Preventive Dermatology

Robert A. Norman (Ed.)

Preventive
Dermatology
Dr. Robert A. Norman
8002 Gunn Highway
Tampa, Florida,
33626 USA

ISBN: 978-1-84996-020-5     e-ISBN: 978-1-84996-021-2

DOI: 10.1007/978-1-84996-021-2
Springer Dordrecht Heidelberg London New York

Library of Congress Control Number: 2010920241

© Springer-Verlag London Limited 2010

No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written per-
mission from the Publisher, with the exception of any material supplied specifically for the purpose of
being entered and executed on a computer system, for exclusive use by the purchaser of the work.

Printed on acid-free paper

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

 Foreword

In his latest book, Dr. Robert A. Norman introduces us to the intriguing concept of
preventive dermatology. Although dermatologists have long been patient advocates
and have stressed vigorously on the importance of sun avoidance and protection,
there is still much more that we can do to prevent disease.
Dr. Norman and his skilled coterie of collaborators discuss two distinct types of
prevention in dermatology: the prevention of skin diseases and the prevention of sys-
temic disorders, some with only very indirect connections to the skin. The first is
fairly well known to dermatologists; the second is truly an emerging concept of great
importance.
Educational efforts to prevent or at least control skin disease may range from the
proper use of sunscreens to weight loss in psoriatic patients, the avoidance of trigger
factors in rosacea, proper skin care in atopic dermatitis, or adoption of a low-fat diet
to decrease the incidence of actinic keratosis and nonmelanoma skin cancer. Another
good example is the use of vaccines to protect against diseases such as herpes zoster
and genital HPV infection in females.
This book, however, looks beyond the prevention of skin diseases to suggest that
dermatologists view their patients through a more holistic lens. This means treating
the entire patient not just the skin. Thus Dr. Norman suggests that we be more proac-
tive in addressing health issues such as obesity, smoking, stress management, and
nutrition. Consider, for example, the psoriatic patient, whose disease must now be
treated as a systemic disorder predisposing to the very serious risks of the metabolic
triad.
As dermatologists, we deal with numerous chronic diseases, seeing some patients
repeatedly over many years. This longitudinal interaction offers an excellent platform
for the practice of preventive dermatology.
Read and enjoy this book. It could make you a better dermatologist.

Professor and Chairman John E. Wolf, Jr., MD

Department of Dermatology
Baylor College of Medicine

v
 Preface

This is the first book fully dedicated to prevention in dermatology. It seems almost
counterintuitive to take on this task, because so much of what we do in dermatology
is based on repair and restructuring of skin maladies. But with the shortage of derma-
tology providers and the shift to cosmetics and procedures, it is urgent to make sure
our patients are given a fair chance to succeed in the fast-changing world of modern
health care. Although we are specialists in skin care, we are health care providers
first, and should treat our patients with a holistic and caring approach that includes
prevention.
We live in a world between expectation and reality – and our goal as providers is to
help ourselves and our patients anticipate problems and provide solutions. A smoker
may have expectations of invincibility. Like many of you, I have succeeded most often
in getting the person to quit by appealing to the vanity of the smoker by pointing out
the accumulated wrinkles if he or she persists. If that method works, it is a success!
Time’s arrow only moves in one direction – forward – and chronological aging
takes a toll on all of us, especially visible on the most recognizable features of our
facial skin. A rising tide of boomers are arriving daily at the shores of older age and
demanding more help, including prevention of skin problems.
Much can be done to prevent the disfiguring effects brought on by the abuse of
sun, nicotine and alcohol, excess weight, mobility and exercise difficulties, dysfunc-
tional nutrition, improper hygiene, lack of immunizations, poor reading and compre-
hension skills, inadequate cosmetic repair, and many other problems. Preventive
dermatology focuses on ways we can minimize skin problems, and maximize and
enjoy the time we have been given.
We have highly effective sunscreens, a plethora of information about skin care on
the internet, and more prevention and treatment modalities than ever before. But even
the most informed patients need guidance, and that is why you need the information
included in this book. I hope you share this information with your colleagues and
patients, and this first book on prevention in dermatology is a springboard for many
more books, ideas, and discussions to improve the quality of our lives.

Tampa, FL Dr. Robert A. Norman

2010

vii
 Acknowledgment

Thanks to all my patients, friends and family, professors, chapter authors, and to the
great people at Springer, including Grant Weston, Balasaraswathi Jayakumar, Barbara
Lopez-Lucio, and others, who helped give birth to this book.
Dr. Robert A. Norman

ix
 Contents

Part I  Prevention — an Overview

  1 Stress, Relaxation, and General Well-Being . . . . . . . . . . . . . . . . . . . . . . 3

Nana Smith and Francisco A. Tausk

  2 Smoking, Obesity/Nutrition, Sun, and the Skin . . . . . . . . . . . . . . . . . . . 17

Robert A. Norman and Max Rappaport

  3 Raising Awareness on the Health Literacy Epidemic . . . . . . . . . . . . . . 21

Michelle C. Duhaney

  4 Domestic Violence, Abuse, and Neglect: Indicators for Dermatology . . 35

Jina P. Lewallen and Susan R. Adams

  5 Working with Other Healthcare Providers . . . . . . . . . . . . . . . . . . . . . . 47

Jina P. Lewallen, Carolyn Lazaro Tuturro, and Angelo Turturro

  6 The Future of Dermatological Therapy and Preventive Dermatology . . . 57

Robert A. Norman

Part II  Common Problems and Treatment in Dermatological Prevention

  7 Prevention of Drug Reactions and Allergies in Dermatology . . . . . . . . 63

Lisa C. Hutchison and Oumitana Kajkenova

  8 Xerosis and Stasis Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Margaret E. M. Kirkup

  9 Photoprotection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Camile L. Hexsel and Henry W. Lim

10 Biologics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Panoglotis Mitropoulos and Robert A. Norman

11 Occupational Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Athena Theodosatos and Robert Haight

xi
xii Contents

12 Diagnosis and Prevention of Bullous Diseases . . . . . . . . . . . . . . . . . . . . 115

Supriya Venugopal and Dedee F. Murrell

13 Diagnosis and Prevention of Atopic Eczema . . . . . . . . . . . . . . . . . . . . . 137

Stefan Wöhrl

14 Prevention of Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

Gwynn Coatney and Robert A. Norman

15 Sports Dermatology: Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

Brian B. Adams

16 Prevention of Cosmetic Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

Zoe Diana Draelos

17 Nutrition, Vitamins, and Supplements . . . . . . . . . . . . . . . . . . . . . . . . . . 187

Evangeline B. Handog and Trisha C. Crisostomo

Part III  Sexually Transmitted Diseases, Viral Diseases, and Vaccines

18 Vaccines for Viral Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

Ivan D. Camacho and Brian Berman

19 Prevention of Sexually Transmitted Diseases from Office to Globe . . . 211

Kim K. Dernovsek

20 Current Vaccinations in Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . 233

Kamaldeep Singh and Robert A. Norman

Part IV  Wounds, Surgery, and Dermatological Prevention

21 Prevention of Skin Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

Dirk M. Elston

22 Wound Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

Cynthia A. Fleck

23 Prevention of Surgical Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

Michael R. Hinckley

24 Prevention of Keloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281

Hillary E. Baldwin

Appendix 1 Patient Handouts: Preventive Dermatology Topics ��������������� 293

Robert A. Norman and Lana H. McKinley

Appendix 2 Skin Performance Assessment Questionnaire������������������������� 303

Robert A. Norman

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
 Contributors

Brian B. Adams , MD, MPH  Department of Dermatology,

University of Cincinnati, Cincinnati, OH, USA
Susan R. Adams, BA, MSW (LCSW ACADC CCDP-D, QMRP) 
Department of Health Science (Addiction Studies),
University of Central Arkansas, Conway, AR, USA
Hillary E. Baldwin, MD  Department of Dermatology,
SUNY – Brooklyn, Brooklyn, NY, USA
Brian Berman, MD, PhD  Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
Ivan D. Camacho, MD  Department of Dermatology and Cutaneous Surgery,
University of Miami, Miami, FL, USA
Gwynn E. Coatney, DO  Department of Family Medicine,
University of Medicine and Dentistry of New Jersey, Stratford, NJ, USA
Trisha C. Crisostomo, MD  Section of Dermatology,
Research Institute for Tropical Medicine, Muntinlupa City, Philippines
Kim K. Dernovsek, MD  Department of Dermatology and Family Medicine,
University of Colorado Health Sciences Center, Pueblo, CO, USA
Zoe Diana Draelos, MD  Department of Dermatology,
Duke University School of Medicine, 2444 North Main Street, High Point,
Durham, North Carolina NC 27262
Michelle C. Duhaney, DO  Department of Family Medicine,
Broward General Medical Centre, Fort Lauderdale, FL, USA
Dirk M. Elston, MD  Department of Dermatology,
Geisinger Medical Center, Danville, PA, USA
Cynthia A. Fleck, MBA, BSN, RN, ET/WOCN, CWS, DNC, CFCN 
The American Academy of Wound Management (AAWM), Past President,
The Association for the Advancement of Wound Care (AAWC), Past Director,
Medline Industries, Inc., Vice President, Clinical Marketing, St. Louis, MO, USA
Robert Haight, MD, MS, PH  Consultant Sarasota, Private Practice Sarasoda
Florida, FL, USA

xiii
xiv Contributors

Evangeline B. Handog, MD, FPDS  Department of Dermatology,

Asian Hospital and Medical Center, Filinvest Corporate City,
Mutinlupa, Alabang, Philippines
Camile L. Hexsel, MD  Department of Dermatology,
Henry Ford Hospital, Detroit, MI, USA
Michael R. Hinckley, MD  Department of Dermatology,
Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA
Lisa C. Hutchison, PharmD, MPH  Department of Pharmacy Practice,
College of Pharmacy, University of Arkansas for Medical Sciences,
Little Rock, AR, USA
Oumitana Kajkenova, MD  Department of Geriatrics,
Thomas and Lyon Longevity Clinic, University of Arkansas for Medical Sciences,
Little Rock, AR, USA
Margaret E. M. Kirkup, MBChB, MRCP  Department of Dermatology,
Weston General Hospital, Weston-super-Mare, Avon, UK
Jina P. Lewallen, LCSW, MA  Department of Geriatrics,
University of Arkansas for Medical Sciences, Little Rock, AR, USA
Henry W. Lim, MD  Department of Dermatology,
Henry Ford Hospital, Detroit, MI, USA
Lana H. McKinley, BS, MS IV  College of Osteopathic Medicine,
Nova Southeastern University, Fort Lauderdale-Davie, FL, USA
Panoglotis Mitropoulos, DO  Camp Long Troop Medical Clinic, South Korea
Dedee F. Murrell, MA (Cambridge) BMBCh (Oxford) FAAD (USA) MD
(UNSW)  Department of Dermatology, St. George Hospital,
University of NSW Medical School, Sydney, Australia
Robert A. Norman, DO, MPH  Nova Southeastern University,
Ft. Lauderdale, Florida and Private Practice, Tampa, FL, USA
Max J. Rappaport, BA  Ist Year Medical Student LECOM Bradenton, Florida
Kamaldeep Singh, DO  Internal Medicine Resident,
Stony Brook University Hospital, Stony Brook, NY, USA
Nana Smith, MD  Department of Dermatology,
University of Rochester, Rochester, NY, USA
Francisco A. Tausk, MD  Department of Dermatology and Psychiatry,
University of Rochester, Rochester, NY, USA
Athena Theodosatos, DO, MPH  Department of Family Medicine,
Florida Hospital, Winter Park, FL, USA
Angelo Turturro, PhD, DADT  Graduate Gerontology Program,
School of Social Work, University of Arkansas at Little Rock, Little Rock, AR, USA
Contributors xv

Carolyn Lazaro Turturro, PhD, CHES  Graduate Gerontology Program,

School of Social Work, University of Arkansas at Little Rock,
Little Rock, AR, USA
Supriya Venugopal, BSc (Med) MBBS (UNSW)  Department of Dermatology,
St. George Hospital, University of NSW Medical School,
Sydney, Australia
Stefan Wöhrl, MD, MSc  Department of Dermatology,
Division of Immunology, Allergy and Infections Diseases (DIAID),
Medical University of Vienna, Vienna, Austria
 Part
I
Prevention — An Overview
 Stress, Relaxation, and General Well-Being
Nana Smith and Francisco A. Tausk
Your pain is the breaking of the shell that encloses your understanding. … It is the bitter potion by
which the physician within you heals your sick self. Therefore trust the physician, and drink his
remedy in silence and tranquility…
We instinctively understand that, in general, stress is
an uncomfortable and deleterious physical and emo-
tional state. However, it is often difficult to recognize
and control. In dermatology, stress can be both a con-
sequence and an instigator of disease. This chapter will
explore (1) definitions of stress, (2) the interplay
between stress and the skin, and (3) various stress-
reducing modalities.
1.1 Stress
Stress encompasses a myriad of emotional and physi-
cal triggers which have a taxing effect on our bodies.
Stress can be acute or chronic. As humans, we are well
adapted to acute stress. Imagine the changes in our
predecessors’ heart rate and blood flow in response to
the proximity of a predator. However, it could be
argued that the concept of chronic stress is a creation
of the modern world. Our ability to adapt to chronic
stress is not necessarily innate and requires a much
more creative and active approach.
Stress can be considered as a disruption of balance
which triggers various adaptive responses. Hans Selye,
N. Smith (*)
Department of Dermatology, University of Rochester,
Rochester, NY, USA
e-mail: nananamibia_smith@urmc.rochester.edu
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_1, © Springer-Verlag London Limited 2010
1
From The Prophet, Khalil Gibran
a 1930s endocrinologist, coined the term stress and
defined it in terms of the General Adaptation Syndrome.
Throughout his career he performed various experi-
ments which showed that animals respond to stress in
three stages. In the General Adaption Syndrome, the
first stage is alarm. The physiology of this stage is well-
understood and represents an acute response to stress.
The sympathetic nervous system is activated, releasing
catecholamines (CA) such as epinephrine and norepi-
nepharine. This is the fight-or-flight response which
causes blood to flow toward large muscular groups and
away from the gastrointestinal system, the skin, and
other organs. Walter Cannon, who in the 1920s first
coined the term “fight or flight”1 described the
responses of the sympathetic nervous system and adre-
nal gland to environmental stressors.2 The hypotha-
lamic-pituitary-adrenal (HPA) axis is also stimulated,
which releases hormones such as cortisol. Resistance is
the second stage. Here the body’s coping resources are
gradually diminished. In the final, exhaustion stage, the
resources are depleted and the subject is unable to
maintain homeostasis. Interestingly, the fight-or-flight
response may now briefly reappear. However, with con-
tinued stressors, the adrenal gland and the immune sys-
tem are sufficiently taxed and illnesses begin to
manifest. This is analogous to a state of chronic stress.
The term allostasis refers to the balance between
stressors and coping mechanisms; it is the ability
to  adapt to maintain balance and stability. This is
a  slightly different framework for stress than that
defined by Seyle.3 Allostasis is different from
3
4 N. Smith and F. A. Tausk
homeostasis in that homeostasis is concerned with
minute-to-minute regulation of bodily functions in a
very narrow range whereas in allostasis the range is
much wider. McEwen views the consequences of
chronic stress as a type of allostatic load which can
build up and lead to disease. In the ideal situation, a
person is presented with a stressor, the body compen-
sates by initiating certain stress responses, and when
the stressor is gone, the stress response is shut off. In
this situation, there is little allostatic load. Conditions
in which allostatic load can build up include frequent
stressor over time, lack of adaptation to stressors
(decreased response to stressors over time), inability
to shut down a stress response, and inadequate initial
response which leads to compensations by other stress
responses.4
Acute and chronic stresses have different effects on
our bodies. The effects are seen in the cardiovascular
and endocrine/metabolic systems, the brain, and the
immune system.
1.2 Stress, Immune Function,
and the Skin
There is a complex interplay between stressors, the
central nervous system, the endocrine system, immune
function, and the skin. The HPA axis is stimulated by
signals which are processed in the hypothalamus and
the brain stem (locus ceruleus [LC]). In response to
Fig.  1.1  The hypothalamic-pituitary-adrenal (HPA) axis and
immunity. The identification of an external perceived stressor by
the brain results in the activation of the paraventricular nucleus
of the hypothalamus and the closely interconnected locus coer-
uleus. CRF is secreted from the hypothalamus and transported
through the portal circulation to the pituitary, where it induces
the release of ACTH from the anterior pituitary into the general
circulation. The effect of this molecule results in the secretion of
glucocorticosteroids and to a lesser extent CA from the adrenal
gland. Cortisol will act as a negative feedback on the hypothala-
mus, inhibiting the release of CRF. The cells of the locus coer-
uleus have a rich neuronal connection with the PVN, and activate
the sympathetic system which results in the secretion of epi-
nephrine and nor-epinephrin. Both the cathecholamines and cor-
tisol have a potent effect on the immune system. They modulate
antigen presenting cells and macrophages inhibiting their activ-
ity and the production of IL-12 and IL-18, and they mediate the
differentiation of naïve T helper cells towards the TH2 constel-
lation, in detriment of the development of TH1 mediated immu-
these stressors, the hypothalamus secretes corticotro-
phin-releasing hormone (CRH). From the hypothala-
mus, CRH-containing neurons communicate with the
brain stem and spinal cord. CRH release further acti-
vates the HPA axis by causing the release of peptides
from the pituitary. The peptides, such as adrenocorti-
cotropic hormone (ACTH), enkephalins, and endor-
phins, are produced by the differential cleavage of
pro-opiomelanocortin (POMC). ACTH induces release
of glucocorticoids (GC) such as cortisol from the adre-
nal cortex. Activation of the noradrenergic pathways
by CRH-containing neurons results in secretion of nor-
peinephrine (NE) by the sympathetic nervous system
and release of NE and epinephrine (EPI) from the
adrenal medulla. These are called CA. The activation
of the sympathetic nervous system and the adrenal cor-
tex and the subsequent release of hormones and neu-
rotransmitters have significant effects on the immune
system (Fig. 1.1).
In general, Th1-derived cytokines (IFN-a, IL-2) are
considered proinflammatory whereas Th2-derived
cytokines (IL-4, IL-5, IL-10) are considered anti-
inflammatory. Both GCs and CAs have the ability to
create a shift toward the Th2 pathway by up-regulating
Th2-cytokine production and also by suppressing APC
production of IL-12 and Th1 cytokine synthesis5
(Fig. 1.1). APC-derived IL-12 is one of the main induc-
ers of Th1 cytokine synthesis.6 Therefore, chronic
stress is essentially immunosuppressive. Furthermore,
immune challenges such as bacterial infections can
result in the release of bacterial lipopolysaccharides
nity. This results in tilting the balance towards humoral immunity
by increasing the production of IL-4, IL-5, and IL-13, which
activate B-cells, mast cells, and eosinophils, increasing the aller-
gic inflammatory response. The chronic dampening of cell-
mediated immunity could result in an impaired ability to confront
effectively the development of infectious or tumoral insults. On
the other hand, internal stressors are exemplified here by bacte-
rial infections. The released bacterial lipopolysaccharides (LPS)
bind to toll-like receptors on macrophages, and through NFkB
induce the production of IL-1 and IL-6. These cytokines are able
to cross the blood–brain barrier and reach the hypothalamus,
where they stimulate the secretion of CRF, initiating the activa-
tion of the HPA axis. In this manner, infections have the poten-
tial to shift the immune balance favoring the humoral TH2
mediated response. Diseases that involve this arm of the immune
system such as autoimmune or allergic diseases would deterio-
rate during the presence of stressors of the internal as well as
external kind. Stimulation (straight arrows). Inhibition (broken
arrows). Reproduced with permission from Harth et al104
1  Stress, Relaxation, and General Well-Being
(LPS) which induces the nuclear factor (NF) kb medi-
ated secretion of IL-1 and IL-6. These cytokines are
responsible for fatigue, somnolence, and fever. These
cytokines (IL-1, IL-6) stimulate the hypothalamic
stress response in a positive feedback loop (Fig. 1.1).
One main mechanism for the ability of GCs to ­suppress
APCs is by inhibiting the costimulatory molecules
STRESS
5
necessary for T cell activation. GCs also decrease the
ability of neutrophils to find sites of inflammation
(decreased chemotaxis) and to attach to vascular
endothelium and extravasate into the tissue.
The skin itself is a major source of central neuroen-
docrine stress mediators and has fully active peripheral
equivalents of central stress responses systems. For
Inflammation
6 N. Smith and F. A. Tausk
example, skin cells produce a variety of neuropeptides,
hormones, and neurotransmitters which have been
implicated in modulating immune function in the skin,
communicating with the hypothalamus, and playing a
role in the development of skin diseases. The brain can
affect inflammatory conditions in the skin but stimuli
received by the skin can also influence the immune,
endocrine, and nervous systems.7
Stress decreases wound-healing capacities. Kiecolt-
Glaser et al found that in normal, healthy dental ­students,
the time to heal a mucosal wound was approximately 3
days slower at the time of examination.8 They also
showed that married couples with hostile interactions
had impaired wound healing compared to happier cou-
ples. These findings may be explained by the effects of
stress on matrix metalloproteinases (MMPs) and the
tissue inhibitors of metalloproteinases (TIMPs).9, 10
Tausk et  al investigated the effects of stress in mice
induced by the smell of fox urine (a natural predator).
Mice exposed to stress showed delayed wound healing
compared to control mice (unpublished data).
As most dermatologists have witnessed from their
patients, skin disease is often worsened or initiated by
stressful situations. Patients even associate conditions
that have not been described in the literature as being
stress-associated with increased stress in their lives.
The stressor need not be emotional in nature; we are
well aware of dermatologic conditions associated with
recent illness, a type of physical stress. Emotional
stressors have been associated with the development or
worsening of a variety of dermatologic diseases includ-
ing acne, vitiligo, alopecia areata, lichen planus, sebor-
rheic dermatitis, telogen effluvium, herpes simplex
infections, pemphigus, urticaria, psoriasis, angioedema
atopic dermatitis, hyperhidrosis, neurotic excoriations,
warts, cysts, and more.11–18
Stress has been reported to both precede the onset
of psoriasis19 and to trigger flares.20, 21 The observation
that led to further study of psoriasis and stress involved
psoriasis patients who have undergone physical
trauma. In some cases, where there was traumatic dis-
connection of sensory nerves, the psoriatic skin in the
innervated areas resolved. When the fibers regener-
ated and sensitivity returned, the psoriatic plaques
returned. It was hypothesized that local neuropeptides
where responsible for the persistence of psoriatic
plaques. It was later discovered that not only do psori-
atic plaques have different content of neuropeptides
such as SP (substance P), VIP (vasoactive intestinal
peptide), CGRP(calcitonin gene-related protein), and
NGF (nerve growth factor) but the density of nerve
fibers in the plaques is elevated.22–25 Increased levels
of NGF causes T cell and keratinocyte proliferation,
mast cell degranulation, and memory T cell chemot-
axis, which are all features seen in psoriasis.26–28 The
HPA axis in psoriasis patients also exhibits an insuf-
ficient production of cortisol in the face of experimen-
tal stressors.29, 30
In atopic dermatitis, stress can also worsen the
existing disease and stimulate flares.31, 32 In experimen-
tal studies, stress has been found to interfere with the
barrier function of the skin.33 When the straum cor-
neum is unable to recover from transepidermal water
loss, the barrier is disrupted, inviting various infectious
agents and allergens to initiate a disease flare.34 Another
explanation for the connection between stress and
atopic dermatitis is that, much as in psoriasis, patients
with this disease have an insufficient HPA axis response
to stress.35–37 Interestingly, the circulating leukocytes in
patients with atopic dermatitis have a higher number of
GC receptors than control patients. Therefore, and per-
haps in compensation for a blunted HPA response,
when immune cells are exposed to even a small amount
of cortisol produced by stress they are hyperactive
along the cortisol-induced Th2 pathway.38 This is det-
rimental, as IL-4 and IL-10 activate mast cells, eosino-
phils, and IgE production which further worsens atopic
dermatitis. The worsening of atopic dermatitis in the
face of stress may also be, in part, caused by the effects
of epinephrine.39
Episodes of urticaria, especially adrenergic urti-
caria, have been associated with stressful events. Again,
the cortisol-induced upregulation of Th2 cytokines,
leading to the activation and degranulation of mast
cells could explain this phenomenon40 as well as the
fact that mast cell CRH receptors41 are upregulated
under stress.
Stress also plays a role in infections of the skin
including those bacterial, viral, and fungal in nature.42–46
In rats, stressed by restraining them, HSV is reactivated
in the dorsal root ganglion. Epidemiologic studies have
found that in humans it is chronic, not necessarily acute
stress which is associated with more frequent out-
breaks.46,47 Various stress-reducing techniques have
been shown to reduce outbreak frequency.48
In both human and animal studies, stress has been
linked to malignancy, perhaps by suppressing lympho-
cyte and especially natural killer (NK) cell activity.49–62
1  Stress, Relaxation, and General Well-Being
Parker et al reported findings linking stress to skin can-
cer in mice.63 Two groups of mice were exposed to UV
light; one group was stressed by the smell of a predator
and the other group was not. The stressed group devel-
oped squamous cell carcinomas (SCCs) significantly
earlier than the nonstressed group (SCC at week 8 vs.
week 21, p < 0.05). This observation was confirmed by
another group.64 Stress-reducing interventions have
shown a survival benefit for patients with malignan-
cies.65 For example, patients with metastatic melanoma
had an increased 6-year survival rate when a stress-
reducing and psychological intervention was made.66
Again, this may be linked to altered NK function under
stressful situations.67 In other studies, the cytotoxic
function of the lymphocytes in older adults and in
immunocompetent medical students was altered by
chronic stress; relaxation training increased this cyto-
toxic function.68, 69 Other mice models have shown that
chronic stress suppresses lymphocyte proliferation,
increases metastases risk and growth of the primary
tumor.70–72
1.3 Epidemiology
Use of various stress-reducing modalities for skin dis-
ease is common among dermatologic patients through-
out the world.73
A study performed in Leeds and South Wales in the
United Kingdom investigated the use of complemen-
tary and alternative medicine (CAM) among patients
presenting to an outpatient dermatology clinic. Three
hundred and two completed questionnaires in Leeds
and 415 in South Wales revealed that about 20% of
Leeds patients and 5% of South Wales patients used
aromatherapy. Faith or spiritual healing was used in
about 10% in each group. Hypnotherapy was used in
approximately 10% of Leeds patients and 5% of South
Wales patients. Massage was used by around 15% of
Leeds patients.74 Researchers elsewhere conducted
109 face-to-face interviews of patients referred to con-
tact dermatitis clinic and found that aromatherapy was
used by 18%.75 A German study conducted a validated
questionnaire in 1,288 patients; 73 patients with atopic
dermatitis under conventional therapy and 59 patients
under alternative-medical therapy. In the alternative
therapy group 65% used autogenic training and 43%
used relaxation procedures for their skin disease. The
7
numbers were 29 and 13% respectively for the conven-
tional group.76 A study of 198 patients from the derma-
tology clinic at Show Chwan Memorial Hosp in
Changhua City, Taiwan found that aromatherapy
(4.6%), Qi-gong/Tai-Chi/yoga (r%), religion (1.5%),
and meditation/hypnosis (0.5%) were used.77 A self-
administered questionnaire from 70 patients with atopic
dermatitis referred to the university clinic at Oregon
Health and Science University revealed that hypnosis
(10.3%), massage (10.3%), and biofeedback (3.4%)
were commonly used.78
1.4 Stress-Reducing Modalities
In the realm of CAM, it is the mind–body interven-
tions that have the most obvious implications for stress
reduction. Use of mind–body interventions by the gen-
eral American public is common (though not necessar-
ily among dermatology patients). In 2002, mind–body
techniques, including relaxation, meditation, guided
imagery, biofeedback, and hypnosis were used by
about 17% of the adult US population. Prayer was used
by 45% of the population for health reasons.79
These modalities have shown their use in a variety
of conditions: from coronary artery disease80 and pain
control81, 82 to managing the symptoms of cancer and
the side effects of its treatment.83–85
There are a multitude of case reports, case series,
and some clinical trials suggesting that various mind–
body interventions are useful in dermatologic condi-
tions. The findings which relate to dermatology will be
presented at the end of each of the following sections
where appropriate. We will now look more closely into
various stress-reducing techniques which may be help-
ful for people with skin disease.
1.4.1 Yoga
Yoga is a spiritual practice which incorporates physi-
cal activity (breathing exercises and poses or postures)
and meditation to create a connection between the
mind and body.86 It has been used in India for over
5,000 years as a system of healing and a framework for
how to live one’s life and obtain spiritual enlighten-
ment. In the West, however, it grew popular as a form
8 N. Smith and F. A. Tausk
of exercise. Yoga was first introduced to the American
society in the late nineteenth century by Swami
Vivekananda. He believed that India had an abundance
of spiritual wealth and that yoga could help those in
Western societies to achieve spiritual well-being. Most
yoga classes consist of a combination of physical exer-
cises, breathing exercises, chanting, and meditation.
Yoga may improve resistance to psychological stress,
decrease feelings of bodily self-objectification, and
promote a feeling of wholeness, balance, and well-
being.86, 87
According to a survey by the National Center for
CAM, yoga was the fifth most commonly used CAM
therapy (2.8%) in the United States during 2002.79 It is
thought by its practitioners to prevent specific diseases
by keeping “energy meridians” open and “life energy”
(Prana) freely flowing. Yoga is usually performed in
group classes. Sessions are conducted at least once a
week and for approximately 45  min. Yoga has been
used to lower blood pressure, reduce stress, and improve
coordination, flexibility, concentration, sleep, and diges-
tion. It has also been used as supplementary therapy
for such diverse conditions as cancer, diabetes, asthma,
AIDS, and irritable bowel syndrome.88
There are many different styles of yoga; each has a
particular emphasis.
Hatha is a term that can encompass many of the
physical types of yoga. It is slow-paced and gentle and
is a good introduction to the basic yoga poses. Vinyasa,
which means breath-synchronized movement, is a
more vigorous style in which various poses (sun salu-
tations) are connected to certain breathing techniques.
Ashtanga, or power yoga is not recommended for
beginning students. This is an intense, fast-paced style
in which the poses are sequentially performed leading
to a fluid movement from one pose to the other. Iyengar
yoga is focused on bodily alignment and is interested
in the details of each posture. The poses are typically
held much longer than in other styles and props such as
blankets, blocks, and straps are also used. This is a
good style for beginners. Bikram yoga or hot yoga is
practiced in a 95–100°room, which creates a sauna-
like effect that is thought to be cleansing and good for
the muscles. Anusara combines an emphasis on align-
ment with the belief that there is intrinsic goodness in
all beings. These classes are good for students of dif-
fering abilities and are very calming. Kundalini is an
energizing form of yoga which is aimed at freeing
“dormant spiritual energy” at the base of the spine and
allowing it to move upwards. Jivamukti yoga is ath-
letic, physically challenging but highly meditative.
The focus is on fitness. Integral yoga is a gentle Hatha
style which follows the teachings of Sri Swami
Sachidananda, who came to the United States in the
1960s. It is aimed at helping people integrate yoga’s
teachings into everyday life. Sivananda is a traditional,
more lifestyle approach to yoga. The class structure is
rigid and is based on five principles: proper exercise,
proper breathing, proper relaxation, proper diet (vege-
tarian), and positive thinking and meditation. Kripalu
yoga is focused on healing. It is great for beginning
students and teaches inner focus and meditation, focus
on alignment, breath, and presence of consciousness.
Integrative yoga was designed for medical and main-
stream wellness settings (hospitals and rehab). It
involves gentle postures, guided imagery, and breath-
ing techniques for treating specific health issues. It
emphasizes holistic healing.
1.4.2 Deep Breathing
Deep breathing is the act of breathing deep into your
lungs by expanding your diaphragm rather than breath-
ing shallowly by expanding your rib cage. It is also
called diaphragmatic breathing, abdominal breathing,
or belly breathing. When you breathe deeply your
abdominal wall expands rather contracts. It is often
used for hyperventilation and anxiety. To perform dia-
phragmatic breathing one should sit or lie wearing
loose comfortable clothing. One hand is placed on the
chest and one on the abdomen. Inhale through the nose
or pursed lips. During inhalation, the abdomen should
expand or press outward, the chest should not. Slowly
exhale through pursed lips and then rest and repeat.
The inhalation and exhalation times should be about
equal. This method of stress reduction may be difficult
for people with diaphragmatic dysfunction from vari-
ous respiratory or neuromuscular conditions.
1.4.3  Tai Chi
Tai chi originated in China as a martial art. Over time,
people also began to use it for health purposes. Tai
chi  incorporates a series of exercises that mimic the
1  Stress, Relaxation, and General Well-Being
movements of certain animals with concepts of flexi-
bility and meditation. The body moves slowly and gen-
tly, while the person is breathing deeply and meditating.
Tai Chi practitioners believe that tai chi helps the flow
of “vital energy” called qi. One can practice alone or in
a group. Many movements are named for animals or
birds, such as “White Crane Spreads Its Wings.” The
simplest styles of tai chi incorporate 13 movements
into a routine, but more complex routine can be learned.
The entire body is always in motion as one movement
flows into another. The upper body is kept upright and
it is important to concentrate and not be distracted.
Breathing should be deep, relaxed, and focused. People
practice tai chi for a variety of health purposes includ-
ing pain control, stress reduction, insomnia, enhancing
coordination, flexibility and balance, and overall well-
being. Tai chi is practiced by many people in China,
even in hospitals and clinics. It is especially beneficial
for the elderly.
1.4.4 Progressive Relaxation
Progressive muscle relaxation was developed by an
American physician Edmund Jacobson in the early
1920s as a stress reduction technique. It remains popu-
lar with modern physical therapists. The goal is to
reduce anxiety and the effects of stress of the muscula-
ture. Jacobson found that the technique is also effective
against ulcers, insomnia, and hypertension. Progressive
relaxation is similar to autogenic training which is a
form of self-hypnosis. The technique involves progres-
sively tensing and then relaxing every consciously con-
trolled muscle group until the entire body is relaxed;
the sequence usually goes from head to foot. It is best
done lying down on the floor or a bed.
1.4.5 Aromatherapy
Aromatherapy is the use of plant-derived essential
oils as a form of supportive care to improve quality of
life and reduce stress and anxiety. Fragrant oils have
been used for health purposes for thousands of years
and in a variety of cultures. Essential oils (or volatile
oils) are derived from various parts of the plant (leaves,
bark, peel) and are usually extracted using alcohol.
9
They are very concentrated. Aromatherapy likely
works through smell receptors in the nose communi-
cating with the brain’s limbic system and altering
mood and emotions. The volatile oils are either inhaled
by using a diffuser, or applied topically (usually in a
diluted form) as part of a massage, poultice, or bath.
Aromatherapy may improve quality of life in patients
with cancer with regard to reducing side effects such
as nausea, anxiety, and insomnia. Safety testing on
essential oils shows few side effects when they are
used as directed. Some essential oils have been approved
as ingredients in food and are classified as GRAS
(generally recognized as safe) by the US Food and
Drug Administration. However, allergic contact or
irritant dermatitis may occur in aromatherapists or in
patients using aromatherapy, especially with long
periods of skin contact. Photosensitivity may develop
when citrus or other oils are applied to the skin before
sun exposure. Lavender and tea tree oils have been
found to have hormone-like effects similar to estrogen
and also block or decrease the effect of androgens.
Applying lavender and tea tree oils to the skin over a
long period of time has been linked to gynecomastia
in prepubescent boys. Essential oils with aldehyde or
phenols structures especially cause an irritant derma-
titis. Oils with ketone derivatives can cause neurotox-
icity in epileptics, pregnant women, and babies.
Sassafras oil and calamus oil have been shown to be
carcinogenic.89, 90
Stevensen reviewed the dermatologic applications of
various essential oils. Some of the antiseptic oils were
geranium, petitgrain, winter savory, and tea tree oil.
Juniper berry has anti-inflammatory properties whereas
frankincense is an immunostimulant. French lavender is
useful for burns, cajeput for genital herpes, and chamo-
mile and lavender are good for stress reduction.89
Bensouilah also reviewed the use of aromatherapy
in psoriatic patients to reduce disease severity and
symptoms and to increase quality of life. Several anti-
inflammatory oils were listed which may be helpful in
psoriasis including achillea millefolium, borage oil,
evening primrose oil, sweet  almond oil, jojoba wax,
tamanu oil (for the scalp especially), calendula, and
avocado oil.90
When mice with experimental contact hypersensi-
tivity were exposed to terpinyl acetate (which has a
herbal lavender woody smell) and valerian oil in the
presence of stress, the contact hypersensitivity wors-
ened. The theory is that if stress is immunosuppressive,
10
which would mute a contact dermatitis, stress reduction
(via pleasant scents) would attenuate some of this immu-
nosuppression and a more florid skin response would be
seen. Valerian oil was also found to downregulate stress-
induced plasma corticosterone levels in the mice.91
Another study in mice suggested that the smell of
­tuberose, lemon, oakmoss, and labdanum reduces some
of  the immunologic effects of high-pressure-induced
stress.92 Finally, in human volunteers, the smell of
­lavender and rosemary decreased saliva cortisol and
increased free radical scavenging activity.93
A randomized controlled double blind trial of aro-
matherapy for alopecia areata was performed in 86
patients in an outpatient setting. Patients were random-
ized to massaged thyme, rosemary, lavender, and
cedarwood oil mixed in carrier oils (jojoba and grape-
seed) vs. the carrier oils alone. These oils were mas-
saged onto the scalp daily for 7 months and results
were evaluated at 3 and 7 months in terms of dermotol-
ogist-evaluated photographs and computer analysis of
severity. Forty-four percent of patients in the aro-
matherapy group vs. 15% of patients in the control
group showed improvement at the end of the trial
(p > 0.008).94
1.4.6 Massage
Massage therapy refers to a group of practices and
techniques involving pressing, rubbing, and manipula-
tion of the muscles and other soft tissues of the body.
Most often the hands and fingers are used but fore-
arms, elbows, feet, hot stones, and other tools are
sometimes used. Some examples are Swedish mas-
sage, deep tissue massage, and shiatsu massage. A
2002 national survey on Americans’ use of CAM (pub-
lished in 2004) found that 5% of the 31,000 partici-
pants had used massage therapy in the preceding 12
months, and 9.3% had ever used it.79 People use mas-
sage for a variety of reasons including pain relief, reha-
bilitation, stress reduction, and general well-being.
Patients with a deep vein thrombosis, bleeding disor-
ders or on anticoagulation, peripheral vascular disease,
osteoporosis or recent fracture, tumors, open or heal-
ing wounds, neuropathy, or myopathies should consult
their physician before receiving massage.
In addition to providing stress reduction, massage
may be beneficial in certain dermatologic conditions
N. Smith and F. A. Tausk
for other reasons. For example, emollients may be more
effectively applied by massage in patients with atopic
dermatitis, psoriasis, other dermatitic conditions, and
icthiosis. Massage is often used as an adjuvant to com-
pression stockings in lymphadema clinics. There is
some theoretic suggestion that massage may help pre-
vent fibrosis which may be useful in combination with
conventional therapies for morphea and other fibrotic
disorders. In general, touching the skin of our patients
communicates lack of repulsion and judgment which is
incredibly important in conditions like psoriasis which
cause profound feelings of stigma and alienation.
1.4.7 Mindfulness Meditation
Meditation refers to a group of techniques, the goal of
which is to enhance health and wellness through the
quiet focusing attention and maintenance of an open
mind. Most time meditation involves a specific pos-
ture. People who practice meditation can often increase
relaxation, calmness, and mental balance and enhance
coping. Research using functional magnetic resonance
imaging (fMRI) suggests that the areas of the brain
involved in paying attention and in the control of the
autonomic nervous system are stimulated during medi-
tation. A large national survey on Americans’ use of
CAM, found that nearly 8% of the participants had
used meditation specifically for health reasons during
the year before the survey.79 Mindfulness meditation
has its origins in Buddhism. The concept is that one
is  fully present during the meditation process; this
involves being “mindful” or aware of thoughts, emo-
tions, and physical feelings (including breath), what-
ever they may be.
Gaston et  al performed a randomized, controlled
trial to evaluate the efficacy of meditation as an adjunc-
tive treatment for scalp psoriasis. For 20 weeks, 24
subjects were randomly allocated to one of four
groups:  meditation, meditation and imagery, waiting
list for treatment, and a treatment-free control. Eighteen
­subjects completed the trial. The meditation group
did home meditation for 30 min daily. Subjects were
allowed to continue their conventional psoriasis medi-
cations. The investigators used a blinded clinical sever-
ity score consisting of thickness, erythema, and scale
and surface area. Using a Spearman’s coefficient,
the  group was measuring the relationship over time
1  Stress, Relaxation, and General Well-Being
between psoriasis and stress. The investigators found a
significant difference between meditation vs. the con-
trol groups for treatment of psoriasis (r > 0.30, p < 0.01),
with no impact of imagery. The clinical assessment
also strongly supported this finding.95
Kabat, Zinn, et al performed a controlled trial with
two independent randomization steps: randomization
into ultraviolet B (UVB) vs. psoralen and ultraviolet A
(PUVA) cohorts and randomization into use of a mind-
fulness-based stress reduction audiotape during light
therapy vs. no audiotape. Patients received either UVB
or PUVA therapy 3 times weekly until their psoriasis
cleared or they dropped out of the study. During their
light therapy, half of the subjects listened to tapes that
encouraged being mindful of breathing, of body sensa-
tion, of ambient sounds, thoughts, and feelings and
encouraged visualization of UV light slowing down the
division of skin cells. The other half (control) received
light therapy in silence. Thirty-seven subjects with
moderate to severe psoriasis participated in the study.
Their rate of psoriatic lesion clearing was assessed on
four occasions in three independent ways: directly by
unblinded clinic nurses, directly by blinded physicians,
and indirectly via lesion photographs by blinded physi-
cians. Time to first response, time to turning point, and
time to halfway clearing were measured. In the UVB
group there was a significantly shorter time to turn-
ing  point and time to halfway clearing compared to
­controls (p > 0.005, 0.002, respectively). In the PUVA
group there was no significant difference between
groups. Using Cox-proportional hazards regression
models which adjust for confounding factors such as
years with psoriasis and initial psychological state,
estimated response time-to-clearance curves were con-
structed. These estimated curves showed a significantly
shorter time-to-clearance between mindfulness tape
and no mindfulness tape groups.96
1.4.8 Biofeedback
Biofeedback is a procedure which provides the subject
with feedback about certain bodily functions with the
assistance of certain instruments. It provides a sort of
mirror for various types of biological information. One
is connected to a machine that monitors heart beat,
muscle tone, skin temperature or resistance, and elec-
tric potential of the brain (EEG) for instance. The
11
subject receives information about the activity level of
those functions in the form of visual or auditory sig-
nals. The goal is to consciously control these functions
to reach a desired state (i.e., reduced skin temperature
in psoriasis). The most common forms of biofeedback
are galvanic skin response, electromyographic bio-
feedback, thermal biofeedback, and electroencephalo-
graphic rhythm biofeedback. The electromyographic
biofeedback (which measures variations in muscle
electric potential) is best for anxiety states. Two phases
are usually performed. There is a relaxation phase in
which the practitioner gathers information about the
patient’s life experiences, difficulties relaxing, and
various images, thoughts, or sensations. The technical
phase is when the therapist takes measurements and
helps the patient overcome obstacles to relaxation.
Usually 10–20 sessions are needed, with 1–2/week.
Patients are encouraged to practice at home for 20 min
a day using elementary portable instruments. The goal
is that control of the function becomes automatic such
that the subject can reproduce it in stressful situa-
tions.97 The most reasonable application in dermatol-
ogy would be for neurodermatitis and related disorders
(tricotillomania) and for pruritis.
Keinan et al treated 32 subjects in a 3-month ran-
domized, double-blind, controlled trial in which sub-
jects were divided into three groups. One group was
trained to do biofeedback and relaxation techniques,
one relaxation only and the third group received no
treatment. Efficacy was evaluated by a six-point symp-
tom severity scale which ranged from no symptoms to
very severe symptoms and by a symptom improvement
scale, a nine-point scale ranging from complete remis-
sion to extreme worsening. No significant changes in
symptom severity scale or symptom improvement
scale were found.98
Biofeedback has also been reported to have efficacy
in hyperhydrosis and Raynaud’s disease.
1.4.9 Autogenic Training
Autogenic training is a form of self-hypnosis and relax-
ation which is usually used for stress control. Stewart
and Thomas treated 18 adults with extensive atopic
dermatitis with hypnotherapy, relaxation, and  stress
management. During the hypnotherapy patients received
direct suggestions for nonscratching behavior, skin
12
comfort and coolness, and ego strengthening. Patients
also received instructions on self-hypnosis. In this non-
randomized controlled clinical trial, significant reduc-
tions in itching, scratching, sleep disturbance, and
tension were found compared to the control group. Use
of topical steroids decreased by 60% at 16 weeks.99
1.4.10 Hypnosis
Hypnosis was initially described in the late eighteenth
century by Franz Anton Mesmer and was further
developed by Milton Erickson in modern times. It is an
altered state of consciousness in which the suggestions
from someone else, the environment, or from oneself,
allow the imagination to create a vivid reality. People
innately have different levels of suggestiveness; in
other words, people who are highly suggestible are
more likely to benefit from hypnosis. It is difficult to
predict a person’s level of suggestiveness.
Many case reports of dermatologic conditions
responding to hypnosis have been published.95 These
include clearing of congenital ichthiosiform erythro-
derma of Brocq, erythromelalgia, herpes simplex, acne
excoriee, alopecia areata, trichotillomania, neuroder-
matitis, furuncles, rosacea, vitiligo, and others. There
have been case series of the efficacy of hypnosis for
urticaria. Nonrandomized controlled trials exist for
atopic dermatitis and, for verruca vulgaris, psoriasis
and relaxation during procedures, there have been ran-
domized controlled trials. Controlled studies using
direct suggestion in hypnosis (DSIH) for warts show
success rates between 27 and 55%. Children respond
especially well.100
Tausk and Whitmore used hypnosis to treat psoriasis
in a randomized, controlled, single-blind, 3-month
study. Eleven patients with mild-to-moderate stable
psoriasis were randomized to one of two groups: hyp-
nosis with active suggestion or neutral hypnosis. In the
active treatment, group subjects were asked to image
the conventional therapy which they believed to be most
effective for their psoriasis. Only subjects who were
identified as being highly or moderately suggestible
were included in the study. Subjects were treated with
weekly hypnosis sessions for 3 months according to the
treatment group; then the investigator was unblinded
and both groups received active suggestion hypnosis for
3 more months. Psoriasis severity was assessed using
N. Smith and F. A. Tausk
the Psoriasis Area and Severity Index (PASI) and was
performed by a different, blinded investigator. Results
showed that highly suggestible individuals vs. moder-
ately suggestible individuals had a significant improve-
ment in psoriasis severity (p < 0.05).101
1.4.11 QI Gong/Reiki/Healing Touch
Energy medicine is a CAM modality that deals with
energy fields of two types: veritable and putative. The
veritable energies are those that can be measured; they
use vibrations, electromagnetic forces, visible light,
and monochromatic radiation (i.e., LASER) for exam-
ple. Putative energy cannot be measured. CAM modal-
ities which claim to alter this subtle, immeasurable
energy are reiki, qi gong, and healing touch.
Qi gong is practiced commonly in clinics and hos-
pitals of China. It is a branch of traditional Chinese
medicine which is aimed at restoring balance and the
free flow of qi or life energy. Reiki is a similar practice
that originated in Japan. Therapeutic touch is perhaps
the Western equivalent of the prior two modalities. All
three involve movement of the practitioner’s hands
over the patient’s body to sense and ultimately manip-
ulate energy throughout the body.
The evidence for these modalities is mixed and
sparse. However, to the extent that they reduce stress,
reiki, qi gong, and healing touch may be useful in der-
matology patients.
1.4.12 Prayer
Particularly devastating dermatologic conditions have
the potential to alter our patients’ sense of spiritual
well-being. Sometimes a sense of spirituality may allow
a patient to better cope with a particular condition or
diagnosis, other times patients feel a sense of divine
punishment from their skin condition. It is important to
know the role that spirituality plays in our patients’
lives, to the extent that we can support any positive
attributes it may add to conventional management. If
the patient obtains emotional support from his/her spir-
ituality it would be appropriate to encourage patients to
speak with a chaplain, clergy member, or spiritual
leader regarding the condition. Dermatologists, and
1  Stress, Relaxation, and General Well-Being
any physician, should respectfully support the patient’s
use of spirituality to cope with their disease. If one
feels comfortable, it is appropriate to both pray for and
with patients when they are facing difficult times or
decisions.102
In an Austrian study, 215 patients with melanoma
were interviewed about their interests in CAM and rea-
sons for pursuing this. More than half had an interest
in nonconventional therapies. Interested subjects had a
more active coping style, a tendency toward religious-
ness, and need to search for personal meaning in their
disease than noninterested subjects. They also believed
that they were receiving less emotional support from
their physicians than the other group and expressed
interest in getting more of such support.103
1.5 Conclusion
As dermatologists, we have no less of an obligation to
practice in the context of a bio-psycho-social model
than other physicians. We should make it a habit to ask
our patients about their stress levels and to what extent
it contributes to their skin disease. It is also important
to have practical advice to offer patients in terms of
stress reduction techniques. To the extent of our con-
trol, the office setting and the personal experiences
patients encounter in the clinic should be relaxing and
promoting of the healing process. Also, in order to
effective carry out our responsibilities as physicians,
each of us should frequently monitor and control the
stress in our own lives so that optimal care of our
patients is not compromised.
References
  1. Cannon WB. The Wisdom of the Body. New York: Norton;
1932
  2. Selye H. The Stress of Life. New York: McGraw-Hill; 1956
  3. Sterling P, Eyer J. Allostasis: a new paradigm to explain
arousal pathology. In: Fisher S, Reason J, eds. Handbook of
Life Stress, Cognition and Health. New York: John Wiley;
1988:629–649
  4. McEwen BS. Protective and damaging effects of stress
mediators. Seminars in Medicine of the Beth Israel Deaconess
Medical Center. N Engl J Med. 1998;338(3):171–179
  5. Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 pat-
terns, pro/anti-inflammatory cytokines and susceptibility to
disease. Trends Endocrinol Metab. 1999;10(9):359–368
13
  6. Trinchieri G. Interleukin-12 and the regulation of innate
resistance and adaptive immunity. Nat Rev. 2003;3(2):
133–146
  7. Marucha PT, Kiecolt-Glaser JK, Favagehi M. Mucosal
wound healing is impaired by examination stress. Psychosom
Med. 1998;60(3):362–365
  8. Stamenkovic I. Extracellular matrix remodelling: the role of
matrix metalloproteinases. J Pathol. 2003;200(4):448–464
  9. Yang EV, Bane CM, MacCallum RC, et  al Stress-related
modulation of matrix metalloproteinase expression. J Neuro­
immunol. 2002;133(1–2):144–150
10. Chiu A, Chon SY, Kimball AB. The response of skin disease
to stress: changes in the severity of acne vulgaris as affected
by examination stress. Arch Dermatol. 2003;139(7):
897–900
11. Papadopoulos L, Bor R, Legg C, Hawk JL. Impact of life
events on the onset of vitiligo in adults: preliminary evidence
for a psychological dimension in aetiology. Clin Exp Dermatol.
1998;23(6):243–248
12. Barisic-Drusko V, Rucevic I. Trigger factors in childhood
psoriasis and vitiligo. Coll Antropol. 2004;28(1):277–285
13. Gulec AT, Tanriverdi N, Duru C, et al The role of psycho-
logical factors in alopecia areata and the impact of the dis-
ease on the quality of life. Int J Dermatol. 2004;43(5):
352–356
14. Chaudhary S. Psychosocial stressors in oral lichen planus.
Aust Dental J. 2004;49(4):192–195
15. Cohen F, Kemeny ME, Kearney KA, et al Persistent stress as
a predictor of genital herpes recurrence. Arch Intern Med.
1999;159(20):2430–2436
16. Goldberg IA, Brenner S. Pemphigus vulgaris triggered by
rifampin and emotional stress. Skinmed. 2004;3(5):294
17. Berrino AM, Voltolini S, Fiaschi D, et al Chronic urticaria:
importance of a medical-psychological approach. Allerg
Immunol. 2006;38(5):149–152
18. Naldi L, Peli L, Parazzini F, Carrel CF. Family history of
psoriasis, stressful life events, and recent infectious disease
are risk factors for a first episode of acute guttate psoriasis:
results of a case-control study. J Am Acad Dermatol. 2001;
44(3):433–438
19. Fortune DG, Richards HL, Griffiths CE, Main CJ.
Psychological stress, distress and disability in patients with
psoriasis: consensus and variation in the contribution of ill-
ness perceptions, coping and alexithymia. Br J Dermatol.
2002;41:157–174
20. Fortune DG, Richards Hl, Griffiths CE, Main CJ. Psychologic
factors in psoriasis: consequences, mechanisms, and inter-
ventions. Dermatol Clin. 2005;4:681–694
21. Farber RSP, EM RSK. Role of nerve growth factor in
RANTES expression by keratinocytes. Acta Derm Venereol.
2000;80(4):247–250
22. Nickoloff BJ, Schroeder JM, von den Driesch P, et al Is pso-
riasis a T-cell disease? Exp Dermatol. 2000;9:357–375
23. Farber EM, Nall L. Psoriasis: a stress-related disease. Cutis.
1993;51(5):322–326
24. Farber EM, Nickoloff BJ, Recht B, Fraki JE. Stress, sym-
metry, and psoriasis: possible role of neuropeptides. J Am
Acad Dermatol. 1986;14(2 Pt 1):305–311
25. Aloe L, Alleva E, Fiore M. Stress and nerve growth factor:
findings in animal models and humans. Pharmacol Biochem
Behav. 2002;73(1):159–166
14
26. Raychaudhuri SP, Jiang WY, Farber EM. Psoriatic keratino-
cytes express high levels of nerve growth factor. Acta Derm
Venereol. 1998;78(2):84–86
27. Raychaudhuri SP, Jiang WY, Smoller BR, Farber EM. Nerve
growth factor and its receptor system in psoriasis. Br J
Dermatol. 2000;143(1):198–200
28. Richards HL, Ray DW, Kirby B, et al Response of the hypo-
thalamic-pituitary-adrenal axis to psychological stress
in  patients with psoriasis. Br J Dermatol. 2005;153(6):
1114–1120
29. Schmid-Ott GJR, Jaëger B, et  al Stress induced endocrine
and immunological changes in psoriasis patients and healthy
controls. Psychother Psychosom. 1998;67:37–42
30. Langan SM, Bourke JF, Silcocks P, Williams HC. An explor-
atory prospective observational study of environmental fac-
tors exacerbating atopic eczema in children. Br J Dermatol.
2006;154(5):979–980
31. Faulstich ME, Williamson DA, Duchmann EG, et  al Psy­
chophysiological analysis of atopic dermatitis. J Psychosom
Res. 1985;29(4):415–417
32. Altemus M, Rao B, Dhabhar FS, et al Stress-induced changes
in skin barrier function in healthy women. J Invest Dermatol.
2001;117(2):309–317
33. Zane L. Psychoneuroendocrinimmunodermatology: pathophys-
iological mechanisms of stress in cutaneous disease. In: Koo
JYM, Lee CS, eds. Psychocutaneous Medicine. New York:
Marcel Dekker; 2003:65–95
34. Buske-Kirschbaum A, Jobst S, Psych D, et  al Attenuated
free cortisol response to psychosocial stress in children with
atopic dermatitis. Psychosom Med. 1997;59(4):419–426
35. Buske-Kirschbaum A, Geiben A, Hollig H, et  al Altered
responsiveness of the hypothalamus-pituitary-adrenal axis
and the sympathetic adrenomedullary system to stress in
patients with atopic dermatitis. J Clin Endocrinol Metab.
2002;87(9):4245–4251
36. Rupprecht M, Rupprecht R, Kornhuber J, et al Elevated gluco-
corticoid receptor concentrations before and after glucocorti-
coid therapy in peripheral mononuclear leukocytes of patients
with atopic dermatitis. Dermatologica. 1991;183:100–105
37. Schmid-Ott G, Jaeger B, Meyer S, et al Different expression
of cytokine and membrane molecules by circulating lym-
phocytes on acute mental stress in patients with atopic der-
matitis in comparison with healthy controls. J Allergy Clin
Immunol. 2001;108:455–462
38. Delgado M, Fernandez-Alphonso MS, Fuentes A. Effect of
adrenaline and glucocorticoids on monocyte cAMP-specific
phospodiesterase (PDE4) in a monocyte cell line. Arch
Dermatol Res. 2002;294:190–197
39. Theoharides TC, Donelan JM, Papadopoulou N, et al Mast
cells as targets of corticotropin-releasing factor and related
peptides. Trends Pharmacol Sci. 2004;25(11):563–568
40. Papadopoulou N, Kalogeromitros D, Staurianeas NG, et al
Corticotropin-releasing hormone receptor-1 and histidine
decarboxylase expression in chronic urticaria. J Invest
Dermatol. 2005;125(5):952–955
41. Biondi M, Zannino LG. Psychological stress, neuroimmu-
nomodulation, and susceptibility to infectious diseases in
animals and man: a review. Psychother Psychosom. 1997;66
(1):3–26
42. Bailey MT, Engler H, Sheridan JF. Stress induces the trans-
location of cutaneous and gastrointestinal microflora to
N. Smith and F. A. Tausk
s­ econdary lymphoid organs of C57BL/6 mice. J
Neuroimmunol. 2006;171(1–2):29–37
43. Rojas IG, Padgett DA, Sheridan JF, Marucha PT. Stress-
induced susceptibility to bacterial infection during cutane-
ous wound healing. Brain Behav Immun. 2002;16(1):74–84
44. Buske-Kirschbaum A, Geiben A, Wermke C, et  al Pre­
liminary evidence for Herpes labialis recurrence following
experimentally induced disgust. Psychother Psychosom.
2001;70(2):86–91
45. Cohen S, Frank E, Doyle WJ, et al Types of stressors that
increase susceptibility to the common cold in healthy adults
[see comments]. Health Psychol. 1998;17(3):214–223
46. Cohen S, Tyrrell DA, Smith AP. Psychological stress and
susceptibility to the common cold [see comments]. N Engl J
Med. 1991;325(9):606–612
47. VanderPlate C, Kerrick G. Stress reduction treatment of
severe recurrent genital herpes virus. Biofeedback Self Regul.
1985;10(2):181–188
48. Yang EV, Glaser R. Stress-induced immunomodulation:
implications for tumorigenesis. Brain Behav Immun. 2003;17
(suppl 1):S37–S40
49. Reiche EM, Nunes SO, Morimoto HK. Stress, depression,
the immune system, and cancer. Lancet Oncol. 2004;5(10):
617–625
50. Reiche EM, Morimoto HK, Nunes SM. Stress and depres-
sion-induced immune dysfunction: implications for the
development and progression of cancer. Int Rev Psychiatr.
2005;17(6):515–527
51. Lillberg K, Verkasalo PK, Kaprio J, et al Stressful life events
and risk of breast cancer in 10, 808 women: a cohort study.
Am J Epidemiol. 2003;157(5):415–423
52. Riley V. Psychoneuroendocrine influences on immunocom-
petence and neoplasia. Science. 1981;212(4499):1100–1109
53. Wu W, Yamaura T, Murakami K, et al Social isolation stress
enhanced liver metastasis of murine colon 26–L5 carcinoma
cells by suppressing immune responses in mice. Life Sci.
2000;66(19):1827–1838
54. Ramirez AJ, Craig TK, Watson JP, et al Stress and relapse of
breast cancer [see comments]. BMJ. 1989;298(6669):291–293
55. Havlik RJ, Vukasin AP, Ariyan S. The impact of stress on
the clinical presentation of melanoma. Plast Reconstr Surg.
1992;90(1):57–61; discussion 2-4
56. Reynolds P, Kaplan GA. Social connections and risk for can-
cer: prospective evidence from the Alameda County Study.
Behav Med. 1990;16(3):101–110
57. Jacobs JR, Bovasso GB. Early and chronic stress and their
relation to breast cancer [In Process Citation]. Psychol Med.
2000;30(3):669–678
58. Grossarth-Maticek R, Eysenck HJ, Boyle GJ, et  al
Interaction of psychosocial and physical risk factors in the cau-
sation of mammary cancer, and its prevention through psy-
chological methods of treatment. J Clin Psychol. 2000;56(1):
33–50
59. Laudenslager ML, Ryan SM, Drugan RC, et al Coping and
immunosuppression: inescapable but not escapable shock
suppresses lymphocyte proliferation. Science. 1983;221
(4610):568–570
60. Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G. Evidence
that stress and surgical interventions promote tumor devel-
opment by suppressing natural killer cell activity. Int
J Cancer. 1999;80(6):880–888
1  Stress, Relaxation, and General Well-Being
61. Ben-Eliyahu S. The promotion of tumor metastasis by sur-
gery and stress: immunological basis and implications
for  psychoneuroimmunology. Brain Behav Immun. 2003;
17(suppl 1):S27–S36
62. Parker J, Klein SL, McClintock MK, et  al Chronic stress
accelerates ultraviolet-induced cutaneous carcinogenesis.
J Am Acad Dermatol. 2004;51(6):919–922
63. Saul AN, Oberyszyn TM, Daugherty C, et al Chronic stress
and susceptibility to skin cancer. J Natl Cancer Inst. 2005;
97(23):1760–1767
64. Spiegel D, Bloom JR, Kraemer HC, Gottheil E. Effect of
psychosocial treatment on survival of patients with meta-
static breast cancer [see comments]. Lancet. 1989;2(8668):
888–891
65. Fawzy FI, Fawzy NW, Hyun CS, et al Malignant melanoma.
Effects of an early structured psychiatric intervention, cop-
ing, and affective state on recurrence and survival 6 years
later. Arch Gen Psychiatr. 1993;50(9):681–689
66. Herberman RB, Ortaldo JR. Natural killer cells: their roles
in defenses against disease. Science. 1981;214:24–30
67. Kiecolt-Glaser JK, Garner W, Speicher C, et al Psychosocial
modifiers of immunocompetence in medical students. Psy­
chosom Med. 1984;46(1):7–14
68. Glaser R, Rice J, Speicher CE, et al Stress depresses inter-
feron production by leukocytes concomitant with a decrease
in natural killer cell activity. Behav Neurosci. 1986;100(5):
675–678
69. Riley V. Psychoneuroendocrine Influences on immunocom-
petence and neoplasia. Science. 1981;212:1100–1109
70. Wu W. Social isolation stress enhanced liver metastasis of
murine colon 26–L5 carcinoma cells by suppressing immune
responses in mice. Life Sci. 2000;66:1827–1838
71. Laudenslager ML. Coping and immunosuppression: ines-
capable but not escapable shock supresses lymphocyte pro-
liferation. Science. 1983;221:568–570
72. Ernst E. The use of complementary therapies by dermato-
logical patients: a systematic review. Br J Dermatol. 2000;
142:857–861
73. Baron SE, Goodwin RG, Nicolau N, et  al Use of comple-
mentary medicine among outpatients with dermatologic con-
ditions within Yorkshire and South Wales, United Kingdom.
J Am Acad Dermatol. 2005;52:589–594
74. Nicolaou N, Johnston GA. The use of complementary medi-
cine by patients referred to a contact dermatitis clinic.
Contact Derm. 2004;51:30–33
75. Augustin M, Zschocke I, Buhrke U. Attitudes and prior
experience with respect to alternative medicine among der-
matological patients: the Freiburg questionaire on attitudes to
naturopathy (FAN). Res Complement Med. 1999;6 (suppl 2):
26–29
76. Chen Yu-Fu, Chang JS. Complementary and alternative
medicine use among patients attending a hospital dermatol-
ogy clinic in Taiwan. Int J Dermatol. 2003;42:616–621
77. Simpson EL, Basco M, Hanifin J. Cross-sectional survey of
complementary and alternative medicine use in patients with
atopic dermatitis. Am J Contact Derm. 2003;14:144–147
78. Barnes PM, Powell-Griner E, McFann K, Nahin RL. Comple­
mentary and alternative medicine use among adults: United
States, 2002. CDC Advance Data Report #343. 2004
79. Rutledge JC, Hyson DA, Garduno D, et al Lifestyle modifi-
cation program in management of patients with coronary
15
artery disease: the clinical experience in a tertiary care hos-
pital. J Cardiopulm Rehabil. 1999;19(4):226–234
80. Luskin FM, Newell KA, Griffith M, et al A review of mind/
body therapies in the treatment of musculoskeletal disorders
with implications for the elderly. Altern Ther Health Med.
2000;6(2):46–56
81. Astin JA, Shapiro SL, Eisenberg DM, et al Mind-body medi-
cine: state of the science, implications for practice. J Am
Board Fam Pract. 2003;16(2):131–147
82. Mundy EA, DuHamel KN, Montgomery GH. The efficacy
of behavioral interventions for cancer treatment-related side
effects. Sem Clin Neuropsychiatr. 2003;8(4):253–275
83. Irwin MR, Pike JL, Cole JC, et  al Effects of a behavioral
intervention, Tai Chi Chih, on varicella-zoster virus specific
immunity and health functioning in older adults. Psychos­
omatic Med. 2003;65(5):824–830
84. Kiecolt-Glaser JK, Marucha PT, Atkinson C, et al Hypnosis
as a modulator of cellular immune dysregulation during
acute stress. J Consult Clin Psychol. 2001;69(4):674–682
85. yoga.about.com Yoga and Your Health, by Ann Pizer; 2008
Accessed 12.1.08
86. Cancer.gov. Pain control: Support for People with Cancer;
2008 Accessed 25.1.08
87. Deutsch J, Anderson E. Complementary Thera­pies for Phys­
ical Therapy: A Clinical Decision-Making Approach. Chap­
ter 8: Therapeutic Aspects of Yoga. St. Louis, MO: Saunders/
Elsevier; 2008
88. Stevensen CJ. Aromatherapy in dermatology. Clin Dermatol.
1998;16:689–694
89. Bensouilah J. Psoriasis and aromatherapy. Int J Aromatherap.
2003;13:2–8
90. Hosoi J, Tanida M, Tsuchiya T. Mitigation of stress-induced
suppression of contact hypersensitivity by odorant inhala-
tion. Br J Dermatol. 2001;145:716–719
91. Fujiwara R, Komori T, Noda Y, et al Effects of a long-term
inhalation of fragrances on the stress-induced immunosup-
pression in mice. Neuroimmunomodulation. 1998;5(6):
318–322
92. Atsumi T, Tonosaki K. Smelling lavender and rosemary
increases free radical scavenging activity and decreases cor-
tisol level in saliva. Psychiatr Res. 2007;150:89–96
93. Hay I, Jamieson M, Ormerod AD. Randomized trial of aro-
matherapy: successful treatment for alopecia areata. Arch
Dermatol. 1998;134:1349–1352
94. Gaston L, Crombez J, Lassonde M, et al Psychological stress
and psoriasis: experimental and prospective correlational
studies. Acta Derm Venereol (Stockh). 1991;156:37–43
95. Kabat-Zinn J, Wheeler E, Light T, et al Influence of a mind-
fullness meditation-based stress reduction intervention on
rates of skin clearing in patients with moderate to severe
psoriasis undergoing phototherapy (UVB) and photochemo-
therapy (PUVA). Psychosomatic Med. 1998;60:625–632
96. Sarti MG. Biofeedback in dermatology. Clin Dermatol.
1998;16:711–714
97. Keinan G, Segal A, Gal U, Brenner S. Stress management
for psoriasis patients: the effectiveness of biofeedback and
relaxation techniques. Stress Med. 1995;11(1):235–241
98. Schenefelt PD. Complementary psychocutaneous therapies
in dermatology. Dermatol Clin. 2005;23:723–734
99. Bellini MA. Hypnosis in dermatology. Clin Dermatol. 1998;
16:725–726
16
100. Tausk FA, Whitmore E. A pilot study of hypnosis in the
treatment of patients with psoriasis. Psychother Psychosom.
1998;68:221–225
101. Thomsen RJ. Spirituality in medical practice. Arch Derm.
1998;134:1443–1446
102. Sollner W, Zingg-Schir M, Rumpold G, Fritsch P. Attitude
toward alternative therapy, compliance with standard
N. Smith and F. A. Tausk
t­reatment, and need for emotional support in patients with
melanoma. Arch Derm. 1997;133:316–321
103. Branzzini B, Ghersetich I, Hercogava J, Lotti T. The neuro-
immuno-cutaneous-endocrine network: relationship bet­
ween mind and skin. Dermatol Ther. 2003;16:123–131
104. Harth W, Gieler U, Kusnir D, Tausk FA. Clinical Management
of Psychodermatology. Heidelberg: Springer; 2009
 Smoking, Obesity/Nutrition,
Sun, and the Skin
Robert A. Norman and Max Rappaport
It is well-known that costs for medical problems asso-
ciated with smoking, obesity, malnutrition, and sun
damage are very high, making it extremely important
to push the notion of prevention in all of these cases.
Between 1995 and 1999, it has been estimated that the
United States spent $157 billion in healthcare costs.1
The costs associated with medical costs in the United
States attributed to inactivity alone are around $75 bil-
lion.2 Many medical issues are preventable, which an
uninformed person may not realize. But information
on the risks of smoking, obesity, or tanning is well-
documented and readily available. Still today there are
around 1.25 billion smokers who will die an average of
7 years earlier than their nonsmoking counterparts.3
About 30% of people worldwide are considered to be
obese and the numbers have been increasing dramati-
cally ever since the 1980s.4, 5 Every year according to
the World Health Organization (WHO),6 sun damage
causes 60,000 premature deaths and the loss of 1.5
million disability-adjusted life years (DALYs); in addi-
tion almost 30 million Americans tan indoors every
year.7 Health risks associated with these three high-
risk factors have become common knowledge in many
countries. Yet doctors see patients seeking healthcare
related to damage done by one or more of these risks
time and time again. The most difficult and expensive
approach will always be to treat the complications
related to a risky behavior after an accumulation of
damage, thus – as with anything else in life – prevent-
ing a problem before it occurs is always the best option.
R. A. Norman (*)
Nova Southeastern University, Ft. Lauderdale,
Florida and Private Practice, Tampa, FL, USA
e-mail: skindrrob@aol.com
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_2, © Springer-Verlag London Limited 2010
2
All three of these risky behaviors are preventable.
Positive behavioral changes, even after damage, can be
extremely beneficial to a person’s future health.
2.1 Smoking
The dangers of smoking cigarettes have become well-
known; though the damage to the skin has been less
studied. The smoke released from burning cigarettes at
temperatures of 830–900°C contains some 5,000
chemicals. Many of these are hydrophobic agents that
can diffuse through many cell membranes, reaching to
the far ends of the body’s precious organs, including
the skin.3, 8 Many of the dangerous chemicals are in the
form of free radicals and oxidants, which can cause the
malfunction of many biological functions and create
cell damage. Smoking has been shown to increase
many symptoms associated with aging: altered hor-
mone production, reduced fertility, cancer, cardiovas-
cular and respiratory disease, and diseases of the lung,
esophagus, pharynx, larynx, stomach, pancreas, blad-
der, uterine, cervix, and skin.3, 8–10
Smoking causes premature aging of the skin by
affecting the color, tone, and wrinkling. Smoking can
also increase the risk for developing psoriasis, mela-
noma, squamous cell carcinomas on lips and oral
mucosa, acne, and hair loss. Smoking also causes
poor wound healing due to reduction of oxygen and
nutrients to the skin.9,11–14 Many of the mechanisms
that can explain these findings are complex and inex-
act. Premature skin aging may be caused in part by
the same mechanisms which seem to cause the entire
body’s aging process.15 The premature death of smok-
ers follows similar old-age-related illnesses of non-
smokers such as osteoporosis, cancers, macular
17
18
degeneration, and cardiovascular diseases.12 The
acceleration of aging in smokers may be caused in
part by actual damage to the body or from destruction
of chemicals needed to prevent aging in the body by
causing molecular malfunctioning, leading to an
increase in tumor development and a reduction in
wound healing.3 Another theory on the causation of
premature wrinkling of the skin may be increased
elastosis in the skin. It has been found that the amount
of wrinkling is directly related with the amount and
duration of cigarettes smoked. The mechanism by
which wrinkling occurs on the skin may be the same
as the mechanism by which collagen and elastin in
the lungs are damaged. Lastly, there is an idea that the
skin damage is caused by extended exposure to
intense heat while smoking.12 Smoking also affects
the levels of antioxidants in the body, accounting for
premature aging. Many of the chemicals in the ciga-
rette smoke cause damage that has been shown to
decrease cutaneous blood flow and immune responses
in the blood and decrease the level of vitamin C, vita-
min E, circulating levels of nitrous oxide, and plasma
concentrations, while increasing lipid peroxidation.8
Health damage and premature deaths caused by
smoking are in a large part preventable. An emphasis
on preventing new smokers is important because quit-
ting can be a difficult process. Every year almost 15
million smokers attempt to quit smoking in the United
States, with around one million in specific cessation
programs.13 This very small proportion of the actual
smokers shows how difficult quitting can be. While
people hear from everyone around them, including the
media, that smoking is bad for their health, a health-
care provider must always push further intervention.
Talking to parents of pediatric patients and directly to
pediatric patients as early as possible is the primary
role of the physician. Increasing education in schools
about the dangers of smoking can also be a powerful
tool to reduce new smoking behavior. It has been
shown that health education programs using negative
images to discourage smoking is more effective than
positive images.16 Actual, real-life, positive role mod-
eling by older students, parents, and teachers may be
just as effective. While young smokers imagine the
typical smoker as smart, good-looking, and consider-
ate, nonsmokers perceive smokers as dull, childish,
and confused. Reinforcement of the nonsmokers’
beliefs is important by positive role modeling.16 For
youths who have already begun smoking, knowledge
R. A. Norman and M. Rappaport
that smoking may increase the rate of facial aging may
increase their likeliness of quitting.13 Informing young
smokers of the positive health benefits of quitting may
be a powerful tool. It is known, for example, that the
risk of psoriasis decreases with every year of smoking
cessation and becomes insignificant 20 years after a
smoker has quit.13
2.2 Obesity and Nutrition
Obesity is another preventable disorder that, if gone
untreated, can lead to a number of medical complications
including orthopedic and metabolic problems, disrupted
sleep, weakened immune system, impaired mobility,
increased blood pressure, and hypertension. Psychosocial
consequences include low self-esteem and depression.
Long-term consequences include cardiovascular disease,
insulin resistance, type 2 diabetes, hyperlipidemia, gall
bladder disease, osteoarthritis, and certain cancers. When
looking at prevention, it is important to note that obese
children tend to grow into obese adults.4
Skin complications related to obesity include5,17,18:
• Acanthosis nigricans
• Acrochordons
• Keratosis pilaris
• Hyperandrogenism and hirsutism
• Striae distensae
• Adiposis dolorosa and fat redistribution
• Lymphedema
• Chronic venous insufficiency
• Plantar hyperkeratosis
• Cellulitis
• Hidradenitis suppurativa
• Psoriasis
• Insulin resistance syndrome
• Tophaceous gout
• Changes in cutaneous sensation and temperature
regulation
• Foot pain
• Candidiasis
• Intertigo
• Candida folliculosis
• Erythrasma
• Tinea cruris
• Folliculitis
• Necrotizing fasciitis
2  Smoking, Obesity/Nutrition, Sun, and the Skin 19

