Inflammatory memory in psoriasis: From remission to recurrence.

The routine use of targeted systemic immunomodulatory therapies has transformed outcomes for people with severe psoriasis, with skin clearance (clinical remission) rates up to 60% at 1 year of biologic treatment. However, psoriasis may recur following drug withdrawal, and as a result, patients tend to continue receiving costly treatment indefinitely. Here, we review research into the "inflammatory memory" in resolved psoriasis skin and the potential mechanisms leading to psoriasis recurrence following drug withdrawal.

International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council.

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons.

Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method.

Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria.

Single-cell analysis of psoriasis resolution demonstrates an inflammatory fibroblast state targeted by IL-23 blockade.

Biologic therapies targeting the IL-23/IL-17 axis have transformed the treatment of psoriasis. However, the early mechanisms of action of these drugs remain poorly understood. Here, we perform longitudinal single-cell RNA-sequencing in affected individuals receiving IL-23 inhibitor therapy.

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.

In Silico and In Vitro Analysis of IL36RN Alterations Reveals Critical Residues for the Function of the Interleukin-36 Receptor Complex.

Generalized pustular psoriasis is a potentially life-threatening skin disease, associated with IL36RN disease alleles. IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), a protein that downregulates the activity of IL-36 cytokines by blocking their receptor (IL-36R). Although generalized pustular psoriasis can be treated with IL-36R inhibitors, the structural underpinnings of the IL-36Ra/IL-36R interaction remain poorly understood.

Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi-ethnic Johor Bahru, Malaysia.

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.

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.

A viewpoint on the genetic determinants of generalised pustular psoriasis.

Generalised pustular psoriasis (GPP) is a rare and severe neutrophilic skin disorder, manifesting with acute episodes of pustulation and systemic upset. The discovery of recessive IL36RN mutations associated with GPP has transformed our understanding of disease drivers, paving the way for the development of targeted anti-IL36 therapeutics. In the light of these remarkable successes, this viewpoint reviews the significance of IL36RN mutations in GPP, their functional impact and their correlation with clinical phenotypes.

Pericarditis and Autoinflammation: A Clinical and Genetic Analysis of Patients With Idiopathic Recurrent Pericarditis and Monogenic Autoinflammatory Diseases at a National Referral Center.

Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti-interleukin-1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP.

Single-cell analysis implicates T17-to-T2 cell plasticity in the pathogenesis of palmoplantar pustulosis.

Background: Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat.

Objective: We sought to investigate the immune pathways that underlie the pathogenesis of PPP.

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.

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

Background: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1.

Objectives: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP.

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.

Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis.

Importance: Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied.

Objective: To examine the factors associated with PPP severity.

Design, Setting, And Participants: An observational, cross-sectional study of 2 cohorts was conducted.

Loss-of-Function Myeloperoxidase Mutations Are Associated with Increased Neutrophil Counts and Pustular Skin Disease.

The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.