Clinical and Basic Immunodermatology Clinical and Basic Immunodermatology

Edited by Anthony A. Gaspari, MD Department of Dermatology University of Maryland School of Medicine Baltimore, MD USA Stephen K. Tyring, MD, PhD Department of Dermatology University of Texas Medical School at Houston Houston, TX USA Editors Anthony A. Gaspari, MD University of Maryland School of Medicine Baltimore, MD USA

Stephen K. Tyring, MD, PhD University of Texas Medical School at Houston Houston, TX USA

ISBN 978-1-84800-164-0 e-ISBN 978-1-84800-165-7 DOI 10.1007/978-1-84800-165-7

British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library

Library of Congress Control Number: 2008923739

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Printed on acid-free paper

9 8 7 6 5 4 3 2 1 springer.com Preface

In 1981, the first edition of Clinical Immunodermatology was published, with Dr. Mark Dahl as the editor and sole contributor. This textbook filled a real need for residents in training, as the focus of this textbook was immuno- logically mediated skin disease. It certainly was critical and highly enjoyable reading for me when I began my dermatology residency in 1982 at Emory University. Its second edition in 1985 and the third and final edition in 1996 saw further improvements in this outstanding textbook. It has been a tremen- dous asset for all of those interested in the immune system, and how it plays a protective and pathologic role in skin diseases. The critical features of this textbook were its concise nature, simple diagrams, and clear and direct style of delivering fundamental information about the role of the immune system and its relevance to skin diseases. All of these features made this textbook well appreciated by residents and clinicians. This textbook really was the brainchild of Dr. Mark Dahl, and reflected well his lucid approach to teaching, organizing information, and presenting a complex topic in such a high-quality product. Fortunately for our specialty, Dr. Dahl remains active in academic dermatology, teaching, patient care, and publishing. Over the past twelve years, much has changed, stimulating Steve Tyring and I to revisit this important subject. There has been an explosion of information in the fields of cellular, molecular, innate, adaptive immunity, and immuno- pharmacology. In parallel, these advances have been applied to and translated to a better understanding and treatment of a number of common and less common dermatologic diseases. There are also a number of new therapeutic agents that are targeted therapies, or have an immune mechanism. All of these developments have occurred during the blossoming of the information age. Thus, we decided that it was no longer possible to present a single or even a dual authored/edited textbook. Steve Tyring and I decided to pursue the recruitment of national and international experts to author chapters on their respective areas of expertise. Hence, our approach for this important endeavor is that of a multiauthored collection of chapters that would be integrated into this book. Despite the different approach, our goal is to present the latest information related to fundamentals of the skin immune system, as well as a disease-focused textbook in the same concise, readable, and easily digested format that was initially developed by Dr. Dahl. We thank Dr. Dahl for his vision and his original book, which has had pro- found influence on generations of dermatologists. We have strived to enhance the teaching of cutaneous immunology, particularly as related to skin disease, to the next generations of young dermatologists who will be caring for patients

v vi Preface afflicted with immune-based skin diseases. We would be delighted if our text- book triggered the kind of interest in immunology that was stimulated in Steve and I during our training.

