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Background: Urticaria is characterized by inappropriate mast cell degranulation leading to the development of wheals and/or angioedema. Twin and family studies indicate that there is a substantial heritable component to urticaria risk., Objective: Our aim was to identify genomic loci at which common genetic variation influences urticaria susceptibility., Methods: Genome-wide association studies of urticaria (including all subtypes) from 3 European cohorts (UK Biobank, FinnGen, and the Trøndelag Health Study [HUNT]) were combined through statistical meta-analysis (14,306 urticaria cases and 650,664 controls). Cases were identified via electronic health care records from primary and/or secondary care. To identify putative causal variants and genes, statistical fine-mapping, colocalization, and interrogation of publicly available single-cell transcriptome sequencing resources were performed., Results: Genome-wide significant associations (P < 5 × 10 -8 ) were identified at 6 independent loci. These included 2 previously reported association signals at 1q44 and the human leucocyte antigen region on chromosome 6. Genes with expected or established roles in mast cell biology were associated with the 4 other genome-wide association signals (GCSAML, FCER1A, TPSAB1, and CBLB). Colocalization of association signals consistent with the presence of shared causal variants was observed between urticaria susceptibility and increased expression of GCSAML (posterior probability of colocalization [PP coloc ] = 0.89) and FCER1A (PP coloc  = 0.91) in skin., Conclusion: Common genetic variation influencing the risk of developing urticaria was identified at 6 genomic loci. The relationship between genes with roles in mast cell biology and several association signals implicates genetic variability of specific components of mast cell function in the development of urticaria., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Physical urticaria is a type of urticaria in which recurrent wheals and/or angioedema occur following exposure of the skin to a physical stimulus. It is classified according to its triggers, which may be mechanical (friction, pressure, and vibration), thermal (cold and heat), or solar electromagnetic radiation. Symptoms of different physical urticarias can develop following specific activities that expose patients to an eliciting stimulus and may be variably accompanied by mucosal involvement and systemic symptoms, including nausea, headache, or even anaphylaxis. Differentiation of physical urticaria from other chronic urticarias requires careful clinical assessment and confirmatory provocation testing, which in turn can inform appropriate management. This clinical review provides an evidence-based summary of the epidemiology, clinical features, pathogenesis, diagnostic work-up, and management of physical urticaria., Competing Interests: Conflicts of interest S.M.M. is a sub-investigator and C.T. is a principal and (national) chief investigator on the Pfizer-funded ALLEGRO clinical trial in alopecia areata. C.T. provides consulting services to Pfizer; sits on the scientific advisory board of Zura Bio Limited; and has received speaker fees from Leo Pharma. M.M. is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Amgen, Aralez, ArgenX, AstraZeneca, Celldex, Centogene, CSL Behring, FAES, Genentech, GlaxoSmithKline, GI Innovation, Gilead, Innate Pharma, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Roche, Sanofi/Regeneron, Third HarmonicBio, and UCB. C.E.G. has sat on advisory boards for Novartis, GlaxoSmithKline and Sanofi, has provided consultancy services for Celltrion Healthcare and Argentix, and is on the steering committees of Blueprint Medicines and AB Science., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest McSweeny is a sub-investigator and Tziotzios is a principal and (national) chief investigator on the Pfizer-funded ALLEGRO clinical trial in alopecia areata. Dr Tziotzios provides consulting services to Pfizer and has received speaker fees from Leo Pharma. Drs Kloczko, Chadha, Sarkany, Fassihi, and McGrath have no conflicts of interest to declare.

Solar urticaria is a rare, immunologically mediated photodermatosis in which activation of cutaneous mast cells is triggered by specific wavelengths of solar electromagnetic radiation. This manifests clinically as the rapid development of cutaneous itch, erythema and wheal formation after several minutes of sun exposure. Disease mechanisms in solar urticaria remain incompletely elucidated and there have been few recent investigations of its pathobiology. Historic passive transfer experiments performed during the twentieth century provide support for a 'photoallergy' model of disease pathogenesis, wherein molecular alteration of a putative chromophore by solar electromagnetic radiation produces mast cell activation via an IgE-dependent mechanism. However, this model does not account for several observations made during passive transfer experiments nor does it explain a range of subsequent clinical and photobiological observations made in solar urticaria patients. Furthermore, increased understanding of the molecular dynamics underpinning cutaneous mast cell responses highlights the need to reformulate our understanding of solar urticaria pathogenesis in the context of this contemporary scientific landscape. In this review, we discuss the current understanding of solar urticaria pathogenesis and, by incorporating recent scientific and clinical observations, develop new hypotheses to drive future investigation into this intriguing disorder., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)