Long-term effectiveness and safety of upadacitinib for Japanese patients with moderate-to-severe atopic dermatitis: a real-world clinical study.

BACKGROUND: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). METHODS: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. RESULTS: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. CONCLUSIONS: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.

Real-world effectiveness and safety of bimekizumab in Japanese patients with psoriasis: A single-center retrospective study.

Bimekizumab, which suppresses both interleukin (IL)-17A and IL-17F, has recently been approved as a biologic for psoriasis. We aimed to evaluate the real-world effectiveness and safety of bimekizumab for psoriasis and to identify predictive factors for its treatment responsiveness. We analyzed 36 Japanese patients with psoriasis (19 with psoriasis vulgaris and 17 with psoriatic arthritis) from May 2022 to September 2023. All patients received bimekizumab (320 mg every 4 weeks) until week 16. Seventeen patients (43.2%) had experienced bio-switch. The median (interquartile range) baseline total psoriasis area and severity index (PASI) was 6 (3.2-20.0). Total PASI rapidly and significantly decreased at week 4 by a median 79.8% from baseline, and gradually decreased thereafter. The PASI on the trunk, and upper and lower limbs rapidly and significantly decreased at week 4 compared to baseline and plateaued thereafter. The neutrophil-to-lymphocyte ratio and neutrophil number significantly decreased at week 16 compared to baseline. At weeks 4, 8, 12, and 16, the achievement rate of absolute PASI ≤2 was 72.2%, 80.6%, 92.9%, and 96.4%, respectively; that of absolute PASI ≤1 was 41.7%, 61.3%, 85.7%, and 82.1%; that of PASI 75 was 55.5%, 52.9%, 69.7%, and 75.8%; that of PASI 90 was 36.1%, 50.0%, 57.6%, and 62.9%; and that of PASI 100 was 19.4%, 38.2%, 51.5%, or 57.6%, respectively. Linear multivariate regression analysis revealed that younger age was associated with a higher percentage reduction of total PASI at weeks 4 and 8. There were no serious or fatal adverse events during treatment. In conclusion, bimekizumab rapidly and remarkably reduced the total PASI together with high achievement rates of absolute PASI ≤1 and ≤2, and with favorable safety in real-world clinical practice. Younger age may be a predictive factor for a good treatment response to bimekizumab.

Effectiveness of Dose Increase in Upadacitinib from 15 mg to 30 mg for Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Clinical Practice in Japan.

BACKGROUND: Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. OBJECTIVES: We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. METHODS: In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. RESULTS: Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. CONCLUSIONS: These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as a treatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.

Predictive factors for responders to upadacitinib treatment in patients with atopic dermatitis.

BACKGROUND: Janus kinase 1 inhibitor upadacitinib is therapeutically effective for atopic dermatitis (AD). However, predictive factors for high responders to upadacitinib have not been established in real-world clinical practice. OBJECTIVES: To identify predictive factors for responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥ 2-point improvement from basal IGA. METHODS: A retrospective study was conducted from August 2021 to July 2023 on 159 AD patients treated with upadacitinib 15 mg and 52 patients with 30 mg. Patients in each group were categorized into responders (achievers of IGA 0/1 at week 12) and non-responders (non-achievers). We compared baseline values of clinical and laboratory parameters between responders and non-responders. Logistic regression analysis was used to detect variables predicting responders. Receiver-operating characteristic curves were used for evaluating prediction capabilities of the variables. RESULTS: In logistic regression analysis, responders to 15 mg upadacitinib were associated with lower total EASI and higher age whereas responders to 30 mg were associated with lower LDH and lower IgE. CONCLUSIONS: Lower total EASI and higher age may predict responders to upadacitinib 15 mg while lower IgE and lower LDH may predict responders to 30 mg.

Real-world biologic treatment patterns and healthcare resource utilization in psoriasis patients using an insurance claims database in Japan.

BACKGROUND: With advent of newer treatments for psoriasis, real-world use of biologics in Japan is evolving. METHODS: This retrospective study utilized data from patients with ≥1 psoriasis-related biologic claims record between January 2016 and December 2020 in Japan to evaluate treatment patterns, healthcare resource utilization (HCRU), and associated costs. Data were analyzed using descriptive statistics. RESULTS: Of 1,614 eligible patients, 72.5% were male, 29.2% had comorbid hypertension and 26.6% had comorbid cardiovascular disease. Interleukin (IL)-17 and tumor necrosis factor alpha (TNFα) inhibitors were commonly prescribed across lines of treatment, while IL-23 inhibitors were most considered for switches (92% of switches were from IL-12/23/IL-17/TNFα inhibitors). The overall mean adherence rate for all classes was 80.1%, but adherence varied across biologics. Infliximab and IL-23 inhibitor users exhibited optimal medical possession ratios, reflecting the best adherence rates. Overall HCRU (visits/patient-year) was 9.05 for outpatient visits, 0.09 for inpatient hospitalization, and 0.5 for psoriasis-related phototherapy. HCRU associated with hospitalization was slightly higher for bio-experienced patients and so was the overall costs per patient-year relative to bio-naïve patients. CONCLUSION: Variable adherence rates observed suggest the need for improvement in treatment management with different biologics. Bio-experienced patients burdened by disease progression and treatment switches may result in increased HCRU.

