The 2013/2014
Dermatology In-Review
Study Guide
Companion to the
Dermatology In-Review
Online Study System
Edited by

C. W...
The questions and answers, statements or opinions contained in this Study Guide or Web Site
have not been approved by Gald...
K E Y

F E A T U R E S

The 2013/2014 Dermatology In-Review Study Guide is formatted for quick study and easy
reference. T...
K E Y

F E A T U R E S

Shaded Text
Shaded text emphasizes certain words or phrases that should be focused on. It is prese...
Dear Colleague,
With great pleasure we provide you with the 2013/2014 Dermatology In-Review
Study Guide from Educational T...
F A C U L T Y
Authors
Andrew F. Alexis, MD, MPH
Director, Skin of Color Center
St. Luke’s-Roosevelt Hospital
Assistant Cli...
F A C U L T Y

Erika Gaines Levine, MD

Maria Patricia Rivas-Bondavalli, MD

Private Practice
Haddonfield, NJ

Private Pra...
F A C U L T Y

L. Magaly Villafradez-Diaz, MD
Research Fellow, Mohs, Dermatologic and
Laser Surgery Department of Dermatol...
Contents
Chapter 1 	

Basic Science and Structure of Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
4.14	 Lichen Sclerosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...
5.15	Histiocytoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...
Chapter 9 	

Pediatric Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...
Chapter 15 	

Dermatologic and Cosmetic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
1 Basic Science and Structure of Skin
Kelley Redbord, MD
Peter Schalock, MD
Bruce E. Strober, MD, PhD

C o n t e n t s
1.1...
1.1 EPIDERMIS
Epidermis
•	 Compliled of the following cells:
–  Keratrocytes - 80%
–  Melanocytes - base layer
–  Langerha...
Table 1–2.  Keratin Expression Patterns
Type II Type I

Location

Hereditary Disease Association

1

Suprabasal keratinocy...
• Integrins regulate adhesion and initiation of differentiation
• Not all basal cells have potential to divide
• Stem cell...


•  amellar granules—A type of membrane bound uTIP
L
a amellar granules deliver lipid precursors into
L
intracellular st...
– Degraded into urocanic acid and pyrrolidone
carboxylic acid;  both hydrate stratum corneum
and block UV radiation
– Stor...
Figure 1-1. Skin Adhesion Molecules with Corresponding Diseases

8  2013/2014  Dermatology In-Review  l  Committed to Your...
Table 1-4.  Epidermolysis Bullosa
Condition

Defect

EBS

K5, K14, plectin

EBS –herpetiformis (Dowling Meara)

K5, K14 (h...
Table 1-5. Keratinocyte Integrin Receptors
Integrin

Ligand

b1 Family
a1b1

Fibrillar collagen, laminin

a2b1

Fibrillar ...
– Expression limited to basal layer of epidermis
– Coordinates linkage between intermediate filaments and extracellular ma...
Sublamina Densa
Type VII Collagen
• Targeted auto-antigen in epidermolysis bullosa acquisita and bullous lupus erythematos...
• Spheroid melanosomes produce yellow or red pheomelanin; have microvesicular internal 	
structure
•  elanin transfer invo...
• Two stages in the Langerhans life cycle:
1.) In epidermis, ingest and process antigens, are weak     
     stimulators o...
Table 1–6.  Types of Collagen and Tissue Distribution
I (85%)

Mature Skin, Bone, Tendon (except bone marrow
and cartilage...
• Returns skin to normal configuration after being stretched
• Elastic fibers: 90% elastin, wrapped by fibrillin microfibr...
Papillary Dermis
• Young or healthy skin: small diameter collagen fibrils and oxytalan elastic fibers
• Aging or actinical...
and eosinophilic chemotactic factor of anaphylaxis. Produce IL-8 (strong neutrophil chemotactic factor) - Produce PqD2 and...
Linear IgA Disease
• BPAg2 (180kD) (Collagen XVII) - may be the 97 kd fragment

