The 2012/2013
Dermatology In-Review
Study Guide
Companion to the
Dermatology In-Review
Online Practice Exam and Study Syst...
© 2012 Published by SanovaWorks
Edited by C. William Hanke MD, FACP
All rights reserved. No part of this book may be repro...
iv  2012/2013 Dermatology In-Review l Committed to Your Future
uTIP
aPhenol is cardiotoxic, nephrotoxic and hepatotoxic.
P...
Key Features  v
Mnemonic Boxes
Pearl Boxes
Note Pages
Each chapter is followed by a series of Note Pages that should be us...
vi  2012/2013 Dermatology In-Review l Committed to Your Future
Dear Colleague,
With great pleasure we provide you with the...
Andrew F. Alexis, MD, MPH
Director, Skin of Color Center
St. Luke’s-Roosevelt Hospital
Assistant Clinical Professor of Der...
viii  2012/2013 Dermatology In-Review l Committed to Your Future
Jeffrey L. Marx, MD
Clinical Associate Professor, Departm...
Faculty  ix
L. Magaly Villafradez-Diaz, MD
Research Fellow, Mohs, Dermatologic and
Laser Surgery Department of Dermatology...
x  2012/2013 Dermatology In-Review l Committed to Your Future
Contents
Chapter 1 	 Basic Science and Structure of Skin. . ...
Table of Contents  xi
Chapter 4 	 General Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
xii  2012/2013 Dermatology In-Review l Committed to Your Future
Chapter 5	 Dermatopathology. . . . . . . . . . . . . . . ....
Chapter 7	 Medical Mycology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....
xiv  2012/2013 Dermatology In-Review l Committed to Your Future
Chapter 10 	 Cutaneous Manifestations of Systemic Disease....
Chapter 15 	 Dermatologic and Cosmetic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...
Basic Science and Structure of Skin    1Report a Problem/FeedbackReport a Problem/Feedback
1 Basic Science and Structure o...
Basic Science and Structure of Skin    3Report a Problem/FeedbackReport a Problem/Feedback
1.1 EPIDERMIS
Epidermis
•	 Comp...
4  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Type I...
Basic Science and Structure of Skin    5Report a Problem/FeedbackReport a Problem/Feedback
Table 1-2.  Desmosomal Proteins...
6  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Stratu...
Basic Science and Structure of Skin    7Report a Problem/FeedbackReport a Problem/Feedback
Figure 1-1. Skin Adhesion Molec...
8  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Table ...
Basic Science and Structure of Skin    9Report a Problem/FeedbackReport a Problem/Feedback
Lamina Lucida
Hemidesmosome
• A...
10  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
– Mol...
Basic Science and Structure of Skin    11Report a Problem/FeedbackReport a Problem/Feedback
• Keratinocytes can produce bo...
12  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Merke...
Basic Science and Structure of Skin    13Report a Problem/FeedbackReport a Problem/Feedback
1.2 DERMIS
Dermis
• Collagen, ...
14  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Colla...
Basic Science and Structure of Skin    15Report a Problem/FeedbackReport a Problem/Feedback
Anetoderma
• Decreased desmosi...
16  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Mast ...
Basic Science and Structure of Skin    17Report a Problem/FeedbackReport a Problem/Feedback
1.3 ANTIGENS IMPLICATED IN AUT...
18  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
Antig...
Basic Science and Structure of Skin    19Report a Problem/FeedbackReport a Problem/Feedback
Epithelialization
• Begins hou...
20  2012/2013  Dermatology In-Review  l  Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback
• Ang...
Basic Science and Structure of Skin    21Report a Problem/FeedbackReport a Problem/Feedback
• Matrix keratinocytes: Above ...
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Dermatology in review etas 2012-2013
Upcoming SlideShare
Loading in...5
×

Dermatology in review etas 2012-2013

12,859

Published on

Published in: Health & Medicine, Education
0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
12,859
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
395
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide

Dermatology in review etas 2012-2013

  1. 1. The 2012/2013 Dermatology In-Review Study Guide Companion to the Dermatology In-Review Online Practice Exam and Study System Edited by C. William Hanke, MD, MPH, FACP   Associate Editors Michael 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. © 2012 Published by SanovaWorks Edited by C. William Hanke MD, 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 ISBN 978-0-9820321-9-0 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.
