GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.

Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci.

Human skin CD141 dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2.

Skin immune homeostasis is a multi-faceted process where dermal dendritic cells (DDCs) are key in orchestrating responses to environmental stressors. We have previously identified CD141CD14 DDCs as a skin-resident immunoregulatory population that is vitamin-D (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141 VitD3 moDCs. We demonstrate that CD141 DDCs and CD141 VitD3 moDCs share key immunological features including cell surface markers, reduced T cell stimulation, IL-10 production, and a common transcriptomic signature.

Manuka honey activates the aryl hydrocarbon receptor: Implications for skin inflammation.

Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH down regulates IL-4-induced CCL26 expression in immortalized keratinocytes. As MH contains potential ligands of the Aryl Hydrocarbon Receptor (AHR), a key regulator of skin homeostasis, we hypothesize that this effect is mediated via AHR activation.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic.

Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence.

Biomarkers of systemic treatment response in people with psoriasis: a scoping review.

Background: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.

Objectives: To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.

Biomarkers of disease progression in people with psoriasis: a scoping review.

Background: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis.

The identification of robust endotypes-disease subgroups of clinical relevance-is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom-based cross-sectional datasets-an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)-we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02-positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry.

Guardians of the barrier: Microbiota engage AHR in keratinocytes to mantain skin homeostasis.

The skin barrier is critical in ensuring homeostasis, yet factors influencing its development, repair, and maintenance are ill-defined. In this issue of Cell Host & Microbe, Uberoi et al. demonstrate the skin microbiota's role in maintaining barrier integrity via AHR signaling in keratinocytes, which has implications for skin disease management.

Defining trajectories of response in patients with psoriasis treated with biologic therapies.

Background: The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives: To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Meeting Report: Psoriasis Stratification to Optimize Relevant Therapy Showcase.

A stratified medicine approach for the treatment of psoriasis promises greater certainty of clinical decision making through prediction of response on the basis of clinical, pharmacological, and -omics data from an individual patient. As yet, there is no predictive model for treatment response in routine clinical use for psoriasis. The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium is a United Kingdom Medical Research Council‒funded, academic‒industrial stratified medicine consortium established with the objective of discovering the predictors and stratifiers of response of psoriasis to biologic therapies.

CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway.

The AHR is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as a critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway downmodulates skin inflammatory responses in animal models and psoriasis clinical samples. In this study, we identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signaling in the context of skin inflammation.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

Background: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments.

Objectives: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation.

Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020.

Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection.

Oral immunotherapy in children with IgE-mediated hen's egg allergy: Follow-ups at 2.5 and 7 years.

Background: The present report was a follow-up investigation at 2.5- and 7-year intervals of a previous study of 20 children with moderate-to-severe immunoglobulin E (IgE) mediated hen's egg (HE) allergy who received oral immunotherapy (OIT) with raw HE. The study design of the previous study divided the 20 subjects into two groups of 10 each: (1) group 1, the OIT group (OIT-G), and, (2) group 2, an age-matched control group (C-G).

An analysis of IL-36 signature genes and individuals with knockout mutations validates IL-36 as a psoriasis therapeutic target.

Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (T17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes.

AP1S3 Mutations Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36 Production.

Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations.

Consensus Conference on Clinical Management of pediatric Atopic Dermatitis.

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents.