Subtypes of atopic dermatitis: From phenotype to endotype

Allergology International, Год журнала: 2021, Номер 71(1), С. 14 - 24

Опубликована: Июль 31, 2021

Atopic dermatitis (AD) is a heterogenous disorder and can be classified into different types. Stratification of subtypes may enable personalized medicine approaches. AD categorized the IgE-high, extrinsic subtype IgE-normal, intrinsic subtype. While major possessing skin barrier impairment (high incidence filaggrin mutations), occupies about 20% with female dominance preserved barrier. Extrinsic exhibits protein allergy food allergy, but shows metal possibly in association suprabasin deficiency. In particular, accumulated knowledge has more clearly characterized AD. European American (EA) Asian have been also proposed. patients are by unique blended immune dysregulation feature phenotype between EA those psoriasis. another ethnic study, loss-of-function mutations not prevalent African AD, Th1/Th17 attenuation Th2/Th22 skewing were seen these patients. Recent endotype classification provides new insights for other allergic disorders. Endotype defined as molecular mechanisms underlying visible features/phenotype. repertoire harbors activation type 2 cytokines, 1 IL-17/IL-22, epidermal barrier, abnormalities intercellular lipids. Classification attempted serum markers. These lines evidence indicate need or precision appropriate each

Язык: Английский

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Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5)

Journal of the American Academy of Dermatology, Год журнала: 2021, Номер 85(1), С. 62 - 70

Опубликована: Фев. 17, 2021

Язык: Английский

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Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE– and Institute of Medicine–based recommendations

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 132(3), С. 274 - 312

Опубликована: Дек. 18, 2023

Язык: Английский

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Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(5), С. 2684 - 2684

Опубликована: Фев. 28, 2022

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% children 10% adults in high-income countries. The prevalence incidence have increased recent years. onset mostly occurs childhood, although some cases may persist adult life or even manifest middle age (adult-onset AD). pathophysiology made a complex net, genetic background, barrier dysfunction, innate adaptive immune responses, as well itch contribute disease development, progression, chronicization. One important features dehydration, mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, antigen penetration. In accordance "outside-inside" theory pathogenesis, context an altered epidermal barrier, antigens encounter presentation cells (APCs), such Langerhans dendritic cells, leading their maturation Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), induce IgE-mediated sensitizations part pathogenic mechanisms AD. this review, we discuss role cytokines pathogenesis AD, considering patients various clinical phenotypes. Moreover, describe cytokine patterns at different phases evolution, relation phenotypes/endotypes, including age, race, intrinsic/extrinsic subtypes. We outcomes current biologics corroborate presence multiple axes involved background A deep insight into correlation between related forms crucial step towards increasingly personalized, therefore more efficient therapy.

Язык: Английский

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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 4, 2023

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted largest AD GWAS to date (discovery N = 1,086,394, replication 3,604,027), combining previously reported cohorts with additional available data. We 81 loci (29 novel) in European-only analysis (which all replicated separate European analysis) 10 multi-ancestry (3 novel). Eight variants from at least one of populations tested (European, Latino or African), while two may be specific individuals Japanese ancestry. showed enrichment for DNAse I hypersensitivity eQTL associations blood. At each locus prioritised candidate genes by integrating multi-omic The implicated are predominantly immune pathways relevance atopic inflammation some offer drug repurposing opportunities.

Язык: Английский

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Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis

Journal of Allergy and Clinical Immunology, Год журнала: 2021, Номер 149(2), С. 624 - 639