  3. 3. iv  2012/2013 Dermatology In-Review l Committed to Your Future uTIP aPhenol is cardiotoxic, nephrotoxic and hepatotoxic. Patients must have cardiac monitoring during phenol peeling to detect cardiac arrhythmias aChemical peeling of the neck is generally avoided because of the risk of hypertrophic scarring • 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 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.  Tip Boxes The 2012/2013 Dermatology In-Review Study Guide is formatted for quick study and easy reference. The following elements will appear throughout the text to aid in the preparation for your exams: Call-Outs Look for the Call-Out arrows within the text. They are used in different ways to highlight key information. K E Y F E A T U R E S Tip Boxes highlight exam-relevant information for quick study. Call-Outs may also appear before paragraphs. When this is seen, the whole paragraph is high-yield information. Call-Out arrows can be seen before pertinent bullet points throughout the chapters. Keep an eye out for arrows sitting in a shaded box. These signify more than one important bullet point.  •  Seen in Birt-Hogg-Dube The online study guide features purple text which indicates that the material is NEW for the 2012/2013 year. Note: If just a table head or figure name is in purple, it means the entire table or figure is new. Purple Text 
  4. 4. Key Features  v Mnemonic Boxes Pearl Boxes 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. 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. 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. K E Y F E A T U R E S Shaded Text Helpful mnemonic memory cues are displayed in Mnemonic Boxes throughout the chapters. Pearl Boxes are used to stress information that is commonly found on exams. MNEMONIC Subepidermal Split PLAID Pemphigoid (bullous) Lupus (bullous SLE) Acquisita (EBA) IgA, linear Dermatitis herpetiformis PEARL w Variant: Brunsting-Perry pemphigoid: no mucosal involvement, blisters on patches of erythema on head/neck with scarring/scarring alopecia w Treatments: Topical/intralesional/PO steroids, dapsone, cyclophosphamide, azathioprine
  5. 5. vi  2012/2013 Dermatology In-Review l Committed to Your Future Dear Colleague, With great pleasure we provide you with the 2012/2013 Dermatology In-Review Study Guide from Educational Testing and Assessment Systems (ETAS). 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 Practice Exam 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
  6. 6. 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 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 Erika Gaines Levine, MD Private Practice Haddonfield, NJ William R. Levis, MD Clinical Assistant Professor, Departments of Medicine and Dermatology New York University Langone Medical Center New York, NY Faculty  vii F A C U L T Y Authors
  7. 7. viii  2012/2013 Dermatology In-Review l Committed to Your Future 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 Jennifer B. Perone, MD Surgical Dermatology Associates, PA Denton, TX Dori Rausch, MD Private Practice Coronado, CA Kelley Pagliai Redbord, MD Dermatology and Dermatologic Surgery Group of Northern Virginia Vienna, VA Maria Patricia Rivas-Bondavalli, MD Private Practice Hollywood, FL Ellen Roh, MD Instructor of Dermatology Harvard Medical School/Massachusetts General Hospital, Department of Dermatology Boston, MA 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 Assistant Professor New York University Langone Medical Center New York, NY Jeffrey M. Weinberg, MD Attending, Department of Dermatology St. Luke’s-Roosevelt Hospital Center, and Beth Israel Medical Center New York, NY Voraphol Vejjabhinanta, MD Post-doctoral Fellow in Mohs, Laser and Dermatologic Surgery, Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Miami, FL Irene Vergilis-Kalner, MD Clinical Assistant Professor of Dermatology Robert Wood Johnson Medical School Somerset, NJ Associate Mohs, Cosmetic, and Reconstructive Surgeon Skin Lasers Surgery Center of NY NJ NY, NJ F A C U L T Y
  8. 8. Faculty  ix 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 Jeremy A. Brauer, MD 2010/2011 Chief Resident New York University School of Medicine Program New York, NY Chung-Yin Stanley Chan, MD 2010/2011 Chief Resident Baylor College of Medicine Program Houston, TX Melinda R. Mohr, MD 2010/2011 Chief Resident Eastern Virginia Medical School Norfolk, VA Special Recognition Cynthia Bartus, MD Dermatology In-Review Cram Pack Updates Private Practice Atlanta, GA Adam Friedman, MD Dermatology In-Review Workshop Instructor, Director of Dermatologic Research, Department of Dermatology 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 F A C U L T Y
  9. 9. x  2012/2013 Dermatology In-Review l Committed to Your Future Contents Chapter 1  Basic Science and Structure of Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Kelley Redbord, MD Peter Schalock, MD Bruce E. Strober, MD, PhD 1.1 Epidermis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Dermis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.3 Antigens Implicated in Autoimmune Diseases and Other Annoying Factoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 1.4 Wound Healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 1.5 Maturational. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1.6 Hair Follicle Biology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 1.7 Sebaceous Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 1.8 Eccrine Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 1.9 Apocrine Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 1.10 Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.11 Nerves and Receptors of the Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.12 Immunofluorescence Patterns - Direct. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 1.13 Connective Tissue Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Chapter 2  Immunodermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Eric Huang, MD, PhD William R. Levis, MD Georgia B. Schuller-Levis, PhD 2.1 The Innate and Adaptive Immune Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 2.2 Cells of the Innate and Adaptive Immune System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 2.3  Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 2.4  Antibodies and Complement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 2.5  Major Histocompatibility Complex and HLA Disease Associations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 2.6  Non-Steroidal Immunologic Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Chapter 3 Genodermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Arash Kimyai-Asadi, MD Irene Vergilis-Kalner, MD 3.1 X-linked Recessive Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3.2 X-linked Dominant Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3.3 Hereditary Blistering Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3.4 Ichthyoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 3.5 Palmoplantar Keratodermas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.6 Disorders with Hypopigmentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 3.7 Disorders with Pigmented Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.8 Vascular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 3.9 Connective Tissue Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.10 Diseases of the Hair and Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3.11 Diseases with Malignant Potential. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 3.12 Disorders with Immunodeficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 3.13 DNA and Chromosomal Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 3.14 Keratinopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 3.15 Disorders of Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
