The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies

Abstract

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of Th22, Th17/IL-23 and Th1 cytokine pathways, depending on the subtype of the disease. In this review, we discuss our current understanding of the AD immune map in both early-onset as well as chronic disease. Clinical studies using broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD, as non-lesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients suffering from moderate-to-severe disease.

Translational drug discovery and development with the use of tissue‐relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy

“…[60,61] Indeed, the biology of this pathway has become a major focus of cytokine-targeting biologics for the treatment of AD and includes targeting IL-4, IL-13 and IL-5 as downstream effector cytokines, as well as TSLP and IL-33, which would function as upstream drivers of type 2 responses. [63] Consequently, there remains an important need to more precisely profile the immunological nature of AD at the level of individual patients and to understand the contributions of pathways that fall on the outskirts of type 2 immunity or beyond. AD in Asian patients has been shown to include a Th17-associated response that is similar to that seem in psoriasis while infant AD possesses a stronger IL-22-associated response than is found in adult AD.…”

Atopic Dermatitis: Early Treatment in Children

“…In addition, treatment resulted in improvement of other endpoints, including pruritus, symptoms of anxiety, and depression, and quality of life. A Phase 2a, open-label trial of 78 children and adolescents, ages 6–18, with moderate-to-severe AD (NCT02407756) demonstrated mean improvement of pruritus and EASI scores, especially in the younger cohort, at increasing subcutaneous doses (from 2–4mg/kg) [104•]. Dupilumab is a promising therapy in AD and is expected to alter future management of the disease towards a more personalized approach.…”

Dermatitis atópica severa e hiper-IgE

“…3,4 En Latinoamérica, la prevalencia promedio de la DA en niños es de 11.3 %, 5 con un rango entre 6 y 30.8 % en esa misma población y entre 1 y 3 % en la población adulta. Las variaciones en la prevalencia dependen del grupo examinado, país, clima y método de recolección de la información, entre otros factores.…”