Subcorneal Pustular Dermatosis (IgA Pemphi...
• Fibrin and fibronectin act as provisional matrix for infiltrating monocytes, fibroblasts, and
newly formed blood vessels...
•  igration is a result of a combination of chemotactic factors, direct guidance by contact,
M
and loss of nearest neighbo...
•  ibrin: First extracellular matrix to be deposited; for effective hemostasis, interaction must
F
occur with platelets (v...
•  ritical line of Auber: Widest diameter of the bulb; bulk of mitotic activity that gives rise to
C
the hair and the inne...
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  1. 1. The 2013/2014 Dermatology In-Review Study Guide Companion to the Dermatology In-Review Online Study System Edited by C. William Hanke, MD, MPH, FACP Associate Editors Michael K. Lichtman, MD Cynthia Bartus, MD Emily Tierney, MD Aimee L. Leonard, MD Ross Levy, MD Sherry Hsiung, MD Bruce Strober, MD   Sponsored by
  2. 2. The questions and answers, statements or opinions contained in this Study Guide or Web Site have not been approved by Galderma Laboratories, L.P., and Galderma Laboratories, L.P. will not be held responsible for any questions and answers, statements or opinions, contained in the Study Guide, Web Site, or any supplementary materials. Any questions about the content of Dermatology In-Review should be directed to Educational Testing and Assessment Systems, Inc. which controls the content and owns all copyrights in the materials. All components are intended for use by U.S. dermatology physicians only. The publishers of this guide will use reasonable efforts to include up-to-date and accurate information on this guide, but make no representations, warranties, or assurances as to the accuracy, currency or completeness of the information provided. The publishers of this guide shall not be liable for any damages or injury resulting from your access to this guide, or from your reliance on any information provided in this guide. This guide is intended for U.S. physicians only and is not in any means intended for use by the general public. ISBN 978-0-9858025-0-9 © 2013 Published by Educational Testing and Assessment Systems, a product of SanovaWorks Edited by C. William Hanke MD, MPH, FACP All rights reserved. No part of this book may be reproduced in any form or by any means, without permission in writing from the publisher. Printed in the United States of America
  3. 3. K E Y F E A T U R E S The 2013/2014 Dermatology In-Review Study Guide is formatted for quick study and easy reference. The below elements will appear throughout the text to aid in the preparation for your exams. Note that the Study Guide intentionally uses redundancy to further your learning by repetition. Tip Boxes Tip Boxes highlight exam-relevant information for quick study. u TIP P ahenol is cardiotoxic, nephrotoxic and hepatotoxic. Patients must have cardiac monitoring during phenol peeling to detect cardiac arrhythmias a hemical peeling of the neck is generally avoided C because of the risk of hypertrophic scarring Call-Outs Look for the Call-Out arrows within the text. They are used in different ways to highlight key information. Call-Out arrows can be seen before pertinent bullet points throughout the chapters.  •  Seen in Birt-Hogg-Dube Keep an eye out for arrows sitting in a shaded box. These signify more than one important bullet point.  • Caused by a deficiency in uropoprhyrinogen decarboxylase (UROD); may be inherited, sporadic or associated with Hepatitis C • Sporadic form may occur in association with HCV; in one study 82% of patients with PCT had HCV-antibodies Call-Outs may also appear before paragraphs. When this is seen, the whole paragraph is high-yield information. It is defined as a sudden appearance and increment in size of multiple SKs. The eruption is classically described to appear in a “Christmas tree” pattern and may occur anywhere in the body; however; the most common location is the back and the chest. Its association with an internal malignancy remains controversial.  Red Text The online study guide features red text which indicates that the material is NEW for the 2013/2014 year. Reference Chapter 16 for an example. iv  2013/2014 Dermatology In-Review l Committed to Your Future
  4. 4. K E Y F E A T U R E S Shaded Text Shaded text emphasizes certain words or phrases that should be focused on. It is presented in a variety of ways: within Call-Outs, in tables, and throughout the chapter’s text. It is defined as a sudden appearance and increment in size of multiple SKs. The eruption is classically described to appear in a “Christmas tree” pattern and may occur anywhere in the body; however; the most common location is the back and the chest. Its association with an internal malignancy remains controversial. Mnemonic Boxes Helpful mnemonic memory cues are displayed in Mnemonic Boxes throughout the chapters. MNEMONIC Subepidermal Split PLAID Pemphigoid (bullous) Lupus (bullous SLE) Acquisita (EBA) IgA, linear Dermatitis herpetiformis Pearl Boxes Pearl Boxes are used to stress information that is commonly found on exams. PEARL w ariant: Brunsting-Perry pemphigoid: no mucosal V involvement, blisters on patches of erythema on head/neck with scarring/scarring alopecia w reatments: Topical/intralesional/PO steroids, T dapsone, cyclophosphamide, azathioprine Note Pages Each chapter is followed by a series of Note Pages that should be used for your own annotations, study tips, and mnemonics. These pages should be taken out of your three-ring binder each year and placed in your new edition of Dermatology In-Review. Key Features  v
  5. 5. Dear Colleague, With great pleasure we provide you with the 2013/2014 Dermatology In-Review Study Guide from Educational Testing and Assessment Systems (ETAS), a product of SanovaWorks. Authored by over 20 leading academic faculty from all the various fields within dermatology, the contributing authors have provided a study guide that is essential for residents seeking comprehensive yet concise Board review material. The purpose of this study guide is to provide a source of high-yield Board study content to be used with the Online Study System (DermatologyInReview.com/Galderma). Together these tools provide relevant information and methods to prepare you for your exams. This program has been made possible through the support of Galderma Laboratories, L.P. We are grateful for their commitment to education. Good luck on your exams! Sincerely, C. William Hanke, MD, MPH, FACP Professor of Dermatology University of Iowa Carver College of Medicine Iowa City, IA Clinical Professor of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis, IN vi  2013/2014 Dermatology In-Review l Committed to Your Future
  6. 6. F A C U L T Y Authors Andrew F. Alexis, MD, MPH Director, Skin of Color Center St. Luke’s-Roosevelt Hospital Assistant Clinical Professor of Dermatology Columbia University College of Physicians Surgeons New York, NY Sonal Choudhary, MD Post-Doctoral Research Fellow, Department of Dermatology and Cutaneous Surgery University of Miami, Miller School of Medicine Miami, FL George W. Elgart, MD Professor of Dermatology Director of Dermatopathology Department Department of Dermatology and Cutaneous Surgery University of Miami School of Medicine Miami, FL Adam Friedman, MD, FAAD Director of Dermatologic Research Director of the Basic Science/Translational Research Fellowship Associate Residency Program Director Albert Einstein College of Medicine Bronx, NY Anthony Gaspari, MD Chairman of Dermatology Director, Cutaneous Immunopathology Laboratory Professor of Dermatology University of Maryland Medical Center Baltimore, MD Valerie Harvey, MD Assistant Professor of Dermatology Eastern Virginia Medical School Norfolk, VA Alysa R. Herman, MD Voluntary Instructor of Dermatology and Cutaneous Surgery University of Miami School of Medicine Miami, FL Eric Huang, MD, PhD Private Practice New York, NY Ming H. Jih, MD, PhD DermSurgery Associates Houston, TX Arash Kimyai-Asadi, MD DermSurgery Associates Houston, TX Christine J. Ko, MD Associate Professor of Dermatology and Pathology, Department of Dermatology Yale University New Haven, CT Evelyn K. Koestenblatt, MS, MT (ASCP) Clinical Research Administrator, Department of Opthalmology and Visual Sciences Montefiore Medical Center Bronx, NY Jennifer Ledon, MD Medical Student Research Fellow University of Miami Miller School of Medicine Department of Dermatology Cutaneous Surgery Miami, FL Faculty  vii
  7. 7. F A C U L T Y Erika Gaines Levine, MD Maria Patricia Rivas-Bondavalli, MD Private Practice Haddonfield, NJ Private Practice Hollywood, FL William R. Levis, MD Ellen Roh, MD Clinical Assistant Professor, Departments of Medicine and Dermatology New York University Langone Medical Center New York, NY Instructor of Dermatology Harvard Medical School/Massachusetts General Hospital, Department of Dermatology Boston, MA Michael K. Lichtman, MD Jessica Savas, MD Assistant Professor of Dermatology Boston University School of Medicine Boston, MA Medical Student Research Fellow University of Miami Miller School of Medicine Department of Dermatology Cutaneous Surgery Miami, FL Jeffrey L. Marx, MD Clinical Associate Professor, Department of Dermatology New York University Langone Medical Center New York, NY Keyvan Nouri, MD Associate Professor of the Department of Dermatology and Otolaryngology Director of the Mohs, Dermatologic and Laser Surgery Director of Surgical Training for the Department of Dermatology and Cutaneous Surgery University of Miami School of Medicine Miami, FL Georgia B. Schuller-Levis, PhD Head - Laboratory of Cellular Immunology Department of Immunology New York State Institute for Basic Research Staten Island, NY Peter C. Schalock, MD Assistant Professor of Dermatology Harvard Medical School/Massachusetts General Hospital, Department of Dermatology Boston, MA Bruce E. Strober, MD, PhD Jennifer B. Perone, MD Assistant Professor New York University Langone Medical Center New York, NY Surgical Dermatology Associates, PA Denton, TX Jeffrey M. Weinberg, MD Private Practice Coronado, CA Attending, Department of Dermatology St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center New York, NY Kelley Pagliai Redbord, MD Voraphol Vejjabhinanta, MD Dermatology and Dermatologic Surgery Group of Northern Virginia Vienna, VA Post-doctoral Fellow in Mohs, Laser and Dermatologic Surgery, Department of Dermatology and Cutaneous Surgery Dori Rausch, MD viii  2013/2014 Dermatology In-Review l Committed to Your Future
