Pruritus

Laurent Misery · Sonja StänderEditors

Pruritus

EditorsLaurent MiseryDepartment of DermatologyCHU Brest29200 BrestFrancelaurent.misery@chu-brest.fr

Sonja StänderDepartment of DermatologyCompetence Center PruritusUniversity Hospital MünsterVon-Esmarch-Str. 5848149 MünsterGermanysonja.staender@uni-muenster.de

ISBN 978-1-84882-321-1 e-ISBN 978-1-84882-322-8DOI 10.1007/978-1-84882-322-8Springer London Dordrecht Heidelberg New York

Library of Congress Control Number: 2009943295

© Springer-Verlag London Limited 2010Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licenses issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers.The use of registered names, trademarks, etc., in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use.Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

v

Foreword

Toward the end of the last century (1994), I edited the first comprehensive medical textbook on itch. Since that time, clinical interest and research in itch have blos-somed. (Afterwards, therefore, because of? A pleasing but grandiose notion.)

There is now an International Forum for the Study of Itch (www.itchforum.net), and it has sponsored four International Workshops for the Study of Itch, where everything from chemical receptors to specific itch neurons to itch inhibitors to treatment in the clinic has been discussed.

Over just the past 15 years there has been progress in every aspect of itch: neuro-anatomy, neurophysiology, molecular biology, diagnosis, terminology, classification, and treatment. You will find it all here.

In this book, every imaginable aspect of pruritus,* from bench to bedside, has been covered by experts. Misery and Ständer – both recognized across the globe as leading itch workers – have now produced the itch book for the twenty-first century.

Jeffrey D. Bernhard, MD, FRCPedin

*“Itch” and “pruritus” are synonymous and may be used interchangeably. According to the great philosopher Willard V.O. Quine, “Faced with two terms for the same thing, one tends to cast about for a distinction.”Most people now agree that giving these two terms different meanings is confusing, not to mention that “itch” is easier to say and to spell.

vii

Foreword

The American poet Ogden Nash tells us that “happiness is having a scratch for every Itch” – and there is much truth in that pithy aphorism. Unfortunately effective and practical solutions for the chronically itchy patient still remain elusive and those of us who work in the clinic are faced all too frequently with the very unhappy patient complaining of excruciating and intractable itching despite our best efforts.

Up to the latter years of my career, itching – though the dominant symptom of skin disease – has attracted little or no attention from physiologists. When it had received attention in the past, it has all too often been relegated to the Cinderella status of a mild form of pain, despite self-evident differences such as the withdrawal reflex response to pain versus the scratch response to itch. Even that acute observer of skin physiology Thomas Lewis in his classic text “The blood vessels of the human skin and their responses”, in which he devotes several chapters to the actions of histamine, does not once mention itching.

However, it has been my good fortune, during the new millennium, to witness an upsurge of interest in the mechanisms of itch at a molecular level, resulting in impres-sive advances in the understanding of the neurophysiology of itching, which offers real prospects of progress in the management of the itchy patient. These advances have been facilitated by the utilisation of advances in neurophysiological technology including microneurography and positron emission tomography of the human brain, and by improved methods of quantifying itch and its deleterious effect on quality of life. The realisation that itch can be generated centrally, by dysregulation of afferent neuronal traffic within the CNS – a concept espoused by the late neurophysiologist Pat Wall – has also had an impact on therapeutic strategies for itch.

Although this book is not the first devoted to bringing together the multiple strands of research on itch, it has the advantage of a more solid foundation of new insights, particularly at a basic molecular level and also realistic prospects for the emergence of treatments. Edited by Laurent Misery and Sonja Ständer, both of whom are in the forefront of current research in this field, the book successfully encapsulates all major advances. Their clinical background accounts for the emphasis placed in the book on translational research and there is much which should be of interest to the practising physician as well as the researcher.

Altogether, this book will prove an invaluable acquisition to the libraries of the laboratory and the clinic alike.

Malcolm W. Greaves Emeritus Professor of Dermatology, The Cutaneous Allergy Clinic,

St John`s Institute of Dermatology, St Thomas’ Hospital, Lambeth Palace Rd, London SE1 7EH UK

ix

Foreword

I am delighted to write this foreword for the book – Pruritus – by Laurent Misery MD and Sonja Ständer MD and congratulate both of them on this excellent contribution. For many years they have pioneered clinical and experimental research on cutaneous neurobiology and neuroinflammation which ultimately has resulted in an improved understanding of itch as well as the development of novel therapeutic strategies.

