Clinical and Histopathologic Study of Apocrine-Type Mixed Tumor of the Skin.

ABSTRACT: Mixed tumor of the skin (MTS) is a tumor characterized by folliculosebaceous-apocrine differentiation. Because of the wide range of histological variations, understanding the unique features of MTS can help improve diagnosis. This study describes the histopathological characteristics of MTS, mainly apocrine-type MTS (AMT), using 166 cases of AMT. We found that nodular aggregates of myoepithelial cells, mucinous changes in the stroma, and follicular differentiation were standard characteristic features of MTS. Among the cases studied, 67% showed prominent follicular germinative cells and 40% showed prominent lipomatous metaplasia in the stroma. These cases often pose difficulties for the diagnosis of AMT because of insufficient evidence of sweat glands or myoepithelial cell differentiation. This is the first study to examine how the histological features of AMT change as the tumor extends deeper into the dermis. We found that the proportion of AMT with folliculosebaceous differentiation and large lumina increased as it got deeper into the dermis. Histopathological diagnosis of MTS is vital because the clinical symptoms lack specificity. This study enhances our understanding of the histopathological characteristics of MTS.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.

BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%). CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial.

BACKGROUND: Atopic dermatitis (AD) is characterized by microbial dysbiosis, immune dysregulation, and an impaired skin barrier. Microbial dysbiosis in AD involves a reduction in diversity primarily driven by an increased abundance of Staphylococcus aureus. Tralokinumab, an approved treatment for adults with moderate-to-severe AD, improves the skin barrier and immune abnormalities by specifically targeting the interleukin 13 cytokine, but its impact on the skin microbiome is unknown. OBJECTIVE: To investigate how tralokinumab affects the skin microbiome by examining the lesional skin of adults with moderate-to-severe AD from the phase 3 ECZTRA 1 trial (NCT03131648). METHODS: Microbiome profiling, S aureus abundance, and biomarker data were assessed in a subset of ECZTRA 1 participants (S aureus abundance at baseline and week 16; microbiome profiling at baseline, and week 8/16; and serum sampling before dose and week 4/8/16/28/52). RESULTS: Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci. LIMITATIONS: Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives. CONCLUSION: Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin.

The disease burden of pediatric patients with atopic dermatitis in Japan.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin condition that is associated with significant patient burden and decreased health-related quality of life (HRQoL). We report results of the real-world Epidemiology of Children with Atopic Dermatitis Reporting on their Experience study in Japanese pediatric patients, focusing on the impact of AD severity on disease burden. METHODS: Children and adolescents aged 6 months to 17 years (or their caregivers/parents) completed an online survey between September 26, 2018, and March 5, 2019. Patients with diagnosed AD (i.e., met International Study of Asthma and Allergies in Childhood criteria and had a self-reported AD diagnosis) were evaluated for disease severity using the Patient-Oriented Eczema Measure (POEM). Impact of AD severity on AD symptoms (itching, pain, and sleep disturbance), disease flares, atopic comorbidities, healthcare resource utilization, school days missed, and HRQoL were assessed. RESULTS: Of 5702 Japanese pediatric patients, 547 had diagnosed AD and were included in this analysis. Based on POEM scores, AD severity was clear/mild in 346 patients (63.3%), moderate in 177 (32.5%), and severe in 24 (4.4%). Across all age groups (i.e., less than 6, 6-11, and 12-17 years), increased AD severity was associated with increased AD symptom severity, number of flares, atopic comorbidities, healthcare resource utilization, and school absences, as well as worsened HRQoL. CONCLUSIONS: This population-based study of Japanese children and adolescents showed that greater AD severity had a high impact on disease burden.

Dietary Fiber Inulin Improves Murine Imiquimod-Induced Psoriasis-like Dermatitis.

Psoriasis is a chronic skin disease with interleukin (IL)-17-dominated inflammation and hyperproliferation of epidermis. Dietary fiber is fermented by the gut microbiome into short-chain fatty acids (SCFAs) that manifest anti-inflammatory effects. We examined if feeding with an inulin-enriched high-fiber diet (HFD) might improve topical imiquimod-induced psoriasis-like dermatitis in mice. HFD reduced thickening and total severity scores of imiquimod-induced dermatitis and reduced epidermal thickness, inflammatory infiltrates, including Ly6G+ neutrophils, and epidermal Ki67+ proliferating cells. HFD reduced mRNA levels of IL-17A, IL-17F, IL-22, IL-1ß, tumor necrosis factor (TNF)-α, CXCL1, CXCL2, and keratin 16 and increased those of transforming growth factor (TGF)-ß1 and cyclin-dependent kinase inhibitor 1A in imiquimod-induced dermatitis. In 16S rRNA sequencing of the gut microbiome, imiquimod increased relative abundance of phylum Firmicutes, while HFD increased that of phylum Bacteroidota and genus Bacteroides. HFD increased serum and fecal concentrations of SCFA propionate. Oral propionate reduced inflammatory infiltrates and epidermal Ki67+ cells and reduced mRNA levels of IL-17A, IL-17F, IL-17C, IL-22, IL-1ß, IL-6, TNF-α, CXCL1, CCL20 and increased those of TGF-ß1and IL-10 in imiquimod-indued dermatitis. Dietary inulin supplementation improves imiquimod-induced psoriasis-like dermatitis partially via propionate, and may be a promising adjunctive therapy for psoriasis.

