Papers of the Week

Atopic dermatitis (AD) is a common, chronic-relapsing inflammatory skin disease with significant disease burden. Genetic and environmental trigger factors contribute to AD, activating two of our largest organs, the nervous and immune system. Dysregulation of neuro-immune circuits plays a key role in the pathophysiology of AD causing inflammation, pruritus, pain, and barrier dysfunction. Sensory nerves can be activated by environmental or endogenous trigger factors transmitting itch stimuli to the brain. Upon stimulation, sensory nerve endings also release neuromediators into the skin contributing again to inflammation, barrier dysfunction and itch. Additionally, dysfunctional peripheral and central neuronal structures contribute to neuroinflammation, sensitization, nerve elongation, neuropathic itch, thus chronification and therapy-resistance. Consequently, neuro-immune circuits in skin and central nervous system may be targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids, ions excite/sensitize sensory nerve endings not only induce itch but further aggravate/perpetuate inflammation, skin barrier disruption, and pruritus. Thus, targeted therapies for neuro-immune circuits as well as pathway inhibitors (e.g., kinase inhibitors) may be beneficial to control pruritus in AD either in systemic and/or topical form. Understanding neuro-immune circuits and neuronal signaling will optimize our approach to control all pathological mechanisms in AD, inflammation, barrier dysfunction and pruritus.