  8. 8. F A C U L T Y L. Magaly Villafradez-Diaz, MD Research Fellow, Mohs, Dermatologic and Laser Surgery Department of Dermatology and Cutaneous Surgery University of Miami School of Medicine Miami, FL Katherine L. White, MD Northampton Dermatology Associates Northampton, MA Andrea L. Zaenglein, MD Associate Professor of Dermatology and Pediatrics Penn State/Milton S. Hershey Medical Center Hershey, PA Priya Swamy Zeikus, MD Private Practice Faculty at Univeristy of Texas Southwestern Medical School Dallas, TX Resident Advisory Board Taylor DeFelice, MD, MPH 2011/2012 Chief Resident New York University School of Medicine Program New York, NY Alicia Ogram, MD 2011/2012 Chief Resident Washington Hospital Center/Georgetown University Washington, DC Special Recognition Cynthia Bartus, MD Dermatology In-Review Cram Pack Updates Private Practice Atlanta, GA Adam Friedman, MD Workshop Chapter Editor Exam Cram Live Moderator and Contributor Dermatology In-Review Reviewer Director of Dermatologic Research Director of the Basic Science/Translational Research Fellowship Associate Residency Program Director Albert Einstein College of Medicine Bronx, NY John G. Hancox, MD Dermatology In-Review Cram Pack/Boot Camp Mountain State Dermatology Clarksburg, WV Christine Liang, MD Dermatology In-Review Exam Cram Pack Update Clinical Instructor, Department of Dermatology Brigham and Women’s Hospital Boston, MA Stephen Z. Smith, MD Dermatology In-Review Recertification Cram Pack Update Private Practice Louisville, KY William E. Rietkerk, MD, MBA 2011/2012 Chief Resident New York Medical College Metropolitan Hospital Center New York, NY Faculty  ix
  9. 9. Contents Chapter 1  Basic Science and Structure of Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Epidermis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Dermis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 1.3 Antigens Implicated in Autoimmune Diseases and Other Annoying Factoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 1.4 Wound Healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1.5 Maturational. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 1.6 Hair Follicle Biology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 1.7 Sebaceous Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.8 Eccrine Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.9 Apocrine Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.10 Nails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.11 Nerves and Receptors of the Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.12 Immunofluorescence Patterns - Direct. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 1.13 Connective Tissue Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Chapter 2  Immunodermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.1 The Innate and Adaptive Immune Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 2.2 Cells of the Innate and Adaptive Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 2.3  Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 2.4  Antibodies and Complement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 2.5  Major Histocompatibility Complex and HLA Disease Associations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 2.6  Non-Steroidal Immunologic Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Chapter 3 Genodermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3.1 X-linked Recessive Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.2 X-linked Dominant Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.3 Hereditary Blistering Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.4 Ichthyoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 3.5 Palmoplantar Keratodermas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.6 Disorders with Hypopigmentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 3.7 Disorders with Pigmented Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 3.8 Vascular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.9 Connective Tissue Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3.10 Diseases of the Hair and Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 3.11 Diseases with Malignant Potential. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 3.12 Disorders with Immunodeficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 3.13 DNA and Chromosomal Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 3.14 Keratinopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 3.15 Disorders of Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Chapter 4  General Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 4.1 Acne Vulgaris. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 4.2 Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.3 Psoriasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.4 Psoriatic Arthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 4.5 Reiter’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 4.6 SAPHO Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 4.7 Sneddon-Wilkinson Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 4.8 Lichen Planus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 4.9 Atopic Dermatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 4.10 Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 4.11 Alopecia: Other Forms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 4.12 Vitiligo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 4.13 Pityriasis Rubra Pilaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 x  2013/2014 Dermatology In-Review l Committed to Your Future
  10. 10. 4.14 Lichen Sclerosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 4.15 Granuloma Annulare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 4.16 Hirsutism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 4.17 Amyloidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 4.18 Calciphylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 4.19 Angioedema. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 4.20 Carcinoid Syndrome and Flushing Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 4.21 Lupus Erythematosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 4.22 Scleroderma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 4.23 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 4.24 Sjogren’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 4.25 Connective Tissue Disease: Serology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 4.26 Relapsing Polychondritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 4.27 Behçet’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 4.28 Livedo Reticularis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 4.29 Leukocytoclastic Vasculitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 4.30 Cryoglobulinemia and Cryofibrinogenemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4.31 Acanthosis Nigricans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 4.32 Lipodystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.33 Hyperlipoproteinemias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 4.34 Xanthomatosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 4.35 Vitamin Deficiencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 4.36 Diabetes and Skin Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.37 Langerhans Cell Histiocytosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 4.38 Cutaneous T-Cell Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 4.39 Pyoderma Gangrenosum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 4.40 Sweet’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 4.41 Erythema Annulare Centrifugum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 4.42 Erythema Elevatum Diutinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 4.43 Erythema Nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 4.44 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 4.45 Cutaneous Sarcoidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 4.46 Perforating Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 4.47 Elastosis Perforans Serpiginosa. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 4.48 Reactive Perforating Collagenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 4.49 Cutaneous Features and Disorders of Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 4.50 Pruritus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 4.51 Scleredema. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 4.52 Nephrogenic Fibrosing Dermopathy/Nephrogenic Systemic Fibrosis. . . . . . . . . . . . . . . . . . . . . . . . . 151 Chapter 5 Dermatopathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 5.1 Normal Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 5.2 Stains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 5.3 Immunohistochemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 5.4 Acantholytic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 5.5 Adnexal/Epithelial Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 5.6 Alopecias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 5.7 Bullous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 5.8 Cysts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 5.9 Deposition Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 5.10  Drug Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 5.11  Fat Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 5.12 Fibrous/Fibrohistiocytic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 5.13 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 5.14 Granulomatous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 Table of Contents  xi