• Gas gangrene the necessary and available protection to prevent ill-

• Leg ulcerations nesses associated with sun damage. Many factors
• Plantar hyperkeratosis affect the level of UVR a person can receive yearly,
from distal factors such as ozone levels, cloud cover,
Skin disorders attributed to malnutrition include scurvy,
latitude, season, and lower atmospheric pollution, to
pellagra, ariboflavinosis, vitamin A deficiency, phryno-
proximal factors such as sun-seeking, sun-protecting
derma, and kwashiorkor.19, 20 Treatment of obese patients
behaviors, genetic skin pigmentation, and cultural
can also lead to a number of complications including
dress and behaviors.6 UVR damage can suppress cell-
difficulty in treating wounds and abnormal medicine
mediated immunity in the body, have an adverse affect
dosages.5
on the eyes and skin, and increase the risk of cancer.
Obesity prevention and nutritional education to the
Absence of UVR can produce an insufficiency of
youth must be a powerful tool in the fight to prevent
vitamin D, increasing the risk of other complications
more obese adults. There are a number of factors that
including rickets, osteomalacia, osteoporosis, and
may be affecting the increased prevalence in obesity
tuberculosis.21
both in adults and in children. The list includes the
The skin is especially susceptible to damage from
individual’s genetic makeup including psychological
the sun; it is the first organ of the body to come in con-
tendencies; the individual family’s eating habits and
tact with UVR rays and covers the entire surface of the
amount of active behaviors while at school, school
body. Specific damage to the skin caused by sun dam-
food, availability of vending machines, and cheap and
age include malignant melanoma, cancer of the lip,
readily available high-calorie, low-nutrition foods
squamous cell carcinoma, basal cell carcinoma, sun-
including fast foods. While many factors such as genet-
burn, photo-aging (wrinkles), psoriasis, and other pho-
ics and societal may not be readily changed, preven-
todermatoses such as solar urticaria, photoallergic
tion will always be easier than treatment.
contact dermatitis, actinic prurigo, polymorphic light
Treating at-risk overweight kids before they become
eruption, and hydroa vacciniforme.21
obese is extremely important. Care must be taken in
Any skin damage caused by the sun is almost
school-based obesity prevention programs to prevent
entirely preventable. For proper protection sunscreen
stigmatizing overweight children or pushing already
with reapplications is necessary; wearing hats and
underweight children further in that dangerous direc-
long-sleeve shirts when in the sun is also recom-
tion.4 Prevention programs must promote exercise,
mended. Be aware of your risk category; people with
how to eat healthily, and the dangers associated with
lighter skin tend to burn more easily. People who spend
becoming obese. The most effective prevention plans
their work days out-of-doors should be aware of the
must be effective, sustainable, and not harm the partici-
risks and take similar precautions.
pants. Extreme low-calorie diets (<700 daily calories)
A general risk that should be addressed by the phy-
with a lack of fruits, vegetables, fish, and eggs can lead
sician is the fact that intentional sun damage to gain a
to a deficiency in many essential vitamins and cause
tan, even if using sunscreen, is a risk for all the same
malnutrition disorders, such as phrynoderma, usually
skin damages caused by sun damage without sun-
found in undeveloped nations. If detected early, diets
screen. Knowledge on the damages caused by the sun
rich in the missing vitamins and nutrients can be imple-
is well-known and yet ignored by too many of today’s
mented to prevent these disorders.20 Positive role mod-
youth and adults.
eling and education must be used by all those who teach
or influence children from the earliest age possible, of
the dangers and risks of not taking care of their bodies.
2.4 Synergy of Risk and Integrating
Prevention
2.3 Sun Damage
It is clear that smoking, exposure to UVR rays, obe-
Many societies today value the appearance of a dark, sity, and poor nutrition can lead to a number or derma-
rich tan, causing many people to expose themselves tological issues that are entirely preventable. It has
to high levels of ultraviolet radiation (UVR) without been noted that persons who participate in one type of
20
risky behavior are more likely to participate in others.
Therefore, it is necessary to consider that a combina-
tion of risk factors may be synergistic in nature, thus
accelerating damage by just one risk factor. When
looking at prevention, education in all of these risk fac-
tors must be addressed in part and as a whole. Positive
role modeling by older peers, teachers, parents, and
even physicians is extremely important in the battle of
prevention. It has been noted that the more ambiguous
a prevention plan is and the larger the number of pos-
sible options it offers, the more it is perceived with
skepticism about its effectiveness and the more it is
met with inaction.22
Another tool in fighting the three risks simultane-
ously is directing education at those in the process of
smoking cessation, as persons trying to change one
aspect of their life may be more inclined to change
other aspects of their life at the same time.23 Finally, it
is clear that action taken must be aimed at the younger
populations to further educate persons on the risks
associated with risky behaviors and the ease of pre-
venting the harmful and deadly effects of smoking,
malnutrition, obesity, and sun damage.
References
  1. World Health Organization. World No Tobacco Day 2004.
Tobacco and Poverty: A Vicious Circle. http://www.emro.who.
int/tfi/wntd2004/Kit-Part1.htm; 2008 Accessed 29.12.08
  2. World Health Organization. Physical Activity. http://www.
who.int/dietphysicalactivity/publications/facts/pa/en/; 2008
Accessed 29.12.08
  3. Bernhard D, Moser C, Aleksandar Backovic A, Wick G.
Cigarette smoke – an aging accelerator? Exp Gerontol. 2007;
42:160–165
  4. Doak CM, Visscher TLS, Renders CM, Seidell JC. The pre-
vention of overweight and obesity in children and adoles-
cents: a review of interventions and programmes. Obes Rev.
2006;7:111–136
  5. Scheinfeld NS. Obesity and dermatology. Clin Dermatol.
2004;22:303–309
  6. Lucas R, Prüss-Üstün A, World Health Organization, et al
Solar ultraviolet eadiation: global burden of disease from
R. A. Norman and M. Rappaport
solar ultraviolet radiation. Environmental Burden of Disease
Series, No. 13. http://www.who.int/uv/publications/solaradgbd/
en/index.html; 2008 Accessed 28.12.08
  7. Jung K, Seifert M, Herrling T, Fuchs J. UV-generated free
radicals (FR) in the skin: their prevention by sunscreens and
their induction by self-tanning agents. Spectrochim Acta Part
A Mol Biomol Spectrosc. 2008;69(5):1423–1428. Epub 2007
  8. Nicita-Mauro V, Lo Balbo C, Mento A, et al Smoking, aging
and the centenarians. Exp Gerontol. 2008;43(2):95–101
  9. Merimsky O, Inbar M. Cigarette smoking and skin cancer.
Clin Dermatol. 1998;16:585–588
10. Shulman A, Wolf R. Cigarette smoking, hormonal changes,
and the skin. Clin Dermatol. 1998;16:595–598
11. Morita A. Tobacco smoke causes premature skin aging.
J Dermatol Sci. 2007;48:169–175
12. Boyd AS, Stasko T, Lloyd E, et  al Cigarette smoking–
associated elastotic changes in the skin. J Am Acad
Dermatol. 1999;41:23–26
13. Setty AR, Curhan G, Choi HK. Smoking and the risk of pso-
riasis in women: Nurses’ Health Study II. Am J Med. 2007;
120:953–959
14. Odenbro A, Gillgren P, Bellocco R, et al The risk for cutane-
ous malignant melanoma, melanoma in situ and intraocular
malignant melanoma in relation to tobacco use and body
mass index. Br J Dermatol. 2007;156:99–105
15. Demierre MF, Brooks D, Koh HK, Geller AC. Public knowl-
edge, awareness, and perceptions of the association between
skin aging and smoking. J Am Acad Dermatol. 1999; 41(1):
27–30
16. Piko BF, Bak J, Gibbons FX. Prototype perception and
smoking: are negative or positive social images more impor-
tant in adolescence? Addict Behav. 2007;32:1728–1732
17. Hidalgo LG. Dermatological complications of obesity. Am J
Clin Dermatol. 2002;3(7):497–506
18. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin:
skin physiology and skin manifestations of obesity. J Am
Acad Dermatol. 2007;56:901–916
19. Lee BY, Hogan DJ, Ursine S, et al Personal observation of skin
disorders in malnutrition. Clin Dermatol. 2006;24:222–227
20. Di Stefani AD, Orlandi A, Chimenti S, Bianchi L. Phryn­
oderma: a cutaneous sign of an inadequate diet. CMAJ.
2007;177(8):855–856
21. World Health Organization: WHO Annexes: Annex 1. www.
who.int/entity/uv/health/solaruvradann1.pdf; 2008 Accessed
28.12.08
22. Han PKJ, Moser RP, Klein WMP. Perceived ambiguity about
cancer prevention recommendations: associations with can-
cer-related perceptions and behaviours in a U.S. population
survey. Health Expect. 2007;10:321–336
23. Simmons VN, Vidrine JI, Brandon TH. Smoking cessation
counseling as a teachable moment for skin cancer preven-
tion: pilot studies. Am J Health Behav. 2008;32(2):137–145
 Raising Awareness on the Health
Literacy Epidemic
Michelle C. Duhaney
Low health literacy is common in the United States of
the twenty-first century. The ability to process and under­
stand basic health information and function appropri-
ately in today’s healthcare environment requires basic
reading and mathematical skills.1, 2 These basic skills are
often taken for granted by patients with adequate health
literacy. It is likely that most physicians will encounter
on a daily basis patients who cannot read or spell, which
is a barrier to accurate medical diagnosis and optimal
treatment.3
The magnitude of the association between inade-
quate health literacy and mortality has captured the
attention of many. The nature of this problem is com-
plex and effectively addressing it is important to
America’s well-being.4 In a study of elderly patients
enrolling in a Medicare-managed care plan, inadequate
health literacy independently predicted all-cause mor-
tality and death due to cardiovascular events. This study
concluded that the crude mortality rate for patients with
inadequate health literacy was relatively high at 39.4%.5
In an era that has seen breakthrough drug regimens and
life-saving treatments the effect of low health literacy
on the mortality rate is alarming.2, 5
Health literacy is therefore gaining momentum
among researchers. Research over the last 15 years has
attempted to assess the nature and scope of health lit-
eracy and the impact that low health literacy has on
the delivery of quality healthcare in the United
States3, 4 Several studies have shown that patients with
inadequate health literacy have decreased knowledge
and understanding about diseases, especially chronic
M. C. Duhaney
Department of Family Medicine, Broward General Medical
Centre, Fort Lauderdale, FL, USA
e-mail: doctorduhaney@gmail.com
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_3, © Springer-Verlag London Limited 2010
3
diseases such as diabetes and hypertension.5, 6 Patients
with inadequate health literacy also have decreased
medication adherence, increased involvement in risky
health behaviors, and a poor understanding of preven-
tive health measures.6, 7
Low health literacy impacts more than the mortality
rate; patients with inadequate health literacy have increased
rates of hospitalization. If not appropriately addressed,
America’s healthcare costs will continue to rise.6
Many researchers have documented the relationship
between health literacy of adults in the United States
and adverse health outcomes. A limited number of stud-
ies have been done, however, to assess the link between
parental/caregiver health literacy and the health out-
come of our nation’s children.5 In the few studies that
have been documented, low parental health literacy has
been linked to behaviors that negatively impact a child’s
health.5 A patient’s level of education, age, race, ethnic-
ity, and culture also impact the outcome of healthcare,
contribute to patient compliance, and even affect health-
care costs.1, 8 It is not surprising, therefore, that by
improving literacy, health outcomes will also improve.
Many cognitive assessment tools are now available
to measure health literacy. These tools assess a patient’s
recognition of medical terms and ability to interpret
written health materials.1 Since approximately 90 mil-
lion adults have fair-to-poor literacy and 21–23% of
adults read at the lowest reading level, other interven-
tions such as educational videotapes or DVDs and
color-coded medication schedules may improve the
delivery of healthcare.1, 9 America has realized that
quality healthcare relies on effective communication
between patients and involving members of the health-
care team. Although attempts have been made to
increase health literacy and in turn improve patients’
understanding through effective communication, the
scope is not broad enough and certainly the pace is not
21
22
fast enough to make the progress that is necessary.4, 10
Awareness of this epidemic must be further increased
and more research should be done.11
3.1 Introduction
Health literacy has been defined “as the degree to
which individuals have the capacity to obtain, process
and understand basic health information and services
needed to make appropriate health decisions.”12 The
American Medical Association (AMA) expanded on
the definition and defined health literacy “as a constel-
lation of skills” which includes the ability to do basic
reading and perform basic numerical tasks.1 A patient’s
inability to perform these basic tasks acts as a barrier
to accurate medical diagnosis and optimal treatment.
This inadequacy of health literacy contributes to a
weak healthcare system in the United States. Patients
become noncompliant, chronic diseases become more
difficult to control, and healthcare costs continue to
rise.1 A significant proportion of adults in the United
States are impacted by this epidemic. According to a
report from the Institute of Medicine (IOM), almost
50% of Americans have difficulty understanding basic
printed health information.1, 7 The 2003 national assess-
ment of adult literacy (NAAL) revealed that approxi-
mately 90 million American adults have fair-to-poor
literacy.1, 12 Effective patient–physician communica-
tion is therefore the key element to accurate medical
diagnosis and optimal treatment. It is recommended
that physicians elicit patient comprehension of disease
processes.13 Effective communication will lead to
improved patient satisfaction and medication adher-
ence and subsequently improved health outcome.11, 13, 14
Physicians also need to be cognizant that health liter-
acy is compounded by a patient’s age, race and ethnic-
ity, culture, language spoken, and historical experiences
with racial and ethnic disparities that have led to mis-
trust of the heathcare system.1, 15
3.2 Epidemiology
In today’s society, the patients with the greatest
­healthcare needs may have the least ability to perform
basic reading and mathematical tasks.11 A recent
M. C. Duhaney
government study estimated that over 89 million
American adults have limited health literacy.1 A sys-
tematic review estimated that 21–23% of adults read at
the lowest reading level which is approximately fifth
grade or lower.1 Inadequate health literacy in America
is surprisingly common. A 2003 survey categorized
US health literacy rates into four groups: proficient
(11%), intermediate (53%), basic (22%), and below
basic (14%).16 Health literacy becomes more compli-
cated in elderly patients and in patients whose primary
language is not English. Elderly patients may have a
limited ability to read information pertinent to their
health because of declining cognitive and sensory
function.1, 17 In fact, the majority of patients older than
60 years have inadequate literacy.1 The ability to read
and comprehend prescription bottles, appointment
slips, and other essential health-related materials is
decreased in the elderly.1, 15 Approximately 80% of the
elderly in the United States have a limited ability in
filling out forms, such as those requested in physician
waiting rooms.1 A survey of patients at two US public
hospitals revealed that 35% of English-speaking
patients and 62% of Spanish-speaking patients had
fair-to-poor health literacy.1,9 A majority of these
patients may avoid seeking medical attention because
they are in denial or because they are embarrassed.1
Limited health literacy has been linked to delayed
medical diagnosis.6,18 Once a diagnosis is made, phy-
sicians may encounter patients who have a difficulty
understanding their medical condition and the need
for using preventive health measures.6,18 Adherence to
medical instructions and self-management skills may
also become problematic.6
Not only is there an association between low health
literacy and morbidity, but low health literacy has been
linked to an increase in the mortality rate. A 5-year
prospective study of 2,500 adults with the average age
of 75.6 was analyzed. After adjusting for demographic
and socioeconomic status (SES), comorbid conditions
and patient-health-related behaviors, there was a two-
fold increase in the mortality rate.18 In another pro-
spective study, the crude mortality rate for patients
with inadequate health literacy was 39.4%. The rates
for the participants with marginal and adequate health
literacy were 28.7 and 18.9% respectively.5
The NAAL survey estimated that 14% of adults in
the United States have below basic level of prose
literacy, the ability to use “printed and written infor-
mation to function in society, to achieve one’s goals,
3  Raising Awareness on the Health Literacy Epidemic
and to develop one’s knowledge and potential.”9
Document literacy is the ability to read and compre-
hend documents such as drug or food labels.9 Twelve
percent of adult patients are estimated to have below
basic document literacy.9 Many patients are unable to
understand prescription labels. Although 71% with
inadequate health literacy correctly said “Take two
tablets by mouth twice daily,” only 35% could demon-
strate this instruction in a study done to assess patient
comprehension.19 Another report found that 24–58%
of patients did not understand directions to take a med-
ication on an empty stomach.19 The NAAL survey also
showed that 22% of adults are estimated to have below
basic quantitative literacy. Quantitative literacy is
defined as the ability to perform quantitative or math-
ematical tasks. Patients with inadequate quantitative
literacy may be able to add up all the numbers on a
bank slip, but they cannot, for example, compare
ticket prices for some events.9 The elderly are more
likely to have chronic and multiple medical comor-
bid conditions. These patients may have a difficult
time with health literacy because of decreased sen-
sory and cognitive function and as a result may have
a difficult time controlling their chronic and comor-
bid conditions.1,17 On the basis of NAAL, it was ana-
lyzed that the patients over the age of 64 with below
basic prose literacy, basic document literacy, and
basic quantitative literacy accounted for 23, 27, and
34% respectively.9
3.3 Health Literacy Assessment Tools
During the past decade, the magnitude of the health
literacy epidemic in America and the effect it has had
on health outcome and mortality has received consid-
erable attention. Patients with inadequate health liter-
acy have a complex array of difficulties which
influence diagnosis and disease management.6, 11 It
remains unclear whether screening patients for health
literacy improves health outcome. A common mistake
is to rely on patients’ own assessment of their level of
health literacy. The majority of patients who have
inadequate health literacy will say that they know
more than they really do and overstate their reading
competence.1 Patients with low literacy often are too
embarrassed to admit that they do not understand and
therefore refuse to ask their physician to explain or
23
repeat relevant information regarding their health.1
Many have told no one about their handicap including
their spouses and family members. Although the evi-
dence is insufficient to conclude that screening
improves patient–physician communication and sub-
sequently morbidity and mortality, many types of
standardized literacy assessment tools are now avail-
able.1, 5 They measure the health literacy and assess a
patient’s recognition of healthcare terms. They also
assess a patient’s ability to interpret written health
materials.1 The rapid estimate of adult literacy in
medicine (REALM) and test of functional health lit-
eracy in adults (TOFHLA) were developed specifi-
cally to measure patients’ health literacy.7 Although
both the REALM and TOFHLA are valid and easily
administered, the REALM is the most commonly
used tool.7 Since its introduction in 1991 the REALM
has been identified as the quickest of the two, taking
less than 5 min to complete and can easily be admin-
istered by a nurse or other members of the medical
staff.1 The REALM is a word recognition test. It is
comprised of 66 medical terms that are arranged in
order of increasing complexity.7 During the adminis-
tration of this test patients are asked to read down the
list and pronounce as many words as they can. The
examiner uses standard dictionary pronunciation as
the scoring standard and assigns a score based on the
number of words pronounced correctly.7 One point is
given for each word that is correctly pronounced.
Scores therefore vary from 0 to 66. A score of 0 indi-
cates that none of the words were pronounced cor-
rectly and a score of 66 indicates that all the words
were pronounced correctly.7 The scores are then
matched to a grade equivalent. A score of 0–18 would
be equivalent to third grade or less, 19–44 would be
equivalent to fourth to sixth grade, 45–60 would be
equivalent to seventh to eighth grade and 61–66
would be equivalent to high school.1,7 The TOFHLA
is also available for use by healthcare professionals
and is available in both Spanish and English. Although
the TOFHLA provides a more thorough assessment
of a patient’s ability to comprehend, it is less practi-
cal for today’s use and it is more time-consuming.1 It
takes approximately 22 min to administer.7 There is a
short form of TOFHLA called the S-TOFHLA that
takes approximately 7 min.7
In a well-written report, the validity of a new and
rapid literacy assessment instrument was discussed.
The newest vital sign (NVS) was introduced in 2005
24
with the intention of addressing the speed and accu-
racy of health literacy assessment.12 NVS is now avail-
able in both English and Spanish and uses the TOFHLA
as the reference standard.20 NVS was developed from a
series of scenarios that were created by a panel of
health literacy experts. The candidate scenarios
included instructions from a prescription for headache
medicine, a consent form for coronary angiography,
instructions for self-care and management of heart
failure, an ice cream nutrition label, and instructions
for an asthma medication that included a tapering ste-
roid dose.12 Patients were asked to read these health-
related scenarios and then demonstrate their ability to
use the information by answering certain questions
about each scenario.20 Since one has to be able to do
basic reading and perform basic mathematical tasks in
order to survive in today’s healthcare environment,
some of the scenarios did involve both reading and
mathematical concepts.1,12, 20 The scenario that best
determined the literacy level was the one with the ice
cream nutrition label.12 The average completion time
for the English version was 2.9 min. The Spanish ver-
sion took on average more time to complete.12 In
detecting marginal health literacy, NVS may be more
sensitive than TOFHLA. The specificity of NVS is
similar to or better than other screening tools such as
the widely used CAGE questionnaires to detect alco-
hol abuse and the screening methods to detect arthri-
tis.20 Like REALM and TOFHLA, NVS has its
limitations. The Spanish version was not as good as
the English version.20 The primary care practices that
were involved in the study did not fully represent all
primary care practices. They were selected because
they had a high percentage of Spanish-speaking
patients. Among these Spanish-speaking patients the
percentage of males was relatively small.20 Despite
these limitations the NVS has advantages over the
REALM and TOFHLA. In the future, studies should
examine the validity of NVS in both primary and
nonprimary care setting and whether raising a physi-
cian’s awareness to the issue of health literacy results
in better health outcome.20
During the last 15 years, research has shown that
patients with inadequate health literacy often have a
poorer understanding of their medical diagnosis and
are less likely to utilize disease management tech-
niques. These patients tend to underuse health promot-
ing and disease prevention programs and often engage
themselves in risky health behaviors.7 The number of
M. C. Duhaney
patients that are affected is alarming. On the basis of
these findings, more research should concentrate on
improving screening methods. Physicians should also
pay special attention to informal behavioral cues that
may help detect low health literacy. Patients with inad-
equate health literacy often attempt to identify their
medications by looking at the pill instead of the medi-
cation label. Other behavioral cues include frequent
misspelling or turning in incomplete medical forms.12
Making excuses and mimicking others may also be
signs suggestive of inadequate health literacy.1
3.4 The Nature of this Epidemic
The magnitude and the consequence of low health lit-
eracy are of concern to many, especially when one
considers the effect it has had on morbidity and mor-
tality. Many researchers describe low literacy as a
silent epidemic.9 The problems are numerous and com-
plex and for that reason health literacy has been receiv-
ing considerable attention. Patients with inadequate
health literacy have a difficult time using the health-
care system. These patients may refuse to keep doc-
tor’s appointments because they may not be able to
register for health insurance or even follow simple
driving directions. Once these patients arrive at the
office they may not be able to complete medical forms
because they cannot read or follow simple instructions
and once that appointment is over they may not know
when to follow up.1 Physicians should be alert for this
problem because most patients are too embarrassed to
admit that they have a literacy issue. Patients with
inadequate health literacy are less likely to participate
in health promotion and disease prevention programs.
They have a poor understanding of disease-preventive
measures such as pap smears, mammography, and
colonoscopy. Not only do these patients have less basic
health knowledge and worse self-management skills,
but they are more likely to be hospitalized.1,6 Even after
adjusting for other factors associated with increased
risk for hospitalization, studies conclude that patients
with inadequate health literacy are more likely to be
hospitalized.12 Patients with inadequate health literacy
have 29–52% higher hospitalization rates.5 One study
showed that adult males with inadequate health liter-
acy would commonly present with advanced stage
prostate cancer. It was suggested that those with
3  Raising Awareness on the Health Literacy Epidemic
inadequate health literacy delayed seeking medical
attention and presented in the very late stages of the
disease.12 Other diseases like diabetes and hyperten-
sion require a patient to be health literate in order to be
adequately controlled. Diabetes and hypertension are
chronic diseases that require the patient to be educated
to avoid adverse health outcomes.14 Patients with
hypertension may need to understand how to take mul-
tiple medications. The intricacies involved with self-
management of diabetes often get ignored in a patient
with inadequate health literacy. Patients with inade-
quate reading and mathematical skills often have a dif-
ficult time monitoring home glucose levels and
administering insulin.14 In an observational study of
408 patients with type 2 diabetes, inadequate literacy
was associated with poor glycemic control and an
increase in the rate of diabetic retinopathy.21 In another
study of over 500 patients hospitalized for diabetes,
only 50% of patients with inadequate literacy knew the
symptoms of hypoglycemia compared to 94% with
adequate literacy.14 Ninety-two percent of patients with
hypertension who had adequate literacy knew that a
blood pressure reading of 160/100  mmHg was high
while only 55% of patients with low health literacy
were able to evaluate this reading.14
3.5 Education and Health Literacy
A patient’s level of education plays a vital role in their
understanding that lifestyle and behavioral modifica-
tions are required when managing diseases. Especially
when managing diabetes and hypertension, health lit-
eracy must be up to par to achieve adequate control
and to prevent adverse outcomes such as death.14 Most
health-related materials are written at the tenth grade
level or higher. The majority of adults have a difficult
time comprehending these health-related materials
since most adults read between the eighth and ninth
grade level.1 Patients with poor reading and poor math-
ematical skills may have a difficult time reading food
labels and calculating calories. Health literacy is thus
associated with diet and medication adherence. In a
report of 2,659 predominantly poor patients at two
public hospitals, up to 58% of patients did not under-
stand the direction to take a medication on an empty
stomach.14 Proper medication administration is crucial
to adequate disease management. Physicians need to
25
elicit their patients’ understanding. Evidence clearly
links patient–physician communication to patient
adherence and health outcome. Patients in general
recall or comprehend as little as half of what physi-
cians convey.13 This is even lower in a patient with
inadequate literacy. In a study that used direct observa-
tion to measure the extent to which primary care physi-
cians assess patient recall and comprehension during
diabetic patient encounters, it was found that these
physicians rarely assessed recall or comprehension of
new concepts.13 This reflects a missed opportunity to
improve and enhance patient compliance and ulti-
mately improve disease management.13 There is clear
evidence that improving a patient’s comprehension
of a disease improves medication adherence and dis-
ease outcome. Ensuring recall and comprehension
becomes especially important in our diabetic and
hypertensive patients since they must cope with the
complex nature of their disease and the intricacies of
self-management.13
3.6 Age and Health Literacy
The impact of age on clinical care is important. As
age increases, so do the deficits in literacy.1 Elderly
patients may have a difficult time reading and compre­
hending information regarding their health because of
an increased time since formal education. Decreased
cognitive and sensory function also compounds this
problem of health literacy. The majority of patients
older than 60 years have low health literacy. Eighty
percent have a difficult time filling out forms such as
insurance forms and the ones they have to complete in
physician waiting rooms.1 To determine the ­prevalence
of low functional health literacy among Medicare
enrollees, a cross-sectional survey of new enrollees
in health plans of a national managed care organiza-
tion was done.6,17 After adjusting for years of school
completed and cognitive impairment, a patient’s
reading ability was seen to decline with  age.17
Approximately 30% of English-speaking patients
and 50% of Spanish-speaking patients had low or
marginal health literacy.17 The study concluded that
elderly managed care enrollees may not be able to
function appropriately in a health-care setting. Low
health literacy may impair their understanding and
thus limit their ability to care for themselves and their
26
medical problems.17 Higher total medical and emer-
gency costs are associated with low health literacy in
the elderly. Patients tend to avoid outpatient doctors’
offices because they are embarrassed about their
inability to fill out paperwork. They may find emer-
gency rooms easier to use because information is
taken and forms filled out by others.9
Elderly patients with low health literacy and high
prevalence of chronic conditions may have increased
levels of depression.22 Investigators also sought to
determine whether older adults with inadequate health
literacy were more likely to report depressive symp-
toms.22 Overall, 13% of the respondents were classi-
fied as being depressed.22 Although some patients with
inadequate health literacy are unaware of their handi-
cap; others feel significant shame and decreased
worth.1,22 One study found that among those patients
who admitted that they had a reading problem, the
majority did not disclose this information to their
spouse or family22; 19% of subjects had never even dis-
closed their inability to read to their healthcare pro-
vider.22 Such embarrassment may lead to social
isolation. It is possible that these feelings of embar-
rassment and shame could lead to a higher prevalence
of depression. In fact, individuals in the study who had
less social support had significantly higher odds of
being depressed.22 Data generally suggest that the
higher the level of education a person attains the fewer
depressed symptoms they will have. Some studies pro-
pose that this may be due to a greater financial success,
improved lifestyle behaviors, and improved problem-
solving capacity.22 The investigators also sought to
determine whether the potential relationship between
health literacy and depression may be mediated by
health status. Some literature suggests that there is a
strong predictive power of health status on depres-
sion.22 Especially among the elderly, there may be
higher rates of depression because of low health liter-
acy coupled with a high prevalence of chronic condi-
tions.22 Even after controlling for other factors, it was
found that individuals who were inactive and exercised
less than twice a week were twice as likely to have
symptoms of depression.22 In the cross-sectional sur-
vey, patients with low health literacy were more likely
to report that they were depressed than those patients
with adequate health literacy. This was mostly
explained by their worse health status. This relation-
ship between depression and poor health status ­suggests
the need to research ways to improve patients’ health.
M. C. Duhaney
Patients may need to be referred for social support to
help with their ­depression and exercise programs to
increase exercise ­tolerance and compliance.22
3.7 Parental Health Literacy
and Pediatric Health
Health literacy is now gaining momentum among
researchers. Many studies have been done to assess the
relationship between adult health literacy and health
outcomes. A limited number of studies have been done
to evaluate the association between parental literacy
and a child’s health outcome. In the few studies that
have been done, low parental health literacy has been
linked to behaviors that have a negative impact on chil-
dren’s health.12 The REALM was utilized in a study of
600 pregnant women. After controlling for age, race,
marital status, living with a smoker, and current smok-
ing status, the study concluded that pregnant women
with inadequate health literacy had significantly less
knowledge about the negative effects that smoking had
on their babies’ health.12 In fact, 66% of the pregnant
women with at least a ninth grade level of education
were more concerned about the effects of smoking and
their babies’ health as compared to only 37% of women
who had a third grade level of education or lower.12
The issue of not initiating breastfeeding and how this
may affect a baby’s health were also studied. A study
done by Kaufman and coworkers on primarily low
SES mothers showed that those women with at least a
ninth grade education were more likely to breastfeed
for at least 2 months. This was estimated to be 54% as
compared to 23% of parents with a seventh or eighth
grade level of education.12 All parents are required to
receive information on childhood immunization. One
study found that this information is written above the
tenth grade level of reading. In fact, a study of docu-
ments available through the American Academy of
Pediatrics found that the reading levels of asthma man-
agement plans ranged from eighth grade to twelfth
grade.12 Most adults in the United States read at the
eighth grade level and below.1 One study assessed
asthma care measures in children who presented for
care in an outpatient clinic and found that children of
parents with low health literacy were more likely to
have emergency department visits and had more
3  Raising Awareness on the Health Literacy Epidemic
hospita­lizations.12 Screening for parents/caregivers is
not easy. Most physicians do not screen parents due to
time constraints and they may also lack the knowledge
on how to intervene when they discover that a parent
has inadequate health literacy.12
3.8 Childhood and Adolescent
Health Literacy
There may be a link between child and adolescent
health literacy and their own health outcome. Only a
limited number of studies have been done to assess
this possible link.12 One study was done on 3,000 stu-
dents in Australia that found an association between
adolescent literacy level and substance use, namely
tobacco.12 The same study concluded that there is a
link between the health literacy of adolescent boys
and alcohol misuse.12 A study done of over 350 US
children concluded that there is a link between low
literacy and carrying weapons and participating in
fights at school.12 Recently a study was done to assess
the link between child health literacy, parent health
literacy and childhood obesity. Adjustments were
made for the children’s age, gender, insurance,
eating-self efficacy, exercise self efficacy, exercise
activity, grade in school and reported reading level
and the parents’ primary language spoken at home
and body mass index.12 After adjusting these con-
founders it was found that low child health literacy as
opposed to low parent health literacy had an associa-
tion with body mass index Z-scores.12 Although
research is limited, some studies have concluded that
a child’s health is impacted not only by parental/care-
giver health literacy but also by the health literacy of
the child. It is unclear whether screening children and
adolescent for health literacy is necessary. In December
2006, a screening tool called the REALM-Teen was
developed to assess health literacy in the adolescent
population.12 The REALM-Teen is a word recogni-
tion test intended for grades 6 through 12. It allows
physicians to recognize adolescent patients that read
health-related information below their grade-reading
level.12 This screening tool takes no more than 5 min
to administer. Similar to the other screening tools
used to assess health literacy in adults, the REALM-
Teen has its limitations as it is only available in
English.12
27
3.9 Culture, Race, Ethnicity,
and Health Literacy
Health literacy is significantly impacting the delivery of
healthcare in America. Not only does a patient’s age,
level of education, language spoken affect the delivery of
healthcare, but sociocultural factors, race, and ethnicity
also impact the healthcare system.1, 8, 23 Culture, race, and
ethnicity influence a patient’s belief and health prac-
tices.12, 23 It is essential that healthcare providers deliver
care that is sensitive to the needs of patients from differ-
ent cultures, race, and ethnicity.8, 23 Achieving cultural
competence is a multifaceted project.8 There has been
growing interest in preparing healthcare providers to care
for patients with different cultural backgrounds.8 Despite
this interest, only a few studies have been done to exam-
ine efforts to educate healthcare providers in cross-cul-
tural care.8, 23 By 2015, it is estimated that over 50% of
patients that will be seeking primary care will be of the
racial and ethnic minorities.8 Cultural differences between
patients and healthcare providers influence communica-
tion, patients’ adherence, and health outcome.23 Certain
patients may be viewed as having inadequate health lit-
eracy because they have beliefs and practices that are not
understood by healthcare professionals. These misunder-
standings can lead to negative health outcomes. The role
of mistrust in the healthcare system by racial and ethnic
minorities is also an important aspect in medical care.
African Americans especially carry with them the con-
tinuing legacy of the Tuskegee Syphilis Study that con-
tributes to mistrust in the healthcare system.8, 24, 25 A
physician’s full understanding of this historical experi-
ence is necessary in achieving optimal patient–physician
encounter.8 The Society of General Internal Medicine
Health Disparities Task Force made recommendations to
address the racial and ethnic health. The Task Force rec-
ommends examining and understanding patients’ atti-
tudes such as mistrust. It was also recommended that the
correct skills are needed to effectively communicate
across cultures, languages, and literacy levels.
3.10 Health Literacy and Mortality
Patients with inadequate health literacy face enormous
obstacles. During the last 15 years researchers have
shown that there is some association between inadequate
28
health literacy and poor understanding of chronic dis-
eases, poor self-management skills and underuse of health
promoting/disease prevention programs.5, 7 Unfortunately,
patients with inadequate health literacy are at an increased
risk for adverse health outcomes including death. One
study reported that among community-dwelling adults
aged 70–79 years, there was an association between the
performance on the REALM and mortality. Worse per-
formance during this screening was associated with
higher mortality rates.5 A prospective cohort study was
performed on 3,260 medicare-managed care enrollees
in the four previously mentioned US metropolitan areas
of Cleveland, Houston, Tampa, and the Ft. Lauderdale/
Miami area.5 This prospective cohort study was designed
to determine if there is a relationship between health lit-
eracy and mortality and whether low health literacy
independently predicts overall and cause-specific mor-
tality.5 Health literacy is essential for managing health
conditions.1, 12 It is a cornerstone for patient safety in
twenty-first-century America. In the study, the partici-
pants were of the age 65 years and older. Race/ethnicity,
level of education, chronic health conditions, physical
and mental health were some of the areas that were
assessed. The patients involved in the cohort study were
also asked to complete the short form of the TOFHLA,
the S-TOFHLA.5 The S-TOFHLA included two reading
passages and four mathematical questions to assess the
participants’ ability to read and perform numerical tasks.
Among the 3,260 participants the number of partici-
pants with adequate literacy, marginal literacy, and
inadequate literacy were 2,094, 366, and 800 respec-
tively.5 According to the results of this prospective
cohort study, elderly patients with poor health literacy
have higher incidence of all cause mortality and cardio-
vascular death.5 A participant’s health literacy was
determined or measured by reading fluency which
according to the authors “was a more powerful variable
than education for examining the association between
SES and health.” The study analyzed differences in
mortality during a 6-year period. The National Death
Index was used to identify the deaths through 2003.5 Of
the 3,260 participants, a total of 815 participants died
during an average follow-up period of 67.8 months.5
For those participants with inadequate health literacy,
the crude mortality rate was 39.4% compared with
28.7% in those participants with marginal health liter-
acy. Participants with adequate health literacy had the
lowest crude mortality rate of 18.9%.5 Cardiovascular
disease was the cause of death in 11.7% of participants;
M. C. Duhaney
which accounts for a total of 380 participants. Those
participants with inadequate health literacy had higher
rates of mortality secondary to cardiovascular disease
(19.3%) as compared to those with marginal health lit-
eracy and adequate health literacy whose rates were
16.7 and 7.9% respectively.5 Although the crude cancer
mortality rates were higher in patients with inadequate
literacy, multivariate analyses had similar rates. The
authors have therefore concluded that “participants
with inadequate health literacy had higher risk-adjusted
rates of cardiovascular death but not death due to
cancer.”
The authors explored several possible explanations
for the association between health literacy and mortal-
ity. Smoking, alcohol use, and physical activity were
examined to determine if these behaviors could explain
the higher mortality rate among those with inadequate
health literacy. Health behaviors were found to be only
weakly predictive of mortality.5 This was also the case
when the authors explored the association between the
amount of years a participant completed in school and
the rate of mortality. In bivariate analyses, years of
school completed had a weak association with mortal-
ity. In multivariate analyses, the amount of years of
school completed did not significantly predict mortal-
ity. Since many individuals progress through the school
system without meeting desired requirements, the
authors also concluded that the number of years com-
pleted in school is not a true measure of educational
accomplishment.5 For the elderly, the number of years
completed in school does not capture or account for
lifelong learning or age-related declines in reading flu-
ency.12 For this reason, the authors concluded that flu-
ency was a more powerful variable than education.
Inadequate health literacy is associated with poor
self-management of chronic diseases such as diabe-
tes and hypertension.1, 6 Medication adherence also
becomes affected. To function appropriately in today’s
healthcare system, patients need to be able to perform
numerical tasks. HIV-positive patients, for example,
must be able to follow dosing instructions to properly
manage their disease. Use of health promoting/disease
prevention measures such as cancer screening and
immunization are lower among those with inadequate
health literacy.5 One study done on patients aged
50 years and older concluded that patients with inad-
equate health literacy were less knowledgeable about
colorectal cancer screening.26 The authors of the July
23rd issue concluded that the association between
3  Raising Awareness on the Health Literacy Epidemic
health literacy and adverse outcomes such as death is
probably secondary to the cumulative effect of multi-
ple causes.5 Countless numbers of patients are at risk
in today’s healthcare system because they do not
­possess adequate health literacy. Inadequate health
­literacy correlates with decreased knowledge about
diseases, decreased medication adherence, increased
involvement in risky health behaviors, and a poorer
understanding of preventive health measures. Patients
with inadequate health literacy are therefore at an
increased risk for adverse health outcomes. The
adverse health outcome that is most concerning is
untimely death, since in most cases, death could be
avoided if patients had adequate knowledge about dis-
eases and diagnoses were not delayed. As a result,
improvements in communication and possibly improve-
ments in screening will more than likely be necessary
to reduce the association between health literacy and
mortality.12, 20 According to Baker et al, “To achieve this
goal, we must further elucidate the causal pathways
linking health literacy and adverse health outcomes
and use this information to design more comprehen-
sive and effective interventions.”5
3.11 Addressing Health Literacy
Inadequate health literacy is surprisingly common in
the United States. People of all ages, races, ethnicities,
cultures, and education levels are challenged by this
problem. During the past decade, the consequence that
poor health literacy has had, America’s healthcare sys-
tem has been receiving considerable attention. Many
will agree that achieving a health-literate America is a
multifaceted project. The AMA became the first
national medical organization to adopt a policy that
recognizes that there is a causal pathway to how inad-
equate health literacy negatively affects medical diag-
nosis and treatment.12 The AMA’s Council on Scientific
Affairs, through an Ad-Hoc Committee on Health
Literacy, published a report in 1999.1, 12 The report
adopted five statements. It was identified in the first
statement that limited health literacy is a barrier to
medical diagnosis and effective treatment.12 The
remaining statements recommended increasing public
awareness, promoting the education of the medical
community, supporting assessment of health literacy,
and encouraging research on health literacy.1, 12 The
29
joint commission on accreditation of healthcare orga-
nizations (JCAHO) added health literacy benchmarks
for hospitals to achieve. JCAHO mandated that hospi-
tals and other health organizations assess patients’
knowledge and provide instructions that patients can
easily understand.14 The IOM convened a Committee
on Health Literacy. Composed of experts from a wide
range of academic disciplines, this committee was cre-
ated to define the nature and scope of the problem, to
identify any obstacles to solving this problem, to assess
all the approaches that have been attempted and to
identify goals for health literacy and suggest approaches
to reach these goals.4, 10 In 2004, the IOM issued a
well-written 345-page report, Health literacy: a pre-
scription to end confusion. In the words of the IOM
report, “efforts to improve quality, reduce cost, and
reduce disparities cannot succeed without simultane-
ous improvements in health literacy.”10 The first find-
ing of the Health Literacy Committee was that health
literacy is “based on the interaction of the individuals’
skills with health contexts . . . the healthcare system,
the education system and broad social and cultural fac-
tors at home, at work and in the community.”10 The
healthcare system does not carry sole responsibility for
creating a health-literate America. The responsibility
must be shared among several sectors in today’s soci-
ety. In the IOM health literacy report recommendations
were made to increase both Federal and non-federal
funds for research.10 Future research should focus on
improving the health literacy screening methods.
Research should also focus on techniques to improve
health education.11 It was also recommended that in
order to fulfill accreditation requirements, schools
should implement National Health Education stan-
dards and funds should be increased to achieve these
standards.10 Professional schools should also incorpo-
rate health literacy into their curricula. Private and
public healthcare systems should get involved and help
to identify ways to improve health literacy in America.
Accreditation bodies such as JCAHO should incorpo-
rate health literacy assessment in data collection and
healthcare information systems.10
In the report by the JCAHO titled “What did the
doctor say?”: Improving health literacy to protect
patient safety it was identified that inadequate health
literacy complicates the communication process
between healthcare workers and patients.27 Effective
patient–physician communication has a direct link
to improved understanding of diseases, increased
30
medication adherence, and subsequently improved
health outcomes. Sociocultural factors complicate
the communication process between healthcare pro-
viders and patients. During an encounter, three cul-
tures come into play; the culture of the patient, the
culture of the physician, and the culture of medi-
cine. America is now in an era where technology is
producing numerous breakthrough drug regimens
and life-saving treatments.2 Patients who have a dif-
ficult time with health literacy miss out on the life-
saving interventions and generally have worse
health outcomes. The Joint Commission encourages
accredited organizations to ensure patients’ under-
standing by providing information both written and
oral in a way that they can understand.2 Many physi-
cians rely on written health information that are
often written at a grade level above most patients’
understanding.1 More than half the written medical
information has a readability level at the tenth grade
level or higher.12 In order to facilitate patient under-
standing, written healthcare materials should be
short and simple.1, 12 In a randomized controlled trial
the effectiveness of using a low literacy educational
handout in increasing pneumococcal vaccine rates
was demonstrated.1 Patients who received this one
page instruction sheet written for fifth grade level
were 4 times more likely to discuss the vaccine with
their physician.1, 12 It is recommended that materials
should be written at the fourth through eighth grade
level for the general public to comprehend. The
National Institute of Health convened a Plain
Language Coordinating Committee that proposed
that written materials should be in “plain language.”
Plain language was defined as “clear writing that
tells the reader exactly what the reader needs to
know without unnecessary words or expressions.”12
Educational videotapes, pictorial illustrations, and
simplified brochures may also improve understand-
ing.9,12 Oral communication is another strategy that
has been proposed. Healthcare providers should
avoid using medical jargon and should speak slowly
when providing verbal health related information.1,12
Speaking slowly may prove more beneficial to the
elderly since they have a relative decline in cogni-
tive and sensory function. Determining whether or
not a patient understands what was said or what was
provided in a written form is also very important in
a patient–physician encounter. To assess a patient’s
understanding, physicians should have patients
M. C. Duhaney
repeat in their own words what was said.1 This
method is called the “teach back” strategy.1 To facil-
itate full comprehension, a combination of methods
such as oral and written may prove beneficial.
To improve communication some patients may ben-
efit from group sessions. In fact, research has demon-
strated that group sessions improve communication
and subsequently improve behavioral and health out-
comes.12 Patients with inadequate health literacy often
feel embarrassed and by offering this method of com-
munication some patients may find it easier to discuss
their health issues. It is essential to deliver care that is
sensitive to different races/ethnicities. Culture plays a
vital role in shaping an individual’s health beliefs and
practices. By utilizing educational programs that take
into consideration cultural preferences, patients may
become more involved and learning will be facili-
tated.12 A number of studies have been done to prove
the effectiveness of the individualized approach to
patient education. At this point in time there is no gen-
eral consensus that the individualized approach is more
effective in improving communication. A one-to-one
counseling program was designed for pregnant African
American and Hispanic women from WIC (women,
infants, and children) who had limited health literacy
and smoked.12 Smoking cessation materials were also
provided. Women that were randomized were more
likely to quit smoking at the 9-month follow-up ses-
sion.12 The relapse rate was also relatively low for
ex-smokers.12
Parents have a very strong influence on the health
of their children because they are responsible for
managing health conditions and at the same time pre-
venting adverse health outcomes. Studies that have
addressed improving the understanding of adults with
low health literacy also have implications that are
important for the pediatric population.12 All parents
are required to receive immunization schedules and
vaccine information at well-child visits. Since these
documents are written at an eleventh grade reading
level this poses a threat to those with limited health
literacy.12 In 2005 the American Academy of Pediatrics
formed a Health Literacy Project Advisory Committee
to address the issue of health literacy as it relates to
the pediatric population.12 As mentioned earlier,
approximately 50% of American adults are unable to
understand printed healthcare materials.1 A brief
screening test may prove beneficial in identifying the
parents that have inadequate health literacy. Adolescent
3  Raising Awareness on the Health Literacy Epidemic
health literacy assessment is also of importance to
many researchers. The REALM-Teen allows physi-
cians to assess health literacy in children that are in
grades 6 through 12.12 One disadvantage of the
REALM-Teen is that it is only available in English.
It is essential that healthcare workers deliver care
that is sensitive to the needs of patients that are from
different races/ethnicities and cultures. The authors
of a well-written article titled Viewpoint: cultural com-
petence and the African American experience with
healthcare in the February 2007 issue of Academic
Medicine proposed that awareness of historical infor-
mation of different ethnicities and race may improve
communication.8 The authors identified key influences
such as slavery and the Tuskegee syphilis study that
have led to African American patients’ mistrust in the
healthcare system.8 Patients with inadequate health lit-
eracy may have delayed diagnosis of medical condi-
tions because they do not seek medical attention in the
early stages of their disease. This could certainly be
secondary to some cultural practices that involve the
use of home remedies, mistrust in today’s healthcare
system, or simply because patients have poor under-
standing about their health.1, 8 Whether patients have
inadequate health literacy that is compounded by mis-
trust in America’s healthcare system or not, the authors
proposed increasing awareness through cultural edu-
cation as a method of improving communication in a
clinical setting.8 The Joint Commission also recog-
nizes that addressing culture and even language is
essential to quality healthcare.2 In 2006, the Joint
Commission implemented standards that required the
documentation of patients’ language and communica-
tion need by accredited organizations.2
At some point in most people’s lives, healthcare
decisions must be made because they are faced with
medical conditions that require medical intervention.
Patients with diabetes, for example, need their blood
sugars to be properly managed to avoid adverse
health outcomes. Widespread improvements in
patients’ understanding will likely be a necessity if
there is to be a reduction in the association between
health literacy and adverse health outcomes such as
death.5 Interventions that extend beyond the patient
physician encounter should also be addressed.28
Considering that today’s healthcare system has
placed a myriad of demands on patients, researchers
have proposed multidisciplinary support teams and
outreach activities.28 Recently, management strategies
31
for chronic diseases were developed for those patients
with inadequate health literacy.28 These strategies
which included education and follow-up methods for
patients with diseases such as diabetes and heart fail-
ure appear to be effective.28
In a pilot survey study that assessed the knowledge
of colorectal cancer screening in patients 50 years and
older, it was found that patients with limited health lit-
eracy were less likely to be knowledgeable about the
screening method.26 A different approach for improving
the education of patients with inadequate health literacy
was studied.12 In a randomized control trial, healthcare
providers were trained on screening guidelines for col-
orectal cancer and on methods to improve communica-
tion with patients with limited health literacy.12 Two
thousand VA patients were involved in this trial and
were provided with information on colorectal screening
via video and a simple and clear pictogram brochure.12
The trial concluded that patients with inadequate health
literacy (health literacy level less than the ninth grade)
had an increased likelihood in completing colorectal
screening test.12 Although further studies are recom-
mended on assessing provider training methods, this
method may prove beneficial at improving patient
understanding and health outcomes.
3.12 Conclusion
The future of America’s healthcare system depends on
ingenuity and the commitment of necessary resources
to improve patient–physician communication and
subsequently improve patients’ health outcomes.
Accepting the fact that health literacy is an issue in the
United States is a crucial first step. Healthcare workers
need to be more cognizant of the issues associated with
inadequate health literacy as they impact patients’ mor-
bidity and mortality and America’s healthcare costs.
Becoming aware of these issues of health literacy as
they relate to the patient, to healthcare, and society will
enable better planning of care.27 After accepting that
approximately 90 million adults have fair to poor lit-
eracy and that 21–23% of adults read at the lowest
reading level, the next crucial step is identifying
patients with these deficits.1 No simple method of
identifying patients with inadequate health literacy
exists and this is complicated by the fact that most are
hesitant to disclose their limitations because they are
32
too embarrassed.1, 29 Simply asking a patient for his or
her highest level of education attained is not an accu-
rate assessment of the patient’s health literacy.12 One
study found a difference of 4.8 grade levels between
educational attainment and the actual level the patients
read.12 During the last 15 years, research has focused
on several screening methods. Most physicians do not
utilize these screening instruments because of time
constraints. Others may lack the knowledge on how to
address the issue of inadequate health literacy when
they indentify a patient with this deficit.12 During the
past decade, the magnitude of inadequate health liter-
acy and consequences it has had on America’s health-
care system have been receiving attention. Although
research is now gaining momentum the pace is not fast
enough and the scope is not broad enough.10 The time
is now to reach a resolution. We are certainly in an era
where there are drug regimens and technology that can
save patients’ lives. There should be no reason, there-
fore, that countless numbers of patients have poor
health outcomes and are dying from health conditions
that can be cured or at least treated. One study con-
cluded that the crude mortality rate of patients with
inadequate health literacy was highest at almost 40%
relative to those participants with marginal and ade-
quate health literacy which were 28.7 and 18.9%
respectively.5 Patients with inadequate health literacy
have a vast array of communication difficulties and
therefore are less likely to effectively self-manage dis-
eases or utilize preventive services.1,6,14 Physicians
need to be aware of certain behaviors that are sugges-
tive of inadequate literacy skills such as frequently
missing appointments, noncompliance with medica-
tion, incompletely filling out forms, misspellings, need
for assistance, and mimicking others.1,12 Physicians
also need to evaluate themselves on their own literacy
and identify areas that need improvement. One area
that must be improved is the understanding of different
cultures and ethnicities. Effective communication
across different cultures and ethnicities is directly
linked to improved patient satisfaction and increased
adherence.23 Adverse health outcomes that may be
associated with inappropriate treatment of chronic dis-
eases such as diabetes and hypertension can be avoided
if there is effective communication between patients
and physicians. Both direct and indirect causal path-
ways that link inadequate health literacy to adverse
health outcomes must be further explored and this
information should be used to design interventions.5
M. C. Duhaney
Pediatric health is dependent on the health literacy
of parents/caregivers. By addressing the communica-
tion between parents/caregivers and physicians,
adverse health outcomes that affect children may be
avoided. The American Academy of pediatrics in
2005 formed a committee to address issues of inade-
quate health literacy and how it relates to the pediatric
population.12 In the well-written article Health liter-
acy and pediatric health by Yin, MD et  al the
American academy of pediatrics health literacy proj-
ect advisory committee was introduced.12 The article
stated that this committee is in the process of develop-
ing an agenda to address the challenges that parents
with inadequate health literacy may face and how this
affects the health of America’s children.12 Among the
projects proposed by the committee were parent
handouts in English and Spanish and health literacy
guidebook for pediatricians. Although the committee
is developing an agenda to address the impact of low
literacy and the pediatric population there is limited
research on this topic.12
The 2004 IOM report suggested that the healthcare
system should not be solely responsible for addressing
health literacy in America but instead other areas of
society such as the education system should play a
vital role. Direct involvement of patients should also
be encouraged. In developing educational materials, a
patient’s direct involvement may empower him or her
to, for example, avoid risky behaviors, use preventive
services, and subsequently improve his or her own
health.30 Future research should explore the usefulness
of screening and address the improvements in educa-
tional techniques. Certainly, the increased cost associ-
ated with inadequate health literacy needs effective
intervention.11 Now is the time to make this happen.
The issues associated with this health literacy epidemic
should not be ignored. Awareness must be increased to
effectively achieve a health-literate America.
References
  1. Keenan J, Safeer R. Health literacy: the gap between physi-
cians and patients. Am Fam Phys. 2005;72:463–468
  2. Murphy–Knoll L. Low health literacy puts patients at risk.
J Nurs Care Qual. 2007;22:205–209
  3. Anon. Health literacy. Report of council on scientific affairs.
JAMA. 1999;281:552
3  Raising Awareness on the Health Literacy Epidemic
  4. Kindig DA, Nielsen-Bohlman L, Panzer AM. Health literacy:
a prescription to end confusion. N Engl J Med. 2005;
352:947–948
  5. Baker DW, Gazmararian JA, et al Health literacy and mortal-
ity among elderly persons. Arch Intern Med. 2007; 167:
1503–1509
  6. Baker DW, Gazmararian JA, Wolf MS. Health literacy and
functional health status among older adults. Arch Intern
Med. 2005;165:1946–1952
  7. Wallace L. Patients’ health literacy skills: the missing demo-
graphic variable in primary care research. Ann Fam Med.
2006;4:85–86
  8. Eiser AR, Ellis G. Viewpoint: cultural competence and the
African American experience with health care: the case for
specific content in cross–cultural education. Acad Med.
2007;82(2):176–183
  9. Marcus EN. The silent epidemic – the health effects of illit-
eracy. N Engl J Med. 2006;355:339–341
10. Kindig DA, Parker RM. Beyond the institute of medicine
health literacy report: are the recommendations being taken
seriously. J Gen Intern Med. 2006;21(8):891–892
11. Kellerman R, Rudd R, et al Health literacy: report of the
council on scientific affairs. Ad Hoc Committee on Health
Literacy for the Council on Scientific Affairs, American
Medical Association. JAMA. 1999;282:525–527
12. Dreyer BP, Forbis SG, Yin HS. Health literacy and pediatric
health. Curr Probl Pediatr Adolesc Health Care. 2007;37:
258–286
13. Bindman AB, Castro C, Schillinger D, et al Physician com-
munication with diabetic patients who have low health lit-
eracy. Arch Intern Med. 2003;163:83–90
14. Baker DW, Nurss JR, et al Relationship of functional health
literacy to patients’ knowledge of their chronic disease. A
study of patients with hypertension and diabetes. Arch Intern
Med. 1998;158:166–172
15. Betancourt JR, Bowles J, et al Recommendations for teach-
ing about racial and ethnic disparities in health and health
care. Ann intern Med. 2007;147(9):654–665
16. Baer J, Kutner REF, Greenberg E. National assessment of
Adult Literacy (NAAL). A first look at the literacy of
America’s adults in 21st century. Available at: <http://nces.
ed.gov/naal>; 2009 Accessed 16.04.09
33
17. Baker DW, Gazmararian JA, Fehrenbach SN, et  al Health
literacy among medicare enrollees in a managed care organi-
zation. JAMA. 1999;281:545–551
18. Satterfield S, Sudore RL, Yaffe K, et al Limited Literacy and
mortality in the elderly: the health, aging and body composi-
tion study. J Gen Intern Med. 2006;21:806
19. Bass PF, Davis TC, Wolf MS, et al Literacy and misunder-
standing prescription drug labels. Ann Intern Med. 2006;
145:887
20. Weiss BD, Mays MZ, Martz W, et al Quick assessment of
literacy in primary care: the newest vital sign. Ann Fam Med.
2005;3:514–522
21. Grumbach K, Piette J, Schillinger D, et  al Association of
health literacy with diabetes outcomes. JAMA. 2002;288:475
22. Baker D, Blazer DG, Gazmararian J, et  al A multivariate
analysis of factors associated with depression. Evaluating
the role of health literacy as a potential contributor. Arch
Intern Med. 2000;160:3307–3314
23. Flores G. Culture and the patient–physician relationship:
achieving cultural competency in health care. J Pediatr.
2000;136:14
24. Thomas SB, Quinn SC. Public health then and now. The
Tuskegee Syphilis Study, 1932 to 1972: implications for
HIV education and AIDS risk education programs in black
community. Am J Public Health. 1991;81:1498–1504
25. White RM. Misinformation and misbeliefs in the Tuskegee
Study of Untreated Syphilis fuel mistrust in the health care
system. J Natl Med Assoc. 2005;97:1566–1573
26. Brownlee CD, McCoy TP, Miller DP, et  al The effect of
health literacy on knowledge and receipt of colorectal cancer
screening: a survey study. BMC Fam Pract. 2007;8:16
27. Ross J. Health literacy and its influence on patient safety.
J Peri Anes Nurs. 2007;22:220–222
28. Bennett L, Davis TC, Wolf MS, et al Literacy, self efficacy,
and HIV medication adherence. Patient Educ Couns. 2007;
65:253–260
29. Parikh NS, Parker RM, Nurss JR, et  al Shame and health
literacy: the unspoken connection. Patient Educ Couns.
1996;27:33–39
30. Comings JP, Rudd RE. Learner developed materials: an
empowering product. Health Educ Q. 1994;21:313–327
 Domestic Violence, Abuse, and Neglect:
Indicators for Dermatology
Jina P. Lewallen and Susan R. Adams
4.1 Introduction
This chapter will discuss the prevalence of domestic
violence and abuse and/or neglect of patients and the
dermatologic indicators for assessment, diagnosis, and
treatment. This chapter includes the following:
• A definition and view of domestic violence, abuse,
and/or neglect
• Review of current literature to include national and
global statistics that demonstrate the prevalence of
these issues
• Mandated reporting laws and process
• Assessment and diagnosis for the dermatologist
• Multidisciplinary approach in treatment
• Case studies
• Follow-up issues
4.2 Definitions
We need to begin with a definition of domestic vio-
lence, abuse (physical and sexual), and neglect. To
understand sexual abuse and domestic violence, we
must first agree on what these are. The United States
Centers for Disease Control and Prevention1 defines
domestic violence as:
Actual or threatened physical or sexual violence, or psy-
chological/emotional abuse by a spouse, ex-spouse, boy-
friend/girlfriend, ex-boyfriend/ex-girlfriend, or date. Some
of the common terms that are used to describe intimate
J. P. Lewallen (*)
Department of Geriatrics, University of Arkansas for Medical
Sciences, Little Rock, AR, USA
e-mail: lewallenjinap@uams.edu
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_4, © Springer-Verlag London Limited 2010
4
partner violence are domestic abuse, spouse abuse, domes-
tic violence, courtship violence, battering, marital rape
and date rape.
Domestic violence is a pattern of abusive and threaten-
ing behaviors that may include physical, emotional,
economic, and sexual violence as well as intimidation,
isolation, and coercion. The purpose of domestic vio-
lence is to establish and exert power and control over
another; men most often use it against their intimate
partners, such as current or former spouses, girlfriends,
or dating partners. While other forms of violence within
the family are also serious, this chapter will address the
unique characteristics of violence against women in
their intimate relationships.
Domestic violence is a behavior that is learned
through observation and reinforcement in both the
family and society. It is not caused by genetics or ill-
ness. Domestic violence is repeated because it works.
Domestic violence allows the perpetrator to gain con-
trol of the victim through fear and intimidation. Gaining
the victim’s compliance, even temporarily, reinforces
the perpetrator’s use of these tactics of control. More
importantly, however, the perpetrator’s abusive behav-
ior is reinforced by the socially sanctioned belief that
men have the right to control women in relationships
and the right to use force to ensure that control.2
Sexual abuse refers to any sexual activity perpe-
trated against another person, against their will or
without consent. Child sexual abuse is defined as sex-
ual violation of a child who cannot give consent.
In the United States and several countries, medical
and social service professionals, along with law
enforcement and the clergy, are mandated by law to
report any suspected abuse or neglect to law officers.
After the report is made, a follow-up to determine
abuse or neglect is made, usually within 24–72  h.
Failure to report by professionals can result in loss of
35
36
licensure or privilege to work in that profession.
Dermatologists fall within this category.
Practitioners should also be aware of the importance
of informed consent when treating patients. It is crucial
in the development of trust in creating the therapeutic
alliance. Informed consent in relation to abuse cases
includes an understanding between patient and practitio-
ner regarding the role of mandated reporting. This should
be in addition to standard disclosure and understanding
statements related to treatment options and risks.
Other types of violence perpetrated against women
and children can be seen in child and elder abuse.
There are a smaller percentage of men who are victims
of domestic abuse and the number of male children is
significant in cases of sexual abuse.
4.3 Common Characteristics of Victims
Victims may share common characteristics regardless
of age or sex. They are often overwhelmed by feelings
of helplessness and dependency. Presentation of anxi-
ety or anger, along with multiple physical complaints,
may be present during the diagnostic interview. Victims
may feel responsible for the abuse or neglect and will
often provided detailed explanations for the perpetra-
tors actions. Typically, symptoms of depression and
low self-esteem will also be a factor. In addition to the
injuries sustained, emotional trauma and damage per-
sists long after physical health is restored. It is com-
mon for children and adults to “try harder” to prevent
future attacks. Understanding the futility of this mis-
sion is difficult for victims to comprehend.
4.3.1 Children
Federal legislation provides a foundation for the states
by identifying a minimum set of acts or behaviors that
define child abuse and neglect. The federal child abuse
prevention and treatment act (CAPTA),3 as amended
by the Keeping Children and Families Safe Act of
2003 defines child abuse and neglect as, at minimum:
Any recent act or failure to act on the part of a parent or
caretaker which results in death, serious physical or emo-
tional harm, sexual abuse or exploitation; or An act or
failure to act which presents an imminent risk of serious
harm.
J. P. Lewallen and S. R. Adams
This definition of child abuse and neglect refers spe-
cifically to parents and other caregivers. A “child”
under this definition generally means a person who is
under the age of 18 or who is not an emancipated
minor. Children with special needs are at a higher risk
of abuse or neglect. Many times children will wear the
history of their trauma including scars, physical abnor-
malities, or disabilities. Head injury is a major cause of
death and permanent disability for children under the
age of two; therefore, special attention should be given
to internal ear and eye exams. Bones and joints are
manipulated to assess for tenderness and range of
motion. Addressing eating patterns, sleeping patterns,
problems swallowing, and mastery of age-appropriate
tasks are also areas for assessment.
4.3.2 Elder Abuse and Domestic Violence
Elder domestic abuse is a pattern of violence started
earlier in life that has persisted in later years. It may
also begin in later life due to strains of retirement, dis-
ability, or illness that comes in aging years. Like
domestic violence in early years, the perpetrators are
usually male.
Elder sexual abuse is any nonconsensual contact
with an older person. This includes fondling, oral,
anal, vaginal sex, pornography, and other sexual acts
meant to demean, injure, or mental or emotionally
trauma as a result of contact.
Physical abuse is any physical contact that results in
injury, pain, or impairment. This includes hitting, kick-
ing, biting, and inappropriate restraint of an elderly
person.
Psychological abuse and financial abuse are also of
importance and should be noted. According to the
national incident study on elder abuse:
• Female elders are abused at a higher rate than males,
after accounting for their larger proportion in the
aging population.
• Our oldest elders (80 years and over) are abused
and neglected at 2–3 times their proportion of the
elderly population.
• In almost 90% of the elder abuse and neglect inci-
dents with a known perpetrator, the perpetrator is a
family member, and two-thirds of the perpetrators
are adult children or spouses.
4  Domestic Violence, Abuse, and Neglect: Indicators for Dermatology
4.3.3 Warning Signs
It is important for every healthcare provider to be
aware of and act on signs and symptoms of abuse while
creating a safe environment for the elderly person to
report without fear of continued mistreatment from
family and/or caregivers.
The National Elder Abuse Incidence Study4 pre-
pared for the administration for children and families
and the administration on aging in the US Department
of Health and Human Services gives the signs and
symptoms shown in Table 4.1 to assist healthcare pro-
fessionals in what to look for when investigating pos-
sible abuse of children and elderly persons.
4.4 Mandatory Reporting
Victims of domestic abuse or sexual abuse need imme-
diate medical care. In the United States, healthcare
providers are mandated by state laws to report sus-
pected abuse or neglect of any patient they treat.
According to the child welfare information gateway,5
all states, the District of Columbia, the Commonwealth
of Puerto Rico, and the US territories of American
Samoa, Guam, the Northern Mariana Islands, and the
Virgin Islands have statutes identifying mandatory
reporters of child maltreatment. A mandatory reporter is
a person who is required by law to make a report of child
maltreatment under specific circumstances. Approxi­
mately 48 states, the District of Columbia, Puerto Rico,
and the territories have designated individuals, typically
by professional group, who are mandated by law to
report child maltreatment. Individuals typically desig-
nated as mandatory reporters have frequent contact with
children. Such individuals may include:
• Physicians
• Social workers
• School personnel
• Healthcare workers
• Mental health professionals
• Childcare providers
• Medical examiners or coroners
• Law enforcement officers
The same applies for all ages of suspected abuse or  The role of the healthcare provider in detecting and
neglect victims. Each state determines who is a man- preventing abuse begins with the first look or assess-
dated reporter. Failure to report, in many states, can ment of the patient. For dermatology, assessment of
37
result in fines, penalties, and loss of licensure to prac-
tice. Check with your local authority.
Reporting is mandatory whenever a healthcare pro-
fessional suspects domestic violence, abuse, or neglect,
whether or not it is proven. Some professionals are
very sensitive about reporting suspected abuse for fear
of misreporting or repercussions over unproved reports.
However, the law protects mandatory reporters from
prosecution if the report is not proven. It is important
to remember that you must report and failure to do so
can affect your practice in the future.
4.5 Common Characteristics of Abusers
Along with an awareness of possible victims, practitio-
ners should also be cognizant of possible perpetrators
as well. It is not unusual for the abuser to bring the
victim to medical appointments and to insist on being
part of the interview.
Persons who abuse lack control over aggressive
impulses that lead to explosive behavior. The offenders
will often explain their behavior as a form of “disci-
pline” and necessary. Emotional immaturity is a com-
mon problem, as is the inability to process situations in
an appropriate manner. Narcissism is also a common
characteristic that leads to difficulty in engaging and
maintaining adult relationships. This egocentric view
interferes with the abusers’ ability to recognize the
needs of others. They may also view their potential
victims as objects responsible for meeting their needs.
Persons who abuse have a tendency to be suspicious
of everyone with whom they are in contact. On some
level, there is recognition that their behavior is abnor-
mal in relation to society’s expectations and they fear
exposure. There are no obvious signs of mental illness,
substance abuse, or related symptoms that can easily
establish the identity of an offender, so it is important
to be aware of indicators in order to obtain additional
information about your patients and their situations.
4.6 Role of Healthcare Provider
38 J. P. Lewallen and S. R. Adams