Effectiveness and safety of deucravacitinib treatment for moderate-to-severe psoriasis in real-world clinical practice in Japan.

BACKGROUND: Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. OBJECTIVES: We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. METHODS: We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. RESULTS: At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50-80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. CONCLUSIONS: Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.

Dietary habits in adult Japanese patients with vitiligo.

Vitiligo is an autoimmune skin disease with acquired depigmentation. Dietary habits may modulate the pathogenesis of vitiligo. We evaluated dietary habits in adult Japanese patients with nonsegmental vitiligo, and compared their results with those of age- and sex-matched controls. We also examined the relationship between dietary habits and Vitiligo Area Scoring Index (VASI), or vitiligo on different anatomical sites. The intakes of energy, nutrients, and foods in the participants were analyzed using a brief-type self-administered diet history questionnaire. Patients with vitiligo showed higher body mass index (BMI) and lower intakes of manganese, vitamin D, pulses, and confection, compared with controls. Multivariate logistic regression analysis showed that vitiligo was associated with high BMI. VASI was higher in males than in females, and negatively correlated with age or intakes of potatoes and vegetables other than green/yellow vegetables. Linear multivariate regression analysis showed that high VASI was associated with younger age. Multivariate logistic regression analysis showed that moderate to severe vitiligo (VASI ≥ 4.25) was associated with male sex and longer disease duration. Multivariate logistic regression analyses showed the following association with vitiligo on respective anatomical sites: high intake of eggs and dairy products and high VASI on the head or neck, high intake of oils and fats and high VASI on the trunk, high intake of cereals and high VASI on the upper limbs, male sex and high VASI on the lower limbs, and high BMI and high VASI on the hands or feet. In conclusion, the control of obesity might have prophylactic or therapeutic effects on vitiligo.

Correlation Analysis of Clinician- and Patient-Reported Outcomes Among Japanese Adults with Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing condition with high disease burden and impact on health-related quality of life (HRQoL). Correlations between clinician- and patient-reported outcomes tend to be poor, and limited data in Asian patients are available. METHODS: ADDRESS-J was a prospective, non-interventional, longitudinal study that evaluated the real-world effectiveness and safety of AD treatment in Japanese adults (aged 20-59 years) with moderate-to-severe AD. Three clinician-reported AD severity outcomes (Investigator's Global Assessment, Eczema Area and Severity Index, and body surface area affected), three dermatological patient-reported outcomes (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Worst Itch Numerical Rating Scale), and two general HRQoL patient-reported outcomes (5-dimension EuroQoL questionnaire and EuroQol Visual Analog Scale) were collected at baseline and every 3 months throughout the 24-month observation period. Four biomarkers were also analyzed when available (thymus and activation-regulated chemokine [TARC], lactate dehydrogenase [LDH], total immunoglobulin E [IgE], and peripheral blood eosinophil counts [PB EOS]). Spearman's correlation coefficients were calculated using all available pooled data from baseline through 24 months. RESULTS: Correlations between the three clinician-reported outcomes were high/very high (Spearman's correlation coefficients 0.76-0.92); those between the three dermatological patient-reported outcomes were moderate (0.53-0.64), and those between the clinician-reported and dermatological patient-reported outcomes were low/moderate (0.37-0.51). Correlations between the general HRQoL patient-reported outcomes and the clinician-reported and dermatological patient-reported outcomes were negligible-moderate (0.26-0.60). Biomarker correlations with the clinician-reported and dermatological patient-reported outcomes were low/moderate for TARC and LDH (0.44-0.63), but negligible/low for PB EOS and total IgE (0.01-0.41). CONCLUSIONS: These results show that clinician- and patient-reported outcomes do not necessarily correlate well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when assessing disease severity/impact, planning treatment, and assessing response to treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) Identifier UMIN000022623.

