Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet, Год журнала: 2022, Номер 400(10356), С. 908 - 919

Опубликована: Сен. 1, 2022

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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Systematic review of the association between short‐chain fatty acids and allergic diseases

Allergy, Год журнала: 2024, Номер 79(7), С. 1789 - 1811

Опубликована: Фев. 23, 2024

Abstract We performed a systematic review to investigate the current evidence on association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced suggested as one mechanism how gut microbiome affects risk of diseases. Medline, Embase Web Science were searched from data inception until September 2022. identified 37 papers, 17 investigated prenatal or early childhood SCFAs development in childhood, 20 assessed patients with pre‐existing Study design, study populations, outcome definition, analysis method reporting results varied papers. Overall, there was some showing that three main (acetate, propionate butyrate) first few years life had protective effect against diseases, especially for atopic dermatitis, wheeze asthma IgE‐mediated food allergy childhood. The each SCFA disease appeared be different by age assessment. Further research can determine potentially timing specific will useful used treatment prevention

Язык: Английский

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Targeting IL‐13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years

Allergy, Год журнала: 2024, Номер 79(6), С. 1560 - 1572

Опубликована: Апрель 2, 2024

Abstract Background Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)‐13, key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early 2‐year impacts IL‐13 neutralization on serum biomarkers following tralokinumab treatment adults with moderate‐to‐severe AD. Methods Skin biopsies blood samples were from subset patients enrolled the Phase 3 ECZTRA 1 (NCT03131648) long‐term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein immunohistochemistry immunoassay. Results improved transcriptomic profile lesional Week 4. Mean improvements genes dysregulated AD 39% at 16 85% 2 years tralokinumab, 15% worsening placebo. At 16, significantly decreased type (CCL17/TARC, periostin, IgE), reduced epidermal thickness versus placebo, increased loricrin coverage baseline. Two Th2 ( IL4R , IL31 CCL17 CCL26 ), Th1 IFNG Th17/Th22 IL22 S100A7 S100A8 S100A9 ) pathways as well differentiation CLDN1 LOR ). also shifted atherosclerosis signaling pathway SELE IL‐37 toward non‐lesional expression. Conclusion pathology, systemic markers inflammation, towards levels, further highlighting role pathogenesis Clinical Trial Registration NCT03131648, NCT03587805.

Язык: Английский

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Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Dermatology and Therapy, Год журнала: 2022, Номер 12(7), С. 1501 - 1533

Опубликована: Май 21, 2022

Type 2 immunity evolved to combat helminth infections by orchestrating a combined protective response of innate and adaptive immune cells promotion parasitic worm destruction or expulsion, wound repair, barrier function. Aberrant type responses are associated with allergic conditions characterized chronic tissue inflammation, including atopic dermatitis (AD) asthma. Signature cytokines include interleukin (IL)-4, IL-5, IL-9, IL-13, IL-31, mainly secreted from cells, as well IL-25, IL-33, thymic stromal lymphopoietin, particularly epithelial cells. IL-4 IL-13 key players mediating the prototypical response; initiates promotes differentiation proliferation naïve T-helper (Th) toward Th2 cell phenotype, whereas has pleiotropic effect on including, together IL-4, decreased Both implicated in B-cell isotype class switching generate immunoglobulin E, fibrosis, pruritus. regulator eosinophils, is responsible for eosinophil growth, differentiation, survival, mobilization. In AD, IL-31 sensory nerve sensitization itch, leading scratching that further exacerbates inflammation dysfunction. Various strategies have emerged suppress biologics targeting their receptors, Janus kinase inhibitors block intracellular cytokine signaling pathways. Here we review its role inflammatory diseases, current future therapies pathways, focus AD. INFOGRAPHIC.

Язык: Английский

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Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment

Journal of Allergy and Clinical Immunology, Год журнала: 2023, Номер 152(5), С. 1179 - 1195

Опубликована: Июнь 13, 2023

Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus colonization infections. S thought play a role in AD severity.