Table 4.1  Warning signs of abuse and neglect in children and the elderly
General
  Frequent unexplained crying
  Unexplained fear of or suspicion of particular person(s) in the home
  Bruises, black eyes, welts, lacerations, and rope marks
  Bone fractures, broken bones, and skull fractures
  Open wounds, cuts, punctures, untreated injuries, and injuries in various stages of healing
  Stains, dislocations, and internal injuries/bleeding
  Broken eyeglasses/frames
  Physical signs of being subjected to punishment and signs of being restrained
  Laboratory findings of medication overdose or underutilization of prescribed drugs
  An elder’s report of being hit, slapped, kicked, or mistreated
  An elder’s sudden change in behavior
  A caregiver’s refusal to allow visitors to see an elder alone
Sexual abuse
  Bruises around the breasts or genital area
  Unexplained venereal disease or genital infections
  Unexplained vaginal or anal bleeding
  Torn, stained, or bloody underclothing
  An elder’s report of being sexually assaulted or raped
Emotional and psychological abuse
  Emotional upset or agitation
  Extreme withdrawal and noncommunication or nonresponsiveness
  An elder’s report of being verbally or emotionally mistreated
Neglect
  Dehydration, malnutrition, untreated bedsores, and poor personal hygiene
  Unattended or untreated health problems
  Hazardous or unsafe living conditions (e.g., improper wiring, no heat or no running water)
  Unsanitary or unclean living conditions (e.g., dirt, fleas, lice on person, soiled bedding, fecal/urine smell, inadequate clothing)
  An elder’s report of being neglected
Abandonment
  The desertion of an elder at a hospital, nursing facility, or other similar institution
  The desertion of an elder at a shopping center or other public location
  An elder’s own report of being abandoned
Self-neglect
  Dehydration, malnutrition, untreated or improperly attended medical conditions, and poor personal hygiene
  Hazardous or unsafe living conditions (e.g., improper wiring, no indoor plumbing, no heat, or no running water)
  Unsanitary or unclean living quarters (e.g., animal/insect infestation, no functioning toilet, fecal/urine smell)
  Inappropriate and/or inadequate clothing, lack of necessary medical aids (e.g., eyeglasses, hearing aid, dentures)
  Grossly inadequate housing or homelessness
4  Domestic Violence, Abuse, and Neglect: Indicators for Dermatology
bruises, cuts, and abrasions can be relevant in the diag-
nosis of a skin disease or condition, or of suspected
abuse. There are many skin conditions that mimic signs
of abuse and will be discussed later in the chapter.
One of the most difficult problems caused by these
family dynamics is treatment noncompliance. As noted,
offenders may be very suspicious of any medical pro-
fessional attempting to engage the victim. They may
discourage the patient from keeping return appoint-
ments or refuse to allow private interviews with the vic-
tim. They may have multiple caregivers in order to
avoid arousing suspicion.
4.6.1 Patient Interviews
When working with patients, interviews should be non-
threatening and nonjudgmental. It is easy to become
part of the abusive system rather than a possible haven.
Beginning the interview by asking general, nonthreat-
ening questions will help the client feel more at ease.
Making basic inquires into patients needs will indicate
the willingness to listen and open the doorway to more
detailed communication. Some victims will have a
desire to discuss the situation quickly while others may
choose to be more cautious in their revelations. Once
rapport has been established, it will be necessary to
address the injuries and their possible origins. Patients
will need to know they will have some form of protec-
tion if abuse is revealed to the physician. Accurate refer-
ral information should be maintained in the office.
When evaluating patients for possible abuse, there
are several factors that should be noted in developing
an assessment6 including
• Nonverbal communication between patient and
caregiver, partner, or parent
• Verbal communication between patient and care-
giver, partner, or parent
• Body language of all persons involved
• Balance of communication between patient and
practitioner and caregiver, partner, or parent
• Dominant or submissive behavior of patient and
caregiver, partner, or parent
• Effectual responses to interview material
• Ability to answer questions directly vs. subject
changes and evasive, tangential, or irrelevant answers
• Comfort levels of individuals during interview
39
Practitioners must fully understand the implications of
abuse and mandated reporting and be competent to
safeguard the patient if abuse is suspected.
4.7 Statistics on Abuse, Neglect,
and Violence
Although men can be victims of domestic violence,
abuse, or neglect, reports indicate that while males have
a higher incident of abuse as children, as adults they are
rarely a reported victim. Many potential male victims
do not report for various reasons. Some men feel they
could have prevented the abuse; others victimized by
another male, fear to reveal intimate details of their
sexual orientation. In the elderly, men may fail to report
because they are not cognitively aware that they have
been mistreated. In this case, professionals should take
extra care in assessing for potential abuse. The same
holds true for any elderly or mentally disabled person.
Up to 44% of American women have experienced
some type of domestic violence during their lives,
either as a witness or as a victim.7, 8
The prevalence of violence, abuse, and neglect for
women and children is not limited to the United States.
Globally, that number is even higher; one out of three
women reported being beaten, raped, or abused emo-
tionally or economically during her lifetime.9 Many of
the women reported witnessing or being a victim of
abuse as children.
Outcomes for women and children victims are
many10:
• More than three women are murdered every day by
husbands or boyfriends as a result of domestic
violence.
• One in five high school females report being abused
sexually or physically by a dating partner.
• Half of the men who abuse their wives also abuse
their children.
• Three in four 18-year-old women reported rape or
physical assault by a dating partner, cohabitating
partner, or spouse; corroborating police reports that
showed reported attacks by an acquaintance were
higher than assault by a stranger.
Globally, domestic violence is dependent on definition
of cultural norms and laws. Many countries do not
have laws or enforce laws that deal with domestic
40
violence as they find it culturally acceptable. Some of
these practices are seen in the statistics for global
violence.
Global statistics vary, but indicate prevalence for
abuse through sex and human trafficking, increased
rates of HIV and AIDS in women and children, mur-
der, genital mutilation, and an increase in hospitaliza-
tions for women and children as the result of domestic,
physical, or sexual violence.11
In healthcare practice, cultural norms must be con-
sidered in assessment and treatment of suspected
abuse. While many countries agree on the definition of
domestic violence, sexual abuse, and neglect, some
practice violence as part of their culture.
An example of this can be seen in the practice of
female genital mutilation (FGM), a cultural practice
many would consider physical or sexual abuse of
female children.12
Each year at least two million girls face the risk of
genital mutilation, most of who are between 2 and 8
years old. About 85–114 million females worldwide
have mutilated genitalia. Most of these females reside in
Africa. They encounter pain, trauma, and often, physi-
cal complications (e.g., bleeding, infections, and death).
FGM consists of clitoridectomy (partial or total removal
of the clitoris and/or the labia minora) or infibulation
(total removal of the clitoris, partial or total removal of
the labia minora, and incisions in the labia majora).
FGM is a cultural, not religious, tradition which is
used to prepare girls for womanhood. Muslims,
Christians, some animists, and one Jewish sect practice
FGM, but none of these religions require FGM. It is
used to perpetuate women’s second-class status. FGM
enhances the sexual pleasure of men while genitally
mutilated women sense little or no sexual pleasure.
This denial of sexual pleasure can have psychological
effects on women. These women therefore become
sexual objects and reproductive vehicles for men.
The FGM practitioners vary by area and include tra-
ditional birth attendants, female laypeople, physicians
and other trained health personnel, and women leaders.
African women created the Inter-African Committee
Against Traditional Practices Affecting the Health of
Women and Children in 1984, which serves as the basis
for global action against FGM. African immigrants in
developed countries have taken the practice of FGM
with them. Women in these countries have brought
FGM to the fore and are pressing for laws against it.
Protection from physical and sexual abuse, such as
FGM, is a child’s right. Information on prevalence,
J. P. Lewallen and S. R. Adams
physical, and psychological effects, and religious require-
ments are needed to take action against FGM. Legal
remedies include international action and national law.
Each country’s mass communication systems and popu-
lar culture should be engaged in spreading information
about FGM and in generating discussions on FGM.
In the United States, FMG is considered child abuse
and is reportable to legal and social services agencies.
A report13 that surveyed and analyzed doctors’
reporting records found that one-third of the surveyed
doctors did not keep a record on domestic violence
reported by patients, nor did they report much support,
advice, or resources to those who did report being a
victim. Only 10% of doctors in the survey reported
giving any information on where patients could seek
assistance. A third reported that they were not confi-
dent about counseling patients who reported domestic
abuse. This report demonstrates the need for physi-
cians and other healthcare professionals to get training
and be aware of mandated reporting laws.
Many healthcare settings have diverse populations.
Patients come from different racial, ethnic, or cultural
backgrounds and practitioners need to be aware of cul-
tural norms or differences.
In many cultures, traditional treatments are used
before seeking professional medical treatments. Health­
care practitioners should be knowledgeable about cer-
tain cultural practices as they can also resemble indicators
of abuse. When assessing patients for diagnoses, the
practitioner may observe what looks like abuse indica-
tors, so a complete history of the patient, including cul-
tural norms, is indicated.
Some examples that apply to dermatology can be
seen in therapeutic burning (moxibustion), cupping,
coin rubbing, and pinching.
Moxibustion, or therapeutic burning, is a folk rem-
edy used in Southwest Asia and parts of Africa. Dot
and patterned burns on the abdominal area, arms, and
legs are thought to correlate to the internal energy
channels on the skin. In Korean culture, moxibustion is
used to correct the disharmony in the body due to ill-
ness. The yin and the yang are rebalanced and the
patient is considered healed.
Cupping is a very common folk treatment. A piece
of cotton or material is set afire in the bottom of a glass
or cup and the open mouth of the vessel is quickly
placed on the patient’s back. The heat and suction pro-
duces a bruise or welt and sometimes a burn. The pro-
cedure may be repeated up and down the back of the
patient. The cupped areas are believed to draw out
4  Domestic Violence, Abuse, and Neglect: Indicators for Dermatology
fever and illness. Many people who go for cupping
treatments believe it will eliminate toxins through
breathing and through the skin. It is believed that cup-
ping draws out any illness in the body, leaving the
patient healthier overall.
Coin rubbing or coining is another common folk
remedy for releasing illness or fever from the body. In
the traditional technique, a coin is dipped in oil or
mentholated cream and rubbed across the skin to pro-
duce welts or burns. This practice is believed to restore
balance in the sick patient by withdrawing illness.
In addition to cupping and coining, many Asian
cultures and medicinal practices include pinching. The
treatment involves pinching the neck, bridge of the
nose, and other areas of the skin where the illness is
believed to originate. The pinching is severe enough to
cause dermabrasion or bruising to the skin. This prac-
tice is believed to draw out the bad force or illness and
restores body balance.
Other mimickers of abuse include dermatological
conditions unrelated to previous folk treatments.
Dermatitis as a result of irritants, seborrheic dermati-
tis, pinworms, and scabies can be misdiagnosed by
general practitioners. Referral to dermatology special-
ists is warranted.
Other skin conditions that may mimic abuse warrant
a closer evaluation by the practitioner. There are many
incidents where skin conditions may mimic abuse14:
• Genital warts
• Pigmented vulvar hamartomas
• Darier’s disease
• Lichen sclerosus
• Crohn’s disease
• Localized varicella or zoster infection
• Pseudoverrucous papules
• Hemangiomas
• Urethral prolapse
• Allergic contact dermatitis
4.8 Assessment and Diagnoses
for Dermatology
In assessing the patient for suspected abuse or neglect,
the dermatologist needs to conduct a thorough exami-
nation of the patient, keep accurate documentation,
obtain photographs, and ensure the patient’s safety
during the process.
41
For bruising, True petechiae and purpura, infec-
tions, group A streptococcal infections, Lichen sclero-
sus, vascular malformities, phytophotodermatitis.
Mongolian spots, urticaria/angioedema, pernio to folk
medicine remedies such as “cupping” and Cao gio or
coin rubbing, both used to “draw out fever and disease.”
For mimicking burns: impetigo, diaper dermatitis,
pernio, chemical burns from over-the-counter treat-
ments such as analgesic balm, sunburn can be observed
as inflicted burns and reported as abuse.
In cases as a result of abuse, team care is absolute
in diagnosing, treating, reporting, and follow-up for
the victim. Team care needs to include healthcare
providers, social services, legal authorities to ensure
the safety of the patient, especially in abuse cases
involving minors or elderly who are most often
vulnerable.
4.9 Prevalence
A broad view and understanding of the prevalence of
domestic violence, abuse, and neglect can be found in
Bureau of Justice statistics15 (Table  4.2). On average
since 2001, for nonfatal intimate partner violence,
about one-third of female and male victims reported
that they were physically attacked (Table  4.3) while
two-thirds said that they were threatened with attack,
including threats with a weapon and threats to kill
(Table 4.4). Half of the females suffered an injury from
their victimization. Forty-four percent suffered minor
injuries while 5% were seriously injured; 3% were
raped or sexually assaulted (Table  4.5). More than
one-third of the male victims were injured: 36% with
minor injuries and 4% with major injuries (Table 4.6).
Less than one-fifth of victims reporting an injury
sought treatment following the injury (Table 4.7).
Table 4.2  Average annual percent of threats, attempted attacks,
and physical attacks in nonfatal intimate partner victimization,
2001–2005
Type of violence Percent of victims of intimate
partner violence
Female Male
Attempt or threat 67.2 66.3
Physically attacked 32.8 33.7
100 100
42 J. P. Lewallen and S. R. Adams

Table 4.3  Average annual percent of attacks, by type, in nonfatal Table  4.5  Average annual number and percent of injuries
intimate partner violent crime, 2001–2005 sustained by female victims as a result of nonfatal intimate
Type of attack Percent of victims of partner violence, 2001–2005
nonfatal intimate partner Intimate partner victim Average annual
violence who were attacked Number Percent
Female Male
Total 510,970 100
Raped 7.2 0.8a
Not injured 248,805 48.7
Sexual assault 1.9 0.9
Injured 262,170 51.3
Attacked with firearm 0.5a –
Serious injury 25,710 5
Attacked with knife 2.5 8a
Gunshot wound 595 0.1a
Hit by thrown object 2.1 4.5a
Knife wounds 4,940 1a
Attacked with other weapon 0.8a 1.8a
Internal injuries 3,440 0.7a
Hit, slapped, knocked down 62.7 62.2
Broken bones 12,155 2.4
Grabbed, held, tripped 54.9 26
Knocked unconscious 3,730 0.7a
a
Based on ten or fewer sample cases
“–” Information is not provided because the small number of Other serious injuries 855 0.2a
cases is insufficient for reliable estimates
Rape/sexual assault without 13,350 2.6
additional injuries
Table 4.4  Average annual percent of threats, by type and gender,
in nonfatal intimate partner violence crime, 2001–2005 Minor injuries only 222,670 43.6
Type of threat Percent of victims of Injuries unknown 435 0.1a
nonfatal intimate partner Based on ten or fewer sample cases
a

violence, 2001–2005 Note: total may not add to 100% due to rounding
Female Male
Threatened to kill 26.9 15.1a Table  4.6  Average annual number and percent of injuries
Threatened to rape 0.5a – sustained by male victims as a result of nonfatal intimate partner
violence, 2001–2005
Threatened with harm 59.3 55.3 Average annual
Threatened with a weapon 17.6 22.9 Number Percent

Threw object at victim 7.5 7.4a Total intimate partner victims 104,820 100

Followed/surrounded victim 5.9 1.8 a Not injured 61,285 58.5

Tried to hit, slap, or knock 14.1 12.6 a Injured 43,540 41.5

down victim Serious injury 4,335 4.1a
a
Based on ten or fewer sample cases
“–” Information is not provided because the small number of Minor injuries only 38,050 36.3
cases is insufficient for reliable estimates Rape/sexual assault without 580 0.6a
Note: detail may not add to total because victims may have other injuries
reported more than one type of threat
Injuries unknown 570 0.5a
Based on ten or fewer sample cases
a

4.9.1 Costs of Violence-Related Note: detail may not add to totals due to rounding

Injury in America
v­ iolence annually, at a cost of $37 billion ($33 bil-
lion in productivity losses, $4 billion in medical
The costs of assessing, diagnosing, and treating domes-
treatment).
tic abuse are high. According to the Centers for Disease
• The cost of self-inflicted injuries (suicide and
Control and Prevention16:
attempted suicide) is $33 billion annually ($32 bil-
• Americans suffer 16,800 homicides and 2.2 million lion in productivity losses, $1 billion in medical
medically treated injuries due to interpersonal costs).
4  Domestic Violence, Abuse, and Neglect: Indicators for Dermatology 43

Table 4.7  Average annual percent of medical treatment sought 4.10 Identification and Assessment
as a result of nonfatal intimate partner violence, by gender,
2001–2005 of the Patient
Average annual (%)
Female Male In healthcare settings, many victims of domestic, phys-
Not injured 48.7 58.5 ical, or sexual abuse present themselves for other medi-
Injured 51.3 41.5 cal issues or with unexplained or poorly explained
injuries.
Injured, not treated 32.8 27.9
Some patients present with chronic pain complaints,
Treated for injury 18.5 13.1 some with bruising, scratches, or burns that are not
At scene or home 8.3 9.8 consistent with accidental injury. Patients who are vic-
tims of abuse may cover their common sites of injury
Doctor’s office or clinic 1.3 0.6a
such as arms, neck, breasts, chest, and abdomen with
Hospital 8.7 2.8a clothing, many times inappropriate for the weather. An
Not admitted 8.4 2.8a example of this can be seen in patients coming in with
Admitted 0.3 – turtleneck or long-sleeved shirts in summer. Hats,
gloves, and scarves are also commonly used.
Other locale 0.2 –
In assessing for physical injuries in the healthcare set-
Don’t know – 0.5a ting it is important to make the patient feel safe. Patients
a
Based on ten or fewer sample cases are often reluctant to report abuse or violence for fear of
“–” Information is not provided because the small number of
retribution from abuser, separation from abuser, and
cases was insufficient for reliable estimates
Note: detail may not add to totals due to rounding uncertainty of belief from the provider assessing them
and to uncertainty of what will happen to them if they
report. This is prevalent in domestic violence as the per-
• People aged 15–44 years comprise 44% of the pop- petrator of the abuse is a spouse who has isolated their
ulation, but account for nearly 75% of injuries and partner from family and friends and made her dependent
83% of costs due to interpersonal violence. on him for economic and emotional support.

4.9.2 Result of Violence-Related Injury17 4.10.1 Universal Guidelines

• The average cost per homicide was $1.3 million in
lost productivity and $4,906 in medical costs.
• The average cost per case for a nonfatal assault
resulting in hospitalization was $57,209 in lost pro-
ductivity and $24,353 in medical costs.
• The average cost per case of suicide is $1 million
lost productivity and $2,596 in medical costs.
• The average cost for a nonfatal self-inflicted injury
was $9,726 in lost productivity and $7,234 in medi-
cal costs.
• Economic costs provide, at best, an incomplete
measure of the toll of violence. Victims of violence
are more likely to experience a broad range of
mental and physical health problems not reflected
in these estimates from posttraumatic stress disor-
der to depression, cardiovascular disease, and
diabetes.
These guidelines are globally recognized as a complete
assessment for diagnosis and charting procedures for
evidence for mandated reporting.18
4.10.1.1 Physical Examination
All healthcare providers should implement routine
physical exam techniques that ensure accurate medical
diagnosis:
• Central distribution of injury: face, neck, throat,
chest, abdomen, genitals
• Bilateral distribution of injury to multiple areas
• Contusions, lacerations, abrasions, human bites, or
no evidence of physical trauma despite subjective
complaint by patient/victim
44
• Delay between onset of injury and presentation for
treatment
• Multiple injuries in various stages of healing
• Extent or type of injury inconsistent with patient’s
explanation
• Evidence of alcohol or drug abuse
• Evidence of rape
• Repeated chronic injuries
• Chronic pain, psychogenic pain, or pain due to dif-
fuse trauma without visible evidence
• Documentation of pertinent negative findings should
address all subjective complaints for which there is
no physical evidence
• With the patient’s permission, photographs should
be obtained of visible injuries
Any assessment for domestic violence should be included
as part of psychosocial and mental health assessments.
The stress of domestic violence may aggravate psychiat-
ric disorders. Mental health disorders can be exacerbated
by domestic violence, sexual abuse, or neglect. Some
mental health reactions can be observed and assessed in
the patient as:
• Suicidal thoughts and attempts
• Depression
• Feelings of helplessness
• Substance abuse
• Posttraumatic stress disorder
• Psychoses
In addition, healthcare providers should be especially
alert to injuries and indicators during pregnancy
including:
• Injuries, particularly to the breasts, abdomen, and
genital area
• Substance abuse, poor nutrition, depression, and
late or sporadic access to prenatal care
• “Spontaneous” abortions, miscarriages, and prema-
ture labor
• Rapid heartbeat, asthma, and reported inability to
sleep
4.10.1.2 Charting
Healthcare providers should make a complete, legible
record/chart of their findings. The reporting form is no
substitute for complete documentation in the medical
record. This chart should include:
J. P. Lewallen and S. R. Adams
• A detailed description of patient injuries: type,
extent, age, location, and the use of a body chart
when applicable (see resources at the end of the
chapter)
• Photographs of patient injuries. The patient should
be informed that the photographs are to be used as
possible evidence and give permission.
• The maintenance of physical evidence. Forensic
nurses and technicians collect physical evidence, and
social services are available for emotional assessment
and support during the process of examination.
• The inclusion of relevant past medical history: his-
tory of falls, “accident prone” injuries; social his-
tory: overly concerned partner; history of substance
abuse (including alcohol) by patient or partner; and
sexual history: history of sexually transmitted dis-
eases or rape
• All charts should include comments by the health-
care providers as to whether the explanation offered
for the injury adequately explains the injury.
• The patient’s own words, with the use of quotation
marks, should be entered into the chart in the chief
complaint and history of present illness section(s)
describing the abusive event.
• Name of investigating officer and any action taken
if the police were called.
• Document every detail, even seemingly trivial ones,
such as torn clothing, smeared make-up, broken fin-
gernails, scratches, and bruises.
• Include names of all personnel who examined or
talked with the patient about the injuries or abuse in
the record. All personnel who attend the patient
should have collaborating notes in the chart.
4.10.1.3 Admissibility of Records
Note that records are admissible as evidence if:
• They were made during the “regular course of
business”
• They were made in accordance with routinely fol-
lowed procedures
• They were stored properly and access to them is
limited to staff only
Even if a patient later decides that s/he does not want
to pursue legal remedies, a case can still be proven by
introducing the statements s/he made to people in the
past about what happened. Include anything that might
4  Domestic Violence, Abuse, and Neglect: Indicators for Dermatology
allow you to remember the patient’s attitude, face, and
experience at a later date.
4.11 Clinical Assessments and
Diagnosis for the Dermatologist
In the healthcare setting, domestic violence, sexual
abuse/neglect of children and elderly is diagnosed in
the initial healthcare visit. Dermatology is viewed as a
team member in assessment and diagnosis of abuse or
neglect and is often times called upon to confirm a
report by the primary care practitioner.
While primary practitioners, geriatricians, pediatri-
cians, and family practitioners are all trained in abuse
and neglect, it is often the dermatologist who makes
the definitive diagnosis with skin injuries, rashes, and
other indicators of abuse.
4.12 Multidiciplinary Approach
In domestic violence, abuse, and or neglect, best
­outcomes are reported by using a multidisciplinary
approach. In building a case for domestic violence and
abuse/neglect, a multidisciplinary report offers the
whole picture for events occurred to the patient, and
provides a timeline for outcomes from initial contact
with healthcare systems through treatment and follow-
up. The identification of suspected domestic violence,
abuse or neglect, multidisciplinary teams, including
dermatology, is often the best determiner of abuse.
45
Persons who have been victimized through domes-
tic violence, abuse, or neglect often require medical
care and healthcare providers are most often the initial
point of contact.
References
  1. United States Center for Disease Control, 2000
  2. Anne L. Ganley, Susan Schechter. Domestic Violence: A
National Curriculum for Family Preservation Practitioners.
1995:17–18
  3. Federal Child Abuse Prevention and Treatment Act (CAPTA)
[(42 U.S.C.A. §5106g)], as amended by the Keeping Children
and Families Safe Act of 2003
  4. National Elder Abuse Incidence Study (Final Report, Sept.
1998) prepared for The Administration for Children and
Families and The Administration on Aging in The U.S.
Department of Health and Human Services
  5. Welfare Information Gateway, 2005
  6. Mental Health Psychiatric Nursing
  7. Family Violence Prevention Fund
  8. American Journal of Preventative Medicine, June 2004
  9. UN Commission of the Status of Women, 2/28/00
10. Statistics reviewed from the Bureau of Justice: Crime and
Victim Summary (2000–2002) report
11. World Health Organization report on Gender Based
Violence
12. Toubia N. New York, New York, Women, Ink, 1993. 48 p
13. Forbes.com issue: December 2005
14. Dermatology, Chapter 105, skin signs of Physical Abuse
(McGraw Hill, Access Medicine website
15. Bureau of Justice statistics
16. Centers for Disease Control
17. Corso PS, Mercy JA, Simon TR, et al Medical costs and pro-
ductivity losses due to interpersonal violence and self-
directed violence. Am J Prev Med. 2007;32(6):474–482
18. Family Violence Prevention Fund and Educational programs
Manual for health Care Professionals
 Working with Other Healthcare Providers
Jina P. Lewallen, Carolyn Lazaro Tuturro, and Angelo Turturro
5.1 Introduction
In the treatment of dermatological problems, the multi-
or interdisciplinary approach encourages each disci-
pline to bring its own training, skills, and experience
to the problem-solving and treatment options for com-
plete care of the patient. Each member of the team has
a professional interest in their patient, while working
in a team environment encourages each member to
bring their own skills, experience, and perspective to
the table. This also gives each member the flexibility
to develop a care plan that meets all of the patients
needs, medical and nonmedical. The team approach
can be used for problem solving and for exchange of
information and ideas in caring of the patient for best
outcomes.
This integrated approach to medical care, although
it may appear to be a product of significant recent
changes in medicine (or a result of a more social
approach to medicine pioneered in the 1960s), is actu-
ally much older. Working together with other profes-
sional providers for patient care was first formalized
in 1905 at Massachusetts General Hospital where
there was a consideration of the whole patient and the
relationship between illness and social conditions in
treatment.18
How a multidisciplinary approach works can be
illustrated by considering a scenario in the pathway
of care for the patient. The patient goes to his/her
primary care physician (PCP), who refers the patient
J. P. Lewallen (*)
Department of Geriatrics, University of Arkansas for Medical
Sciences, Little Rock, AR, USA
e-mail: lewallenjinap@uams.edu
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_5, © Springer-Verlag London Limited 2010
5
to a dermatologist. The communication between
these two medical professionals is a vital link to the
overall care of the patient. Nursing staff, lab staff,
and scheduling staff are all needed to efficiently
guide the patient through the healthcare pathway.
Social work staff may assist in coordinating care
through resources and referrals, especially for con-
tinuance of care at home. Psychiatrists, occupational
therapists, and physical therapists may be called on
for collaborative and collateral consultations and
parallel treatments. All of these professionals on the
team play an integral part in total patient care. This is
especially important for dermatological care since
the skin is an external organ and what afflicts the
skin is often seen by other people. Their reactions
can be almost as significant to the patient as the prob-
lem itself.
Multidisciplinary and/or interdisciplinary work has
proven to be most effective when team members:
• Have common goals for healthcare outcomes.
• Have professional and personal commitment to
care.
• Have clarification of their role on the team.
• Have the support and respect of other team mem-
bers for their contributions to the team.
• Have good communication among the team
members.
• Have an environment that promotes these factors.
For teaching and training, multidisciplinary/interdisci-
plinary teams give students a collaborative experience
and view of healthcare delivery that enhances their
own discipline. Students from all areas of healthcare
education programs gain collaborative and extensive
knowledge and skills from each member while learn-
ing about team/group process.
47
48
5.2 The Scope and Extent
of Multidisciplinary Efforts
5.2.1 Scope of Multidisciplinary Efforts
Clark et  al4 report that the joint commission on the
accreditation of healthcare organizations (JCAHO)
requires evidence of disciplines working collabora-
tively as part of its accreditation process in hospitals,
nursing homes, and clinics. Bringing together different
disciplines encourages an exchange of knowledge and
ideas which are applied to the care of the patient. While
each discipline shares basic knowledge and values
(ethics) on patient care, each discipline also brings its
unique contribution to the care and treatment of the
patient from its perspective field.
The need for interdisciplinary, multidisciplinary
teamwork has been recognized most commonly in the
field of geriatrics. This may be because of the multifo-
cal aspects of the diseases of aging and the tendency of
aging to integrate these factors over the lifetime of the
patient. Some of the other areas of medical care, besides
dermatology, where multidisciplinary approaches are
commonplace include:
• Pediatrics
• Emergency medicine
• Oncology
• Ophthalmology, ENT
• Orthopedics
5.2.2 Multidisciplinary Efforts
in Dermatological Care
For dermatological care, some of the professions and
roles that collaborate with the dermatologist include
• Nursing staff, who provide triage, basic medical
assessment, and disease-specific care for patients
• Laboratory staff, who conduct general medical
tests and diagnostics but especially dermatological-
­disease-specific analyses and assessments for patient
treatment (some that require special training)
• Pharmacy staff, who provide drug education and
support for the patient
• Social workers, psychologists, and psychiatrists,
who help with nonmedical concerns and issues for
J. P. Lewallen et al.
the patient during treatment by the dermatologist to
address the complex issues of self-image, social
response, and support for the consequences of der-
mal disease (e.g., psoriasis)
• Genetic counseling staff, who provide genetic test-
ing to confirm dermatological conditions that are
inherited or can be passed on to further generations,
for advice and support
• Health educators, who keep patients informed about
their particular dermatological conditions and treat-
ments and, along with social services, provide sup-
port for total care
• Obstetrics and gynecology, who work with derma-
tology on issues of skin disorders for pregnant
women and as partners in total care of the patient
One consideration that should not be overlooked is that
the list of disciplines involved need not be static as the
patient’s condition evolves, or even the same for differ-
ent dermatological problems. A key aspect of the mul-
tidisciplinary approach is that different disciplines are
called in as needed.
5.2.3 Challenges for Multidisciplinary
Efforts
The challenges of working in multidisciplinary care
teams are universal in working in any team setting.
These are varied, but include:
• Determining who will be in charge of the team. In
dermatological settings, it can be the dermatologist,
or the PCP, or (more problematically) both as equally
in charge. Patients usually need to identify with a
leader who can answer questions and provide a con-
nection between specialties during assessment and
treatment.
• Clinical protocols, which can take varied pathways
from general medical protocol to more specific proto-
col, depending on the patient’s need or medical condi-
tion. The team needs to prioritize protocol for treatment
and identify who will take charge of each procedure.
• Challenges that arise when two or more team mem-
bers cannot agree on treatment protocol. As we
know, there are varied ways to apply caring and
treatment options. It is necessary that the team mem-
bers agree on assessment, diagnosis, and treatment
with the best outcomes for the patient as the ­common
5  Working with Other Healthcare Providers
goal. When challenges arise, the team should have
consensus on which is the first or the best treatment
protocol for the patient. This is a special area of con-
cern since, if this is not done, treatments by different
members can be at cross-purposes with no clear way
to assess whether they are working or not.
• Each team member brings their own experience,
level of education, and expertise which may or may
not be on the same level as other team members.
Team members have the opportunity to share this
knowledge and experience with other team mem-
bers to enrich the experience and to achieve a more
level arena in which to work.
• Each discipline has its own language and philoso-
phy of practice, so consideration for each must be
addressed and an agreed on language/philosophy
needs to be adopted for best patient outcomes.
5.3 Creating and Maintaining
a Multidisciplinary Team
5.3.1 Creating a Team
Creating a multidisciplinary team is bringing team
members from different disciplines together with shared
goals and responsibilities to the patient. Team members
must be able to communicate ideas and solutions
openly. All members should share responsibilities, and
accountability to the care of each patient. They must be
willing to respect and collaborate with each team mem-
bers for the best outcomes in patient care. They must
also be committed to the process of team caring.
Core members of the team must all possess basic
knowledge in medical care and services for the derma-
tology patient. The doctor, nurse, pharmacist, lab, social
services professionals must all be able to communicate
their roles on the team and be able to present team deci-
sion for care to the patient and families or caregivers.
Team members must meet on a regular basis during
the patient’s assessment and treatment phases so they
can monitor the patient’s progress or address any issues
or concerns that arise during treatment. Each team
member should be responsible for their particular piece
of treatment and be able to present findings, address
concerns, and add to the general knowledge and expe-
rience of the team.
49
Multidisciplinary Team for Total Patient Care
Primary
Care
Pharmacy
Dermatology
Laboratory
Patient Oncology
Nursing Social
Services
Health
Education
Fig. 5.1  A model of the structure of a team
Team members should share the lead throughout
the treatment process, depending on the need of the
patient during that phase of treatment in which one
member has expertise. An example of this would be for
a designated person to speak with the pharmacist about
medication concerns, or the surgeon, if surgical inter-
vention is part of the treatment process (Fig. 5.1).
According to the multidisciplinary team approach,
the patient will have a continuum of care throughout
diagnoses and treatment:
The full continuum of care includes prevention, patient
and family education, screening, staging and work-up,
initial and subsequent treatment, follow-up, palliative
and hospice care, and psychosocial services.1
With any discipline, it is important that the philosophy of
treating the whole patient is in the forefront of any pro-
cess. With multidisciplinary care, this may insure that
the whole patient will get the continuum of care from all
aspects, including medical, social, and psychological
viewpoints. Including the patient and family in the team
will enhance the understanding and treatment outcomes
as they will be part of the process, able to access educa-
tion and knowledge about their diagnosis and treatment.
5.3.2 Maintaining a Team
When a team is created it is part of a continuing com-
mitment to multidisciplinary care to include a need for
training and maintaining communication. There is a
50
growing consensus for the need of improved commu-
nication and collaboration among healthcare provid-
ers. Clark3 found that obstacles to effective teamwork
were reported to be turf/territoriality, conflict/commu-
nication, team process, and organizational constraints
with the major participant goal stated to be better col-
laboration at work.
5.3.2.1 Training
The development and evaluation of a teamwork model
using a blend of theory and practical experience has
been found to be important to the development of
effective interdisciplinary strategies of patient care.5
A training program for an interdisciplinary team
might include topics focused on leadership, conflict/
communication challenges, and the relationship of
teamwork with quality improvement for best patient
outcomes.
As an example, Clark3 developed a leadership mod-
ule that included a review of the different types of
leadership styles and ways to cultivate leaders. The
participants of the module discussed their observation
of leadership and ways to promote leadership within
healthcare teams. Teams were encouraged to gather
data to evaluate both the effectiveness of the teamwork
education and practice to avert backtracking to disci-
pline- and department-specific methods when faced
with financial and institutional stress. The relationship
of quality improvement and teams was also presented
with participants breaking-out into small groups to dis-
cuss their own experiences.3
5.3.2.2 Communication
Open and clear communication in multidisciplinary
teams may be challenging but it is essential. Poor
communication among a team of medical specialists
and between family members and providers can
adversely affect patient care and quality of life.16
Patients should not have to answer the same questions
over and over again to different providers. A good
20-min meeting with the family, focusing on that fam-
ily and their concerns, can make admission smoother.16
The quality of communication among a medical team
has been linked to patient and family well-being in
acute care settings.2
J. P. Lewallen et al.
5.4 Special Conditions for Various
Patient Groups
Multidisciplinary work with various patient groups
calls on each team to customize their approach.
5.4.1 Pediatric Patients
Pediatric patients will almost always be unable to be
part of the assessment and treatment plan. Parents or
caregivers will usually need to assume the responsibil-
ity as a team member to advocate for their children the
best course of treatment.
A special case is the occurrence of skin conditions
and disorders that may appear to be normal conse-
quences of childhood activity (like bruises and scrapes)
or may be indicators or abuse or neglect. When skin
conditions are present, the dermatologist can assess
and detect signs of abuse and neglect vs. accidental
injury, benign skin symptoms, and other skin disorders
that can mimic abuse. This is particularly important as
PCPs, nursing staff, social workers, therapists, and
other team members may not have the expertise to dif-
ferentiate between skin disorders that can mimic abuse
and abuse.
This makes the inclusion of the parent as a team
member a complex issue. On the one hand, the report of
the dermatologist can remove the suspicion of abuse
and lead to better support for the patient’s parent in the
team context. On the other hand, the team can be inter-
fered with by the presence of a suspected abuser. It is
important to resolve this issue before bringing the poten-
tial problem into the team. The high price to be paid
when not making this determination may be the effec-
tive exclusion of the patient’s advocate from the team.
5.4.2 Gerontological Patients
Many issues similar to those that arise in pediatric
patients also come up in older patients, especially
when the patient is incapacitated by forms of demen-
tia. In the elderly, skin is oftentimes bruised or
scratched, due to thinning skin and use of anticoagu-
lants given to elderly for prevention of heart attack,
stroke, or deep vein thrombosis (DVT). When there is
5  Working with Other Healthcare Providers
a question of differentiation of diagnosis between
abuse, neglect, and the by-product of medication, thin
skin, or accidental injury, a dermatologist should be
part of the diagnosis team. Working with other health-
care professionals can bring accurate assessments and
diagnoses and enable the team to work collaboratively
in treatment options or report findings as mandated by
law for abuse or neglect.
A different series of issues in elderly patients are
those related to the multifocal origin of problems.
There is rarely, if ever, one thing wrong in the elderly.
Instead there is often a constellation of events that
may be involved. Leg ulcers may arise from a poor
circulation, but lack of exercise (as a result of osteoar-
thritis), nutritional problems (from suppressed inges-
tion as a result of depression), and various other
problems may influence disease progress. Attempts to
address one problem can often set off a series of new
ones. For instance, using antibiotics to fight infections
often results in diarrhea. Diarrhea, in patients receiv-
ing diuretics, can easily result in hypokalemia, even in
the presence of prescribed potassium. Older patients
are more “fragile,” i.e., with fewer reserves, so can fall
into problems sooner. Considering the total patient –
the hallmark of multidisciplinary efforts – becomes
necessary unless the patient is to bounce from one
problem to another.
5.4.3 Psychiatric Patients
These patients present with some of the same prob-
lems as children in that there are questions about who
adequately represents the patient’s interest on the mul-
tidisciplinary team as well as the same issues about
abuse that arise in children and the elderly. However,
the special needs of the psychiatric patients have stim-
ulated interest in a new area termed psychodermatol-
ogy. Focused on the boundary between psychiatry and
dermatology, psychodermatology is concerned with
conditions that involve an interaction between the
mind and the skin.11 Management of psychodermato-
logic disorders requires assessment and treatment, not
only of the skin manifestation but of the psychosocial
factors that may be associated with or exacerbate the
condition.
Koo and Lebwohl divide psychodermatologic dis-
orders into three broad areas. The first consists of
51
patients with primary psychiatric disorders. These
patients may present with delusions of parasitosis
where they believe erroneously that they are infested
with some type of organism. Other examples of pri-
mary psychiatric disorders include neurotic or psy-
chologic excoriations, where patients self-inflict
scratch marks with their own fingernails, and facti-
tial dermatitis, where other instruments besides fin-
gernails are used to damage skin.11 Careful psychiatric
diagnosis and treatment is of utmost important in
this type of disorder and the inclusion of a psychia-
trist on the multidisciplinary team is essential.
The second area includes secondary psychiatric dis-
orders. These disorders may accompany skin condi-
tions simply because of their visibility to other people.
Conditions such as cystic acne, alopecia areata, psoria-
sis, hemangiomas, and Kaposi’s sarcoma may be cause
for psychological and social distress.11 As cited in Koo
and Lebwohl,11 Love12 reports that persons with skin
disorders may encounter discrimination and have dif-
ficulty obtaining employment, and Ginsburg and Link6
notes that discrimination occurs particularly when
their skin disorder appears contagious. The multidisci-
plinary team is the perfect place to approach these
problems in a holistic context, combining education,
referral, counseling, and perhaps adding a legal mem-
ber to the team. In addition, patients with emotional
distress may be helped by the team by referral to a
mental health professional or dermatological support
group.11
The third area, and by far the most common of the
psychodermatologic disorders seen in the clinic are
those that can be termed psychophysiologic disor-
ders.11 Although discussed in context of specific disor-
ders below, the common thread of these disorders is
that these skin conditions that may be exacerbated by
emotional stress. Examples include: acne, eczema,
psoriasis, atopic and seborrheic dermatitis, alopecia
areata, and uticaria (hives). When these skin condi-
tions are recalcitrant to dermatologic treatment, psy-
chosocial or occupational stress may be contributing to
the disorder and warrant further investigation.11 The
treatment of chronic dermatoses may be difficult with-
out addressing stress as an exacerbating factor. The
multidisciplinary team should include members to
address these areas. Stress management or relaxation
techniques and exercise may be beneficial, but some
issues may require counseling or therapy, antianxiety
medication, or psychiatric referral.11
52
5.4.4 Other Patients
Other patients that are especially served by multidisci-
plinary efforts include those with language difficulties,
those with problems in accessing medical care, and the
under- and uninsured.
The nonmedical aspects of multidisciplinary teams
may be more crucial than the medical aspects in some
cases.
5.5 Special Conditions: Various
Dermatological Disorders
Just as various special patient populations can influ-
ence the actions and composition of multidisciplinary
groups, so can the need to address specific dermato-
logical problems.
5.5.1 Wound Healing
Chronic wounds that are resistant to treatment add an
additional risk to the patient and negatively influence
their quality of life.7 Lower extremity ulcers related to
venous insufficiency are the most common type of
chronic ulcer in the United States, followed by diabetic
ulcers of the foot, and pressure ulcers on any body
part.13 Pain, infection, sepsis, and amputation are often
associated with these ulcers.
Problem wounds had traditionally been treated by
different medical specialties and healthcare workers,
but over the last 20 years multidisciplinary wound heal-
ing centers have been developed in the United States as
well as other countries.7 A central clinic that uses the
multidisciplinary approach to wound care can provide
better patient care through more focused and efficient
physician–patient encounters, a larger stock of prod-
ucts, and easy collaboration among specialties.13
Mostrow13 described the process of developing a
multidisciplinary wound clinic using the four Ps: peo-
ple, places, products, and protocols. The specialties
and their perspective that Mostrow13 described include:
• Dermatologist: provides medical care of ulcers with
emphasis on skin care, biopsies potential malignan-
cies, vasculitis, and infections.
J. P. Lewallen et al.
• Vascular surgeon: evaluates patients with impaired
circulation for possible intervention.
• Plastic surgeon: provides special expertise in flaps
and grafts, surgical debridements.
• Orthopedic surgeon: often addresses neuropathic
foot ulcers, offloading pressure of ulcer and assess-
ment of vascular supply.
• Podiatrist: provides general foot care with expertise
in nails, debridement, and footwear issues.
• Nurse practitioner: runs clinic and maintains patient
contact throughout week.
• Other nurses: provide patient care and education
especially in relation to dressing and compression.
Gottrup et al7 tested the hypothesis whether “an inde-
pendent, multidisciplinary wound healing center in an
accepted national expert function of wound healing is
the optimal way to improve prophylaxis and treatment
of patients with problem wounds.”
The results of the study, conducted with 23,802
patients with varying types of wounds and 1,014
patients inpatient, showed that the use of multidisci-
plinary teams led to improvement in healing rates and
a reduction in major amputations as well as a decrease
in the number of admits to the wound center.
Specifically for leg ulceration often caused by
chronic venous leg insufficiency (CVI), health behav-
iors such as cigarette smoking and exercise are asso­
ciated with circulation disorders that can influence
the prognosis of CVI.8 Heinen et  al9 worked with a
multidisciplinary project team to develop a health pro-
motion program for patients with venous ulcers that
supported adherence with compression therapy and
positive lifestyle changes. The program coached
patients toward adherence with compression therapy
and pain management as well as leg and foot care, and
targeted lifestyle behaviors of exercise, smoking, nutri-
tion, and weight management (Heinen 2006).9 The
authors advocated development of lifestyle approaches
for other patients as well.
5.5.2 Melanoma
The incidence of melanoma has risen rapidly over the
past several decades. Melanoma represents the fifth most
common type of cancer yet is one of the leading cancers
accounting for average years of life lost per person.
Often, several disciplines are needed simultaneously
5  Working with Other Healthcare Providers
to optimally diagnose and treat patients with melanoma.
Work-up, treatment, and follow-up recommendations
may differ by physicians and healthcare providers in
separate specialty settings, leading to inconsistencies in
patient management and care.10
Specialty of the primary provider and their practice
patterns have been found to influence the treatment
options offered to patients with melanoma, which in
turn may influence patient outcomes.17 Evidence also
suggests that multidisciplinary programs that coordi-
nate providers and centralize care may increase patient
access to comprehensive melanoma care.17
An example of addressing melanoma in a multidis-
ciplinary context is provided by Johnson et  al10 The
model used was devised by the University of Michigan
multidisciplinary melanoma clinic (MDMC). The pro-
cess begins with the patient who has a diagnosis of
melanoma. The patient goes through the process of
care from the multidisciplinary view. The process is
documented as:10
• Intake
• Direct contact via nursing staff
• Clerical for information packets and appointment
• Clinic visit, to include dermatology, surgery, social
work, physical therapy, occupational therapy, etc.
• Case conference with the multidisciplinary team to
assess and review plan of treatment (patient is
assigned to relevant specialties with the team)
• Specialty visits, treatments
• Conference with multidisciplinary team and family
for updates/changes in treatment
• Documentation management
Each patient is to be treated as “family” with each mul-
tidisciplinary member contributing their knowledge
and expertise in a “turf-less” environment, dedicated
to total care for the patient.
Johnson et al10 found that multidisciplinary mela-
noma care centers can optimize care of patients with
melanoma and can be the most efficient plan of
treatment.
5.5.3 Atopic Dermatitis
Atopic dermatitis (AD), or atopic eczema, is a common
chronic, skin disorder noted by dry, itchy skin that is eas-
ily irritated. AD is the most common relapsing
53
skin disorder in infants and children.15 The scratching
and rubbing of the itchy skin which can cause further irri-
tation and inflammation to the skin is known as the “itch-
scratch” cycle. Although stress or other emotions do not
cause AD, emotions may exacerbate the “itch-scratch”
cycle.15
It has long been recognized that treatment of AD
patients has better outcomes with multidisciplinary
care, especially in patients with moderate-to-severe
disease.14 The multidisciplinary team should include
the PCP, nurses, nurse practitioners, physician assis-
tants, patient advocates, social workers, and health
education professionals.14 Patient education is of spe-
cial significance with emphasis on trigger avoidance,
specific skin care recommendations, and follow-up.
It is also important to be clear and explicit about the
use of topical medications because incorrect use of
these medications is one of the primary reasons for
poor treatment outcomes.15 This is a condition where
the team effort becomes a learning experience for the
whole team. This is because the topical medications
used are quickly evolving and what works best is cur-
rently still being worked out.
Coordinated multidisciplinary care, especially using
nurse practitioners, has been successful, and results in
improved care and improved satisfaction for patients,
families, and healthcare providers alike.15
5.6 Case Study
The following case study is instructive about the mul-
tidisciplinary approach in a dermatological case.
5.6.1 Patient History
Mr. P. is an 80-year-old white male coming in with a
red, scaly spot on the right side of his neck. He is seen
by PCP in local hospital clinic setting.
The PCP reports to Mr. P. that the spot appears to be
an irritation and gives Mr. P. a prescription for steroi-
dal cream, to be applied twice daily.
Mr. P. returns 6 months later to report the red, scaly
spot has grown and has become very itchy. The PCP
reports that this is most likely a fungal infection and
prescribes an antifungal ointment, twice daily.
54
Mr. P. sees a new PCP at a local senior health clinic
and reports the spot on his neck is not getting any
better. He also reports the past year’s treatment with
steroid and antifungal with no resolution. By this time,
the spot has increased in size and remains red and
inflamed. The senior health practitioner refers Mr. P. to
a local dermatology clinic where he was diagnosed
with squamous cell carcinoma and had surgical inter-
vention (MONS) to remove the spot.
The follow-up below is a result of this intervention.
Mr. P. was referred to the local university hospital system
by the senior health clinic to review and assess Mr. P.
5.6.2 Continuation of Care
of Patient Mr. P.
Mr. P. was referred to dermatology for suspected CA
after squamous cell carcinoma ED and C (removed with
electrodesiccation and cutterage) from face previously.
Mr. P. is an 80-year-old white male who is a new
patient. with history of squamous cell carcinoma ED
and C from right jawline by local dermatologist, Dr. M.
The patient also has history of actinic keratoses and
would like to establish dermatologic care here. He
denies any pain, burning, numbness, stinging, or pruri-
tus to his recent skin cancer scars. He does have a few
scaly areas to the face that are occasionally tender.
5.6.3 Physical Examination
Mr. P. is a well-developed, well-nourished white male
in no acute distress. He is the primary caregiver for his
80-year-old wife who has multi-infarct dementia.
5.6.3.1 Integumentary
Scalp, face, neck, back, chest, abdomen, and bilateral
upper extremities are examined. He has numerous ill-
defined, scaly, erythematous papules primarily to the
scalp, forehead, and the sides of his face consistent with
actinic keratoses. He has a well-healed scar to the right
jawline which shows no evidence of recurrence. He has a
few ill-defined scaly, erythematous papules to the fore-
arms and hands as well. He has scattered hyperpigmented
J. P. Lewallen et al.
stuck-on papules consistent with seborrheic keratoses.
The remainder of the exam is unremarkable.
5.6.4 Assessment and Plan
1. Actinic keratoses are treated with cryosurgery for
the destruction primarily to the patient’s central
face, on the cheeks and nose as well as arms and
hands. He was given EFUDEX® to apply primar-
ily to his forehead and scalp for the next 3 weeks,
with a specific recommendation to apply it to treat
the helices of his ears. Education was given on the
use of EFUDEX® as well as the side effects of this
medication.
2. History of squamous cell carcinoma to the right
jawline, no evidence of recurrence at this time.
3. Seborrheic keratoses, benign. Will see in clinic in
3 months.
He was seen with Dr. M. (the dermatologist) with the
attending physician Dr. D.
5.6.5 Dermatological Clinical Staff Call
Patient’s daughter phoned stating that her father had
developed a strong reaction to EFUDEX® and would
like us to call patient. Patient states he has used
EFUDEX® for 20 days and his face is very red and
scabs “oozing” with swelling. Patient was given a
Desonide by Dr. E. (an attending on call) and told to
apply it to the red areas. Per Dr. M.’s review of the case,
patient is to continue the Desonide to the red areas and
apply Vaseline® or Aquaphor® to the areas that are
crusty and oozing. Patient verbalized his understand-
ing. He was also referred to senior health clinic.
5.6.6 Senior Health Clinic Note (Next Day)
Patient was seen in Senior Health Clinic as a walk-in
due to his concern about swelling and possible infec-
tion. History of presenting illness: 80-year-old white
male here today for concern about EFUDEX® treatment
and redness and swelling to the face. He had been to
dermatology a month ago and has been using EFUDEX®
5  Working with Other Healthcare Providers
to the face for treatment of actinic keratoses. Today, he
is observed having pus and drainage to the face and
he is concerned about infection. He denies any fever. He
states swelling is better today, but pus and drainage
worse. Denies any other systemic complaints.
5.6.7 Medications
KEFLEX® 500 mg caps (cephalexin) take one tablet 2
times daily
5.6.8 Dermatological Clinic Follow-Up
Mr. P. was followed up with dermatology about 2
months later with face much better and EFUDEX® and
Desonide completed.
5.6.9 Multidisciplinary Assessment
Mr. P. was seen in two separate clinics, with multiple
team members including
• His PCP who gave the first referral
• Dermatology for assessment and treatment of
actinic keratoses and seborrheic keratoses and his-
tory of squamous cell carcinoma
• Pharmacy which addressed medication education
and information on how to use medicine and their
side effects (of obvious importance in this case)
• Laboratory to review skin samples for diagnosis of
squamous cell carcinoma and evaluate and monitor
general health status
• Nursing staff for dermatology to take calls and
review information and give advice as per doctor on
treatment concerns
• Advanced practical nurse for intervention and concern
for infection after treatment with other medications
• Social work for case management and support dur-
ing care (again a special need in this case because
much of the problem appears to have arisen from
treatment)
All of these team members worked in coordination for
Mr. P.’s best outcome.
55
5.7 Conclusion
Although generally useful, it is evident that for special
patients, such as children, the elderly, and psychiatric
patients, their special needs strongly support the use
of multidisciplinary teams in the efficient resolution
of their dermatological disorders. Also for a series of
common dermatological orders, it is clear that stress,
exercise, patient education, and a holistic approach to
the patient is useful to improving the outcome of their
treatment, sometimes dramatically. As the interface
with the outside world, skin has an important role to
play in how an individual feels about him/herself and
how he/she relates to their social context. As such, it is
not that much of a surprise that a comprehensive
approach, bringing together expertise in the many
areas that contribute to these complex outer and inner
images, is more successful in addressing the problems
that dermatological disorders bring than approaches
that simply treat the skin problem like it had no effect
on the life of the patient. Although multidisciplinary
teams can be a complicated and cumbersome process
at times, the nature of dermatological disorders is also
complicated, with their effects on quality of life of
equal or more concern to patients than the strictly med-
ical problem itself.
References
  1. Anon. The American Federation of Clinical Oncologic
Societies access to quality cancer care: consensus statement.
J Clin Oncol. 1998;164:1628–1630
  2. Boyle DK, Miller PA, Forbes-Thompson SA. Communi­
cations and end-of-life care in the intensive care unit: patient,
family, and clinician outcomes. Crit Care Nurs Q. 2005;
28(4):302–316
  3. Clark PG. Evaluating an interdisciplinary team training
institute in geriatrics: implications for teaching teamwork
theory and practice. Educ Gerontol. 2002;28:511–528
  4. Clark PG, Leinhaus MM, Filinson R. Developing and evaluat-
ing an interdisciplinary team training program: lessons taught
and lessons learned. Educ Gerontol. 2002;28:491–510
  5. Clark PG, Puxty J, Ross LG. Evaluating an interdisciplinary
geriatric education and training institute: what can be learned
by studying processes and outcomes? Educ Gerontol.
1997;23(7):725–744
  6. Ginsburg IH, Link BG. Psychosocial consequences of rejec-
tion and stigma feelings in psoriasis patients. Int J Dermatol.
1993;32:587–591
56
  7. Gottrup F, Holstein P, Jorgensen B, Lohmann M, Karlsmar
T. A new concept of a multidisciplinary wound healing cen-
ter and a national expert function of wound healing. Arch
Surg. 2001;136:765–772
  8. Heinen MM, van Achterberg T, op Reimer WS, et al Venous
leg ulcer patients: a review of the literature on lifestyle
and pain-related interventions. J Clin Nurs. 2004;13(3):
355–366
  9. Heinen MM, Bartholomew LK, Wensing M, Kerkhof P,
Achterberg T. Supporting adherence and healthy lifestyles in
leg ulcer patients: Systematic development of the lively legs
program for dermatology outpatient clinics. Patient Education
and Counseling. 2006;61:279–291
10. Johnson TM, Chang A, Redman B, et  al Management of
melanoma with a multidisciplinary melanoma clinic model.
J Am Acad Dermatol. 2000;42:820–826
11. Koo J, Lebwohl A. Psychodermatology: the mind and skin
connection. Am Fam Physician. 2001;64:1873
J. P. Lewallen et al.
12. Love B, Byrne C, Roberts J, Browne G, Brown B. Adult
­psychosocial adjustment following childhood injury: the effect
of disfigurement. J Burn Care Rehabil. 1987;8:280–285
13. Mostrow EN. Wound healing: a multidisciplinary approach
for dermatologists. Dermatol Clin. 2003;21:371–387
14. Nichol NH, Boguniewicz M. Successful strategies in atopic
dermatitis management. Dermatol Nurs. 2008;suppl:3–19
15. Nicol NH. Multidisciplinary teams are critical in the care of
atopic dermatitis patients. Medscape Dermatol. 2005;6(2)
@2005 Medscape 12/20/2005
16. Penson RT, Kyriakou H, Zuckerman D, Chabner BA, Lynch
TJ Jr. Teams: communication in multidisciplinary care.
Oncologist. 2006;11:520–526
17. Stitzenberg KB, Thomas NE, Ollila DW. Influence of pro-
vider and practice characteristics on melanoma care. Am
J Surg. 2007;193:206–212
18. Tanaka M. Multidisciplinary team approach for elderly
patients. Geriatr Gerontol Int. 2003;3:69–72
 The Future of Dermatological
Therapy and Preventive Dermatology
Robert A. Norman
I generally start off any of my writing in response to
questions I ask myself. And I asked myself many ques-
tions when I pondered the future of the skin and preven-
tion of skin disease. Upon reflecting on the needs of my
patients and others, dozens of possibilities arose from
the myriad images, smells, touch, and sounds that have
filled my head from patient interactions over the years.
Although I began my inquiry with the more utilitar-
ian potential of future skin developments, I also real-
ized, given the enormous influence of esthetics among
Homo sapiens, that the future progression will also
include the “skin as entertainment” arena.
What about the skin as a vehicle for delivery of other
drugs besides creams and ointments? How about provid-
ing a built-in protection for those with a heightened need
for sun protection, such as those unfortunate souls with
the dramatic disease xeroderma pigmentosa? Or even a
safeguard for the mild, fair-haired, red-eyed lass?
What if one could change skin colors based on
mood? I knew of many patients with frustrating blush
disorders that had wished their state of mind was not
so readily visible on their hot red skin. However, oth-
ers may want a change in color, such as a military per-
son who is trying to hide from an approaching enemy.
And of course there will be those who suffer a certain
ennui from their current display of tattoos, and an ever-
changing tableaux would offer an extensive realm of
show and tell.
What will the future of dermatology be like? What
will be the new detection options? What will be the new
treatment options? What will be the new educational
R. A. Norman
Nova Southeastern University, Ft. Lauderdale,
Florida and Private Practice, Tampa, FL, USA
e-mail: skindrrob@aol.com
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_6, © Springer-Verlag London Limited 2010
6
and patient teaching options? How will ethics and
patient selection be challenged? How will integrative
therapies and cosmetic surgeries evolve?
Skin diseases can be expensive and time-consuming
and affect self-esteem, personal relationships, and careers.
They also have health implications – predisposing indi-
viduals to infection, scarring, and other diseases.
As immunosuppressive and laser research are still
in their infancies, the future of these fields appears
boundless with new therapies constantly in develop-
ment. Obviously, the continuous appearance of new
treatments necessitates the regular update and revision
of a physician’s standard practice methods.
Dermatological concerns are among the most com-
mon consults physicians and pharmacists get if you con-
sider hair, skin, and nails. Therapy in dermatology,
particularly in the treatment of psoriasis and eczema, is
changing significantly as new approaches to therapy
reach the market and already-marketed products find
new uses. As a result of the increased understanding of
the molecular mechanisms of skin diseases, dozens of
drugs are in phase II or III trials. The “survivors” in this
arduous contest will reach the market in the near future.
6.1 The Genetic Century
What will be other new treatment options for diseases
such as xeroderma pigmentosum? The disease, charac-
terized by defective DNA repair, with young bearers of
this autosomal recessive condition having severe solar
damage and skin cancers, pigmented dry skin, and eye
abnormalities, have fought an uphill battle for many
years. Incorporating bacterial repair enzyme T4 endo-
nuclease V (T4N5) into a liposomal delivery vehicle
and applying it to the skin results in markedly decreased
57
58
skin damage. With the virtual completion of the Human
Genome Project mapping of 30,000 genes, genomic
maps will be available to guide the efforts to determine
the genetic basis of disease. We will be able to deter-
mine response to treatment and chart a person’s prog-
nosis with greater efficiency. The twenty-first century
will be the “genetic century” as we discover how the
mutations bring on skin disease and the multiple mech-
anisms surrounding their expression.
With specific diseases such as melanoma, hope is on
the horizon to replace traditional chemotherapy. Pills
such as BAY 43-9006 (Sorafenib), which should reach
the market within 3 years, are a new generation of “tar-
geted” therapies that are transforming the treatment of
horrible diseases such as melanoma. The pill attacks the
underlying molecular mechanism and will allow can-
cers to be treated as a chronic disease such as high blood
pressure, diabetes, or depression. Specifically, the new
cancer drug attacks malignant tumors by blocking a
chain reaction inside the cancer cells that allows them to
multiply and attract blood vessels for growth.
6.2 New Skin
The skin is a marvel. In the best circumstances, it heals
itself if broken down, repairing and restoring its for-
mer integrity. It is dour in sorrow, radiates warmth in
love, and shines in tranquillity. The skin is an organ in
and of itself, with its own personality, temperament,
and particular eccentricities.
Its crucial body-covering role is becoming increas-
ingly recognized, as well as the time it can use an out-
side boost. With almost every trauma, it rebounds, but
in burn victims who have lost more than 40% of their
skin surface, a temporary cover by a meshwork of
donor human skin or grafts is needed. In the future,
more lasting and durable skin substitutes will be
needed. Likely candidates will include artificial matri-
ces to grow skin from stem cells taken from the fore-
skin or umbilical cord of newborn infants. Others will
use epidermal cells on an artificial dermis.
Other options are appearing, such as a three-dimen-
sional matrix composed of a combination of human
skin cells and biodegradable polymers. The bilayered
matrix acts as both a foundation and environment on
which the dermal cells grow and shape. The porous
underlayer allows the ingrowth of human dermal cells
R. A. Norman
and the outer layer, entirely synthetic, is designed as a
barrier against infection, water loss, and ultraviolet
light. The human dermal cells taken from neonatal
foreskin are seeded and adhere onto the polymer matrix
and allowed to incubate for several weeks. The cells
multiply and organize themselves into functioning tis-
sue and can be applied to replace damaged skin.
Chemically bonding collagen taken from animal
tendons with glycosaminoglycan (GAG) molecules
from animal cartilage to create a simple model of the
extracellular matrix also may provide a new dermis.
6.3 Teaching, Detection, Therapy,
and the Modern Era
What will be the new educational options in dermatol-
ogy? I discussed this with Ben Barankin, MD. He
stated:
We will have virtual learning on the Internet with person-
alized medical histories and genetic tracking. As more
physicians become computer and Internet savvy, and as
the resources on the Internet improve, a physician will be
able to sit down with the patient and their laptop to show
other people with the same condition on dermatology
atlas websites, as well as to recommend patient support
groups, and other good resources of information. Also,
physicians will be able to take pictures of the patient, and
to show them what their potential scar will look like fol-
lowing the procedure, for those concerned with their scar
appearance. The new computer systems will integrate
digital photography, touch screens, voice recognition,
downloads to pharmacies and HMO’s to streamline the
patient interactions.There will certainly be therapeutic
options for those with genetic diseases. This will include
most probably oral forms of medication that dermatolo-
gists and medical geneticists will collaborate on in terms
of development and provision to patients. There will be
further developments in the treatment of skin cancers
using creams, and children will be vaccinated against a
multitude of wart virus strains so as to prevent their devel-
opment. As far as detection, there will be computers and
robots that will do full-body scans on a semi-annual basis
and be able to compare changes in moles or other concern-
ing external and internal developments. Physicians will be
there to verify these findings, biopsy as necessary, and initi-
ate treatment.
New devices to detect skin cancer and other skin mala-
dies include image analysis and computer-assisted
diagnosis, multispectral imaging and automated diag-
nosis, confocal laser microscopy, optical coherence
tomography, ultrasound, magnetic resonance imaging,
6  The Future of Dermatological Therapy and Preventive Dermatology   59
spectrophotometric intracutaneous analysis, and artifi-
cial neural networks. Continuous research and refine-
ment will allow improvements in detection and
treatment.
Teledermatology (computer-assisted, long-distance
transmission of dermatological cases) will allow detec-
tion and therapeutic suggestions to areas where hands-
on dermatology is limited. Dr. Joe Kvedar of Harvard
Medical School writes, “characterized as time-and
place-independent care delivery, the exploding global
computing network infrastructure (Internet) offers the
opportunity for delivery of care anytime, anywhere.
This care delivery method will enable dermatologists
to offer services in a place-independent fashion and
may interrupt current referral networks.”1
Tania J. Phillips, MD, Professor of Dermatology at
the Boston University School of Medicine, stated:
I think teledermatology will play an increasing role, phy-
sician extenders will be increasingly used, and instru-
ments such as the dermatoscope and other in vivo imaging
techniques will be used. Treatments such as the immune
response modifier molecules and biologics will be
increasingly used for different indications. Hopefully for
wound patients there will be new, affordable cell based
therapies available. For education and teaching I think
that the internet and computer based learning will sup-
plant many of our traditional methods, as they are already
doing!
What else is coming up over the horizon?
Long-lasting fillers that will more permanently
repair defects and make changes are being studied.
The future of these skin enhancers should include a
plethora of exciting new products and techniques.
Face transplants have been done; a radical proce-
dure intended for patients with severe disfigurement.
Although doctors in the past have successfully reat-
tached faces to patients after accidents, transferring
facial tissue and blood vessels from a cadaver to a new
patient may become more common. Although the
transplant also brings a lifetime dependence on expen-
sive immunosuppressant drugs to block rejection of
the new tissue, the operation could offer an improved
future for those who suffer severe burns, cancer, or
gunshot wounds. Of course, the procedure raises major
moral, ethical, and psychological issues.2
At the Georgia institute of technology, researchers
have developed micro-thin implantable films that
release medication according to changes in tempera-
ture. The device will allow patients to forgo daily
injections and pills including insulin, hormone therapy,
chemotherapy, biologics for psoriasis and other der-
matological diseases, and other treatments.3
Hair growth and transplantation will be safer and
the individual, artificial-appearing hair plugs will be a
historical reference. New and more individualized hair
growth drugs will become available. Cloning of indi-
vidual hair cells will allow an unlimited source of
replacement hair.
Mike Morgan, MD, provided his reflections on the
“brave new world of dermatology” and changes to be
expected in diagnosis:
In the near term of the next 20 years the dermatopatholo-
gist will continue to assume the primary responsibility of
diagnosis although there will be changes in who reports
the diagnosis and how it is accomplished. Increasing fis-
cal pressures exerted by third party payers and Medicare
debt will force the application of technologies such as
telepathology, that were initially intended for improving
medical care access, to be subverted under the pretext of
cheaper medical care. Familiarity with this concept by
managed-care executives and its passive approval by der-
matologists will eventuate in diagnosis performed by
anonymous pathologists in offshore locations as has been
recently witnessed in the radiologic field. Domestically,
these technologies and the applied mantra of “economies
of scale” could serve as a rationalization for ­centralization
and a monopoly of diagnostic services by ­well-connected
individuals or singular corporate entities. Ongoing scien-
tific discoveries and the application of nascent technolo-
gies will however eventually lead to wholesale changes
in the diagnosis and management of cutaneous disorders.
The dermatologist of the late twenty-first century will
assume a greater degree of responsibility for diagnosis.
Armed with hand-held spectrophotometric and chemical
detection devices the vast majority of cutaneous neo-
plasms will not only be accurately identified but risk
assessed in situ. Characteristic light diffraction spectra
will differentially fingerprint the types of cutaneous
malignancy and the application of light or sound emitting
devices will precisely gauge the depth of tumor penetra-
tion. Chemical detecting devices programmed to recog-
nize subtle changes in the metabolic by-products of
cancerous cells will complement the light-emitting
devices. Similarly, these devices will be relied upon to
assess the extent of residual disease. Computerized algo-
rithms that reconcile the measured variables of epidermal
thickness, vascular density and depth of inflammatory
infiltrate with preprogrammed archetypes will also per-
mit the assessment and identification of many derma-
toses. Such advances will undoubtedly change the role of
and importance of dermatopathology in the equation of
dermatologic care. As they would be relegated to the
arbitration of equivocal cases or sought in the assessment
of confounding data or following incomplete response to
therapy.
From an ethical standpoint, Internet-based “virtual
details” on new products will become more common.
60
Hopefully, less bias in prescribing based on personal
influence from pharmaceutical companies and more
objective, evidence-based data and research findings
will result. Virtual details will help us to make our own
decisions and not be influenced as much by the “drug
reps” that wish us to sway our prescription-writing
choices toward their products.4
The future of integrative therapies in dermatology, in
particular preventive medicine, botanicals including
antioxidants, hypnosis, and behavioral modification will
allow new detection and treatment options. Based on
research in integrative medicine, new educational and
patient teaching options will be utilized in dermatology.
Future scientific discoveries may demonstrate
humoral connections for many dermatologic diseases
that we have long suspected to be autoimmune. Through
a mixture of good clinical observation and dumb luck,
we will make more connections. However, we must still
discover whether these are an epiphenomena or actu-
ally a factor in disease formation. We may soon look at
the age of dermatological surgery for skin cancers with
a healthy nostalgia when immune therapies and ­vaccines
replace the need for these difficult, ­time-consuming
surgeries.
What about the future detective? We may have skin
detective agencies utilizing bacteriological forensic tech-
niques, pointing to individuals at the scene of a crime.
Perhaps the characteristic microflora of a criminal sus-
pect could be just as important to the detective as a fin-
gerprint or other genetic markers. If an individual’s
microflora, established shortly after birth, remains com-
paratively constant throughout life, a microbial sampling
of room dust, saliva, and so on, might reveal groups of
identifiable organisms which would match the pattern of
a suspect. The particular manner of acquisition of the
many different phage-types of bacteria from mother,
hospital, and early contacts could differentiate two sus-
pects who would support different organisms. By
R. A. Norman
sophisticated phage-typing methods, bacteria could be
called to give evidence in court. The creation of a bio-
chip that can be implanted into the skin of people to
transmit their personal and medical information will be
fodder for legal and scientific inquiry.
Perhaps the old adage about “what you don’t see
can’t hurt you” applies. The huge majority or those crit-
ters that live on the skin are invisible and earn our indif-
ference. And when it does bother us, at least we have
treatments. As far as I know, we are the only species to
have dermatologists, and nail salons, and beauty par-
lors, and a myriad of other sources to rid our body of
real or perceived ailments. I am forever humbled, for
along with my fellow soldiers who fight these ever-last-
ing skin diseases, I know we can never win the battle.
However, when I think about the thousands of patients I
treat with skin problems every year, I hope to provide
solace from the onslaught of our own invaders. I’m glad
I can provide a little help along the way and I’m looking
forward to the future and what more we can offer.
Thanks to Mike Morgan, MD; Lisa Hutchinson,
PharmD, MPH; Ben Barankin, MD; David Elpern, MD;
and Tania Phillips, MD in the preparation of this
chapter.
References
  1. Watson AJ, Bergman H, Kvedar JC. Teledermatology. eMedi-
cine from WebMD. Updated 27 Feb 2007. <http://www.
emedicine.com/derm/topic527.htm>; 2009 Accessed 8.03.09
  2. BBC News. “Woman has first face transplant.” Available
at: <http://news.bbc.co.uk/1/hi/health/4484728.stm>; 2009
Accessed 8.03.09
  3. Heat-controlled Drug Implants Offer Hope for Future.
Available at: <http://www.sciencedaily.com/releases/2004/09/
040914092120.htm>; 2009 Accessed 8.03.09
  4. Norman R. The Woman Who Lost Her Skin and Other
Dermatological Tales. New York: Routledge; 2004
 Part
II
Common Problems and Treatment
in Dermatological Prevention
 Prevention of Drug Reactions
and Allergies in Dermatology 7
Lisa C. Hutchison and Oumitana Kajkenova

