Japanese Dermatological Association Research Articles

Japanese Dermatological Association guidelines: Outlines of Japanese clinical guidelines for basal cell carcinoma 2021.

To summarize the current therapies for skin cancers, the Japanese Skin Cancer Society issued the first guidelines for skin cancers, including melanoma, squamous cell carcinoma, basal cell carcinoma (BCC), and extramammary Paget's disease, in 2007. These guidelines were revised in 2015. Herein, we present the English version of the 2021 edition of the Japanese clinical guidelines for BCC. In the latest edition, all procedures were performed according to the Grading of Recommendations, Assessment, Development and Evaluation systems. The clinical questions that could not be answered were selected for further analysis. A comprehensive literature search, systematic review, and recommendations for each clinical question were determined by a multidisciplinary expert panel comprising dermatologists, a plastic and reconstructive surgeon, and a pathologist. Surgical resection is the gold-standard therapy of BCC. Radiotherapy or topical treatments, other than surgical resection, have been used in some cases. Patients with unresectable or metastatic BCC require systemic therapy. Novel agents, such as immune response modifiers or hedgehog pathway inhibitors, are emerging worldwide for the treatment of BCC. Based on these viewpoints, four relevant clinical questions regarding, surgical resection, radiotherapy, topical treatment, and systemic therapy, were raised in this report that aims to help clinicians select suitable therapies for their patients.

Tackling steroid phobia: Insights from behavioural economics and psychological approaches

AbstractSteroid phobia, characterized by an irrational fear or avoidance of topical corticosteroids, poses a significant challenge to the effective treatment of various skin conditions, including atopic dermatitis (AD) and psoriasis. This issue has its roots in the introduction of topical corticosteroids in the 1950s and has been perpetuated by concerns regarding adverse effects and misinformation. International Dermatological Societies including the Japanese Dermatological Association have endeavored to address this problem by providing information and guidance to physicians and patients, resulting in a better understanding of appropriate steroid use and risk management. Despite these efforts, steroid phobia has not been fully resolved in the world, including in Japan.To shed light on potential solutions, this review explores the field of behavioral economics, which offers insights into human decision‐making processes and cognitive biases. Richard Thaler's concept of nudges emerges as a promising strategy for influencing patients' decision‐making regarding steroid treatments. However, the effectiveness of nudges may vary depending on the strength of an individual's concerns and fears. In cases where patients exhibit strong resistance to steroid use, alternative psychological techniques that establish trust and facilitate clear communication may be more beneficial.This review emphasizes the necessity of adopting a multifaceted approach that integrates principles from behavioral economics and employs complementary psychological strategies to address steroid phobia and enhance treatment adherence in affected patient populations. By combining these approaches, healthcare professionals can tackle the complex nature of steroid phobia and promote better treatment outcomes for patients with skin conditions.

Real-world retention rates and effectiveness of secukinumab in psoriasis: Results from a multicenter cohort study (RAILWAY).

Psoriasis is a chronic, immune-mediated inflammatory skin disease with a high negative impact on patient's quality of life. Secukinumab, the first interleukin 17A inhibitor, has been used for the systemic treatment of psoriasis, but its long-term, real-world retention rates in Japan have not been fully investigated. In this multicenter, noninterventional, retrospective chart review study, the retention rate of secukinumab and its effectiveness among patients with psoriasis in Japan was evaluated up to 5 years. Data of patients who received secukinumab after December 26, 2014, were collected from medical charts obtained from seven sites, all certified for biologics use by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors affecting secukinumab retention, reason for drug discontinuation, and effectiveness data were collected. The primary end point was secukinumab retention rate at week 52. A total of 123 patients were included in the analysis. Of these, 27 patients discontinued secukinumab by week 52, yielding a 78.0% (95% confidence interval, 69.6-84.4) retention rate at week 52. For patients whose Psoriasis Area and Severity Index (PASI) score was available, mean ± standard deviation PASI at baseline and at week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively. During the entire study period, "insufficient response" was the most common reason for discontinuation, and "history of biologics use" was a factor significantly associated with secukinumab discontinuation (hazard ratio, 1.72; p = 0.018). This study demonstrates the real-world retention rate and effectiveness of secukinumab in patients with psoriasis in Japan for up to 5 years and provides clinical insights into psoriasis treatment strategies.