Atopic dermatitis (AD) is a long-term recurring skin disease that needs monitoring over time. Various measures (outcomes) are used to assess the severity of AD and its effect on patients. Some outcomes are based on examinations used by clinicians (doctors). Others are based on questionnaires used by patients themselves to report how severe they feel their AD is, and how it affects their lives. It is not known how well these different measures correlate with one another (how a severity score given by one outcome agrees with that given by another outcome), especially in Asian patients. This analysis used information from ADDRESS-J, a study that followed Japanese adults with moderate-to-severe AD who were treated for AD in the real world for a period of 2 years. It used a statistical method to compare three clinician-reported severity outcomes, three dermatological (skin-related) patient-reported outcomes, and two general health-related quality of life patient-reported outcomes. Agreement between the three clinician-reported outcomes was high or very high. Agreement between the three dermatological patient-reported outcomes was moderate. However, importantly, agreement between the clinician-reported outcomes and the dermatological patient-reported outcomes was low or moderate. Agreement between the general health-related quality of life outcomes and all other dermatological outcomes (whether clinician- or patient-reported) was low or moderate. The study showed that clinician-reported and patient-reported AD outcomes do not necessarily agree well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when evaluating AD, planning treatment, or judging how well patients are responding to treatment.

Epidermal turnover and iron metabolism in senile lentigo.

Senile lentigo (SL) is a pigmentary disorder associated with disrupted epidermal turnover. Trace minerals in the skin are known to regulate keratinocyte proliferation and differentiation. To clarify the role of iron in SL, we compared the expression of molecules related to iron metabolism between SL lesion (lesion) and the surrounding normal skin (nonlesion). Our results revealed that proteins involved in iron uptake and utilization such as transferrin receptor 1, iron regulatory protein 1, mitoferrin 1, and divalent metal transporter 1 were expressed in the lower epidermis in the nonlesion, while expression of them was also observed in the upper epidermis in the lesion. Ferroportin (FPN), involved in iron export, was expressed in the upper epidermis in the nonlesion, but was only scarcely expressed in the upper epidermis in the lesion. Hepcidin, which promotes FPN degradation, was expressed in the lower epidermis in the nonlesion; however, its expression was also observed in the upper epidermis in the lesion. These changes in the expression of molecules involved in iron uptake/export/utilization might reflect the altered iron utilization state in SL, resulting in disruption of keratinocyte differentiation and disturbing epidermal turnover. Our results suggest that the metabolism of iron in keratinocytes in SL differs from that in the normal epidermis, and these changes could be associated with the abnormal epidermal turnover and decreased melanin excretion in SL.

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.

Pediatric psoriasis: Understanding pathological conditions and advances in treatment.

Psoriasis is a long-lasting skin disease that primarily affects the skin, nails, and joints and is characterized by inflammation. Genetic factors contribute to its development and environmental triggers can worsen symptoms. Pathologically, psoriasis is characterized by uncontrolled keratinocyte proliferation and abnormal differentiation, and histological features include acanthosis with inflammatory cell infiltration and neovascularization. Psoriasis often starts in childhood, with about one-third of cases beginning during this time. Its prevalence steadily increases from the ages of 1 to 18 years in a linear fashion. Young people with psoriasis often require treatment throughout their childhood and adolescence, and into adulthood. However, prolonged treatment may increase the risk of complications and adverse events, so it is important to adopt an effective treatment approach that minimizes this risk. In addition, psoriasis is often associated with various comorbidities that may place a great burden on the physical and mental health of the children beyond those due to psoriasis itself. To ensure good long-term health outcomes, individuals with psoriasis should undergo regular screening. Treatment should be provided not only for skin lesions, but also for any comorbidities; however, currently there is not enough evidence on the treatment of pediatric psoriasis and no globally agreed-on guidelines exist for treating psoriasis in children. This article describes the etiology, clinical symptoms, and disease burden of pediatric psoriasis, the pathological conditions and diagnosis of plaque psoriasis, psoriatic arthritis, and generalized pustular psoriasis, and the available treatments for these conditions in Japan.

Early itch relief with upadacitinib predicts later skin clearance in Atopic dermatitis.

BACKGROUND: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. OBJECTIVES: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. METHODS: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. RESULTS: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. CONCLUSIONS: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.

Safety and Efficacy of Upadacitinib for Atopic Dermatitis in Japan: Analysis of the 3-Year Phase 3 Rising Up Study.