Anthony A. Gaspari Stephen K. Tyring Contents

Preface ...... v

Section I Concepts of Fundamental Importance for Understanding Skin Disease

1 Cytokines and Chemokines ...... 3 Oliver A. Perez and Brian Berman

2 Innate and Adaptive Immunity ...... 17 Jan D. Bos and Marcel B.M. Teunissen

3 Neuroimmunology ...... 31 Erica Lee and Richard D. Granstein

4 Stress and Immunity ...... 45 Francisco A. Tausk, Ilia Elenkov, Ralph Paus, Steven Richardson, and Marcelo Label

5 Toll-Like Receptors ...... 67 Donna Bilu Martin and Anthony A. Gaspari

6 Conventional and Unconventional T Cells ...... 85 Scott Roberts and Michael Girardi

7 Complement System ...... 105 Kim B. Yancey and Zelmira Lazarova

8 Cutaneous Dendritic Cells in Health and Disease ...... 119 Mark C. Udey

9 Antimicrobial Peptides ...... 131 H. Ray Jalian and Jenny Kim

10 Photoimmunology ...... 147 Christopher Hansen, Justin J. Leitenberger, Heidi T. Jacobe, and Ponciano D. Cruz, Jr.

11 Angiogenesis for the Clinician ...... 157 Benjamin A. Lefkove, Levi E. Fried, and Jack L. Arbiser

vii viii Contents

Section II Common Skin Diseases

12 Contact Dermatitis: Allergic and Irritant ...... 171 Donald V. Belsito

13 Atopic Dermatitis ...... 193 Thomas Bieber and Julia Prölss

14 Psoriasis ...... 207 Frank O. Nestle

15 The Immunology of Acne ...... 217 Guy F. Webster and Jenny Kim

16 Nonmelanoma Skin Cancer ...... 223 Fergal J. Moloney and Gary M. Halliday

17 Immunobiology and Immune-Based Therapies of Melanoma ...... 245 Mariah R. Brown, John C. Ansel, and Cheryl A. Armstrong

18 Drug Eruptions ...... 263 Craig K. Svensson

19 Cutaneous Vasculitis ...... 277 Sherrif F. Ibrahim and Carlos H. Nousari

20 Immunodermatology and Viral Skin Infection ...... 297 Natalia Mendoza, Anita Arora, Cesar A. Arias, Aron J. Gewirtzman, and Stephen K. Tyring

21 HIV Disease and AIDS ...... 323 Andrew Blauvelt

22 Bacterial Infections ...... 335 Carolyn Senavsky, Noah Craft, and Lloyd S. Miller

23 Parasitic Infections ...... 363 Sidney Klaus

24 Fungal Infections ...... 373 Nahed Ismail and Michael R. McGinnis

25 Cutaneous T-Cell Lymphoma ...... 411 Ellen J. Kim, Camille E. Introcaso, Stephen K. Richardson, and Alain H. Rook

26 Graft-Versus-Host Disease ...... 439 Edward W. Cowen Contents ix

27 Allergic Urticaria ...... 459 Laura M. Gober and Sarbjit S. Saini

Section III Immunopharmacology

28 Biologic Therapies for Inflammatory Disease ...... 481 Emily M. Berger and Alice B. Gotlieb

29 Topical Immune Response Modifiers:Adjuvants ...... 527 Annemarie Uliasz and Mark Lebwohl

30 Topical Immune Response Modifiers: Antiinflammatories ...... 539 Thomas A. Luger and Martin Steinhoff

31 Traditional Immune-Modulating Drugs ...... 551 Stephen E. Wolverton

32 Topical Corticosteroids ...... 561 Ulrich R. Hengge

33 Vaccines ...... 579 Anita Arora, Natalia Mendoza, Anne Marie Tremaine, and Stephen K. Tyring

34 Intravenous Immunoglobulins ...... 605 Doerte Bittner and Alexander Enk

Section IV Autoimmunity, Immunodeficiency, and Immune – Associated Dermatoses

35 Novel Approach to the Evaluation of Primary Immunodeficiencies ...... 617 Clemens Esche and Bernard A. Cohen

36 Iatrogenic Immunodeficiency and Skin Disease ...... 633 Brenda L. Bartlett and Jennifer Z. Cooper

37 Granulomatosis ...... 645 Kurt Q. Lu

38 Vitiligo Vulgaris ...... 661 James J. Nordlund, I. Caroline Le Poole, and Raymond E. Boissy

39 Alopecia Areata ...... 691 Richard S. Kalish and Amos Gilhar x Contents

40 Cutaneous Lupus Erythematosus ...... 703 David F. Fiorentino and Richard D. Sontheimer

41 Fibrotic Skin Diseases ...... 721 Irina G. Luzina and Sergei P. Atamas

42 Pemphigus Family of Diseases ...... 739 Masayuki Amagai

43 The Pemphigoid Spectrum ...... 751 Kelly Nelson, Ning Li, Zhi Liu, and Luis A. Diaz

44 Epidermolysis Bullosa Acquisita ...... 763 Julie Burnett, Jennifer Remington, Mei Chen, and David T. Woodley

45 Immunoglobulin A Dermatoses ...... 771 Todd V. Cartee and Robert A. Swerlick

Index ...... 789 Contributors

Masayuki Amagai, MD, PhD Department of Dermatology, Keio University School of Medicine, Tokyo, Japan

