Pruritus
Laurent Misery · Sonja StänderEditors
Pruritus
EditorsLaurent MiseryDepartment of DermatologyCHU Brest29200 [email protected]
Sonja StänderDepartment of DermatologyCompetence Center PruritusUniversity Hospital MünsterVon-Esmarch-Str. 5848149 Mü[email protected]
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
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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