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Retinoids in Dermatology Series in Dermatological Treatment About the Series Published in association with the Journal of Dermatological Treatment, the Series in Dermatological Treatment keeps readers up to date with the latest clinical therapies to improve problems with the skin, hair, and nails. Each volume in the series is prepared separately and typically focuses on a topical theme. Volumes are published on an occasional basis, depending on the emergence of new developments. Retinoids in Dermatology Ayse Serap Karadag, Berna Aksoy, and Lawrence Charles Parish Facial Skin Disorders Ronald Marks Dermatologic Reactions to Cancer Therapies Gabriella Fabbrocini, Mario E. Lacouture, and Antonella Tosti Acne Scars: Classification and Treatment, Second Edition Antonella Tosti, Maria Pia De Padova, Gabriella Fabbrocini, and Kenneth Beer Phototherapy Treatment Protocols, Third Edition Steven R. Feldman and Michael D. Zanolli Dermatoscopy in Clinical Practice: Beyond Pigmented Lesions, Second Edition Giuseppe Micali and Francesco Lacarrubba Nail Surgery Bertrand Richert, Nilton Di Chiacchio, and Eckart Haneke Abdominal Stomas and Their Skin Disorders, Second Edition Callum C. Lyon and Amanda Smith Textbook of Atopic Dermatitis Sakari Reitamo, Thomas A. Luger, and Martin Steinhoff For more information about this series please visit: https://www.crcpress.com/ Series-in-Dermatological-Treatment/book-series/CRCSERDERTRE Retinoids in Dermatology Edited by Ayse Serap Karadag, MD Department of Dermatology Istanbul Medeniyet University Faculty of Medicine Göztepe Training and Research Hospital Istanbul, Turkey Berna Aksoy, MD Department of Dermatology Bahçeşehir University Faculty of Medicine Istanbul, Turkey Lawrence Charles Parish, MD, MD (Hon) Department of Dermatology and Cutaneous Biology Sidney Kimmel Medical College at Thomas Jefferson University and Jefferson Center for International Dermatology Philadelphia, Pennsylvania, USA CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2020 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-1-138-31477-1 (Hardback) This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not necessarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any elec- tronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or con- tact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Names: Karadag, Ayse Serap, editor. | Aksoy, Berna, editor. | Parish, Lawrence Charles, editor. Title: Retinoids in dermatology / edited by Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish. Other titles: Series in dermatological treatment. Identifiers: LCCN 2019034117 (print) | LCCN 2019034118 (ebook) | ISBN 9781138314771 (hardback ; alk. paper) | ISBN 9780429456732 (ebook) Subjects: MESH: Skin Diseases--drug therapy | Retinoids--therapeutic use | Retinoids--pharmacology Classification: LCC RL120.R48 (print) | LCC RL120.R48 (ebook) | NLM WR 650 | DDC 616.5/061--dc23 LC record available at https://lccn.loc.gov/2019034117 LC ebook record available at https://lccn.loc.gov/2019034118 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Contributors vii 1. The Background of Retinoids .......................................................................................................................................................1 Ayse Serap Karadag, Berna Aksoy, and Lawrence Charles Parish 2. Mechanism of Action of Vitamin A ..............................................................................................................................................3 Sandra Maria Barbalho 3. Mechanism of Action of Topical Retinoids ..................................................................................................................................7 Sümeyre Seda Ertekin and Mehmet Salih Gurel 4. Mechanism of Action of Isotretinoin ..........................................................................................................................................13 Bodo C. Melnik 5. Mechanism of Action of Acitretin ...............................................................................................................................................27 Kaitlyn Lam and Ronald Vender 6. Mechanism of Action of Bexarotene ...........................................................................................................................................33 Catherine M. Ludwig, Claire Wilson, Brandon Roman, and Maria M. Tsoukas 7. Mechanism of Action of Alitretinoin ..........................................................................................................................................37 Ömer Faruk Elmas and Necmettin Akdeniz 8. Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence) ............................................................................................................................................................................41 Jelena Popovic 9. Effects of Retinoids at the Systemic Level .................................................................................................................................51 Sandra Maria Barbalho and Letícia Maria Pescinini-Salzedas 10. New Aspects of Isotretinoin Teratogenicity ...............................................................................................................................55 Bodo C. Melnik 11. Mucocutaneous Side Effects ........................................................................................................................................................61 Tugba Kevser Uzuncakmak and Ayse Serap Karadag 12. Ophthalmologic Side Effects .......................................................................................................................................................67 Remzi Karadag and Fehim Esen 13. Musculoskeletal Side Effects .......................................................................................................................................................73 Filiz Cebeci Kahraman, Vefa Aslı Turgut