7.1 Introduction because the patient has an increased risk because of

specific time-limited factors. Later use of the same
medication may not cause a reaction if the risk factors
Adverse drug reactions are defined as noxious or unin-
have resolved.
tended responses to a drug used in standard doses for
A focus on prevention of adverse drug reactions has
the purpose of prophylaxis, diagnosis, or treatment.8
recently gained national prominence. Because treating
Many side effects to a medication are recognized and
adverse drug events (which include adverse drug reac-
accepted as part of the risk/benefit evaluation in deter-
tions) has been estimated to cost $77 billion in the
mining whether or not it is indicated in a particular
ambulatory patient population of the United States, pre-
patient. For example, diarrhea is a recognized adverse
vention of cutaneous drug reactions is not only a pre-
drug reaction associated with the use of erythromycin
ferred patient outcome, it is also a preferred economic
in 7% of patients.33 However, it is not an intended
outcome.19 It is imperative for the clinician to be aware
response when the drug is used to cure an infection,
of the common cutaneous drug reactions, medications
yet we recognize it as a frequent consequence of oral
most frequently associated with these reactions and
erythromycin use and are willing to accept this risk in
methods to diminish their occurrence and/or severity.
order to achieve the benefit.
Cutaneous drug reactions are one of the most recog-
nized and common types of adverse drug reactions.35
When asked whether they have allergies or adverse 7.1.1 Frequency of Cutaneous
drug reactions, most patients initially report on medi- Drug Reactions
cations which caused them to have a skin rash with
past use. Because most skin rashes develop within 1
To identify if one has been successful in reducing the
week of starting a new medication, this association is
frequency of adverse cutaneous drug reactions, one
reasonable. However, many medications may cause
must first know how often they occur. Several prospec-
cutaneous reactions after several weeks of therapy and
tive studies have focused upon hospitalized patients
require additional detective work to assess the likeli-
and found allergic drug-induced cutaneous reactions to
hood of association with a medication. Also, medica-
occur in up to 6% of hospitalized patients. A wide vari-
tions cause skin changes that are not immunologic in
ability is seen due to differences in study design, par-
their mechanism and develop over an extended period
ticularly when studies rely upon spontaneous reporting,
of time. Finally, some cutaneous drug reactions may
chart review, or patient recall for information. Table 7.1
occur in the patient in particular circumstances only
provides information from epidemiologic studies on
cutaneous drug reactions.
The frequency of cutaneous drug reactions is also
L. C. Hutchison (*) related to the relative usage of specific medications
Department of Pharmacy Practice, College of Pharmacy,
University of Arkansas for Medical Sciences, Little Rock,
that are more likely to cause allergic or other types of
AR, USA skin reactions. In particular, the use of antibiotics in
e-mail: hutchisonlisac@uams.edu the penicillin family is associated with a higher rate of

R. A. Norman (ed.), Preventive Dermatology, 63

DOI: 10.1007/978-1-84996-021-2_7, © Springer-Verlag London Limited 2010
64
Table 7.1  Epidemiologic studies of cutaneous drug reactions
Study Rate (%) Comment
Bigby7 2.2 Seven-year prospective
study in Boston
Hunziker et al18 2.7 Twenty-year prospective
study in Switzerland
Naldi et al24 0.01 Spontaneous reporting over
2 years in Italy
Van der Linden 0.36 Retrospective evaluation of
et al36 medical records over 18
months in The
Netherlands
Rademaker 6 Prospective 6 month survey
et al26 in the hospital setting in
New Zealand
cutaneous drug reactions. One study compared the rate
of drugs received by at least 1,000 patients reported in
nine studies and reported amoxicillin and ampicillin to
cause cutaneous drug reactions at a rate of 1.2–8%.
Sulfonamides, including co-trimoxazole had a rate
of 2.5–3.7% and the rate for cefaclor was 4.8%.5
Amiodarone will cause a slate blue skin discoloration
in 4–9% of patients treated with the drug.39
Risk factors have been identified for some allergic
cutaneous drug reactions. Infection with human immu-
nodeficiency virus or infectious mononucleosis increases
the risk for cutaneous drug reactions. Therefore, an indi-
vidual who received amoxicillin while infected with
mononucleosis may develop a rash; but given the same
antibiotic years later, this individual has no reaction.
Female sex and either very young age or very old age
are inconsistently reported as risk factors.
7.1.2 Serious and Life-Threatening
Cutaneous Drug Reactions
Considering that cutaneous drug reactions are the most
common type of adverse drug reaction, it is fortunate
that they cause serious or life-threatening reactions at
a much lower rate. Depending upon the definition of
“serious,” most reviews place the incidence of serious
cutaneous drug reactions in the range of 1/1,000–
1/100,000 patients treated whether studied in adults or
children.20, 32 Cutaneous skin reactions considered seri-
ous are those which cause skin damage or affect mul-
tiple organs. In a 6-month prospective study of
L. C. Hutchison and O. Kajkenova
hospitalized patients with cutaneous drug reactions,
34% were considered serious because they prompted
hospitalization, prolonged hospitalization, or were
life-threatening. Only 2% were considered life-threat-
ening, but no deaths were reported.13
7.1.3 Preventability of Cutaneous
Drug Reactions
For adverse drug reactions in general, studies indicate
that 28–57% of those that occur in hospitalized patients
are preventable or avoidable.4,9 However, the prevent-
ability rate for cutaneous drug reactions is likely much
lower. Many occur upon first exposure to a medication
or provide no warning when they occur with a subse-
quent exposure. Only one study reports assessment of
preventability based upon consensus between a derma-
tologist and a pharmacologist upon retrospective
review of the patient records. In this study they deter-
mined that 15% of serious cutaneous drug reactions
were preventable but did not elucidate beyond provid-
ing this rate.13 This study was limited to allergic cuta-
neous drug reactions. When one considers the full
spectrum of cutaneous drug reactions that includes
pharmacologic reactions and cumulative reactions,
preventability rates are probably much higher.
7.2 Classification of Adverse
Cutaneous Drug Reactions
Adverse drug events, including cutaneous drug reac-
tions, are classified into one of four types.2 Type A
reactions are those that can be anticipated from the
pharmacologic properties of the medication. These are
expected exaggerations of known pharmacologic
effects, may occur at normal doses, and display a dose-
dependency. They are nonimmunologic in nature. Few
cutaneous drug reactions fall into this category. Type B
reactions are usually unexpected reactions, most of
which are immune-mediated. Many cutaneous drug
reactions fall into this category including urticaria,
petechiae, morbilliform reactions, Stevens–Johnson
syndrome, and toxic epidermal necrolysis. Type C
reactions are associated with cumulative doses of med-
ications over extended periods of time. These are rare
7  Prevention of Drug Reactions and Allergies in Dermatology
for cutaneous drug reactions but include skin discolor-
ations from extended doses of carotenoids or amio-
darone. Finally, Type D reactions are delayed effects
such as teratogenesis or carcinogenesis and are also
rare for cutaneous drug reactions.
7.2.1 Gell-Coombs Classification
of Hypersensitivity Reactions
Because the majority of cutaneous drug reactions fall
into Type B reactions, it is helpful to further subdivide
this category. The Gell-Coombs classification divides
immunologically mediated reactions according to
pathogenesis.25, 27 This is helpful for investigating the
cause of a cutaneous drug reaction or for researchers to
find common links. However, one must realize that the
Gell-Coombs classification tries to pigeon-hole reac-
tions which may have several mechanisms underlying
their development. Nevertheless, the Gell-Coombs
classification system remains widely accepted.
Type 1 reactions are immediate reactions that are
mediated through IgE immunoglobulins. IgE binds to
mast cells causing them to release histamine and other
inflammatory mediators. Urticaria, angioedema, pruri-
tis, and anaphylaxis are examples of this type of immune
reaction. These reactions occur within minutes to hours
after exposure to a medication. Gell-Coombs Type 2
reactions result from the drug combining with cytotoxic
antibodies to cause cell lysis. Examples include drug-
induced pemphigus and petechia resulting from drug-
induced thrombocytopenic purpura.
Gell-Coombs Type 3 reactions are medicated by IgG
or IgM immunoglobulins which form immune com-
plexes. These immune complexes are deposited in the
basement membrane of small blood vessels and activate
complement causing vasculitis or serum sickness. Finally,
Gell-Coombs Type 4 reactions are cell-mediated immune
reactions causing morbilliform exanthematous rashes,
fixed drug eruptions, lichenoid eruptions, Stevens–
Johnson syndrome, and toxic epidermal necrolysis.
7.2.2 Clinical Classification
Cutaneous drug reactions may or may not be immuno-
logic in origin and even if they are immunologic in
65
origin, the immunologic classifications do not always
clearly follow the clinical picture. For these reasons, a
separate classification system based upon the clinical
presentation is useful in the discussion of prevention
and management.28
7.2.2.1 Exanthematous Reactions
Exanthematous reactions are the most common type of
cutaneous drug reaction and can be morbilliform or
maculopapular. Eruptions usually start on the trunk,
spread peripherally, and may be pruritic. With the first
exposure to the culprit drug, the patient will produce
the reaction in 7–14 days, but with rechallenge the rash
occurs more rapidly. Any medication may cause this
type of cutaneous drug reaction, but it is most closely
associated with the penicillins, sulfonamides, antiepi-
leptic drugs, and nonnucleoside transcriptase inhibi-
tors. Patients with infectious mononucleosis or human
immunodeficiency virus have an increased risk of
developing exanthematous reactions when treated with
a penicillin or sulfonamide.
7.2.2.2 Urticaria and Angioedema
Urticaria is the second most frequent cutaneous drug
reaction.34 Pruritic red wheals of various sizes develop
within minutes to hours after exposure to the medica-
tion, and occur rapidly upon rechallenge, although inten-
tional rechallenges are rarely attempted. Angioedema
may affect only limited parts of the face or neck and is
nonpruritic. It may last from 2 h to 5 days. Penicillins
and cephalosporins are most commonly associated with
urticarial reactions but also consider nonsteroidal anti-
inflammatory drugs, phenytoin and carbamazepine as
culprits. Angioedema is seen with angiotensin convert-
ing enzyme inhibitors.
7.2.2.3 Fixed Drug Eruptions
Fixed drug eruptions are well-delineated lesions dusky
red to violet in color that may appear anywhere on the
body, primarily the torso, limbs, lips or genitalia. One
peculiar feature of fixed drug eruptions is that they will
recur in exactly the same location on the body when a
patient is rechallenged with the same medication.
66
Fixed drug eruptions may be confused with macular–
papular eruptions, so their reported frequency is likely
underestimated. Many drugs can cause fixed drug
eruptions including sulfonamides, ciprofloxacin, non-
steroidal anti-inflammatory drugs, phenytoin and
pseudoephedrine.
7.2.2.4 Drug-Induced Erythema Multiforme,
Stevens–Johnson Syndrome,
and Toxic Epidermal Necrolysis
Erythema multiforme, Stevens–Johnson syndrome, and
toxic epidermal necrolysis are considered severe and
life-threatening drug reactions.20 As such, they require
early recognition and discontinuation of all possible
offending agents without delay to avoid serious out-
comes. Systemic symptoms such as fever, lymph-
adenopathy, eosinophilia, sore throat, and cough may
accompany the skin lesions. Some believe these entities
to fit into a continuum with erythema multiforme being
self-limited and benign with lesions occurring symmet-
rically on the extremities and sometimes on the oral
mucosa; Stevens-Johnson syndrome always involves at
least two mucosal lesions but also includes lesions on
multiple organs (eyes, mouth, genitalia, and skin).
Detachment of skin occurs over less than 10% of the
body surface area in Stevens-Johnson syndrome as com-
pared to toxic epidermal necrolysis, where over 30% of
the body surface area may slough off. Patients with toxic
epidermal necrolysis must be treated similarly to burn
victims with so much skin surface affected.
Causative agents most often identified are phenytoin,
carbamazepine, sulfonamides, barbiturates, allopurinol,
minocycline, aminopenicillins, and nonsteroidal anti-
inflammatory agents.20 The importance of discontinu-
ing all potentially responsible medications cannot be
overemphasized. Mortality in one study was 11% for
patients who had prompt discontinuation of causative
agents compared to 27% when drug withdrawal
occurred later.15
7.2.3 Associated Nondermatologic
Symptoms
Cutaneous reactions must include assessment of associ-
ated systemic symptoms along with any skin eruptions.
L. C. Hutchison and O. Kajkenova
When systemic symptoms occur, the cutaneous drug
reaction is considered to be more serious than when
symptoms are limited to the skin and skin structure.
Systemic symptoms may be minor or major. Minor
symptoms include fever, malaise, and arthralgias. Major
symptoms include pharyngitis and lymphadenopathy.
Laboratory evidence of a major reaction may be seen
such as lymphocytosis, eosinophilia, elevated liver func-
tion tests, proteinuria, and renal impairment.20
7.3 General Prevention Principles
Luckily most cutaneous drug reactions are self-limit-
ing once the offending agent is discontinued. However,
the most basic prevention principle is to avoid using a
medication if it is not indicated. Elderly patients in
particular seem to be at risk for overprescribing of
medication and with each additional drug, the risk of
an adverse drug event rises, including the risk for cuta-
neous drug reactions.2
Specific medications have associated recommenda-
tions for prevention of cutaneous reactions when the
drug is required for therapeutic benefit. These recom-
mendations involve the choice of agent, choice of
patient dose, duration of therapy, administration tech-
niques, and monitoring requirements.
7.4 Specific Medications Associated
with Cutaneous Reactions
The following discussion provides examples of each
type of adverse drug reaction. Type A or pharmaco-
logic adverse reactions are seen with corticosteroids.
These are dose-related reactions and can be predicted
with long-term use of high dose and high potency cor-
ticosteroids. Type B or immunologic adverse cutane-
ous reactions are seen with anticonvulsants and with
tumor necrosis factor alpha inhibitors. However, as our
understanding of the mechanisms of reactions increase,
our ability to predict who is at greater risk for these
reactions to anticonvulsant agents has also grown.
Type C or cumulative toxicity is seen with amiodarone
skin discoloration. Finally, Type D or delayed effect
toxicity is a theoretical risk with topical calcineurin
7  Prevention of Drug Reactions and Allergies in Dermatology
inhibitors which are currently under scrutiny to deter-
mine what risk of carcinogenesis they may carry.
7.4.1 Corticosteroids
Both systemic and topical corticosteroids are linked
with cutaneous adverse reactions. Long-term use of oral
corticosteroids has been implicated in development of
localized or disseminated infection caused by gram-
positive bacteria of the genus Nocardia. Cutaneous
involvement can manifest as ulceration, cellulitis or
subcutaneous abscess.3 Lipodystrophy was the most
frequent adverse event reported during the 3-months
use of high dose of prednisone. It has also been consid-
ered the most distressing by the patients and was most
frequent in women and younger patients. Other skin
disorders including hirsutism, spontaneous bruising,
and altered wound healing were noted by 46% of
patients and were more frequent among women.12
Topical corticosteroids cause a multitude of cutane-
ous adverse effects which were first noted after intro-
duction of higher-potency topical steroids like
fludrocortisone.16 Topical steroids have been classified
into very potent, potent, moderately potent, and mild
categories. The most common skin change is atrophy.
Atrophic skin is described as increased in transpar-
ency with increased bruising, tearing, and fragility; the
term “cigarette paper consistency” has been used.
Telangectasias, striae, and ulcerations may also occur.31
Topical corticosteroids suppress cell proliferation,
reduce collagen synthesis, reduce the thickness of the
epidermis and stratum corneum, decrease keratinocyte
size, and reduce the number of fibroblasts. Figure 7.1
depicts marked thinning of the skin due to steroid-
induced atrophy.
Topical steroids have also been associated with
causing acne, rosacea, altered pigmentation, and pho-
tosensitization. These reactions occur more commonly
with higher potency steroids. Contact sensitization
has been reported with a prevalence of 0.2–6%; how-
ever, it is more often associated with lower potency
nonfluorinated corticosteroids such as hydrocortisone
and budesonide.16
Cutaneous adverse effects, particularly skin atro-
phy, from topical corticosteroids can be prevented by
following several measures.6 First, use the least-potent
corticosteroid possible for the least amount of time to
67
Fig. 7.1  Steroid-induced skin atrophy. Photo courtesy of Charles
Goldberg
obtain therapeutic benefit. If very high potency topical
corticosteroids are necessary, consider application
only once daily or alternate treatment with nonsteroid
therapies. Avoidance of occlusive dressings over the
topical corticosteroid will reduce absorption. Use of
creams instead of ointments over face, groin, axillae,
genital, and perineal areas is recommended because
absorption is higher over these sensitive areas. In addi-
tion, increased absorption is anticipated over ulcerated
or atrophic skin.
7.4.2 Topical Calcineurin Inhibitors
Pimecrolimus cream and tacrolimus ointment have
provided a welcome addition to the pharmacological
armamentarium against atopic dermatitis. These agents
reduce the proliferation of T cells and resultant levels
of inflammatory cytokines. The United States Food
and Drug Administration has required manufacturers
to add a black-box warning and medication guide for
patients which communicate that the long-term safety
of these agents has not been established and malig-
nancy is a creditable risk with their long-term use.36
Development of T-cell lymphoma is the primary con-
cern. However, adverse event surveillance in clinical
trials and postmarketing has not found a higher rate of
malignancies in users of pimecrolimus or tacrolimus.
Pharmacokinetic studies indicate that topical applica-
tion of calcineurin inhibitors results in negligible
amounts of systemic absorption. This holds true for
68
children with large percentage of body surface area
treated with the medications.23 It is unlikely that topi-
cal calcineurin inhibitors will found to increase the
risk for lymphoma, although continued surveillance is
warranted.
7.4.3 Anticonvulsants
For many years the anticonvulsants have been tagged
with a high frequency of cutaneous reactions, ranging
from simple rashes to toxic epidermal necrolysis. Over
the decades our understanding of the mechanism by
which these reactions occur has grown. Better under-
standing of the mechanism of cutaneous reactions has
led to recommendations for therapy which help to pre-
vent these reactions from occurring. The rash which
occurs secondary to anticonvulsant medications is tied
to a generalized hypersensitivity reaction that includes
fever, lymph node enlargement, and often hepatitis
along with mucosal blisters and erythematous skin
eruptions.21 Some investigators have called this syn-
drome DRESS (drug reactions with eosinophilia and
systemic signs).14 Anticonvulsants are particularly asso-
ciated with this reaction as it is attributed to an arene
oxide metabolite from the aromatic structure of many
anticonvulsants. In particular phenobarbital, phenytoin,
carbamazepine, and lamotrigine are frequently identi-
fied as causative agents.21,29
The risk for anticonvulsant cutaneous drug reac-
tions ranges from 1 to 10/10,000.22, 30 These aromatic
lipid-soluble drugs are usually oxidized through the
cytochrome P450 system into active and inactive
metabolites. However, a percentage of the metabolism
is routed to form reactive arene oxide metabolites. The
percentage which undergoes this pathway of metabo-
lism is generally small, however, if other pathways are
inhibited or defective, a higher percentage of the reac-
tive metabolite will be produced, increasing the risk
for cutaneous skin reactions.21, 29
Recently, the United States Food and Drug Adminis­
tration informed healthcare professionals that danger-
ous or fatal skin reactions (i.e., Stevens–Johnson
syndrome and toxic epidermal necrolysis), can be
caused by carbamazepine therapy and are significantly
more common in patients with a particular human leu-
kocyte antigen (HLA) allele, HLA-B1502.37 This allele
occurs almost exclusively in patients with ancestry
L. C. Hutchison and O. Kajkenova
across broad areas of Asia, including South Asian
Indians. Patients from these areas should be screened
for the HLA-B1502 allele before starting treatment
with carbamazepine. If these individuals test positive,
carbamazepine should not be started unless the
expected benefit clearly outweighs the increased risk
of serious skin reactions. However, the reactions gen-
erally occur within 2–6 weeks of beginning therapy.22,30
Patients who have been taking carbamazepine for more
than few months without developing skin reactions are
at low risk of these events ever developing from car-
bamazepine. This same mechanism and risk is seen
with phenytoin and phenobarbital and cross-reactivity
is between 40 and 70%.21 Therefore, other anticonvul-
sants such as topiramate, levetiracetam, or gabapentin
should be used rather than anticonvulsants with aro-
matic structures.
Lamotrigine has also been associated with severe
cutaneous reactions, and it is metabolized in the same
manner as carbamazepine.17 Therefore, it likely has the
same increased incidence in Asian populations.
Recommendations to reduce the risk for rash with lam-
otrigine are to initiate therapy at 25  mg daily for 2
weeks, then increase to 50  mg daily for 2 weeks.
Thereafter, doses may be increased by 50–100  mg
every week. Other anticonvulsant medications may
affect these recommendations because they are potent
inducers and inhibitors of the cytochrome P450 sys-
tem. Lamotrigine increases the levels of the epoxide
metabolite of carbamazepine, increasing the risk for
toxicity. Other anticonvulsants reduce plasma levels of
lamotrigine, requiring higher doses to achieve thera-
peutic effects.
7.4.4 Tumor Necrosis Factor
Alpha Inhibitors
Tumor necrosis factor-alpha inhibitors, such as etaner-
cept (Enbrel), adalimunab (Humira), infliximab
(Remicade), and thalidomide have been used in the
treatment of autoimmune and lymphoproliferative dis-
eases. Injection site reactions are common but usually
minor problems. Incidence in a 6-month study of etan-
ercept was 37%. Urticaria can develop as a part of
acute infusion reactions. Current strategies for preven-
tion of acute infusion reactions include premedication
7  Prevention of Drug Reactions and Allergies in Dermatology
with diphenhydramine and acetaminophen 90  min
prior to infusion, or use of loratadine for 5 days prior
to the infusion. Reactions can also be managed by
reducing the rate of infusion. Other adverse cutaneous
effects were reported:
• Interstitial granulomatous dermatitis which devel-
oped within 1–3 months and in some patients a year
later after drug initiation10
• Leucoclastic vasculitis, lichenoid eruption, discoid
lupus erythematous-like eruption, acute folliculitis,
and necrotizing fasciitis7, 11
7.4.5 Amiodarone
Amiodarone is an antiarrhythmic agent used for atrial
fibrillation, ventricular tachycardia, and several other
electrical cardiac disturbances. It has a unique profile
of adverse events, causing corneal micro deposits,
photosensitivity, thyroid disorders, hepatotoxicity, and
pulmonary fibrosis.39 Unique to amiodarone is the risk
for a blue-gray skin discoloration reported to occur in
4–9% of patients treated with the medication. One
hypothesis attributed this hyperpigmentation to der-
mal lipofuscinosis. Macrophages were thought to
accumulate lipofuscin in granular sacs and this activ-
ity was thought to be related to sunlight because hyper-
pigmentation occurs primarily on light-exposed areas
of skin. Other researchers note that amiodarone and
metabolite concentrations in skin with the blue-gray
discoloration have been reported to be 10 times higher
than concentrations in nonpigmented skin. One case
report of amiodarone associated blue-gray hyperpig-
mentation showed no lipofuscin pigments leaving the
authors to conclude that drug and metabolite deposits
in the photo-exposed skin was the primary mechanism
of the reaction.1
Prevention of the blue-gray hyperpigmentation is
related to reducing exposure to the medication. The
lowest effective dose should be used for the shortest
possible time. Case reports of this cutaneous adverse
effect occur after an average of 20 months of treat-
ment. Reversal occurs years after discontinuation of
the drug. A cumulative dose of at least 160 g of amio-
darone is required for the reaction to occur which is
commonly achieved within 3 years of initiation of
therapy at an average dose of 200 mg daily.
69
7.5 Conclusion
Adverse cutaneous drug reactions are common, but
most are not severe or life-threatening. The most effec-
tive means for prevention of these reactions is to reduce
medication exposure by discontinuing medications
that are not indicated, using the lowest effective dose
and limiting the duration of therapy.
References
  1. Ammoury A, Michaud S, et  al Photodistribution of blue-
gray hyperpigmentation after amiodarone treatment: molec-
ular characterization of amiodarone in the skin. Arch
Dermatol. 2008;144(1):92–96
  2. Atkin PA, Veitch PC, et  al The epidemiology of serious
adverse drug reactions among the elderly. Drugs Aging.
1999;14(2):141–152
  3. Baldi BG, Santana AN, et  al Pulmonary and cutaneous
nocardiosis in a patient treated with corticosteroids. J Bras
Pneumol. 2006;32(6):592–595
  4. Bates DW, Leape LL, et al Incidence and preventability of
adverse drug events in hospitalized adults. J Gen Intern
Med. 1993;8(6):289–294
  5. Bigby M. Rates of cutaneous reactions to drugs. Arch
Dermatol. 2001;137(6):765–770
  6. Brazzini B, Pimpinelli N. New and established topical corti-
costeroids in dermatology: clinical pharmacology and thera-
peutic use. Am J Clin Dermatol. 2002;3(1):47–58
  7. Chan AT, Cleeve V, et  al Necrotising fasciitis in a patient
receiving infliximab for rheumatoid arthritis. Postgrad Med
J. 2002;78(915):47–48
  8. Cousins DD. Medication Use: A Systems Approach to
Reducing Errors. Oakbrook Terrace, IL: Joint Commission
on Accreditation of Healthcare Organizations; 1998
  9. Cullen DJ, Bates DW, et al The incident reporting system does
not detect adverse drug events: a problem for quality improve-
ment. Jt Comm J Qual Improv. 1995;21(10):541–548
10. Deng A, Harvey V, et al Interstitial granulomatous dermati-
tis associated with the use of tumor necrosis factor alpha
inhibitors. Arch Dermatol. 2006;142(2):198–202
11. Devos SA, Van Den Bossche N, et al Adverse skin reactions
to anti-TNF-alpha monoclonal antibody therapy. Dermatology.
2003;206(4):388–390
12. Fardet L, Flahault A, et  al Corticosteroid-induced clinical
adverse events: frequency, risk factors and patient’s opinion.
Br J Dermatol. 2007;157(1):142–148
13. Fiszenson-Albala F, Auzerie V, et al A 6-month prospective
survey of cutaneous drug reactions in a hospital setting. Br
J Dermatol. 2003;149(5):1018–1022
14. Gaig P, Garcia-Ortega P, et al Drug neosensitization during
anticonvulsant hypersensitivity syndrome. J Investig Allergol
Clin Immunol. 2006;16(5):321–326
15. Garcia-Doval I, LeCleach L, et al Toxic epidermal necroly-
sis and Stevens-Johnson syndrome: does early withdrawal of
causative drugs decrease the risk of death? Arch Dermatol.
2000;136(3):323–327
70
16. Hengge UR, Ruzicka T, et al Adverse effects of topical glu-
cocorticosteroids. J Am Acad Dermatol. 2006;54(1):1-15;
quiz 16–18
17. Hilas O, Charneski L. Lamotrigine-induced Stevens-
Johnson syndrome. Am J Health Syst Pharm. 2007;64(3):
273–275
18. Hunziker T, Kunzi UP, et  al Comprehensive hospital drug
monitoring (CHDM): adverse skin reactions, a 20-year sur-
vey. Allergy. 1997;52(4):388–393
19. Johnson JA, Bootman JL. Drug-related morbidity and mor-
tality. A cost-of-illness model. Arch Intern Med. 1995;
155(18):1949–1956
20. Knowles SR, Shear NH. Recognition and management of
severe cutaneous drug reactions. Dermatol Clin. 2007;
25(2):245–253, viii
21. Krauss G. Current understanding of delayed anticonvulsant
hypersensitivity reactions. Epilepsy Curr. 2006;6(2):33–37
22. Mockenhaupt M, Messenheimer J, et  al Risk of Stevens-
Johnson syndrome and toxic epidermal necrolysis in new
users of antiepileptics. Neurology. 2005;64(7):1134–1138
23. Munzenberger PJ, Montejo JM. Safety of topical calcineurin
inhibitors for the treatment of atopic dermatitis. Pharmaco­
therapy. 2007;27(7):1020–1028
24. Naldi L, Conforti A, et al Cutaneous reactions to drugs. An
analysis of spontaneous reports in four Italian regions.
Br J Clin Pharmacol. 1999;48(6):839–846
25. Posadas SJ, Pichler WJ. Delayed drug hypersensitivity reac-
tions – new concepts. Clin Exp Allergy. 2007;37(7):989–999
26. Rademaker M, Oakley A, Duffill MB. Cutaneous adverse
drug reactions in a hospital setting. N Z Med J. 1995;
108(999):165–166
27. Rajan TV. The Gell-Coombs classification of hypersensitiv-
ity reactions: a re-interpretation. Trends Immunol. 2003;
24(7):376–379
28. Riedl MA, Casillas AM. Adverse drug reactions: types and treat-
ment options. Am Fam Physician. 2003;68(9):1781–1790
L. C. Hutchison and O. Kajkenova
29. Roychowdhury S, Svensson CK. Mechanisms of drug-
induced delayed-type hypersensitivity reactions in the skin.
Aaps J. 2005;7(4):E834–E846
30. Rzany B, Correia O, et al Risk of Stevens-Johnson syndrome
and toxic epidermal necrolysis during first weeks of antiepi-
leptic therapy: a case-control study. Study Group of the
International Case Control Study on Severe Cutaneous
Adverse Reactions. Lancet. 1999;353(9171):2190–2194
31. Schoepe S, Schacke H, et al Glucocorticoid therapy-induced
skin atrophy. Exp Dermatol. 2006;15(6):406–420
32. Segal A, Doherty K, et  al Cutaneous reactions to drugs in
children. Pediatrics. 2007;120(4):e1082–e1096
33. Semla TP, Beizer JL, et  al Geriatric Dosage Handbook.
Hudson, OH: Lexi-Comp; 2006.
34. Shipley D, Ormerod AD. Drug-induced urticaria. Recognition
and treatment. Am J Clin Dermatol. 2001;2(3): 151–158
35. Svensson C, EW C, et  al Cutaneous drug reactions.
Pharmacol Rev. 2000;53(3):357–379
36. U.S. Food and Drug Administration, (March 10, 2005).
FDA Public Health Advisory Elidel (Pimecrolimus) Cream
and Protopic (Tacrolimus) Ointment. Retrieved 21
December 2009, from http://www.fda.gov/Drugs/
DrugSafety/PublicHealthAdvisories/ucm051760.htm
37. U.S. Food and Drug Administration, (December 12, 2007).
Information for Healthcare Professionals: Dangerous or Even
Fatal Skin Reactions - Carbamazepine (marketed as Carbatrol,
Equetro, Tegretol, and generics). Retrieved 21 Dec­ember
2009, from http://www.fda.gov/Drugs/DrugSafety/Postmarket
DrugSafetyInformationforPatientsandProviders/ucm124718.
htm
38. van der Linden PD, van der Lei J, et  al Skin reactions to
antibacterial agents in general practice. J Clin Epidemiol.
1998;51(8):703–708
39. Vassallo P, Trohman RG. Prescribing amiodarone: an evi-
dence-based review of clinical indications. JAMA. 2007;
298(11):1312–1322
 Xerosis and Stasis Dermatitis
8
Margaret E. M. Kirkup

8.1 Introduction The fact that there is no universally accepted defini-

tion of dry skin has hampered research in this area. It
may be perceived as cosmetic rather than pathological
Dry skin and stasis dermatitis are common conditions of
by some physicians. Indeed there is a spectrum of
senescence although they can occur at any age given the
severity from a few dry patches on the face to a gener-
predisposing constitutional or environmental factors.
alized pruritic condition. Dry skin can be severe and
In this chapter, I will attempt to describe the differ-
symptomatic, involving a detrimental effect on quality
ences between dry and normal skin and the influences
of life. Left untreated, it may be major reason for itch-
which can contribute to dryness with emphasis on
ing, especially in the elderly. Dry skin can be constitu-
those which are reversible before a clinical problem
tional or hereditary. It can be acquired by poor skin
develops. In addition, I shall discuss the nature of and
care or contact with irritants, including friction and
preventative measures possible in stasis dermatitis.
exposure. It can also be a component sign of skin dis-
Knowledge of the microstructure of the epidermis,
ease such as atopic eczema or associated with systemic
particularly the stratum corneum, is important in
diseases, including renal failure, thyroid disease, and
understanding how dry skin occurs and the efficacy of
malignancies. The term xerosis (Greek xeros > dry) is
the preventative measures which are available. Stasis
frequently used interchangeably with “dry skin.” Dry
dermatitis, a common condition of the lower limb, is
skin is considered here to mean skin which is free of
due to failure of the tissue drainage mechanisms. The
dermatological disease but which feels dry and rough
result is abnormality of appearance of the skin includ-
to the touch. The surface appears to lack the normal,
ing discoloration, followed by inflammation. Ultimately
smooth, slightly oily feel and can appear to be covered
fibrosis and ulceration can occur.
in white powdery flakes. In established cases, the skin
Prevention of dry skin requires avoiding contact
has a mosaic-like appearance sometimes described as
with irritant substances, attention to the environment
“crazy paving” or eczema craquelé (Fig.  8.1). Such
of the skin, and regular application of moisturizing and
skin will often be described as feeling “tight” and will
emollient agents. Prevention of stasis dermatitis
lack elasticity. It can and often does itch. It has a ten-
requires avoidance of pooling of blood and tissue flu-
dency to worsen in winter but can also be exacerbated
ids in the lower limbs by exercise, weight control, and
by sun exposure. Dry skin is vulnerable to damage
prompt and continuous treatment of vein and lym-
from friction, shearing forces, and trauma. This can
phatic disease. Also required is prevention of localized
lead to development of fissures, which heal poorly.
xerosis with its loss of skin-barrier function that leaves
Dry skin shows increased penetration by substances,
the limbs vulnerable to dermatitis.
rendering it more susceptible to development of irri-
tant contact dermatitis.1
Chronic stasis dermatitis has several synonyms,
including gravitational eczema, venous stasis eczema,
M. E. M. Kirkup
and varicose eczema. The onset is gradual after many
Department of Dermatology, Weston General Hospital,
Weston-super-Mare, Avon, UK months or years of venous hypertension or lymphedema,
e-mail: maggie@kirkup.plus.com signs of which may be relatively subtle clinically when

R. A. Norman (ed.), Preventive Dermatology, 71

DOI: 10.1007/978-1-84996-021-2_8, © Springer-Verlag London Limited 2010
72
Fig. 8.1  Eczema Craquelé on the thighs
the skin changes begin to appear. Failure of drainage of
the skin and subcutaneous tissue of the leg due to inad-
equacy of the venous or lymphatic systems leads to
malnourishment of those tissues and poor oxygenation
of the cells. However, the mechanism of development
of dermatitis is unclear. The epidermal changes are
speculated to be secondary to alterations in the function
of the dermal blood vessels.2 Signs of chronic venous
stasis disease include edema, varicosities of the veins
due to failure of the valves in the superficial venous sys-
tem or perforating veins and variable skin changes.
There is extravasation of blood into the skin which is
clinically seen as hemosiderin staining (Fig.  8.2).
Dryness and erythema are common features.
Fig. 8.2  Venous stasis disease showing early ulceration, xerosis,
and hemosiderin staining
M. E. M. Kirkup
8.2 Xerosis
8.2.1 Pathogenesis of Xerosis
The major component of the skin which is altered
when dryness occurs is the epidermis, principally the
stratum corneum. Stratum corneum consists of the ter-
minally differentiated keratinocytes known as corneo-
cytes. Corneo­cytes are flattened in shape compared to
the keratinocytes in the deeper layers of the epidermis.
They have no nucleus and consist of a cell envelope sur-
rounding a compacted mass of keratin and amorphous
matrix. Part of this intracellular matrix is a complex mix-
ture of compounds described as the natural moisturizing
factor, the function of which seems to be to retain water
in the stratum corneum. The corneocytes are arranged
rather like a brick wall, the mortar of which consists
mainly of a bilayer of lipid. The effect of this layer is to
waterproof the skin, preventing evaporation and water-
logging, yet allow diffusion of hydrophilic materials.
The cells of the epidermis are held together by des-
mosomes. In the stratum corneum the corresponding
structures, the corneodesmosomes, break down natu-
rally allowing the spent cells to be shed imperceptibly.
Water is necessary for the activity of the enzymes
involved in this process. In xerotic skin there is failure
of the corneocytes to be shed in the normal way. The
corneodesmosomes do not break down at the normal
rate and the cells are shed in clumps, perceived macro-
scopically as scale and roughness (Fig. 8.3). The rough,
dry appearance and feeling is due to this dysfunctional
Fig. 8.3  Very dry skin in an elderly lady
8  Xerosis and Stasis Dermatitis
desquamation but also due to increased evaporation of
water and reduction in intercellular lipid.
Dry skin cannot perform all of its functions. Being
in direct contact with the external environment, the
epidermis is particularly vulnerable to physical and
chemical influences. Dry skin has reduced barrier
function, which renders it more vulnerable to these
environmental influences. This loss of function is in
part due to the reduced levels of lipid and in part due to
the dehydration of the cellular component, allowing
the skin to fissure and permitting entry of chemical
substances and microbiological invaders.
In most cases, it is likely that a combination of
genetic predisposition and environmental influences
are involved. Individual thresholds for barrier function
breakdown are very variable. Contributing environ-
mental factors are
• Cold
• Heat
• Wind
• Low humidity
• Ultraviolet radiation
• Soaps, detergents, and other cleaning products
• Friction
Systemic medication may contribute to dry skin. For
example, diuretics which are very widely used may
have a dehydrating effect on the skin and retinoids
have an effect on keratinization with a dose-related
drying effect.
Measuring skin dryness is essential in experimental
work but is of no practical use in a clinical setting.
Among the measures commonly used are electrical
impedance, which is an indicator of the water content
by its ability to conduct electricity, and transepidermal
water loss (TEWL), an indicator of the protective skin
barrier function.
8.2.2 Epidemiology of Xerosis
Studies reveal that xerosis is one of the most common
abnormalities of older skin.3, 4 Some evidence sug-
gests that females are more likely to describe their
skin as dry at all ages5 and dry skin was found to be
more common in females than males in study of non-
institutionalized older individuals.3 Clinically recog-
nizable xerosis is most common on the face and lower
73
legs and is of increased prevalence with increasing
age. Institutionalized elderly people are at particular
risk due to the conditions of low humidity and high
environmental temperatures often to be found in care
homes and hospitals. Prevalence rates of 29–58% are
reported in nursing home patients.6, 7 It is more diffi-
cult to perform epidemiological studies in noninstitu-
tionalized people and studies in unselected populations
are sparse. Epidemiological studies of skin do not
always include xerosis as a pathological condition.
However, there is a high prevalence of xerosis reported
in several studies of patients attending dermatology
facilities.8, 9
While women are more likely than men to complain
of dry skin, inflamed dry skin known as asteatotic
eczema is more common in men.10, 11 Outdoor workers
are at risk because of exposure to the effect of tempera-
ture extremes, UV radiation, and wind. Definition of
dry skin and cultural values make it difficult to com-
pare populations. There is some evidence that immi-
grant men from East Asia, the Middle East, and North
Africa are more aware of dry skin than other groups
following migration to a Western community.12
8.2.3 Prevention of Xerosis
Prevention of dry skin and treatment of established
cases follow the same principles. These are avoidance
of aggravating factors, manipulation of the micro-envi-
ronment of the skin surface, and application of topical
agents to enhance or support the functions of the stra-
tum corneum. There is limited evidence of benefit
from systemic pharmaceutical agents.
8.2.3.1 Manipulation of the External
Environment of the Skin
The environment needs to be manipulated to avoid
the skin being exposed to extremes of temperature.
Suitable clothing should be worn to protection against
wind, rain, and sunlight. Use of sun-protective topi-
cal agents may help in two ways, both by preventing
UV radiation damage to the DNA of the skin cells
and by having a moisturizing effect. Clothing is being
developed which is made from very fine, smooth
fibers which may have a place in primary prevention
74
of xerosis. Measures should be taken to increase the
humidity of the local environment. This may require
reduction in ambient temperature or adjustment of
the time exposed to air conditioning or central heat-
ing. Some additional increase in moisture in the air
may be gained by placing open containers of water
around the home or workplace. Indoor plants may
also help.
8.2.3.2 Personal Care
Since indoor bathrooms became commonplace in the
twentieth century, there has been a tendency toward
frequent showering and bathing. Millions are spent
every year on advertising soaps, shower and bath gels,
and shampoos. We are encouraged to believe that we
should be sweet-smelling at all times and over-wash-
ing may be a factor in development of xerosis. Water,
soap, and detergent skin-washing liquids are gener-
ally the most common irritants applied to the skin. In
my experience, many people with dry, itchy skin find
the application of water gives temporary relief and
reduces the feeling of dryness. They may need con-
siderable persuasion to convince them to reduce
excess contact with water that, in the long term, is
damaging their skin.
There is a huge industry involved in developing
and marketing skin cleansing products. A study of
commonly used soaps and cleansers in Mexico showed
that the majority of washing agents were irritants as
assessed by a 5-day patch test technique.13 Soaps,
soap-free cleansers, shampoos, shower and bath gels
and creams may be described as “moisturizing” but as
a general rule contain surfactants which strip the natu-
ral lipid from the stratum corneum, contributing to
dryness. Reducing washing frequency and use of
soap-substitutes goes a long way toward preventing
xerosis.
8.2.3.3 Topical Agents
Almost any moisturizer or emollient can be used as a
soap-substitute or applied directly to the skin.
Emollients are skin softeners, reducing the feeling of
roughness; moisturizers also add water to the epider-
mis, improving its function. In practice, they can be
used interchangeably in most cases and the terms are
M. E. M. Kirkup
often used as synonyms. Instruction needs to be given
in how to use these products. While they can be added
to very hot water and whipped into a suspension or
emulsion, allowing use as a liquid skin cleanser, it is
equally effective to use these products by applying
them directly to the skin. Gentle removal with sponge
or flannel in the bath or shower is cleansing and leaves
a pleasant layer of the product on the skin. The water
must not be very hot or cold. Moisturizers and emol-
lient preparations containing antimicrobial agents may
be helpful on a short-term basis where scratching or
other skin trauma increases the risk of infection. Bath
oils and liquid emollients added to the bath water,
form a film on the surface of the water. Some of this
will cling to the skin on leaving the bath giving addi-
tional benefit. Emollients and moisturizers can cause
the surface of the bath to be slippery and extra care is
required to avoid falls, particularly in children and the
elderly.
After bathing, the skin should be gently patted
dry with a soft towel to avoid frictional trauma and a
further layer of emollient or moisturizer applied.
Ideally this should be done before the skin is quite
dry. Emollient or moisturizer should be reapplied
throughout the day to protect from the environment
and prevent development of signs of dryness. The
frequency of application will depend partly on the
severity of the xerosis or tendency to dryness but
should be at least twice daily. Social circumstances
and clothing may well have an influence on what is
practical.
8.2.3.4 Moisturizing
As well as spending vast sums of money on production
and advertising of skin cleansers, the cosmetics and
toiletries industries are investing heavily in developing
and advertising moisturizers. While those at risk from
genetic and environmental factors are well-advised to
be liberal with applications of moisturizing agents,
what is the evidence that regular moisturizing actually
prevents dryness in those at low risk? There is good
evidence that regular moisturizing reduces the inci-
dence of irritant dermatitis in those at risk and prevents
recurrence of the dry skin, suggesting that primary pre-
vention would also be effective.14 Moisturizing has
been shown to have a significantly protective effect
against detergents in healthy volunteers.15
8  Xerosis and Stasis Dermatitis 75

8.2.4 Choice of Moisturizer Moisturizers and emollient ingredients vary. While

and Soap-Substitute
The range of moisturizers available is vast and includes
lotions (solutions, suspensions or emulsions of lipid
and water) creams (emulsions of water in oil or oil in
water), ointments (with hydrophilic or hydrophobic
bases), pastes (solids suspended in a base), and gels.16
The ideal emollient might be a simple preparation,
such as soft white paraffin, which softens the skin
and provides a waterproof film, preventing contact
with irritants and preventing evaporation of water
from the stratum corneum. However, it is not always
cosmetically acceptable to use and can stain clothing
and make skin surface slippery, reducing grip. A bal-
ance has to be struck between cosmesis and effective-
ness. The best topical agent is the one which the
individual will actually use and it may take some time
to find the best one for each individual. Compromise
between effectiveness and cosmetic acceptability
may be necessary.
When xerosis is established, it can take many weeks
of persistence with a good moisturizing regimen before
normal skin barrier function is restored. Secondary
prevention in the form of continued moisturizing and
avoidance of irritants is wise.
the best combination for any given patient may be found
by trial and error, it can be useful for healthcare profes-
sionals to have some knowledge of the constituents of
these products. Ideally, the chosen preparation should
include a humectant, which retains or attracts water, and
a grease or lipid to act as a waterproof barrier, prevent-
ing evaporation of water and protecting the skin from
the influences of an adverse environment. Examples of
humectants are lactic acid, glycerol, and urea. Some
products also contain physiological lipids, which may
improve the differentiation of the epidermis and may
help reform the lipid bilayer.17 Additional ingredients
such as ammonium lactate may improve the efficacy by
keratolysis, thus normalizing desquamation. The risk of
skin irritation and development of contact allergy is
reduced by careful selection of products to avoid irritant
and allergenic ingredients. It may also be necessary to
select different products for different areas of the body
and for different times of day; a heavier, greasier product
may be more acceptable at night than before dressing for
the day. A compromise product is better than none.
Ingredients used in emollient and moisturizer man-
ufacture are shown in Table  8.1. Most commercial
products will also contain preservatives, perfumes,
and emulsifying agents and some contain coloring
materials.