  10. 10. Table of Contents  xi Chapter 4  General Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Priya Swamy Zeikus, MD Bruce E. Strober, MD, PhD Katherine White, MD 4.1 Acne Vulgaris. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.2 Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 4.3 Psoriasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.4 Psoriatic Arthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 4.5 Reiter’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 4.6 SAPHO Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 4.7 Sneddon-Wilkinson Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 4.8 Lichen Planus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 4.9 Atopic Dermatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.10 Alopecia Areata. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 4.11 Alopecia: Other Forms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 4.12 Vitiligo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 4.13 Pityriasis Rubra Pilaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 4.14 Lichen Sclerosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 4.15 Granuloma Annulare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 4.16 Hirsutism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 4.17 Amyloidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 4.18 Calciphylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 4.19 Angioedema. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 4.20 Carcinoid Syndrome and Flushing Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 4.21 Lupus Erythematosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 4.22 Scleroderma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 4.23 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 4.24 Sjogren’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 4.25 Connective Tissue Disease: Serology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 4.26 Relapsing Polychondritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 4.27 Behçet’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 4.28 Livedo Reticularis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 4.29 Leukocytoclastic Vasculitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 4.30 Cryoglobulinemia and Cryofibrinogenemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 4.31 Acanthosis Nigricans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 4.32 Lipodystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 4.33 Hyperlipoproteinemias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 4.34 Xanthomatosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.35 Vitamin Deficiencies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.36 Diabetes and Skin Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 4.37 Langerhans Cell Histiocytosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.38 Cutaneous T-Cell Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 4.39 Pyoderma Gangrenosum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 4.40 Sweet’s Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 4.41 Erythema Annulare Centrifugum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 4.42 Erythema Elevatum Diutinum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 4.43 Erythema Nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 4.44 Mastocytosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 4.45 Cutaneous Sarcoidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 4.46 Perforating Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 4.47 Elastosis Perforans Serpiginosa. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 4.48 Reactive Perforating Collagenosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 4.49 Cutaneous Features and Disorders of Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 4.50 Pruritus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 4.51 Scleredema. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 4.52 Nephrogenic Fibrosing Dermopathy/Nephrogenic Systemic Fibrosis. . . . . . . . . . . . . . . . . . . . . . . . . 149
  11. 11. xii  2012/2013 Dermatology In-Review l Committed to Your Future Chapter 5 Dermatopathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Christine J. Ko, MD 5.1 Normal Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 5.2 Stains. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 5.3 Immunohistochemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 5.4 Acantholytic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 5.5 Adnexal/Epithelial Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 5.6 Alopecias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 5.7 Bullous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 5.8 Cysts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 5.9 Deposition Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 5.10  Drug Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 5.11  Fat Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 5.12 Fibrous/Fibrohistiocytic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 5.13 Genodermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 5.14 Granulomatous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 5.15 Histiocytoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 5.16 Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 5.17 Inflammatory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 5.18 Lymphomas and Markers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 5.19  Melanocytic Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 5.20 Muscle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 5.21 Neural. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 5.22 Pagetoid Spread. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 5.23 Palisading Reactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 5.24 Vascular. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 5.25 Miscellaneous. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206 5.26 Clues for Board Purposes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 5.27 “Bodies”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 Chapter 6  Benign and Malignant Neoplasms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219 Keyvan Nouri, MD Sonal Choudhary, MD Maria Patricia Rivas, MD Voraphol Vejjabhinanta, MD L. Magaly Villafradez-Diaz, MD George W. Elgart, MD 6.1 Seborrheic Keratosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221 6.2 Actinic Keratosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 6.3 Bowen’s Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 6.4 Non-melanoma Skin Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 6.5 Basal Cell Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 6.6 Squamous Cell Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 6.7 Keratoacanthoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 6.8 Malignant Melanoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234 6.9 Merkel Cell Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238 6.10 Cutaneous T-Cell Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240 6.11 Angiosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 6.12 Desmoplastic Trichoepithelioma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 6.13 Dermatofibrosarcoma Protuberans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 6.14 Microcystic Adnexal Carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
