New and emerging treatments for inflammatory itch

Objective: To summarize recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways. Data Sources: Literature search of PubMed, industry websites, and review of the ClinicalTrials.gov database. Study Selections: Peer-reviewed publications and public disclosures by industry relating to chronic pruritus pathophysiology and therapeutics. Results: Histamine and immunoglobulin E remain primary targets for the treatment of itch in the setting of chronic urticaria. More recently, blockade of type 2 immune cell–associated cytokines, including interleukin (IL) 4, IL-13, and IL-31, and the epithelial cell–derived cytokines, specifically IL-33 and thymic stromal lymphopoietin, has and is revolutionizing the treatment of chronic pruritic dermatoses, such as atopic dermatitis and prurigo nodularis. Other novel targets include histamine receptor 4, Janus kinases, κ-opioid receptor, neurokinin 1 receptor, and phosphodiesterase 4. Conclusion: Advances in our understanding of the neuroimmunology of chronic pruritus have led to the identification of new therapeutic targets and the rapid development of cutting-edge clinical trials. Although incredible advances have already been made, chronic itch continues to be an area of great unmet need.