Erdemir, and Melek Aslan Kayıran 14. Neurologic Side Effects ................................................................................................................................................................79 Evren Burakgazi-Dalkilic 15. Psychiatric Side Effects ................................................................................................................................................................83 Joshua Schimmel, Evren Burakgazi-Dalkilic, and Hatice Burakgazi-Yilmaz 16. Gastrointestinal Side Effects .......................................................................................................................................................89 Esra Adışen, Burcu Beksaç, and Mehmet Ali Gürer 17. Endocrine and Metabolic Side Effects .......................................................................................................................................93 Ayse Serap Karadag, Emin Ozlu, and Bodo C. Melnik v vi Contents 18. Other Systemic Side Effects: Cardiovascular, Pulmonary, Otolaryngorhinologic, Genitourinary, Renal, and Immunologic ...............................................................................................................................................................................105 Emin Ozlu, Akif Bilgen, and Ayse Serap Karadag 19. Retinoids in Acne ........................................................................................................................................................................111 Ruta Ganceviciene and Christos C. Zouboulis 20. Retinoids in Hidradenitis Suppurativa/Acne Inversa .............................................................................................................121 Uwe Wollina, Piotr Brzezinski, and André Koch 21. Retinoids in Rosacea ..................................................................................................................................................................125 Marius Rademaker and Harriet Cheng 22. Retinoids in Hair Disorders ......................................................................................................................................................129 Brent J. Doolan and Rodney Sinclair 23. Retinoids in Psoriasis .................................................................................................................................................................135 Uwe Wollina, Piotr Brzezinski, and André Koch 24. Retinoids in Keratinization Disorders .....................................................................................................................................145 Ümit Türsen and Belma Türsen 25. Retinoids in Antiaging Therapy ................................................................................................................................................157 Zehra Aşiran Serdar and Ezgi Aktaş Karabay 26. Retinoids in Other Skin Diseases ..............................................................................................................................................163 Uwe Wollina, Piotr Brzezinski, and André Koch 27. Retinoids in Lymphoma .............................................................................................................................................................171 Robert Duffy and Joya Sahu 28. Retinoids in Cutaneous Chemoprophylaxis ............................................................................................................................177 Robert Duffy and Joya Sahu 29. Guide to Good Clinical Practice for Vulnerable Populations (Infancy, Childhood, Fertile Period, Elderly) ..................183 Elif Yildirim and Berna Aksoy 30. Retinoids and Concomitant Surgery ........................................................................................................................................189 H. Mete Aksoy 31. Retinoids and Concomitant Aesthetic Procedures .................................................................................................................197 Zekayi Kutlubay, Ayşegül Sevim Keçici, and Yalçın Tüzün 32. Laboratory and Clinical Follow-Up .........................................................................................................................................201 Nadide Burcu Öztürk and Berna Aksoy 33. Teratogenicity and Registry Programs ....................................................................................................................................207 Reese L. Imhof and Megha M. Tollefson 34. Management of Vitamin A and Retinoid Side Effects............................................................................................................213 Asli Tatliparmak and Berna Aksoy 35. Future and Novel Unexplored Indications of Retinoids .........................................................................................................217 Kabir Sardana and Ananta Khurana Index ....................................................................................................................................................................................................227 Contributors Esra Adışen Evren Burakgazi-Dalkilic Department of Dermatology Department of Neurology Gazi University Cooper Medical School of Rowan University Faculty of Medicine Cooper University Hospital Ankara, Turkey Camden, New Jersey Necmettin Akdeniz Hatice Burakgazi-Yilmaz Department of Dermatology Department of Psychiatry Istanbul Medeniyet University Cooper Medical School of Rowan University Faculty of Medicine Cooper University Hospital Göztepe Training and Research Hospital Camden, New Jersey Istanbul, Turkey Harriet Cheng Berna Aksoy Department of Dermatology Department of Dermatology Auckland City Hospital Bahçeşehir University Auckland, New Zealand Faculty of Medicine Istanbul, Turkey Brent J. Doolan The Royal Children’s Hospital H. Mete Aksoy Skin & Cancer Foundation Inc. Department of Plastic, Reconstructive, The Royal Melbourne Hospital and Aesthetic Surgery Melbourne, Australia