600 males and 480 females; mean age, 18.8 years) were included in the analysis. The survey items were: (1) diagnostic criteria for hyperhidrosis, (2) Hyperhidrosis Disease Severity Scale, (3) presence of anxiety induced by sweating, and (4) site of the most sweating. The results of multiple logistic regression analysis adjusted for sex and age showed that the odds ratio (OR) for anxiety induced by sweating was significantly higher in participants who screened positive for hyperhidrosis than in those who screened negative (OR, 9.72 [95% CI, 5.80–16.27]). The OR of anxiety induced by sweating was 7.11 (95% CI, 3.99–12.65) for mild/moderate hyperhidrosis and 23.46 (95% CI, 7.15–76.93) for severe hyperhidrosis, compared with those who screened negative for hyperhidrosis. Compared with those who screened negative for hyperhidrosis, the OR for anxiety induced by sweating in those with the palmar, plantar, axillary, and head/face as the site of the most sweating was 7.74 (95% CI, 3.91–15.33), 14.86 (95% CI, 1.83–120.58), 16.92 (95% CI, 5.95–48.14), and 5.38 (95% CI, 1.39–20.74), respectively. Our findings suggest that participants who screened positive for hyperhidrosis, mild/moderate or severe, are at a higher risk of anxiety induced by sweating than participants who screened negative for hyperhidrosis. [ABSTRACT FROM AUTHOR]

Hypohidrotic ectodermal dysplasia is a rare condition characterized by hypohidrosis, hypodontia, and hypotrichosis. The disease can show X‐linked recessive, autosomal dominant or autosomal recessive inheritance trait. Of these, the autosomal forms are caused by mutations in either EDAR or EDARADD. To date, the underlying pathomechanisms or genotype–phenotype correlations for autosomal forms have not completely been disclosed. In this study, we performed a series of in vitro studies for four missense mutations in the death domain of EDAR protein: p.R358Q, p.G382S, p.I388T, and p.T403M. The results revealed that p.R358Q‐ and p.T403M‐mutant EDAR showed different expression patterns from wild‐type EDAR in both western blots and immunostainings. NF‐κB reporter assays demonstrated that all the mutant EDAR showed reduced activation of NF‐κB, but the reduction by p.G382S‐ and p.I388T‐mutant EDAR was moderate. Co‐immunoprecipitation assays showed that p.R358Q‐ and p.T403M‐mutant EDAR did not bind with EDARADD at all, whereas p.G382S‐ and p.I388T‐mutant EDAR maintained the affinity to some extent. Furthermore, we demonstrated that all the mutant EDAR proteins analyzed aberrantly bound with TRAF6. Sum of the data suggest that the degree of loss‐of‐function is different among the mutant EDAR proteins, which may be associated with the severity of the disease. [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 version). As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti‐tumor necrosis factor‐α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti‐interleukin (IL)‐12/IL‐23p40 antibody, which was launched in Japan in 2011. Moreover, after 2015, three IL‐17 inhibitors, the IL‐17A antibody preparations secukinumab and ixekizumab, and an anti‐IL‐17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti‐IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL‐23 inhibitor tildrakizumab, and the anti‐IL‐17A/F antibody bimekizumab were marketed. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors, and patient background factors, sharing such information with patients. The followings can be listed as points to be considered for the selection of biologics: drug effects (e.g., strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g., infections, administration‐related reactions, and relationships with other comorbidities), convenience for patients (e.g., hospital visit intervals, self‐injection, maintenance therapy at clinics, feasibility of drug discontinuation/re‐administration), and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above‐mentioned factors. [ABSTRACT FROM AUTHOR]

To evaluate the outcomes of secukinumab and acitretin use in children with generalized pustular psoriasis (GPP), we compared the efficacy and adverse events of secukinumab in 20 children and acitretin in 16 children with GPP from January 1, 2019, to January 30, 2022. Among the 20 patients treated with secukinumab, the average time for pustules to fade, temperature to normalize, and C‐reactive protein (CRP) to normalize was 3.83, 2.46, and 3.91 days, respectively. All patients recovered (Japanese Dermatological Association severity index score: 0/1) in 3 weeks. The adverse events were abnormal liver enzyme (10%), atopic dermatitis–like lesions (10%), herpes simplex (5%), and neutropenia (10%). For the patients treated with acitretin, the average time for pustules to fade, temperature to normalize, and CRP to normalize was 6, 6.14, and 8.73 days, respectively. The adverse events included mucocutaneous dryness (75%), dyslipidemia (37.5%), and abnormal liver enzyme (25%). These findings demonstrate that secukinumab has more favorable outcomes than acitretin, and secukinumab was well tolerated by the pediatric patients with GPP. [ABSTRACT FROM AUTHOR]

