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

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 4; pp. S65 - S76
• Main Authors: Brunner, Patrick M., Guttman-Yassky, Emma, Leung, Donald Y.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2017; Elsevier Limited
• Subjects: Accreditation; Allergies; Allergy and Immunology; Animals; Anti-Inflammatory Agents - therapeutic use; Atopic dermatitis; Chronic illnesses; Copyright; Cytokines; Cytokines - metabolism; Dermatitis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - therapy; Eczema; Health education; Human subjects; Humans; immune; Immune response; Immunology; Inflammation; keratinocyte; Keratinocytes - physiology; Kinases; Light therapy; Molecular Targeted Therapy; Pathogenesis; Pharmaceutical industry; Psoriasis; Skin; Skin diseases; skin immune map; Studies; targeted therapy; Th17 Cells - immunology; Th2 Cells - immunology; T helper cell; FLG; targeted therapy; immune; AD; AMP; TSLP; OX40L; PDE; T helper cell; EASI; Atopic dermatitis; keratinocyte; JAK; eczema; CRTH2; skin immune map; Prostaglandin DP2 receptor; Eczema Area and Severity Index; Filaggrin; OX40 ligand; Thymic stromal lymphopoietin; Janus kinase; Antimicrobial peptide; Phosphodiesterase
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2017.01.011

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 patients with early-onset and those with chronic disease. Clinical studies with 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 because nonlesional 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 with moderate-to-severe disease.