John C. Ansel, MD Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA

Jack L. Arbiser, MD, PhD Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

Cesar A. Arias, MD, MSc, PhD Department of Dermatology, University of Texas Medical School at Houston, Houston, TX, USA

Cheryl A. Armstrong, MD Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA

Anita Arora, MD Department of Dermatology, University of Texas Health Science Center, Houston, TX, USA

Sergei P. Atamas, MD, PhD Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

Brenda L. Bartlett, MD University of Maryland School of Medicine, Baltimore, MD, USA

Donald V. Belsito, MD Clinical Professor of Medicine (Dermatology), University of Missouri-Kansas City, Kansas City, MO, USA

Emily M. Berger, BA Tufts University School of Medicine, Boston, MA, USA

xi xii Contributors

Brian Berman, MD, PhD Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA

Thomas Bieber, MD, PhD Department of Dermatology and Allergy, Friedrich Wilhelms University, Bonn, Germany

Donna Bilu Martin, MD Department of Dermatology, University of Maryland, Baltimore, MD, USA

Doerte Bittner, MD Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany

Andrew Blauvelt, MD Department of Dermatology and the Department of Molecular Microbiology and Immunology, Oregon Health and Science University and Dermatology Service, Portland, OR, USA

Raymond E. Boissy, PhD Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Jan D. Bos, MD, PhD, FRCP Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Mariah R. Brown, MD Department of Dermatology, University of Colorado at Denver and Health Sciences Center, Aurora, CO, USA

Julie Burnett, MD Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Todd V. Cartee, MD Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

Mei Chen, PhD Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Bernard A. Cohen, MD Department of Dermatology, Johns Hopkins Outpatient Center, Baltimore, MD, USA

Jennifer Z. Cooper, MD University of Maryland School of Medicine, Baltimore, MD, USA Contributors xiii

Edward W. Cowen, MD, MHSc Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Noah Craft, MD, PhD, DTMH Divisions of Dermatology and Adult Infectious Diseases, David Geffen School of Medicine at UCLA and Los Angeles Biomedical Research Institute, Torrance, CA, USA

Ponciano D. Cruz, Jr., MD Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, USA

Luis A. Diaz, MD Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Ilia Elenkov, MD Institute of Neurobiology and Molecular Medicine, Rome, Italy

Alexander Enk, MD, PhD Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany

Clemens Esche, MD Department of Dermatology, Johns Hopkins Outpatient Center, Baltimore, MD, USA

David F. Fiorentino, MD, PhD Assistant Professor of Dermatology and Medicine (Rheumatology), Stanford University School of Medicine, Stanford, CA, USA

Levi E. Fried, BA Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

Anthony A. Gaspari, MD Department of Dermatology, University of Maryland School of Medicine, Baltimore, MD, USA

Aron J. Gewirtzman, MD Department of Dermatology, Center for Clinical Studies, Houston, TX, USA

Amos Gilhar, MD Skin Research Laboratory, Technion-Israel Institute of Technology, Haifa, Israel

Michael Girardi, MD Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA xiv Contributors

Laura M. Gober, MD Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Alice B. Gottlieb, MD, PhD Department of Dermatology, Tufts–New England Medical Center, Boston, MA, USA

Richard D. Granstein, MD Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York–Presbyterian Hospital, New York, NY, USA

Gary M. Halliday, BSc (Hons), PhD, DSc Dermatology Research Laboratories, University of Sydney, Sydney, New South Wales, Australia

Christopher Hansen, MD Department of Dermatology, University of Utah, Salt Lake City, UT, USA