  12. 12. Chapter 7 Medical Mycology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 Evelyn K. Koestenblatt, MS, MT (ASCP) Jeffrey M. Weinberg, MD 7.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 7.2 Superficial Mycoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 7.3 The Dermatophytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 7.4 Subcutaneous Mycosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 7.5 Dimorphic Fungi Causing Systemic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 7.6 Opportunistic Organisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 7.7 Miscellaneous Organisms Causing Fungus-like Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282 7.8 Random Facts and Summary Table. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 Chapter 8  Infectious Diseases of the Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 Andrew F. Alexis, MD, MPH 8.1 Bacterial Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 8.2 Viral Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 8.3 Mycobacterial Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 8.4 Sexually Transmitted Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 8.5 Nonvenereal Trepanomatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305 8.6 Parasitic Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305 8.7 Rickettsial Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 Chapter 9  Pediatric Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 Andrea L. Zaenglein, MD 9.1 Neonatal and Infantile Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 9.2 Childhood Infectious Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 9.3 Pigmented Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 9.4 Dermal Tumors and Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 9.5 Vascular Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326 9.6 Genodermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 a. Photosensitivity Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 b. Premature Aging Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 c. Disorders of Cornification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 d. Hereditary Palmoplantar Keratodermas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338 e. Ectodermal Hypohidrotic Dysplasias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340 f. Hair Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 g. Disorders of Pigmentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 h. Blistering Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344 i. Tumor Suppressor Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345 j. Metabolic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 348 k. Immunodeficiency Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 l. Disorders of the Connective Tissue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350 Table of Contents  xiii
  13. 13. xiv  2012/2013 Dermatology In-Review l Committed to Your Future Chapter 10  Cutaneous Manifestations of Systemic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 Dori Rausch, MD Valerie Harvey, MD Anthony Gaspari, MD 10.1 Cutaneous Manifestations of Hepatitis C Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357 10.2 Cutaneous Manifestations of Thyroid Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 10.3 Cutaneous Manifestations of Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 10.4 Cutaneous Manifestations of Gastrointestinal Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 10.5  Cutaneous Manifestations of Neurologic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 10.6  Cutaneous Manifestations of Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 10.7 Cutaneous Manifestations of Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375 10.8 Porphyrias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 Chapter 11  Disorders of the Hair and Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 Ming H. Jih, MD, PhD 11.1 Hair Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 11.2 Hirsutism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404 11.3 Hypertrichosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406 11.4 Nails. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407 Chapter 12 Bullous and Vesicular Dermatoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417 Christine J. Ko, MD 12.1 Molecular Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419 12.2 Microscopic Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 12.3 Bullous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422 12.4 Diseases that Can Present with Bullae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429 12.5 Vesicular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430 12.6 Common Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433 12.7 Plant Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 12.8 Tips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 12.9 Plant Irritants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437 Chapter 13  Photobiology and Photosensitivity Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441 Jeffrey L. Marx, MD 13.1 Basic Facts about Ultraviolet Light. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443 13.2 Photoimmunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444 13.3 Phototesting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 13.4 Idiopathic Photosensitivity Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 13.5 Photosensitivity from Exogenous Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450 13.6 Diseases Exacerbated by Sunlight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 13.7 Phototherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 13.8 Photochemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 13.9 Sunscreens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 Chapter 14  Plants and Creatures of Dermatologic Significance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 Jennifer B. Perone, MD 14.1 Plant Dermatoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 14.2 Dermatologic Diseases Caused by Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466 14.3 Lice, Spiders, Bugs, and Other Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469 14.4 Ticks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475 14.5 Mites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476 14.6 Exotic Pets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478 14.7 Skin Eruptions Caused by Marine Life. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 14.8 Medications Derived from Plants and Creatures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