Schimmelpenning‐Feuerstein‐Mims syndrome (SFMS), an epidermal nevus disease, features skin lesions including craniofacial nevus sebaceous and extracutaneous anomalies (e.g. brain, eye, and bone). Recent genetic studies implicate HRAS, KRAS, and NRAS genes in somatic mutations. Our case, a 48‐year‐old man, presented with nevus sebaceous on the scalp; pigmented skin lesions on the right side of his neck, back, and chest along the Blaschko lines; a history of epilepsy; and mild intellectual disability. Accordingly, SFMS was suspected. DNA analysis of nevus sebaceous skin and peripheral blood leukocytes showed a pathogenic HRAS variant NM_005343.4:c.34G > A p.(Gly12Ser) in biopsy specimens from different skin layers but not blood, indicating somatic mosaic mutation. Until now, the HRAS p.(Gly12Ser) mutation has been reported in somatic RASopathies but not SFMS. The authors report this mutation in a case of SFMS, review another 15 cases of SFMS, and discuss HRAS c.34G > A p.(Gly12Ser) somatic mutations. RAS mutations of somatic RASopathies share activating hotspot mutations found in cancers, and produce different phenotypes depending on the developmental stage at which the somatic mutations occur. [ABSTRACT FROM AUTHOR]

This is the English version of guidance for the use of oral Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis. Several cytokines, such as interleukin (IL)‐4, IL‐13, IL‐22, IL‐31, thymic stromal lymphopoietin, and interferon‐γ, are involved in the pathogenesis of atopic dermatitis. As oral JAK inhibitors hinder the JAK‐signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of atopic dermatitis. In Japan, as oral JAK inhibitors for atopic dermatitis, a JAK1/2 inhibitor, baricitinib, expanded its authorized indications for atopic dermatitis in 2020. Consequentially, a JAK1 inhibitor, upadacitinib, also expanded its indications to atopic dermatitis in 2021, followed by new approval of another JAK1 inhibitor, abrocitinib, for the use under the Japanese health insurance system. Physicians who intend to use them should sufficiently understand and comply with contents of guidelines prepared by the Japanese Ministry of Health, Labour and Welfare to promote optimal use of these drugs. In the treatment with oral JAK inhibitors, it is important to sufficiently consider disease factors, treatment factors and patient backgrounds, and share them with patients to choose treatment options. Points to be considered for drug selection include the efficacy and safety of drugs, age of patients, and dosage and administration of the drug. This guidance was developed for board certified dermatologists, who are specialized in the treatment of atopic dermatitis, and for promoting proper use of oral JAK inhibitors, taking into account a variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

Facial pigmented spots are one of the phenotypes of skin aging, but no quantitative analysis of spot features such as color intensity, size, anatomical position, and number on the cheek has yet been performed. In the current study, we conducted an epidemiological survey of 454 Japanese women in their 20s to 70s and analyzed age‐related changes and site differences of facial pigmented spots. Using image analysis of high‐resolution digital facial photographs, 4912 individual pigmented spots were quantified according to color, size, anatomical position, and total number on the cheek. As a result of color analysis, the color intensity of individual pigmented spots increased with aging, significantly so between ages 30s and 50s. The age‐related increase in melanin index of facial spots was confirmed in all sites but did not significantly differ between facial subregions. Regarding the size of pigmented spots, the frequency of large spots increased with age, and large spots were detected in all facial sites. The total number of pigmented spots on the entire cheek increased with aging, significantly so between the 20s and 40s. The number of pigmented spots tended to increase from the region near the canthi to the lower cheeks. The number of spots was markedly increased in the buccal regions compared with the infraorbital and zygomatic regions. The data and methodology presented in the current study can link the state of facial pigmentation with the various factors involved in the histological development of pigmented spots, opening new possibilities in the fields of skin pharmacology and dermatology. [ABSTRACT FROM AUTHOR]