Clinical guidance of pyoderma gangrenosum 2022.

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.

A Study of 105 Patients Treated with Omalizumab for Chronic Idiopathic Urticaria

Omalizumab (Xolair®) was approved for the treatment of chronic idiopathic urticaria in 2017. Furthermore, consistent with international guidelines published in 2018, the Urticaria Clinical Practice Guidelines by the Japanese Dermatological Association provide detailed instructions for the use of omalizumab. However, there are no reports summarizing the efficacy of omalizumab in chronic idiopathic urticaria in Japan. The subjects of our study were 105 patients treated with omalizumab 300 mg/month for chronic idiopathic urticaria at Tokyo Medical University Hospital from June 2017 to March 2021, inclusive of 23 male and 82 female patients, with a mean age of 45.4 ± 16.0 and disease duration of 46.9 ± 99.4 months. Three months after treatment, omalizumab was discontinued in 63 patients with a Urticaria Control Test score of 16. The mean number of dose completions was 6.4 ± 4.1. There were nine cases of relapse in which seven of the nine cases discontinued omalizumab within six doses. Most of the relapsed cases improved with re-administration of omalizumab, but it was again discontinued in five cases. Omalizumab has lesser side effects than steroids and cyclosporine, and the criteria for its use were revised in 2018, requiring an allergist or dermatologist to be available to treat adverse events such as asthma and anaphylaxis at the facility or in collaboration with neighboring medical institutions. Omalizumab can also be used in dermatology clinics. The drug is an effective treatment for severe chronic idiopathic urticaria and is anticipated to be used by more dermatologists.

Pharmaceutical payments to Japanese board-certified dermatologists: a 4-year retrospective analysis of personal payments from pharmaceutical companies between 2016 and 2019

There are prevalent financial relationships between dermatologists and pharmaceutical companies in Japan. However, little was known about the extent of whole picture of the personal payments made to dermatologists by pharmaceutical companies. This study aimed to examine the personal payments to the board-certified dermatologists by the Japanese Dermatological Association from the pharmaceutical companies between 2016 and 2019. Using the publicly disclosed payments data by the pharmaceutical companies between 2016 and 2019, we evaluated the magnitude, prevalence, and trends in the personal payments made to all board-certified dermatologists for the lecturing, writing, and consulting compensations. The payments were descriptively analyzed overall and by dermatologist demographics. Additionally, the payment trends were assessed by generalized estimating equation models. Of 6883 active board-certified dermatologists, 3121 (45.3%) received a total of $33,223,806 personal payments between 2016 and 2019. The median per-physician payments and number of payments (interquartile range) were $1737 ($613–$5287) and 4.0 (2.0–10.0) over the 4 years, respectively. Only top 1%, 5%, 10% of dermatologists received 41.7% (95% confidence interval [CI] 38.2–45.1%), 76.9% (95% CI 74.7–79.1%), and 87.6% (95% CI 86.2–88.9%) of overall payments. The number of dermatologists receiving payments and per-dermatologist payments increased by 4.3% (95% CI 3.1‒5.5%, p < 0.001) and 16.4% (95% CI 13.5‒19.4%, p < 0.001) each year. The board-certification in dermatology-oncology, in cosmetic dermatology, and male sex were significantly associated with higher personal payments with relative monetary values of 2.29 (95% CI 1.65–3.19, p < 0.001), 3.16 (95% CI 1.89–5.26, p < 0.001), and 5.38 (95% CI 4.12–7.04, p < 0.001). Less than half of Japanese board-certified dermatologists received lower personal payments from the pharmaceutical companies than those to other specialists. However, these personal payments were increasingly more prevalent and greater over the 4 years.

Acrodermatitis continua of Hallopeau and generalised pustular psoriasis: Should they be the same or different entities?