Bahçeşehir University Faculty of Medicine Robert Duffy Istanbul, Turkey Department of Dermatology and Cutaneous Biology Thomas Jefferson University Sandra Maria Barbalho Philadelphia, Pennsylvania Department of Biochemistry and Nutrition School of Medicine Ömer Faruk Elmas University of Marília Department of Dermatology Faculty of Food Technology of Marília Ahi Evran University São Paulo, Brazil Faculty of Medicine Kırşehir, Turkey Burcu Beksaç Department of Dermatology Vefa Aslı Turgut Erdemir Gülhane Research and Training Hospital Department of Dermatology Ankara, Turkey Istanbul Medeniyet University Faculty of Medicine Akif Bilgen Göztepe Training and Research Hospital Department of Otolaryngology, Head Istanbul, Turkey and Neck Surgery Health Science University Sümeyre Seda Ertekin Ankara Training and Research Hospital Department of Dermatology Ankara, Turkey Aksaray University Faculty of Medicine Piotr Brzezinski Training and Research Hospital Department of Dermatology Aksaray, Turkey Institute of Biology and Environmental Protection Pomeranian Academy Fehim Esen Slupsk, Poland Department of Ophthalmology and Istanbul Medeniyet University 6th Military Support Unit Faculty of Medicine Ustka, Poland Istanbul, Turkey vii viii Contributors Ruta Ganceviciene Ayşegül Sevim Keçici Departments of Dermatology, Venereology, Department of Dermatology Allergology, and Immunology University of Medical Sciences Dessau Medical Center Haydarpaşa Numune Training and Research Hospital Brandenburg Medical School Theodor Fontane Istanbul, Turkey Dessau, Germany Ananta Khurana Department of Dermatology Mehmet Salih Gurel Post Graduate Institute of Medical Education and Research Department of Dermatology Dr RML Hospital Istanbul Medeniyet University Delhi, India Faculty of Medicine Göztepe Training and Research Hospital André Koch Istanbul, Turkey Department of Dermatology and Allergology Städtisches Klinikum Dresden Mehmet Ali Gürer Academic Teaching Hospital of the Technical Department of Dermatology University of Dresden Gazi University Dresden, Germany Faculty of Medicine Ankara, Turkey Zekayi Kutlubay Department of Dermatology Reese L. Imhof Istanbul University Mayo Clinic School of Medicine Faculty of Medicine Rochester, Minnesota Cerrahpaşa Faculty of Medicine Istanbul, Turkey Filiz Cebeci Kahraman Department of Dermatology Kaitlyn Lam Istanbul Medeniyet University MD Program Faculty of Medicine University of Toronto Göztepe Training and Research Hospital Faculty of Medicine Istanbul, Turkey Toronto, Ontario, Canada Ezgi Aktaş Karabay Catherine M. Ludwig Department of Dermatology University of Illinois College of Medicine Bahçeşehir University Chicago, Illinois Faculty of Medicine Istanbul, Turkey Bodo C. Melnik Department of Dermatology, Environmental Medicine and Health Theory Ayse Serap Karadag University of Osnabrück Department of Dermatology Osnabrück, Germany Istanbul Medeniyet University Faculty of Medicine Emin Ozlu Göztepe Training and Research Hospital Department of Dermatology Istanbul, Turkey Düzce University Faculty of Medicine Remzi Karadag Düzce, Turkey Department of Ophthalmology Istanbul Medeniyet University Nadide Burcu Öztürk Faculty of Medicine Department of Dermatology Göztepe Training and Research Hospital Private Practice Istanbul, Turkey Kocaeli, Turkey Melek Aslan Kayıran Lawrence Charles Parish Department of Dermatology Department of Dermatology and Cutaneous Biology Istanbul Medeniyet University Sidney Kimmel Medical College at Thomas Jefferson University Faculty of Medicine and Göztepe Training and Research Hospital Jefferson Center for International Dermatology Istanbul, Turkey Philadelphia, Pennsylvania Contributors ix Letícia Maria Pescinini-Salzedas Megha M. Tollefson School of Medicine Department of Dermatology Department of Pharmacology Mayo Clinic University of Marília Rochester, Minnesota São Paulo, Brazil Maria M. Tsoukas Jelena Popovic Department of Dermatology Laboratory for Human Molecular Genetics University of Illinois College of Medicine Institute of Molecular Genetics and Genetic Chicago, Illinois Engineering Belma Türsen University of Belgrade Department of Dermatology Belgrade, Serbia Private Practice Mersin, Turkey Marius Rademaker Waikato Clinical School Ümit Türsen School of Medicine Department of Dermatology University of Auckland Mersin University Auckland, New Zealand Faculty of Medicine Mersin, Turkey Brandon Roman University of Illinois College of Medicine Yalçın Tüzün Chicago, Illinois Department of Dermatology Medical Park Hospital Joya Sahu Istanbul, Turkey Pathology and Hematology Oncology Cutaneous Lymphoma Multidisciplinary Center Tugba Kevser Uzuncakmak Sidney Kimmel Medical College at Thomas Department of Dermatology Jefferson University Istanbul Medeniyet University Philadelphia, Pennsylvania Faculty of Medicine Istanbul, Turkey Kabir Sardana Department of Dermatology Ronald Vender Post Graduate Institute of Medical MD Program Education and Research University of Toronto Dr RML Hospital Faculty of Medicine Delhi, India Toronto, Ontario, Canada Claire Wilson Joshua Schimmel University of Illinois College of Medicine Cooper Medical School of Rowan University Chicago, Illinois Camden, New Jersey Uwe Wollina Zehra Aşiran Serdar Department of Dermatology and Allergology Department of Dermatology Städtisches Klinikum Dresden Bahçeşehir University Academic Teaching Hospital of the Technical Faculty of Medicine University of Dresden Istanbul, Turkey Dresden, Germany Rodney Sinclair Elif Yildirim Department of Medicine Department of Dermatology University of Melbourne Sanko University Epworth Dermatology Faculty of Medicine Sinclair Dermatology Gaziantep, Turkey Melbourne, Australia Christos C. Zouboulis Asli Tatliparmak Departments of Dermatology, Venereology, Department of Dermatology Allergology, and Immunology Bahçeşehir University Dessau Medical Center Faculty of Medicine Brandenburg Medical School Theodor Fontane Istanbul, Turkey Dessau, Germany

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