Pruritus or Itch is an important danger signal of the body to external noxious stimuli or a variety of diseases involving many organs, which due to lack of knowl-edge has been neglected in the past as the “little sister of pain”. It may develop to be very distressing, and substantially impairing the quality of life and in some cases may even provoke patients to contemplate suicide. The enormous progress in our under-standing of the pathophysiology and molecular basis of pruritus resulted in a new classification of itching. As a consequence, several novel compounds became avail-able and others are currently being investigated to define an individual treatment depending on the underlying cause of itch.

The most current knowledge of the complex epidemiological, clinical, experimen-tal and therapeutic aspects of pruritus is contributed by leading experts in the field. The book has been very thoughtfully divided into three parts, each having a logical sequence of chapters. The first part deals with basic aspects such as neuroanatomy, central and peripheral transmission, neuropeptides and their receptors, neuroimag-ing, tools for measurement and finally animal models. The chapters of the second part are dedicated to the clinical aspects of the different forms of pruritus as well as dis-eases associated with itch and psychological aspects. In the third part several chapters address the most up-to-date therapeutic developments with regard to their specific efficacy for the distinct forms of itch.

I am convinced that this excellent book which provides important insights into a rapidly developing field will be a must for any clinician involved in the management of patients suffering from this distressing symptom. For scientists interested in pruri-tus research this book will provide an excellent update on the most recent developments.

Thomas A. LugerProfessor and Chairman

Department of DermatologyUniversity of Münster

Münster, Germany

xi

Pruritus or itch is an unpleasant sensation that makes a person want to scratch – this definition has remained unchanged for almost 350 years.1,3 However, pruritus as a protection mechanism will exist as long as animals and human beings have skin or fur. Acute and chronic pruritus is also a common manifestation of dermatologic and non-dermatologic diseases. Recent epidemiological studies have revealed that chronic itch is very frequent (in almost one third of the population ).2

All patients suffering from itch know that it is a very disturbing sensation with a high impact on the quality of life. Unfortunately, this major symptom was considered the “little brother” and not severe by comparison to pain until the beginning of the 1990s . The consequences of this paradigm were that research on this field was hin-dered and development of effective antipruritic drugs delayed. Recently, new con-cepts and genuine discoveries of itch have completely modified our understanding of itch and suggested new therapeutic modalities. International collaboration is now really effective, with the creation of the first Society dedicated to pruritus research: the International Forum for Studies on Itch (IFSI) – www.itchforum.net.

Our objectives were to provide a book on itch that would be convenient for doctors who are confronted by patients suffering from itch, by giving practical data on the causes and treatments of pruritus and to present all the new data about pathophysiol-ogy and therapeutics. This book could not have been completed without experts and friends world-wide; therefore we want to thank all the authors who have contributed to this book.

Laurent MiserySonja Ständer

References

1. Bernhard JD. Itch. Mechanisms and Management of Pruritus. Mac Graw-Hill; 1994:454 . 2. Dalgard F, Lien L, Dalen I. Itch in the community: associations with psychosocial factors among

adults. J Eur Acad Dermatol Venereol. 2007;21:1215–1219. 3. Hafenreffer S. Nosodochium, in quo cutis, eique adhaerentium partium, affectus omnes, singu-

lari methodo, et cognoscendi et curandi fidelissime traduntur. Ulm, Typis & expensis Balthasar. Kühnen, reipubl. ibid. typogr. & biblopolae;1660.

Preface

xiii

Part I Neurophysiology

1 Neuroanatomy of Itch ............................................................................... 3Akihiko Ikoma

2 Neuroreceptors and Neuromediators ...................................................... 7Sonja Ständer and Thomas A. Luger

3 The Brain in the Skin: Neuro-Epidermal Synapses .............................. 17Nicholas Boulais and Laurent Misery

4 Central Transmission: From Skin to Brain ............................................ 23Tejesh Surendra Patel and Gil Yosipovitch

5 Modulation of Pruritus: Peripheral and Central Sensitisation ............ 27Martin Schmelz

6 Interaction of Pruritus and Pain ............................................................. 33Martin Schmelz

7 Neuroimaging ............................................................................................ 37Florian Pfab, Michael Valet, Thomas Tölle, Heidrun Behrendt, Johannes Ring, and Ulf Darsow

8 Measurement of Itch ................................................................................. 45Joanna Wallengren

9 Experimental Models of Itch .................................................................... 51Ulysse Pereira and Laurent Misery

Part II Clinics

Section 1

10 Pruritus, Pain and Other Abnormal Skin Sensations ........................... 65Laurent Misery

Contents

xiv Contents

11 The Epidemiology of Pruritus .................................................................. 69Florence Dalgard and Elke Weisshaarh

12 Classification .............................................................................................. 77Sonja Ständer

13 Examination of Patients ........................................................................... 79Elke Weisshaar

Section 2 Dermatology

14 Inflammatory Diseases .............................................................................. 87Jacek C. Szepietowski and Adam Reich

15 Pruritus in Autoimmune Diseases ........................................................... 97Yozo Ishiuji and Alan B. Fleischer, Jr.

