Stephen Erickson1, Aaron Ver Heul2, Brian S Kim3. 1. Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2. Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, Missouri. 3. Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, Missouri; Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: briankim@wustl.edu.
Abstract
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.
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.
Authors: Dorottya Ádám; József Arany; Kinga Fanni Tóth; Balázs István Tóth; Attila Gábor Szöllősi; Attila Oláh Journal: Int J Mol Sci Date: 2022-04-08 Impact factor: 6.208