[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis. OBJECTIVE: To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis. METHODS: In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks. RESULTS: The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with difamilast. LIMITATIONS: Study treatment was limited to 4 weeks. CONCLUSION: Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.

Long-term 2-year safety and efficacy of tralokinumab in adults with moderate-to-severe atopic dermatitis: Interim analysis of the ECZTEND open-label extension trial.

BACKGROUND: Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD. OBJECTIVE: To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis. METHODS: Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points. RESULTS: Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345). LIMITATIONS: Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND. CONCLUSION: Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.

Folliculosebaceous Cystic Hamartoma Arising in Miescher-Type Melanocytic Nevi.

ABSTRACT: Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma consisting of dilated folliculosebaceous units associated with mesenchymal elements. Ansai et al reported that distinctive features of Miescher-type melanocytic nevi (MMCNs) accompanied 4.6% of FSCH; however, there have been no data about how often FSCH features accompany MMCNs. In this study, we used 7829 cases that had been histopathologically diagnosed as MMCNs of the face, neck, and scalp at the Department of Dermatopathology, Nippon Medical School Musashi Kosugi Hospital and observed whether features of FSCH accompanied them. Of the resected MMCNs, 274 of 7829 (3%) were accompanied by features of FSCH. The nose was the most common resection site, followed by the eyebrow area, ear, and cheek. The coexistence rate for the nevi on the nose and features of FSCH was as high as 10%-20%, and its rate increased with age. We found that FSCH appears mostly in seborrheic areas, such as the nose and cheek, which are rich in normal sebaceous glands. This suggests that nevi, especially on and around the nose, may induce FSCH or similar lesions.

Molecular Mechanisms and Targeted Therapies of Advanced Basal Cell Carcinoma.

Among human cutaneous malignancies, basal cell carcinoma is the most common. Solid advances in unveiling the molecular mechanisms of basal cell carcinoma have emerged in recent years. In Gorlin syndrome, which shows basal cell carcinoma predisposition, identification of the patched 1 gene (PTCH1) mutation was a dramatic breakthrough in understanding the carcinogenesis of basal cell carcinoma. PTCH1 plays a role in the hedgehog pathway, and dysregulations of this pathway are known to be crucial for the carcinogenesis of many types of cancers including sporadic as well as hereditary basal cell carcinoma. In this review, we summarize the clinical features, pathological features and hedgehog pathway as applied in basal cell carcinoma. Other crucial molecules, such as p53 and melanocortin-1 receptor are also discussed. Due to recent advances, therapeutic strategies based on the precise molecular mechanisms of basal cell carcinoma are emerging. Target therapies and biomarkers are also discussed.

Executive summary: Japanese guidelines for atopic dermatitis (ADGL) 2021.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study.

BACKGROUND: Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD). OBJECTIVE: To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD. METHODS: Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment. RESULTS: At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P < .001). In part 2, improvements in AD were also seen through week 56. Most adverse events were mild and unrelated to delgocitinib across the study periods. LIMITATIONS: Only Japanese patients were included. In part 2, no control group was included and rescue therapy was allowed. CONCLUSION: Delgocitinib ointment was effective and well tolerated when applied to Japanese pediatric patients with AD for up to 56 weeks.

Association study of transition of laboratory marker levels and transition of disease activity of atopic dermatitis patients treated with dupilumab.

BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab. OBJECTIVES: The purpose of this study was to elucidate whether the association of the transition of laboratory marker levels and transition of disease activity in dupilumab-treated AD patients (present study) was different from that in patients who are not treated with dupilumab (previous study). METHODS: Sixty AD outpatients treated with dupilumab were included in this study. Associations between the transition of the eczema area and severity index (EASI) score and those of above-mentioned laboratory marker levels were evaluated using a mixed effects model of EASI as the response variable, laboratory markers as fixed effects and patients as random effects. RESULTS: The transitions of serum TARC and LDH levels were associated strongly with that of AD activity, but the transitions of serum IgE level and eosinophil numbers were associated with that of AD activity intermediately and weakly, respectively. CONCLUSIONS: Laboratory markers are useful for evaluating the effects of treatments for AD, but the meaning of each laboratory marker depends on the drugs used for treatment.

Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study.

BACKGROUND: Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD). OBJECTIVE: This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment. METHODS: In part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment. RESULTS: At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods. LIMITATIONS: Only Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD. CONCLUSION: Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks.

Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells.

