Novel insights into atopic dermatitis

Abstract

Recent research into the pathophysiology and treatment of atopic dermatitis (AD) has shown notable progress. An increasing number of aspects of the immune system are being implicated in AD, including the epithelial barrier, T_H2 cytokines, and mast cells. Major advances in therapeutics were made in biologic cytokine and receptor antagonists and among Janus kinase inhibitors. We focus on these areas and address new insights into AD epidemiology, biomarkers, endotypes, prevention, and comorbidities. Going forward, we expect future mechanistic insights and therapeutic advances to broaden physicians' ability to diagnose and manage AD patients, and perhaps to find a cure for this chronic condition.

Keywords: Atopic dermatitis; Janus kinase inhibitors; T(H)2; epithelial barrier.

Figure 1.. Novel insights and additions to AD pathogenesis.

This figure highlights novel insights and additions to AD pathogenesis (shown in red), and environmental contribution (blue), and their relevance to key AD associated features including T_H2 immune responses, epidermal inflammation and barrier function, mast cell activation, and pruritus. LTC₄, leukotriene C4; MRGPRX2, Mas-related G protein-coupled receptor-X2; TARC, thymus and activation-regulated chemokine; TRPV3, transient receptor potential vanilloid subfamily V member 1; TSLP, thymic stromal lymphopoietin.

Figure 2.. Novel therapeutic advances in AD.

Left panel, Intersection between therapeutic development and atopic dermatitis (AD) pathogenesis with therapeutic agents shown in red next to their biologic mechanisms of action. Right panel, Janus kinase (JAK) family members dimerize to mediate different cytokine responses. JAK inhibitors (JAKi) inhibit multiple aspects of AD pathogenesis through targeting of select JAK family members (right panel modified from Chovatiya et. al. (93)).

Figure 3.. Novel Insights into AD Comorbidities.

Highlighted comorbidities associated with “Atopic March” or “Non-Atopic” aspects of AD pathogenesis. This includes association of AD disease severity with development of allergic rhinitis and association between AD and development of peanut allergy. Non-Atopic associated comorbidities include association between AD and all-cause mortality, AD associated vascular inflammation, influence of body mass index (BMI) with AD risk, and COVID-19.