  14. 14. Chapter 15  Dermatologic and Cosmetic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 Kelley Redbord, MD Alysa R. Herman, MD 15.1 Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491 15.2 Anesthetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 15.3 Antimicrobial Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 15.4 Prophylactic Antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 15.5 Wound Healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499 15.6 Sutures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501 15.7 Flaps and Grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 502 15.8 Chemical Peels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 504 15.9 Botox and Cosmetic Fillers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 504 15.10 Photoaging and Cosmeceutical Rejuvenation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505 15.11 Liposuction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506 15.12 Lasers and Radiofrequency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506 15.13 Mohs Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507 15.14 Chemotherapeutic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509 15.15 Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509 15.16 On the Horizon. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510 Chapter 16 Dermatopharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519 Erika Gaines Levine, MD 16.1 Antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521 16.2 Antivirals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522 16.3 Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 524 16.4 Topical and Systemic Corticosteroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526 16.5 Cytotoxic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526 16.6 Immunosuppressants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 16.7 Dapsone and Sulfapyridine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 16.8 Antimalarials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530 16.9 Retinoids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531 16.10 Sunscreens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532 16.11 Antiparasitics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533 16.12 Antihistamines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534 16.13 Hormone-related Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534 16.14 Miscellaneous Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 16.15 Biologic Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536 16.16 Drugs in Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537 16.17 Drug Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539 Chapter 17 Literature Review. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547 Peter Schalock, MD Ellen Roh, MD 2001. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 2002. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553 2003. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 2004. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 2005. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569 2006. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 576 2007. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582 2008. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589 2009. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595 2010. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 602 2011. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608 Table of Contents  xv
  15. 15. Basic Science and Structure of Skin    1Report a Problem/FeedbackReport a Problem/Feedback 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 Epidermis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Dermis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.3 Antigens Implicated in Autoimmune Diseases and Other Annoying Factoids . . . . . . . . . . . . . . . . . . 17 1.4 Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 1.5 Maturational . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1.6 Hair Follicle Biology . . . . . . . . . . . . . . . . . . . . . . . . . . 20 1.7 Sebaceous Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 1.8 Eccrine Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 1.9 Apocrine Glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 1.10 Nails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 1.11 Nerves and Receptors of the Skin . . . . . . . . . . . . . . 26 1.12 Immunofluorescence Patterns - Direct . . . . . . . . . 27 1.13 Connective Tissue Diseases . . . . . . . . . . . . . . . . . . . 28
  16. 16. Basic Science and Structure of Skin    3Report a Problem/FeedbackReport a Problem/Feedback 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 • 80% 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 • Keratinocytes are able to release, respond to, and produce TNF-alpha. Causes increased differentiation (Bikle, 1991) Table 1–1. 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 keratinocytes Pachyonychia congenita Jadassohn Lewandowsky type I, focal nonepidermolytic PPK 6b 17 Nail bed Pachyonychia congenita type II, steatocystoma multiplex (Jackson-Lawler) uTIP aAcidic and basic keratins are co-expressed in order to form filamentous structure - obligate heteropolymers” 
  17. 17. 4  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback Type II Type I Location Hereditary Disease Association 8 18 Simple epithelium Cryptogenic cirrhosis hHb1 b6 Hair follicle Monilethrix 19 Bulge cells simple epithelium Paget's = ck7, ck20 20 Merkel cell carcinoma 1 16 Non epidermolytic PPK 17 Steatocystoma Multiplex 5 EBS Mottled pigmentation (non helical V1 domain) 14 EBSC Autosomal recessive 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 bullosa simplex • K19 found in basal cells at transitional boundaries between different types of epithelia • Microfilaments (actin, myosin, and alpha-actinin) assist in upward movement of cells as they differentiate • Integrins regulate adhesion and initiation of differentiation • Not all basal cells have potential to divide • Stem cells give rise to transient amplifying cells • Once basal cell leaves basal layer in humans, normal transit time to stratum corneum is at 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 • 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 • In psoriasis, actinic keratoses, and wound healing suprabasal keratinocytes downregulate 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 • Desmosomal plaque: Six polypeptides, plakoglobin, desmoplakins I and II, keratocalmin, desmoyokin, demoyokin, and band 6 protein (see Table 1.2 for listing of desmosomal proteins and associated diseases) uTIP a Keratin filaments in basal cells insert into desmosomes and hemidesmosomes Table 1–1. Keratin Expression Patterns (cont.)