Pustular psoriasis is characterised by eruptions of neutrophilic sterile pustules. The European Rare and Severe Psoriasis Expert Network consensus defines pustular psoriasis into three subtypes; generalised pustular psoriasis (GPP), palmoplantar pustulosis and acrodermatitis continua of Hallopeau (ACH). Mixed forms are categorised according to their predominant features. However, the Japanese Dermatological Association includes ACH under the diagnosis of GPP. This article aims to review the similarities and differences between ACH and GPP. Based on our review, interleukin (IL)-36RN mutations, the most frequent genetic findings in pustular psoriasis are found most commonly in GPP, followed by ACH. Genotypes of IL-36RN mutations among GPP patients and ACH patients are different between European and Asian ethnicities. IL-36 signalling pathway is the main mechanism. Metabolic diseases are common comorbidities and joint involvement can occur in 20.5%-36.4% of both conditions. Associated plaque psoriasis is more common in GPP than in ACH. Generally, ACH, even the generalised type, does not have systemic inflammation whereas GPP can occur with or without systemic inflammation. ACH can occur before, simultaneously, or after the development of GPP. However, response to treatment for GPP and ACH even in the same patients appear to be different. ACH seemed to be more recalcitrant to treatment than GPP but severe flare of GPP can lead to morbidity and mortality. Although GPP and ACH share genotypes and pathogenesis, we believe that ACH should be classified separately from GPP, and not under diagnosis of GPP. Future research is warranted to satisfactorily distinguish the two conditions.

English version of Japanese guidance for the use of oral Janus kinase inhibitors (JAK1 and TYK2 inhibitors) in the treatments of psoriasis.

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.

Assessment of flare frequency and severity of generalized pustular psoriasis in Japanese patients: A retrospective chart review study

AbstractBackgroundGeneralized pustular psoriasis (GPP) is a rare and often refractory disease, and GPP flares can be life threatening. The rarity of GPP prevents the development and evaluation of effective GPP‐specific treatments and obstructs disease understanding.ObjectivesTo evaluate the frequency and severity of GPP flares and the clinical background and treatment history of patients with GPP in Japan.MethodsThis retrospective, longitudinal, Japanese chart review study included patients diagnosed with GPP (according to Japanese Dermatological Association [JDA] diagnostic criteria), with ≥6 months of continuous observation within 10 years of protocol approval at study sites. Primary outcomes: the frequency and severity of GPP flares during follow‐up. Secondary outcomes: patient characteristics (at time of initial GPP diagnosis) and GPP treatment during follow‐up.ResultsOverall, 205 Japanese patients were included; 106/205 (51.7%) were male, 146/205 (71.2%) were aged &lt;65 years. Few patients had a family history of GPP (7/155, 4.5%) or psoriasis‐related diseases (6/120, 5.0%). At baseline, 36.1% (74/205), 30.7% (63/205) and 33.2% (68/205) of patients had mild, moderate and severe GPP, respectively; GPP flares were reported by 177/205 patients (86.3%), which were mostly moderate in severity (52/205; 25.4%) or severe (99/205; 48.3%). During follow‐up, GPP flares were reported by 70/205 patients (34.1%): 47/205 (22.9%) had 1 flare and 23/205 (11.2%) had ≥2. Among the 106 flare events reported during follow‐up, 1 was mild, 55 were moderate and 50 were severe. The median time to first GPP flare was 7.7 years and the overall incidence of GPP flares during follow‐up was 11.5/100 person‐years. During follow‐up, topical treatment (195/205; 95.1%), systemic therapy other than corticosteroids (177/205; 86.3%) and biologics (163/205; 79.5%) were most frequently used.ConclusionsDuring follow‐up, over one‐third of Japanese patients with GPP experienced mostly moderate‐to‐severe GPP flares, despite available treatments. There remains an unmet need for effective GPP treatment options.

Evaluation of Financial and Nonfinancial Conflicts of Interest and Quality of Evidence Underlying Psoriatic Arthritis Clinical Practice Guidelines: Analysis of Personal Payments From Pharmaceutical Companies and Authors' Self-Citation Rate in Japan and the United States.

