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Inflammatory skin diseases involve various different immune cells in a localised area. Here the authors use spatial transcriptomics to show that disease relevant cytokine transcripts are sparsely expressed in lesional skin, yet are associated with local amplification cascades that promote skin inflammation.

Nailfold capillaroscopy, based on bright-field microscopy, is widely used to diagnose systemic sclerosis (SSc). However it cannot reveal information about venules and arterioles lying deep under the nailfold, nor can it provide detailed data about surface microvasculature when the skin around the nail is thick. These limitations reflect the fact that capillaroscopy is based on microscopy methods whose penetration depth is restricted to about 200 μm. We investigated whether ultra-wideband raster-scan optoacoustic mesoscopy (UWB-RSOM) can resolve small capillaries of the nailfold in healthy volunteers and compared the optoacoustic data to conventional capillaroscopy examinations. We quantified UWB-RSOM-resolved capillary density and capillary diameter as features that relate to SSc biomarkers, and we obtained the first three-dimensional, in vivo images of the deeper arterioles and venules. These results establish the potential of UWB-RSOM for analyzing SSc-relevant markers.

Immune-mediated inflammatory diseases with skin manifestations (skIMIDs) may affect multiple organs. Interdisciplinary care (IC) can overcome the fragmented knowledge used in the management of skIMIDs. In skIMIDs-care, patient and healthcare practitioner (HCP) satisfaction with IC is unknown. Yet, patient experience influences adherence and medical outcomes. Moreover, HCP experience influences professional satisfaction, perception of care quality and autonomy. Thus, measuring patient and HCP experience can identify areas for improvement in care delivery. The aim of this scoping review was to gather evidence on patient- and HCP perceptions on skIMID-IC and their measurement. We systematically searched on 30 August 2023 PubMed/EMBASE/Cinahl/Web of Science. Eligible studies had to address explicitly experience of IC by patients or HCPs. A conceptional synthesis appraised how experiences were measured and IC was perceived by patients and HCPs. The database search resulted in 21 eligible studies. Fourteen described positive patient and HCP experiences with a specific IC programme. These studies were heterogenous on the levels of IC models, medical conditions, measurement methods and outcomes. Despite that patients and HCPs rated such tailored IC models positively, seven studies on a geographically broader region reported less satisfaction with IC. A conceptual analysis identified domains deemed as important regarding IC: 'general satisfaction', 'patient-HCP interaction', 'information', 'functioning of IC', 'benefits of IC'. For patients, 'access to care' and 'disease management' were added. For HCPs 'illness perception' was deemed relevant. The heterogeneous way in how IC experience is captured hinders strong conclusions, which mandates the development of standardized analysis tools. Experience with IC in skIMIDs strongly depends on the context of the provided IC and patient experience seems to be better in local IC programmes than systems rolled out in larger geographical regions. Future need is to develop a core IC outcome set including medical outcomes, process indicators, financial indicators, plus patient and HCP care experience measures., (© 2024 European Academy of Dermatology and Venereology.)

Purpose: Currently, in the treatment of moderate-to-severe psoriasis (PsO) there is a lack of evidence demonstrating optimal biologic treatment response with respect to disease duration. The aim of this post-hoc analysis, using real world data from the Psoriasis Study of Health Outcomes (PSoHO), is to provide evidence if early intervention with biologics is associated with better treatment outcomes and if there is any difference among drug classes or individual biologics., Materials and Methods: For this post-hoc analysis patients were categorised into two subgroups according to shorter (≤2 years) or longer (>2 years) disease duration. Analysis was performed on anti-interleukin (IL)-17A cohort vs other biologics cohort, anti-IL-17A vs other drug classes, and pairwise comparisons of ixekizumab vs individual biologics, provided that the statistical models converged. Analysis investigated the association of disease duration with the proportion of patients achieving 100% improvement in Psoriasis Area Severity Index score (PASI 100) at week 12. Adjusted comparative analyses, reported as odds ratio (OR), were performed using Frequentist Model Averaging (FMA) for each cohort or treatments within each subcategory of the subgroups., Results: At week 12, anti-IL-17A and other biologics cohorts displayed minimal differences in numerical response rate for PASI 100 with respect to disease duration. The anti-IL-17A cohort showed a higher numerical PASI 100 response rate compared to the other biologic cohort irrespective of disease duration (≤2 years: 36.7% vs 21.8%; >2 years: 35.8% vs 21.9%)., Conclusion: Overall, the results do not clearly indicate that treating patients early is critical in achieving optimal patient outcomes. Furthermore, patients treated with ixekizumab show numerically higher response rates relative to other individual biologics irrespective of disease duration.

The skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin. Here, we review recent data on the topographical variations of skin barrier components, the contribution of these variations to the homeostatic function of the skin and their impact on the pathogenesis of specific immune-mediated skin diseases (such as atopic dermatitis and papulopustular rosacea). Recognition of these topographical barrier differences will improve our understanding of skin homeostasis and disease pathogenesis and provide a basis for body site-specific targeted therapies., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival., Methods: Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and ≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis., Results: Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations., Conclusion: We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment., Objectives: This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented., Methods: Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study., Results: Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period., Conclusion: Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD., Objective: This consensus expert opinion statement from the International Eczema Council (IEC) provides a pragmatic approach to prescribing JAKinibs, including choosing appropriate patients, dosing, clinical and lab monitoring, as well as long-term use., Methods: An international cohort of authors from the IEC with expertise in JAKinibs selected topics of interest and were formed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors as well as the IEC Research Committee., Results: We recommend JAKinibs be considered for patients with moderate to severe AD seeking the benefits of rapid reduction in disease burden and itch, oral administration, and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKinibs, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKinib therapy should be current on vaccinations and we provide a generalized framework for laboratory monitoring, though clinicians should consult individual product labels for recommendations as there are variations among the JAKinib class. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in AD patients to assess the durability and safety of continuous long-term use of JAKinibs, combination medication regimens, and the effects of flexible, episodic treatment over time., Conclusions: The decision to initiate a JAKinib should be shared among patient and provider, accounting for AD severity and personal risk/benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)