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Skin pigmentation lightened progressively to a variable extent, as modern humans emigrated out of Africa, but extreme lightening occurred only in northern Europeans. Yet, loss of pigmentation alone cannot suffice to sustain cutaneous vitamin D3 (VD3) formation at the high latitudes of northern Europe. We hypothesized that loss-of-function mutations in the epidermal structural protein, filaggrin (FLG), could have evolved to sustain adequate VD3 status. Loss of FLG results in reduced generation of trans-urocanic acid, the principal endogenous ultraviolet-B (UV-B) filter in lightly-pigmented individuals. Accordingly, we identified a higher prevalence of FLG mutations in northern European populations when compared to more southern European, Asian and African populations that correlates significantly with differences in circulating 25-OH-VD3 levels in these same populations. By allowing additional UV-B penetration and intracutaneous VD3 formation, the latitude-dependent gradient in FLG mutations, likely together with other concurrent mutations in VD3 metabolic pathways, provide a non-pigment-based mechanism that sustains higher levels of circulating VD3 in northern Europeans. At the time that FLG mutations evolved, xerosis due to FLG deficiency was a lesser price to pay for enhanced VD3 production. Yet, the increase in FLG mutations has inadvertently contributed to an epidemic of atopic diseases that has emerged in recent decades.

Background: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex‐specific differences in the safety of systemic psoriasis therapies. Objectives: To examine the real‐world, long‐term safety of systemic psoriasis therapies with sex stratification in drug‐related adverse events (ADRs). Methods: Ten‐year data from adults with moderate‐to‐severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient‐years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t‐tests to compare treatment groups and sex. Results: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2‐fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0‐fold higher drug‐related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non‐significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8‐fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0‐fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug‐related discontinuation rates for most CSTs in females. Conclusion: Females were associated with a significantly higher rate of ADRs and drug‐related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient‐tailored management of psoriasis. [ABSTRACT FROM AUTHOR]

Background: Skin pain in atopic dermatitis (AD) increases with disease severity and is associated with substantial quality of life (QoL) burden. Objectives: The aim of the study was to evaluate abrocitinib efficacy on skin pain and QoL in adults and adolescents with moderate-to-severe AD. Methods: This post hoc analysis included data with abrocitinib administered as monotherapy (pooled phase 2b [NCT02780167] and phase 3 JADE MONO-1 [NCT03349060] and JADE MONO-2 [NCT03575871]) or in combination with topical therapy (phase 3 JADE COMPARE [NCT03720470] and JADE TEEN [NCT03796676]). Patients received oral, once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 or 16 weeks (JADE COMPARE). Skin pain was rated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) skin pain Numerical Rating Scale (NRS) item ("How painful was your skin over the past 24 h?") on a scale from 0 (not painful) to 10 (extremely painful). Itch (Peak Pruritus NRS) and QoL (Dermatology Life Quality Index or Children's Dermatology Life Quality Index) were assessed. Least squares mean (LSM) change from baseline was analyzed using mixed-effects repeated measures modeling. Results: A total of 1,822 patients (monotherapy pool, n = 942; JADE COMPARE, n = 595; and JADE TEEN, n = 285) were analyzed. LSM change from baseline in PSAAD skin pain score was significantly greater with abrocitinib versus placebo from week 2 through week 12 or 16 across all 3 study populations and occurred in a dose-dependent manner. A greater proportion of patients achieved a ≥4-point improvement from baseline in PSAAD skin pain score with abrocitinib (200 mg and 100 mg) versus placebo in the monotherapy pool (56% and 38% vs. 12%; week 12), JADE COMPARE (72% and 52% vs. 26%; week 16), and JADE TEEN (51% and 60% vs. 31%; week 12). Additionally, a greater proportion of patients achieved a stringent threshold of skin pain improvement (PSAAD skin pain score <2) with abrocitinib versus placebo. Adults and adolescents who achieved a ≥4-point improvement in skin pain reported greater QoL improvement than those who did not achieve a ≥4-point improvement. A positive correlation (≥0.3) was observed between skin pain and QoL and separately between skin pain and itch across the 3 study populations. Conclusion: Abrocitinib as monotherapy or in combination with topical therapy improved skin pain and was associated with improved QoL in both adults and adolescents with moderate-to-severe AD across all evaluated studies. [ABSTRACT FROM AUTHOR]

The article discusses the adoption and use of the vIGA-AD scale, a validated scale for measuring the severity of atopic dermatitis (AD). The scale was developed in 2016 to provide a standardized and representative measure of AD severity. The study analyzed data from ClinicalTrials.gov and PubMed to assess the scale's uptake in the AD research community. The results showed an increase in the proportion of studies and publications using the vIGA-AD scale over the years. The article also highlights the limitations of the scale and suggests using it in combination with other outcome measures. The authors conclude that the vIGA-AD scale has been widely adopted by researchers and sponsors as a validated measure of AD severity. [Extracted from the article]

This summary discusses two articles related to hidradenitis suppurativa (HS) and dermatologic care. The first article presents the findings of a survey that examined the attitudes of adult patients with HS towards clinical research during the COVID-19 pandemic. The study found that patients with HS had a more positive view towards research compared to dermatologic patients in general, and those who completed the questionnaire in 2021 had higher scores indicating a more positive view towards research compared to those in 2020. The second article focuses on the unmet needs of patients with HS and highlights the physical, emotional, and social impact of the condition on their lives. It also explores the potential of teledermatology in managing inflammatory skin conditions, particularly during the COVID-19 pandemic. Both articles provide valuable insights into the challenges faced by patients with HS and offer potential solutions to improve their care. [Extracted from the article]

This article presents a Danish nationwide cohort study on the long-term drug survival of biologics in the treatment of hidradenitis suppurativa (HS), a chronic inflammatory skin disease. The study analyzed data from 452 patients who were treated with various biologics between 2005 and 2021. The results showed that the median drug survival time for adalimumab was approximately 8 months, with bio-naïve patients having a significantly longer drug survival time compared to non-naïve patients. The study also reported real-life drug survival data on secukinumab in HS. The findings suggest the need for further research into more effective biologics for HS. [Extracted from the article]

Treat‐to‐target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer‐reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T‐related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician‐ and patient‐reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD. [ABSTRACT FROM AUTHOR]