Опубликована: Авг. 5, 2021

BackgroundAlthough ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known the lymphocytic components skin's innate immune system.ObjectiveTo better understand biologic role lymphoid cells (ILCs), we investigated their phenotypic molecular features under physiologic (normal human skin [NHS]) pathologic (lesional patients with atopic dermatitis [AD]) conditions.MethodsSkin punch biopsies reduction sheets as well blood specimens were obtained from either AD or healthy individuals. Cell and/or tissue samples analyzed by flow cytometry, immunohistochemistry, single-cell RNA sequencing subjected to in vitro/ex vivo culture.ResultsNotwithstanding substantial quantitative differences between NHS skin, found that vast majority ILCs belong CRTH2+ subset reside upper layers. Single-cell ILC-enriched cell confirmed predominance biologically heterogeneous group 2 and, for first time, demonstrated considerable ILC lineage infidelity (coexpression genes typical type [GATA3 IL13] 3/17 [RORC, IL22, IL26] immunity within individual cells) lesional a lesser extent, NHS. Similar events explant cultures vitro expanded peripheral blood.ConclusionThese findings support concept instead being stable entity well-defined components, system consists network highly flexible cellular players are capable adjusting needs challenges environment. Although system. To conditions. Skin culture. Notwithstanding blood. These

Язык: Английский

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Early intervention and prevention of allergic diseases

Allergy, Год журнала: 2021, Номер 77(2), С. 416 - 441

Опубликована: Июль 13, 2021

Food allergy (FA) is now one of the most common chronic diseases childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for development this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental genetic contributions well accepted. A understanding pathogenesis FA an essential first step developing comprehensive prevention strategies that could mitigate epidemic. As it frequently preceded by atopic dermatitis can be prevented early antigen introduction, likely facilitated improper initial presentation immune system. Primary oral exposure antigens allowing via well-developed mucosal system, rather than through disrupted skin epidermal barrier, prevent FA. In review, we present data supporting necessity (1) intact barrier epicutaneous presentation, (2) presence specific commensal bacteria maintain system (3) maternal/infant diet diversity, including vitamins minerals, appropriately timed allergenic food introduction

Язык: Английский

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Atopic dermatitis: pathomechanisms and lessons learned from novel systemic therapeutic options

Journal of the European Academy of Dermatology and Venereology, Год журнала: 2022, Номер 36(9), С. 1432 - 1449

Опубликована: Май 16, 2022

Atopic dermatitis (AD) is a chronic, heterogenous, inflammatory skin disorder associated with high skin-related health burden, typically starting in childhood and often persisting into adulthood. AD characterized by wide range of clinical phenotypes, reflecting multiple underlying pathophysiological mechanisms interactions between genetics, immune system dysregulation environmental factors. In this review, we describe the diverse cellular molecular involved AD, including critical role T-cell-driven inflammation, primarily via T helper (Th) 2- Th17-derived cytokines, many which are mediated Janus kinase (JAK) signaling pathway. These local processes interact sensory neuronal pathways, contributing to manifestations itch, pain sleep disturbance. The recent elucidation pathways has allowed treatment strategies evolve from broad-acting systemic immunosuppressive therapies more targeted agents, JAK inhibitors cytokine-specific biologic agents. Evidence development these reinforced expanded our understanding holds promise for individualized tailored specific subtypes.

Язык: Английский

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Differences between pediatric and adult atopic dermatitis

Pediatric Dermatology, Год журнала: 2022, Номер 39(3), С. 345 - 353

Опубликована: Март 16, 2022

Abstract Atopic dermatitis (AD) is a common disease with broad spectrum of clinical manifestations. AD can manifest differently in adults than children. Core features are similar between children and overall, including lesions affecting flexural areas, presence atopy, xerosis. Adults have more signs chronic disease, higher prevalence different patterns hand eczema, stronger relationship activity emotional factors, whereas exudative lesions, perifollicular accentuation, pityriasis alba, Dennie–Morgan folds, seborrheic dermatitis‐like presentation. These differences may be due part to pathophysiologic compared adults. diseases commonly co‐occur AD, although most do not temporally the “atopic march.” Further research warranted better understand differential roles immune dysregulation, epidermal‐barrier disruption, dysbiosis determine whether such translate into therapeutic efficacy.

Язык: Английский

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Oral Janus kinase inhibitors for atopic dermatitis

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 130(5), С. 577 - 592

Опубликована: Фев. 1, 2023

Язык: Английский

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