To assess financial conflicts of interest (COI) and nonfinancial COI among psoriatic arthritis (PsA) clinical practice guideline (CPG) authors in Japan and the US, and to evaluate the quality of evidence and strength of recommendations of PsA CPGs. We performed a retrospective analysis using payment data from major Japanese pharmaceutical companies and the US Open Payments Database from 2016 to 2018. All authors of PsA CPGs issued by the Japanese Dermatological Association (JDA) and American College of Rheumatology (ACR) were included. Of 23 CPG authors in Japan, 21 (91.3%) received at least 1 payment, with a combined total of $3,335,413 between 2016 and 2018. Regarding 25 US authors, 21 (84.0%) received at least 1 payment, with a combined total of $4,081,629 during the same period. The 3-year combined mean± SD payment per author was $145,018 ± $114,302 in Japan and $162,825 ± $259,670 in the US. A total of 18 authors (78.3%) of the JDA PsA CPG and 12 authors (48.0%) of the ACR PsA CPG had undisclosed financial COI worth $474,663 and $218,501, respectively. The percentage of citations with at least 1 CPG author relative to total citations was 3.4% in Japan and 33.6% in the US. In sum, 71.4% and 88.8% of recommendations for PsA in the JDA and ACR were supported by low or very low quality of evidence. More rigorous cross-checking of information disclosed by pharmaceutical companies and self-reported by physicians and more stringent and transparent COI policies are necessary.

Prevalence, comorbidities, and treatment patterns of Japanese patients with alopecia areata: A descriptive study using Japan medical data center claims database.

Real-world data on alopecia areata (AA) demographics, comorbidities, and treatment patterns are sparse, not only in Japan but worldwide. This cross-sectional study assessed the current prevalence of AA in Japan, including analysis of severe subsets, frequency of comorbidities, and unmet medical needs surrounding treatment. Patients registered in the Japan Medical Data Center claims database (January 2012 to December 2019) and diagnosed with AA were included. Prevalence was calculated yearly, with the most common comorbidities evaluated, and treatments described in the Japanese Dermatological Association AA management guidelines and approved in Japan were included in the analysis. In total, 61 899 patients were diagnosed with AA. Among them, 1497 were diagnosed with severe subtypes. AA prevalence in Japan has been gradually increasing (from 0.16% in 2012 to 0.27% in 2019). The most common comorbidities are allergic rhinitis, atopic dermatitis, and asthma. Depression and anxiety are frequent in these patients, as are autoimmune diseases, e.g., vitiligo, thyroid diseases, and rheumatoid arthritis. Intriguingly, the analysis found Down syndrome to be a comorbidity associated with severe AA in children. The principal treatments were topical corticosteroids, followed by carpronium chloride and cepharanthine. The use of systemic corticosteroids and antihistamines is increased in severe disease. The Japanese Dermatological Association guidelines do not support the use of oral corticosteroids in children; however, in the database, this has been prescribed in up to 2.5% and 9.8% of all pediatric and severe pediatric AA cases, respectively. Despite the limitations of using a claims database, the current study demonstrates that AA prevalence in Japan has gradually increased in recent years, with allergic diseases being the most common comorbidities. The data also imply that there is a need for effective and safe therapies, especially for severe and pediatric cases.

Exploratory analyses of biomarkers in blood and stratum corneum in patients with atopic dermatitis.

Background:The pathogenesis of atopic dermatitis (AD) involves various mediators, including cytokines and chemokines, which are produced by immune cells, such as dendritic cells and lymphocytes, and non-immune cells, such as epidermal cells. Several mediators, including thymus and activation-regulated chemokine (TARC), are used as biomarkers for AD severity and activity. However, additional local and systemic biomarkers of AD are required.Methods:This study will include 10 male patients with AD and 5 healthy adult males (age range: 20–80 years). The Eczema Area and Severity Index will be used to objectively evaluate the clinical findings. In addition, the severity of eruptions will be assessed on a 5-point scale by scoring symptoms (erythema, edema/papules, oozing/crusting, excoriation, lichenification, and xerosis), and the total intensity will be calculated by adding the symptom scores together. Subjective symptoms will be assessed using a peak pruritus numerical rating scale. Laboratory tests, including measurements of peripheral eosinophil count and serum total immunoglobulin E, TARC, and lactate dehydrogenase levels, will be performed. Using blood samples and extracts of stratum corneum samples obtained by tape stripping, we will conduct an exploratory analysis of protein expression using an antibody array to identify mediators whose levels are significantly altered in patients with AD. After 4 to 8 weeks, blood samples and stratum corneum samples will be collected again from AD patients. Moreover, we will examine whether the candidate proteins can be quantified using enzyme-linked immunosorbent assays.Discussion:This is an important study exploring potential local and systemic biomarkers of AD. The results of this study will be clinically meaningful for the discovery of new biomarkers for diagnosing and assessing the severity of AD.