  18. 18. Basic Science and Structure of Skin    5Report a Problem/FeedbackReport a Problem/Feedback Table 1-2. Desmosomal Proteins Protein Location Disease Association(s) Plakoglobin Plaque Naxos syndrome Desmoplakin I/II Plaque Carvajal syndrome Keratocalmin Plaque None described to date Desmoyokin Plaque None described to date band 6 protein Plaque Ectodermal dysplasia/skin fragility syndrome Plakophilin Plaque Ectodermal dysplasia/skin fragility syndrome Envoplakin Plaque Paraneoplastic Pemphigus (210 kD antigen) Desmocalmin Plaque None described to date Desmoglein I Transmembrane AD Striate PPK/Pemphigus foliaceus Desmoglein III Transmembrane Pemphigus vulgaris Desmocollin I Transmembrane Subcorneal Pustular Dermatosis Desmocollin III Transmembrane None described to date • Transmembrane cadherins provide adhesive properties - contain desmoglein I and III, intracellular domains link with intermediate filament 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)  • Lamellar granules—A type of membrane bound intracellular structure, 0.2–0.3 micrometers in diameter; a lysosome with secretory func- 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 uTIP aLamellar granules deliver lipid precursors into intercellular space: glycoproteins, glycolipids, phospholipids, free sterols, and glucosylceramides uTIP aDisease relating to gap junctions: 26 Vohwinkel’s syndrome, KID syndrome, PPK with deafness 30.3 31 erythrokeratoderma variabilis 30 hidrotic ectodermal dysplasia
  19. 19. 6  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback Stratum Granulosum • Keratohyalin granules contain profilaggrin (F granules) and loricrin (L granules contain loricrin at periphery and help form cornified cell envelope) • K1 modified to K2, and K10 to K11 by proteolysis and phosphorylation  • Cornified cell envelope (CE): Proteins synthesized in spinous/granular layers – 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) – Degraded into urocanic acid and pyrrolidone carboxylic acid; both hydrate stratum corneum and block UV radiation – Stored in kit granule  • Transglutaminase: 3 versions that function in crosslinking the CE (calcium-dependent pro- cess). Forms gamma-glutamyl-lysine isodipeptide bonds in the CE, most prominently with involucrin  – TG-1 (type K) - keratinocyte transglutaminase, membrane associated, defect causes lamel- lar ichthyosis type I (TGM1 gene) – 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 • Programmed destruction of granular cell - loss of nucleus, yet retention of keratin filaments and filaggrin matrix – Destruction involves apoptosis transition cells (“T” cells) Stratum Corneum • Transition from Stratum Granulosum accompanied by loss of 45–86% in dry weight • Provides mechanical protection, barrier to water loss and barrier preventing permeation of environmental soluble substances uTIP Basal layer k5, 14 Keratin filaments Spinous layer k1, 10 Lamellar granules (k6, 16 in psoriasis) Granular layer k2, 11 Keratohyalin granules 
  20. 20. Basic Science and Structure of Skin    7Report a Problem/FeedbackReport a Problem/Feedback Figure 1-1. Skin Adhesion Molecules with Corresponding Diseases • 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
  21. 21. 8  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback Table 1-3. 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 • Hemidesmosomal adhesion complex: 1.) hemidesmosomal plaque, 2.) anchoring filaments, and 3.) anchoring fibrils • Know the electron microscopy picture of the basement membrane zone. Figure 1-2. Dermal-Epidermal Junction Components
  22. 22. Basic Science and Structure of Skin    9Report a Problem/FeedbackReport a Problem/Feedback Lamina Lucida Hemidesmosome • Attachment complex for basal keratinocytes and extracellular matrix • Electron-dense domain on the ventral surface of basal keratinocytes - bridge cytoskeleton and cutaneous basement membrane • Proteins: – BPAg1—230 kD protein (desmoplakin) • 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  • Its NC16A domain (target of autoantibodies in bullous pem- phigoid) interacts with alpha-6 integrin extracellularly • Also interacts with laminin 5 extracellularly • Two forms: full-length transmembrane and soluble 120 kDa ectodomain that is shed from cell surface • Integrins: Transmembrane proteins – alpha-6-beta-4 integrin found at sites where keratin intermediate filaments attach – 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 uTIP aDisease Associations (see chapter 12 for more details) BPAg1/BPAg2-NC16A bullous pemphigoid BPAg2 lichen planus pemphigoides portion of BPAg2 linear IgA disease BPAg2-NC16A herpes gestationis BPAg2 C terminal domain cicatricial pemphigoid
  23. 23. 10  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback – 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 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 • Point of attachment for anchoring fibrils composed of type VII collagen (from “above”) and collagens I and III from the dermis “below” Melanocytes • Dendritic cell derived from neural crest • Found in multiple tissues: epidermis, hair matrix, retinal pigment epithelium, ear (stria vascu- laris), leptomeninges, and mucous membranes Skin Melanocytes • In skin, localized to basal layer of epidermis • Functions include: melanin production (melanogenesis), arborize with processes that con- tact keratinocytes (epidermal melanin unit = approximately 36 keratinocytes in contact with one melanocyte), and transfer pigment to keratinocytes
  24. 24. Basic Science and Structure of Skin    11Report a Problem/FeedbackReport a Problem/Feedback • 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 • Tyrosine-DOPA- DOPAquinone, both steps catalyzed by tyrosinase, a copper containing enzyme • DOPAquinone converted to pheomelanin or eumelanin • Tyrosine hydroxylase is not expressed in melanocytes (only in neurons) • Melanin absorbs and scatters ultraviolet radiation (280-400 nm), and thus protects from UV-induced DNA mutations Melanosomes • Contain melanin • Related to lysosomes: positioned after the Golgi apparatus in the secretory pathway • Elliptical melanosomes synthesize brown or black eumelanin; have longitudinally oriented, concentric lamellae • Spheroid melanosomes produce yellow or red pheomelanin; have microvesicular internal structure • Melanin transfer involves the active phagocytosis of the dendritic tips of melanocytes by the 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 • Follicular melanogenesis coupled to hair growth cycle: melanocyte proliferation occurs during early period of anagen • Hair follicle contains melanocyte precursors that can repopulate the interfollicular epidermis • Graying caused by gradual decline in the number of follicular melanocytes; influenced by both age and genes • MC1-R gene mutations associated with red hair uTIP aMelanin has two forms: •  Eumelanin - brown-black, insoluble •  Pheomelanin - red-yellow, alkali-soluble, sulfur-containing aBoth types of melanin made from tyrosine via action of the enzyme tyrosinase