Table 8.1  Ingredients commonly used in emollients and moisturizers

Ingredient Example Primary function
Water – Adds moisture
Fats and oils Liquid paraffin, petrolatum Prevents evaporation
Physiological lipid Cholesterol, ceramides Prevent evaporation and may play a role in
restoration of function of the stratum
corneum
Humectant Glycerol, lactic acid, urea Restore water content of stratum corneum
Antioxidants Tocopherols, gallates Inhibit oxidation
Keratolytics Ammonium lactate Enhance lysis of corneodesmosomes
Preservative (antimicrobial) Parabens, alcohol Reduce microbial growth in opened container
Emulsifying agent Stearic acid, palmitic acid, sodium Collect at interface of two phases to promote
lauryl sulfate emulsification
Perfumes Increase acceptability of the product
Color – Increase acceptability of the product
76
8.2.5 Adverse Effects of Moisturizing
Serious reactions are rare but allergic contact dermati-
tis to contents of these products can occur. Irritant der-
matitis is more common with frequent and prolonged
use of preparations containing potential irritants such
as sodium lauryl sulfate. Humectants such as urea and
lactic acid are associated with causing a subjective
sensation in some individuals.16
8.2.6 Specific Body Areas
Some areas of the body may require special attention.
Among these are hands, feet, and flexures.
8.2.6.1 Hands
Those in occupations which involve frequent unavoid-
able exposure to water, such as domestic cleaners,
catering workers, healthcare workers, hairdressers, and
bar staff will need additional advice on protection of
the hands. Dry skin is the precursor to irritant hand
eczema. It is always best to place a barrier between the
skin and the water where possible. Gloves form a bet-
ter barrier than topical agents. Gloves need to be appro-
priate to the task and may not be easily accepted.
Powdered latex must be avoided to reduce the risk of
latex allergy. Hand washing with an emollient is
acceptable in most settings but liberal and frequent
application of emollients or moisturizers after washing
or other exposure to water is also vital. Wearing gloves
in cold and wet weather will also help prevent drying
of the skin. Cotton gloves can be useful to wear after
liberal application of topical agents.
8.2.6.2 Feet
The skin on the soles of the feet is thick, mainly due to
hyperkeratosis of the stratum corneum, maximal on
weight-bearing areas. While this is likely to be a physi-
ological response it is more pronounced with advancing
age and with obesity and is exacerbated by frictional
stresses including ill-fitting footwear. This thick epider-
mal layer tends to desiccate and crack especially in
middle age and beyond, leading to fissures which can be
M. E. M. Kirkup
deep, painful, and slow to heal. The thick layer itself can
cause difficulty with walking and shoe-fitting. Paring
away the build-up of thick skin may give temporary
relief but the skin responds by rebuilding the thick stra-
tum corneum unless measures are taken to alter the local
environment of the feet. Application of emollients will
soften the hyperkeratotic skin and improve comfort
while helping reduce further build-up. Particular care is
needed in those with diabetes and peripheral ischemia.
8.2.6.3 Flexures
Body flexures are vulnerable areas because the epider-
mis tends to be thin with a thin stratum corneum and
because the skin folds can trap topical agents and irri-
tants if not adequately cleansed. Build-up of sweat,
retained cleaning agents and other applications such as
talcum powder can contribute to the development of
irritation.
8.2.7 Occupational Factors
In the workplace and in domestic cleaning, it is essen-
tial to avoid direct contact of the skin and irritants.
Water is an irritant, especially if contact is prolonged.
Protective gloves are widely available. The gloves cho-
sen need to be appropriate for the task. Nonpowdered
latex should be avoided as it increases the risk of sensi-
tization to latex. It is the duty of the employer to ensure
that appropriate gloves and other protective clothing
are available but it is the duty of the employee to make
sure that they use them. Training may be required.
Regulations exist to protect the workforce against
extremes of temperature. Control of humidity is less
well-regulated.
8.3 Stasis Dermatitis
8.3.1 Introduction
Stasis dermatitis affects the lower legs bilaterally, often
beginning insidiously on the shin or “gaiter” area above
the ankles. It is believed to be due to stasis of tissue
fluids but is an under-researched condition. The stasis
8  Xerosis and Stasis Dermatitis
may not be clinically overt when the skin changes pres-
ent. Reduced efficacy of the activity of the drainage
mechanisms of the lower limbs results in inflammation
and gross changes of appearance of the skin. Etiology
can be multifactorial; lymphatic or venous obstruction
or insufficiency may be implicated. Lymphatic drain-
age can be overwhelmed and impaired by systemic dis-
ease of the cardiovascular, renal or hepatic systems and
by obstruction to the drainage by lymphatic involve-
ment in malignancy or obesity. Local damage to the
lymphatics can occur after deep venous thrombosis
(DVT), repeated attacks of cellulitis, or as a result of
trauma. Congenital lymphatic insufficiency can be
symptomless until adult life. Venous disease may be
overt as in DVT or varicose veins but can occur insidi-
ously in immobility and advancing age when lymphatic
insufficiency is likely to be worsened by venous stasis.
Obesity compounds the problem whatever primary
cause is involved due to increased hydrostatic pressure,
which can overcome the capacity to drain the intersti-
tial tissues. Flow may also become retrograde when the
limbs are dependent and immobile.
8.3.2 Pathogenesis of Stasis Dermatitis
The pathogenesis of stasis dermatitis has not been fully
elucidated. Poorly drained skin demonstrates changes
microscopically before clinical problems present. The
lymphatics are dilated, dermal blood vessel walls
thicken and passage of fluid and cells in either direc-
tion becomes impaired. The inflammatory process
leading to stasis dermatitis seems to involve white
blood cells sequestration in postcapillary venules
which increases cell adhesion leading to leucocyte
activation in the superficial dermal microvasculature.2
This process becomes self-perpetuating. Left untreated
the process leads to fibrosis and ultimately ulceration.
Extravasated blood cells cannot reenter the circulation
and are broken down slowly in situ leading to hemo-
siderin staining (Fig.  8.2). The skin becomes xerotic
and inflammation ensues. Dry skin may itch and
scratching may be the final straw in developing signs
of dermatitis. However, itch is not a prominent clinical
feature in many cases. The “gaiter” area just above the
ankles seems to be the most vulnerable site and this is
the most common site for development of ulceration if
stasis problems are not addressed.
77
Table 8.2  Ankle Brachial Pressure Index (ABPI)
Measure blood pressure in brachial artery as normal
Apply blood pressure cuff to lower limb and inflate
Use handheld Doppler probe over the posterior tibial artery
and dorsalis pedis artery in turn to measure systolic
ABPI = systolic pressure at ankle divided by the systolic pres-
sure at brachial artery. For example, with blood pressure of
170/80 and post tibial pressure of 150, the ABPI = 0.88
8.3.3 Epidemiology of Stasis Dermatitis
There is a slight female preponderance in this condi-
tion. Females have increased risk factors for the condi-
tions which predispose to the development of the
underlying stasis. Frequency increases with advancing
age. It is estimated that 2–5% of the adult population
of the United States shows changes associated with
venous insufficiency.
8.3.4 Predisposing Factors
to Stasis Dermatitis
Factors predisposing to stasis dermatitis are:
• Obesity
• Cardiac failure
• Immobility
• Renal failure
• Advancing age
• Hepatic failure
• Xerosis
• Hypothyroidism
• Venous disease
• Hypoalbuminemia
• Lymphatic obstruction
• Malignancy
• Smoking
8.3.5 Prevention of Stasis Dermatitis
Primary prevention of stasis dermatitis requires correc-
tion of the condition of tissue fluid stasis, reducing pres-
sure on the venous or lymphatic return. This restores the
78
physiological state of tissues toward normal. Depending
on the underlying predisposition, it may not be possible
to completely correct the problem.
Leg elevation, exercise of the lower leg muscula-
ture, compression hosiery, and prevention of xerosis,
as outlined above, all have a part to play.
8.3.5.1 Leg Elevation
Dependency of the lower limb causes the drainage sys-
tems to be under conditions of increased hydrostatic
pressure. Simple elevation of the legs when at rest will
relieve this pressure. This can be achieved by recum-
bence with raising of the foot end of the bed. There are
many comfortable chairs available which include the
facility to raise the feet at least level with the hips.
8.3.5.2 Exercise
The calf muscles act as a pump, aiding venous and
lymphatic return. Simple exercises to increase the
activity of these muscles are a useful adjunct to man-
agement and help prevent the condition. Exercises can
be performed while sitting or recumbent.18 ,19
8.3.5.3 Compression
Where it is not possible to restore the drainage to normal,
external support in the form of compression hosiery or
bandaging will encourage fluid into the deep venous or
lymphatic system and reduce the tissue fluid pressure in
the skin. Compression must not be introduced if it will
compromise the arterial supply of the limb or if there is
any infection present. It is essential to palpate the limb
pulses and observe for signs of ischemia. If there is
doubt, Doppler studies of the pressure in the peripheral
arteries give an indication of suitability for compression
but it may be necessary to formally investigate for arte-
rial disease surgeon before proceeding. A useful rule of
thumb is not to introduce compression if the ankle bra-
chial pressure index (ABPI) is greater than 0.8. The
method of measuring ABPI is shown in Table 8.2.
There are many suppliers of compression hosiery
and many different methods of classification of the
degree of support provided by the products. Compression
hosiery classifications vary from country to country.
Examples of the systems in use are shown in Table 8.3.
M. E. M. Kirkup
Table  8.3  Classification of compression hosiery in various
countries
UK France Germany USA
(mmHg) (mmHg) (mmHg) (mmHg)
Class 1 14–17 10–15 18–21 15–30
Class 2 18–24 15–20 23–32 30–40
Class 3 25–35 20–36 34–46 40+
Class 4 >36 >49
The higher the class of garment, the lower is the
likelihood of compliance. There is some evidence that
there is little difference in reduction of edema between
classes I and II in preulcer states.20 Therefore, to opti-
mize compliance, class I compression may be sufficient
for prevention. As few as 21% of those prescribed com-
pression for venous disease use the compression on a
daily basis.21 The more compressive the garment, the
more difficult it is to put on, the higher grades requiring
considerable dexterity and strength. The physical act of
putting on compression hosiery can be extremely diffi-
cult or impossible for those who have impaired joint
mobility, flexibility, weakness, or cognitive dysfunc-
tion. Many suppliers can provide aids to assist but there
is no substitute for having someone to help.
8.3.5.4 Emollients
Emollient therapy as outlined above is the most appro-
priate topical therapy for reducing the appearance of
stasis dermatitis. Xerosis is an important part of the
pathophysiology of the condition. Application is easier
if there is someone to help as the lower legs can be out
of reach of many obese, elderly, ill people. Application
is best done by smoothing the agent on in the direction
of hair growth to avoid occlusion of follicles.
8.3.5.5 Pharmaceutical Interventions
There is unconfirmed evidence that oral flavonoids,
which are botanical antioxidants, are venotropic and
can help reverse venous stasis disease.22 Other phar-
maceutical agents such as the angiogenesis inhibitor
calcium dobesilate and xanthine derivative pentoxy-
fyline may have a role in management of established
stasis dermatitis but their place in prevention is
untested.23, 24
8  Xerosis and Stasis Dermatitis
References
  1. Smith HR, Rowson M, Basketter DA, McFadden JP. Intra-
individual variation of irritant threshold and relationship to
transepidermal water loss measurement of skin irritation.
Contact Derm. 2004;51:26–29
  2. Cheatle TR, Scott HJ, Scurr JH, et al White cells, venous blood
flow and venous ulcers. Br J Dermatol. 1991;125:288–290
  3. Beauregard S, Gilchrest BA. A survey of skin problem and
skin care regimens in the elderly. Arch Dermatol. 1987;123:
1638–1643
  4. Weisman K, Krakauer R, Wanscher B. Prevalence of skin
disease in old age. Acta Derm Venereol. 1980;60:352–353
  5. Jemec GBE, Serup J. Scaling, dry skin and gender. Acta
Derm Venereol. 1992;177:26–28
  6. Norman RA. Xerosis and pruritus in elderly patients, part 1.
Ostomy Wound Manage. 2006;52:12–14
  7. Smith DR, Atkinson R, Tang S, Yamagata Z. A survey of
skin disease among patients in an Australian nursing home.
J Epidemiol. 2002;12:336–340
  8. Thaiisuttikul Y. Pruritic skin diseases in the elderly.
J Dermatol. 1998;25:153–157
  9. McFadden N, Hande KO. A survey of elderly new patients at
a dermatology outpatient clinic. Acta Derm Venereol.
1989;69:260–262
10. Anderson C. Asteatotic eczema. E medicine, emedicine.
com; 2006
11. Fritsch PO, Reider N. Other eczematous disorders. In:
Bolognia JL, Jorizzo JL, Rapini R, eds. Dermatology.
Philadelphia: Mosby; 2003:218
12. Dalgard F, Holm JO, Svensson A, et  al Self reported skin
morbidity and ethnicity: a population based study in a
Western community. BMC Dermatol. 2006;7:4
79
13. Baranda L, Gonzalez-Amaro R, Torres-Alvarez B, et  al
Correlation between pH and irritant effect of cleansers mar-
keted for dry skin. Int J Dermatol. 2002;41:494–499
14. Simion FA, Abrutyn ES, Draelos Z. Ability of moisturisers
to reduce dry skin and irritation and to prevent their return.
J Cosmet Sci. 2005;56:427–444
15. Ramsing DW, Agner T. Preventive and therapeutic effects of
a moisturizer. Acta Derm Venereol. 1997;77:335–337
16. Loden M. Role of topical emollients and moisturizers in the
treatment of dry skin barrier disorders. Am J Clin Dermatol.
2003;4:771–788
17. Proksch E, Lachapelle J-M. The management of dry skin
with topical emollients – recent perspectives. J Dtsch
Dermatol Ges. 2005;3:768–774
18. Hansson C. Optimal treatment of venous (stasis) ulcers in
elderly patients. Drugs Aging. 1994;5:323–334
19. Padberg FT Jr, Johnston MV, Sisto SA. Structured exercise
improves calf muscle pump function in chronic venous insuf-
ficiency: a randomized trial. J Vasc Surg. 2004;39:79–87
20. Gniadecka M, Karlsmark T, Bertram A. Removal of dermal
oedema with class I and II compression stockings in patients with
lipodermatosclerosis. J Am Acad Dermatol. 1998;39:966–970
21. Raju S, Hollis K, Neglen P. Use of compression stockings in
chronic venous disease: patient compliance and efficacy.
Ann Vasc Surg. 2007;21:790–795
22. Katsenis K. Micronized purified flavonoid fraction (MPFF):
a review of its pharmacological effects, therapeutic efficacy
and benefits in the management of chronic venous insuffi-
ciency. Curr Vasc Pharmacol. 2005;3:1–9
23. Ciapponi A, Laffaire E, Roque M. Calcium dobesilate for
chronic venous insufficiency: a systematic review. Angiology.
2004;55:147–154
24. Pascarella L, Schoenbein GW, Bergan JJ. Microcirculation and
venous ulceration: a review. Ann Vasc Surg. 2005;19:921–927
 Photoprotection
Camile L. Hexsel and Henry W. Lim
Author contributions: Dr. Lim and Dr. Hexsel have
participated in the conception and design, drafting and
critical revision of the chapter for important intellectual
content.
Conflict of interest: Dr. Lim is a consultant for La
Roche-Posay, Orfagen, Johnson and Johnson, and Dow
Pharmaceuticals; and he has received research grant
support from Johnson and Johnson. Dr. Hexsel has no
conflicts of interest to declare.
9.1 Cutaneous Effects
of Ultraviolet Radiation
Ultraviolet (UV) radiation consists of UVC (270–290
nanometers [nm]), ultraviolet B (UVB) (290–320 nm)
and ultraviolet A (UVA), which is further classified
into UVA1 (340–400  nm) and UVA2 (320–340  nm).
UVC radiation does not reach the surface of the earth
as it is filtered by the ozone layer. On the surface of the
earth, there is 20 times more UVA than UVB.
Cutaneous effects of UV radiation can be divided
into acute and chronic. Acute effects include erythema,
edema, blisters, and immediate and delayed pigment
darkening followed by tanning or neomelanogenesis,
acanthosis, and dermal thickening. Exposure to UV
can also induce immunosuppression, vitamin D syn-
thesis, and development of photodermatoses.
Erythema and edema are primarily induced by
UVB, start at 3–4 h after UVB exposure, and peak at
C. L. Hexsel (*)
Department of Dermatology, Henry Ford Hospital,
Detroit, MI, USA
e-mail: chexsel1@hfhs.org
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_9, © Springer-Verlag London Limited 2010
9
8–24 h. They last 24–48 h or longer in light-skinned
individuals. Delayed tanning or neomelanogenesis
peaks at 72 h after UV radiation. UVB-induced delayed
tanning requires a preceding erythemal response and
has a sun protection factor (SPF) of 3.
In contrast to UVB, UVA-induced erythema peaks at
1–2  h after exposure and subsides gradually over
24–72 h. Because of the longer wavelength of UVA, it
takes 1,000-fold more fluence (dose) to induce ery-
thema by UVA compared to UVB. UVA also induces
immediate and delayed pigment darkening followed by
tanning. Immediate pigment darkening (IPD) occurs
within seconds after UVA and visible light irradiation,
and resolves in 2 h; it is due to photo-oxidation of pre-
existing melanin.1 Persistent pigment darkening (PPD)
is also a result of a photo-oxidation and redistribution of
preexisting melanin; PPD persists from 2 to 24 h after
irradiation.1, 2 UVA-induced delayed tanning, which is
secondary to neomelanogenesis, appears usually 3 days
after exposure.1
Chronic effects of UV radiation include photoaging
and the development of actinic keratosis, basal cell car-
cinoma, and squamous cell carcimona.1, 3, 4 Melanoma
has been associated with intermittent intense acute sun
exposure and history of sunburns. The specific wave-
lengths associated with melanoma have not completely
been identified; therefore, although sunburns are asso-
ciated with an increased risk of melanoma, the specific
wavelengths of UV responsible for sunburn may not be
the same wavelengths responsible for the development
of melanoma.3
Although solar radiation comprises a broad range of
wavelengths, several eye disorders are related to UV,
visible and infra-red radiation. Examples of acute
opthalmological effects include photokeratitis (welder’s
flash or snow blindness) from UVC and UVB radiation;
solar retinitis (blue light retinitis or eclipse blindness)
81
82
from unprotected exposure to intense sunlight; retinal
photochemical burn from short-wavelength visible light
(blue–violet light); retinal thermal damage from longer
wavelengths and short pulses of intense visible light.
Long-term effects of UV radiation associated with long-
term exposure to sunlight include age-related macular
degeneration, cataracts, pterygium, and pinguecula.5
9.2 General Photoprotection
Recommendations
and Their Rationales
Cutaneous effects of UV radiation can be effectively
prevented with the use of multiple photoprotection
measures.
UV radiation is more intense between 10 AM and 4
PM.1 Approximately 20–30% of total UV radiation
reaches the earth between 11 AM and 1 PM, and 75%
between 9 AM and 3 PM. Maximal irradiance occurs in
the summer months, although seasonal variation in UV
radiation decreases with latitude. Furthermore, there is
an increase of about 3% in UV reaching the surface per
degree decrease in latitude. Because of the wide range
of geographical, latitude, and time zone distribution,6
the “shadow rule” has been proposed as a simple way to
determine the peak hours of UV radiation. During peak
hours of UV radiation, a person’s shadow is shorter
than their height, while during off-peak hours, it is lon-
ger.4, 6 Therefore, the first recommendation in photopro-
tection is: seek shade during peak hours of UV radiation
(between 10 AM and 4 PM)1 or when one’s shadow is
shorter than one’s height (Table 9.1).4, 6
An effective and widely used photoprotection
method is sunscreen. Discussion of the sunscreen
actives available will be discussed in detail in this
chapter. Correct use, appropriate amounts, and reap-
plication frequency are important factors for the effec-
tiveness of sunscreens. Studies have shown that most
of those who use sunscreens apply them inadequately.
Concentrations of sunscreen used by consumers
(0.5–1  mg/cm2), compared to that used in testing
(2 mg/cm2) is the reason that in-use SPF frequently is
only 20–50% of the labeled SPF value.1, 6 To achieve a
2  mg/cm2 concentration, the average adult should
apply approximately 35 mL evenly, which is the equiv-
alent of a full 1-ounce shot glass. Sunscreen should be
applied 15–30  min before going out in the sun,
C. L. Hexsel and H. W. Lim
Table 9.1  Recommendations for photoprotection
Seek shade during peak hours of UV radiation (between 10
AM and 4 PM or when a person’s shadow is shorter than
their height)
Use sunscreens with broad spectrum UVB and UVA
coverage with minimum sun protection factor (SPF) 15,
preferably 30
First apply sunscreen 15–30 min before sun exposure
followed by another application 15–30 min later
Reapply sunscreen at least every 2 h and after swimming,
perspiring, and towel drying
In addition to sunscreen, use other physical barriers such as
shade, a wide-brimmed hat, tightly woven or specifically
designed protective clothing
In children younger than 6 months of age, use physical
measures for photoprotection (shade, clothing, hat).
If absolutely necessary, use sunscreen limited only on
exposed areas and infrequently
If you are at risk for vitamin D deficiency, take a minimum
of 800–1,000 IU of vitamin D supplementation
If planning multiday sun exposure, use higher SPFs
followed by a second application 15–30 min after sun
exposure.1 The second application can provide up to 3
times increase in photoprotection, thus compensating
for improper first application. Sweating, swimming,
and towel drying can considerably decrease the effi-
cacy of sunscreens1; towel drying can remove up to
85% of a product.4 With swimming and sweating, even
the most water-resistant product requires a more fre-
quent application than every 2 h. Therefore, the second
recommendation in photoprotection is: use sunscreens
with broad-spectrum UVB and UVA coverage and a
minimum SPF 15, preferably 30. Sunscreen should be
reapplied at least every 2 h and after swimming, per-
spiring, and towel drying. Sunscreen should be first
applied 15–30  min before sun exposure followed by
another application 15–30 min later (Table 9.1).
As will be outlined in more detail below, sunscreens
do not provide complete protection to the whole spec-
trum of UV radiation. Therefore, in addition to sun-
screens, other physical barriers, such as shade, a
wide-brimmed hat, tightly woven or specifically designed
protective clothing, and sunglasses are an integral part of
photoprotection strategy.
Because of the higher skin-surface-to-body-weight
ratio, and because the metabolism and excretion of
absorbed substances are not completely developed in
children under 6 months of age, it is recommended that
9  Photoprotection 83

for children younger than 6 months of age, photoprotection Table 9.2  Sunscreen drugs listed in the 1999 FDA sunscreen
be achieved by physical measures (shade, clothing, hat). monographa
If absolutely necessary, limited and infrequent use of Inorganic sunscreen drugs
sunscreen on exposed areas may be done.1 The 1999 Titanium dioxide
sunscreen monograph recommends that physicians be Zinc oxide
consulted for the use of sunscreen in this age group.7
Organic sunscreen drugs
Vitamin D oral supplementation is practical and
inexpensive. Therefore, oral vitamin D supplementa- UVB
tion is recommended for individuals at risk for vitamin Para-aminobenzoic acid (PABA)
D deficiency. These individuals at risk of vitamin D
Padimate O
deficiency include those living in northern latitudes
(above 35°), elderly, housebound, and darker-skinned Octinoxate
individuals. Intake of vitamin D should be 400–800 Cinoxate
IU/day depending on the age, for individuals at low Octisalate
risk for vitamin D deficiency; the recommended intake
Homosalate
of vitamin D for high-risk individuals is 800–1,000 IU/
day or up to 50,000  IU of vitamin D per month Trolamine salycilate
(Table 9.1).4 Octocrylene
Other factors should be considered for effective Ensulizole
photoprotection. Multiday exposure affects the sensi-
UVA
tivity to the sun since erythema peaks at 8–24 h of sun
exposure. Therefore, higher SPFs are recommended Oxybenzone
for multiday sun exposure.1 Various surfaces cause Sulisobenzone
significant reflection of UV radiation. Snow reflects
Dioxybenzone
30–80% of absorbed radiation, sand 15–30%, water
less than 5%, and most ground surfaces less than 10%. Avobenzone
UV radiation can penetrate through water to a depth of Meradimate
60  cm. Although complete cloud cover reduces sur- FDA Food and Drug Administration; UVB ultraviolet B; UVA
face UV radiation by approximately 50%, light scat- ultraviolet A
a
All listed as United States adapted name (USAN)
tered cloud cover has minimal impact on surface UV
radiation.8

labeling requirements.1,7 A proposed amendment to

9.2.1 Sunscreens
Organic sunscreens, previously called chemical sun-
screens, act by absorbing UV radiation in the UVB
and/or UVA spectra. Inorganic filters, previously called
physical sunscreens, act by either reflecting or absorb-
ing UV radiation, depending on the particle size.1
Sunscreens have been shown to prevent both acute and
most chronic effects of UV radiation.3,  9, 10
In the United States, the Food and Drug Adminis­
tration (FDA) regulates sunscreens as over-the-coun-
ter drugs. The most recent version of the final FDA
sunscreen monograph was issued in 1999 with a list
of 16 approved sunscreen drugs (Table 9.2), approved
maximum concentration, testing procedures, and
the 1999 monograph was published in August, 2007.2
There are two different methods available for appli-
cation of FDA approval for sunscreen drugs: the new
drug application (NDA), and the time and extent appli-
cation (TEA). To be considered for TEA approval, the
FDA requires submission of the data acquired from at
least 5 years of over-the-counter marketing of the prod-
uct in the same country outside the United States.11
Various broad-spectrum sunscreen products con-
taining ecamsule (terephtalydene dicamphor sulfonic
acid, Mexoryl SX™) were recently approved by the
FDA, the first one in July 2006.12 Ecamsule is not listed
among the approved sunscreen drugs since ecamsule-
containing products were approved as final products
rather than individual UV sunscreen drugs by the NDA
process.
84
9.2.2 Organic UVB Filters
SPF is the ratio of the dose of UV radiation (290–400 nm)
needed to produce one minimal erythema dose (MED) on
sunscreen-protected skin (2 mg/cm2 of product) over the
dose needed to produce one MED on unprotected skin.1, 3
Therefore, SPF is a reflection of predominantly the
erythemogenic effect of UVB, and to a lesser extend,
UVA2.
A proposed amendment to the 1999 monograph
was published by the FDA on 27 Aug 2007.2 Key
propositions comprise a new grading system for UVB
and UVA protection, a cap of the SPF at 50+, and sev-
eral recommendations in directions of use and label-
ing, including the requisite of a sun alert statement
warning.
In the 2007 amendment, the FDA suggests modify-
ing the acronym “SPF” from “SPF” to “UVB sunburn
protection factor” to better differentiate the biologic
effects of UVB and UVA. Furthermore, a grading sys-
tem for UVB sunburn protection factor was proposed
based on the following four categories: low UVB sun-
burn protection (SPF 2 £ 15), medium UVB sunburn
protection (SPF 15 £ 30), high UVB sunburn protec-
tion (SPF 30–50), highest UVB sunburn protection
(SPF over 50).
The FDA is of the opinion that there are no current
data reporting the accuracy and reproducibility of SPF
values over 50. Thus, the FDA proposes that manufac-
turers label their products with the specific SPF values
up to, but no greater than 50; those products with
SPF>50 would be labeled as 50+. Products would need
to have SPF of 60 to obtain a SPF50+.2
FDA-approved UVB sunscreen drugs are listed in
Table 9.2. Several important points regarding UVB fil-
ters listed in Table 9.2 need to be made.
Octinoxate (ethylhexyl methoxicinnamate, Parsol
MCX™) is the most widely used UVB sunscreen drug
in the United States. Octinoxate has maximum peak
absorption at 311 nm but it is less potent and photo-
stable than Padimate O, and hence, requires additional
photostable UVB drugs, or stabilizers, to achieve a
high SPF value. Octisalate (ethyl hexyl salicylate),
homosalate (homomenthyl salicilate), and octocrylene
(2-ethylhexyl-2-cyano-3, 3-diphenylacrylate) are pho-
tostable; they are often combined with other sunscreen
drugs to enhance the photostability of the final
product.
C. L. Hexsel and H. W. Lim
9.2.3 Organic UVA Filters
The 2007 proposed amendment to the FDA sunscreen
monograph presents a new grading system of the level
of UVA protection, comprising a four-star rating sys-
tem that ranges from low, medium, high, to highest
UVA protection (Table 9.3). The rating system is based
on both in vivo and in vitro testing procedures.
The PPD test is proposed by the FDA as the standard
method of in vivo UVA testing. UVA protection factor
is subsequently determined by the ratio of the minimal
pigmentation dose in sunscreen-protected skin to the
minimal pigmentation dose in unprotected skin, evalu-
ated between 3 and 24 h after the irradiation.2
Since UVA2 is the portion of UVA mostly repre-
sented in the PPD testing,13 the FDA proposed an
in vitro testing that provides a measure of UVA1 pro-
tection, specifically, the ratio of UVA1 absorbance to
total UV (290–400 nm) absorbance.
When discordances between in  vitro and in  vivo
test results occur, the final rating will be the lowest rat-
ing determined by either of these two methods. For
example, a product with an in vivo UVA-PF of 15 and
an in  vitro UVA1/UV ratio of 8 would be rated as a
three-star product.
FDA-approved organic UVA sunscreen drugs are
listed in Table  9.2. The FDA recently approved sun-
screen products containing ecamsule (terephtalydene
dicamphor sulfonic acid, Mexoryl SX™). There are at
least five ecamsule-containing sunscreen products in
the US market.
Oxybenzone (benzophenone-3, Bp-3), is a photo-
stable UVB and UVA2 filter; it is the most common
cause of photoallergic contact dermatitis from UV
Table  9.3  Grading system of the level of UVA protection
recommended by the FDA in the 2007 proposed amendment of
the 1999 sunscreen monograph
Star UVA-PF UVA1/UV Rating
None <2 <0.2 No UVA
protection
* 2 to <4 0.2–0.39 Low
** 4 to <8 0.4–0.69 Medium
*** 8 to <12 0.7–0.95 High
**** >12 >0.95 Highest
UVA ultraviolet A; FDA Food and Drug Administration; UV
ultraviolet; UVA-PF ultraviolet A protection factor
9  Photoprotection
filters.1 Avobenzone (butyl methoxydibenzoylmethane,
Parsol 1789™) is the best UVA1 sunscreen drug avail-
able in the United States; however, it is photolabile and
must be combined with photostable UVB sunscreen
drugs; in some products, nonultraviolet-filter stabiliz-
ers, such as diethylhexyl 2,6-naphtalate, are also used.1
Other broad-spectrum and intrinsically photostable
UVB and UVA sunscreen actives, currently unavailable
in the United States, include silatriazole (drometriazole
trisiloxane, Mexoryl XL™), bisoctrizole (methylene-bis-
benzotriazoyl tetramethylbutylphenol, Tinosorb M™),
and bemotrizinol (anizotriazine, bis-ethylhexyloxyphe-
nol methoxyphenol triazine, Tinosorb S™)11; the last two
are undergoing the FDA TEA approval process.1, 11
9.2.4 Inorganic Filters
Inorganic sunscreen drugs are photostable; they photo-
protect by reflecting or absorbing UV radiation,
depending on the particle size. They are less efficient
UV absorbers than organic UV filters. Thick coating is
required to achieve satisfactory degree of reflection.
Reducing the particle size considerably improves cos-
metic acceptability, but also results in less scattering of
visible light and shifts the protection toward shorter
wavelengths and toward absorbency function. Opaque
inorganic sunscreen actives may protect against visible
light-induced photosensitivity.
Microfine zinc oxide is a photostable sunscreen drug
that protects from the UVB to the UVA1 range. Microfine
titanium dioxide is a photostable sunscreen drug that is
conversely more protective in the UVB and UVA2 range.
Titanium dioxide has a higher refractive index and is
therefore whiter, despite a smaller particle size.1, 3
9.2.5 Contact, Photocontact,
and Phototoxic Reactions
to Sunscreen
Considering the widespread use of sunscreens, irritant
and allergic contact, photocontact allergic and photo-
toxic reactions to sunscreen are rare. Currently oxy-
benzone is the most common contact photoallergen,
replacing para-aminobenzoic acid (PABA), which is
85
not as frequently used anymore. The UVB filters
­methylbenziledene ­camphor, octinoxate and ensuli-
zole, padimate O, and UVA filters avobenzone and
sulizobenzone may only rarely induce contact allergic
and photoallergic reactions.1, 3
9.2.6 Controversies on Sunscreens
9.2.6.1 Compensation Hypothesis
The compensation hypothesis postulates that the use of
high SPF sunscreen may encourage longer exposure to
UV radiation, resulting in higher exposure to UVA
radiation. Therefore, sunscreens could theoretically
increase skin cancer susceptibility, especially mela-
noma.6 However, a systematic review by Dennis et al.14
that examined 18 heterogeneous case control studies
published from 1966 to 2003 found no association
between melanoma and sunscreen use.3, 14
9.2.6.2 Hormonal Effects
In vitro, Schlumpf et  al.15 demonstrated an increased
MCF-7 breast cancer cell proliferation after exposure
to five different UVB filters. In vivo, they also demon-
strated a dose dependent increase in uterine weight of
immature Long-Evans rats after oral administration of
two UVB filters, enzacamene and octinoxate. In addi-
tion, a dose-dependent increase in uterine weight in
immature hairless rats after dermal administration of
enzacamene was reported.15 Another study from the
same group by Ma et al. reported the in vitro antian-
drogenic activity of the sunscreen drugs oxybenzone
and homosalate in the human breast carcinoma cell
line MDA-kb2.16 Nakagawa and Suzuki reported the
estrogenic effect of some hydroxylated intermediates
of sulizobenzone in human breast cancer cells in vitro.17
It should be noted that the doses of sunscreen drug
products used were unrealistically high compared to
human exposure scenarios.1 Furthermore, a study by
Janjua et al.18reported no effects on reproductive hor-
mone levels in 32 volunteers after topical application
of oxybenzone, octinoxate, and enzacamene, daily for
5 days.18 The scientific committee of cosmetic prod-
ucts and nonfood products, a European Committee
based in Belgium, stated that the relative estrogenic
86
potencies of UV sunscreen products were about one
million less than estradiol, the positive control sub-
stance used in these studies.1
Therefore, while the reported estrogenic effect of
UV sunscreen actives is still not completely clear, it
most likely has no biologic relevance in otherwise
healthy human subjects.
9.2.7 Other Topical, Oral, and Dietary
Photoprotection Agents
These agents are listed in Table 9.4. Selected ones are
discussed below.
UVB can induce immunosuppression by generating
damage to DNA, directly via the formation of cyclobu-
tane pyrimidine dimers (CPD), or indirectly, via reac-
tive oxygen species formation. Photolyase, a DNA
repair enzyme has been shown to decrease the number
of UVB-induced dimers by 40–45% in human skin
when applied immediately after UVB exposure1 and
therefore, prevents immunosuppression, erythema, and
sunburn formation.19 T4 endonuclease V is a bacterial
DNA excision repair enzyme that repairs CPD in DNA.
Its liposome form used as topical treatment was shown
to remove dimers in DNA in the epidermis of animals
and human beings, and nearly completely prevented
UV-induced upregulation of IL-10 and tumor necrosis
factor-alpha messenger RNAs. Application of T4 endo-
nuclease V immediately after UV exposure partially
protects against sunburn cell formation, local suppres-
sion of contact hypersensitivity, and suppression of
delayed-type hypersensitivity and has minimal or no
effect on UV-induced skin edema.1 Topical application
of T4 endonuclease V for 1 year lowered the rate of
development of actinic keratoses and basal cell carci-
nomas in patients with xeroderma pigmentosum.1, 19
UV irradiation generates short DNA fragments dur-
ing the course of excision repair process. One small
single-stranded DNA fragment, thymidine dinucle-
otide, has been extensively studied. Thymidine dinu-
cleotides mimic cellular responses to UV radiation
including increased DNA repair, reversible cell growth
arrest, tumor necrosis factor-alpha expression and
secretion, induction of IL-10 expression, and enhanced
melanogenesis. Some of these effects are mediated
through activation of p53 and increased messenger
RNA levels for the responsible proteins. In human
C. L. Hexsel and H. W. Lim
fibroblasts, pretreatment with thymidine dinucleotide
enhances activation of p53 and p53-upregulated pro-
teins. Therefore, thymidine dinucletides may play a
role in photoprotection.
Antioxidants agents have been administered both
orally and topically for photoprotection. Topical anti-
oxidants are inefficient UV filters and have low SPF;
therefore, they are commonly used in combination
with sunscreens to enhance their efficacy. They are less
potent than sunscreens in preventing sunburn. The
limitations of topical antioxidants are the requirement
of compliance with application, difficulties with diffu-
sion into the epidermis, instability, and dose or con-
centration-dependent effectiveness. Commonly used
antioxidants in sunscreen products include vitamin E
and vitamin C.
Topical application of calcitriol (1,25-dihydroxyvi-
tamin D3, 1,25 hydroxyvitamin D), the active form of
vitamin D, has been reported to inhibit UVB-induced
sunburn cell formation in mice skin by inducing the
expression of metallothionein,1,20 a sulhydryl-rich pro-
tein that acts as a potent radical scavenger.
Green tea, consumed regularly by two-thirds of the
world’s population, contains four main polyphenolic
compounds, (-)-epicatechin (EC), (-)-epicatechin gal-
late (ECG), (-)-epigallotechin (EGC), and (-)-epigallo-
techin-3-gallate (EGCG). EGCG is considered the
main polyphenol responsible for the antioxidant
effects.21 Green tea polyphenols have absorption maxi-
mum at 273 nm, in the UVC range. These compounds
exhibit anti-inflammatory activity, causing inhibition
of UV radiation-induced skin erythema, edema, deple-
tion of the epidermal antioxidant defense system,
induction of epidermal cycloxygenase and ornithine
decarboxylase enzyme activities, immunosuppression,
a decrease in the number of sunburn cells, downregula-
tion of UVB-induced production of IL 10, increased
production of IL12, suppression of contact hypersensi-
tivity,21 and inhibition of phosphorilation of MAPKs
and NF-kB pathways.1 Effects on photocarcinogenesis
include a decrease tumor burden, inhibition on the for-
mation and size of malignant and nonmalignant tumors
and regression of these tumors in mice with established
tumors, enhanced UVB-induced increases in epider-
mal wild type p53, p21 and apoptotic sunburn. EGCG
has also been reported to inhibit UV-induced lipid per-
oxidation, to restore UV-induced decrease in glutathi-
one levels, to prevent CPD formation, to reduce
prostaglandin metabolites, particularly prostaglandin
9  Photoprotection 87

Table 9.4  Photoprotective agents other than sunscreens

Agent Photoprotective properties Source
T4 endonuclease V, Repair of cyclobutane pyrimidine dimer Bacterial DNA excision
Photolyase enzyme
Thymidine dinucleotide Enhancement of melanogenesis, increase of DNA repair Synthetic
Alpha tocopherol Reduction of erythema, sunburn cell formation, chronic UVB-induced Plants and vegetables,
(vitamin E) photodamage, photocarcinogenesis. Reduction in epidermal dietary supplements
Langerhans cell density and contact hypersensitivity
L-ascorbic acid Reduction of erythema, sunburn cell formation, UVB-induced Plants and vegetables,
(vitamin C) immunosuppression and contact hypersensitivity dietary supplements
Carotenoids Protective against squamous cell carcinoma, visible light-induced retinal Plants and vegetables,
damage and aged-related macular degeneration, reduction in dietary supplements
photosensitivity in patients with erythropoietic protoporphyria
Calcitriol Induction of metallothionein (scavenger of free radicals). Induction of Synthesized in kidneys
(1,25-dihydroxyvi- p53 protein expression, improved survival of keratinocytes post-UV after diet and sun
tamin D3) radiation, reduction in nitric oxide products, sunburn cells, cyclobu- exposure
tane pyrimidine dimers (CPD) formation
Zinc Antioxidant, reduction in sunburn cell formation, UVA1-induced early Diet and dietary
and delayed apoptosis of fibroblasts supplements
2-Furildioxime Iron chelator, reduction of erythema, sunburn cell formation, acanthosis, Synthetic
infiltration of inflammatory cells
Polyphenolic Antioxidant Green tea
compounds
Caffeine Enhancement of apoptosis, reduction in the formation of nonmalignant Plant
and malignant tumors and photodamage
Caffeic acid and Antioxidant and radial scavenging Plants and vegetables
ferulic acid
Genistein Protection against UV-induced inflammation and immunosuppression, Soybean, Greek oregano,
UV-induced carcinogenesis, photoaging, contact hypersensitivity Greek sage, ginko
biloba extract
Equol Protection against UV-induced inflammation and immunosuppression, Red clover
UV-induced carcinogenesis by induction of metallothionein
Flavonoid cocoa Protection against UV-induced inflammation, skin thickening, and Diet
epidermal water loss
Pomegranate extract Inhibits the phosphorilation of NF-kB and MAPK pathways, reduces Fruit extract
UV-induced inflammation, hyperplasia, hydrogen peroxide and CPD
formation
Cistus Free radical scavenging and inhibition of lipid peroxidation Mediterranean shrubs
Plant xyloglucans Prevention of UVB-induced systemic immunosuppression Tamarind seeds
Aloe plant poly/ Suppression of delayed-type and contact hypersensitivity Aloe barbadensis
oligosaccharide
Polypodium leucotomos Antioxidant and antiinflammation Plant extract
Omega-3 polyunsatu- Decrease of sunburn cell formation, inflammation, UVA provocation Fish oil
rated fatty acid response
N-acetylcysteine (NAC) Increase of glutathione level (endogenous antioxidant) Synthetic
88 C. L. Hexsel and H. W. Lim

E2, which plays a major role in skin tumor promotion. 9.2.9 Clothing

Effects of green tea polyphenols in photoaging include
the inhibition of UVB-induced expression of matrix
Clothing is an essential part of photoprotection not only
metalloproteinases and reduction of UVB-induced
for the general population, but also and especially for
collagen cross-linking.1
particular groups of the population such as children,
The plant extract Polypodium leucotomos does
employees exposed to artificial sources of UV radia-
not have significant absorption in either UVB or
tion, and those working outdoors and performing out-
UVA range. In humans and animal models, the plant
door recreational activities and hobbies4, 25 photosensitive
extract Polypodium leucotomos exhibits antioxidant
patients,25 and patients with risk factors for skin cancer.
and anti-inflammatory properties.1 Other proposed
UV protection factor (UPF) is the measurement of
effects include prevention of UV-induced photoi-
UV photoprotection of fabrics. UPF is measured
somerization of trans-urocanic acid,22 suppression of
in vitro with a spectrophotometer that determines the
the production of nitric oxide and induction of TNF
transmission of UVA and UVB through fabrics. This
alpha expression,23 and prevention of UV-induced
in vitro method was reported to be accurate and repro-
apoptosis in human keratinocytes and fibroblasts.24
ducible, particularly for samples with UPF below 50,1
After topical and oral administration, Polypodium
and appears to be the most suitable method for the
leucotomos was reported to increase the UV dose
evaluation of UPF.3
required for IPD, MED, minimal melanogenic dose
Recent advances in clothing photoprotection have
and minimal phototoxic dose. In humans, oral and
included specifically designed clothing with UPF, and
topical administration of Polypodium leucotomos
the development of regulation standards of photopro-
was shown to be photoprotective against psoralen-
tection by clothing, the first one being the Australian/
UVA-induced phototoxic reaction and pigmentary
New Zealand standard issued in July 1996. Subsequently,
and histological changes.
other standards have been developed, such as the United
Fish oil, which is rich in omega-3 polyunsaturated
Kingdom, the European and the United States. These
fatty acid, has been shown to decrease UVB-induced
standards usually address the minimum UPF and the
sunburn cell formation and inflammation and reduce
minimum recommended body coverage for photopro-
UVA provocation response. Due to the latter proper-
tection (e.g., trunk, upper arms).25
ties, it has been used for patients with polymorphous
Several factors affect the UPF of fabrics, and should
light eruption; however, relatively large amount of fish
be taken into account when using clothing as a photo-
oil needs to be ingested for such effect; therefore it is
protection method. These include the construction and
not widely used for the management of this condition.
the color of fabrics, hydration, washing and wearing,
N-acetylcysteine (NAC) is an agent that increases
chemical treatments, stretching, and distance of the
the levels of the endogenous antioxidant glutathione.
fabric from the skin.1, 25
Topical application of NAC before UVB exposure can
Clothing with tightly woven fibers (wool and syn-
protect against immunosuppression in mice. The
thetic materials such as polyester) and thick fibers have
mechanism of action is unclear. NAC has also been
higher UPF than loosely woven (cotton, linen, acetate,
reported to have antioxidant properties against UVA
and rayon) and thin fabrics. Typical summer cotton
cytotoxicity in human fibroblasts.1
T-shirts provide UPF of five to nine, and when wet, the
UPF decreases to only three to four. Denim provides
UPF of 1,700.
9.2.8 Shade When wet, changes in the UPF are variable due to
scattering and absorption properties of the fabrics. In
The sun protection provided by shade varies with general, hydration results in a decline in the UPF
diurnal variation of the angle of the sun and the because the presence of water in the interstices of the
amount of area or density of coverage provided.1, 6 fabrics enhances UV transmission. Conversely, the UPF
Shade alone reduces solar irradiation by 50–95% and frequently increases when the textile becomes wet in
is, therefore, an important adjuvant of other photopro- fabrics made of viscose or silk, or those that have been
tective measures.3 treated with broad-spectrum UV absorbers.1
9  Photoprotection
Washing shrinks and reduces the gaps between fibers.
UPF is also affected by chemical treatment of the fab-
rics with optical brightening agents and UV absorbers.
Optical brightening agents are compounds which that
absorb the energy and fluoresce at the visible light range,
leading to reduced UV transmission and the appearance
of being bright.1 White fabrics with an optical whitening
agent have slightly higher UPF than other pale-colored
fabrics.25 Dark-colored fabrics have greater UPF and
visible light absorption than light-colored fabrics.1
The laundry additive containing UV absorber
Tinosorb FD has been shown to result in significantly
increased UPF than fabrics exposed to regular washing.
The UPF decreases considerably when fabrics are
stretched. Unstretched Lycra (DuPont, Wilmington,
Del) may block 100% of UV radiation; on the other
hand, the UPF may decrease to two when stretched.
Another factor that affects the UPF of fabrics is the
distance of the fabric from the skin. The closer to the
skin, the lesser the photoprotection the fabric provides
because the smaller the distance is between the fabric
and the skin, the lesser the diffusion of the UV beam
reaching the skin.1
9.2.10 Hats
Hats can provide protection not only to the face and
neck, but are highly recommended for scalp protection
of individuals with alopecia or thin or short hairs.6
Photoprotection of hats depends on the brim width,
material, and weaving. A wide-brimmed hat (>7.5 cm)
has SPF 7 for nose, three for cheek, five for neck, and
two for chin. Medium-brimmed hats (2.5–7.5 cm) pro-
vide SPF 3 for nose, two for cheek and neck, and none
for chin, whereas narrow-brimmed hats provide SPF
1.5 for nose, and little protection for chin and neck.1
9.2.11 Makeup
Foundations containing UV filters with high SPF are
of great value and recommended for daily photopro-
tection. Foundation makeup without sunscreen pro-
vides SPF 3–4 due to its pigment content. This
photoprotective property and ability to create an even
89
cosmetic film on the skin surface lasts up to 4 h after
application; ­subsequent decrease in photoprotective
property is due to migration into the dermatoglyphs
and accumulation in the follicular ostia. The loss in
photoprotective property could occur in a shorter
period as a result of perspiration, tearing, sebum pro-
duction, and accidental removal. Thus, reapplication
at least every 2  h is recommended for patients who
rely on their facial foundation engaging in outdoor
activities.1
9.2.12 Sunless Tanning Agents
Dihydroxy acetone, the active ingredient of sunless tan-
ning preparations have an SPF of two, and has photo-
protective properties against UVA and the low end of
visible light for approximately 5–6 days.1, 3 It acts by an
oxidative effect that changes skin color to orange–
brown; the color binds chemically to the stratum cor-
neum and does not interfere with normal skin function.1
Dihydroxy acetone may provide some protection against
UVA and visible light induced photodermatosis.26
9.2.13 Sunglasses
Sunglasses should reduce glare and provide protection
against UV radiation. UV radiation is recognized to be
potentially hazardous to the structure of the eyes, pre-
dominantly the cornea, lens, and retina. The cornea
absorbs wavelengths below 295  nm, the crystalline
lens between 295 and 400 nm and the retina between
400 and 1,400 nm; thus visible and infrared light are
transmitted to the retina.
Sunglasses standards have been developed to ensure
quality, performance, and adequate protection to con-
sumers. Australia, Europe, and the United States have all
developed standards. While the Australian and European
standards are mandatory, the United States standard is
voluntary and not followed by all manufacturers.
Sunglasses have been classified in three categories:
cosmetic (which provide minimal UV protection),
general purpose (which reduce the glare of bright light)
and special purpose sunglasses (which are indicated
for specific activities such as skiing and going to the
90
beach). Furthermore, polarizing lenses reduce glare
but do not add UV-blocking properties. For general
purpose sunglasses, the United States standard (ANZI
Z80.3) requires less than 1% of the wavelengths below
310 nm to be transmitted.
For ideal photoprotection, sunglasses should wrap
around the eyes maximizing eye and eyelid protection,
since a significant amount of UV can reach unpro-
tected eyes. For added photoprotection, a wide-
brimmed hat is recommended to reduce the level of
radiation reaching the eyes.
Extensive and dark-tinted sunglasses can cause
pupillary dilatation and increase lid opening, thus
resulting in increased UV exposure to the lens of the
eye. Clear glasses absorb the vast majority of UVB
radiation but no UVA radiation, thus, for UVA protec-
tion a plastic film containing zinc, chrome, nickel or
other metals with broad spectrum UV coverage is rec-
ommended. There is no regulation regarding lens color;
in spite of this, the effect of the color should not inter-
fere with the ability to see color-coded signals, espe-
cially red and green traffic signals. Neutral gray and
amber brown are two popular colors that allow color
discrimination. Only visible light, not UV radiation, is
required for human vision. Therefore the ideal sun-
glasses should substantially reduce UV to cornea and
lens, including that from lateral directions. Additional
retinal protection can be accomplished with lenses that
reduce the transmission of short-wavelength violet/
blue light since this portion of visible light is consid-
ered to be hazardous to the retina.
9.2.14 Window Glass
In daily activity, considerable time is spent indoors and
in vehicles. Contemporary residential and commercial
architectural design increasingly incorporates more and
larger window areas. Nonetheless, exposure to UV radia-
tion through architectural window glass and automobile
glass is generally unappreciated. Recent developments in
the glass industry have resulted in window glass that pro-
vides broad UV protection without the historically asso-
ciated loss of visible light transmission. Factors affecting
the UV protective properties of glass are glass type, glass
color, interleave between glass and glass coating. In con-
trast, thickness of glass has limited effect on the proper-
ties of visible light and UV transmission.
C. L. Hexsel and H. W. Lim
Window glasses can have a single pane of glass
(monolithic glass); however, this type of glass was
largely replaced by insulating glass units, which com-
prise two or more panes of glass separated by a perim-
eter spacer to keep the glasses apart and sealed with
curable adhesive material to hold the pieces together.
While standard glass filters out UVB but not UVA,
visible light, and infrared radiation, several types of
glass are now available commercially in which the use
of additional filters for UVA and infrared radiation are
incorporated.
The interlayer is virtually invisible. It can filter 99%
of UV (up to 380 nm). It also reduces the transmission
of sound. Laminated glass is widely used in automo-
biles, airports, museums, schools, sound studios, and
large public spaces.
9.2.15 Automobile Glass
For safety reasons, all car windshields are made of
laminated glass, which is produced by binding two
pieces of glass together with a plastic interlayer; if bro-
ken, glass fragments will adhere to the interlayer rather
than fall free. Laminated glass blocks the vast portion
of UVA radiation. On the other hand, rear and side
windows are usually made from nonlaminated glass
that transmits a significant amount of UVA. Yet, it is
possible to add tints to rear and side windows to reduce
the transmission of UVA radiation, visible and infrared
light resulting in reduced unwanted heat gain and min-
imizing the fading of the interior components.
Photosensitive patients are advised to choose vehi-
cles with complete laminated window glass packages
or to apply a plastic film to nonlaminated rear and side
windows. Nevertheless, this does not substitute gen-
eral photoprotection measures such as sunscreen and
protective clothing use.5
9.3 Summary
Effective photoprotection measures should be under-
taken by all individuals to prevent transitory and per-
manent harmful effects of UV radiation. If possible,
sun exposure should be avoided during peak hours of
UV radiation (between 10 AM and 4 PM1 or when
one’s shadow is shorter than one’s height).4, 6 Since
9  Photoprotection
often sun avoidance during those hours is not possible
or practical, other effective photoprotection measures
should be undertaken. Sunscreens with broad spectrum
UVB and UVA coverage of minimum SPF 15, prefer-
ably 30, should be correctly applied at least every 2 h
and after swimming, perspiring, and towel drying. To
account for frequent inadequacy of application, sun-
screen should be first applied 15–30  min before sun
exposure followed by another application 15–30 min
later. Sunscreens do not completely block all UV radi-
ation, especially UVA. The use of physical barriers in
addition to sunscreen, such as shade, a wide-brimmed
hat, tightly woven or specifically designed protective
clothing, sunglasses and window glass is an essential
adjunctive method of photoprotection to sunscreen.
Children younger than 6 months of age should be
photoprotected mainly by physical measures. Oral
vitamin D supplementation is recommended for indi-
viduals at risk for vitamin D deficiency.1
References
  1. Kullavanijaya P, Lim HW. Photoprotection. J Am Acad
Dermatol. 2005;52:937-958; quiz 959–962
  2. Food and Drug Administration. 21 CFR Parts 347 and 352.
Sunscreen drug products for over-the-counter human use:
proposed amendment of final monograph; proposed rule.
Federal Register 2007;72:49070–49122
  3. Lautenschlager S, Wulf HC, Pittelkow MR. Photoprotection.
Lancet. 2007;370:528-537
  4. Palm MD, O’Donoghue MN. Update on photoprotection.
Dermatol Ther. 2007;20:360–376
  5. Tuchinda C, Srivannaboon S, Lim HW. Photoprotection by
window glass, automobile glass, and sunglasses. J Am Acad
Dermatol. 2006;54:845–854
  6. Eide MJ, Weinstock MA. Public health challenges in sun
protection. Dermatol Clin. 2006;24:119–124
  7. Food and Drug Administration. Sunscreen drug products for
over–the-counter human use; final monograph. Food and
Drug Administration, HHS. Final rule. Federal Register
1999;64: 27666–27693
  8. Rai R, Srinivas CR. Photoprotection. Indian J Dermatol
Venereol Leprol. 2007;73:73–79
  9. Green A, Williams G, Neale R, et al Daily sunscreen appli-
cation and betacarotene supplementation in prevention of
basal-cell and squamous-cell carcinomas of the skin: a ran-
domised controlled trial. Lancet. 1999;354:723–729
10. van der Pols JC, Williams GM, Pandeya N, et al Prolonged
prevention of squamous cell carcinoma of the skin by ­regular
91
sunscreen use. Cancer Epidemiol Biomark Prev. 2006;15:
2546–2548
11. Tuchinda C, Lim HW, Osterwalder U, Rougier A. Novel
emerging sunscreen technologies. Dermatol Clin. 2006;24:
105–117
12. The FDA approves new over-the-counter sunscreen. FDA
consumer 2006;40:4
13. Bissonnette R, Allas S, Moyal D, Provost N. Comparison of
UVA protection afforded by high sun protection factor sun-
screens. J Am Acad Dermatol. 2000;43:1036–1038
14. Dennis LK, Beane Freeman LE, VanBeek MJ. Sunscreen
use and the risk for melanoma: a quantitative review. Ann
Intern Med. 2003;139:966–978
15. Schlumpf M, Cotton B, Conscience M, et  al In vitro and
in vivo estrogenicity of UV screens. Environ Health Perspect.
2001;109:239–244
16. Ma R, Cotton B, Lichtensteiger W, Schlumpf M. UV filters
with antagonistic action at androgen receptors in the
MDA-kb2 cell transcriptional-activation assay. Toxicol Sci.
2003;74:43–50
17. Nakagawa Y, Suzuki T. Metabolism of 2-hydroxy-4-meth-
oxybenzophenone in isolated rat hepatocytes and xenoestro-
genic effects of its metabolites on MCF-7 human breast
cancer cells. Chem Biol Interact. 2002;139:115–128
18. Janjua NR, Mogensen B, Andersson AM, et  al Systemic
absorption of the sunscreens benzophenone-3, octyl-meth-
oxycinnamate, and 3-(4-methyl-benzylidene) camphor after
whole-body topical application and reproductive hormone
levels in humans. J Invest Dermatol. 2004;123:57–61
19. Verschooten L, Claerhout S, Van Laethem A, et al New strat-
egies of photoprotection. Photochem Photobiol. 2006;82:
1016–1023
20. Lee J, Youn JI. The photoprotective effect of 1, 25-dihy-
droxyvitamin D3 on ultraviolet light B-induced damage in
keratinocyte and its mechanism of action. J Dermatol Sci.
1998;18:11–18
21. Afaq F, Mukhtar H. Botanical antioxidants in the prevention
of photocarcinogenesis and photoaging. Exp Dermatol.
2006;15:678–684
22. Capote R, Alonso-Lebrero JL, Garcia F, et  al Polypodium
leucotomos extract inhibits trans-urocanic acid photoisomer-
ization and photodecomposition. J Photochem Photobiol.
2006;82:173–179
23. Janczyk A, Garcia-Lopez MA, Fernandez-Penas P, et al A
Polypodium leucotomos extract inhibits solar-simulated
radiation-induced TNF-alpha and iNOS expression, tran-
scriptional activation and apoptosis. Exp Dermatol. 2007;
16:823–829
24. Alonso-Lebrero JL, Dominguez-Jimenez C, Tejedor R, et al
Photoprotective properties of a hydrophilic extract of the fern
Polypodium leucotomos on human skin cells. J Photochem
Photobiol. 2003;70:31–37
25. Gies P. Photoprotection by clothing. Photodermatol Photo­
immunol Photomed. 2007;23:264–274
26. Deleo V. Sunscreen use in photodermatoses. Dermatol Clin.
2006;24:27–33
 Biologics
Panoglotis Mitropoulos and Robert A. Norman
Modern advances in our understanding of immuno-
logic processes, along with discoveries in disease
pathophysiology, have led to the development of inno-
vative therapeutic tools. In several fields of medicine,
biologic response modifiers, selective immunoregula-
tory drugs, or simply biologics are now being used in
the treatment of conditions for which either no other
effective therapies exist or the existing therapies pro-
vide substandard therapeutic results.
Biologic agents comprise a variety of medicinal
products already in use, such as vaccines, human cells
and tissues, recombinant therapeutic proteins, allergenic
products, blood components, and human gene therapy
products. The term biologics, however, is more com-
monly used to describe a class of medications produced
by means of biological processes involving recombi-
nant DNA technology. These are immunoregulators and
bioengineered proteins, such as fusion proteins, chi-
meric or fully humanized monoclonal antibodies, or
recombinant cytokines that directly interfere with the
pathological effects of T cells.
10.1 Indications
Currently, the only US Food and Drug Administration-
approved indication of biologics in dermatology is for
the treatment of psoriasis (Table 10.1).1–5
Nonetheless, the treatment potential of these medi-
cations has led to their off-label use for several other
conditions in dermatology. Some of these include
P. Mitropoulos (*)
Camp Long Troop Medical Clinic, South Korea
e-mail: panagiotis.mitropoulos@amedd.army.mil
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_10, © Springer-Verlag London Limited 2010
10
pemphigus vulgaris, paraneoplastic pemphigus, epi-
dermolysis bullosa acquisita, primary cutaneous B-cell
lymphoma, dermatomyositis, atopic dermatitis, chronic
urticaria, sarcoidosis, granuloma annulare, Sweet’s
syndrome, lupus erythematosus, and several other
granulomatous, autoimmune, inflammatory, and neu-
trophilic dermatoses.1
For psoriasis, biologics do not constitute first-line
treatment. Biologic therapy should be reserved for
moderate-to-severe plaque psoriasis, and in cases
where traditional treatments do not appear to be ade-
quate or are contraindicated. Current initial therapies
for psoriasis include topical agents (corticosteroids,
coal tar, anthralins, vitamin A and D derivatives) and
systemic agents (methotrexate, cyclosporine, retin-
oids) as well as phototherapy.
Biologic therapy may be reasonable for patients
who fall in two or more of the following categories:
• Age ³18 year old
• Chronic (³6 months) moderate/severe plaque
psoriasis
• Psoriasis-area severity index (PASI) score of ten or
more (or body surface area (BSA) of 10% or greater
if PASI score not applicable), and a dermatology
quality life index (DQLI) of less than ten
• Inadequate response or intolerance to standard
therapy
• Higher than average risk of developing clinically
important drug-related toxicity with the standard
treatments
• Significant coexistent unrelated morbidity (i.e.,
unstable congestive heart failure [CHF], liver dis-
ease) which precludes the use of systemic agents
like cyclosporine or methotrexate
• Disease requiring repeated inpatient management
for control
93
94 P. Mitropoulos and R. A. Norman

Table 10.1  Currently FDA approved biologics for treatment of psoriasis and psoriatic arthritsis1–5
Name Type Principal mechanism FDA approval
of action
Alefacept (Amevive®) Fusion protein/Immunoglobulin T-cell depletory Psoriasis
G1 (IgG1)
Etarnecept (Enbrel®) Fusion protein/Soluble tumor TNF-a antagonist Psoriasis, psoriatic
necrosis factor-alpha arthritis
(TNF-a) receptor
Infliximab (Remicade®) Chimeric monoclonal TNF-a antagonist Psoriasis, psoriatic
antibody arthritis
Adalimumab (Humira®) Fully humanized TNF-a antagonist Psoriasis, psoriatic
monoclonal antibody arthritis
Ustekinumab (Stelara) Chimeric monoclonal Human monoclonal antibody Psoriasis, psoriatic
antibody targets the activity of cytokines arthritis
interleukin-12 (IL-12) and
interleukin-23 (IL-23)

• Patient not receiving any immunosuppressive medi- Table  10.2  Administration and dosing of biologics for the
cations except those used for the treatment of treatment of psoriasis
Drug Route of Recommended
psoriasis
administration dosage
• Presence of psoriatic arthritis
Alefacept Intramuscular or IM: 15 mg injection once
(Amevive®) Intravenous a week for 12 weeks