33007 Efficacy of spesolimab for the treatment of GPP flares across prespecified patient subgroups in the Effisayil 1 study

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening autoinflammatory disease characterized by recurrent flares of sterile pustules that occur with or without systemic inflammation. The 12-week, double-blind, randomized, placebo-controlled Effisayil 1 study (NCT03782792) demonstrated that spesolimab, an anti-interleukin 36 receptor antibody, is associated with rapid pustular and skin clearance in patients with a GPP flare. Here we report the efficacy of spesolimab across prespecified patient subgroups (sex, age, race, body mass index, GPP Physician Global Assessment [GPPGA] pustulation subscore at baseline, GPPGA total score at baseline, Japanese Dermatological Association GPP severity score at baseline, plaque psoriasis at baseline, and IL-36 receptor antagonist gene mutation [IL36RN] status) in Effisayil 1.

Real-world data on the use of secukinumab and acitretin in pediatric generalized pustular psoriasis.

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.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results.

IntroductionWe report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217).MethodsPatients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved “much improved” or “very much improved” on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician’s Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0–52.ResultsOf 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response (“improved” or “remission”). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients.ConclusionCZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified.Trial RegistrationClinicalTrials.gov identifier, NCT03051217.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00741-x.

Increased serum levels of CCL3, CXCL8, CXCL9, and CXCL10 in rosacea patients and their correlation with disease severity.

Rosacea is a common chronic inflammatory skin disease involving millions of patients worldwide. Previous studies have highlighted the upregulation of a variety of chemokines in the skin lesions of both rosacea patient and rosacea-like mouse model. However, the serum levels of these chemokines and their clinical significance have not been explored before. In this study, we aimed at examining the serum levels of a series of chemokines (including CCL2, CCL3, CCL20, CXCL1, CXCL8, CXCL9, CXCL10, and CXCL12) implicated in rosacea and their correlation with disease severity. Bio-Plex Pro Human Chemokine Assays were used to measure the serum levels of these chemokines. Investigator's Global Assessment (IGA) was applied for assessing the papules/pustules of rosacea patients, while persistent erythema was evaluated by the Clinician's Erythema Assessment (CEA). Our results revealed that the serum concentration of CCL3, CXCL8, CXCL9, and CXCL10 were markedly elevated in rosacea patients compared to healthy controls. Among them, the levels of CCL3, CXCL8, and CXCL9 were positively correlated with the IGA score, while serum CXCL9 and CXCL10 were positively related with the CEA score of rosacea patients. What's more, the expression of the corresponding receptors of CCL3 (Ccr1), CXCL8 (Cxcr1 and Cxcr2), CXCL9, and CXCL10 (Cxcr3) were all significantly increased in the skin lesions of rosacea-like mouse model with CXCR2 and CXCR3 highly expressed in rosacea patient skins. Our results indicated that CCL3, CXCL8, CXCL9, and CXCL10 might potentially serve as serum indicators for rosacea and could assist the severity evaluation of disease. Findings in this study would also potentially help to develop new targeted therapies for rosacea in future. © 2022 Japanese Dermatological Association.