INTRODUCTION: Upadacitinib is an oral Janus kinase inhibitor approved in multiple countries for moderate-to-severe atopic dermatitis (AD). Here we present long-term data for up to 3 years of continuous upadacitinib treatment in Japanese patients with AD. METHODS: Rising Up was a phase 3, randomized, multicenter study in Japan investigating the safety and efficacy of upadacitinib in patients with moderate-to-severe AD. Patients aged 12-75 years (weight ≥ 40 kg if < 18 years) were randomized 1:1:1 to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo through week 16 (all in combination with topical corticosteroids). At week 16, patients who received placebo were rerandomized 1:1 to upadacitinib 15 mg or 30 mg; topical corticosteroids were optional per investigator discretion from weeks 16-160. Safety was assessed by monitoring adverse events (AEs). Efficacy assessments included patients who achieved ≥ 75%/≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), clear/almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), or a ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (WP-NRS). RESULTS: Of 272 patients enrolled, 230 completed the study. Through week 160, the long-term incidence rate of overall AEs was numerically higher with upadacitinib 30 mg than 15 mg; rates of serious AEs, AEs considered possibly related to study drug, AEs leading to discontinuation, and AEs of special interest were generally low and similar between dose groups. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were generally greater with upadacitinib 30 mg than 15 mg and maintained through week 160 with either dose. CONCLUSION: For up to 3 years of continuous treatment, upadacitinib was well tolerated in Japanese patients, with a similar safety profile to that of short-term studies and durable long-term response rates for skin clearance and itch improvement. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03661138.

[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.

Effectiveness of switching from baricitinib 4 mg to upadacitinib 30 mg in patients with moderate-to-severe atopic dermatitis: a real-world clinical practice in Japan.

BACKGROUND: Atopic dermatitis (AD) is a chronic eczematous disease with severe pruritus. Janus kinase (JAK) inhibitors, upadacitinib, baricitinib, and abrocitinib, are systemic treatments for AD. The outcomes of switching from one JAK inhibitor to another have not been examined. OBJECTIVES: We assessed the outcomes of switching from baricitinib 4 mg to upadacitinib 30 mg in Japanese patients with moderate-to-severe AD. METHODS: Twenty patients treated with baricitinib 4 mg, showing insufficient response or adverse events, were switched to treatment with upadacitinib 30 mg. We evaluated total eczema area and severity index (EASI), EASI at head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and peak pruritus numerical-rating scale (PP-NRS) at baseline (start of baricitinib), weeks 0 (time of switching), and 4 and 12 after switching. RESULTS: Total EASI, EASI at each anatomical site, EASI of each clinical sign, and PP-NRS were markedly reduced at weeks 4 or 12 compared to week 0. Achievement rates of more than 75% or 90% reduction of EASI from baseline significantly improved after switching. CONCLUSIONS: Switching from baricitinib 4 mg to upadacitinib 30 mg effectively improved rash and pruritus.

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.

Effectiveness and Safety of Upadacitinib in Combination with Topical Corticosteroids in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis.

Purpose: To investigate the therapeutic effectiveness and safety of Janus kinase 1 inhibitor upadacitinib in adolescent patients with atopic dermatitis (AD). Patients and Methods: This study examined therapeutic effectiveness and safety of upadacitinib for 39 Japanese adolescent patients (aged 12-17 years) diagnosed with moderate-to-severe AD from August 2021 to January 2023. The patients were treated with upadacitinib 15 mg/day plus twice daily topical corticosteroids. Total eczema area and severity index (EASI) or EASI on head and neck, upper limbs, lower limbs, and trunk or for erythema, edema/papulation, excoriation, or lichenification, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and laboratory indexes were assessed at weeks 0, 4, and 12 of treatment. Treatment-emergent adverse events were recorded. Results: Total EASI or EASI on 4 anatomical sites or for 4 rash types, ADCT, and PP-NRS were significantly reduced at week 4 and 12 compared to week 0. The achievement rates at weeks 4 or 12 were 64.1% or 62.5% for EASI 75, 93.5% or 73.1% for ADCT <7-point, and 80.6% or 60% for PP-NRS ≥4-point improvement, respectively, indicating their peak at week 4 and slight decrease at week 12. The percent reduction of EASI for excoriation was higher than that for lichenification or edema/papulation at week 4 or week 12, respectively. The percent reductions of EASI for erythema and edema/papulation on head and neck were lower than those on lower limbs at week 12. Total eosinophil counts (TEC) and IgE reduced at week 4 compared to week 0 while TARC, IgE, TEC, and LDH increased at week 12 compared to week 4. Conclusion: These results suggest therapeutic effectiveness and tolerability of upadacitinib and support its therapeutic usefulness for adolescent AD patients.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. OBJECTIVES: We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. MATERIALS & METHODS: Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. RESULTS: Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. CONCLUSION: The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.