Human mucosal tissues and skin contain two distinct types of dendritic cell (DC) subsets, epidermal Langerhans cells (LCs) and dermal DCs, which can be distinguished by the expression of C-type lectin receptors, Langerin and DC-SIGN, respectively. Although peripheral blood monocytes differentiate into these distinct subsets, monocyte-derived LCs (moLCs) induced by coculture with GM-CSF, IL-4, and TGF-ß1 coexpress both Langerin and DC-SIGN, suggesting that the environmental cues remain unclear. In this study, we show that LC differentiation is TGF-ß1 dependent and that cofactors such as IL-4 and TNF-α promote TGF-ß1-dependent LC differentiation into Langerin+DC-SIGN- moLCs but continuous exposure to IL-4 blocks differentiation. Steroids such as dexamethasone greatly enhanced TNF-α-induced moLC differentiation and blocked DC-SIGN expression. Consistent with primary LCs, dexamethasone-treated moLCs express CD1a, whereas monocyte-derived DCs (moDCs) express CD1b, CD1c, and CD1d. moDCs but not moLCs produced inflammatory cytokines after stimulation with CD1b and CD1d ligands mycolic acid and α-galactosylceramide, respectively. Strikingly, CD1a triggering with squalene on moLCs but not moDCs induced strong IL-22-producing CD4+ helper T cell responses. As IL-22 is an important cytokine in the maintenance of skin homeostasis, these data suggest that CD1a on LCs is involved in maintaining the immune barrier in the skin.

Linear IgA bullous dermatosis associated with ulcerative colitis: A case report and literature review.

We report the case of a 59-year-old Japanese woman who developed linear IgA bullous dermatosis during treatment for ulcerative colitis that manifested as pruritic vesicles with erythema on the trunk and scalp. Histopathological examination revealed subepidermal bulla with neutrophil and eosinophil infiltration in the upper dermis. Direct immunofluorescence revealed linear IgA deposits at the basement membrane zone, and indirect immunofluorescence using split skin revealed IgA reaction to the epidermal side (lamina lucida type). We reviewed 33 reported cases of linear IgA bullous dermatosis associated with ulcerative colitis and found that ulcerative colitis preceded the onset of linear IgA bullous dermatosis in 94% of the patients and that IgA-positive patients in split skin indirect immunofluorescence all showed the lamina lucida type, indicating that target antigens for serum IgA antibodies may reside in the lamina lucida. Regarding the pathogenetic association of ulcerative colitis and linear IgA bullous dermatosis, intestinal inflammation may induce the exposure and presentation of intestinal antigens that are cross-reactive to cutaneous antigens, stimulating autoimmune response to antigens of cutaneous basement membrane zones.

Dietary habits in Japanese patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. METHODS: We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. RESULTS: Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test ≦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. CONCLUSIONS: Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.

Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis.

BACKGROUND: Topical delgocitinib (JTE-052), a novel Janus kinase inhibitor, had been shown to be clinically effective in adults with atopic dermatitis (AD). However, the efficacy of topical delgocitinib in pediatric patients with AD remained unclear. OBJECTIVE: We sought to evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD. METHODS: In this phase 2 clinical study (JapicCTI-173553) Japanese patients aged 2 through 15 years with AD were randomized in a 1:1:1 ratio to receive 0.25% or 0.5% delgocitinib ointment or vehicle ointment twice daily for 4 weeks. The primary efficacy end point was the percentage change from baseline in the modified Eczema Area and Severity Index score at the end of treatment (EOT). RESULTS: At EOT, modified Eczema Area and Severity Index scores in both delgocitinib groups were significantly reduced compared with that in the vehicle group. The least-squares mean percentage change from baseline was -54.2% in the 0.25% group and -61.8% in the 0.5% group versus -4.8% in the vehicle group (P < .001 for both comparisons). Similarly, all other efficacy parameters, including Investigator's Global Assessment and pruritus scores, in both delgocitinib groups were significantly improved compared with those in the vehicle group at EOT. Adverse events in both delgocitinib groups were mild in severity, and no serious adverse events were reported. CONCLUSIONS: Delgocitinib ointment improved clinical signs and symptoms in pediatric patients with AD and was well tolerated. These study results indicate that delgocitinib ointment can be a promising therapeutic option for pediatric patients with AD.

Nutrition and Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular diseases, or inflammatory bowel diseases. Psoriasis patients often show unbalanced dietary habits such as higher intake of fat and lower intake of fish or dietary fibers, compared to controls. Such dietary habits might be related to the incidence and severity of psoriasis. Nutrition influences the development and progress of psoriasis and its comorbidities. Saturated fatty acids, simple sugars, red meat, or alcohol exacerbate psoriasis via the activation of nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 inflammasome, tumor necrosis factor-α/interleukin-23/interleukin-17 pathway, reactive oxygen species, prostanoids/leukotrienes, gut dysbiosis or suppression of regulatory T cells, while n-3 polyunsaturated fatty acids, vitamin D, vitamin B12, short chain fatty acids, selenium, genistein, dietary fibers or probiotics ameliorate psoriasis via the suppression of inflammatory pathways above or induction of regulatory T cells. Psoriasis patients are associated with dysbiosis of gut microbiota and the deficiency of vitamin D or selenium. We herein present the update information regarding the stimulatory or regulatory effects of nutrients or food on psoriasis and the possible alleviation of psoriasis by nutritional strategies.

Japanese guidelines for atopic dermatitis 2020.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.