Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment

Abstract

Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients’ quality of life. Although distinctions exist between these diseases, both are characterized by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of aetiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state. The Th17/IL-23 pathway also has an important role in psoriasis. The role of systemic inflammation in AD and psoriasis is supported by the occurrence of non-cutaneous comorbidities that affect patients, most of which intensify morbidity and disability associated with lesional skin. Atopic dermatitis is associated with allergic disorders consisting of the “atopic march,” whereas psoriasis is frequently accompanied by psoriatic arthritis. Patients with both disorders are at significantly higher risk of obesity, metabolic disorders, and cardiovascular diseases, all of which feature inflammatory components in their pathology models. These insights have led to novel therapeutics aimed at addressing psoriasis by targeting tumor necrosis factor- and Th17-related cytokine pathways. The success of these agents in psoriasis management is driving new therapeutic approaches for moderate-to-severe AD, including agents targeting the Th2 and Th17/Th22 cytokine pathways.