Язык: Английский

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Targeting Skin Barrier Function in Atopic Dermatitis

The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2023, Номер 11(5), С. 1335 - 1346

Опубликована: Фев. 20, 2023

Язык: Английский

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The dynamic balance of the skin microbiome across the lifespan

Biochemical Society Transactions, Год журнала: 2023, Номер 51(1), С. 71 - 86

Опубликована: Янв. 6, 2023

For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and developing therapeutics to foster this balance. However, single idealized balance may not exist. The changes across lifespan. This is reflected in dynamic shifts of microbiome's diverse, inter-connected community microorganisms with age. While there are core microbial taxa, precise composition for any individual person determined by local physiology, genetics, microbe–host interactions, microbe–microbe interactions. As a key interface environment, surface its appendages also constantly exchanging microbes close personal contacts environment. Hormone fluctuations immune system maturation drive age-dependent physiology support different structures over time. Here, we review recent insights into factors shape throughout life. Collectively, works summarized within highlight how, depending where lifespan, our supports robust communities, while still maintaining features unique us. will how disruptions can influence risk dermatological diseases as well impact lifelong health.

Язык: Английский

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Filaggrin and beyond

Annals of Allergy Asthma & Immunology, Год журнала: 2023, Номер 132(2), С. 187 - 195

Опубликована: Сен. 25, 2023

Atopic dermatitis (AD) is the most common inflammatory skin disease worldwide, affecting 20% of children and 5% adults. One critical component in pathophysiology AD epidermal barrier, with its outermost layer, stratum corneum (SC), conferring biochemical properties that enable resilience against environmental threats maintain homeostasis. The barrier may be conceptualized as a key facilitator complex interactions between genetics, host immunity, cutaneous microbiome, exposures. genetic risk factor for development persistence loss-of-function mutation FLG, recent advances genomics focusing on rare variant discovery, establishment pathogenic mechanisms, exploration role other differentiation gene variants AD. Aberrant type 2 responses down-regulate transcription genes, alter composition SC lipids, induce further injury through neurocutaneous feedback loop itch-scratch cycle. dysbiotic epidermis exhibits reduced bacterial diversity enhanced colonization Staphylococcus Malassezia species, which contribute to both direct action toxins perpetuation cascades. Enhanced understanding each mechanisms underpinning disruption has led novel topical systemic molecules, including interleukin (IL)-4Ra, IL-13, PDE4, Janus-associated kinase inhibitors, whose clinical effectiveness exceeds conventional treatment modalities. In this narrative review, we aim summarize current above-mentioned pathophysiological therapeutic focus genetic, cellular, molecular development.

Язык: Английский

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Skin microbiome dysbiosis and the role of Staphylococcus aureus in atopic dermatitis in adults and children: A narrative review

Journal of the European Academy of Dermatology and Venereology, Год журнала: 2023, Номер 37(S5), С. 3 - 17

Опубликована: Май 26, 2023

Abstract A dysfunctional epidermal barrier, which may be associated with mutations in the filaggrin gene genetically predisposed individuals or harmful effects of environmental agents and allergens, contributes to development atopic dermatitis (AD) due an interplay between epithelial immune defence cutaneous microbiome. The skin patients AD is frequently over‐colonized by biofilm‐growing Staphylococcus aureus , especially during flares, causing dysbiosis microbiota a decrease bacterial diversity that inversely correlates severity. Specific changes microbiome can present before clinical onset infancy. Additionally, local anatomy, lipid content, pH, water activity sebum secretion differ children adults generally correlate predominant microbiota. Considering importance S. AD, treatments aimed at reducing over‐colonization rebalance microbial help manage reduce flares. Anti‐staphylococcal interventions will contribute superantigens proteases cause damage inflammation barrier while concomitantly increasing proportion commensal bacteria secrete antimicrobial molecules protect healthy from invading pathogens. This review summarizes latest data on targeting treat children. Indirect therapies, including emollients ‘plus’, anti‐inflammatory topicals monoclonal antibodies, have impact control diversity. Direct antibacterial (antiseptics/topical systemic antibiotics), innovative specifically (e.g. anti‐ endolysin, autologous bacteriotherapy), effective alternatives mitigate against increase resistance allow proportionate

Язык: Английский

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