  11. 11. 5.15 Histiocytoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 5.16 Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 5.17 Inflammatory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 5.18 Lymphomas and Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 5.19  Melanocytic Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197 5.20 Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 5.21 Neural. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 5.22 Pagetoid Spread. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 5.23 Palisading Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 5.24 Vascular. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 5.25 Miscellaneous. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208 5.26 Clues for Board Purposes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 5.27 “Bodies”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 Chapter 6  Benign and Malignant Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 6.1 Seborrheic Keratosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 6.2 Actinic Keratosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 6.3 Bowen’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227 6.4 Non-melanoma Skin Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 6.5 Basal Cell Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 6.6 Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232 6.7 Keratoacanthoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 6.8 Malignant Melanoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 6.9 Merkel Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241 6.10 Cutaneous T-Cell Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 6.11 Angiosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 6.12 Desmoplastic Trichoepithelioma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 6.13 Dermatofibrosarcoma Protuberans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248 6.14 Microcystic Adnexal Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 Chapter 7 Medical Mycology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257 7.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 7.2 Superficial Mycoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 7.3 The Dermatophytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 7.4 Subcutaneous Mycosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 7.5 Dimorphic Fungi Causing Systemic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277 7.6 Opportunistic Organisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 7.7 Miscellaneous Organisms Causing Fungus-like Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 7.8 Chapter 8  Random Facts and Summary Table. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 Infectious Diseases of the Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 8.1 Bacterial Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 8.2 Viral Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 8.3 Mycobacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303 8.4 Sexually Transmitted Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 8.5 Nonvenereal Trepanomatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 8.6 Parasitic Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 8.7 Rickettsial Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 xii  2013/2014 Dermatology In-Review l Committed to Your Future
  12. 12. Chapter 9  Pediatric Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 9.1 Neonatal and Infantile Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 9.2 Childhood Infectious Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 9.3 Pigmented Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 9.4 Dermal Tumors and Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 9.5 Vascular Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 9.6 Genodermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 Chapter 10  Cutaneous Manifestations of Systemic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 10.1 Cutaneous Manifestations of Hepatitis C Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 10.2 Cutaneous Manifestations of Thyroid Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 10.3 Cutaneous Manifestations of Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 10.4 Cutaneous Manifestations of Gastrointestinal Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 10.5  Cutaneous Manifestations of Neurologic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 10.6  Cutaneous Manifestations of Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 10.7 Cutaneous Manifestations of Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380 10.8 Porphyrias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389 Chapter 11  Disorders of the Hair and Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397 11.1 Hair Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399 11.2 Hirsutism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410 11.3 Hypertrichosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412 11.4 Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413 Chapter 12 Bullous and Vesicular Dermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423 12.1 Molecular Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 12.2 Microscopic Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427 12.3 Bullous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428 12.4 Diseases that Can Present with Bullae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 12.5 Vesicular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 12.6 Common Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439 12.7 Plant Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441 12.8 Tips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442 12.9 Plant Irritants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443 Chapter 13  Photobiology and Photosensitivity Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .447 13.1 Basic Facts about Ultraviolet Light. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449 13.2 Photoimmunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450 13.3 Phototesting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 13.4 Idiopathic Photosensitivity Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 13.5 Photosensitivity from Exogenous Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 13.6 Diseases Exacerbated by Sunlight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 13.7 Phototherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 13.8 Photochemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 13.9 Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 Chapter 14  Plants and Creatures of Dermatologic Significance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465 14.1 Plant Dermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467 14.2 Dermatologic Diseases Caused by Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 14.3 Lice, Spiders, Bugs, and Other Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475 14.4 Ticks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481 14.5 Mites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 14.6 Exotic Pets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485 14.7 Skin Eruptions Caused by Marine Life. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486 14.8 Medications Derived from Plants and Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 Table of Contents  xiii
  13. 13. Chapter 15  Dermatologic and Cosmetic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 15.1 Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499 15.2 Anesthetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505 15.3 Antimicrobial Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507 15.4 Prophylactic Antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507 15.5 Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509 15.6 Sutures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512 15.7 Flaps and Grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514 15.8 Chemical Peels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517 15.9 Botox and Cosmetic Fillers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 518 15.10 Photoaging and Cosmeceutical Rejuvenation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519 15.11 Liposuction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519 15.12 Lasers and Radiofrequency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 520 15.13 Mohs Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522 15.14 Chemotherapeutic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523 15.15 Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523 15.16 On the Horizon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 524 Chapter 16 Dermatopharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531 16.1 Antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 16.2 Antivirals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536 16.3 Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538 16.4 Topical and Systemic Corticosteroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540 16.5 Cytotoxic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540 16.6 Immunosuppressants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543 16.7 Dapsone and Sulfapyridine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543 16.8 Antimalarials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544 16.9 Retinoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545 16.10 Sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546 16.11 Antiparasitics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547 16.12 Antihistamines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 16.13 Hormone-related Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548 16.14 Miscellaneous Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 16.15 Biologic Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 550 16.16 Drugs in Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 16.17 Drug Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553 16.18 Drug Vehicles and Absorption Mechanism of Actions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 556 Chapter 17 Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 2003. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 567 2004. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 2005. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578 2006. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585 2007 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591 2008. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598 2009. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605 2010. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611 2011. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 618 2012. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 627 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635 xiv  2013/2014 Dermatology In-Review l Committed to Your Future
  14. 14. 1 Basic Science and Structure of Skin Kelley Redbord, MD Peter Schalock, MD Bruce E. Strober, MD, PhD C o n t e n t s 1.1 1.2 Dermis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 1.3 Antigens Implicated in Autoimmune Diseases and Other Annoying Factoids . . . . . . . . . . . . . . . . . . 18 1.4 Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1.5 Maturational . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 1.6 Hair Follicle Biology . . . . . . . . . . . . . . . . . . . . . . . . . . 22 1.7 Sebaceous Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.8 Eccrine Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.9 Apocrine Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.10 Nails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.11 Nerves and Receptors of the Skin . . . . . . . . . . . . . . 27 1.12 Immunofluorescence Patterns - Direct . . . . . . . . . 28 1.13 Report a Problem/Feedback Epidermis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Connective Tissue Diseases . . . . . . . . . . . . . . . . . . . 30 Basic Science and Structure of Skin    1
