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Pathogenesis and Treatment of Chronic Pruritus

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Pathogenesis and Treatment of Chronic Pruritus Pathogenesis and of Chronic Treatment Pruritus • Shawn G. Kwatra Pathogenesis and Treatment of Chronic Pruritus Edited by Shawn G. Kwatra Printed Edition of the Special Issue Published in Medicines www.mdpi.com/journal/medicines Pathogenesis and Treatment of Chronic Pruritus Pathogenesis and Treatment of Chronic Pruritus Editor Shawn G. Kwatra MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editor Shawn G. Kwatra Johns Hopkins University School of Medicine USA Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Medicines (ISSN 2305-6320) (available at: https://www.mdpi.com/journal/medicines/special issues/pathogenesis chronic pruritus). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03943-100-7 (Hbk) ISBN 978-3-03943-101-4 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editor .............................................. vii Kyle A. Williams and Shawn G. Kwatra Emerging Research in Chronic Pruritus: From Bedside to Bench and Back Again Reprinted from: Medicines 2020, 7, 24, doi:10.3390/medicines7050024 ................ 1 Katherine A. Whang, Raveena Khanna, Jamael Thomas, Crystal Aguh and Shawn G. Kwatra Racial and Gender Differences in the Presentation of Pruritus Reprinted from: Medicines 2019, 6, 98, doi:10.3390/medicines6040098 ................ 7 Christina D. Kwon, Raveena Khanna, Kyle A. Williams, Madan M. Kwatra and Shawn G. Kwatra Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis Reprinted from: Medicines 2019, 6, 97, doi:10.3390/medicines6040097 ................ 15 Katherine A. Whang, Sewon Kang and Shawn G. Kwatra Inpatient Burden of Prurigo Nodularis in the United States Reprinted from: Medicines 2019, 6, 88, doi:10.3390/medicines6030088 ................ 25 John-Douglas Matthew Hughes, Taylor E. Woo, Micah Belzberg, Raveena Khanna, Kyle A. Williams, Madan M. Kwatra, Shahzeb Hassan and Shawn G. Kwatra Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis Reprinted from: Medicines 2020, 7, 4, doi:10.3390/medicines7010004 ................ 35 Subuhi Kaul, Micah Belzberg, John-Douglas Matthew Hughes, Varun Mahadevan, Raveena Khanna, Pegah R. Bakhshi, Michael S. Hong, Kyle A. Williams, Annie L. Grossberg, Shawn G. Kwatra and Ronald J. Sweren Comorbidities in Mycosis Fungoides and Racial Differences in Co-Existent Lymphomatoid Papulosis: A Cross-Sectional Study of 580 Patients in an Urban Tertiary Care Center Reprinted from: Medicines 2020, 7, 1, doi:10.3390/medicines7010001 ................. 45 Micah Belzberg, Valerie A. Larson, Raveena Khanna, Kyle A. Williams, Yevgeniy Semenov, Sonja St¨ander, Anna L. Grossberg and Shawn G. Kwatra Association between Itch and Cancer in 3836 Pediatric Pruritus Patients at a Tertiary Care Center Reprinted from: Medicines 2019, 6, 99, doi:10.3390/medicines6040099 ................ 57 Amy H. Huang, Benjamin H. Kaffenberger, Adam Reich, Jacek C. Szepietowski, Sonja St¨ander and Shawn G. Kwatra Pruritus Associated with Commonly Prescribed Medications in a Tertiary Care Center Reprinted from: Medicines 2019, 6, 84, doi:10.3390/medicines6030084 ................ 67 Shawn G. Kwatra, Emily Boozalis, Amy H. Huang, Cory Nanni, Raveena Khanna, Kyle A. Williams, Yevgeniy R. Semenov, Callie M. Roberts, Robert F. Burns, Madison Krischak and Madan M. Kwatra Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists Reprinted from: Medicines 2019, 6, 114, doi:10.3390/medicines6040114 ............... 75 v Akishi Momose, Micihihiro Yabe, Shigetoshi Chiba, Kenjirou Kumakawa, Yasuo Shiraiwa and Hiroki Mizukami Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus Reprinted from: Medicines 2019, 6, 110, doi:10.3390/medicines6040110 ............... 83 Michela Iannone, Agata Janowska, Valentina Dini, Giulia Tonini, Teresa Oranges and Marco Romanelli Itch in Chronic Wounds: Pathophysiology, Impact, and Management Reprinted from: Medicines 2019, 6, 112, doi:10.3390/medicines6040112 ............... 91 Ian P. Harrison and Fabrizio Spada Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis Reprinted from: Medicines 2019, 6, 76, doi:10.3390/medicines6030076 ................ 