Ulrich R. Hengge, MD, MBA Department of Dermatology, Heinrich-Heine University, Duesseldorf, Germany

Sherrif F. Ibrahim, MD, PhD Department of Dermatology, University of Rochester, Rochester, NY, USA

Camille E. Introcaso, MD Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Nahed Ismail, MD, PhD Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

Heidi T. Jacobe, MD Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, USA

H. Ray Jalian, MD Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Richard S. Kalish, MD, PhD† Department of Dermatology, Stony Brook University Medical Center, Stony Brook, NY, USA

† Deceased. Contributors xv

Ellen J. Kim, MD Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Jenny Kim, MD, PhD Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Sidney Klaus, MD Department of Dermatology, VA Medical Center, Dartmouth Medical School, White River Junction, VT, USA

Marcelo G. Label, MD Department of Dermatology, Hospital Ramos Mejía, Buenos Aires, Argentina

Zelmira Lazarova, MD Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA

Mark Lebwohl, MD Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA

Erica Lee, MD Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York–Presbyterian Hospital, New York, NY, USA

Benjamin A. Lefkove, BA Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

Justin J. Leitenberger, BS Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, USA

I. Caroline Le Poole, PhD Department of Pathology, Loyola University Medical Center Maywood, IL, USA

Ning Li, PhD Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Zhi Liu, PhD Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Kurt Q. Lu, MD Department of Dermatology, University Hospitals Case Medical Center Case Western Reserve University, Cleveland, OH, USA xvi Contributors

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

Irina G. Luzina, MD, PhD Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

Michael R. McGinnis, PhD, ABMM Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

Natalia Mendoza, MD Department of Dermatology, Universidad El Bosque, Bogota, Colombia

Lloyd S. Miller, MD, PhD Division of Dermatology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Fergal J. Moloney, MD, MRCPI Dermatology Research Laboratories, University of Sydney, Sydney, New South Wales, Australia

Kelly Nelson, MD Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

Frank O. Nestle, MD St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, Kings’ College London School of Medicine at Guy’s Kings’ College and St. Thomas Hospitals, London, UK

James J. Nordlund, MD Department of Dermatology, Wright State Boonshoft School of Medicine, Dayton, OH, USA

Carlos H. Nousari, MD Department of Dermatology, University of Miami, Miami, FL, USA

Ralf Paus, MD Department of Dermatology, University Hospital Schleswig-Holstein, Luebeck, Germany; Department of Cutaneous Medicine, School of Translational Medicine, University of Manchester, Manchester, UK

Oliver A. Perez, MD Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA

Julia Prölss, MD Department of Dermatology and Allergy, Friedrich Wilhelms University, Bonn, Germany Contributors xvii

Jennifer Remington, MD Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Stephen K. Richardson, MD Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Steven Richardson, MD Oakwood Hospital, Dearborn, MI, USA

Scott Roberts, PhD Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA

Alain H. Rook, MD Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Sarbjit S. Saini, MD Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Carolyn Senavsky, MD Division of Dermatology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Richard D. Sontheimer, MD Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

Martin Steinhoff, MD, PhD Department of Dermatology, University of Münster, Münster, Germany

Craig K. Svensson, PharmD, PhD College of Pharmacy, Nursing and Health Sciences, Purdue University West Lafayette, IN, USA

Robert A. Swerlick, MD Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA

Francisco A. Tausk, MD Department of Dermatology and Psychiatry, University of Rochester School of Medicine, Rochester, NY, USA

Marcel B.M. Teunissen, PhD Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands xviii Contributors

Anne Marie Tremaine, MD Department of Dermatology, Center for Clinical Studies, Houston, TX, USA

Stephen K. Tyring, MD, PhD, MBA Department of Dermatology, University of Texas Medical School at Houston, Houston, TX, USA

Mark C. Udey, MD, PhD Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Annemarie Uliasz, MD Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA

Guy F. Webster, MD, PhD Jefferson Dermatology Associates, Philadelphia, PA, USA

Stephen E. Wolverton, MD Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA

David T. Woodley, MD Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Kim B. Yancey, MD Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, USA