  15. 15. 1.1 EPIDERMIS Epidermis • Compliled of the following cells: –  Keratrocytes - 80% –  Melanocytes - base layer –  Langerhans cells suprabasal 2-8% –  Merkel cells basal layer Keratinocyte  • Ectodermal derivation during first few weeks of embryonic dulp • 90% of total population of epidermis • 30 different keratins: 20 epithelial and 10 nail keratins - 40–70 kD –  Bind to each other in the rod region • Acidic keratins: K9–K20, chromosome 17 • Basic keratins: K1–8, chromosome 12 • Intermediate Filaments (see also Bullous and Vesicular Dermatoses chapter) –  Type I = acidic keratins 9–20, chromosome 17 –  Type II = basic keratins 1–8, chromosome 12 –  Type III = vimentin, glial fibrillary acidic protein (GFAP), desmin, peripherin –  Type IV = neurofilaments –  Type V = nuclear lamins –  Type VI = nestin Table 1-1. Intermediate Filaments Type 1 Type 2 Type III Type VI Type V Others Keratins Keratins Vimentin NF-L Lamin A/C Filensin Desmin NF-H Lamin B1 Phakinin GFAP NF-M Lamin B2 Periperin a-Internexin Syncoilin Nestin Synemin • Keratinocytes are able to release, respond to, uTIP a cidic and basic keratins are co-expressed in order to A and produce TNF-alpha. Causes increased form filamentous structure - obligate heteropolymers” differentiation (Bikle, 1991) Report a Problem/Feedback Basic Science and Structure of Skin    3
  16. 16. Table 1–2. Keratin Expression Patterns Type II Type I Location Hereditary Disease Association 1 Suprabasal keratinocytes Ichthyosis hystrix of Curth-Macklin Diffuse non-epidermolytic PPK (Unna-Thost) 1 10 Suprabasal keratinocytes Bullous congenital ichthyosiform erythroderma, EHK (corrugated scale) 1 9 Palmoplantar suprabasalar keratinocytes Epidermolytic PPK, diffuse nonepidermolytic PPK 2e 10 Upper spinous and granular layers Ichthyosis bullosa of Siemens (milder EHK) 3 12 Cornea Meesmann’s corneal dystrophy 4 13 Mucosal epithelium White sponge nevus (Cannon) - buccal 5 14 Basal keratinocytes Epidermolysis bullosa simplex 1.) Dowling Meara (head or tail of central rod domain) 2.) Koebner (segment 1a or 2b of rod domain) 3.) Weber Cockayne (nonhelical parts) 5 15 Mucosal basal layer 6a 16 Outer root sheath, hyperproliferative Pachyonychia congenita Jadassohn Lewandowsky keratinocytes type I, focal nonepidermolytic PPK 6b 17 Nail bed Pachyonychia congenita type II, steatocystoma multiplex (Jackson-Lawler) 8 18 Simple epithelium Cryptogenic cirrhosis Hair follicle Monilethrix 19 Bulge cells simple epithelium Paget's = ck7, ck20 20 Merkel cell carcinoma hHb1 b6 1 16 Non epidermolytic PPK 17 Steatocystoma Multiplex 5 EBS Mottled pigmentation (non helical V1 domain) 14 EBSC Autosomal recessive 14 Naegeli - Franceschetti - Jadassohn syndrome Stratum Germinativum (Basale) Basal cells contain ornithine decarboxylase (marker for proliferative activity) Stimulated by: trauma, UV, EGF, estrogens, β agonists, tumor promoters Inhibited by: protein deprivation in psoriatic skin (by retinoids and steroids) • The basal layer • K5 and K14 expressed - defective in epidermolysis uTIP a  eratin filaments in basal cells insert into K bullosa simplex desmosomes and hemidesmosomes • K19 found in basal cells at transitional boundaries between different types of epithelia •  icrofilaments (actin, myosin, and alpha-actinin) assist in upward movement of cells as they M differentiate 4  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  17. 17. • Integrins regulate adhesion and initiation of differentiation • Not all basal cells have potential to divide • Stem cells give rise to transient amplifying cells •  nce basal cell leaves basal layer in humans, normal transit time to stratum corneum is at O least 14 days, and transit through stratum corneum to desquamation requires 14 days, 28 days total Stratum Spinosum • Rounder nucleus, more flattened appearance • Contain lamellar granules • Lamellar granules contain ceramides • K5/K14 still present, but not made de novo in this layer • New synthesis of K1/K10 - keratinization-specific keratins, characteristic of epidermis, markers of terminal differentiation • n psoriasis, actinic keratoses, and wound healing suprabasal keratinocytes downregulate I K1/K10 and make K6/K16 (mRNA always present for K6/K16, but only translated during proliferation) • Hyperproliferative states k6, k16, ki-67, α3β, integrin • Desmosomes form “spines,” calcium-dependent structures that promote adhesion •  esmosomal plaque: Six polypeptides, plakoglobin, desmoplakins I and II, keratocalmin, D desmoyokin, demoyokin, and band 6 protein (see Table 1.2 for listing of desmosomal proteins and associated diseases) Table 1-3. Desmosomal Proteins Protein Plakoglobin Desmoplakin I/II Keratocalmin Desmoyokin band 6 protein Plakophilin Envoplakin Desmocalmin Desmoglein I Desmoglein III Desmocollin I Desmocollin III Location Plaque Plaque Plaque Plaque Plaque Plaque Plaque Plaque Transmembrane Transmembrane Transmembrane Transmembrane Disease Association(s) Naxos syndrome Carvajal syndrome None described to date None described to date Ectodermal dysplasia/skin fragility syndrome Ectodermal dysplasia/skin fragility syndrome Paraneoplastic Pemphigus (210 kD antigen) None described to date AD Striate PPK/Pemphigus foliaceus Pemphigus vulgaris Subcorneal Pustular Dermatosis None described to date u TIP •  ransmembrane cadherins T a isease relating to gap junctions: D provide adhesive properties 26 Vohwinkel’s syndrome, KID syndrome, PPK with deafness - contain desmoglein I and III, 30.3 31 erythrokeratoderma variabilis intracellular domains link with intermediate filament 30 hidrotic ectodermal dysplasia cytoskeleton • Gap junctions more abundant in stratum spinosum compared to stratum basale – Communication between cells – More differentiated keratinocytes have more abundant gap junctions (few in basal cell layer) Report a Problem/Feedback Basic Science and Structure of Skin    5
  18. 18.  •  amellar granules—A type of membrane bound uTIP L a amellar granules deliver lipid precursors into L intracellular structure, 0.2–0.3 micrometers intercellular space: glycoproteins, glycolipids, in diameter; a lysosome with secretory funcphospholipids, free sterols, and glucosylceramides tion. They are lamellated bodies, containing ceramide, are found intracellularly in upper level keratinocytes; they discharge. Ceramide is the major lipid for barrier function of the skin – First appear in stratum spinosum, but primary activity in stratum corneum – Discharge their contents into the extracellular space at the junction of the granular and horny layers, establishing a barrier to water loss, and, with filaggrin, mediate stratum corneum adhesion – Deliver lipid precursors into intercellular space: glycoproteins, glycolipids, phospholipids, free sterols, and glucosylceramides (predominant lipid of stratum corneum) – Commonly used synonym is “Odland bodies” – Flegel’s disease—Decreased lamellar granules – Harlequin ichthyosis—Lamellar granules uniformly abnormal or absent. Defect in ABCA12 at 2q34 (also defective in lamellar ichthyosis type II) – X-linked ichthyosis—Steroid sulfatase missing in lamellar granules. Increased levels of the beta fraction of cholesterol sulfate can be identified by serum lipoprotein electrophoresis. Prenatal diagnosis can be accomplished by measurement of decreased estrogen levels and the presence of nonhydrolyzed sulfated steroids in maternal urine Stratum Granulosum • Keratohyalin granules contain profilaggrin (F granules) and loricrin (L granules contain loricrin at periphery and help form cornified cell envelope) + KIF • K1 modified to K2, and K10 to K11 by proteolysis and phosphorylation • Lamellar granules originated in golgi  •  ornified cell envelope (CE): Proteins synthesized in spinous/granular layers C – Durable, protein/lipid polymer formed within differentiating keratinocytes  – Eventually exists outside of cornified cells – Components include: • Envoplakin – Homologous to desmoplakin. May link the CE to desmosomes and to keratin filaments • Involucrin – Cross-linked by transglutaminase in granular layer to an insoluble cell boundary • Loricrin – In upper spinous layer and throughout the stratum granulosum – 75% of CE’s mass (major protein component of CE) – Vohwinkel syndrome variant associated – Filament aggregating activity – In Psoriasis: i loricrin, h involucrin, i filaggrin • Filaggrin (histadine rich) Filament Aggregating Activity - defect causes Ichthyosis vulgaris – Profilaggrin converted to monomeric filaggrin subunits when granular layer transformed to cornified layer; a calcium-dependent process – Thought to promote aggregation and disulfide bonding of keratin filaments in cornified cell (like a glue) 6  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  19. 19. – Degraded into urocanic acid and pyrrolidone carboxylic acid; both hydrate stratum corneum and block UV radiation – Stored in kit granule  •  ransglutaminase: 3 versions that function in T crosslinking the CE (calcium-dependent process). Forms gamma-glutamyl-lysine isodipeptide bonds in the CE, most prominently with involucrin u TIP Basal layer k5, 14 Spinous layer k1, 10 Lamellar granules (k6, 16 in psoriasis) k2, 11 Keratohyalin granules Granular layer Keratin filaments  –  G-1 (type K) - keratinocyte transglutaminase, membrane associated, defect causes lamelT lar ichthyosis type I (TGM1 gene) and non-bulluous congenital ichthyosiform erythroderma (T9M1 + ALOX12B + ALOXE3) – TG-2 (type C) - fetal epidermis and basal layer of adult epidermis, soluble – TG-3 - present in hair follicles and differentiated epidermal cells, soluble. Present in sublamina densa - antigen for dermatitis herpetiformis. 77 kDa •  rogrammed destruction of granular cell - loss of nucleus, yet retention of keratin filaments P and filaggrin matrix – Destruction involves apoptosis transition cells (“T” cells) – Terminal differentiation is initiated by increase in calcium gradient in suprabasal epidermis Stratum Corneum • Transition from Stratum Granulosum accompanied by loss of 45–86% in dry weight •  rovides mechanical protection, barrier to water loss and barrier preventing permeation of P environmental soluble substances • Keratin in filaggrin rich matrix • Normal SC cells have no nuclei; may persist in incompletely keratinized cells (parakeratosis) • Bricks - Corneocytes; Mortar-extracellular lipid matrix (from loricrin)/lamellar lipid barrier Epidermal Differentiation • Triggered by calcium • CE: 1.) crossed linked envoplakin, periplakin, involving along innes cell membrane, 2.) lamellar granule 6 extrusion into extracellular space 3.) loricrin crosslinks envelope 4.) keratin and filaggrin crosslink Report a Problem/Feedback Basic Science and Structure of Skin    7