  25. 25. 12  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback 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 • Make synaptic connection with neurons (the Merkel cell-neurite complex); neurochemical transmission occurs between an activated Merkel cell and its neuron Langerhans Cells • Bone-derived, CD34+, antigen-processing and presenting cells of monocyte/macrophage lineage migrate from bone marrow in embryonic development and continue to repopulate epidermis during lifetime • Found in the skin and other epithelial tissues: oral mucosa, esophagus, vagina • Also found in lymph nodes and dermis • 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 • Once a Langerhans cell encounters and processes a given antigen it “matures” and migrates to a local lymph node, where it then presents the antigen to a naïve (or resting) T-cell, activating that T-cell • Central to the pathogenic processes of atopic der- matitis, psoriasis, allergic contact dermatitis, and infections such as Leishmaniasis • Functionally impaired by ultraviolet radiation. After 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 uTIP aThe most important cells for recognition, uptake and processing of antigens in the skin and presenting these antigens to naïve T-cells aCharacteristic finding on electron microscopy - Birbeck granules- tennis racket shaped bodies in the cell. Be able to identify an electron micros- copy image of a Langerhans Cell
  26. 26. Basic Science and Structure of Skin    13Report a Problem/FeedbackReport a Problem/Feedback 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 • Adult dermis: types I, III, and V; type I accounts for 85% of collagen; type III accounts for 10%; type V accounts for 5% • Lysyl hydroxylase and proline hydroxylase crosslinks col- lagen (desmosine residues) - vitamin C required cofactor (copper and Vitamin B6 also) for function of enzyme - vitamin C deficiency = Scurvy • Type I III are major interstitial fiber forming collagens Table 1–4. 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), bul- lous 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 uTIP aComposed of three chains that vary according to collagen type. All have Gly-X-Y amino acid motif that repeats where X and Y are proline an hydroxy- proline
  27. 27. 14  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback Collagen Diseases Ehlers-Danlos Syndromes • Excessive stretchability and fragility of the skin with a tendency toward easy scar formation (“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 • Forms complex meshwork extending from lamina densa of the DEJ through the dermis and into the hypodermis • Returns skin to normal configuration after being stretched • Elastic fibers: 90% elastin, wrapped by fibrillin microfibrils (mutated in Marfan’s) • Desmosine and isodesmosine are typical amino acids found in elastic fibers, and crosslink 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
  28. 28. Basic Science and Structure of Skin    15Report a Problem/FeedbackReport a Problem/Feedback Anetoderma • Decreased desmosine • Loss of and fragmentation of elastic fibers Dermal Matrix Components • Proteoglycans and glycosaminoglycans → ground substance that surrounds the fibrous constituents of the dermis; 0.2% of dry weight of the dermis • Proteoglycans consist of a “core protein” with a glycosaminoglycan such as hyaluronic acid 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 • Mucopolysaccharidoses represent genetic storage diseases resulting from abnormal lyso- somal function and subsequent accumulation of these substances. → Hurler’s (Alpha-L- iduronidase), Hunter’s (Iduronate sulfatase), for example. See Genodermatoses Chapter for more detail on these conditions 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
  29. 29. 16  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback Mast Cells Table 1–5. 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 • Greatest density in the papillary dermis, in sheaths of the appendages, and around blood vessels and nerves of the subpapillary plexus • Diseases: Mastocytosis, solitary mastocytoma, diffuse erythrodermic mastocytosis, TMEP, UP • Derived from bone marrow-residing CD34+ stem cells  • Proliferation depends on the c-kit receptor and its ligand stem-cell factor (SCF). Mutations in c-kit may result in mastocytosis or piebaldism • Stain CD34+, C-Kit, stem cell factor (SCF), giemsa, teledyne, leder stain (naphthol chloroac etate esterase) • Produced and stored in preformed secretory granules - many inflammatory mediators such as histamine, heparin, tryptase, chymase, carboxypeptidase, neutrophil chemotactic factor, and eosinophilic chemotactic factor of anaphylaxis. Produce IL-8 (strong neutrophil chemo- tactic 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 • Secretory granules are released by a variety of stimuli, and process. Degranulation is identical regardless of stimulus • Degranulation produces vascular smooth muscle contraction, increases vascular permeabil- ity, tissue edema, and the recruitment of inflammatory cells • Responsible for immediate-type hypersensitivity reactions and participate in chronic inflammatory 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 • Allow the rapid shunting of blood from the arterioles to venules, bypassing capillaries - occurs primarily in palms and soles • Disease processes include glomus tumor and glomangioma
  30. 30. Basic Science and Structure of Skin    17Report a Problem/FeedbackReport a Problem/Feedback 1.3 ANTIGENS 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) 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) • 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 1–6. Blistering D/O Antigen Inherited AI K5, 14 EBS Dowling Meara Plectin EBS - MD PNP BPAG2 Generally atrophic benign EB EB, CP
  31. 31. 18  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback 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 • Critical event is availability of surface that promotes adsorption and activation of specific coagulation pro-enzymes • Clot provides a scaffolding for recruitment of cells to injured site • Fibrin and fibronectin act as provisional matrix for infiltrating monocytes, fibroblasts, and newly formed blood vessels • Clearance of clot matrix is as important as deposition, and inadequate removal of provisional 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 • Migrate with monocytes concurrently, but arrive first in great numbers because of their abundance in circulation • Chemoattractants for PMNs: Fibrinogen/fibrin split products, C5a, leukotrienes • If wound contamination controlled, PMN migration ceases within a few days, and PMN’s 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 • Adherence to matrix stimulates expression of cytokines and growth factors FGF, IL-1, TGF- alpha, PDGF, and TGF-beta, therefore facilitating transition from inflammation to repair • Proliferation phase: epithelization granulation collagen deposit; Angiogenesis (stimulated by TNFα) Table 1–6. Blistering D/O (cont.)