IV: 7 5 mg bolus once a

10.2 Dosage and Administration week for 12 weeks

Etarnecept Subcutaneous Twice a week 50 mg

(Enbrel®) (SC) injection for 3
There are two methods of administration for the bio- months; then once a
logic agents currently used in dermatology (Table 10.2), week for maintenance
subcutaneous (SC) or intravenous (IV). Since these Infliximab Intravenous Initially: Infusion (over
medications are composed of relatively large molecules, (Remicade®) 2–3 h) 5 mg/kg on
parenteral administration, rather than oral, ensures bet- weeks 0, 2, and 6;
ter absorption and bioavailability. then one infusion
every 8 weeks for
Following appropriate education and demonstration maintenance
from their physician, patients may choose to self-inject
Adalimumab SC Initial dose of 80 mg;
themselves at home subcutaneously according to their
(Humira®) then 40 mg once
recommended dosing regimen. Intravenous adminis- bi-weekly starting a
tration should be completed at a clinic or other medical week after initial dose
environment under the supervision of a physician. Ustekinumab SC 45 mg (for pts < 200 lbs)
(Stelara) at week 0, 4 & q 12
weeks
90 mg (for pts > 200) at
week 0, 4 & q 12
10.3 Side Effects weeks

The side effects of biologic medications vary. The

most frequently reported event with all biologics is asthenia, myalgia, or arthralgia. Typically, these symp-
skin irritation at the site of injection. Other common toms are mild and transient. They are most likely to
adverse reactions may include flu-like symptoms, occur after the first two initial treatments and generally
headache, dizziness, chills, low-grade fever, nausea, do not recur with subsequent doses.
10  Biologics
Overall, biologics are well-tolerated and contrary
to the conventional systemic antipsoriatic agents (meth-
otrexate, cyclosporine) they have a limited organ-toxic-
ity profile. Biologics are being used successfully in
patients with renal insufficiency or hepatic dysfunction;
when indicated they may be preferable to the aforemen-
tioned traditional systemic psoriasis treatments. The
most serious side effects of biologic therapy are related
to their immunosuppressive and immunoregulatory
properties.
10.3.1 Infections
There is an increased risk of reactivation of latent
infections or emergence of new infections associated
with tumor necrosing factor (TNF)-a (alpha) inhibi-
tion. All the biologics currently used in dermatology
contribute to immunosuppression via their depleting or
modulation effect on B cells, T-cells, cytokines, or
other molecules of the body’s immune mechanism.
Upon infection, TNF-a (alpha) plays a key role in the
recruitment of defense cells to the site of infection, and
in the formation and maintenance of granulomas.
Tuberculosis (TB) and other serious opportunistic
infections, including histoplasmosis, listeriosis, asper-
gillosis, toxoplasmosis, coccidioidomycosis, candidi-
asis, cutaneous Nocardia, and pneumocystosis, have
been reported in both clinical research and postmark-
ing surveillance settings.6–8 Physicians must be cau-
tious when prescribing biologics to patients who reside
in geographical areas where the aforementioned dis-
eases may be endemic. Additionally, the risk for oppor-
tunistic infections increases further more in patients
who are receiving one or more immunosuppressant
agents, or are HIV positive.
10.3.2 Neurological Disease
Development or worsening of nervous system disor-
ders, including demyelinating diseases such as multi-
ple sclerosis, transverse myelitis, seizures, Parkinson’s
disease, and optic neuritis, has been documented
in patients who were receiving treatment with biolog-
ics.8,9 It is suggested that biologic agents be withheld
95
from patients who have a history of, or a first degree
relative with, a demyelinating disease.
10.3.3 Cardiovascular Disease
Higher incidence of mortality and hospitalization for
worsening heart failure has been documented in
patients with moderate-to-severe CHF (New York
Heart Association classes III or IV) who were being
treated with TNF-a (alpha) antagonists and, specifi-
cally, infliximab, and etarnecept.3,8 Caution should be
used when using TNF inhibitors in patients with unsta-
ble cardiac dysfunction.
10.3.4 Hepatitis/Hepatic Dysfunction
Several clinical studies have demonstrated evidence of
hepatic enzymes elevation with use of all of the bio-
logic medications.6,10 These abnormalities are thought
to be confounded by comorbid conditions and concom-
itant use of medications, as nonsteroidal anti-inflamma-
tory drugs (NSAIDs), methotrexate, or cyclosporine
have also been associated with hepatic dysfunction.
Autoimmune hepatitis and liver damage is a rare
but increasingly recognized serious complication of
treatment with the TNF-a (alpha) blocking agent, inf-
liximab. It is noteworthy that a number of cases of
liver failure resulting in liver transplantation or death
have been reported in patients receiving infliximab.11–13
Signs of severe hepatic reaction may include jaundice,
cholestasis, and marked elevation (more than 5 times
the upper limit of normal) in liver enzymes. The rest
of the biologic medications used in the treatment of
psoriasis have more favorable hepatic dysfunction
profile which mainly involves a mild increase in liver
enzymes.
Some reports are emerging regarding fulminant
hepatic failure in patients with chronic hepatitis B
virus (HBV) infection. HBV reactivation has been
reported very rarely in patients with chronic hepatitis
B infection receiving a biologic medication.3, 8, 14 This
is why serologic screening for viral hepatitis (HBV
and hepatitis C virus) is recommended prior to initia-
tion of therapy with biologics. For patients who are
96 P. Mitropoulos and R. A. Norman

hepatitis B surface antigen (HBsAg)-positive, prophy- described. Leucopenia and thrombocytopenia, although
laxis with lamivudine or other antiviral agent should not common, are recognized side effects of TNF-
be considered. Roux and colleagues evaluated the blocking therapy.3,18 The exact mechanism of cytope-
safety of TNF inhibitors in patients with concurrent nias as a result of TNF-block therapy is still unclear.
chronic viral hepatitis.15 Their retrospective study
demonstrated that TNF inhibitors can be given safely
in patients with chronic hepatitis B who were receiv-
ing lamivudine, and no changes were seen in their 10.3.7 Malignancy
serum aminotransferase levels.
The risk for developing malignancies (non-Hodgkin
lymphoma, melanoma, and nonmelanoma skin cancer)
10.3.5 Occurrence of Autoantibodies while under therapy with biologic medications has
and Autoimmunity been investigated. However, no compelling evidence
exists that biologics are directly related to an increase
in the rate of malignancies.3,19 Specifically, in patients
The development of antibodies (human antichimeric
with psoriasis, no clear findings identify whether lym-
antibodies, antinuclear antibodies, antidouble stranded
phoma risk is associated with disease severity, treat-
DNA antibodies, anticardiolipin, antiphospholipid
ment, other unidentified factors, or a combination of
antibodies) and autoimmune disorders has been asso-
factors.20
ciated with TNF-a (alpha) antagonism treatment.7
Patients who have been exposed to more than 1,000 J
TNF-a (alpha) instigates its immunosuppressive
cumulative dosage of psoralen and UVA (PUVA) (more
effect by regulating antigen-presenting cell functions
than 200 treatments) may be at increased risk for cuta-
and apoptosis of potentially autoreactive T cells.
neous malignancies.21 The risk is greatest for squamous
Therefore, antagonizing TNF and its suppressive effects
cell carcinomas, but melanoma is not excluded.
may lead to the development or unmasking of autoim-
Nonmelanoma skin cancer is not an absolute contrain-
mune diseases. There are reports of lupus-associated
dication to biologic therapy. Nevertheless, because
antibodies occurring after administration of biologics.7
these patients represent a particular, high-risk group,
Patients may develop positivity for antinuclear antibod-
caution is warranted when considering biologics.
ies (ANAs), antihistone, and anti-DNA. However, no
The known excess of malignancies in immunosup-
evidence exists that patients who develop new autoanti-
pressed populations, and the known immunosuppres-
bodies are at significantly increased risk of developing
sive effects of the biologic agents do, however, provide
lupus-like syndrome or lupus erythematosus.6, 7, 16
a biologic basis for concern and justification for the
Although progressive reduction in ANA titers takes
initiation of additional epidemiologic studies to con-
place after discontinuation of treatment the majority of
firm a clear association. Meanwhile, current practice
patients will remain ANA-positive.17 Furthermore, for-
recommendation should probably not go any further
mation of antibodies against the biologic drug itself is an
than awareness that certain malignancies have been
emerging issue. Autoantibodies formation and autoim-
associated with biologics, and alertness for any suspi-
munity appears to be more commonly associated with
cious symptoms should be maintained.
infliximab therapy, than treatment with etarnecept, and
only limited reports exist for adalimumab.7,11,13 Whether
these antibodies attenuate the efficacy of the treatment
or whether they have no measurable effect on the activ- 10.3.8 Anaphylaxis/Allergic Reactions
ity of the agent has yet to be determined.
Formation of antibodies against the biologic drug itself
has been reported. More specifically, antibodies against
10.3.6 Blood Disorders infliximab have been associated with immediate
as  well as delayed hypersensitivity reactions.7,8,22
Rare reports of patients developing pancytopenia and Symptoms may range from mild urticaria and pruritus
aplastic anemia on infliximab and etarnecept have been to more severe anaphylaxis, hypotension, and shock. A
10  Biologics
reaction may develop during or within 2  h of inflix-
imab infusion, and it is most likely to occur during the
first and second infusion. Reinstitution of infliximab
after a prolonged period without treatment (more than
16 weeks) can cause a delayed hypersensitivity or
serum-like sickness reaction. Symptoms of delayed
reaction may include muscle or joint pain with fever or
rash, itching, swelling of the hands, lips or face, diffi-
culty swallowing, nettle-type rash, sore throat, and
headache. There has been promising success in
decreasing the risk of infusion reactions with daily low
dose of corticosteroids.22,23 In addition, diphenhy-
dramine 25–50 mg IV 1.5 h prior to infusion is com-
monly practiced. All patients receiving infliximab
infusions must be medically observed for 1–2  h fol-
lowing the infusion in case a reaction develops.
Individuals who are sensitive to latex should be
careful not to handle the rubber cover in the single pre-
filled autoinjectors of adalimumab (Humira) and etar-
necept (Enbrel).4,24
10.3.9 Pregnancy/Breast-Feeding
All the biologic medications currently in use in derma-
tology are pregnancy category B (no human studies
conducted, but no adverse effects have been noted in
animal studies). An exception to this is efalizumab
which has been labeled category C (animal reproduc-
tion studies have shown an adverse effect on the fetus
and there are no adequate and well-controlled studies
in humans). Since no human data is available, initia-
tion of biologic therapy should be avoided in women
who are pregnant, planning for pregnancy, or currently
breast-feeding. For women of reproductive age, effi-
cient contraception methods should be suggested and
implemented prior to therapy.
10.4 Treatment Risk Reduction
Strategies
Not all patients are suitable candidates for treatment
with a biologic agent. Appropriate patient selection is
key in order to achieve treatment success and avert
potential unfavorable outcomes. A thorough physical
97
examination and detailed personal and family medical
history should be an essential part of all patient encoun-
ters. Even for a patient with a “clean bill of health,” the
physician should offer the option of treatment with
biologics to those patients who they feel will be com-
pliant with the dosing schedule and with follow-up vis-
its, and will comprehend how to self-assess and report
the onset of signs or symptoms that may signal the
onset of an adverse event.
10.4.1 Treatment Exclusion Criteria
Biologics are generally not indicated for patients who
meet one or more of the following criteria:
• Active TB
• Moderate to severe CHF
• History of demyelinating disease or optic neuritis
• Hepatitis B or C positivity
• HIV positivity
• Active infections (i.e., chronic leg ulcers, persistent
or recurring chest infections, indwelling urinary
catheter)
• Septic arthritis or sepsis of prosthetic joint within
last 12 months
• Pregnancy, planning to become pregnant, or cur-
rently breast-feeding
• Premalignant states
• Patients who have had extensive immunosuppres-
sant therapy or prolonged PUVA treatment
10.4.2 Baseline Screening Tests
Specific, guidelines regarding objective screening and
monitoring prior to and during treatment with biolog-
ics have not been established. In accordance with good
clinical practice, baseline and follow-up laboratory
tests and imaging studies ought to be offered to all
patients when considering therapy with a biologic
agent. Initial laboratory testing and subsequent moni-
toring should be determined on an individual basis
according to patient, region of practice, and medica-
tion to be utilized.
The United States FDA only mandates TB testing
prior to initiating treatment with adalimumab and
98 P. Mitropoulos and R. A. Norman

infliximab. However, because of the increased risk of 10.4.3.1 Physical Examination

granulomatous disease with all immunoregulatory
medications it is prudent to offer TB screening (tuber-
culin purified protein derivative [PPD] and/or a chest
X-ray) to all patients who are being considered for treat-
ment. Table 10.3 lists the current FDA-mandated labo-
ratory and imaging testing according to biologic agent.
A number of patients may already be receiving med-
ications for the same or different medical condition. A
psoriasis patient may already be on an immunosuppres-
sant medication, such as methotrexate. In this case, if
biologic therapy is considered, a stricter monitoring
strategy may be implemented. The recommended base-
line studies shown in Table  10.3 may be used as a
guideline. Ultimately, it should be each patient’s medi-
cal history, family history, social history, physical
examination, and individualized risk assessment that
directs the appropriate screening and monitoring.
10.4.3 Periodic Monitoring
Close, routine follow-up physical examination and
laboratory testing, although not FDA-mandated, are
reasonable in order to evaluate the safety of the bio-
logic drug the patient is receiving along with its thera-
peutic efficacy.
Patient health status should be monitored regularly and
any changes or pertinent positives in the review of sys-
tems need to be identified and addressed promptly,
with special attention to:
• Symptoms and signs of infection
• Symptoms and signs of CHF
• Symptoms and signs of demyelinating disease
10.4.3.2 Laboratory Tests
Many patients do well and feel fine while on biologics
and may not see the need for frequent follow-up visits
and tests. Regular reevaluation, however, is strongly
recommended as biologics are not benign medications.
Monthly evaluations are prudent during the initial
months of treatment. If the progression of treatment is
satisfactory then patient and physician may agree to
decrease frequency of follow-up to every 3 months
and, subsequently, to every 6 months. At a minimum,
monitoring tests should include:
• Complete blood count (CBC)
• Liver function tests (LFT)
• Renal function tests (RFT)

Table 10.3  Guidelines for screening and monitoring studies according to biologic agent
Drug FDA required
Alefacept (Amevive®) Baseline CD4 level; monitor
biweekly. Withhold treatment
for at least 1 month if
CD4 < 250 cells/mL
Etarnecept (Enbrel®) None mandated
Infliximab (Remicade®) PPD and/or Chest X-ray for latent
TB screening
Adalimumab (Humira®) PPD and/or Chest X-ray for latent
TB screening
Ustekinumab (Stelara) PPD and/or Chest X-ray for latent
TB screening
Recommended (non-FDA-man- Recommended
dated) baseline screening (non-FDA-mandated)
periodic monitoring
PPD/Chest X-ray, complete blood CBC, LFT, RFT, and
count (CBC) with differential, clinical evaluation
liver function tests (LFT), renal every 6 months
function tests (RFT), b-hcg, HIV
PPD/Chest X-ray, RFT, LFT,
Hepatitis B and C serology,
b-hcg, HIV
CBC, RFT, LFT, Hepatitis B and C
serology, b-hcg, HIV
CBC, RFT, LFT, Hepatitis B and C
serology, b-hcg, HIV
CBC, RFT, LFT, Hepatitis B and C CBC, LFT, RFT, and
serology, b-hcg, HIV clinical evaluation
every 6 months
10  Biologics 99

10.4.4 Tuberculosis Risk • Measles, mumps, and rubella (MMR)

Before initiating biologic therapy, all patients must have
their TB risk assessed.25 This should include a history of
any prior TB infection and treatment, BCG (bacillus
Calmette Guérin) vaccination, a thorough clinical exam-
ination, and a chest X-ray. The chest X-ray needs to be
taken as close as possible to the planned start date of the
biologic therapy.25 A PPD test is advised. However, one
should keep in mind that the accuracy and reliability of
the tuberculin skin test is significantly affected by immu-
nosuppressive therapy. If the patient is currently on
immunosuppressive medications, such as methotrexate
or cyclosporine, the PPD test should be regarded as
unreliable. The same holds true for patients who have
stopped immunosuppressive therapy for a period of less
than 3 months from the test.
Referral to a pulmonologist or TB specialist is war-
ranted for individuals with a positive PPD, abnormal
chest X-ray, or history of TB infection.25 If the patient
is found to have active TB infection or have had inad-
equate treatment of past infection, then appropriate TB
treatment should be commenced. Initiating biologic
therapy in this case is contraindicated.
If the patient is found to have had adequate treat-
ment of a previous TB infection, then biologic therapy
may be initiated. However, a repeat chest X-ray 3
month after the initiation of therapy should be acquired
to help rule out TB reoccurrence.25
For patients with normal chest X-ray, negative PPD
(less than 5  mm induration), and no history of TB,
therapy with biologic medications may be initiated.
• BCG
• Poliomyelitis (oral Sabin vaccine)
• Yellow fever
• Typhoid (oral)
• Varicella (Varivax)
• Zoster (Zostavax)
• Smallpox (Vaccinia)
If for any reason a patient requires a live vaccination
while on therapy with a biologic agent, it would be
prudent that therapy be stopped at least 2 weeks prior
to immunization and, ideally, not be resumed until at
least 4 weeks after.
10.4.6 Withdrawal of Therapy
As with any medication, treatment should be promptly
withdrawn in the event of an adverse event. According
to the circumstances, withdrawal may be temporary or
permanent. Table 10.4 lists some of the reasons ther-
apy with a biologic medication should be interrupted:
• If a patient develops lupus-like symptoms, blood
tests for antinuclear antibodies and antidouble-
stranded DNA antibodies should be repeated before
considering any further treatment.
• If disease response is unsatisfactory after 3–6
months of treatment, switching to a different bio-
logic agent may be appropriate. Failure of one agent
to produce results does not equate failure of the
medication class as a whole.26
• A high index of suspicion for infection should be
kept at all times and appropriate screening should
be undertaken if required.

10.4.5 Vaccinations Table 10.4  Indications for withdrawal of biologic therapy

Permanent withdrawal Temporary withdrawal of
Seasonal influenza vaccine is not mandated but recom- of treatment treatment
mended and commonly administered to patients who Malignancy
are being treated with biologics. The exception to this Severe drug-related
is the intranasal FluMist vaccine which is a live, atten- toxicity
uated influenza virus vaccination product and its Drug-associated allergic Pregnancy
administration to patients who are on immunosuppres- reaction
sants, including biologics, is contraindicated.5
Neurological symptoms Need for surgical procedure
Several other live, attenuated vaccines currently licensed
for use and distribution in several countries, including the Congestive heart failure Severe intercurrent infection
(CHF)
United States are also contraindicated in patients who
are receiving biologic therapy. These include: Lupus-like symptoms
100
• Patient should be educated to promptly report any
neurologic events including visual changes.
• Therapy should be discontinued 2–4 weeks prior to
any major surgical procedure and not resume until
at least 4 weeks after.
• Effective contraception in women of reproductive
age and avoidance of breast-feeding while on bio-
logics is warranted.
10.5 Combination Therapy/
Concomitant Medications
Hepatotoxicity and nephrotoxicity have been associ-
ated with the most commonly used systemic psoriasis
treatment agents, methotrexate and cyclosporine.
Combining these traditional agents with biologic ther-
apy may achieve not only improved therapeutic efficacy
but also a decrease in the risk of end organ toxicity. The
concern of combination therapy leading to increased
immunosuppression and its consequences has been
addressed. However, there are a number of case reports
in literature of successful use of biologic agents concur-
rently with methotrexate. Additionally, phototherapy is
generally considered safe to implement concomitantly
with biologic agents.
To date, no long-term clinical studies on quantify-
ing risks and benefits of combination therapy exist,
and therefore combination therapy should only be cau-
tiously recommended. As our knowledge and experi-
ence with this class of medication increases, the
intricacies and potential of combination therapy will
continue to be refined.
10.6 Pediatrics
Treatment of psoriasis in children is challenging. Trials
of biologic agents for managing psoriasis in children are
being conducted but information is currently limited
and the long-term safety profile still being evaluated. To
date, none of the biologics in use in dermatology are
FDA-approved for treating psoriasis in individuals less
than 18 years of age.
Etarnecept has been approved for treatment of juvenile
rheumatoid arthritis (JRA) for children as young as 4
years of age. Both psoriasis and rheumatoid arthritis share
P. Mitropoulos and R. A. Norman
similarities in their pathogenesis at the molecular level.
The fact that a biologic agent has succeeded in studies and
gained approval for use in children with JRA foreshad-
ows potential future approval for the use of these agents
in children with psoriasis and/or psoriatic arthritis.
10.7 Elderly
The elderly (65 years of age or older) take more medica-
tions (prescription and nonprescription) than any other
age group. The risk of side effects and drug–drug inter-
action increases proportionally with the number of med-
ications. Additionally, the more medications a patient is
asked to take the higher the risk of nonadherence. One
should also keep in mind that as the body ages the phar-
macokinetics and pharmacodynamics of drugs are also
altered. However, there are no studies to date that indi-
cate any differences in the safety or efficacy of biologic
agents between older and younger patients.
Certain additional practical considerations should
be implemented prior to initiating biologic therapy to
treat psoriasis in an older individual:
• Obtain complete medication history that includes pre-
scription, nonprescription, and herbs. Patient should
be instructed to bring medications in at every visit.
• Discontinue any medications if the benefit is mar-
ginal or if a nonpharmacologic alternative exists.
• Be sure the patient understands how to take the
medication. If necessary write and provide clear
instructions for the patient and anyone who is assist-
ing in treatment.
• Be sure the patient understands the potential risks
and side effects of each drug taken.
• In-home support and supervision should be
encouraged.
• Because of the increased risk of infections in
the  elderly a higher suspicion index should be
maintained.
• Consider the cost of the drug.
Safe medication use in the elderly requires vigilance and
awareness from everyone involved in the patient’s treat-
ment. Everyone should be alert for any subtle changes
that may signal a potential adverse event. It is especially
important to keep track of all maintenance drugs and
ensure they are taken properly. The patient must
10  Biologics
u­ nderstand and feel comfortable in directing all medical
questions and concerns promptly to their physician.
References
  1. Alexis AF, Strober BE. Off-label dermatologic uses of anti-
TNF-a therapies. J Cutan Med Surg. 2005;9:296–302
  2. Biogen Inc. Amevive (alefacept), package insert. 2008
  3. Desai SB, Furst DE. Problems encountered during anti-
tumour necrosis factor therapy. Best Pract Res Clin
Rheumatol. 2006;20(4):757–790
  4. Immunex Corporation. Enbrel (etarnecept), package insert.
2008
  5. National Psoriasis Foundation. Flu vaccines warranted
for psoriasis patients. 2004. At: www.psoriasis.org; 2008
Accessed 15.01.08
  6. Jackson Mark J. TNF-a inhibitors. Dermatol Ther. 2007;
20(4):251–264
  7. Rott S, Mrowietz U. Recent developments in the use of bio-
logics in psoriasis and autoimmune disorders. The role of
antibodies. BMJ. 2005;330:716–720
  8. Tandon VR, Mahajan A, Khajuria V, Kapoor V. Biologics
and challenges ahead for the physician. Indian Acad Clin
Med. 2006;7(4):334–343
  9. Robinson WH, Genovese MC, Moreland LW. Demyelinating
and neurological events reported in association with tumor
necrosis factor alpha antagonism: by what mechanisms
could tumor necrosis alpha antagonists improve rheumatoid
arthritis but exacerbate multiple sclerosis. Arthritis Rheum.
2001;44:1977–1983
10. Suissa S, Ernst P, Hudson M, et al Newer disease modifying
antirheumatic drugs and the risk of serious hepatic adverse
events in patients with rheumatoid arthritis. Am J Med.
2004;117(2):87–92
11. Centocor. Remicade (infliximab), package insert. 2007
12. Tobon GJ, Cañas C, Jaller JJ, et  al Serious liver disease
induced by infliximab. Clin Rheumatol. 2007;26(4):578–581
13. United States Food and Drug Administration. Safety alerts
for drugs, biologics medical devices, and dietary supple-
ments. Remicade (infliximab). Washington, DC: FDA, 2004.
At: http://www.fda.gov/medwatch/SAFETY/2004/safety04.
htm#Remicade2; 2008 Accessed 2.02.08
101
14. Thiele DL. Is anti-TNF therapy safe in patients with rheu-
matic disease who also have concurrent B or C chronic hepa-
titis? Nat Clin Pract Rheumatol. 2007;3:130–131
15. Roux CH, Brocq O, Breuil V, et  al Safety of anti-TNF-a
therapy in rheumatoid arthritis and spondylarthropathies
with concurrent B or C chronic hepatitis. Rheumatology.
2006;45(10):1294–1297
16. Eriksson C, Engstrand S, Sunddqvist KG, Rantapaa-
Dahlqvist S. Autoantibody formation in patients with rheu-
matoid arthritis treated with anti-TNF alpha. Ann Rheum
Dis. 2005;64:403–407
17. Vermeire S, Noman M, Van Assche G, et al Autoimmunity
associated with anti-tumor necrosis factor alpha treatment in
Crohn’s disease: a prospective cohort study. Gastroenterology.
2003;125(1):32–39
18. Pathare SK, Heycock C, Hamilton J. TNFa blocker-induced
thrombocytopenia. Rheumatology. 2006;45(10):1313–1314
19. Wolfe F, Michaud K. The effect of methotrexate and
­anti-tumor necrosis factor therapy on the risk of lymphoma
in rheumatoid arthritis in 19, 562 patients during 89, 710
person-years of observation. Arthritis Rheum. 2007;56:
1433–1439
20. Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ.
Lymphoma rates are low but increased in patients with pso-
riasis: results from a population-based cohort study in the
United Kingdom. Arch Dermatol. 2003;139(11):1425–1429
21. Lindelöf B, Sigurgeirsson B, Tegner E, et al. PUVA and can-
cer: a large-scale epidemiological study. Lancet. 1991;338
(8759):91–93
22. Baert F, De Vos M, Louis M, et al. Immunogenicity of inflix-
imab: how to handle the problem? Acta Gastroenterol Belg.
2007;70(2):163–170
23. Augustsson J, Eksborg S, Ernestam S, et al Low-dose gluco-
corticoid therapy decreases risk for treatment-limiting infu-
sion reaction to infliximab in patients with rheumatoid
arthritis. Ann Rheum Dis. 2007;66:1462–1466
24. Abbot Laboratories. Humira (adalimumab), package insert.
2008
25. Ledingham J, Wilkinson C, Deighton C. British thoracic
society (BTS) recommendations for assessing risk and man-
aging tuberculosis in patients due to start anti-TNF-a treat-
ments. Rheumatology. 2005;44(10):1205–1206
26. Menter A, Hamilton TK, Toth DP, et al Transitioning patients
from efalizumab to alternate psoriasis therapies: findings
from an open-label, multicenter, Phase IIIb study. Int J
Dermatol. 2007;46(6):637–648
 Occupational Dermatology
11
Athena Theodosatos and Robert Haight

11.1 Introduction friction, electricity, and ionizing radiation can, under

some circumstances, be occupational. Water can even
cause skin lesions under the right conditions. Toxins
Occupational medicine specializes in treating patients
and infectious agents are found in some workplaces.
with injuries and illnesses from exposures in the work-
The classic occupational skin diseases were chloracne
place. People often encounter very harsh environments
and chrome ulcers. Those diseases are rare in the
in the workplace. Although today’s workplace in gen-
developed world today. Less acute skin lesions such as
eral is considerably tamer than that of the past, skin
hyperpigmentation, leukoderma, alopecia, and licheni-
problems remain a serious issue.1
fication can be occupational.1–3 Other dermatoses are
The bureau of labor statistics (BLS) calculates the
the major differential to consider when evaluating
frequency of work-related injuries and illnesses for
occupational skin disorders. Any nondermatologist
private industry. According to BLS, skin diseases
who deals with occupational skin lesions must be able
accounted for 15.6% of the nonfatal illnesses in private
to differentiate them from dermatitis and the other
industry in 2004.2 This is hardly insignificant. Many
common nonwork-related diagnoses. This means that
occupational medicine physicians rarely see skin dis-
the physician needs to be able recognize and under-
orders. This might be because occupational skin prob-
stand them.
lems are from specific exposures which are associated
with specific industries. These industries do not have a
uniform geographic distribution.2

11.2.1 Relevant History

11.2 Diagnosis Occupational skin disorders require a detailed history

Occupational dermatology includes a broad spectrum
of disorders but the majority are acute and chronic
contact dermatitis. The most commonly cited are irri-
tant contact dermatitis and allergic contact dermatitis.
Since sunlight can be an occupational exposure, skin
disorders caused by the sun can therefore be consid-
ered work-related for some jobs. Likewise, skin inju-
ries from other physical agents like hot, cold, pressure,
A. Theodosatos (*)
Department of Family Medicine, Florida Hospital,
Winter Park, FL, USA
e-mail: athenatheo@hotmail.com
of the skin findings and a work history. The basic ques-
tions to consider when evaluating an occupational skin
disorder include:
• What does the patient do for a living?
• How long has the patient been doing this job? (the
position)
• What is the patient exposed to at work? (Chemicals?
Physical agents?)
• What personal protective equipment does the patient
use at work?
• Has there been any change to any of the processes
at work?
• Do other people at work have similar skin conditions?
• What is the patient exposed to outside of work?

R. A. Norman (ed.), Preventive Dermatology, 103

DOI: 10.1007/978-1-84996-021-2_11, © Springer-Verlag London Limited 2010
104
• Has the patient had a work-related skin disorder in
the past?
• Has the patient had any exposure-related skin
disorders?
• Does the patient have any nonwork-related skin
disorders?
• Does the patient have any chronic medical conditions?
• Does the patient have any allergies or a history of
atopy?
• Does the patient take any medications?
Material safety data sheet (MSDS) is a brief description
of a chemicals physical properties and health effects.1, 2
Data that should be included are: chemical identity; haz-
ardous ingredients; physical and chemical characteris-
tics; fire and exposure hazard data; reactivity data; health
hazards; precautions for safe handling and use; and con-
trol measures. Although the Hazardous Communication
Standard (29 CFR 1910.1200) requires employers to
have an MSDS on all of the chemicals to which workers
might be exposed, they may be little help to the medical
professional except for providing the names of the
chemicals to which an employee was exposed.1–3
11.3 Worker’s Compensation
Each state has a different worker’s compensation system.
Each of these systems has so many idiosyncrasies that
dealing with them has become a major part of the prac-
tice of occupational medicine. Not surprisingly, the will-
ingness of other specialists to deal with these systems is
related to how the reimbursement compares to that of
other payers and how difficult the rules are to deal with.4
Part of the extra awkwardness of a worker’s com-
pensation system comes from the extra dimension of
work-relatedness. Causation is a topic that is unique to
occupational medicine. To thrive in the realm of occu-
pational medicine, specialists need to have some
understanding of causation.4
11.3.1 Assessing Causation
Causation is often a matter of major contention. The
worker’s compensation system is a compromise. As
with most compromises, neither party is satisfied. The
employers and the insurance companies would prefer
that an injury not be labeled as work-related. The injured
A. Theodosatos and R. Haight
worker has an interest in an occupational etiology. Often,
not only is payment for the injury on the line but disabil-
ity compensation is at stake. This is many times more
than enough money to inspire litigation. Highly con-
tested cases might require an independent medical
examination (IME). In IMEs, the physician is approached
as a consultant to answer specific questions. Causation
is a very common question. If a dermatologist or another
specialist wants to get some of IME business, the ability
to discuss causation intelligently becomes important.4 In
particular, hand dermatitis and nail disorders require
careful evaluation since many of them may be work-
related or nonwork-related.5
Contact dermatitis is the most common occupa-
tional skin disorder.3 Mathias suggested that the pres-
ence of four of seven criteria favor an occupational
dermatitis4:
1. Is the clinical appearance consistent with contact
dermatitis?
2. Are there workplace exposures to potential cutane-
ous irritants or allergens?
3. Is the anatomic distribution of dermatitis consis-
tent with cutaneous exposure in relation to job
task?
4. Is the temporal relationship between exposure and
onset consistent with contact dermatitis?
5. Are nonoccupational exposures excluded as prob-
able causes?
6. Does dermatitis improve away from work expo-
sure to the suspected irritant or allergen?
7. Do patch or provocation test identify a probable
causal agent?
Mathias also suggested that a preexisting dermatitis can
probably be said to be aggravated if new dermatitis has
occurred on a skin surface that was not previously
affected or the dermatitis has become more severe in an
area that was already affected by the preexisting derma-
titis. If an aggravation has developed, the above seven
criteria can be used to determine if the aggravation is
due to a superimposed occupational dermatitis.4
11.3.2 Determination of Impairment
When a worker’s compensation patient reaches the
point of maximum medical improvement, the physician
determines the degree of permanent impairment. The
level of impairment is a frequent point of contention
11  Occupational Dermatology
because it affects the amount of compensation. The
American Medical Association publishes the Guides to
the Evaluation of Permanent Impairment to help to
standardize the determination of impairment ratings. A
number of states have developed their own guides to
calculating impairment ratings.1,4
There is a chapter that provides criteria for rating
permanent impairment due to skin disorders. There are
five classes of impairment due to skin disease with
impairment ratings ranging from 0 to 95%. The class
of impairment is determined by whether the signs and
symptoms are present intermittently or constantly, if
there is limitation of the activities of daily living, and
if they require intermittent or constant treatment.6
11.4 Phototoxic Reactions
and Photoallergic Reactions
A phototoxic reaction occurs when a chemical forms
free radicals by reacting with ultraviolet light. Classically,
phototoxic reactions occur in workers that are exposed
to tars. Photoallergic reactions occur when an allergen is
produced from an interaction of a chemical with light.
Photosensitivity can refer to phototoxic or photoallergic
responses. Either form of photosensitivity requires that
both the chemical and the proper wavelength of light are
present. These reactions can occur following topical
exposure or an internal dose.7
11.5 Occupational Acne
Folliculitis is an inflammation of the hair follicles. It
may be caused by irritants or infections. The folliculi-
tis is seen in the areas that are exposed to the irritant
chemical. Acne is most commonly seen with expo-
sures to oils and tars.1, 3
Chloracne is a specific folliculitis caused by haloge-
nated aromatic hydrocarbons,1 most often polychlorinated
biphenyls (PCBs). Small, straw-colored cysts typically
occur on the sides of the forehead, around the lateral
aspects of the eyelids, and behind the ears. The neck,
groin, chest, back, and buttocks may also be involved.
The nose is rarely involved. While an ordinary folliculitis
normally resolves in a week or less, chloracne may persist
for decades.1 This is not surprising because the serum
half-life of highly chlorinated PCBs is 15 years.1
105
11.6 Pigment Changes
Some authors differentiate occupational vitiligo from
leukoderma. Both are acquired depigmentation disor-
ders with selective destruction of melanocytes. A num-
ber of chemicals are implicated in occupational vitiligo
from leukoderma. The major difference is that contact
vitiligo may spread beyond the areas of contact while
leukoderma remains confined to the areas of contact.8
Hypopigmentation can be a nonspecific consequence
of contact dermatitis or burns.
Hyperpigmentation is caused by an increase in mel-
anin production. This most often occurs with coal tar
pitch, psoralens, heavy metals, and ionizing and non-
ionizing radiation.8
11.7 Occupational Skin Cancers
Occupational exposures are seldom considered for
skin cancers. It is estimated that occupational expo-
sures account for 2% or less of cancers.9 Cancer may
be caused by occupational exposure to chemical car-
cinogens such as polycyclic aromatic hydrocarbons or
radiation from exposure to the sun or X-rays. Skin can-
cers can also arise from scarring of burns acquired in
the workplace.10 Carcinogens to be considered in the
indoor air include: tobacco smoke, radon, and pollut-
ants from cooking and heating.9
11.8 Occupational Skin Infections
Worker can be exposed to a number of organisms that
can result in a skin infection. The organisms can often
be predicted based on the occupation and the exposure
(Table 11.1).1, 3
11.9 Skin Notations
The absorption of chemicals through the skin depends
on a number of factors. These include: solute concen-
tration, exposure time, the amount of skin surface
exposed, the anatomical site of the exposed skin, and
the hydrophobicity of the chemical.1
106
Table 11.1  Occupational exposures and infectious agents
Exposure Infectious agent
Any skin trauma Staphylococcus, Streptococcus
Fresh- or saltwater fish, Erysipelothrix rhusiopathiae
crustacea, poultry (gram-positive rod)
Wet work Candida
Soil, foliage Sporotrichosis
Fish tanks Mycobacterium marinum
Healthcare Scabies
Healthcare (puncture) Herpes simplex
Sheep, goats Orf
11.10 Specific Industries and Exposures
Since solar radiation can be an occupational exposure,
photoaging, skin cancer, phototoxic, and photoallergic
reactions can be attributed to occupational skin dis-
ease.7 Segmental vibration can result in Raynaud’s
phenomenon.
Chromium (VI) is a powerful skin irritant. Although
rarely seen today in the developed world, exposure can
cause painful ulcers known as chrome holes.1, 3, 7
11.11 Occupational Dermatitis
About 15% of all workplace injuries are due to derma-
toses.11 It is therefore an important area of medicine for
physicians and healthcare workers. Morbidity associ-
ated with these occupational exposures is significantly
high in the working population and the cost of care is
continually rising. The ultimate goal should be to
enable healthcare workers to be able to assess risk fac-
tors and develop interventions that will reduce job-
related skin injury and disease.11
Occupational contact dermatitis is an inflammatory
skin condition that can develop with exposure to vari-
ous agents in the workplace. The two most common
forms are irritant and allergic contact dermatitis.12 It is
important to differentiate between the two forms
because, although treatment may be the same, diagno-
sis and prevention strategies differ. Irritant dermatitis
is a cutaneous inflammatory reaction that results from
a direct cytotoxic effect of a chemical or physical
A. Theodosatos and R. Haight
agent. Allergic contact dermatitis is an acquired sensi-
tivity to different substances that produce inflamma-
tory reactions in those who have been previously
sensitized to the allergen.12, 13 Approximately 80% of
the cases of contact dermatitis have been shown to be
due to chemical irritants and about 20% have been
shown to be due to allergic reactions.11 Some new data
suggest that allergic contact dermatitis may actually be
more prevalent than irritant dermatitis.13 The 5-year
study indicated an under-diagnosis of allergic dermati-
tis based on the under-utilization of patch testing.
Comparison studies in other countries showed higher
rates of diagnosis of allergic contact dermatitis in mul-
tiple studies. Results suggest the need for a wider array
of allergens to be used in patch testing and also encour-
age a stronger emphasis on performing patch testing.13
The importance of proper patch testing and patience
needed by the physician and patient in order to diagno-
sis the correct condition is also underscored.13
11.11.1 Causes
The skin initially becomes red and may burn or itch
when it comes in contact with an irritating or sensitiz-
ing substance. After the initial contact cutaneous ery-
thema sets in, small vesicles and papules can develop.
Later scales and crusts form. The most commonly
affected areas are the hands and forearms. Although
the most commonly affected areas are the exposed
regions of the body, if the offending agent is a chemi-
cal, it has the ability to soak through the clothing and
affect the normally unexposed areas such as the chest,
back, and upper thighs. If the causative agent does not
remain in contact with the skin, the rash will disap-
pear. Sometimes it may take a few weeks or longer for
complete resolution of the skin reaction. One factor
that significantly increases the time it takes for the
dermatitis to resolve is prolonged length of exposure.
Prolonged or chronic exposure leads to hyperpigmen-
tation, fissure formation, and often, secondary infec-
tions. Other factors that increase resolution time
include increased age, due to the altered skin response
that occurs as our skin ages, and pigmentation; darker
skin burning more easily than lighter. Genetic predis-
position and environmental factors such as extremes
in temperature may also lead to lengthy recovery
times.11–13
11  Occupational Dermatology
Women have been noted to be more likely to develop
occupational hand dermatitis than men. This may be
due to occupations that many women have that increase
their risk for exposure to irritating chemicals and other
substances. An example may be kitchen work and other
household cleaning jobs that women tend to do more
than men.14, 15 The presence of atopic dermatitis or aller-
gic contact dermatitis has been associated with more
severe outcomes. Lower socioeconomic status has been
postulated as a possible risk factor for development of
occupational contact dermatitis.15 Prolonged sick leave
and frequent change of jobs are common in individuals
with a chronic job-related skin dermatosis.16
Almost any substance has the ability to cause a skin
reaction; the most frequently encountered ones will be
mentioned here. Irritant dermatitis is most often
encountered with use of scented soaps and detergents,
other cleaning agents, and many food varieties. Allergic
contact dermatitis is often caused by plants, dyes, rub-
ber additives, nickel, and plastic resins. Certain occu-
pations may increase risk of exposure and development
of contact dermatitis. Agriculture and manufacturing
jobs have been shown by the BLS to be the highest
affected occupations.2 Construction workers have a
substantial risk of developing irritant or allergic der-
matitis. Within construction, tile workers and terrazzo
workers have a strikingly high incidence of occupa-
tional skin disease.11, 12 Hairdressers also have a high-
risk of developing hand dermatitis; 50% have been
shown to develop it within the first 3 years of begin-
ning work.17 Massage therapists are at increased risk of
developing hand dermatitis, mainly due to the use of
aromatherapy products in massage oils. Their patients
are also at increased risk for occupational dermatitis
from the sensitizing effects of massage oils.18
An uncommon but interesting cause of occupational
dermatosis has been documented in some hairdressers
and dog groomers.19 In these cases, the affected indi-
viduals developed an inflammatory response to pene-
tration of hair fragments into the interdigital spaces of
the hands. The affected individuals had a recurrence of
erythema, papules, and draining pustules in the inter-
digital web spaces and went on to require foreign body
removal of the hairs. Eventually, they were diagnosed
with trichogranuloma, also known as a pilonidal sinus.
Antibiotics are generally resistant in this condition,
therefore prevention is key. The use of gloves and
prompt removal of any embedded hairs is encouraged.
This condition, although rare, is important to be aware
107
of because multiple sinuses can form leading to fistula
formation and further morbidity.19
The food industry is a known source of exposure to
various agents responsible for dermatological prob-
lems. The seafood processing centers have been
reported to be a cause of dermatitis in up to 78% of
workers in a study done in South Africa. The study
reveals a major cause for contact dermatitis develop-
ment to be unprotected skin exposure, due to the lack
of protective equipment.20 The majority of seafood
industry related skin conditions were found to be due
to particular irritants such as spices, onions, garlic, and
vinegar.20
Antimicrobial allergy from plastic gloves is a rare
cause of allergic contact dermatitis. It has been reported
that some people have had hand dermatitis developing
after using gloves that were manufactured with ben-
zisothiazolinone, which is a biocide used in the manu-
facture of disposable polyvinyl chloride (PVC) gloves.
It may benefit patients to have patch testing done with
benzisothiazolinone if they experience a skin reaction
after using PVC gloves.21
Latex allergies have been increasing drastically in
the United States. Latex is a known contributor to
morbidity and mortality in the hospital and the only
way to improve the adverse reactions associated with
latex is education of the causes, signs and symptoms,
and prevention measures. Avoidance is the only way
to prevent allergic reactivation but proper diagnosis
via patch testing and serological assays are also very
important in making sure the proper diagnosis was
made.22 Latex gloves are the primary barrier used in
healthcare settings for protection against infection.
Natural latex is produced from the Havea brasiliensis
tree.23 A coagulation process occurs after the liquid is
collected from the tree and mixed with other chemi-
cals. The demand for latex gloves has been growing,
resulting in less refined production procedures. Latex
allergies may occur from a delayed hypersensitivity or
an immediate hypersensitivity reaction. If symptoms
develop within 30 min, the reaction is immediate and
skin findings such as erythema and vesicle formation
develop. This reaction is due to the proteins in the
latex. Experts believe that the change in the manufac-
turing process that increased the natural rubber latex
proteins has been a huge factor in the development of
allergic reactions.22, 23 Other contributing factors
include better awareness and universal precautions
leading to increased glove use.
108
The most severe, immediate allergic reaction to
natural rubber latex proteins is an IgE-mediated (type 1)
hypersensitivity.24, 25 Once sensitization occurs the next
exposure will lead to a more serious reaction. Despite
the increased recognition of latex rubber allergies,
powder-free gloves and patient education has led to a
decrease in the number of latex allergies overall.26
11.11.2 Patch Testing
The patch test can help to identify the offending agent
in a patient with contact dermatitis. The role of a sus-
pected material as an inciting agent can be supported
by the observation of an inflammatory response after it
is applied to an unaffected area of skin.
The patch test is performed by applying solids, liq-
uids, or powders to the back under metallic disks or in
a hydrogel suspension.27 The procedures are standard-
ized in respect to the concentration of antigen, type of
vehicle, character of the vehicle, and the testing and
interpretation procedure. The Finn chamber test uses
aluminum cups, which are affixed with polyacrylate
adhesive tape.28 The True test uses strips of tape with
measured amounts of antigen in hydrophilic gel film
on 9 × 9 mm patches.29 Standardized concentrations of
chemicals are applied to the back in vertical rows and
covered with hypoallergenic tape. The patch test
remains in place for 48 h.
In occupational medicine it is important to deter-
mine what materials will be informative based on the
history and physical examination. The patch test should
never be performed with unknown exposure chemicals
that the employee might bring with him. Simply using
a standard panel may not provide the necessary infor-
mation. For instance, in a study where the number of
antigens was increased to 49, an additional 12.4% of
the patients were defined as allergic.1,27–29 In occupa-
tional medicine, the potential for a fruitless result is
increased by the fact that there are more exposures that
may not be recognized by the primary care physician.
If done correctly, the patch test can distinguish an
irritant from an allergen. This is an issue because many
allergens are also irritants. To do this it is important to
use a concentration of the agent that will usually only
cause a reaction in sensitized patients. The assumption
is that patients who are allergic will react against the
agent at a concentration below that at which an irritant
A. Theodosatos and R. Haight
reaction will be observed. Using the proper dilution
and understanding the mechanisms of the reactions is
the key.27
The exposed area is examined at the time that the
test is removed and again 24–72 h later. The reactions
are quantified: a weak positive reaction (+) is defined
by erythema, infiltration, and discrete papules. A
strong positive reaction (++) is defined by erythema,
infiltration, papules, and discrete vesicles. An extreme
positive reaction (+++) is defined by coalescing vesi-
cles or bullae. A patient that has an extreme reaction
will be capable of reacting to a lower concentration of
antigen than a patient with a 1+ reaction. Interpreting
the skin reactions is a skill which must be developed
through experience. If the intensity of the reaction
increases between 24 and 48 h, this supports an aller-
gic reaction; a decrease of intensity favors an irritant
reaction.27–29
11.11.2.1 TRUE Test
The 24 antigen patches used in the TRUE test are listed
in Table  11.2.27 Wood alcohol is found in cosmetics,
soaps, and topical medications. Potassium dichromate
may cause a reaction in patients who are allergic to
cement, tanned leather, welding fumes, cutting oils,
antirust paints, or other industrial chemicals. Colophony
is a resin that is found in cosmetics, adhesives, and
industrial and household products. Parabens are used
as preservatives in a number of topical preparations.
Balsam of Peru is found in cosmetics, topical medica-
tions, and foods. Ethylenediamine dihydrochloride
may cause a reaction in patients who are allergic to
topical medications, eye drops, anticorrosive agents, or
industrial solvents. Cobalt is found in cement, metal
plated objects, and paints. The p-tert-butylphenol
formaldehyde resin reacts in patients who are allergic
to waterproof glues, bonded leather, construction
materials, paper, or fabrics. Epoxy resins are found in
two-part adhesives, surface coatings, and paints. The
carba mix may react in individuals who are allergic to
rubber products, leather glues, pesticides, vinyl soaps,
or disinfectants. Patients that are allergic to preserva-
tives in cosmetics, skin products, polishes, or cleaners
may react to quaterium-15. Patients that are allergic to
rubber products, adhesives, flea sprays or powders, or
film emulsion may react to mercaptobenzothiazole.
11  Occupational Dermatology 109

Table 11.2  Antigen patches used in the true test Table 11.3  Rule of nines
Nickel sulphate Body area Total body surface area (%)

Wood alcohol Each upper limb 9

Neomycin sulphate Each lower limb 18

Potassium dichromate Anterior and posterior trunk 18 anterior, 18 posterior

Caine mix Head and neck 9

Fragrance mix Perineum and genitalia 1

Colophony
Paraben mix
each side of the patient’s upper back approximately
Negative control
5  cm from the midline. Cleaning with potential irri-
Balsam of Peru tants is unnecessary and may interfere with the test.
Ethylenediamine dihyrochloride The test is removed 48 h later. The reactions are inter-
preted at 72–96 h after the application of the test. The
Cobalt dichloride
reactions are interpreted as shown in Table 11.3. The
p-tert-Butylphenol formaldehyde resin more positive the test the more likely is that it repre-
Epoxy resin sents a true allergic reaction. The patient should be
Carba mix instructed to return if a late reaction occurs 4–5 days
after the application. This is most often seen with
Black rubber mix
p-phenylenediamine.1,27–29
Cl+Me- Isothiazolinone Application of the test during an extensive ongoing
Quaternium-15 dermatitis may intensify the reaction. The application
to a previously affected site may result in a false posi-
Mercaptobenzenzothiazole
tive. A false positive may also result from hyperirrita-
p-Phenylenediamine ble skin. False negatives may result from inadequate
Formaldehyde contact between the allergen and the skin or corticos-
Mercapto mix teroid use.27
Thimerosol
Thiuram mix
11.11.2.2 Finn Chamber

Workers that are allergic to dyed textiles, printing ink,
or photo developer may react to p-phenylenediamine.
Formaldehyde is found in fabric finishes, plastics, syn-
thetic resins, glues, textiles, and a number of construc-
tion materials.
The negative control is an uncoated polyester patch.
The manufacturer claims that this panel accounts for
80% of the cases of allergic contact dermatitis.1,27–29
Dehydrated forms of these standardized antigens
are incorporated into hydrophilic gels and attached to
waterproof backings. There is no allergen preparation
required on the part of the physician. The patches are
simply placed on the patient’s back where perspiration
will dehydrate the antigen. The antigens are supplied
in two panels. The panels are applied to healthy hair-
less skin that is free of any dermatological lesions on
The Finn chamber test uses (8 or 12 mm) aluminum or
polypropylene (8, 12, or 18) coated chambers. The
chambers must be filled by the clinician. Like the
TRUE test the Finn test is applied to the upper back
and utilizes an occlusive method. The makers of the
Finn test recommend cleaning the skin with alcohol if
necessary. The test is removed in 1–2 days. A ring-
shaped depression at the time of removal verifies that
there was adequate occlusion. The test is read 20 min
after the chambers are removed and 3–7 days after
application. The patient should avoid vigorous activity
or shower while the test is in place.28
The Finn chamber offers a choice in antigens but
requires more work from the physician. Since the anti-
gen concentration (depending on the selection of the
examiner) may be less standardized, there is more of
110
an opportunity for an irritant reaction to cause confu-
sion. Drying of the filter paper may result in a false
negative. Using the causative agent in an insufficient
strength will also result in a false negative test. False
positives may be observed due to the aluminum.28
Patch testing will not be helpful if the causative
agent is omitted. An allergic reaction pattern along with
the right indicates an allergic contact dermatitis. In
contrast, an irritant reaction does not add significant
support to an irritant contact reaction. The patch test is
the only technique available to demonstrate that an
allergen causes an allergic contact dermatitis. As with
any test the patch test must be considered in the context
of the patient’s history and physical examination.27–29
11.11.3 Prevention and Treatment
of Occupational Dermatitis
The use of gloves has been a significant factor in the
reduction of hand dermatitis, but improper glove use
has led to more severe dermatitis due to the repeated
exposure to chemicals and or irritating substances.30
These findings show a need to make sure that proper
glove use is taught and encouraged in the workplace.
There are a variety of mechanisms that can lead to glove
failure. When gloves are used more than once the chance
to be exposed to the contaminated exterior of the glove
is increased.31 Permeation of small amounts of certain
chemicals through the glove occurs if the glove is worn
longer than the breakthrough time, which is the mini-
mum time needed for a particular chemical to diffuse
through the glove. Penetration through a glove occurs
when an opening or hole develops in the glove.30, 31
Altered skin pH has also been shown to play a role in
the development of dermatitis.32 Gloves have the ability
to maintain skin pH and therefore reduce dermatitis.
Gloves should be changed frequently and examined for
defects often to minimize the chance of contamination
and development of hand dermatitis.30–33
There are many ways to intervene and treat patients
with occupational dermatitis. Some of the most com-
mon treatments are barrier creams and moisturizers.33
Other treatments are more effective for moderate-to-
severe dermatitis, including topical steroid creams.
Eventually, nonsteroidal creams should be used
because they do not cause thinning of the skin.31,–33
A. Theodosatos and R. Haight
11.12 Burns
Although we have improved strategies to decrease
morbidity and mortality in burn patients, skin care is
often neglected. Reports show that there are over two
million burn injuries each year in the United States.
They result from direct or indirect transfer of heat to
the body and they are encountered in a variety of work-
places. Prompt treatment is important to avoid infec-
tions and long-term sequlae.34 The location, type, and
classification of a burn help determine the aggressive-
ness needed in its treatment. Acute treatment with
wound debridement helps decrease the risk for hyper-
trophic scar formation and allows donor sites to be
found if a skin graft is needed.35 Burned skin is fragile
and very susceptible to sunburn. Without appropriate
postburn care, skin breakdown occurs. Pruritus, caused
by the destruction of the sebaceous glands, is a symp-
tom of healing burns. These glands are destroyed most
commonly in full-thickness burns but can be seen in
some partial-thickness burns. Treatment of pruritus is
generally accomplished with emollient creams and
short-term antihistamine use.34–36 Scar formation is
hastened and cosmetic outcomes improved when
tretinoin creams, topical steroids and hydroquinones
are used. The treatment time varies but usually lasts for
several months. Proper patient education and involve-
ment of multiple healthcare professionals in treatment
and follow-up yield the best results.35
11.12.1 Chemical Burns in the Workplace
Industrial exposures are a frequent cause of chemical
burns. Cleaning products and agricultural products are
also common offending agents resulting in many
chemical burns. These burns account for 2.1–6.5% of
admissions to burn units. The cutaneous manifesta-
tions of chemical burns include necrosis at the site of
injury with surrounding erythema and blistering. The
greater the depth of the chemical burn, the more per-
sistent the necrosis is. Chemical agents that can lead to
systemic complications include various acids, oxidiz-
ing agents, protoplasmic poisons, and vesicants.37–39
Acids and alkalis cause injury to the body by differ-
ent mechanisms. Most acids denature proteins when
they come in contact with the skin and produce a coag-
ulative necrosis. Hydrofluoric (HF) acids are different
11  Occupational Dermatology
in that they produce a liquefactive type of necrosis,
like alkalis. Chemicals that cause liquefactive necrosis
may result in more extensive burns because they are
able to extend further and deeper into the skin. The
process leading to liquefactive necrosis starts with
denaturation of proteins and saponification of fats.35–39
History and physical exam should not only focus on
the history obtained by the affected person. The physi-
cian examining the patient should try and obtain the
container that the substance was in and also contact
poison control. The mode of exposure is also very
important, in addition to the duration of exposure.
Once airway, breathing, and circulation are maintained,
special attention must be made to keep burned patients
from becoming hypothermic. Further injury preven-
tion is also important; therefore removal of contami-
nated clothing and attention to the area of affected skin
is necessary.40, 41
Oral burns may lead to contractures of the orophar-
ynx. These burns typically result from caustic lye
ingestion. Initial oral and gastrointestinal symptoms
are erythema, swelling, and pain. Later progression to
drooling, stridor, and airway obstruction may develop.
Ocular exposures need immediate decontamination
followed by a thorough ophthalmologic evaluation.
Decontamination with irrigation should be continued
until the pH of the eye is returned to normal (pH 7–8).
Ophthalmologic evaluation should also include fluo-
rescein staining to check for corneal abrasions. Slit
lamp examination can be helpful in evaluating the
anterior chamber of the eye, following the ocular irri-
gation and examination.34, 39
Cutaneous burn depth and size should be carefully
documented. First degree burns are superficial and
present as erythematous areas with intact sensation.
Second degree burns are deeper involving varying lev-
els of the dermis. They can form blisters although sen-
sation is still intact. Third degree burns are known as
full-thickness burns, as they involve all layers of the
dermis. They appear swollen, dry, mottled, and white
and they do not elicit any sensation. Fourth degree
burns go deeper into the muscle or bone.34, 36
Burn severity is determined by the depth and total
body surface area involved. Total body surface area is
estimated using the rule of nines (Table  11.3). This
rule estimates a percentage of the body involved by
each body part.
HF acid has many applications and is a common
cause for severe chemical injury. It can be found in
111
plastics, pesticides, fertilizers, high octane fuels, and
heavy duty household cleaners. There are two forms:
anhydrous HF and aqueous HF. The anhydrous form is
stronger and more deadly than the aqueous form, but
the majority of HF burns are due to the aqueous form.
These burns manifest as pain, erythema, blister forma-
tion, and finally tissue destruction. Since this acid is
mostly found in household cleaners the affected site is
usually the fingertips. HF causes injury by first pene-
trating the epidermis and then lipophilic fluoride ions.
Finally, it goes into the cells where it binds calcium
and magnesium. When this occurs, necrosis of soft tis-
sue begins and pain develops from the immobilization
of calcium.39
Phenol is a weak organic acid with a variety of uses
in medicine. It is used frequently for facial peels and
topical and injectable anesthetics. It damages the skin
through corrosive effects, which cause the skin the
slough. Skin exams may reveal partial-thickness burns,
although full-thickness burns are also common. Phenol
is rapidly absorbed and systemic symptoms are a major
concern. Systemic findings include: premature ven-
tricular contractions, tachycardia, hypotension, central
nervous system (CNS) depression, and finally respira-
tory failure.41
Chromic acid burns produce localized coagulative
necrosis and sometimes gastrointestinal, renal, and
CNS complications. When chromium is absorbed it
produces a hexavalent form that can be absorbed by
red blood cells and bind hemoglobin, impairing its
oxygen-carrying capacity. Formic acid is also used in
industry and it produces a localized chemical burn
similar to one caused by chromic acid. One major sys-
temic effect is acidosis, which develops when formic
acid interferes with cellular respiration. Complex aci-
dosis increases proximal tubule reabsorption, decreas-
ing formic acid excretion. Other systemic findings are
hypotension, hematuria, hemoglobinuria, renal failure,
and end organ damage.34–38
Alkali agents are also common causes of chemical
burns. Some frequently encountered alkali agents
include: anhydrous ammonia, cement burns and airbag
injuries.42 Anhydrous ammonia is a colorless gas found
in cleaning products used in the home. These burns
may appear grayish-yellow in appearance in partial-
thickness burns and leathery and white in full-thick-
ness burns. Cement burns are encountered in the lower
extremities of some construction workers.37 These
burns develop from calcium oxide penetration, causing
112
a liquefactive type of necrosis. The skin is damaged
from abrasions due to the coarse consistency of cement.
Airbag injuries are associated with the release of
sodium azide and sodium hydroxide.42 It has been esti-
mated that skin injuries account for approximately 8%
of all injuries from airbag deployment. White phos-
phorus can cause corrosive damage to the skin by a
chemical and thermal combined burn. This oxidizing
agent is used in weaponry, some fertilizers, and fire-
works. Immediate removal of this chemical from the
skin is important to prevent the progression to systemic
effects, such as liver and kidney damage.38 Sulfur mus-
tard is a blistering agent, used in the past in warfare.
This chemical has the ability to cause the skin to blister
after an asymptomatic period. This blistering effect
mostly involves the intertriginous areas, although it
does spread easily. They may coalesce and form larger
bulla. Systemic effects are also observed, therefore
prompt treatment is important. Betadine is an antisep-
tic containing water, iodine, and polyvinyl pyrrolidine.
It has the ability to cause burns especially on areas of
the skin that are not dried properly. Dependent areas of
the body are most commonly affected. Other skin
cleansing agents must be used with caution, especially
in babies and the elderly.43 Table 11.4 lists some com-
mon burn-causing chemical agents, their uses, and
medical treatment.
Laboratory studies can be useful in burns that are
known to cause systemic effects and in burns involv-
ing mild-to-moderate amounts of skin. The common
Table 11.4  Chemical agents, their uses, and medical management
Chemical agent Uses
Hydrofluoric (HF) acid Fertilizers, pesticides, dyes,
plastics, and household cleaners
Phenol, carbolic acid, Sewage treatment, topical and systemic
hydoxybenzene anesthetics, chemical face peels
Chromic acid Dye production
Formic acid Descaling agent, rubber processor
Cement Construction products
White phosphorus Weaponry, manufacture of insecticides
and fertilizers, fireworks
A. Theodosatos and R. Haight
systemic effects that occur vary by the type of chem-
ical involved. Fluid and electrolyte monitoring may
be necessary to identify patients needing closer
monitoring in the hospital. Initial management of
any burn patient requires removal of the offending
agent. Next, contaminated clothes should be removed
and affected areas of the skin should be irrigated.
Earlier irrigation has been shown to limit burn depth
and also decrease the duration of time spent in the
hospital. Fluid resuscitation is important in chemical
burns because these burns tend to be deeper in the
tissue than other types of burns. Irrigation dilutes
the chemical and removes unreacted chemicals from
the skin. Burn treatment also includes pain manage-
ment, physical therapy, and occupational therapy.
Sometimes skin grafting may be needed along with
cosmetic reconstruction. Some studies have shown
that certain biological dressings can be used effec-
tively in second degree burns. For example, xeno-
derm can lead to a reduction in dressing times,
reduce hospital stay, and decrease the formation of
scars.34, 44
Burn patients who receive the earliest care have
been shown to have the best clinical outcomes. In order
to be able to treat a burn patient appropriately early on,
healthcare providers need to be have a clear clinical
picture of the different types and causes of burns, espe-
cially in the workplace. This can be accomplished by
setting up burn education and prevention measures,
especially in high-risk jobs.34, 44
Medical management
Irrigation, ammonium compounds (to inactivate free
fluoride ions), calcium gluconate gels
(neutralization), and sometimes debridement
Irrigation, polyethylene glycol (PEG)
Irrigation, phosphate buffers,
thiosulfate soaks, EDTA
Irrigation, IVF hydration, bicarbonate
therapy, folic acid, dialysis (severe)
Irrigation, dry lime, soap and water
Irrigation, wet compresses, and
surgical debridement
11  Occupational Dermatology
References
  1. Rom WM. Environmental and Occupational Medicine. 3rd
ed. Philadelphia: Lippincott-Raven; 1998
  2. US Department of Labor, US Bureau of Labor Statistics.
Occupational Injuries and Illnesses: counts, rates, and char-
acteristics, 2004. Bulletin 2584. 2006
  3. Emmett EA. Occupational dermatitosis. In: Fitzpatrick TB,
Eisen AZ, Wolf K, et  al eds. Dermatology in General
Medicine. 3rd ed. New York: McGraw-Hill; 1987
  4. Mathias CGT. Contact dermatitis and workers’ compensa-
tion: criteria for establishing occupational causation and
aggravation. J Am Acad Derm. 1989;20(5):842–848
  5. Dhir H. Hand dermatitis and nail disorders of the workplace.
Clin Occup Environ Med. 2006;5(2):381–396
  6. Cocchiarella L, Anderson GBJ. Guides to the Evaluation of
Permanent Impairment. 5th ed. Chicago: American Medical
Association; 2000
  7. Pharda V, Gruber F, Kastelan M, et al Occupational skin dis-
eases caused by solar radiation. Coll Antropol. 2007;31(1):
87–90
  8. Boissy RE, Manga P. On the etiology of contact/occupa-
tional vitiligo. Pigment Cell Res. 2004;17(3):208–214
  9. Boffetta P. Epidemiology of environmental and occupational
cancer. Oncogene. 2004;23(38):6392–6403
10. Gawkrodger DJ. Occupational skin cancer. Occup Med.
2004;54(7):458–463
11. McCall BP, Horwitz IB, Feldman SR, Balkrishnan R.
Incidence rates, costs, severity, and work-related factors of
occupational dermatitis-A workers compensation analysis of
Oregon 1990–1997. Arch Dermatol. 2005;141:713–718
12. Rietschel RL. Occupational contact dermatitis. Lancet.
1997;349:1093–1095
13. Kucenic MJ, Belsito DV. Occupational allergic contact der-
matitis is more prevalent than irritant contact dermatitis: a 5
year study. J Am Acad Dermatol. 2002;46:695–699
14. Robinson JK, Ramos-e-Siliva M. Women’s dermatologic
diseases, health care delivery, and socioeconomic barriers.
Arch Dermatol. 2006;142:362–364
15. Cvetkovski RS, Zachariae R, et al Prognosis of occupational
hand eczema. Arch Dermatol. 2006;142:305–311
16. Olsen J, Mathiesen L, et al Relation between diagnoses on
severity, sick leave and loss of job among patients with occu-
pational hand eczema. Br J Dermatol. 2004;152:93–98
17. Worth A, Arshad SH, Sheikh A. Occupational dermatitis in
a hairdresser. Br Med J. 2007;335:399
18. Crawford GH, Katz KA, Ellis E, James WD. Use of aro-
matherapy products and increased risk of hand dermatitis in
massage therapists. Arch Dermatol. 2004;140:991–996
19. Vaccaro M, Guarneri F, Barbuzza O, et al A prickly pair. Am
J Med. 2007;120:1026–1027
20. Jeebhay MF, Lopata AL, Robins TG. Seafood processing in
South Africa: a study of working practices, occupational
health services and allergic problems in the industry. Occup
Med. 2000;50:406–413
21. Aalton-Korte K, Alanko K, et al Antimicrobial allergy from
polyvinyl chloride gloves. Arch Dermatol Oct. 2006;142:
1326–1330
113
22. Wilkinson SM, Beck MH. Allergic contact dermatitis from
latex rubber. Br J Dermatol. 1996;134:910–914
23. Sinha A, Harrison PV. Latex glove allergy among hospital
employees: a study in the north-west of England. Occup
Med. 1998;48:405–410
24. Woods JA, Lambert S, Thomas AE, et  al Natural rubber
latex allergy: spectrum, diagnostic approach, and therapy.
J Emerg Med. 1997;15:71–85
25. Bock M, Schmidt A, et al Occupational skin disease in the
construction industry. Br J Derm. 2003;149:1165–1171
26. Henning A, et al Primary prevention of natural rubber latex
allergy in the German health care system through educa-
tion and intervention. J Allergy Clin Immunol. 2002;110:
318–323
27. True Test Physician’s Reference Manual. At: www.truetest.
com; 2009 Accessed 17.02.09
28. Finn Chamber on Scanpor. At: www.epitest.fi; 2009 Accessed
17.02.09
29. Marks JG, Belsito DV, DeLeo VA, et al Clinical and labora-
tory studies: North American contact dermatitis group patch
test for the determination of delayed- type hypersensitivity
to topical allergens. J Am Ac Derm. 1998;38(6):911–918
30. Saary J, et al A systematic review of contact dermatitis treat-
ment and prevention. J Am Acad Dermatol. 2005;53:
843–855
31. Soonyou K, Lauren S, et al Role of protective gloves in the
causation and treatment of occupational irritant contact der-
matitis. J Am Acad Dermatol. 2006;55:891–896
32. Mirza R, et al A randomized, controlled, double blind study
of the effect of wearing coated pH 5.5 latex gloves compared
with standard powder free latex gloves on skin pH, transepi-
dermal water loss and skin irritation. Contact Derm. 2006;
55:20–25
33. Wigger-Alberti W, Elsner P. Prevention of irritant contact
dermatitis-new aspects. Immunol Allergy Clin N Am. 1997;
17:443–450
34. Monafo WW. Initial management of burns. N Engl J Med.
1996;335(21):1581–1586
35. Ho WS, Chan HH, Ying SY, et al Skin care in burn patients:
a team approach. Burns. 2001;27:489–491
36. Kales SN, Christiani DC. Acute chemical emergencies.
N Engl J Med. 2004;350(8):800–808
37. Spoo J, Elsner P. Cement burns: a review 1960–2000.
Contact Derm. 2001;45(2):68–71
38. Chou TD, Lee TW, Chen SL, et al The management of white
phosphorus burns. Burns. 2001;27(5):492–497
39. Hatzifotis M, Williams A, Muller M, et al Hydrofluoric acid
burns. Burns. 2004;30(2):156–159
40. Browne TD. The treatment of hydrofluoric acid burns.
Occup Med. 1974;24:80–89
41. Horch R, Spilker G, Stark GB. Phenol burns and intoxica-
tions. Burns. 1994;20(1):45–50
42. Corazza M, Bacilieri S, Morandi P. Airbag dermatitis.
Contact Derm. 2000;42(6):367–368
43. Maenthaisong R, Chaiyakunapruk N, et  al The efficacy of
aloe vera used for burn wound healing: A systematic review.
Burns. 2007;33:713–718
44. Cox RD. Burns, Chemical. At www.emedicine.com; 2008
Accessed 15.05.08. Chemical burns
 Diagnosis and Prevention
of Bullous Diseases
Supriya S. Venugopal and Dedee F. Murrell
12.1 Introduction
Bullous diseases may be broadly divided into the
inherited, autoimmune, and infectious types. This
chapter will deal with each in turn: how to diagnose
and how to, where possible, prevent these from occur-
ring or worsening.
12.2 Inherited Bullous Diseases
12.2.1 Epidermolysis Bullosa
Epidermolysis bullosa is a blistering disease occurring
at birth or shortly after birth, characterized by the ten-
dency to develop blisters spontaneously or after sus-
taining minimal trauma. There are many different
types of epidermolysis bullosa. The three main inher-
ited subtypes (Table 12.1), classified according to the
level at which skin cleavage occurs, include:
• Epidermolysis bullosa simplex (EBS)
• Junctional epidermolysis bullosa (JEB)
• Dystrophic epidermolysis bullosa (DEB)
EBS is characterized by intradermal skin cleavage
above the basement membrane at the level of the kerati-
nocytes. In JEB, blister formation occurs at the level of
D. F. Murrell (*)
Department of Dermatology, St. George Hospital,
University of NSW Medical School, Sydney, Australia
e-mail: d.murrell@unsw.edu.au
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_12, © Springer-Verlag London Limited 2010
12
the lamina lucida, and DEB is characterized by blister
formation in the sublamina densa.65 The classification
of EB has been upgraded67 and at the time of writing
this chapter the terminology was being further
revised and upgraded to include some additional
syndromes.68
EBS is a blistering disorder affecting the basal layer
of the epidermis. Most cases are caused by mutations in
the genes encoding keratin 5 (K5) and keratin 14 (K14)
and are characterized by cytolysis within the basal layer
of the epidermis.163 Patients with the Dowling-Meara
type of EB simplex (EBS-DM) can have severe blister-
ing at birth, but this tends to markedly improve as the
patient grows older and by early adulthood, patients
rarely develop blisters.135 Additional features are hyper-
keratosis of the palms and soles, and herpetiform group-
ing of blisters.36 In EBS-DM, some of the keratin
filaments are organized into dense, circumscribed
clumps that sometimes connect with either hemidesmo-
somes or desmosomes.12 Transmission electron micros-
copy (TEM) is highly specific for the diagnosis of the
EBS-DM, though it has variable sensitivity.104, 213
There are multiple important considerations with
respect to the ultrastructural findings in autosomal
recessive EBS (R-EBS) and autosomal recessive EBS
associated with muscular dystrophy (EBS-MD). In
R-EBS, there may be an ablation of K14 expression and
also a lack of visible keratin filaments in basal but not
suprabasal keratinocytes.112, 214 Autosomal recessive
EBS is associated with the following findings: a lack of
integration of keratin filaments with hemidesmosomes,
neuro­muscular disease, and mutation of the plectin
gene.64, 147
JEB is an autosomal recessive disorder character-
ized by blisters that develop within the lamina lucida.
Clinical manifestations aid in subtype classification in
particular, generalized (Herlitz, H-JEB) type, which is
115
116 S. S. Venugopal and D. F. Murrell