  20. 20. Figure 1-1. Skin Adhesion Molecules with Corresponding Diseases 8  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  21. 21. Table 1-4. Epidermolysis Bullosa Condition Defect EBS K5, K14, plectin EBS –herpetiformis (Dowling Meara) K5, K14 (head or tail of central rod domain) EBS –Weber Cockayne (palms/soles) K5, K14 (nonhelical parts) EBS –Koebner K5, K14 (segment 1a or 2b of rod domain) EBS –muscular dystrophy Plectin JEB –lethal, Herlitz Laminin 5 (LAMB3 gene) JEB –pyloric atresia Alpha-6-Beta-4 integrin Dominant DEB (Cockayne Touraine, hyperplastic, Albopapuloid Pasini) atrophic white scars Collagen VII (Col 7A1) RDEB Hallopeau-Siemens Collagen VII (Col 7A1) Bart’s syndrome Collagen VII EB acquisita Collagen VII EBS - mottled pigmentation K5 (nonhelical VI domain) EBS -AR K14 Basement Membrane Zone (Refer to Figure 1-2) • Site of interaction between epidermis and dermis • Three layers – 1.) Lamina lucida, 2.) Lamina densa, 3.) Sub-lamina densa •  emidesmosomal adhesion complex: 1.) hemidesmosomal plaque, 2.) anchoring filaments, and H 3.) anchoring fibrils • Know the electron microscopy picture of the basement membrane zone Figure 1-2. Dermal-Epidermal Junction Components Report a Problem/Feedback Basic Science and Structure of Skin    9
  22. 22. Table 1-5. Keratinocyte Integrin Receptors Integrin Ligand b1 Family a1b1 Fibrillar collagen, laminin a2b1 Fibrillar collagen, laminin a3b1 Fibronectin, laminin 5, denatured collagen a5b1 Fibronectin a6b1 b4 Family Laminin a6b4 av Family Laminin 5 avb1 Fibronectin, vitronectin avb3 Vitronectin, fibronectin, fibrinogen, denatured collagen avb5 Vitronectin avb6 Fibronectin, tenascin Lamina Lucida Hemidesmosome • Attachment complex for basal keratinocytes and extracellular matrix •  lectron-dense domain on the ventral surface of basal keratinocytes - bridge cytoskeleton E and cutaneous basement membrane • Proteins: – BPAg1—230 kD protein (desmoplakin) noncollagenous glycoprotein • Intracellular at attachment plaque • Member of the plakin family and homologous to desmoplakin • Attaches intermediate filaments (keratins) to hemidesmosomal plaque • Belongs to the gene family including desmoplakin I – BPAg2—180 KD protein (collagen XVII) • Transmembrane protein • Interacts with BPAg1, beta-4 integrin, and plectin intracellularly  • ts NC16A domain (target of I u TIP autoantibodies in bullous pem- a isease Associations (see chapter 12 for more details) D phigoid) interacts with alpha-6 BPAg1/BPAg2-NC16A bullous pemphigoid integrin extracellularly BPAg2 lichen planus pemphigoides • Also interacts with laminin 5 portion of BPAg2 linear IgA disease extracellularly • Two forms: full-length BPAg2-NC16A herpes gestationis transmembrane and soluble 120 BPAg2 C terminal domain cicatricial kDa ectodomain that is shed pemphigoid from cell surface • Integrins: Transmembrane proteins – alpha-6-beta-4 integrin found at sites where keratin intermediate filaments attach 10  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  23. 23. – Expression limited to basal layer of epidermis – Coordinates linkage between intermediate filaments and extracellular matrix of the basement membrane – Beta-4 membrane proximal domain interacts with plectin and its distal domain interacts with BP180; absence of beta-4 prevents hemidesmosomal assembly – Extracellular alpha-6 domain binds laminin 5 – Defect in beta-4 seen in cicatricial pemphigoid with ocular involvement only – Defects in alpha-6-beta-4 results in JEB with pyloric atresia • Plectin: Member of the plakin family – Links intermediate filaments to the plasma membrane and crosslinks various hemidesmosomal proteins – Mutations result in epidermolysis bullosa simplex with muscular dystrophy Anchoring Filaments • Laminin 5 and BP180 are major components • Laminins – Glycoproteins with at least 14 members of the family – Cross-shaped assembly of three classes of polypeptides – Span from plasma membrane of basal keratinocytes to lamina densa – Two major roles: 1.) structural network in basement membrane to which other proteins attach; 2.) signaling – Molecules that interact with other proteins (such as integrins) to transmit morphogenetic information to the cell’s interior – Laminin 5 (major component of anchoring filaments; also called epiligrin) and laminin 6 isoforms are found in the DE junction of human skin and mucous membranes • Uncein – 19DEJ1-Ag – Associated with anchoring filaments • Fibronectin – Central function in wound healing – Secreted by myofibroblasts - stimulated by EGF and thrombin – Allows fibroblasts to adhere to ECM, provides “scaffolding” for collagen fibrils (Bolognia) and assists in wound contraction • Nidogen – Also called entactin – Dumbbell-shaped – Binds to laminin 1 Lamina Densa Type IV Collagen • Functions in structural support and confers flexibility to basement membrane • Highly cross-linked, forming a lattice • Primary component of anchoring plaques Heparan Sulfate Proteoglycan • Negatively charged, thus is a permeability barrier Report a Problem/Feedback Basic Science and Structure of Skin    11
  24. 24. Sublamina Densa Type VII Collagen • Targeted auto-antigen in epidermolysis bullosa acquisita and bullous lupus erythematosus • Mutated in dystrophic epidermolysis bullosa • Primary constituent of anchoring fibrils • Homotrimeric protein Anchoring Plaques • Composed of type IV collagen •  oint of attachment for anchoring fibrils composed of type VII collagen (from “above”) and P collagens I and III from the dermis “below” Melanocytes • Dendritic cell derived from neural crest •  ound in multiple tissues: epidermis, hair matrix, retinal pigment epithelium, ear (stria vascuF laris), leptomeninges, mucous membranes, ciliary body, choroid, iris, and enteric ganglion cells Skin Melanocytes • In skin, localized to basal layer of epidermis •  unctions include: melanin production (melanogenesis), arborize with processes that conF tact keratinocytes (epidermal melanin unit = approximately 36 keratinocytes in contact with one melanocyte), and transfer pigment to keratinocytes • Keratinocytes can produce both growth and inhibitor factors for melanocytes – Growth—beta-FGF and TGF-alpha – Inhibitory—IL-1, IL-6, TGF-beta • Be able to recognize a melanocyte on electron microscopy Melanin Synthesis •  yrosine-DOPA- DOPAquinone, both steps catalyzed by tyrosinase, a copper containing T enzyme • DOPAquinone converted to pheomelanin or eumelanin uTIP M •  yrosine hydroxylase is not expressed in melanocytes a elanin has two forms: T •  Eumelanin - brown-black, insoluble (only in neurons) •  heomelanin - red-yellow, alkali-soluble, P •  elanin absorbs and scatters ultraviolet radiation M sulfur-containing (280-400 nm), and thus protects from UV-induced a oth types of melanin made from tyrosine B via action of the enzyme tyrosinase DNA mutations Melanosomes • Stages of melanosomes – Stage 1: spherical – Stage 2: episoidal – Stage 3: matrix is melanized – Stage 4: melanization is completed • Contain melanin • Related to lysosomes: positioned after the Golgi apparatus in the secretory pathway •  lliptical melanosomes synthesize brown or black eumelanin; have longitudinally oriented, E concentric lamellae 12  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  25. 25. • Spheroid melanosomes produce yellow or red pheomelanin; have microvesicular internal structure •  elanin transfer involves the active phagocytosis of the dendritic tips of melanocytes by the M keratinocytes and hair cortex cells • Melanin distributed preferentially to more basally located keratinocytes • Oculocutaneous albinism (OCA) – Defect in melanin synthesis due to: • Tyrosinase (OCA1) (melanosomes arrest in stage I or II) • P-gene (OCA2) • TRP-1 gene (OCA3) Differences in Skin Color: More Darkly Pigmented Races Show • A greater production of melanosomes in the melanocytes • Individual melanosomes with a higher degree of melanization • Larger melanosomes • Higher degree of dispersion of melanosomes in the keratinocytes • A slower rate of melanosome degradation Hair Melanocytes • Melanin unit exists in proximal anagen bulb: one melanocyte and five keratinocytes •  ollicular melanogenesis coupled to hair growth cycle: melanocyte proliferation occurs during F early period of anagen • Hair follicle contains melanocyte precursors that can repopulate the interfollicular epidermis •  raying caused by gradual decline in the number of follicular melanocytes; influenced by G both age and genes • MC1-R gene mutations associated with red hair Merkel Cells • Mechanoreceptors at sites of high tactile sensitivity • Located at the basal level of the epidermis • Keratinocytic deformation induces secretion of chemokines by Merkel cells • Location varies: hair-bearing skin and glabrous skin of the digits and lips, oral cavity, and ORS hair follicle  • Keratin 20 (ck20) is a specific and reliable marker of Merkel cells and perinuclear dots •  ake synaptic connection with neurons (the Merkel cell-neurite complex); neurochemical M transmission occurs between an activated Merkel cell and its neuron Langerhans Cells •  one-derived, CD34+, antigen-processing and presenting cells of monocyte/macrophage B lineage migrate from bone marrow in embryonic development and continue to repopulate epidermis during lifetime •  ontains CD207 (Langerin) C •  ound in the skin and other epithelial tissues: oral mucosa, esophagus, vagina F • Also found in lymph nodes and dermis Report a Problem/Feedback Basic Science and Structure of Skin    13