99 Lisa L. Zhai, Kevin T. Savage, Connie C. Qiu, Annie Jin, Rodrigo Valdes-Rodriguez and Nicholas K. Mollanazar Chronic Pruritus Responding to Dupilumab—A Case Series Reprinted from: Medicines 2019, 6, 72, doi:10.3390/medicines6030072 ................113 Raveena Khanna, Emily Boozalis, Micah Belzberg, John G. Zampella and Shawn G. Kwatra Mirtazapine for the Treatment of Chronic Pruritus Reprinted from: Medicines 2019, 6, 73, doi:10.3390/medicines6030073 ................129 vi About the Editor Shawn G. Kwatra is an Assistant Professor of Dermatology at the Johns Hopkins University School of Medicine. He is Director of the Johns Hopkins Itch Clinic and the Itch Fellowship Program. His areas of clinical expertise include chronic pruritus, prurigo nodularis, atopic dermatitis, and dermatology for ethnic skin. Dr. Kwatra’s primary clinical and translational research interest is in the pathogenesis and treatment of chronic pruritus. He is supported by the Dermatology Foundation’s Medical Dermatology Career Development Award. vii medicines Editorial Emerging Research in Chronic Pruritus: From Bedside to Bench and Back Again Kyle A. Williams and Shawn G. Kwatra * Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-410-955-5933 Received: 21 April 2020; Accepted: 26 April 2020; Published: 29 April 2020 Abstract: This Medicines special issue highlights emerging research spanning from epidemiology to diagnostic workup, pathogenesis, and therapeutics for patients suffering from chronic pruritus. The special issue contains 13 articles reporting relevant epidemiologic and experimental data on chronic pruritus. Keywords: pruritus; itch; treatment; therapeutic; pathogenesis; epidemiology 1. Introduction This editorial serves as an introduction to the special issue “Pathogenesis and Treatment of Chronic Pruritus” and contains an overview of various known causes of chronic pruritus and emerging therapeutics. Chronic pruritus is itch that lasts greater than six weeks and is associated with a variety of dermatologic, systemic, neurologic, and psychiatric etiologies. Itch negatively impacts patient quality of life and has devastating psychosocial consequences. The manuscripts published in this special issue are also a showcase of the current understanding of the pathogenesis of chronic pruritus, along with its epidemiology, diagnostic workup, and therapeutic approaches used to treat chronic pruritus. 2. Epidemiology Chronic pruritus can arise in association with many disease processes and affects many patient populations. Thus, epidemiologic studies are needed to gain a better understanding of the burden of disease. In this special issue, a cross-sectional study of over 18,000 itch patients seen at a tertiary care center showed that African American and female patients were more likely to experience pruritus than their white or male counterparts [1]. Furthermore, African American patients were less likely to see a dermatologist than other racial groups, suggesting disparities in care [1]. Additionally, African Americans were more likely to be diagnosed with prurigo nodularis (PN), lichen planus (LP), and atopic dermatitis (AD), which highlight areas for future translational studies. Finally, females were more likely to have comorbid autoimmune or psychiatric conditions [1]. This study’s results were supported when their data was compared to nationally available data. A major focus of this special issue is placed on prurigo nodularis. PN is a chronic itchy skin condition characterized by severely pruritic nodules that cause a significant negative impact on patient quality of life [2,3]. Kwon et al. performed a systematic review to provide a thorough testing and diagnostic evaluation algorithm for PN patients [4]. In particular, the study highlighted the need for baseline laboratory screening with complete blood cell count (CBC), complete metabolic panel (CMP), thyroid, liver, and kidney function tests, HIV serology, and hepatitis B and C serologies. Additional testing may be indicated based on individual patient’s clinical history and review of systems [4]. Whang et al. sought to better characterize the epidemiology and disease burden of this condition by performing a cross-sectional study of the 2016 National
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