  32. 32. Basic Science and Structure of Skin    19Report a Problem/FeedbackReport a Problem/Feedback 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 • Cells in all layers of migrating epidermis contain keratins 5 and 14 (usually only found in 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 • If basement membrane destroyed, migration occurs over provisional matrix of collagen type V, fibrin, fibronectin • Migrating cells both traverse over wound coated with provisional matrix and through wound using an array integrin receptors to guide the path • Collagenase is produced to assist in migration • Migration and dissection results in eschar sloughing • Migration is a result of a combination of chemotactic factors, direct guidance by contact, 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 • Composed of new capillaries, macrophages, fibroblasts and blood vessels, which move into 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 • Fibroplasia is granulation tissue that arises from fibroblasts, and is a mixture of fibroblasts and extracellular matrix (ECM) • Monocytes → macrophages → secretion of growth factors (also from platelets) → fibroblast proliferation and activation of fibroplasia • Once migrated into a wound, protein synthesis occurs to create the ECM/collagen matrix • Wound contraction ensues during second week of healing → governed by wound fibro- 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
  33. 33. 20  2012/2013 Dermatology In-Review l Committed to Your Future Report a Problem/FeedbackReport a Problem/Feedback • Angiogenesis initiated by plasma leak, release of FGF, and subsequent activation of collage- nase to break down the basement membrane on which the endothelial cells rest • The endothelial cells project pseudopods through the basement membrane and subse- 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 • Fibrin: First extracellular matrix to be deposited; for effective hemostasis, interaction must occur with platelets (via GPIIb-IIIa integrin); fibroblasts require fibronectin for migration into a fibrin clot • Fibronectin: circulates in blood and binds fibrin • Hyaluronan (hyaluronic acid): linear polymer (member of glycosaminoglycans); major com- 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 • Pregerm stage: focal crowding of epidermal basal nuclei match by a cluster of mesenchy- mal cells beneath the basement membrane • Crowding of basal keratinocytes causes a slight bud on underside of epidermis—termed the follicle germ or primitive hair germ • Follicle peg: Result of the elongation of follicle germ into a cord of epidermal cells that grows into dermis perpendicular to skin surface • Tip of the epithelial cord becomes matrix portion of the bulb • Outgrowths of cells from the outer root sheath give rise to the presumptive sebaceous gland (uppermost) and the bulge (lowermost)—the insertion site of the arrector pili muscle • Dermal papilla: Deepest portion of the bulbous hair peg that forms an invagination sur- rounding the bulk of the underlying mesenchymal cells
  34. 34. Basic Science and Structure of Skin    21Report a Problem/FeedbackReport a Problem/Feedback • Matrix keratinocytes: Above the BM overlying the dermal papilla—give rise to hair shaft 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 2.) Huxley’s layer 3.) Cuticle • Hair shaft: Three compartments 1.) Cuticle 2.) Cortex—forms bulk of hair 3.) Medulla—central • Critical line of Auber: Widest diameter of the bulb; bulk of mitotic activity that gives rise to the hair and the inner root sheath occurs below this level The Hair Cycle Anagen • 84%, 3-4 years • Follicle traverses entire epidermis • Matrix keratinocytes in the bulb region proliferate rapidly; these cells are pluripotent cells capable of differentiating into cuticle, cortex and medulla of hair shaft • Divided into six substages (I to VI): the first five called collectively proanagen—defined by progressively higher levels of new hair tip position within the follicle; the 6th stage, metana- gen 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  • Stimulus induces the abrupt cessation of mitotic activity in rapidly dividing hair matrix cells; 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 No keratohyalin granules uTIP aInside to outside. Cuticle - IRS - Huxley-Henle - ORS - glassy/vitreous

×