  26. 26. • Two stages in the Langerhans life cycle: 1.) In epidermis, ingest and process antigens, are weak stimulators of T-cells 2.) Activated Langerhans cells that have contacted antigen and can strongly stimulate naïve T-cells u TIP •  nce a Langerhans cell encounters and processes O T a given antigen it “matures” and migrates to a local a he most important cells for recognition, uptake and processing of antigens in the skin lymph node, where it then presents the antigen to a and presenting these antigens to naï e T-cells v naïve (or resting) T-cell, activating that T-cell aCharacteristic finding on electron microscopy •  entral to the pathogenic processes of atopic derC Birbeck granules- tennis racket shaped bodies in matitis, psoriasis, allergic contact dermatitis, and the cell. Be able to identify an electron microsinfections such as Leishmaniasis copy image of a Langerhans Cell •  unctionally impaired by ultraviolet radiation. After F UV radiation, Langerhans cells are impaired in the ability to present antigen and are depleted in number • Located in all layers of epidermis, but mostly in suprabasal layer • Adheres to cells by e-cadherin, produce IL-1 • Disease processes involving Langerhans Cells (all S-100 and CD1a + with Birbeck granules in cytoplasm): – Letterer-Siwe disease – Hand-Schüller-Christian disease – Eosinophilic granuloma – Hashimoto-Pritzker disease – Can be infected with HIV – Produces IL-I, expresses E-Cadherin (to adhere to KC) • Stains (+) CD45 (ICA or OKTG), ATP ase (1st marker to develop), S100, Fc Receptor (+), C3, CD1a, actin, vimentin • Kidney shaped nucleus, Birbeck granules on EM 1.2 DERMIS Dermis • Collagen, elastic fibers, Matrix, Cells (fibroblasts, monocytes, phagocytes, mast cells, dermal dendrocytes, glomus cells) Collagen • Primary dermal constituent 75% of dry weight of skin • Provides tensile strength and elasticity •  dult dermis: types I, III, and V; type I accounts for 85% of collagen; type III accounts for A 10%; type V accounts for 5% u TIP •  ysyl hydroxylase and proline hydroxylase crosslinks col- a omposed of three chains that vary L C lagen (desmosine residues) - vitamin C required cofactor according to collagen type. All have Gly-X-Y amino acid motif that repeats (copper and Vitamin B6 also) for function of enzyme where X and Y are proline an hydroxyvitamin C deficiency = Scurvy proline •  ype I III are major interstitial fiber forming collagens T 14  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  27. 27. Table 1–6. Types of Collagen and Tissue Distribution I (85%) Mature Skin, Bone, Tendon (except bone marrow and cartilage) COL1A1/2—Ehlers-Danlos syndrome (EDS) Arthrochalasia type Osteogenesis Imperfecta II Cartilage, Vitreous Relapsing polychondritis III (10%) Fetal Skin, Blood Vessels, Intestines Wound repair, COL3A1—EDS Vascular type IV Basement Membranes Alport and Goodpasture syndrome V (5%) Ubiquitous COL5A1/2—EDS Classical type VI Aorta, Placenta Congenital muscular dystrophy without skin findings VII Anchoring Fibrils, Amnion Dystrophic epidermolysis bullosa (EB), bullous lupus, cicatricial pemphigoid VIII Cornea—Descemet’s membrane Corneal dystrophy IX Cartilage No associated skin disease X Cartilage No associated skin disease XI Cartilage No associated skin disease. Stickler Marshall syndromes (ophthalmic disease) XII Cartilage fibroblasts No associated skin disease XIII Fibroblasts No associated skin disease XIV Skin, placenta, tendon, Cartilage, muscle No associated skin disease XV Placenta No associated skin disease XVI Placenta No associated skin disease XVII Anchoring filaments Junctional EB, generalized atrophic benign EB, bullous pemphigoid XVIII Liver, kidney, placenta XIX Rhabdomyosarcoma Rhabdomyosarcoma Collagen Diseases Ehlers-Danlos Syndromes •  xcessive stretchability and fragility of the skin with a tendency toward easy scar formation E (“fish-mouth” scars) • Calcification of the skin to produce pseudotumors • See Chapter 3, Genodermatoses, for description of types Random Associated Diseases: • Osteogenesis Imperfecta abnormal type I collagen • Homocystinuria: Abnormal crosslinking of collagen because of mutated β cystathione synthase • Tenascin-X: Autosomal recessive type EDS similar to Classic type. Associated with collagen fibrillinogenesis Elastic Fibers • 4% of dry weight of the skin •  orms complex meshwork extending from lamina densa of the DEJ through the dermis F and into the hypodermis Report a Problem/Feedback Basic Science and Structure of Skin    15
  28. 28. • Returns skin to normal configuration after being stretched • Elastic fibers: 90% elastin, wrapped by fibrillin microfibrils (mutated in Marfan’s) •  esmosine and isodesmosine are typical amino acids found in elastic fibers, and crosslink D fibrillin requires lysyl oxidase (copper-dependent process) • Oxytalan fibers: contain no elastin; run perpendicular from DEJ within superficial papillary dermis • Elaunin fibers: have less elastin and more fibrillin; run parallel in thin bands within the reticular dermis • Elastic fibers turn over slowly in the skin and are damaged by ultraviolet radiation Elastin Diseases Cutis laxa • Fibulin 5 gene defect • Decreased desmosine and lysyl oxidase • Fragmentation and loss of elastic fibers Marfan’s Syndrome • Decreased fibrillin I • Fragmentation of elastic fibers, especially aortic Congenital Contractural Arachnodactyly • Mutation in fibrillin 2 Pseudoxanthoma Elasticum • MDRP (multiple drug resistant protein) • ABCC6 gene defect—(adenosine triphosphate binding cassette subfamily C member 6) • Increased glycosaminoglycans on elastic fibers • Calcium deposition • Accumulation of fragmented and calcified elastic fibers Buschke-Ollendorf Syndrome • LEMD3 (a.k.a. MAN1) gene defect • Increased desmosine • Increased amount of thickened elastic fibers Anetoderma • Decreased desmosine • Loss of and fragmentation of elastic fibers Dermal Matrix Components •  roteoglycans and glycosaminoglycans → ground substance that surrounds the fibrous P constituents of the dermis; 0.2% of dry weight of the dermis •  roteoglycans consist of a “core protein” with a glycosaminoglycan such as hyaluronic acid P binding to the core protein; other glycosaminoglycans include dermatan sulfate, heparan sulfate, and chondroitin sulfate  • Can bind up to 1000 times their volume and regulate water-binding capability of the dermis •  ucopolysaccharidoses represent genetic storage diseases resulting from abnormal lysoM somal function and subsequent accumulation of these substances. → Hurler’s (Alpha-Liduronidase), Hunter’s (Iduronate sulfatase), for example. See Genodermatoses Chapter for more detail on these conditions 16  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  29. 29. Papillary Dermis • Young or healthy skin: small diameter collagen fibrils and oxytalan elastic fibers • Aging or actinically damaged skin: mature elastic fibers that are large and dense • High density of fibroblast cells that proliferate rapidly Reticular Dermis • Large diameter collagen fibers with mature, branching elastic fibers • Elastic and collagen bundles increase in size progressively toward the hypodermis Cells of the Dermis Fibroblast • Derived from mesenchyme • Produces extracellular matrix framework • Synthesizes soluble mediators that may constitute signaling between the dermis and epidermis • Wound healing - produce fibroplasia and wound contraction (myofibroblasts) Mononuclear Phagocytic Cells • Monocytes, macrophages, and dermal dendrocytes from bone marrow • All phagocytic skin macrophages express CD11c, CD6; CR4 (CD11c) = b2 integrin that binds; C3b+ stimulates phagocytosis • Macrophage functions – Phagocytic – Processing and presenting antigens to naïve T-cells – Microbiocidal through production and release of lysozyme, peroxide, and superoxide – Tumoricidal – Secretory (cytokines, growth factors, etc.) – Involved in coagulation, atherogenesis, wound healing and tissue remodeling – CD11a = LFA (binds to (CAM-2) – CD11b = Mac-1 on phagocytes binds to LCAM Mast Cells Table 1–7. Mast Cells Mast Cell Type Mediator Location T Type Tryptase only Bowe and respiratory mucosa TC Type Typrtase and Chymase Skin, GI, submucosa C Type Chymase only Skin, lymph node •  reatest density in the papillary dermis, in sheaths of the appendages, and around blood G vessels and nerves of the subpapillary plexus •  iseases: Mastocytosis, solitary mastocytoma, diffuse erythrodermic mastocytosis, TMEP, UP D • Derived from bone marrow-residing CD34+ stem cells  • roliferation depends on the c-kit receptor and its ligand stem-cell factor (SCF). Mutations P in c-kit (CD117) may result in mastocytosis or piebaldism • Stain CD34+, C-Kit, stem cell factor (SCF), giemsa, teledyne, leder stain (naphthol chloroac etate esterase) •  roduced and stored in preformed secretory granules - many inflammatory mediators such P as histamine, heparin, tryptase, chymase, carboxypeptidase, neutrophil chemotactic factor, Report a Problem/Feedback Basic Science and Structure of Skin    17
  30. 30. and eosinophilic chemotactic factor of anaphylaxis. Produce IL-8 (strong neutrophil chemotactic factor) - Produce PqD2 and tryptase • Release without storing - growth factors, cytokines, and leukotrienes including prostaglandin D2 • Preformed mediator in mast cell - serine proteases (tryptase), heparin, histamine •  ecretory granules are released by a variety of stimuli, and process. Degranulation is identical S regardless of stimulus •  egranulation produces vascular smooth muscle contraction, increases vascular permeability, D tissue edema, and the recruitment of inflammatory cells •  esponsible for immediate-type hypersensitivity reactions and participate in chronic inflamR matory conditions • Histologically: Round or oval nucleus and dark staining granules • Mast cell mediators: tryptase, chymase, cathepsin G, histamine, heparin, IL-4, IL-13, IL 3, IL5, GMCSF, TNF-alpha, CCL3, leukotrienes C4D4EF, platlet activating factor Mast Cell Mediators • Tryptase, chymase, cathepsin a, histamine, heparin, IL-4, IL-V, IL3, IL5, GM-CSF, TNF-alpha, CCL3, leukotrienes C4D4E, Platelet activity factor Dermal Dendrocytes • Subset of antigen-presenting cells function in the afferent limb of the immune response • Derived from bone marrow • Found in papillary dermis and upper reticular dermis • Highly phagocytic, same as melanophages in the dermis that contain ingested pigment • Likely the cell of origin in benign proliferative tumors such as dermatofibromas or fibroxanthomas Glomus Cells • Derived from Susquet-Hoyer canals • Vascular smooth muscle cells •  llow the rapid shunting of blood from the arterioles to venules, bypassing capillaries A occurs primarily in palms and soles • Disease processes include glomus tumor and glomangioma 1.3  NTIGENS A IMPLICATED IN AUTOIMMUNE DISEASES AND OTHER ANNOYING FACTOIDS Paraneoplastic Pemphigus • Plectin (500 kd) • Desmoplakin I (250 kd), II (210 kd) • BPAg1 (230 kd) • Envoplakin (210 kd) • Periplakin (190 kd) • Unknown 170 kd antigen • Dsg 1, 3 (160 kd, 130 kd) Pemphigus Vulgaris • Desmoglein 3 (130 kd), coprecipitates with plakoglobin (85 kd) Pemphigus Foliaceus • Desmoglein 1 (160 kd) 18  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  31. 31. Linear IgA Disease • BPAg2 (180kD) (Collagen XVII) - may be the 97 kd fragment Subcorneal Pustular Dermatosis (IgA Pemphigus, Sneddon-Wilkinson Disease) • Desmocollin 1 (115 and 105 kd) Intraepidermal Neutrophilic IgA Dermatosis • Desmoglein 3 Pemphigoid Gestationis • BPAg2 (180 kd) Cicatricial Pemphigoid (Mucous Membrane) • BPAg2 (180 kd) C-terminal domain • Laminin 5 - antiepiligrin CP • Laminin 6 • β-4 integrin - Ocular CP • Type VII collagen The Plakin Family • Envoplakin (210 kd) • Periplakin (190 kd) • Desmoplakin (250 kd) • BPAg1 (230 kd) • Plectin (500 kd) Table 1–8. Blistering D/O Antigen Inherited K5, 14 EBS Dowling Meara AI Plectin EBS - MD PNP BPAG2 Generally atrophic benign EB EB, CP Antigen Inherited AI a6b4 Integrin JEB = gatric atresia b4 integrin ocular CP Laminin V JEB CP with maln Collagen VII DEB Collayenous domain EBA noncollagenous domain Bullous LE Collapse domain 1.4 WOUND HEALING Inflammatory Stage Clot Formation • Initial step in wound healing • Provisional matrix for cell migration • Functions in hemostasis Coagulation •  ritical event is availability of surface that promotes adsorption and activation of specific C coagulation pro-enzymes • Clot provides a scaffolding for recruitment of cells to injured site Report a Problem/Feedback Basic Science and Structure of Skin    19