16 Urticaria ..................................................................................................... 103Ulrike Raap, Alexander Kapp, and Bettina Wedi

17 Pruritic Skin Diseases in Travellers......................................................... 111Eric Caumes

18 Pruritus in Cutaneous T-cell Lymphoma ................................................ 121Tobias Görge and Meinhard Schiller

19 Anal Pruritus ............................................................................................. 125Sylvia Proske and Wolfgang Hartschuh

20 Secondary Reactive Conditions in Pruritic Skin .................................... 129Joanna Wallengren

21 Aquadynia and Aquagenic Pruritus........................................................ 137Laurent Misery

22 Sensitive Skin ............................................................................................. 141Laurent Misery and Sonja Ständer

Section 3 Pruritus in Neurology

23 Neurogenic Pruritus with Cerebral and/or Medullary Abnormalities ............................................................................................ 145Camille Fleuret and Laurent Misery

24 Localized Neuropathic Pruritus .............................................................. 151Martin Marziniak, Esther Pogatzki-Zahn, and Stefan Evers

25 Brachioradial Pruritus ............................................................................. 157Martin Marziniak and Sonja Ständer

xvContents

26 Other Neurological Causes of Itch .......................................................... 163Martin Marziniak, Esther Pogatzki-Zahn, and Stefan Evers

Section 4 Pruritus in Internal Medicine

27 Chronic Kidney Disease-Associated Pruritus......................................... 167Thomas Mettang

28 Pruritus in Patients with Hepatobiliary Diseases .................................. 177Andreas E. Kremer, Ronald P.J. Oude-Elferink, and Ulrich Beuers

29 Endocrine Diseases .................................................................................... 189Elke Weisshaar

30 Pruritus in the Course of Malignancy ..................................................... 191Zbigniew Zylicz and Malgorzata Krajnik

31 Drugs .......................................................................................................... 195Jacek C. Szepietowski and Adam Reich

Section 5 Psychosomatics and Psychiatry

32 Interaction Between Pruritus and Stress or Other Psychosomatic Factors .............................................................................. 207Laurent Misery

33 Psychosomatic Aspects and Psychiatric Conditions .............................. 211Gudrun Schneider

34 Psychosomatics and Psychiatry: Psychological Approach .................... 217Sabine Dutray and Laurent Misery

35 Psychogenic Pruritus ................................................................................ 223Laurent Misery

Section 6 Other Specialities

36 Pruritus in Children.................................................................................. 231Matthieu Gréco and Laurent Misery

37 Pruritus Vulvae.......................................................................................... 243Micheline Moyal-Barracco

Part III Treatment

Section 1

38 General Principles and Guidelines .......................................................... 257Elke Weisshaar

xvi Contents

Section 2 Topical

39 Menthol ...................................................................................................... 263Laurent Misery and Sonja Ständer

40 Capsaicin .................................................................................................... 265Laurent Misery

41 Topical Immunomodulators ..................................................................... 269Laurent Misery

42 Cannabinoid-Receptor Agonists .............................................................. 271Sonja Ständer

43 Other Topical Treatments ........................................................................ 273Laurent Misery

Section 3 Systemical

44 Antihistamines ........................................................................................... 277Caroline Gaudy-Marqueste

45 Anticonvulsants for the Treatment of Pruritus ...................................... 289Nora V. Bergasa and Deewan Deewan

46 Opioid Receptor Antagonists or Agonists ............................................... 297Laurent Misery

47 Serotonin Reuptake Inhibitors and Other Antidepressants in the Treatment of Chronic Pruritus ..................................................... 301Zbigniew Zylicz and Małgorzata Krajnik

48 Systemic Immunosuppressants in the Treatment of Pruritus ............... 307Silvia Moretti, Francesca Prignano, and Torello Lotti

49 Other Systemic Treatments ...................................................................... 311Sonja Ständer

Section 4 Other Approaches

50 Psychological Intervention ....................................................................... 317Sabine Dutray and Laurent Misery