Real-world blood examination screening data before initiation of biologics for psoriasis patients.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Biologics have been available for the treatment of patients with refractory psoriasis since 2010 in Japan, and as of December 2021, 10 biologics were available. The Biologics Review Committee of the Japanese Dermatological Association for Psoriasis recommends blood examination tests for antinuclear antibodies (ANA), Krebs von den Lugen (KL)-6, hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis C virus (HCV) antibodies, HIV antibodies, human T-cell leukemia virus (HTLV)-1 antibodies, β-D-glucan, and the T-cell spot (T-SPOT) test before initiation of biologics at screening. In this study, we evaluated the use of biologics for 127 psoriasis patients and the blood examination screening data before initiation of biologics in the real-world setting. Tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors were initiated for 54 (42.5%), 36 (28.3%), and 37 (29.1%) patients, respectively. The numbers of patients positive for ANA, HBsAg, HBsAb, HBcAb, HCV antibody, HIV antibody, HTLV-1 antibody, and T-SPOT were 27 (21.3%), 0 (0%), 22 (17.3%), 20 (15.7%), three (2.4%), zero (0%), one (0.8%), and 4 (3.1%), respectively. The numbers of patients whose KL-6 and β-D-glucan levels were higher than the reference values were seven (5.5%) and seven (5.5%), respectively. In the real-world setting, it is sometimes unavoidable to use biologics for those patients with abnormal data although careful monitoring is necessary.

Clinical practice guidelines for pseudoxanthoma elasticum (2017): Clinical Practice Guidelines for Pseudoxanthoma Elasticum Drafting Committee

Pseudoxanthoma elasticum (PXE) is a progressive hereditary disease that affects tissues such as the skin, retina, blood vessels, and gastrointestinal tracts. Therefore, comprehensive medical care across clinical departments specialized in specific organs is needed to provide the best clinical practices to PXE patients. The Japanese version of clinical guidelines developed by the Japanese Dermatological Association was published in 2017, and aimed to promote equal accessibility of PXE-related medical care. Here, the English version of Japanese guideline is reported, and is intended to be worldwide reference for medical care of PXE.

Training and Retaining Physician‒Scientists in Dermatology: Japan

Recently, the number of dermatologists who pursue scientific research careers has been dwindling in Japan. One of the major reasons for the reduction is the recent alterations of the Japanese medical specialty training system. Our strategies against the decline of young dermatologists’ desire to be physician‒scientists include the establishment of a simultaneous PhD program for specialty course trainees, the establishment of a young academician-fostering seminar by the Japanese Society for Investigative Dermatology, and support for studying abroad by the Japanese Dermatological Association.

Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines.

Alopecia areata (AA) is a relatively common nonscarring hairloss disease characterized by an autoimmune response to anagen hair follicles (HFs). Accumulated evidence suggests that collapse of the HF immune privilege subsequent to triggering events, represented by viral infection, leads to autoimmune response in which autoreactive cytotoxic CD8+NKG2D+ T cells mainly target exposed HF autoantigens. AA had been recognized as type 1 inflammatory disease, but recent investigations have suggested some roles of type 2- and Th17-associated mediators in AA pathogenesis. The significance of psychological stress in AA pathogenesis is less emphasized nowadays, but psychological comorbidities, such as depression and anxiety, attract greater interest in AA management. In this regard, the disease severity may not solely be evaluated by the extent of hair loss. Use of trichoscopy markedly improved the resolution of the diagnosis and evaluation of the phase of AA, which is indispensable for the optimization of treatment. For the standardization of AA management, the establishment of guidelines/expert consensus is pivotal. Indeed, the Japanese Dermatological Association (JDA) and other societies and expert groups have published guidelines/expert consensus reports, which mostly recommend intralesional/topical corticosteroid administration and contact immunotherapy as first-line treatments, depending on the age, disease severity, and activity of AA. The uniqueness of the JDA guidelines can be found in their descriptions of intravenous corticosteroid pulse therapy, antihistamines, and other miscellaneous domestically conducted treatments. Considering the relatively high incidence of spontaneous regression in mild AA and its intractability in severe subsets, the importance of course observation is also noted. Evidenced-based medicine for AA is currently limited, however, novel therapeutic approaches, represented by JAK inhibitors, are on their way for clinical application. In this review, the latest understanding of the etiopathogenesis and pathophysiology, and update on therapeutic approaches with future perspectives are summarized for AA, following the current version of the JDA AA management guidelines.