  32. 32. • Fibrin and fibronectin act as provisional matrix for infiltrating monocytes, fibroblasts, and newly formed blood vessels •  learance of clot matrix is as important as deposition, and inadequate removal of provisionC al matrix may lead to fibrosis; proteolytic enzymes such as plasminogen and plasmin are the major proteins Platelets in Wound Healing (First Response) • Aggregation and adhesion required • Release many mediators, including ADP, and clotting factors • Fibrin clot and thrombin act as nidus for further adhesion and aggregation • Platelets release PDGF, EGF, fibronectin, and TGF-alpha and –beta which promote new tissue growth Neutrophils in Wound Healing •  igrate with monocytes concurrently, but arrive first in great numbers because of their M abundance in circulation • Chemoattractants for PMNs: Fibrinogen/fibrin split products, C5a, leukotrienes • f wound contamination controlled, PMN migration ceases within a few days, and PMN’s I become entrapped within the wound clot, undergo apoptosis or phagocytosed by macrophages Monocytes in Wound Healing  • Macrophages are REQUIRED for wound healing - without macrophages, there is no healing • Monocyte chemoattractants include fragments of collagen, elastin, and fibronectin • Macrophages debride tissue through phagocytosis and digestion of organisms, tissue debris, and effete PMN’s • Secrete collagenase •  dherence to matrix stimulates expression of cytokines and growth factors FGF, IL-1, TGFA alpha, PDGF, and TGF-beta, therefore facilitating transition from inflammation to repair •  roliferation phase: epithelization granulation collagen deposit; Angiogenesis (stimulated by P TNFα) Epithelialization • Begins hours after injury • Keratinocytes from residual epithelial structures leapfrog each other • Wound epidermal cells have lateral mobility by virtue of dissolution of intercellular desmosomes •  ells in all layers of migrating epidermis contain keratins 5 and 14 (usually only found in C basal epidermis) and keratins 6 and 16; this phenotype resembles that found in lesional psoriatic skin • One to two days after injury, cells at wound margin proliferate • f basement membrane destroyed, migration occurs over provisional matrix of collagen type I V, fibrin, fibronectin •  igrating cells both traverse over wound coated with provisional matrix and through M wound using an array integrin receptors to guide the path • Collagenase is produced to assist in migration • Migration and dissection results in eschar sloughing 20  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  33. 33. •  igration is a result of a combination of chemotactic factors, direct guidance by contact, M and loss of nearest neighbor, but not by proliferation • Once basement membrane proteins reappear, epidermal cells revert to their normal phenotype • 1st degree burn - basement membrane intact • 2nd/3rd degree burn - basement membrane destroyed Granulation Tissue • Four days after injury, granulation tissue forms •  omposed of new capillaries, macrophages, fibroblasts and blood vessels, which move into C wound space as a unit • Formation of granulation tissue dependent on presence of fibronectin • Ordered sequence of matrix deposition: fibronectin → collagen III → collagen I • Granulation tissue primarily contains collagen type III 1.5 MATURATIONAL Fibroplasia and Wound Contraction •  ibroplasia is granulation tissue that arises from fibroblasts, and is a mixture of fibroblasts F and extracellular matrix (ECM) •  onocytes → macrophages → secretion of growth factors (also from platelets) → fibroblast M proliferation and activation of fibroplasia • Once migrated into a wound, protein synthesis occurs to create the ECM/collagen matrix •  ound contraction ensues during second week of healing → governed by wound fibroW blasts’ ability to act like smooth muscle cells (myofibroblasts), anchored by collagen bundles • Large bundles of actin-containing microfilaments appear in these fibroblasts • Fibroplasia in wound repair ends with apoptosis of fibroblasts at or around day ten of healing • 30% of normal strength Neovascularization • Soluble factors that stimulate angiogenesis: VEGF, TGF, angiogenin, angiotropin, and others • Angiogenesis occurs during first week of wound repair •  ngiogenesis initiated by plasma leak, release of FGF, and subsequent activation of collageA nase to break down the basement membrane on which the endothelial cells rest •  he endothelial cells project pseudopods through the basement membrane and subseT quently migrate into the connective tissue space Tissue Remodeling • Endothelial cells are first to apoptose, then myofibroblasts, and macrophages, leaving an acellular scar • Progression of events over time: early formation of types I, III, and V collagen, collagen bundles grow in size • Increasing wound tensile strength, and proteoglycans are deposited increasing wound resilience to • Deformation Report a Problem/Feedback Basic Science and Structure of Skin    21
  34. 34. •  ibrin: First extracellular matrix to be deposited; for effective hemostasis, interaction must F occur with platelets (via GPIIb-IIIa integrin); fibroblasts require fibronectin for migration into a fibrin clot • Fibronectin: circulates in blood and binds fibrin •  yaluronan (hyaluronic acid): linear polymer (member of glycosaminoglycans); major comH ponent of early granulation tissue; produced by fibroblasts Strength of Scar • 5% at one week • 20% at three weeks • 70% at one year 1.6 HAIR FOLLICLE BIOLOGY Embryology • First primordial hair follicles form at nine weeks gestation on eyebrows, upper lip, and chin • Remaining follicles develop at four to five months in a cephalad to caudal direction • New follicles cannot develop in adult skin • Ectodermal origin, hair papilla - mesoderm Follicular Morphogenesis • Exchange of signals between epithelial and mesenchymal cells •  regerm stage: focal crowding of epidermal basal nuclei match by a cluster of mesenchyP mal cells beneath the basement membrane •  rowding of basal keratinocytes causes a slight bud on underside of epidermis—termed the C follicle germ or primitive hair germ •  ollicle peg: Result of the elongation of follicle germ into a cord of epidermal cells that F grows into dermis perpendicular to skin surface • Tip of the epithelial cord becomes matrix portion of the bulb •  utgrowths of cells from the outer root sheath give rise to the presumptive sebaceous O gland (uppermost) and the bulge (lowermost)—the insertion site of the arrector pili muscle •  ermal papilla: Deepest portion of the bulbous hair peg that forms an invagination surD rounding the bulk of the underlying mesenchymal cells •  atrix keratinocytes: Above the BM overlying the dermal papilla—give rise to hair shaft M and inner root sheath; melanocytes responsible for the pigmentation of the hair dispersed among these matrix cells • Outer root sheath: Most peripheral epithelial cells of the follicle; most likely not formed from matrix cells Hair Follicle Organization • Outer root sheath (trichilemmal keratin): most peripheral of cellular components • Inner root sheath: Three compartments, stains red because citrulline 1.) Henle’s layer - keratinizes first uTIP 2.) Huxley’s layer anside to outside. Cuticle - IRS - Huxley-Henle - ORS - glassy/vitreous I 3.) Cuticle • Hair shaft: Three compartments 1.) Cuticle No keratohyalin granules 2.) Cortex—forms bulk of hair 3.) Medulla—central 22  2013/2014 Dermatology In-Review l Committed to Your Future Report a Problem/Feedback
  35. 35. •  ritical line of Auber: Widest diameter of the bulb; bulk of mitotic activity that gives rise to C the hair and the inner root sheath occurs below this level The Hair Cycle Anagen • 84%, 3-4 years • Follicle traverses entire epidermis •  atrix keratinocytes in the bulb region proliferate rapidly; these cells are pluripotent cells M capable of differentiating into cuticle, cortex and medulla of hair shaft •  ivided into six substages (I to VI): the first five called collectively proanagen—defined by D progressively higher levels of new hair tip position within the follicle; the 6th stage, metanagen defined by emergence of hair shaft above the skin surface • End of anagen: apoptosis • Scalp: Lasts 2 to 6 years • Leg: 19–26 weeks • Arm: 6–12 weeks • Mustache: 4–14 weeks Anagen Effluvium • Frequently seen following administration of cancer chemotherapeutic agents  •  timulus induces the abrupt cessation of mitotic activity in rapidly dividing hair matrix cells ; S hair shaft thins and then breaks at skin surface • Occurs within days to weeks of the stimulus • Entirely reversible with cessation of drug therapy Causes • Antimetabolites • Alkylating agents • Mitotic inhibitors • Thallium • Boron • Examples: doxorubicin, the nitrosureas, and cyclophosphamide Catagen • 2%, club ends, 3 weeks • Scalp hairs show gradual thinning and lightening of uTIP E aarly and excessive loss of club hairs from the pigment at the base of the hair shaft • Melanocytes in the matrix cease producing melanin, the normal resting follicles in the scalp •   hysical stress such as: surgery, anemia, P and undergo apoptosis traction or systemic illness • Involution lower 2/3rds by keratinocyte apoptosis •   sychological stress P • Matrix keratinocytes abruptly cease proliferating, •   ndocrine causes such as: hypo or hyperthyE roidism or peri-/postmenopausal states undergo terminal differentiation •   utritional deficiencies: biotin, iron, protein N •  t end of catagen, the follicular papilla comes to A (Kwashiorkor), zinc, essential fatty acid or rest at the bottom of the permanent calorie deficiency (marasmus or starvation portion of the hair follicle diets) Telogen • ~14%, duration 3 months • Hair has club-shaped proximal end, and is typically shed from the follicle Report a Problem/Feedback •  Hypervitaminosis A •  Parturition •  Fever •  Drugs Basic Science and Structure of Skin    23

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