Original StudyChronic Itch of Unknown Origin Is Associated With an Enhanced Th2 Skin Immune ProfileDehner, Carina MD, PhD*; Chen, Lu MD†; Kim, Brian MD, MTR, FAAD*,‡,§; Rosman, Ilana S. MD*,‡Author Information *Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO; †The Institute for Dermatopathology, Newtown Square, PA; ‡Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO; and §Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO. Correspondence: Ilana S. Rosman, MD, Washington University, Dermatopathology Center, 660 S Euclid Ave, Box 8118, St. Louis, MO 63110 (e-mail: [email protected]). The authors declare no conflicts of interest. IRB approval status: Reviewed and approved by Washington University, St. Louis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.amjdermatopathology.com). The American Journal of Dermatopathology: November 2021 - Volume 43 - Issue 11 - p 773-775 doi: 10.1097/DAD.0000000000001902 Buy SDC Metrics Abstract Chronic pruritus of unknown origin (CPUO) is described as chronic itch lasting longer than 6 weeks in the absence of a defined skin rash and any known causative disease process. A retrospective study was performed on biopsy samples from patients with CPUO and normal controls to compare the immune profiles of these patients with healthy individuals. We used dual CD3/T-bet and CD3/GATA3 immunohistochemical staining to assess for T-cells expressing Th1 versus Th2 transcription factors, respectively. Our data showed that CD3+ cells of patients with CPUO co-express significantly more GATA3 compared with normal controls. Meanwhile, the normal control skin showed a much more balanced T-bet/GATA3 ratio of co-expression. Our data suggest an enrichment of Th2 cells in CPUO skin by T cell/GATA3 co-staining, supporting that CPUO is increasingly considered a type 2/Th2 cell-associated disease. We thus speculate that type 2 cytokine blockade-based therapies may represent effective treatments for CPUO. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.