51 Ultraviolet Phototherapy of Pruritus ...................................................... 325Joanna Wallengren

52 Itch and Acupuncture ............................................................................... 335Laurent Misery and Laurence Potin-Richard

xviiContents

Section 5 Future Perspectives

53 Future Perspectives: Outlook ................................................................... 341Sonja Ständer and Laurent Misery

Index ................................................................................................................... 343

xix

Contributors

Heidrun Behrendt ZAUM – Center for Allergy and Environment, Division of Environmental Dermatology and Allergy Helmholtz Zentrum/TUM, Technische Universität München, Munich, Germany

Nora V. Bergasa Department of Medicine, Metropolitan Hospital Center, New York, USA

Ulrich Beuers Department of Gastroenterology and Hepatology, Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Nicholas Boulais Laboratory of Skin Neurobiology, Unit of Compared and Integrative Physiology, University Hospital of Brest, Brest, France

Eric Caumes Département des Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière, Paris, France

Florence Dalgard Institute of General Practice and Community Medicine, University of Oslo and Judge Baker Children’s Center, Harvard Medical School, Boston, Massachusetts, USA

Ulf Darsow Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany

Deewan Deewan Medicine, Woodhull Medical and Mental Health Center, Brooklyn, New York, USA

Sabine Dutray Dermatology, University and Regional Hospital Center, Brest Cedex, France

Stefan Evers Department of Neurology, University of Münster, Münster, Germany

Alan B. Fleischer, Jr. Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

xx Contributors

Camille Fleuret Service de Dermatologie, CHIC Laënnec, Quimper, France

Caroline Gaudy-Marqueste Dermatology Department, STE Marguerite Hospital, Marseille, France

Tobias Görge Department of Dermatology, University Hospital Münster, Münster, Germany

Matthieu Gréco Department of Dermatology, University Hospital, Brest, France

Wolfgang Hartschuh Department of Dermatology, University of Heidelberg, Heidelberg, Germany

Akihiko Ikoma Department of Dermatology, University of California, San Francisco, San Francisco, USA

Yozo Ishiuji Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan

Alexander Kapp Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany

Malgorzata Krajnik Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland

Andreas E. Kremer Department of Gastroenterology and Hepatology, Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Torello Lotti Department of Dermatology, Faculty of Medicine, University of Florence, Florence, Italy

Thomas A. Luger Department of Dermatology, University of Münster, Münster, Germany

Martin Marziniak Department of Neurology, University of Münster, Münster, Germany

Thomas Mettang Nephrology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany

Laurent Misery Department of Dermatology and Laboratory of Skin Neurophysiology, University of Western Brittany, Brest, France

Silvia Moretti Department of Dermatology, Faculty of Medicine, University of Florence, Florence, Italy

Micheline Moyal-Barracco Department of Dermatology, Hôpital Ambroise Paré, Boulogne, France

xxiContributors

Ronald P.J. Oude-Elferink Department of Gastroenterology and Hepatology, Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Tejesh Surendra Patel Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA

Ulysse Pereira Department of Dermatology, University Hospital, Brest, Bretagne, France

Florian Pfab Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany

Esther Pogatzki-Zahn Department of Anesthesiology, University of Münster, Münster, Germany

Francesca Prignano Department of Dermatology, Faculty of Medicine, University of Florence, Florence, Italy

Sylvia Proske Department of Dermatology, University of Heidelberg, Heidelberg, Germany

Ulrike Raap Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany

Adam Reich Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland

Laurence Richard University Hospital of Brest, Brest, France

Johannes Ring Department of Dermatology and Allergy, Technische Universität München, Munich, Germany

Meinhard Schiller University Hospital Münster, Department of Dermatology, Münster, Germany

Martin Schmelz Department Anesthesiology and Intensive Care Medicine, Karl Feuerstein Professorship, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Gudrun Schneider Department of Psychosomatics and Psychotherapy, University of Münster, Münster, Germany

Sonja Ständer Competence Center Pruritus, Department of Dermatology, University of Münster, Münster, Germany

xxii Contributors

Jacek C. Szepietowski Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland

Thomas R. Tölle Department of Neurology, Technische Universität München, Munich, Germany

Michael Valet Department of Neurology, Technische Universität München, Munich, Germany

Joanna Wallengren Department of Dermatology, University Hospital, Getingev, Lund, Sweden

Bettina Wedi Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany

Elke Weisshaar Department of Clinical Social Medicine, Occupational and Environmental Dermatology, University Hospital of Heidelberg, Heidelberg, Germany

Gil Yosipovitch Departments of Dermatology and Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Zbigniew Zylicz Dove House Hospice, East Riding of Yorkshire, Hull, UK