Table 12.1  The major EB types, subtypes, and the associated

targeted proteins (Fine et al 2008)
Major EB type Major EB Targeted proteins
subtypes
Epidermolysis Suprabasal Plakophilin-1
bullosa simplex Basal Desmoplakin
(EBS) Keratins 5 and 14;
plectin; a6b4
integrins
Junctional JEB-Herlitz Lam332
epidermolysis JEB-other Lam 332; Col XVII;
bullosa (JEB) a6b4 integrins
Dystrophic Dominant Collagen VII
epidermolysis Recessive Collagen VII
bullosa (DEB)
Kindler syndrome – Kindlin 1 Fig. 12.1  H-JEB with groin involvement exacerbated by nappies

or embryonic-appearing ultrastructure. Severely affected

lethal, and a generalized but less severe (non-Herlitz,
individuals are associated with either the absence of
nH-JEB) type.68 H-JEB is caused by mutations in one
hemidesmosomes or have reduced numbers of hemides-
of the three genes encoding the anchoring filament
mosomes lacking subbasal dense plates.66
components of laminin 5, now referred to as Lam332
Laminin 5 is a glycoprotein comprising three sub-
(LAMA3, LAMB3, and LAMC2).137 nH-JEB is caused
units: alpha 3, beta 3, and gamma 2. These subunit
by less deleterious mutations in the aforementioned
chains are encoded by the following genes: LAMA3
genes or mutations in the gene that encodes type XVII
(localized to chromosome 18q),15 LAMB3 (at 1q32),
collagen or BP180, known as COL17A1.111,136,137
and LAMC2 (at 1q25–31),194 respectively. These have
Classical sites of involvement include the buttocks,
been proposed as candidate genes in Herlitz disease.
mouth, back of the scalp, and periungual areas.52
Studies have demonstrated that mutations in any one
Absent or dystrophic nails, enamel hypoplasia, laryn-
of these three genes may be associated with the Herlitz
geal edema or stenosis, profound growth retardation,
­phenotype.1, 116, 165 Mutations in LAMB3 have also been
anemia, and the presence of exuberant granulation tis-
shown to underlie non-Herlitz JEB,136, 137 and recently
sue, particularly on the trunk and on periorificial and
mutations in the genes encoding (b)4 integrin and the
periungual sites, are also features. Epidermolysis
180-kDa bullous pemphigoid (BP) antigens have also
bullosa, usually but not necessarily in the lamina lucida,
been demonstrated (Fig. 12.2).136, 137, 195
associated with pyloric atresia (EB-PA), manifests with
neonatal blistering and gastric anomalies. EB-PA is
known to be caused by mutations in the hemidesmo-
somal genes ITGA6 and ITGB4, encoding the alpha6
and beta4 integrin polypeptides, respectively.157
Herlitz JEB skin demonstrates a split at the dermal–
epidermal junction with minimal dermal inflammation
(Fig.  12.1). Immunofluorescence mapping (IFM) and
electron microscopy (EM) studies confirm the level of
cleavage to be through the lamina lucida.
Hemidesmosomes may be significantly reduced, small,
and lacking normal subbasal plates.189 More severely
affected patients may display absence or marked reduc-
tion in density of the subbasal dense plate along the
­dermoepidermal junction. In addition, a reduction in Fig. 12.2  Grouped blistering and postinflammatory change in
hermidesmosome count is associated with a rudimentary EBS-DM
12  Diagnosis and Prevention of Bullous Diseases
DEB may be inherited in an autosomal dominant
(DDEB) and an autosomal recessive manner (RDEB).
Mutations in the type VII collagen gene (COL7A1)
gene result in both RDEB and DDEB.47 RDEB is fur-
ther subclassified into:
• RDEB-GS: Generalized Severe type
• RDEB-nGS: Generalized non severe type
• Inversa RDEB
• Centripetal RDEB
• Pruriginosa RDEB
• Pretibial RDEB
The generalized severe type (RDEB-GS) is character-
ized by generalized lesions and scarring of the hands
and feet, leading to fusion of the digits pseudosyndac-
tyly and severe mucosal involvement. The milder
RDEB-nGS type can be localized or generalized, in
contrast with RDEB-GS is associated with very mild
or no pseudo-syndactyly, and less frequent extra-cuta-
neous involvement (Fig. 12.3).67
The precise diagnosis of EB is crucial for molecular
diagnosis and is the key for prevention using prenatal
diagnosis. There are three main modalities for the diag-
nosis of EB. These include:
• Transmission electron microscopy (TEM)
• Immunofluorescence antigenic mapping
• Genetic studies
Ultrastructural examination demonstrates the level of skin
cleavage, allowing discrimination of epidermolytic, junc-
tional, and dermolytic types of EB. Immunofluorescence
Fig.  12.3  Gastrostomy in RDEB-HS to prevent malnutrition,
osteoporosis. Protective nonstick dressing to prevent blistering
117
antigenic mapping (IFM) is a convenient and rapid
method for classification and involves the localization of
previously defined components within certain ultrastruc-
tural regions of the dermoepidermal junction.
TEM allows direct visualization and quantification
of specific ultrastructural features. TEM was first used
as a diagnostic tool in EB in the early 1960s by
Pearson154, 155 which allowed for the first accurate
method of distinguishing between the various types of
EB. Further developments and refinement of TEM
methods have allowed for the diagnosis of further sub-
classification in the major types of EB. TEM may help
establish a definitive diagnosis not only of major vari-
ants of EB, but also of main subtypes.11 TEM is per-
formed on tissue that is stained with uranyl acetate,
lead citrate, and osmium tetroxide. The tissue is visu-
alized under EM with a specific focus on the level of
skin cleavage present. TEM also allows measurement
of the number of keratin tonofilaments, hemi­
desmosones, subbasal dense plates, and anchoring
fibrils.154,155
Alternative methods to the diagnosis of EB include
IFM, first described by Hintner et al98 IFM has been
aided by the discovery of several individual basement
membrane zone (BMZ) antibodies. IFM is a powerful
diagnostic tool for EB when combined with immuno-
histochemical mapping of these BMZ monoclonal
antibodies. IFM determines the precise level of skin
cleavage of a specimen by determining the site of
binding by a series of antibodies directed to these
BMZ antigens, with known ultrastructural binding
sites.63
There are many reasons for favoring the use of IFM
compared with TEM in modern dermatological prac-
tice in the diagnosis of EB. Yiasemides et  al213 con-
cluded that TEM and IFM were appropriate first-line
techniques of choice in the diagnosis of EB. The study
concluded that despite the lack of statistical signifi-
cance, IFM consistently had higher sensitivity, speci-
ficity, and predictive values in the diagnosis of all three
subtypes of EB compared with TEM. There are also
several other reasons to favor the use of IFM as opposed
to TEM. TEM requires a long training period and sam-
ple preparation is more laborious, often taking days to
weeks to complete. As a result of skills shortage, TEM
is not readily available in all hospitals and laboratories.
In addition, interpretation of the skin biopsy using
TEM may lead to greater mistakes in diagnosis. This is
due to the relatively small area of the specimen sample
118
that is visualized, which may result in the blister being
missed. This may also result in the overestimation or
underestimation of the number of fibrils and other
structural components in EB. At high magnifications,
artifactual spaces may be misinterpreted for cleavage
sites. Other diagnostic misinterpretations include
reporting nonspecific dense bundles of keratin fila-
ments as clumped tonofilaments (i.e., resulting in the
diagnosis of EBS-DM).213
Due to the variance in the ultrastructural findings in
the various subsets of EB, TEM faces difficulties in the
accurate diagnosis of the various different subgroups
in EB. This is perhaps one of the main reasons why
TEM appears to be less accurate in subset diagnosis of
EB compared with IFM. Morphometric analysis in
JEB demonstrates marked desmosomal heterogene-
ity.190 In more severe recessive generalized DEB cases,
morphometric analysis has shown a total absence of
anchoring fibrils.35
Immunohistochemical staining of collagen IV in
formalin fixed and paraffin-embedded samples fol-
lowed by examination under a light microscope is a
more rapid alternative to TEM. EBS variants are diag-
nosed by the presence of collagen IV staining at the
floor of the blister. The positive staining in the roof of
the blister establishes the diagnosis of dystrophic vari-
ants of EB. The present technique identifies collagen
IV within the lamina densa and subsequently does not
allow differentiation between EB simplex and junc-
tional EB.23
12.2.1.1 Prevention of EB
Prenatal genetic diagnosis (PND) has most frequently
been performed for the following subtypes of EB, as
they are the most severe59–61,138,180:
• Recessive dystrophic EB - generalized severe
• Herlitz junctional EB
• Junctional EB associated with congenital pyloric
atresia
However, in some countries there are differing ethical
paradigms which have allowed PND for “milder”
forms of EB, since these may not be perceived to be
“mild” by the patients themselves or their carers. These
include non-Herlitz JEB141 and dominant dystrophic
EB118 and disorders in the EB umbrella, skin fragility
ectodermal dysplasia and Kindler syndrome.59–61, 68
S. S. Venugopal and D. F. Murrell
Prenatal diagnosis for EB was initially done by
examination of a fetal skin biopsy with EM and/or
immunohistochemistry.55, 56, 91, 92, 171 In the 1990s, the
genes responsible for respective EB subtypes and the
family-specific mutations were identified, as mentioned
above. This led to the feasibility of DNA-based PND
using fetal DNA extracted from amniocentesis at 12–15
weeks initially and later from chorionic villous sam-
pling at about 10 weeks. Direct assessment of previ-
ously identified pathogenic mutations or the use of
indirect linkage markers have been the methods used
for the majority of DNA-based PND in RDEB.180
Mutational analysis of the type VII collagen gene,
COLA1 or haplotype analysis using a number of well-
described informative polymorphisms within or flank-
ing COL7A1, if the mutation(s) has/have not been
identified are some of the assesment methods used.138
Fetal skin biopsy has several disadvantages and has
been superseded by molecular diagnosis. A fetal skin
biopsy can only be obtained later in gestation, usually
16 weeks or more, and is associated with a relatively
high rate of miscarriage.66 Mutation detection using
fetal amniocytes or chorionic villous sampling can be
performed earlier and as they are less invasive and
have lower risks of miscarriage. However, fetal skin
biopsy remains an option in those rare cases in which
mutations cannot be identified and linked markers are
not available to be used for prenatal diagnosis. Very
few obstetricians have experience with fetal skin biop-
sies, however. Prenatal diagnosis can be greater than
98% accurate and is highly beneficial in pregnancy
screening for mutations or informative markers.158
Analyzing the sequence traces with the aid of com-
puter software, rather than by hand, is mandatory now-
adays to reduce human errors. Analysis of fetal skin
biopsies and DNA-based prenatal tests allow the diag-
nosis of an affected fetus to be made once pregnancy is
established, and can result in considerable emotional
and physical distress for the parents contemplating the
prospect of termination.59–61
Preimplantation genetic diagnosis (PGD) is a tech-
nique involving a single cell biopsy from the six-to-ten
cell blastomere stage of the fertilized embryo pro-
ceeded by DNA mutational analysis.86 Less DNA is
needed if genome wide markers are used.59–61 Disease-
free embryos are then implanted into the uterus,
thereby avoiding any pregnancy termination proce-
dures usually associated with conventional PND
methods.
12  Diagnosis and Prevention of Bullous Diseases
Mothers who decide to give birth to a baby known
to have EB or at high-risk of EB can prevent some of
the blistering associated with birth trauma in these
infants by undergoing a planned Caesarian section
rather than a normal vaginal delivery.
12.3 Autoimmune Bullous Diseases
Autoimmune bullous diseases are associated with
autoimmunity against structural components which
maintain cell–cell and cell-matrix adhesion in the skin
and mucous membranes.139 They include those where
the skin blisters at the BMZ (BP, herpes gestationis,
mucous membrane pemphigoid [MMP], linear IgA
dermatosis [LAD], epidermolysis bullosa acquisita
[EBA], bullous lupus and dermatitis herpetiformis
[DH]) and those where the skin blisters within the epi-
dermis (pemphigus vulgaris [PV], pemphigus folia-
ceus [PF] and other subtypes of pemphigus88).
Due to the considerable overlap in the clinical pre-
sentation of these conditions, diagnosis of autoimmune
bullous skin conditions can be challenging. Detection
of tissue-bound and circulating serum autoantibodies
and characterization of their molecular specificity is an
important modality for diagnosis. In the past decade,
there have been several advances in diagnostic modali-
ties for autoimmune bullous skin conditions.
12.3.1 Pemphigus
Pemphigus is a word derived from the Greek work “pem-
phix” meaning bubble or blister and is a ­life-threatening
autoimmune blistering disease, characterized by intraepi-
thelial blister formation.95, 96, 102, 124 Circulating autoanti-
bodies directed against intercellular adhesion struc­tures
result in the loss of adhesion between the keratinocytes.5, 17
The incidence of pemphigus is approximately 1 in
100,000 people.186 The variants of pemphigus are deter-
mined according to the level of intraepidermal split for-
mation. There are five main variants of pemphigus. These
include PV, PF, pemphigus erythematosus, drug-induced
pemphigus, and paraneoplastic pemphigus (PNP).
The hallmark of pemphigus is acantholysis, an
intradermal split formation due to the loss of adhesion
119
between epidermal keratinocytes. This may result in
the development of the Tzanck phenomenon (the
rounding of single epidermal cells due to the loss of
cell–cell attachment). Inflammatory cell infiltrates of
the involved skin are generally absent. PF and PV are
usually characterized by suprabasilar loss of adhesion
leaving a single layer of basal keratinocytes attached to
the dermoepidermal basement membrane (tombstone
pattern). PF is associated with a superficial split forma-
tion in the subcorneal layer.
Tissue-bound IgG or IgA in a characteristic netlike
intercellular distribution pattern within the epidermis,
commonly associated with precipitation of C3 is
­demonstrated on direct immunofluorescence micros-
copy. Indirect immunofluorescence microscopy, the
gold standard in pemphigus, reveals the presence of
serum autoantibodies against desmosomal antigens.
Pemphigus sera show a characteristic netlike intercel-
lular staining of IgG with human skin as a substrate.
Other substrates such as monkey esophagus, guinea
pig esophagus, or rat bladder epithelium may be used
in the diagnosis of PNP.110
Immunoserological tests such as enzyme-linked
immunosorbent assay (ELISA) confirm the diagnosis
of pemphigus and results can be used to determine dis-
ease activity. The development and commercial use of
ELISA has provided higher sensitivity and specificity
in making the diagnosis of pemphigus subtypes.105
ELISA alone is insufficient to diagnose the condition.
Immunoserological tests can provide valuable infor-
mation on the clinical course of pemphigus, and can
also be used as a diagnostic and prognostic indicator in
the management of pemphigus.
Desmoglein 35,7 and desmoglein 137,57 are the tar-
gets for autoantibodies in PV and PF, respectively. In
active PV, immunoblot analysis with recombinant
Dsg3 demonstrated that anti-Dsg3 of the IgG4, IgA,
and IgE subtypes predominate; however, chronic
remittent PV is characterized by IgG1 and IgG4
autoantibodies.22,88,120,185
PV is the most common variant of pemphigus with
an incidence of 0.1–0.5 per 100,000 population, and
higher among Jewish patients.3 The diagnosis of PV is
made using four major criteria. These consist of:
• Clinical findings
• Light microscopic findings
• Direct immunofluorescence findings
• Indirect immunofluorescence findings95, 143
120
Fig. 12.4  Erosions and crusting of the scalp in a patient with
pemphigus vulgaris (PV)
PV is the most common subtype of pemphigus
(Fig. 12.4). It is a potentially life-threatening autoim-
mune vesiculobullous disorder characterized by non-
scarring, fragile vesicles and bullae involving the
mucosae with varying cutaneous involvement. PV usu-
ally presents in adults and can affect anywhere in the
body but predominantly affects the buccal and labial
mucosa. This condition is characterized by Nikolsky’s
sign: the application of slight pressure on the blisters
resulting in their spread to neighboring areas. Histo­
logical studies of PV lesions usually demonstrate
acantholysis in the suprabasilar part of the epidermis.
Typical findings include IgG and/or C3 binding to the
intracellular cement substance (ICS) in the mid-lower
or entire epidermis of perilesional skin or mucosa on
DIF.2,125,176,177 PV is associated with autoantibodies to
130-kDa glycoprotein Dsg3 and secondary develop-
ment of antibodies to 160-kDa glycoprotein Dsg1 anti-
gens, when the skin is involved.186 Acetylcholine
receptors on keratinocytes have also been reported as a
possible further target antigen in PV.82,181,196
PF generally has a benign clinical course and most
frequently presents on the scalp, face, and upper trunk
and is characterized by erythema, scaling, and crusting
lesions and spares the mucus membranes.186 An
endemic version of PF, fogo selvagem (FS), is endemic
to an Indian reservation in Brazil. The cause of this
may be environmental and in particular may be due to
saliva components of insects which may initiate the
spread of the disease; the exact cause is not known but
S. S. Venugopal and D. F. Murrell
as it has also been reported in unrelated people moving
in to the reservation, not just those from the indigenous
population there, it suggests an environmental agent.49
Penicillamine is also a known causative agent in PF.26
Other drugs and environmental agents/chemicals may
be associated with triggering PV. Exposure to pesti-
cides and occupational exposure to metal vapor were
associated with an increased risk of pemphigus.31
Brenner et  al32 discussed the importance of various
exogenic factors in triggering pemphigus including
drugs, particularly those containing thiol and phenol
groups, calcium channel blockers, ultraviolet radia-
tion, burns, X-rays, neoplasms, nutritional factors, emo-
tional stress, hormones and pregnancy, viruses and
vaccinations. There are a number of cases in which
exposure to viral disease, in particular herpes simplex,
Epstein Barr virus, cytomegalovirus or human herpes
viruses, have been associated with PV or PF.
Pemphigus erythematosus or Senear-Usher syn-
drome is a localized variant of PF. It is characterized
by the presence of a malar erythema, similar to the
rash of lupus erythematosus, also extending to sun-
exposed areas of the scalp, face, and upper trunk.186
Histological and immunopathological studies confirm
the diagnosis of PF. Histopathological examination of
PF lesions show subcorneal acantholytic bullae.
Binding of IgG and/or C3 to the ICS in the upper stra-
tum malphigii is demonstrated on (DIF) studies of per-
ilesional skin.176
PNP, a rare autoimmune bullous disease related to
underlying neoplasia, is characterized by severe, painful
mucosal erosions and polymorphous skin lesions.10 PNP
occurs in patients with underlying malignancies such as
non-Hodgkin’s lymphoma, chronic lymphocytic leuke-
mia, and thymoma.8 PNP is associated with autoanti-
bodies to Dsg1, desmoglein3 (Dsg3) and plakins, a
characteristic that differentiates this from the other vari-
ants of pemphigus.41 Histopathologic hallmarks include
acantholysis and interface dermatitis or keratinocyte
necrosis.100 PNP is characterized by the development of
autoantibodies directed against multiple antigens, pre-
dominantly of the plakin family of intermediate fila-
ment-associated proteins and the desmogleins of the
cadherin family in desmosomes.6,24,89,164
PV is strongly associated with the human leukocyte
antigen (HLA) serotypes HLA-DR4 and HLA-DR6.188
Ahmed et  al4 reported low levels of autoantibody in
48% of healthy relatives of PV patients, and the inheri-
tance of antibody positivity was linked to the DR4 and
12  Diagnosis and Prevention of Bullous Diseases
DR6 haplotype. Greater than 95% of PV patients pos-
sess one or both of these haplotypes.191 However, popu-
lation studies report the differing prevalence of alleles
in various ethnic groups and concluded that in the non-
Jewish population, eight alleles were positively associ-
ated and one allele was negatively associated with PV.123
The two candidate alleles, most likely to contribute to
disease susceptibility in the non-Jewish population,
included DRB1*0402 and DQB1*0503. DRB1*0402
was determined to be the sole allele likely to confer sus-
ceptibility to PV in Ashkenazi Jewish patients.
The global knowledge of PV is quickly advancing;
however, there is a dearth of multicenter trials focused
on effective strategies for the treatment of pemphigus
and multiplicity of outcome measures used.133 In 2005,
the International Pemphigus Definitions Group pro-
posed a consensus statement which provided clear
definitions of pemphigus.
The consensus statement on disease endpoints and
therapeutic response for pemphigus142 divides pemphi-
gus disease activity into the following categories:
1. Early endpoints
(a)  Baseline
(b)  Control of disease activity
(c)  End of consolidation phase
2. Late end points
(a)  Complete remission off therapy
(b)  Complete remission on therapy
−− Minimal therapy
−− Minimal adjuvant therapy
−− Partial remission off therapy
−− Partial remission on minimal therapy
3. Relapse/flare
4. Treatment failure
Early endpoints provide a useful clinical indicator for
clinicians regarding the commencement of differing
treatment regimes. The baseline is classified as the
day that the treating practitioner initiates treatment.
Control of disease activity is defined as the time at
which there is cessation of new lesions in conjunction
with the healing of preexisting lesions. In the majority
of cases the expected time period in this stage is
weeks. The end of the consolidation phase is the time
period in which no new lesions have developed over a
minimum period of 2 weeks. This phase is also char-
acterized by the healing of most lesions, and most
medical practitioners would consider the weaning of
steroids.
121
Late endpoints of disease activity may be reached
with or without therapy. Complete remission off ther-
apy is characterized by the absence of new lesions over
a 2-month period post cessation of therapy. Minimal
therapy constitutes treatment with less than or equal
to, 10 mg/day of prednisone or the equivalent and/or
the use of minimal adjuvant therapy for a duration of at
least 2 months. Minimal adjuvant therapy comprises
half the dose required to be defined as treatment fail-
ure. Partial remission off therapy is classified as devel-
opment of lesions post cessation of treatment that heal
within 1 week without treatment. The patient must be
off systemic therapy for 2 months to be classified in
this category. Patients may suffer a partial remission
on minimal therapy when they develop new lesions
that heal within a week whilst receiving minimal ther-
apy. Topical steroids also constitute minimal therapy.
A relapse/flare is defined by the development of
three or more new lesions which persist without heal-
ing for greater than a week or by the extension of pre-
existing established lesions. Treatment failure results
when there is no change in disease activity despite
treatment on therapeutic doses of systemic steroids
and other agents whose doses and durations were
agreed by international consensus.142
12.3.2 Neonatal Pemphigus
and Prevention
Neonatal PV is an autoimmune disease secondary to
transplacental transferrance of IgG antibodies.51 The
first neonatal PV case was reported in 1975 after a
woman with PV gave birth to a newborn who exhibited
a positive direct immunofluorescence staining to epi-
dermal acantholytic cells in a Tzanck preparation.175
Pemphigus antibodies have been detected in fetal car-
diac blood83 and cord blood199 in other stillborns.
Pregnancy may precipitate PV or aggravate PV
which has been in remission. The timing of conception
should probably be targeted to a period of clinical
remission, with low IF titers and the choice and dosage
of maternal medications should take into account pos-
sible fetal effects.174
Patients with PV tend to develop their skin lesions
during the first or second trimester or immediately
postpartum.113 The improvement of PV during the
third trimester may be due to rising endogenous
122
corticosteroid production by the chorion and conse-
quent immunosuppression.200
Transplacental transmission of maternally derived
intercellular substance reactive IgG antibodies to the
fetus, may result in clinical manifestation of PV in the
neonate. This is supported by findings of circulating
pemphigus antibodies in fetal plasma and its deposi-
tion in fetal skin, having the characteristic skin lesions
of PV.199
The serum titer of pemphigus antibodies does not
appear to influence neonatal outcome and there is no
definite correlation between severity of the maternal
disease and the neonatal outcome.94 The treatment of
choice is oral corticosteroids and plasmapheresis
should be reserved for severe cases resistant to high
dose corticosteroid therapy. Because of the significant
risk of fetal loss, regular fetal monitoring, along with
ultrasonography, is recommended.94
Vaginal delivery is the method of choice. Although
local trauma sustained during a natural delivery can
extend and impair recovery, Caesarean sections are
generally discouraged because both the disease pro-
cess and corticosteroid therapy can impair wound heal-
ing. Breast-feeding is not contraindicated but local
lesions can occur and there is the theoretical possibil-
ity of passive transfer of PV IgG antibodies from
mother to baby.80
There are several case reports of the cutaneous side
effects of penicillamine, in particular PF, and is also
implicated in patients with rheumatoid arthritis and
systemic sclerosis.202 Reports of pemphigoid are less
common.
Mashiah and Brenner134 have reported various envi-
ronmental and pharmacological aetiological factors in
pemphigus. The acronym PEMPHIGUS was proposed
to summarize these factors: PEsticides, Malignancy,
Pharmaceuticals, Hormones, Infectious agents, Gastro­
nomy, Ultraviolet radiation, and Stress.33 Drugs reported
to induce pemphigus are divided into three main groups
according to their chemical structure:
• Drugs containing a sulfhydryl radical, thiol drugs,
including penicillamine, captopril, gold sodium
thiomalate, penicillin, and piroxicam, and others.
• Phenol drugs, containing phenolic compounds,
including rifampicin, levodopa, aspirin, heroin, and
others.
• Nonthiol nonphenol drugs, including some of the
calcium channel blockers, angiotensin converting
S. S. Venugopal and D. F. Murrell
enzyme inhibitors, and nonsteroidal anti-inflamma-
tory drugs (NSAIDs), in addition to dipyrone, and
glibenclamide.29,33,81
Also recently reported has been the triggering of local-
ized pemphigus by imiquimod used to treat nonmela-
noma skin cancer.40,129
Garden materials and pesticides are an important
cause of contact pemphigus.27 Infectious diseases and
immunizations have been implicated in inducing or
exacerbating pemphigus, including viruses of the
Herpetoviridae family.32
Certain foods have also been purported to induce or
trigger pemphigus, in particular foods containing an
allium, phenol, thiol, or urshiol group.28,193 Several
studies point to the possible contribution of emotional
stress as a precipitating factor in pemphigus,25,31 and
pemphigus has long been considered a photosensitive
disease.109
Acantholysis in pemphigus may be due to the induc-
tion of interleukin-1a and tumor necrosis factor-a
release by keratinocytes resulting in the regulation and
synthesis of complement and proteases like plasmino-
gen activator.34, 87
PV is uncommon in neonates and children and is a
disease predominantly of the third to sixth decades of
life.152 PV in neonates is caused by maternal autoim-
mune disease with transplacental transmission of IgG
antibodies.44,166,197 It is controversial whether therapy
with corticosteroids, azathioprine, or plasmapheresis
in affected pregnant women is of benefit to the neo-
nate.174 In adults with PV, autoantibodies to Dsg 3 lead
to mucosal blistering, whereas blistering of the skin is
usually caused by autoantibodies to Dsg 1.9 In contrast
to the skin of adults, antibodies to Dsg 3 may induce
blisters in the skin of neonates.170
There are several reported cases of neonatal PV.
Neonatal PV is generally associated with a good prog-
nosis and is due to transplacental transmission of IgG
autoantibodies.44, 166 In addition, the autoantibodies to
Dsg 3 predominantly belong to the IgG4 subclass.152
The pathogenic process leading to blistering in adults
with PV is autoantibodies to Dsg3, whereas in neo-
nates it is associated with autoantibodies to Dsg1.9
This is because the IgG4 anti-Dsg1 antibodies can
cross the placenta and therefore the manifestation is in
the skin rather than mucous membranes. In PV, mater-
nal autoantibody titers appear to correlate well with
disease activity in the newborn and mother. This is in
12  Diagnosis and Prevention of Bullous Diseases
contrast to the correlation in those with FS.48 Alvarez
et al169 reported that this entity shares similar clinical
and immunopathological features with the nonen-
demic form of PF seen in the rest of the world. The
majority of the mothers with FS showed moderately
low titers of PF autoantibodies and the babies’ cord
sera showed low titers or no autoantibodies. Therefore,
it was concluded that the placenta may function as an
“in-vivo immunoadsorbent” of pathogenic antibodies.
However, Avalos-Diaz et al14 demonstrated the repro-
duction of clinical, histological, and immunological
features of PF in neonatal mice after intraperitoneal
injection of anti-Dsg1 autoantibodies from the cord
blood of a baby with PF. The exact mechanism of neo-
natal protection in PF is unknown.
There are several proposed theories for the absence
of clinical disease in the newborn with mothers with
PF. Wu et  al211 demonstrated that protection against
blisters induced by PF antibodies is provided by des-
moglein 3 expression in the superficial epidermis in
neonates. Hence in the rare cases of neonatal PF, the
infants may lack the normal neonatal expression of
desmoglein 3 in the upper epidermis, or the mothers
may produce antidesmoglein 3 antibodies. Ishii et al106
reported a patient with PF in whom PV subsequently
developed. This case suggests that mothers who deliver
infants with bullous pathology may have undergone an
antigenic shift and may be producing antidesmoglein 3
antibodies as well.
12.3.3 Bullous Pemphigoid
BP was first described by Lever in 1953 as a subepi-
dermal blistering disease. Its immunohistological fea-
tures include dermal–epidermal junction separation,
an inflammatory cell infiltrate in the upper dermis, and
BMZ-bound autoantibodies.124 These autoantibodies
show a linear staining at the dermal–epidermal junc-
tion, activate complement, and recognize two major
hemidesmosomal antigens, BP230 (BPAG1) and
BP180 (BPAG2 or type XVII collagen).130
BP typically affects the elderly, with most cases
occurring in patients greater than 60 years of age. Its
incidence is approximately 6.1–7/million in European
countries.41, 187 BP is the most common autoimmune
blistering disease and typically presents with lesions on
the trunk, proximal extremities, and flexural surfaces,
123
and involves the oral mucosa in 20% of cases.41 There
is ongoing research into the possibility that BP is asso-
ciated with increased incidence of digestive tract, blad-
der and lung malignancies. However these associations
may be age related rather than directly due to BP. Other
autoimmune disorders such as rheumatoid arthritis,
Hashimoto’s thyroiditis, dermatomyositis, lupus ery-
thematosus, and autoimmune thrombocytopenia have
been described.96 There are several clinical variants of
BP and these include:187
• Erythematous and oedematous BP
• Vesicular BP
• Localized BP
• Seborrheic pemphigoid
• Vegetating BP
• Dyshidrosiform pemphigoid
• Nodular BP
• Cicatricial pemphigoid (mucus membrane pemphi­
goid)
• Localized scarring pemphigoid
• Disseminated scarring pemphigoid
• Herpes gestationis (pemphigoid gestationis)
The gold standard for diagnosis is direct immunoelectron
microscopy and ELISA assays for BP 230 and BP 180,
but these two tests are not routinely available in many
countries. More recently, ELISA assays for BP 230 and
BP 180 with bacterially derived recombinant proteins
have been developed, which have been shown in recent
studies to increase the sensitivity in diagnosing BP.
Light microscopy is useful in initial classification;
however in the early stages of the disease or in atypical
cases of BP, this technique is not diagnostic. The find-
ings on light microscopy include subepidermal blister
formation with a dermal inflammatory infiltrate pre-
dominantly composed of neutrophils and eosinophils.
In the early phases of BP, subepidermal clefts and
eosinophilic spongiosis are present.124
DIF demonstrates the deposition of IgG and C3 at
the BMZ.54 BP may be differentiated by the separation
of skin layers at the dermoepidermoid junction using
salt split skin, where autoantibodies bind to the upper
portion of the split, as they are binding within the
hemidesmosome and lamina lucida.41
Indirect immunoflourescence (IIF) is used to detect
autoantibody titers and is a useful diagnostic technique
for the diagnosis and evaluation of disease activity in
BP. The major pathogenic epitope is the noncollagenous
124
extracellular domain (NC 16A) of the 180-kDa trans-
membrane hemidesmosomal protein (BPAG2). The
extracellular portion of BP antigen 180 contains 15
collagenous and 16 noncollagenous domains contain-
ing different antigenic sites recognized by autoantibod-
ies from several blistering diseases including BP, MMP,
and linear immunoglobulin a disease.217 IIF studies are
positive for circulating IgG antibodies in 60–80% of
patients and the antibodies bind to the epidermal side of
saline separated normal human skin.96 Several studies
have reported that the circulating antibody titers detected
by IIF are not a reliable indicator of disease activity.
Moreover, it is reported that IIF titers of BP patients’
sera mainly reflect the amount of circulating anti-BPAG1
antibodies rather than of the pathogenic anti-BPAG2
antibodies.153 Autoantibodies to BP antigen 180 and BP
antigen 230 are detected in the sera using immunoblot
and immunoprecipitation studies in 60–100% of cases.96
IIF is sufficient for the serological diagnosis of BP in
most cases however in cases that are negative on IIF,
immunoblot studies may reveal circulating antibodies,
particularly to BPAg2.77
Recently, the measurement of circulating patho-
genic antibodies in BP patients has been commercially
possible using an ELISA kit using the NC16A domain
recombinant protein (BP180 ELISA kit).192 concluded
that the ELISA index measured by this commercially
available kit correlated better with disease activity than
the IIF titers, and may be a useful tool to evaluate the
disease activity and to assess the effectiveness of the
treatment of BP. The combination of BP230 ELISA
and BP180 ELISA is a highly sensitive method for the
diagnosis of BP.215 A recent study by Sitaru et  al184
investigated the ELISA system using NC16A tetram-
ers instead of monomers, and found it to be a sensitive
and specific tool for the diagnosis and monitoring of
BP and PG. The sensitivity and specificity of the new
antitetrameric NC16A ELISA were 89.9 and 97.8%
respectively. The study also concluded that the levels
of circulating autoantibodies against BP180 paralleled
disease activity in the pemphigoid patients.
Alternatively, BP may be diagnosed by investiga-
tion of the blister fluid. Although the blister fluid is not
a more sensitive substrate than serum, obtaining the
fluid involves a less traumatic procedure than venepunc-
ture, making it particularly applicable to children and
elderly patients. This may be a useful adjunct method
for detecting BMZ antibody titer, subclass, and com-
plement fixing activity in BP.216
S. S. Venugopal and D. F. Murrell
12.3.3.1 Prevention of Bullous Pemphigoid
In 1970, drug-induced BP was first reported secondary
to salicylazosulfapyridine in an 11-year-old child.16
The association between drugs and BP is being increas-
ingly reported in the literature including frusemide,
penicillins, sulfasalazine, and ibuprofen.178
Shachar et  al178 postulated that nonimmunological
mechanisms involve splitting at the dermoepidermal
junction in drug-induced BP, independent of autoanti-
bodies or other immune factors. Immunological mech-
anisms are generally of two types. Firstly, the drug
produces an antigenic stimulus or, secondly, the drug
has a direct regulatory effect on the immune system
and results in immune dysregulation and autoantibody
production.
Calcium channel blockers may result in drug
induced BP. Brenner et al concluded that drug induced
BP may be as a result of induced alterations in calcium
concentrations.30 The study found that normal human
skin explants cultured in the presence of nifedipine at
different concentrations resulted in intraepithelial
splitting (pemphigus type) which showed cell–cell
dyshesion among the keratinocytes and subepithelial
splitting (pemphigoid type) displaying dermoepider-
mal cleft formation. The study also concluded that the
type of pathological change was donor-specific and
not concentration-related.30 This study has not been
reproduced elsewhere, however.
Several case reports have been published linking
penicillamine as a causative factor for BP.127,131,202
There is strong evidence to suggest that drug-induced
pemphigoid reverses with cessation of the offending
medications and hence clinicians must be vigilant
when drug-induced pemphigoid is suspected.
12.3.4 Pemphigoid Gestationis
Pemphigoid gestationis, previously referred to as her-
pes gestationis, is a pregnancy-associated nonviral
autoimmune subepidermal blistering disease. It is not
related to herpes virus infections; the old term herpes
gestationis rather describes the occurrence of herpeti-
form lesions as part of the clinical picture of this con-
dition.58, 179 Gestational pemphigoid is also known as
“herpes gestationis” or “pemphigoid gestationis.” It
typically occurs during the second or third trimesters
12  Diagnosis and Prevention of Bullous Diseases
of pregnancy and resolves after delivery. It clinically
presents with urticarial plaques, which develop into
tense vesicles in the periumbilical area. The lesions
may generalize and typically reappear in subsequent
pregnancies. This condition is immunologically identi-
cal to BP.
Linear deposition of C3 and, less frequently, of
immunoglobulin G along the cutaneous BMZ, detected
on direct immunofluorescence microscopy are immu-
nopathological hallmarks of pemphigoid gestationis.179
Indirect complement fixation immunofluorescence
identifies circulating immunoglobulin G autoantibod-
ies, termed herpes gestationis factor and is identified in
the sera of the majority of pemphigoid gestationis
patients. Deposition of immunoreactants to the upper
portion of the lamina lucida, directly beneath the
plasma membrane of basal keratinocytes is evident on
immunoelectronmicroscopy.179 The 16th noncollage-
nous A domain of BP antigen 180 is the major target of
autoantibodies in pemphigoid gestationis.43,79,128,182 The
antigenic sites are clustered within the membrane-
proximal portion of this domain.43,128,182,183 ELISA
using recombinant BP antigen 180 is a sensitive tool
for the detection and monitoring of levels of autoanti-
bodies in pemphigoid gestationis.183
Gestational pemphigoid may be rarely associated
with a choriocarcinoma, hydatiform mole, or premature
birth. It is clinically important to differentiate PG from
polymorphic urticarial plaques of pregnancy (PUPPP).
Both conditions have similar presentations and have
differing fetal and maternal prognostic implications.
Powell et al162 found NC16a ELISA as highly sensitive
and highly specific in differentiating PG from PUPPP,
and a valuable tool in the serodiagnosis of PG.
12.3.5 Mucous Membrane Pemphigoid
MMP, formerly known as cicatricial pemphigoid, is a
heterogeneous group of autoimmune subepidermal
blistering diseases associated most commonly with
autoantibodies to BP 180 and less frequently with
those to laminin 5 or type VII collagen. In addition, a
few cases have been described with autoantibodies to
the b4 subunit of a6b4 integrin.126
MMP is an autoimmune bullous disease that pri-
marily affects mucous membranes leading to a scar-
ring phenotype. This is in contrast to BP where healing
125
predominantly occurs without scarring. Patients can be
classified as low or high risk. Low-risk patients have
lesions which are limited to the oral mucosa and skin.
High-risk patients have involvement of other mucosal
surfaces resulting in significant morbidity. MMP
patients produce autoantibodies to two recognized
components of the dermoepidermal BMZ: BP180 and
laminin 5 (Lam332).18 IgG reactivity to Lam332 of the
MMP and BP sera was not significantly associated
with IgG reactivity against other autoantigens of the
BMZ, such as BP180 or BP230. Thus, the established
Lam332 ELISA may be a valuable novel diagnostic
and prognostic parameter for MMP.18
12.3.6 Epidermolysis Bullosa Acquisita
EBA is an acquired bullous disease characterized by
immunoglobulin G (IgG) autoantibodies that react
with type VII collagen in the anchoring fibrils, result-
ing in bullae formation at the dermoepidermal junc-
tion.210 The autoantibodies specifically bind to the
145-kDa amino-terminal domain (NC1).122,208 EBA is a
rare disease with an incidence of 0.17–0.26/million
people in Western Europe and usually presents in the
fourth to fifth decades of life, but has been reported in
childhood.20,84,218 Roenigk et al172 was the first to set the
initial diagnostic criteria for EBA.
The etiology of EBA is unknown; however an auto-
immune pathogenesis is postulated.209,210 Bullous sys-
temic lupus erythematosus (SLE) compared with EBA
also display autoantibodies against type VII collagen.73
The association of EBA and bullous SLE with HLA
major histocompatibility (MHC) class II cell surface
antigen, HLA-DR2 further supports the autoimmune
hypothesis for EBA (Fig. 12.5).74,96
There are two main phenotypes. These include the
classic noninflammatory mechanobullous type and the
inflammatory type. Patients with the classic nonin-
flammatory mechanobullous type have marked skin
fragility with blisters and erosions at trauma sites.
Healing results in scarring and milia. The inflamma-
tory type71 can be difficult to differentiate from BP,
cicatricial pemphigoid, and chronic bullous dermatosis
of childhood.151 Previous studies have reported that at
least 50% of patients with EBA show a BP-like clinical
presentation and 10% of patients with the clinical pre-
sentation of BP may actually have EBA.72
126
Fig. 12.5  Milia and atrophic scarring on the dorsal fingers in
classical epidermolysis bullosa acquisita (EBA). Sites exposed
to chronic trauma have most of the blistering
On direct and indirect immunofluorescence testing,
linear IgG and C3 deposits on the basement membrane
are found in both BP and EBA.62 Dermal–epidermal
separation with sodium chloride or suction can be a
useful technique demonstrating IgG deposits at the
DEJ, but immunoblotting confirms the diagnosis.103,115
Direct immunoelectron microscopy is the gold stan-
dard of diagnosis and demonstrates IgG deposits either
within or below the lamina densa of the BMZ.41
Blisters in EBA and bullous systemic lupus erythe-
matosus (BSLE) are due to defective adhesion of the
lamina densa subregion of the epithelial basement
membrane to the underlying dermis. Previous studies
of a small number of EBA patients show recognition
by autoantibodies of proteolytic fragments containing
the 145-kDa noncollagenous domain of type VII col-
lagen. Interference with the adhesion function of type
VII collagen may occur due to antibodies binding to
fibronectin homology regions within the 145-kDa non-
collagenous domain and contribute to lamina densa-
dermal dysadhesion in epidermolysis bullous acquisita
and bullous SLE.75
Lapiere et  al identified four major immunodomi-
nant epitopes localized within the amino-terminal,
noncollagenous (NC-1) domain in patients with EBA.
Sera from patients with bullous SLE (BSLE) revealed
a similar pattern of epitopes to EBA, suggesting that
the same epitopes could serve as autoantigens in both
blistering conditions. Chen et  al42 recently described
that the pathogenic antibodies in EBA have been shown
to bind to the cartilage matrix domain (CMP) of type
S. S. Venugopal and D. F. Murrell
VII collagen. This study also showed that passive
transfer of EBA autoantibodies directed against the
CMP subdomain into mice are pathogenic and recom-
mended that further fine mapping of the pathogenic
epitope to a smaller region with the 227 AA CMP sub-
domain may also facilitate the development of effec-
tive peptide therapy for EBA.
12.3.7 Dermatitis Herpetiformis
DH is a relatively rare skin disorder with an estimated
incidence of 1:10,000 in the United Kingdom and typi-
cally presents in patients in their third or fourth
decades. In Anglo-Saxon and Scandinavian popula-
tions the prevalence is between 10 and 39 per 100,000.
DH is much less common in blacks and Asians. Men
are slightly more likely to be affected than females
with a ratio of approximately 3:2.46
The typical lesions in DH include intensely pruritic
eruptions of erythematous papules or vesicles distrib-
uted symmetrically along extensor surfaces. The areas
most commonly affected are the extensor surfaces of
the elbows and knees, and the buttocks and scalp. The
diagnosis of DH is based on clinical presentation,
biopsy for hematoxylin and eosin, and direct immuno-
fluorescence.198 Definitive diagnosis of DH depends on
the direct immunofluorescence finding of granular or
fibrillar IgA deposits along the BMZ.161 In DH, dermal
papillary edema and neutrophil infiltration are seen.
A biopsy of an intact vescicle demonstrates a subepi-
dermal blister with neutrophils. The hallmark finding
on direct immunofluorescence testing in DH is granu-
lar deposition of IgA in the dermal papillae of perile-
sional skin.70,146,220 DH typically has a chronic course
with exacerbations and remissions. DH can be associ-
ated with a gluten-sensitive enteropathy which is iden-
tical to Celiac disease (CD). Most affected patients are
asymptomatic however may develop steatorrhea,
abnormal D-xylose absorption, or anemia caused by
iron or folate deficiency.114
Two-thirds of patients have a small intestinal enterop-
athy with villous atrophy as seen in CD. However, the
remaining third also show evidence of gluten sensitivity
in the intestine. Gluten challenge in these patients
results in villous atrophy. The initial treatment of the
rash is gluten withdrawal in combination with one of
the following three drugs: dapsone, sulphapyridine, or
12  Diagnosis and Prevention of Bullous Diseases
sulphamethoxypyridazine.69 Despite DH being a skin
manifestation of CD, many patients with DH may not
complain of gastrointestinal symptoms.146
Patients with DH have a high incidence of autoim-
mune disorders including thyroid disease, pernicious
anemia, and insulin-dependent diabetes, and should be
screened for these conditions on a yearly basis. There
is also an increased incidence of lymphoma.69 DH
patients can suffer from both B-Cell and T-cell lym-
phomas. Hervonen et  al97 concluded that patients
adhering to a strict gluten-free diet had a reduced inci-
dence of lymphoma.
DH must be considered as a differential diagnosis for
patients with a diagnosis of eczema, unresponsive to
treatment. Eczema generally presents in early child-
hood, characterized by intraepidermal vesicles and bul-
lae at sites of spongiosis.19,159 Screening for DH can be
performed by testing for tissue transglutaminase anti-
bodies or antiendomysial antibodies (AEmA).38,156
However, the gold standard is a skin biopsy for routine
histologic examination and direct immunofluores-
cence.76 In summary, key findings that can confirm a
diagnosis of DH include: clinical findings, DIF detec-
tion of typical junctional IgA deposits, and positive
serum tests for coeliac disease. Any two of these three
findings are consistent with DH.21 Adherence to a strict
gluten-free diet requiring avoidance of foods containing
wheat, rye, or barley can prevent outbreaks of DH.69
12.3.8 Linear IgA Dermatosis
LAD, an acquired subepidermal blistering skin dis-
ease, presents with vesicular or bullous skin lesions,
often with herpetiform arrangement, and is associated
with intense burning and pruritus. It can be differenti-
ated from DH and BP by the linear deposits of IgA in
the BMZ. The disease is not associated with a gluten-
sensitive enteropathy. Histopathological findings
include subepidermal blisters and intrapapillary
microabscesses.
There are two clinical phenotypes reported: adult
and childhood LAD (chronic bullous dermatosis of
childhood). Childhood LAD usually remits in 64% of
subjects by the age of 6–8 years.50 The adult type
of LAD predominantly presents in the fourth decade or
later, has a slight female predisposition, and a remis-
sion rate of 48%.204
127
LAD is caused by the presence of IgA autoantibod-
ies against different dermoepidermal antigens and is
characterized by a homogeneous linear band of IgA
deposition along the BMZ.167 Frequently recognized
antigens are a 180-kDa protein, presumably BP anti-
gen II, a 120-kDa, and a 97-kDa molecule, related pro-
teins associated with breakdown products of collagen
type XVII.219, 221 The following antigenic proteins are
also reported: BP230,78 collagen VII90, 209 and antigens
of molecular weights of 100, 110–120, 145, 160–180,
200, 220, 230, 255, and 285 kDa.53, 205, 212
LAD1 and LADB97, BP 230, LAD 285, and colla-
gen VII are the target antigens.99,132 EM studies have
shown that serum from patients with LAD binds to the
lamina lucida as well as the sublamina densa regions.107
IgA autoantibodies also bind to the NC16 transmem-
brane epitope as well as the COL15 and Ecto 2 epitopes,
located at the carboxyl terminus of the ectodomain in
BP 180.219,41 The gold standard for diagnosis of LAD is
direct immunofluorescence showing linear deposits of
IgA along the BMZ.39
12.3.8.1 Prevention
Collier et al45 stated that there were no contraindications
to pregnancy in patients with LAD, and recommended
that therapy be reduced or ceased whenever possible
during pregnancy, with particular emphasis on counsel-
ing regarding the possibility of relapse post partum.
Medications reported to induce LAD include amio-
darone, ampicillin, captopril, cefamandole, cyclosporine,
diclofenac, glibenclamide, interferon-[gamma], inter-
leukin 2, lithium, penicillin G, phenytoin, piroxicam,
somatostatin, sulfamethoxazole/trimethoprim, and
vigabatrin.117, 160 Up to two-thirds of LAD cases may be
drug-induced, and vancomycin is the offending drug in
approximately half of the drug-induced LAD cases.160
Vancomycin-induced LAD (VILAD) has a heteroge-
neous clinical presentation. It may be difficult to dif-
ferentiate VILAD from other common blistering
disorders, such as BP or DH.121 VILAD can present
with targetoid erythema multiforme-like lesions, pap-
ules, vesicles, and bullae, predominantly located on the
extremities (90%) and trunk (77%).144
Histological findings in VILAD include subepider-
mal bullae with a predominately neutrophilic infiltrate
and basal cell vacuolization and these features distin-
guish it from other blistering conditions such as PF or
128
PV.144 Clinical differentials for VILAD include
­erythema multiforme, Stevens-Johnson syndrome (SJS),
and toxic epidermal necrolysis. VILAD can be distin-
guished morphologically from these conditions by the
absence of interface changes and keratinocyte necro-
sis.140, 148
Perilesional skin biopsy DIF in VILAD reveals
strong linear deposition of IgA along the BMZ, whereas
BP is characterized by a linear IgG deposition along
the BMZ. VILAD cannot be differentiated from idio-
pathic LAD, but the differing clinical course of these
diseases suggests differing pathogenesis.144 Sponta­
neous remission post vancomycin withdrawal has been
observed in previously reported cases of VILAD.
Based on available evidence, autoantibody mediated
bullae formation is postulated as the pathogenesis of
VILAD.121,168,206
12.3.9 Other Drug-Induced
Bullous Diseases
12.3.9.1 Toxic Epidermal Necrolysis
Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) are rare, life-threatening, bullous cuta-
neous diseases generally considered as immune-mediated
reactions to drugs resulting in severe cutaneous adverse
reactions (SCAR), characterized by epidermal necrosis,
extensive detachment of the epidermis, erosions of mucous
membranes, and severe constitutional symptoms.85
The majority of TEN cases are related to chemicals
systemically administered as drug therapy. The drugs
implicated in most series were antibacterial sulfon-
amides, anticonvulsants, allopurinol, pyrazolone deriv-
atives, and, less frequently, other NSAIDs.93 The
SCAR study included 245 patients with TEN and SJS
in Europe and confirmed the responsibility of the
“classical culprit” drugs: antibacterial sulfonamides
(cotrimoxazole); aromatic anticonvulsants (phenobar-
bital, phenytoin, carbamazepine); some antibiotics
(aminopenicillins, quinolines, cephalosporins); some
NSAIDs (tenoxicam, piroxicam), chlormezanone, and
allopurinol.173 Most of these drugs are therapeutic and
may not be avoided, as the overall risk of SCAR is low.
However, if there are early signs of SCAR, then these
drugs are the likeliest causes and should be ceased.
They should then be avoided completely in future, as
S. S. Venugopal and D. F. Murrell
these are potentially life-threatening drug reactions.
Wearing a medicalert bracelet with the name of the
culprit is worthwhile as a preventative to being given
the SCAR-inducing drug again.
12.4 Infective Causes
Herpes simplex virus (HSV), also known as Human
Herpes virus, has two strains: HSV1 and HSV2 and
typically causes blisters in the skin, mucus membranes
or the genitals. HSV becomes latent after the primary
infection in the cell bodies of the nerves in the area of
the primary infection. Transmission of the virus occurs
with contact of carriers with active HSV. The vectors
for HSV transmission include saliva, semen, vaginal
fluid, and shed skin from active lesions. Herpes may
also be transmitted to an infant during childbirth,
which may result in aseptic meningitis. HSV1 may be
prevented by simple measures such as not kissing
when active lesions are present, and HSV2 can be pre-
vented by barrier contraception and avoidance of sex
when the blisters are active; however viral shedding
may occur even without blisters.
Erythema multiforme (EM) is a disease of multiple
etiologies and often recurs. It results in a polymorphic
eruption caused by exposure to medication or various
infections, in particular HSV.13,119 The most common
predisposing factor for EM is HSV. Other causes
include mycoplasma and fungal disease. The medica-
tions predisposing to EM, outlined in the SCAR
study, include: antibacterial sulfonamides, anticon-
vulsants (phenobarbital, phenytoin, carbamazepine,
and valproic acid), oxicam NSAIDs, chlormezanone,
allopurinol, and acetaminophen in countries other than
France, imidazole antifungal agents, corticosteroids
for systemic use, aminopenicillins, cephalosporins,
quinolones, and tetracyclines.173
Differences in case selection in terms of subsets
of EM studied may have partly resulted in wide vari-
ations in the detection of HSV DNA (36–75%) by
polymerase chain reaction (PCR) in EM.145 Kokuba
et  al119 state that HSV associated erythema multi-
forme pathology includes a delayed-type hypersen-
sitivity component and is mechanistically distinct
from drug-induced erythema multiforme. Diagnostic
tests for HSV-induced erythema multiforme include
serum hematology and biochemistry tests, blood and
12  Diagnosis and Prevention of Bullous Diseases
vesicle cultures, punch biopsy for histological exam-
ination, and PCR.
Oral acyclovir is used to suppress erythema multi-
forme associated with HSV. EM is not prevented if
oral acyclovir is administered after a herpes simplex
recurrence is evident, and it is of no value after ery-
thema multiforme has occurred. There is some ques-
tion whether prevention of erythema multiforme may
be achieved with continuous topical treatment with
acyclovir to sites affected by recurrent herpes.101
Herpes zoster (HZ), commonly known as shingles,
is a disease caused by the varicella zoster virus (VZV)
and is characterized by a painful, vesicular skin rash.
The virus may remain dormant in the nerve cell bodies
and trigger latent infections, typically in a dermatomal
distribution. It particularly affects immunocomprised
patients, resulting in significant morbidity.
Clinical findings are often sufficient to diagnose
HZ. Atypical presentations may be confirmed on viral
culture, direct immunoflourescence assay or PCR.
Laboratory techniques can be particularly helpful
when differentiating between VZV and zosteriform
herpes simplex.201
Oxman et al150 found that use of the zoster vaccine,
live attenuated Oka/Merck VZV vaccine, reduced the
incidence of postherpetic neuralgia by 66% and HZ by
51%, and concluded that the vaccine markedly reduced
the morbidity and postherpetic neuralgia associated
with HZ in patients older than 60. Also, the treatment
of HZ with oral acyclovir can reduce residual pain
after 6 months in almost 50% of immunocompetent
adults.108 Wood et  al207 found that acyclovir reduced
zoster-related pain duration and prevalence by half.
Combined acyclovir and prednisone therapy can
improve quality of life in relatively healthy patients
older than 50 years of age with localized HZ.203
Orf virus is an exanthemous disease caused by a
parapox virus predominantly affecting sheep and
goats. Orf is a zoonotic disease and may be transmitted
to humans via direct contact from the infected animals.
Infection in humans results in a self-limiting and
benign course in immunocompetent individuals result-
ing in purulent papules with localized symptoms.
Prevention of the Orf virus can be achieved by using
gloves and good personal hygiene, particularly when
working with infected animals.149
Acknowledgment  The authors would like to thank Ms. Kezia
Gaitskell of Oxford University Medical School for proofreading
of this manuscript.
129
References
  1. Aberdam D, Galliano MG, Vailly J, et al Herlitz’s junctional
epidermolysis bullosa is linked to mutations in the gene
(LAMC2) for the gamma 2 subunit of nicein/kalinin (lami-
nin 5). Nat Genet. 1994;6:299–304
  2. Ahmed AR, Graham J, Jordan RE, Provost TT. Pemphigus:
current concepts. Ann Intern Med. 1980;92:396–405
  3. Ahmed AR, Yunis EJ, Khatri K. Major histocompatibility
complex haplotype studies in Ashkenazi Jewish patients
with Pemphigus Vulgaris. Proc Natl Acad Sci USA. 1991;
87:7658–7662
  4. Ahmed AR, Mohimen A, Yunis EJ, et al Linkage of pemphi-
gus vulgaris antibody to the major histocompatibility com-
plex in healthy relatives of patients. J Exp Med. 1993;
177:419
  5. Amagai M, Klaus-Kovtun V, Stanley JR. Auto-Ab against a
novel epithelial cadherin in pemphigus vulgaris, a disease of
cell adhesion. Cell. 1991;67:869–877
  6. Amagai M, Nishikawa T, Nousari HC, et  al Antibodies
against desmoglein 3 (pemphigus vulgaris antigen) are pres-
ent in sera from patients with paraneoplastic pemphigus and
cause acantholysis in  vivo in neonatal mice. J Clin Invest.
1998;102:775–782
  7. Amagai M, Hashimoto T, Komai A, et  al Usefulness of
enzyme-linked immunosorbent assay using recombinant
desmogleins 1 and 3 for serodiagnosis of pemphigus. Br
J Dermatol. 1999;140:351–357
  8. Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol.
1997;12:77–96
  9. Anhalt GJ. Making sense of antigens and antibodies in pem-
phigus. J Am Acad Dermatol. 1999;40:763–766
10. Anhalt GJ, Kim SC, Stanley JR, et al Paraneoplastic pem-
phigus. N Engl J Med. 1990;323:1729–1735
11. Anton-Lamprecht I. The skin. In: Papadimitriou JM,
Henderson DW, Spagnolo V, eds. Diagnostic Ultrastructure
of Non-Neoplastic Diseases. 5th ed. Edinburgh: Churchill
and Livingstone; 1992
12. Anton-Lamprecht I, Schnyder UW. Epidermolysis bullosa
herpetiformis Dowling-Meara: a report of a case and path-
omorphogenesis. Dermatologica. 1982;164:221–235
13. Aurelian L, Kokuba H, et al Understanding the pathogenesis
of HSV-associated erythema multiforme. Dermatology.
1998;197(3):219–222
14. Avalos-Diaz E, Olague-Marchan M, Lopez-Swiderski A,
Herrera-Esparza R, Diaz LA. Transplacental passage of
maternal pemphigus foliaceus autoantibodies induces neona-
tal pemphigus. J Am Acad Dermatol. 2000;43(6):1130–1134
15. Baudoin C, Miquel C, Blanchet-Bardon C, et al Herlitz junc-
tional epidermolysis bullosa keratinocytes display heteroge-
neous defects of nicein/kalinin gene expression. J Clin
Invest. 1994;93:862–869
16. Bean SF, Good RA, Windhorst DB. Bullous pemphigoid in
an 11-year-old boy. Arch Dermatol. 1970;102:205–208
17. Bedane C, Prost C, Thomine E, et al Binding of autoantibod-
ies is not restricted to desmosomes in pemphigus vulgaris:
comparison of 14 cases of pemphigus vulgaris and 10 cases
of pemphigus foliaceus studied by western immunoblot and
immunoelectron microscopy. Arch Dermatol Res. 1996;288:
343–352
130
18. Bekou V, Thoma-Uszynski S, Wendler O, et al Detection of
laminin 5-specific auto-antibodies in mucous membrane and
bullous pemphigoid sera by ELISA. J Invest Dermatol.
2005;124(4):732–740
19. Beltrani VS, Boguneiwicz M. Atopic dermatitis. Dermatol
Online J. 2003;9:1
20. Bernard P, Vaillant L, Labeille B, et al Incidence of distribu-
tion of subepidermal autoimmune skin diseases in three
French regions. Arch Dermatol. 1995;131:48–52
21. Beutner EH, Baughman RD, Austin BM, Plunkett RW,
Binder WL. A case of dermatitis herpetiformis with IgA
endomysial antibodies but negative direct immunofluo-
rescent findings. J Am Acad Dermatol. 2000;43:
329–332
22. Bhol K, Ahmed AR, Aoki V, Mohimen A, Nagarwalla N,
Natarajan K. Correlation of peptide specificity and IgG sub-
class with pathogenic and nonpathogenic autoantibodies in
pemphigus vulgaris: a model for autoimmunity. Proc Natl
Acad Sci USA. 1995;92:5239–5243
23. Bolte C, Gonzalez S. Rapid diagnosis of major variants of
congenital epidermolysis bullosa using a monoclonal anti-
body against collagen type IV. Am J Dermatopathol. 1995;
17(6):580–583
24. Borradori L, Trueb RM, Jaunin F, et al Autoantibodies from
a patient with paraneoplastic pemphigus bind periplakin, a
novel member of the plakin family. J Invest Dermatol.
1998;111:338–340
25. Brenner S, Bar-Nathan EA. Pemphigus vulgaris triggered by
emotional stress. J Am Acad Dermatol. 1984;11:524–525
26. Brenner S, Wolf R, Ruocco V. Drug-induced pemphigus.
I. A survey. Clin Dermatol. 1993;11(4):501–505
27. Brenner S, Wolf R, Ruocco V. Contact pemphigus: a subgroup
of induced pemphigus. Int J Dermatol. 1994;33:843–845
28. Brenner S, Ruocco V, Wolf R, De Angelis E, Lombardi ML.
Pemphigus and dietary factors. In vitro acantholysis by allyl
compounds of the genus Allium. Dermatology. 1995;190:
197–202
29. Brenner S, Bialy-Golan A, Ruocco V. Drug-induced pem-
phigus. Clin Dermatol. 1998;163:393–397
30. Brenner S, Ruocco V, Bialy-Golan A, et al Pemphigus and
pemphigoid-like effects of nifedipine on in vitro cultured nor-
mal human skin explants. Int J Dermatol. 1999;38(1):36–40
31. Brenner S, Tur E, Shapiro J, et al Pemphigus vulgaris: envi-
ronmental factors. Occupational, behavioral, medical, and
qualitative food frequency questionnaire. Int J Dermatol.
2001;40:562–569
32. Brenner S, Sasson A, Sharon O. Pemphigus and infections.
Clin Dermatol. 2002;20:114–118
33. Brenner S, Mashiah J, Tamir E, Goldberg I, Wohl Y.
Pemphigus: an acronym for a disease with multiple etiolo-
gies. Skinmed. 2003;2:163–167
34. Brenner S, Ruocco V, Ruocco E, Srebrnik A, Goldberg I.
A  possible mechanism for phenol-induced pemphigus.
Skinmed. 2006;5(1):25-26; quiz 27–28
35. Bruckner-Tuderman L. Collagen VII and bullous disorders
of the skin. Dermatology. 1994;189:16–20
36. Brust MD, Lin AN. Epidermolysis bullosa: practical manage-
ment and clinical update. Dermatol Nurs. 1996;8(2):81–89
37. Calvanico NJ, Martins CR, Diaz LA. Characterization of
pemphigus foliaceus antigen from human epidermis. J Invest
Dermatol. 1991;96(6):815–821
S. S. Venugopal and D. F. Murrell
38. Caproni M, Cardinali C, Renzi D, Calabro A, Fabbri P.
Tissue transglutaminase antibody assessment in dermatitis
herpetiformis. Br J Dermatol. 2001;144:196–197
39. Cauza K, Hinterhuber G, Sterniczky B, et al Unusual clinical
manifestation of linear IgA dermatosis: a report of two cases.
J Am Acad Dermatol. 2004;51:112–117
40. Champagne G, Roca M, Martinez A. Successful treatment
of a high-grade intraepithelial neoplasia with imiquimod,
with vulvar pemphigus as a side effect. Eur J Obstet Gynecol
Reprod Biol. 2003;109:224–227
41. Chaudhari P, Marinkovich MP. What’s new in blistering dis-
orders? Curr Allergy Asthma Rep. 2007;7(4):255–263
42. Chen M, Doostan A, Bandyopadhyay P, et al The cartilage
matrix protein subdomain of type VII collagen is pathogenic
for epidermolysis bullosa acquista. Am J Pathol. 2007;
170(6):2009–2018
43. Chimanovitch I, Schmidt E, Messer G, et al IgG1 and 0IgG3
are the major immunoglobulin subclasses targeting epitopes
within the NC16A domain of BP180 in pemphigoid gesta-
tionis. J Invest Dermatol. 1999;113:140–142
44. Chowdhury MMU, Natarajan S. Neonatal pemphigus vul-
garis associated with mild oral pemphigus vulgaris in the
mother during pregnancy. Br J Dermatol. 1998;139:
500–503
45. Collier PM, Kelly SE, Wojnarowska F. Linear IgA disease
and pregnancy. Acad Dermatol. 1994;30(3):407–411
46. Cotell S, Robinson ND, Chan LS. Autoimmune blistering
skin diseases. Am J Emerg Med. 2000;18(3):288–299
47. Dang N, Klingberg S, Marr P, Murrell DF. Review of col-
lagen VII sequence variants found in Australasian
patients with dystrophic epidermolysis bullosa reveals
nine novel COL7A1 variants. J Dermatol Sci. 2007;46(3):
169–178
48. Diaz LA, Sampaio SA, Rivitti EA, et al Endemic pemphigus
foliaceus (fogo selvagem). I: Clinical features and immu-
nopathology. J Am Acad Dermatol. 1989;20:657–659
49. Diaz LA, Arteaga LA, Hilario-Vargas J, et al Antidesmoglein-1
antibodies in onchocerciasis, leishmaniasis and Chagas dis-
ease suggest a possible aetiological link to Fogo Selvagem.
J Invest Dermatol. 2004;123:1045–1051
50. Dippel E, Orfanos CE, Zouboulis C. Linear IgA dermatosis
presenting with erythema annulare centrifugum lesions:
report of three cases in adults. J Eur Acad Dermatol Venereol.
2001;15(2):167–170
51. Dugan EM, Anhalt GJ, Diaz LA. Pemphigus. In: Jordan RE,
ed. Immunologic Diseases of the Skin. Norwalk, CN:
Appleton and Lange; 1991:279–291
52. Eady RA, Tidman MJ. Junctional epidermolysis bullosa. In:
Wojnarowska F, Briggaman RA, eds. Management of
Blistering Diseases. London: Chapman and Hall Medical;
1992:213–224
53. Egan CA, Zone JJ. Linear IgA bullous dermatosis. Int J
Dermatol. 1999;38:818–827
54. Egan CA, Lazarova Z, Darling TN, Yee C, Yancey KB.
Anti-epiligrin cicatricial pemphigoid: clinical findings,
immunopathogenesis, and significant associations. Medicine.
2003;82(3):177–186
55. Elias S. Use of fetoscopy for the prenatal diagnosi of heredi-
tary skin disorders. Curr Probl Dermatol. 1987;16:1–3
56. Elias S, Emerson DS, Simpsos JL, Shulman LP, Holbrook
KA. Ultrasound guided fetal skin sampling for prenatal
12  Diagnosis and Prevention of Bullous Diseases
diagnosis of genodermatoses. Obstet Gynecol. 1994;83:
337–341
57. Emery DJ, Diaz LA, Fairley JA, Lopez A, Taylor AF,
Giudice GJ. Pemphigus foliaceus and pemphigus vul-
garis autoantibodies react with the extracellular domain
of desmoglein-1. J Invest Dermatol. 1995;104(3):
323–328
58. Engineer L, Bhol K, Ahmed AR. Pemphigoid gestationis: a
review. Am J Obstet Gynecol. 2000;183:483–491
59. Fassihi H, Eady RA, Mellerio JE, et al Prenatal diagnosis for
severe inherited skin disorders: 25 years’ experience. Br J
Dermatol. 2006;154(1):106–113
60. Fassihi H, Renwickb PJ, Blackb C, McGrath JA. Single
cell PCR amplification of microsatellites flanking the
COL7A1 gene and suitability for preimplantation genetic
diagnosis of Hallopeau-Siemens recessive dystrophic
epidermolysis bullosa. J Dermatol Sci. 2006;42:
241–248
61. Fassihi H, Grace J, Lashwood A, et  al Preimplantation
genetic diagnosis of skin fragility-ectodermal dysplasia syn-
drome. Br J Dermatol. 2006;154(3):546–550
62. Feliciani C, Fasciocco D, Franchi A, Amerio P. Epidermolysis
bullosa acquisita in a 10-year-old Albanian boy. Br J
Dermatol. 1997;137(2):307–308
63. Fine JD. Laboratory tests for epidermolysis bullosa. Derma­
topathol Clin. 1994;12:123–132
64. Fine JD, Stenn J, Johnson L, et al Autosomal recessive epi-
dermolysis bullosa simplex: generalized phenotypic features
suggestive of junctional or dystrophic epidermolysis bullosa,
and association with neuromuscular diseases. Arch Dermatol.
1989;125:931–938
65. Fine JD, Bauer EA, Briggaman RA, et al Revised clinical
and laboratory criteria for subtypes of inherited epider-
molysis bullosa. A consensus report by the Subcommittee
on Diagnosis and Classification of the National
Epidermolysis Bullosa Registry. J Am Acad Dermatol.
1991;24:119–135
66. Fine JD, Bauer EA, Mcguire J, Moshell A. Non molecular
diagnostic testing of epidermolysis bullosa: current tech-
niques, major findings, and relative sensitivity and specific-
ity. In: Fine JD, Bauer EA, McGuire J, Moshell A, eds.
Epidermolysis Bullosa, Clinical, Epidemiologic, and Lab­
oratory Advances and the Findings of the National
Epidermolysis Bullosa Registry. Baltimore, MD: The John
Hopkins University; 1999
67. Fine JD, Eady RA, Bauer EA, et al Revised classification for
inherited epidermolysis bullosa: report of the second Inter_
national Consensus Meeting on diagnosis and classification
of epidermolysis bullosa. J Am Acad Dermatol.
2000;42:1051–1066
68. Fine J D, Eady RA, Bauer EA, Bauer J, Bruckner-Tuderman
L, Heagerty A, Hintner H, Hovnanian A, Jonkman MF,
Leigh I, McGrath JA, Mellerio JE, Murrell DF, Shimizu H,
Uitto J, Vahlquist A, Woodley D, Zambruno G, Revised
Consensus for Definitions of Epidermolysis Bullosa. J Am
Acad Dermatol 58(June): 931–950, 2008 (in press Dec 2007;
advance on line March 2008)
69. Fry L. Dermatitis herpetiformis. Baillieres Clin Gastroenterol.
1995;9(2):371–393
70. Fry F. Dermatitis herpetiformis: problems, progress, and
prospects. Eur J Dermatol. 2002;12:523–531
131
71. Gammon WR, Briggaman RA, Wheeler CE. Epidermolysis
bullosa acquisita presenting as an inflammatory bullous dis-
ease. F Am Acad Dermatol. 1982;7:382–387
72. Gammon WR, Briggaman RA, Woodley DT, et  al
Epidermolysis bullosa acquisita-a pemphigoid-like disease.
J Am Acad Dermatol. 1984;11:820–832
73. Gammon WR, Woodley DT, Dole KC, Briggaman RA.
Evidence that basement membrane zone antibodies in
bullous eruption of systemic lupus erythematosus recog-
nized epidermolysis bullosa acquista auto antigens. J Invest
Dermatol. 1985;84:472–476
74. Gammon WR, Heise ER, Burke WA, Fine JD, Woodley DT,
Briggaman RA. Increased frequency of HLA-DR2 in patients
with autoantibodies to epidermolysis bullosa acquista anti-
gen; evidence that the expression of autoimmunity to type
VII collagen is HLA class II allele associated. J Invest
Dermatol. 1988;91:228–232
75. Gammon WR, Murrell DF, Jenison M, et al Autoantibodies
to type VII collagen recognize epitopes in a fibronectin-like
region of the noncollagenous (NC1) domain. J Invest
Dermatol. 1993;100:618–622
76. George DE, Browning JC, Hsu S. Medical pearl: dermatitis
herpetiformis – potential for confusion with eczema. J Am
Acad Dermatol. 2006;54(2):327–328
77. Ghohestani R, Kanitakis J, Nicolas JF, Cozzani E, Claudy A.
Comparative sensitivity of indirect immunofluorescence to
immunoblot assay for the detection of circulating antibodies
to bullous pemphigoid antigens 1 and 2. Br J Dermatol.
1996;135(1):74–79
78. Ghohestani RF, Nicolas JF, Kanitakis J, Claudy A. Linear
IgA bullous dermatosis with IgA antibodies exclusively
directed against the 180- or 230-kDa epidermal antigens. J
Invest Dermatol. 1997;108:854–858
79. Giudice GJ, Emery DJ, Zelickson BD, Anhalt GJ, Liu Z,
Diaz LA. Bullous pemphigoid and herpes gestationis autoan-
tibodies recognize a common non-collagenous site on the
BP180 ectodomain. J Immunol. 1993;151:5742–5750
80. Goldberg NS, DeFeo C, Krishenbaum N. Pemphigus vul-
garis and pregnancy: risk factors and recommendations. J
Am Acad Dermatol. 1993;28:877–879
81. Goldberg I, Kashman Y, Brenner S. The induction of pem-
phigus by phenol drugs. Int J Dermatol. 1999;38:
888–892.
82. Grando SA. Autoimmunity to keratinocyte acetylcholine
receptors in pemphigus. Dermatology. 2000;201(4): 290–295
83. Green D, Maize JC. Maternal pemphigus vulgaris with
in  vivo bound antibodies in the stillborn fetus. J Am Acad
Dermatol. 1982;7:388–392
84. Hakimian J, Koransky J, Murrell DF. Childhood Epidermolysis
Bullosa Acquista. Proceedings of the 54th Annual American
Academy of Dermatology.Washington; 1996
85. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes
Bavinck JN, Sidoroff A, Naldi L, Dunant A, Viboud C,
Roujeau JC, EuroSCAR Study Group. Allopurinol is the
most common cause of Stevens-Johnson syndrome and toxic
epidermal necrolysis in Europe and Israel. J Am Acad
Dermatol. 2008;58(1):25–32
86. Handyside AH, Kontogianni EH, Hardy K, Winston
RML. Pregnancies from biopsied human preimplantation
embryos used by Y specific DNA amplification. Nature.
1990;344:768–770
132
  87. Hashimoto K, Wun TC, Baird J, Lazarus GS, Jensen PJ.
Characterization of keratinocyte plasminogen activator
inhibitors and demonstration of the prevention of pemphi-
gus IgG-induced acantholysis by a purified plasminogen
activator inhibitor. J Invest Dermatol. 1989;92(3):
310–314
  88. Hashimoto T, Konohana A, Nishikawa T. Immunoblot
assay as an aid to the diagnoses of unclassified cases of
pemphigus. Arch Dermatol. 1991;127:843–847
  89. Hashimoto T, Amagai M, Watanabe K, et al Characterization
of paraneoplastic pemphigus autoantigens by immunoblot
analysis. J Invest Dermatol. 1995;104:829–834
  90. Hashimoto T, Ishiko A, Shimizu H, et al A case of linear
IgA bullous dermatosis with IgA anti-type VII collagen
autoantibodies. Br J Dermatol. 1996;134:336–339
  91. Heagerty AH, Kennedy AR, Gunner DB, Eady RA. Rapid
prenatal diagnosis and exclusion of epidermolysis bullosa
using novel antibody probes. J Invest Dermatol. 1986;86(5):
603–605
  92. Heagerty AH, Eady RA, Kennedy AR, et al Rapid prenatal
diagnosis of epidermolysis bullosa letalis using GB3 mono-
clonal antibody. Br J Dermatol. 1987;117(3):271–275
  93. Heimbach DM, Engrav LH, Marvin JA, et al Toxic epider-
mal necrolysis: a step forward in treatment. JAMA. 1987;
257:2171–2175
  94. Hern S, Vaughan Jones SA, Setterfield J, et al Pemphigus
vulgaris in pregnancy with favourable fetal prognosis. Clin
Exp Dermatol. 1998;23(6):260–263
  95. Hertl M. Humoral and cellular autoimmunity in autoim-
mune bullous skin disorders.   Int Arch Allergy Immunol.
2000; 122:91–100
  96. Hertl M. Autoimmune bullous skin disorders. In:
Autoimmune Disease of The Skin. Pathogenesis, Diagnosis,
Management. New York, Springer Wien; 2005
  97. Hervonen K, Vornanen M, Kautiainen H, Collin P, Reunala T.
Lymphoma in patients with dermatitis herpetiformis and their
first-degree relatives. Br J Dermatol. 2005;152(1):82–86
  98. Hintner H, Stingl G, Schuler G, et al Immunofluorescence
mapping of antigenic determinants within the dermal-epi-
dermal junction in mechanobullous diseases. J Invest
Dermatol. 1981;76:113–118
  99. Hirako Y, Niishizawa Y, Sitaru C, et  al The 97k-Da
(LABD97) and 120-kDa (LAD-1) fragments of bullous
pemphigoid antigen 180/type XVII collagen have different
N-termini. J Invest Dermatol. 2003;121:1554–1556
100. Horn TD, Anhalt GJ. Histologic features of paraneolastic
pemphigus. Arch Dermatol. 1992;128:1091–1095
101. Huff JC. Acyclovir for recurrent erythema multiforme
caused by herpes simplex. J Am Acad Dermatol. 1988;18:
197–199
102. Huilgol SC, Black MM. Management of the immunobullous
disorders. II. Pemphigus. Clin Exp Dermatol. 1995;20:
283–293
103. Inauen P, Hunziker TH, Gerber H, et al Childhood epider-
molysis bullosa acquisita. Br J Dermatol. 1994;131:
898–900
104. Ishida-Yamamoto A, McGrath JA, Chapman SJ, et  al
Epidermolysis Bullosa simplex (Dowling-Meara type) is a
genetic disease characterized by an abnormal keratin-fila-
ment network involving keratins K5 and K14. J Invest
Dermatol. 1991;97:959–968
S. S. Venugopal and D. F. Murrell
105. Ishii K, et al Characterization of autoantibodies in pemphi-
gus using antigen-specific enzyme linked immunosorbent
assays with baculovirus expressed recombinant desmog-
leins. J Immunol. 1997;159:2010–2017
106. Ishii K, Amagai M, Ohata Y, et al Development of pemphi-
gus vulgaris in a patient with pemphigus foliaceus antides-
moglein antibody profile shift confirmed by enzyme-linked
immunosorbent assay. J Am Acad Dermatol. 2000;42:
859–861
107. Ishiko A, Shimizu H, Masunaga T, et al 97-kDa linear IgA
bullous dermatosis (LAD) antigen localizes to the lamina
lucida of the epidermal basement membrane. J Invest
Dermatol. 1996;106:734–738
108. Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of
treating herpes zoster with oral acyclovir in preventing pos-
therpetic neuralgia. A meta-analysis. Arch Intern Med.
1997;157(8):909–912
109. Jacobs SE. Pemphigus erythematosus and ultraviolet light.
A case report. Arch Dermatol. 1965;91:139–141
110. Jiao D, Bystryn JC. Sensitivity of indirect immunofluores-
cence, substrate specificity and immunoblotting in the
diagnosis of pemphigus. J Am Acad Dermatol. 1997;37:
211–216
111. Jonkman MF, De Jong MCJM, Heeres K, et  al 180-kD
bullous pemphigoid antigen (BP180) is deficient in gener-
alized atrophic benign epidermolysis bullosa. J Clin Invest.
1995;95:1345–1352
112. Jonkman MF, Heeres K, Pas HH, et al Effects of keratin 14
ablation on the clinical and cellular phenotype in a kindred
with recessive epidermolysis bullosa simplex. J Invest
Dermatol. 1996;107:764–769
113. Kaplan RP, Callen JP. Pemphigus-associated diseases and
induced pemphigus. Clin Dermatol. 1983;1:42–71
114. Katz SI. Dermatitis herpetiformis. In: Freedberg IM, Eisen
AZ, Wolff K, et  al, eds. Fitzpatrick’s Dermatology in
General Medicine. New York, NY: McGraw-Hill; 1999
115. Kirtschig G, Wojnarowska F, Marsden RA, et al Acquired
bullous diseases of childhood: re-evaluation of diagnosis by
indirect immunofluorescence examination on 1 M NaCl split
skin and immunoblotting. Br J Dermatol. 1994;130: 610–616
116. Kivirikko S, McGrath JA, Abderam D, et al A homozygous
nonsense mutation in the alpha 3 chain gene of laminin 5
(LAMA3) in lethel (Herlitz) junctional epidermolysis
bullosa. Hum Mol Genet. 1995;4:959–962
117. Klein PA, Callen JP. Drug-induced linear IgA bullous
­dermatosis after vancomycin discontinuance in a patient
with renal insufficiency. J Am Acad Dermatol. 2000;42:
316–323
118. Klingberg S, Mortimore R, Parkes J, et al Prenatal diagno-
sis of dominant dystrophic epidermolysis bullosa, by COL7A1
molecular analysis. Prenat Diagn. 2000;20(8): 618–622
119. Kokuba H, Aurelian L, et al Herpes simplex virus associ-
ated erythema multiforme (HAEM) is mechanistically
distinct from drug-induced erythema multiforme: inter-
feron-gamma is expressed in HAEM lesions and tumor
necrosis factor-alpha in drug-induced erythema multiforme
lesions. J Invest Dermatol. 1999;113(5):808–815
120. Kricheli D, David M, Frusic-Zlotkin M. The distribution of
pemphigus vulgaris IgG subclasses and reactivity with des-
moglein 3 and 1 in pemphigus patients and first degree rela-
tives. N J Dermatol. 2000;143:337–342
12  Diagnosis and Prevention of Bullous Diseases
121. Kuechle MK, Stegemeir E, Maynard B, et al Drug-induced
linear IgA bullous dermatosis: report of six cases and review
of the literature. J Am Acad Dermatol. 1994;30: 187–192
122. Lapiere JC, Woodley DT, Parente MG, et al Epitope map-
ping of type VII collagen. Identification of discrete peptide
sequences recognized by sera from patients with acquired
epidermolysis bullosa. J Clin Invest. 1993;92:1831–1839
123. Lee E, Lendas KA, Chow S, et  al Disease relevant HLA
class II alleles isolated by genotypic, haplotypic, and
sequence analysis in North American Caucasians with pem-
phigus vulgaris. Hum Immunol. 2006;67(1–2):125–139
124. Lever WF. Pemphigus. Medicine. 1953;32:1–123
125. Lever WF. Pemphigus and pemphigoid. J Am Acad
Dermatol. 1979;1:2–31
126. Leverkus M, Bhol K, Hirako Y, et al Cicatricial pemphig-
oid with circulating autoantibodies to beta4 integrin,
bullous pemphigoid 180 and bullous pemphigoid 230. Br
J Dermatol. 2001;145(6):998–1004
127. Levy RS, Fisher M, Alter NA. Penicillamine: review and
cutaneous manifestations. J Am Acad Dermatol. 1983;8:
548–558
128. Lin MS, Gharia M, Fu CL, et al Molecular mapping of the
major epitopes of BP180 recognized by herpes gestationis
autoantibodies. Clin Immunol. 1999;92:285–292
129. Lin R, Ladd DJ, Powell DJ, Way BV. Localized pemphigus
foliaceus induced by topical imiquimod. Arch Dermatol.
2004;140:889–890
130. Liu Z. Bullous pemphigoid: using animal models to study
the immunopathology. J Invest Dermatol Symp Proc. 2004;
9(1):41–46
131. Mackenzie-Wood A, Kirkham B, Hart K, Murrell DF. Second
Case of Bullous Pemphigoid like Eruption Induced by
D-Penicillamine. Mini Consults in Dermatology Volume VI,
American Academy of Dermatology. Mosby-Year Book; 1999
132. Marinkovich MP, Taylor TB, Keene DR, et al LAD-1, the
linear IgA bullous dermatosis autoantigen, is a novel 120-
kDa anchoring filament protein synthesized by epidermal
cells. J Invest Dermatol. 1996;106:734–738
133. Martin LK, Murrell DF. Treatment of pemphigus: the need
for more evidence. Arch Dermatol. 2008;144(1):100–101
134. Mashiah J, Brenner S. Medical pearl: first step in managing
pemphigus – addressing the etiology. J Am Acad Dermatol.
2005;53(4):706–707
135. McGrath JA, Ishida-Yamamoto A, Tidman MJ, Heagerty
AHM, Schofield OMV, Eady RAJ. Epidermolysis bullosa
simplex (Dowling-Meara). A clinicopathological review.
Br J Dermatol. 1992;126:421–430
136. McGrath JA, Gatalica B, Crhistiano AM, et al Mutations in
the 180kD bullous pemphigoid antigen (BPAG2), a hemi-
desmosomal transmembrane collagen (COL17A1), in gen-
eralised atrophic benign epidermolysis bullosa. Nat Genet.
1995;11:83–86
137. McGrath JA, Pulkkinen L, Christiano AM, et  al Altered
laminin 5 expression due to mutations in the gene encoding
the beta 3 chain (LAMB3) in generalised atrophic benign
epidermolysis bullosa. J Invest Dermatol. 1995;104:
467–474
138. McGrath JA, Dunnill MG, Christiano AM, et al First tri-
mester DNA-based exclusion of recessive dystrophic epi-
dermolysis bullosa from chorionic villous sampling. Br
J Dermatol. 1996;134(4):734–739
133
139. Mihai S, Sitaru C. Immunopathology and molecular diag-
nosis of autoimmune bullous diseases. J Cell Mol Med.
2007;11(3):462–481
140. Mofid MZ, Costarangos C, Bernstein B, et al Drug-induced
linear immunoglobulin A bullous disease that clinically
mimics toxic epidermal necrolysis. J Burn Care Rehabil.
2000;21:246–247
141. Murrell DF, Pasmooij AM, Pas HH, et  al Retrospective
diagnosis of fatal BP180-deficient non-Herlitz junctional
epidermolysis bullosa suggested by immunofluorescence
(IF) antigen-mapping of parental carriers bearing enamel
defects. J Invest Dermatol. 2007;127(7):1772–1775
142. Murrell DF, Amagai M, Barnadas MA, et  al Consensus
statement on definitions of disease endpoints and therapeu-
tic response for pemphigus. JAAD. 2008;58(6):1043–1046
143. Mutasim DF. Autoimmune bullous diseases: diagnosis and
management. Dermatol Nurs. 1999;11:15–21
144. Neughebauer BI, Negron G, Pelton S, Plunkett RW, Beutner
EH, Magnussen R. Bullous skin disease: an unusual aller-
gic reaction to vancomycin. Am J Med Sci. 2002;323(5):
273–278
145. Ng PP, Sun YJ. Detection of herpes simplex virus genomic
DNA in various subsets of erythema multiforme by poly-
merase chain reaction. Dermatology. 2003;207(4):349–353
146. Nicolas ME, Krause PK, Gibson LE, Murray JA. Dermatitis
herpetiformis. Int J Dermatol. 2003;42:588–600
147. Niemi K-M, Sommer H, Kero M, et  al Epidermolysis
bullosa simplex associated with muscular dystrophy with
recessive inheritance. Arch Dermatol. 1988;124:551–554
148. Nousari HC, Kimyai-Asadi A, Caeiro JP, et  al Clinical,
demographic, and immunohistologic features of vancomy-
cin-induced linear IgA bullous disease of the skin. Medicine.
1999;78:1–8
149. Nuemberger S, Driscoll A, Gabel P, et al Orf virus infection
in humans-New York, Illinois, California and Tennessee
2004–2005. JAMA. 2006;55:65–68
150. Oxman MN, Levin MJ, Johnson GR, et  al A vaccine to
prevent herpes zoster and postherpetic neuralgia in older
adults. N Engl J Med. 2005;253(22):2271–2284
151. Park SB, Cho KH, Youn JL, Hwang DH, Kim SC, Chung
JH. Epidermolysis bullosa acquisita in childhood-a case
mimicking chronic bullous dermatosis of childhood. Clin
Exp Dermatol. 1997;22(5):220–222
152. Parlowsky T, Welzel J, Amagai M, Zillikens D, Wygold T.
Neonatal pemphigus vulgaris: IgG4 autoantibodies to des-
moglein 3 induce skin blisters in newborns. J Am Acad
Dermatol. 2003;48(4):623–625
153. Pas HH, De Jong MC, Jonkman MF, Heeres K, Slijper-Pal IJ,
Van der Meer JB. Bulllous pemphigoid: serum antibody titre
and antigen specificity. Exp Dermatol. 1995;4: 372–376
154. Pearson RW. Studies on the pathogenesis of epidermolysis
bullosa. J Invest Dermatol. 1962;39:551–575
155. Pearson RW, Spargo B. Electron microscopic studies
of dermal-epidermal separation in human skin. J Invest
Dermatol. 1961;36:213–224
156. Peters MS, McEvoy MT. IgA antiendomysial antibodies
in dermatitis herpetiformis. J Am Acad Dermatol. 1989;21:
1225–1231
157. Pfendner E, Uitto J. Plectin gene mutations can cause epi-
dermolysis bullosa with pyloric atresia. J Invest Dermatol.
2005;124(1):111–115
134
158. Pfendner EG, Nakano A, Pulkkinen L, Christiano AM,
Uitto J. Prenatal diagnosis for epidermolysis bullosa: a
study of 144 consecutive pregnancies at risk. Prenat Diagn.
2003;23(6):447-456
159. Phelps RG, Miller MK, Singh F. The varieties of eczema:
clinicopathologic correlation. Clin Dermatol. 2003;25:
95–100
160. Plunkett RW, Chiarello SE, Beutner EH. Linear IgA bullous
dermatosis in one of two piroxicam-induced eruptions: a
distinct direct immunofluorescence trend revealed by the
literature. J Am Acad Dermatol. 2001;45:691–696
161. Powell GR, Bruckner AL, Weston WL. Dermatitis herpeti-
formis presenting as chronic urticaria. Pediatr Dermatol.
2004;21(5):564–567
162. Powell AM, Sakuma-Oyama Y, Oyama N, et al Usefulness
of BP180 NC16a enzyme-linked immunosorbent assay in
the serodiagnosis of pemphigoid gestationis and in differ-
entiating between pemphigoid gestationis and pruritic urti-
carial papules and plaques of pregnancy. Arch Dermatol.
2005;141(6):705–710
163. Premaratne C, Klingberg S, Glass I, Wright K, Murrell D.
Epidermolysis bullosa simplex Dowling-Meara due to an
arginine to cysteine substitution in exon 1 of keratin 14.
Australas J Dermatol. 2002;43(1):28–34
164. Proby C, Fujii Y, Owaribe K, et al Human autoantibodies
against HD1/plectin in paraneoplatic pemphigus. J Invest
Dermatol. 1999;112:153–156
165. Pulkkinen L, Christiano AM, Gerecke D, et al A homozy-
gous nonsense mutation in the beta 3 chain gene of laminin
5 (LAMB3) in Herlitz junctional epidermolysis bullosa.
Genomics. 1994;24:357–360
166. Rabinowitz LG, Esterly NB. Inflammatory bullous diseases
in children. Dermatol Clin. 1993;11:565–581
167. Rao CL, Hall RP. III, Linear IgA dermatosis and chronic
bullous disease of childhood. In: Freedberg IM, Eisen AZ,
Wolff K, Austen KF, Goldsmith LA, Katz SI, eds.
Dermatology in General Medicine. New York: McGraw-
Hill; 2003
168. Richards SS, Hall S, Yokel B, et al A bullous eruption in an
elderly woman. Vancomycin-associated linear IgA derma-
tosis (LAD). Arch Dermatol. 1995;131:1447–1451
169. Rocha-Alvarez R, Friedman H, Campbell IT, Souza-Aguiar
L, Martins-Castro R, Diaz LA. Pregnant women with
endemic pemphigus foliaceus (fogo selvagem) give birth to
disease-free babies. J Invest Dermatol. 1992;99:78–82
170. Rock B, Martins CR, Theofilopoulos AN, et al The patho-
genic effect of IgG4 autoantibodies in endemic pemphigus
foliaceus (fogo selvagem). N Eng J Med. 1989;320:
1463–1469
171. Rodeck CH, Eady RA, Gosden CM. Prenatal diagnosis of
epidermolysis bullosa letalis. Lancet. 1980;1(8175):
949–952
172. Roenigk HH, Ryan JG, Bergfeld WF. Epidermolysis
bullosa acquista: Report of three cases and review of all
published cases. Arch Dermatol. 1971;103:1–10
173. Roujeau JC, Kelly JP, Naldi L, et al Medication use and the
risk of Stevens-Johnson syndrome or toxic epidermal
necrolysis. N Engl J Med. 1995;333:1600–1607
174. Ruach M, Ohel G, Rahav D, Samueloff A. Pemphigus vul-
garis and pregnancy. Obstet Gynecol Surv. 1995;50(10):
755–760
S. S. Venugopal and D. F. Murrell
175. Ruocco V, Rossi A, Astarita C, et al A congenital acantho-
lytic bullous eruption in the newborn infant of a pemphigus
mother. Ital Gen Rev Dermatol. 1975;12:169–174
176. Scott JE, Ahmed AR. The blistering diseases. Med Clin
North Am. 1998;82:1239–1283
177. Scully C. A review of mucocutaneous disorders affecting
the mouth and lips. Ann Acad Med Singap. 1999;28:
704–707
178. Shachar E, Bialy-Golan A, Srebrnik A, Brenner S. “Two-
step” drug-induced bullous pemphigoid. Int J Dermatol.
1998;37(12):938–939
179. Shimanovich I, Bröcker EB, Zillikens D. Pemphigoid
gestationis: new insights into the pathogenesis lead to
novel diagnostic tools. Br J Obstet Gynaecol. 2002;109:
970–976
180. Shimizu H, Suzumori L. Prenatal diagnosis as a test for
genodermatoses: its past, present and future. J Dermatol Sci.
1999;19:1–8
181. Sison-Fonacier L, Bystryn JC. Heterogeneity of pemphigus
vulgaris antigens. Arch Dermatol. 1987;123:1507–1510
182. Sitaru C, Powell J, Shimanovich I, et al Pemphigoid gesta-
tionis: maternal sera recognise epitopes restricted to the
N-terminal portion of the extracellular domain of BP180
not present on its shed ectodomain. Br J Dermatol. 2003;
149:420–422
183. Sitaru C, Powell J, Messer G, Brocker EB, Wojnarowska F,
Zillikens D. Immunoblotting and enzyme-linked immuno-
sorbent assay for the diagnosis of pemphigoid gestationis.
Obstet Gynecol. 2004;103(4):757–763
184. Sitaru C, Dahnrich C, Probst C, et al Enzyme-linked immu-
nosorbent assay using multimers of the 16th non-collage-
nous domain of the BP180 antigen for sensitive and specific
detection of pemphigoid autoantibodies. Exp Dermatol.
2007;16(9):770–777
185. Späth S, Riechers R, Borradori L, Zillikens D, Bdinger L,
Hertl M. Detection of autoantibodies of various subclasses
(IgG1, IgG4, IgA, IgE) against desmoglein 3 in patients
with acute onset and chronic pemphigus vulgaris. Br
J Dermatol. 2001;144:1183–1188
186. Stanley JR. Pemphigus. In: Freedberg IM, ed. Fitzpatrick’s
Dermatology in General Medicine. 6th ed. New York:
McGraw Hill; 1999:654–666
187. Stanley JR. Bullous pemphigoid. In: Freedberg IM, ed.
Fitzpatrick’s Dermatology in General Medicine. 6th ed.
New York: McGraw Hill; 1999:574–580
188. Szafer F, Brautbar C, Tzfoni E, et al Detection of disease-
specific restriction fragment length polymorphisms in pem-
phigus vulgaris linked to the DQw1 and DQw3 alleles of
the HLA-D region. Proc Natl Acad Sci USA. 1987;84:
6542
189. Tidman M, Eady RA. Hemidesmosomes heterogeneity in
junctional epidermolysis bullosa revealed by morphometric
analysis. J Invest Dermatol. 1986;86:51–56
190. Tidman M, Eady RA. Diagnosis and diagnostic techniques.
In: Wojnarowska F, Briggaman RA, eds. Management of
Blistering Diseases. London: Chapman and Hall; 1990
191. Todd JA, Acha-Orbea H, Bell JI, et al A molecular basis for
MHC class II–associated autoimmunity. Science. 1988;
240:1003
192. Tsuji-Abe Y, Akiyama M, Yamanaka Y, Kikuchi T, Sato-
Matsumura KC, Shimizu H. Correlation of clinical severity
12  Diagnosis and Prevention of Bullous Diseases
and ELISA indices for the NC16A domain of BP180 mea-
sured using BP180 ELISA kit in bullous pemphigoid.
J Dermatol Sci. 2005;37(3):145–149
193. Tur E, Brenner S. Diet and pemphigus. In pursuit of exog-
enous factors in pemphigus and fogo selvagem. Arch
Dermatol. 1998;134:1406–1410
194. Vailley J, Szepetowski P, Pedeutour F, et al The genes for
nicein/kalinin 125kDa and 100kDa subunits, candidates for
junctional epidermolysis bullosa, map to chromosome
1q32 and 1q25–q31. Genomics. 1994;21:286–288
195. Vidal F, Aberdam D, Miquel C, et al Integrin beta 4 muta-
tions associated with junctional epidermolysis bullosa with
pyloric atresia. Nat Genet. 1995;10:229–234
196. Vu TN, Lee TX, Ndoye A, et al The pathophysiological sig-
nificance of nondesmoglein targets of pemphigus autoimmu-
nity. Development of antibodies against keratinocyte
cholinergic receptors in patients with pemphigus vulgaris and
pemphigus foliaceus. Arch Dermatol. 1998;134(8): 971–980
197. Waananukul S, Pongprasit P. Childhood pemphigus. Int
J Dermatol. 1999;38:29–35
198. Warren SJ, Cockerell CJ. Characterization of a subgroup of
patients with dermatitis herpetiformis with nonclassical his-
tologic features. Am J Dermatopathol. 2002;24(4): 305–308
199. Wasserstrum N, Laros RK Jr. Transplacental transmission
of pemphigus. JAMA. 1983;249(11):1480–1482
200. Weinberg ED. Pregnancy-associated depression of cell-
mediated immunity. Rev Infect Dis. 1984;6:814–831
201. Weinberg JM. Herpes zoster: epidemiology, natural history,
and common complications. J Am Acad Dermatol. 2007;57
(6):130–135
202. Weller R, White MI. Bullous pemphigoid and penicillamine.
Clin Exp Dermatol. 1996;21(2):121–122
203. Whitley RJ, Weiss H, Gnann JW Jr, et al Acyclovir with and
without prednisone for the treatment of herpes zoster. A ran-
domized, placebo-controlled trial. The National Institute of
Allergy and Infectious Diseases Collaborative Antiviral
Study Group. Ann Intern Med. 1996;125(5): 376–383
204. Wojnarowska F, Marsden RA, Bhogal B, Black MM.
Chronic bullous disease of childhood, childhood cicatricial
pemphigoid, and linear IgA disease of adults. A compara-
tive study demonstrating clinical and immunopathologic
overlap. J Am Acad Dermatol. 1988;19:792–805
205. Wojnarowska F, Whitehead P, Leigh IM, Bhogal BS, Black
MM. Identification of the target antigen in chronic bullous
disease of childhood and linear IgA disease of adults. Br
J Dermatol. 1991;124:157–162
206. Wojnarowska F, Allen J, Collier P. Linear IgA disease: a
heterogenous disease. Dermatology. 1994;189:52–56
207. Wood MJ, Kay R, Dworkin RH, Soong SJ, Whitley RJ.
Oral acyclovir therapy accelerates pain resolution in
patients with herpes zoster: a meta-analysis of placebo con-
trolled trials. Clin Infect Dis. 1996;22:341–347
135
208. Woodley DT. Epidermolysis bullosa acquista. Prog
Dermatol. 1988;22:1
209. Woodley DT, Briggaman RA, O’Keefe EJ, Inman AO,
Queen LL, Gammon WR. Identification of the skin base-
ment-membrane autoantigen in epidermolysis bullosa
acquisita. N Engl J Med. 1984;310:1007–1013
210. Woodley DT, Burgeson RE, Lunstrum G, et al Epidermolysis
bullosa acquisita antigen is globular carboxyl terminus of
type VII procollagen. J Clin Invest. 1988;81:683–687
211. Wu H, Wang ZH, Yan A, et al Protection against pemphi-
gus foliaceus by desmoglein 3 in neonates. N Engl J Med.
2000;343:31–35
212. Yamane Y, Sato H, Higashi K, Yaoita H. Linear immuno-
globulin A (IgA) bullous dermatosis of childhood: identifi-
cation of the target antigens and study of the cellular
sources. Br J Dermatol. 1996;135:785–790
213. Yiasemedes E, Walton J, Marr P, Villaneuva EV, Murrell
DF. A comparative study between transmission electron
microscopy and immunofluorescence mapping in the diag-
nosis of epidermolysis bullosa. Am J Dermatopathol.
2006;28(5):387–394
214. Yiasemides E, Trisnowati N, Su J, Dang NN, Klingberg S,
Marr P, Chow CW, Orchard D, Varigos G, Murrell DF:
Clinical heterogeneity in recessive epidermolysis bullosa due
to mutations in the keratin 14 gene, KRT14. Clin Exp
Dermatol. Nov 2008; 33(6):689–97
215. Yoshida M, Hamada T, Amagai M, et  al Enzyme-linked
immunosorbent assay using bacterial recombinant proteins
of human BP230 as a diagnostic tool for bullous pemphig-
oid. J Dermatol Sci. 2006;41(1):21–30
216. Zhou S, Wakelin SH, Allen J, Wojnarowska F. Blister fluid
for the diagnosis of subepidermal immunobullous diseases:
a comparative study of basement membrane zone autoanti-
bodies detected in blister fluid and serum. Br J Dermatol.
1998;139(1):27–32
217. Zillikens D. Acquired skin disease of hemidesmosomes.
J Dermatol Sci. 1999;20:134–154
218. Zillikens D, Wever S, Roth A, Hashimoto T, Brocker EB.
Incidence of autoimmune subepidermal blistering dermato-
sis in a region of central Germany. Arch Dermatol. 1995;
131:957–958
219. Zillikens D, Herzele K, Georgi M, et al Autoantibodies in a
subgroup of patients with linear IgA disease react with
the  NC16A domain of BP180. J Invest Dermatol. 1999;
113:947–953
220. Zone JJ. Skin manifestations of celiac disease. Gastroen­
terology. 2005;128:S87–S91
221. Zone JJ, Taylor TB, Meyer LJ, Petersen MJ. The 97 kDa
linear IgA bullous disease antigen is identical to a portion
of the extracellular domain of the 180 kDa bullous pemphi-
goid antigen, BPAG 2. J Invest Dermatol. 1998;110:
207–210
 Diagnosis and Prevention
of Atopic Eczema 13
Stefan Wöhrl

