New and Emerging Treatments for Inflammatory Itch.

Objective Chronic pruritus, or itch lasting >6 weeks, is a common symptom and has a profoundly negative impact on quality of life. While many primary dermatologic disorders such as atopic dermatitis and chronic urticaria are characterized by pruritus, numerous other allergic, hepatobiliary, lymphoproliferative, neurologic, and renal disorders are associated with chronic pruritus. Itch involves complex interactions orchestrated by a variety of factors released from and acting on the skin, immune system, and the sensory nervous system. This review summarizes recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways. Data Sources Literature search via 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 (IgE) remain primary targets for the treatment of itch in the setting of chronic urticaria. More recently, blockade of type 2 immune cellassociated cytokines including IL-4, IL-13, IL-31, and the epithelial cell-derived cytokines, specifically IL-33 and TSLP, has, and is, revolutionizing the treatment of chronic pruritic dermatoses such as atopic dermatitis and prurigo nodularis. Other novel targets also include histamine receptor 4 (H4R), Janus kinases (JAKs), kappa opioid receptor (KOR), neurokinin 1 receptor (NK-1R), and phosphodiesterase 4 (PDE4). Conclusion Advances in our understanding of the neuroimmunology of chronic pruritus has 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.