Atopic dermatitis (AD), a common, chronic-relapsing inflammatory skin disease, causes a significant disease burden. Genetic and environmental factors trigger AD, ultimately activating 2 of the largest organs, i.e., the nervous system and the immune system. Several neuroimmune circuits are dysregulated in AD, which triggers inflammation, pruritus, pain and barrier dysfunction. Environmental or endogenous trigger factors can activate sensory nerves and transmit itch stimuli to the brain. On stimulation, sensory nerve endings also release neuromediators into the skin, which contributes again to inflammation, barrier dysfunction and itch. Additionally, dysfunctional peripheral and central neuronal structures cause neuroinflammation, sensitization, nerve elongation and neuropathic itch, thus chronification and therapy resistance.

Consequently, neuroimmune circuits in skin and central nervous system may be suitable targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids and ions excite/sensitize sensory nerve endings, which not only provoke itch but further aggravate/perpetuates inflammation, skin barrier disruption and pruritus as well. Thus, targeted therapies for neuroimmune circuits and pathway inhibitors (e.g., kinase inhibitors) may help control pruritus in AD either in systemic and/or topical form. Understanding neuroimmune circuits and neuronal signaling can control inflammation, barrier dysfunction and pruritus.

Source: Steinhoff M, Ahmad F, Pandey A, et al. Neuroimmune communication regulating pruritus in atopic dermatitis. J Allergy Clin Immunol. 2022;149(6):1875-98.