13.1 Introduction explained? Although it has been observed for a long

time that the predisposition for atopic diseases is
highly inherited,6 human genes cannot have changed
Atopic eczema (AE) is a chronic, highly prevalent,
within the past century and other factors have to be
inflammatory skin disease with a characteristic phe-
involved. “Western lifestyle” has often been accused
notype and distribution pattern. A variety of terms
as one of the causes of the “allergy epidemic.”7 The
have been created to describe this characteristic phe-
“hygiene hypothesis” postulates that the neonatal
notype. The historic terms “neurodermitis” and “neu-
immune system needs microbial and parasitic infec-
rodermatitis”1 were replaced later by the term “atopic
tion for full maturation and that the much-too-clean
dermatitis” and finally “AE.”2 The term AE will be
environment of childhood nowadays shifts the
used in this chapter because it is the proposed term in
immune system from tolerance toward allergy to
the World Allergy Organization (WAO) guideline of
environmental allergens.8 Although attractive, this
2004.2 AE often occurs together with allergic rhi-
theory has been challenged lately.9 Others speculated
noconjunctivitis and bronchial asthma. These three
that modern housing conditions lead to increased
entities are referred to as “atopic diseases” or “aller-
allergen exposition and that this contributes to higher
gic diseases.” The atopic diseases have the highest
rates of sensitization to indoor allergens such as stor-
levels of incidence in the first decades of life.3
age and house dust mites in 33% or to cat dander in
Typically, AE is the earliest symptom in the life of
13% of the patients suffering from AE when com-
infants, then continues to allergic rhinoconjunctivitis
pared with nonatopic controls (25 and 4%, respec­
and, finally, ends with allergic bronchial asthma. The
tively).10
term “atopic march” was coined for this natural
So, environmental conditions have changed. Both
course of the disease complex.4
abnormal immunologic response to harmless aller-
Over the past decades, the prevalence of AE has
gens and inadequate epidermal barrier function lead
steadily increased to affect now about 1 out of 10
to the development of AE; “Western lifestyle,” for
young children and 2 out of 100 adults in the Western
example, directly changed environmental factors
societies.5 A large worldwide study with more than
affecting the skin. The frequency of daily personal
50 participating countries showed that the increase
washing has increased dramatically in the past
of atopic diseases has become less steep in recent
decades. The average use of water for this purpose
years but is still on the rise.5 How can this be
increased from 11 L in 1961 to 51 L in 1997.11 Using
soap and other detergents during washing aggravates
the situation and has also increased. The use of soap
S. Wöhrl and personal wash detergents in the UK increased
Department of Dermatology, Division of Immunology,
Allergy and Infectious Diseases (DIAID),
from £76 million in 1981 to £453 million (inflation
Medical University of Vienna, Vienna, Austria adjusted) in 2001 while the population remained
e-mail: stefan.woehrl@meduniwien.ac.at nearly stable.12

R. A. Norman (ed.), Preventive Dermatology, 137

DOI: 10.1007/978-1-84996-021-2_13, © Springer-Verlag London Limited 2010
138
13.2 Pathophysiology
13.2.1 Skin Physiology
The skin is the largest organ and serves as a barrier
between the interior and the exterior world. It protects
the body from desiccation and from xenobiotics. The
epidermal barrier function has been visualized as a
“brick wall” with the corneocytes – the flattened kera-
tinocytes of the upper epidermis – serving as the bricks
and the lipid lamellae as cement13 (Fig. 13.1).12, 14 The
lipid lamellae are secreted by the corneocytes and are
composed mainly of ceramides, cholesterol, fatty acids,
and cholesterol esters.15 These substances form the so-
called “cornified envelope” and surround the corneo-
cytes. The main function of the lipid lamellae is the
prevention of water loss. The integrity of these lamellae
can be reduced by washing the skin with mild deter-
gents, e.g., soaps. Other important structures are the
corneodesmosomes, modified desmosomes of the
Stratum corneum. They lock the corneocytes together.
Corneodesmosomes provide the Str. corneum with the
strength to resist against shearing forces.12 These struc-
tures can be visualized as iron rods (Fig. 13.1). Upon
normal epidermal turnover, the corneodesmosomes are
cleaved in the upper corneal layer by endogenous ser-
ine proteases such as the Str. corneum chymotryptic
enzyme to facilitate epidermal shedding. A fine balance
has to be kept for maintaining epidermal homeostasis.
Exaggerated corneodesmolysis by endogenous or
Staphylococci and house dust mite enzymes leads to
epidermal thinning and decreased barrier function,
decelerated endogenous cleavage to squamation.
Fig. 13.1  The “brick wall”
model of the upper epidermis,
modified after Taïeb14 and
Cork et al12: in this model,
the corneocytes – the flattened
Stratum corneum
keratinocytes of the upper
epidermis – are visualized as
bricks and the lipid lamella,
almost a synonym for the
“cornified envelope,” as
cement. The main function of
the lipid lamella is to
waterproof the epidermis. The
corneodesmosomes are
visualized as iron rods that
provide resistance to shearing
forces
S. Wöhrl
Cork et  al.12 speculate that skin thickness is an
important key to explain the mystique behind the pre-
dilection sites of AE. The eyelids are reported to have
the lowest skin thickness, followed by genitals, flex-
ural forearm and the posterior auricular region.12 The
thickness of the elbow flexures is unknown but the
ones of the palms and soles are the thickest. Skin thick-
ness is also associated with percutaneous penetration
of topically applied drugs like corticosteroids. Neonatal
skin is not fully mature in respect of barrier function
and percutaneous penetration is elevated in compare
with adult skin.16
13.2.2 Genetics
There is a strong genetic background for all kinds of
atopic diseases. Until recently, the focus has been on
the immunologic side. In 1999, Taïeb14 hypothesized
that genes involved in the epidermal barrier function
might also play an important role in the etiology of AE.
In a very important study, Palmer et al.17 showed that
two loss-of-function deletions in the gene encoding for
filaggrin are associated with a high risk for suffering
from AE. Around 49% of the European population are
heterozygous carriers for this allele.18 Interestingly,
carriers of the mutated allele are not only at higher risk
for AE but also for bronchial asthma. A recent meta-
analysis of nine studies on filaggrin mutations in AE
pinned the odds ratio for carriers down to four when
compared with noncarriers.18
Also other factors contribute to the reduced barrier
function of atopic skin; for example, the normal
Corneocyte
Lipid lamella
Corneodesmosome
13  Diagnosis and Prevention of Atopic Eczema
un-inflamed skin of AE patients contains less ceramide
and sphingosine than that of nonatopic controls.15
13.2.3 Immunology and Allergy
13.2.3.1 Immunology
Although the breakdown of the skin barrier is an
important aspect in the initiation phase of AE, there
has been the long-term clinical observation that
using potent immunosuppression (e.g., cyclosporine)
stops skin inflammation and leads to long-term
remission.
The immunologic response to antigens in atopic
patients differs from nonatopic controls. Atopics
have a pronounced immunological response of Th2
cells to external antigens with a characteristic
cytokine profile, namely interleukin-4 (IL-4), IL-5,
IL-9, and IL-13. IL-4 differentiates naïve T-helper 0
cells (Th0) into Th21 and together with IL-13 pro-
motes isotype-switching of B-cells to IgE produc-
tion.19 IL-4 upregulates Fce [epsilon] receptor I
expression on dendritic cells facilitating allergen
uptake in dendritic cells and allergen presentation to
other immunologic cell types. Finally, it suppresses
the production of Th1-type cytokines like IFN-g
(gamma) and IL-12.20 IL-5 attracts and stimulates the
growth of eosinophils. These are the reasons for the
elevated serum IgE levels and the eosinophilia in dif-
ferential blood counts from patients suffering from
atopic diseases.
Interestingly, AE lesions are biphasic in nature. Th2
cytokines predominate in acute AE lesions, whereas
the Th1 cytokines IFN-g (gamma) and IL-12 outweigh
in chronic eczema.21
Regulatory T-cells are key players in self-tolerance
and tolerance to environmental antigens such as aller-
gens. Their upregulation is a key feature of regaining
tolerance to allergens with specific immunotherapy.22
Verhagen et  al.23 showed that regulatory T-cells are
missing in AE skin lesions.
13.2.3.2 Allergy
Sensitization with specific IgE to food and aeroaller-
gens is an important contributor to symptom severity
in atopic patients. Food is the major allergen in infants
139
of up to 2 years and may cause skin rashes in around
35% of pediatric AE patients.24 Milk protein, hen’s
egg, soy, wheat, peanut, tree nut, fish, and shellfish are
the most important food allergens. Among them, milk
is the predominant allergen in infants. The prognosis
for food allergy in young children is good. Eighty per-
cent will outgrow their symptoms by their fifth birth-
day with the exception of peanut allergy, which persists
in 80% of the patients.24 Three-and-a-half to 4% of
adult Americans have specific IgE to food allergens.24
Contrasting AE as the main manifestation of food
allergy in young children, food-allergic adults tend to
suffer from other type-1 allergic manifestations like
urticaria, angioedema, gastrointestinal symptoms, or
anaphylaxis.
Sensitization to aeroallergens like birch, grass, and
ragweed pollen as well as house dust mite and cat dan-
der comes into fore from the age of 2 years and above.
The degree of sensitization to house dust, mite, and
fungal allergens was shown to correlate with symptom
severity in AE patients.25 Patients with a primary sensi-
tization to pollen aeroallergens may cross-react to the
same allergenic components in food laying the base
for typical syndromes (e.g., the “oral allergy syn-
drome” to apples and tree nuts in birch-pollen–allergic
patients or the “mugwort-celery-spice” syndrome in
patients sensitized to profilins).26
A subset of severely affected AE patients has specific
IgE against the superoxide manganese dismutase, an
inducible human stress enzyme. It is one of several
described self-antigens that were termed “atopy related
autoantigens.”20 Patients with high levels of self-IgE-
autoantibodies suffer from a more severe disease than
those without and belong to the subgroup with an onset
in early childhood.27 The human superoxide manganese
dismutase cross-reacts with that from the skin-coloniz-
ing yeast Malassezia sympodialis. A high colonization
with Malassezia sympodialis was described as an impor-
tant trigger for AE.28
13.2.4 Disease-Aggravating Factors
13.2.4.1 Stress and Itch
Patients with AE suffer from chronic itch that typically
intensifies periodically. Scratch marks are a frequent
clinical sign of severely affected patients. Pruritus has
several pathophysiological dimensions:
140
• The central “neurogenic” itch is generated in the cen-
tral nervous system in response to circulating prurito-
gens as in cholestasis or in response to intraspinal
morphines.29
• “Psychogenic” itch is also produced in the central
nervous system and aggravated by emotional stress.20
The immune system of patients with AE reacts to
psychological stress with a higher elevation of IL-4,
IL-5, and CLA+, a T cell activation marker, than
healthy controls.30 This means that psychological
stress influences an atopic immune system in a more
pronounced way than a healthy one.
• The peripheral “pruritoreceptive itch” is generated
in inflamed skin.29
Itch is mediated by sensory peripheral nerves. Sensory
peripheral nerves can be activated by histamine type 1,
2, and 3 receptors as well as by Substance P. Mast cells
are an important booster of pruritus by releasing hista-
mine but also other mediators such as tryptase and
mast cell chymase.31 Their number is increased in
lesional as well as nonlesional skin of atopic patients.32
Dermal contacts between mast cells and peripheral
nerve fibers as well as the number of nerval fibers
themselves are increased in atopic skin.33 The latter
can be (partly) explained by elevated levels of the
nerve-growth promoting neurotrophins in the serum of
patients with AE.34
IL-31 is a recently described cytokine. Its overex-
pression in transgenic mice leads to severe pruritus and
AE-like dermatitis.35 IL-31 expression is increased in
the epidermis of atopic patients when compared with
healthy controls.36 Interestingly, the IL-31 serum levels
do not differ between both patients groups.
13.2.4.2 Superinfection with Staphylococci
and Herpes Virus
Exacerbations of AE are often accompanied by infec-
tion with Staphylococcus aureus.37 The bacterium S.
aureus is not part of the normal skin flora and only 36%
of healthy nonatopic children are colonized in their
nostrils, the natural reservoir.38 In contrast, more than
90% of inflammatory and 76% of noninflammatory AE
skin lesions are colonized with S. aureus.39 S.  aureus
produces several enterotoxins that can serve as superan-
tigens.40 A subset of AE patients also produces mea­
surable specific IgE against these superantigens.41
S. aureus produces ceramidase, further aggravating the
S. Wöhrl
lack of ceramides in atopic skin (see Sect.  13.2.1).
Also, staphylococcal enterotoxin leads to rapid upregu-
lation of the pruritogenic IL-31 in atopic patients aggra-
vating their itch sensation42 (see Sect. 13.2.4.1).
Also, innate immunity is reduced in AE patients.
Human skin expresses antibacterial peptides that inhibit
bacterial growth of Staphylococci, so-called cathelici-
dins and b (beta)-defensins. It was shown that the pro-
duction of both peptides is reduced in lesional as well
as nonlesional skin of AE patients.43 Cathelicidins also
provide resistance to viral infection. AE patients with a
very low epidermal cathelicidin activity are prone to
recurrent, severe infections with herpes viruses, the so-
called “eczema herpeticum.”44
13.3 Diagnosis of Atopic Eczema
13.3.1 Clinical Presentation
The case presentation of AE is age-dependent. While
infants typically suffer from facial eczema and a cradle
cap – an eczema of the scalp – toddlers and adoles-
cents tend to suffer from flexural eczema as cardinal
symptoms. Eyelid eczema is another characteristic
presentation in 21% of young adults.45 Other typical
variants are neck and hand eczema as well as the so-
called “atopic winter feet.” More clinical features of
AE in adults are listed Table 13.1.46
The clinical spectrum of AE is very broad, ranging
from very mild variants presenting as fingertip eczema
(“pulpitis sicca”) to a generalized erythromatous rash.47
In difficult cases, scratch marks can be observed as a
sign of the severe pruritus.
13.3.2 Diagnostic Criteria
According to the 2004 WAO definition, “atopic derma-
titis” should be referred to as “AE.”2 The term AE
should stay restricted to patients with elevated total
IgE of >150  kU/L and sensitization to aero- and/or
food-allergens proved either by skin tests or by mea-
suring specific serum IgE. According to current data,
80% of adult AE patients are monosensitized to at least
one allergen and should be classified as AE.20 Formerly,
this type of AE was called “extrinsic atopic dermati-
tis.”1 The other 20% of patients can be classified as
13  Diagnosis and Prevention of Atopic Eczema
Table 13.1  Diagnostic features of AE according to Hanifin and
Rajka46
Major criteria: 3 of 4 Pruritus
present
Typical morphology and
distribution of skin lesions
Chronic or chronically relapsing
dermatitis
Personal or family history of
atopy
Minor criteria: 3 of 23 Xerosis
present Ichthyosis/palmar hyperlinear-
ity/keratosis pilaris
Immediate (type I) skin test
reactivity
Elevated serum IgE
Early age of onset
Tendency toward cutaneous
infections/impaired
cell-mediated immunity
Tendency toward nonspecific
hand or foot dermatitis
Nipple eczema
Cheilitis
Recurrent conjunctivitis
Dennie-Morgan infraorbital fold
Keratoconus
Anterior subcapsular cataracts
Orbital darkening
Facial pallor/erythema
Pityriasis alba
Anterior neck folds
Itch when sweating
Intolerance to wool and lipid
solvents
Perifollicular accentuation
Food intolerance
Course influenced by environ-
mental/emotional factors
White dermographism/delayed
blanch
suffering from “nonatopic eczema,”2 formerly known
as “intrinsic atopic dermatitis.”1 It remains to be seen
whether this classification will find acceptance in the
dermatologic community.
Currently, there are no definitive criteria for the
diagnosis of AE. In 1980, Hanifin and Rajka46 were the
first to set up rules for the definition of AE. They based
their definition on extensive dermatological criteria.
Three out of four main and 3 out of 28 minor criteria
must be fulfilled for the diagnosis of AE (Table 13.1).46
The UK working party developed much simpler criteria
141
Table 13.2  Diagnostic criteria for diagnosing AE according to
the UK working party48
Major criterion: 1 of 1 Itchy skin condition in the
present preceding 12 months
Minor criteria: 3 of 5 Onset <2 years
present
History of flexural
involvement
History of a generally dry skin
Personal history of other
atopic disease or atopic
disease in first degree
relatives when age of
patient <4 years
Visible dermatitis as per
photographic protocol
depending on the presence of just one main and three
out of five minor criteria (Table 13.2).48 Although the
approach of the UK criteria is much simpler, both ways
of defining AE show good agreement on comparison.49
Hence, for daily practice, use of the UK criteria seems
to be sufficient and is recommended by the British
National Institute for Health and Clinical Excellence
(NICE) guidelines on the management of AE in chil-
dren of up to 12 years.50
13.3.3 Allergologic Workup
The allergologic workup should begin with a careful
dermatological examination. Several clinical scoring
systems have been published for objectivation
(e.g.,  SCORAD – score atopic dermatitis [1993]). A
careful history-taking should give special regard to a
family history for atopic diseases, to a worsening of
the eczema after exposure to certain foods, to exposure
to environmental allergens such as pets or job related
allergens, and to hints of other atopic diseases such as
bronchial asthma.
The performance of skin prick tests and/or the mea-
surement of specific IgE should be performed to assess
the sensitization to type-1 environmental and food
allergens as well as the measurement of total serum
IgE. Under special circumstances, skin prick tests with
fresh food may be performed as “prick to prick tests.”
A lung function must be performed whenever bron-
chial asthma is suspected.
In daily practice, the clinical relevance of sensitiza-
tion to foods often remains unresolved. Food challenge
142
is the gold standard for the confirmation of the clinical
relevance of the sensitization in the patient. It can be
performed open label or, in severe cases, as double
blind, placebo-controlled, food challenge.
The atopy patch test (APT) is derived from the
patch test performed for assessing contact dermatitis
with type-4 allergens. It was developed with the aim to
make oral food challenges superfluous. In an APT, a
type-1 allergen is tested either in the form of a com-
mercial extract or as fresh food (e.g., milk) in Finn
chambers (Epitest Ltd Oy, Tuusula, Finland) on either
the back or the lateral upper arm. The current European
guideline recommends using preferably fresh food
whenever possible.51 The sensitivity of APTs with
fresh food is higher.52 While the specificity of the APT
is good, the sensitivity is low, so that its value in daily
practice is still a matter of debate.53
Alternative medicine is quite popular among AE
patients.54 Some methods of questionable validity are
offered by health professionals and nonprofessionals
alike. Some of them can cause considerable harm to
patients, especially if they are leading to wrong recom-
mendations (e.g., unnecessary elimination diets). The
measurement of serum IgG levels to food allergens is
one such method. Its clinical value has not yet been
demonstrated and should therefore not be performed in
AE patients.55
13.3.4 Differential Diagnoses
The most important differential diagnoses to AE are
other variants of eczema. In adults, irritant eczema often
occurs in combination with AE, such as nummular and
dyshidrotic (pompholyx) eczema. Palmoplantar psoria-
sis must be differentiated from AE in patients with exclu-
sive eczema of the palms and soles. Chronic eczema can
lead to type-4 sensitization and contact allergy that
should be considered as a differential diagnosis.56
Scabies infection must be considered, especially if
other family members are also affected. In newborns
with a cradle cap, seborrheic dermatitis is an important
differential diagnosis.
Cutaneous T cell lymphomas should be considered
in elderly patients with very chronic eczematous
lesions, in particular when they are reappearing at the
same sites after several courses of topical corticoster-
oid treatment.
S. Wöhrl
Genetic disorders must be considered in young
patients as they can mimic AE. Ichthyosis vulgaris is
the most common keratinization disorder. One in 250
UK school children is affected. Patients present with
dry skin, flexural ichthyosis, and palmar hyperlamel-
losis. Interestingly, they carry the same mutations in
the filaggrin gene that put patients at risk for AE.57
Netherton syndrome is a rare congenital syndrome
characterized by ichthyosiform erythroderma, hair
shaft abnormalities, and atopic diathesis. It could be
linked to a defect in the SPINK5 gene, a serine pro-
tease.58 The recently described IPEX syndrome is
caused by a very rare mutation of the FoxP3 gene that
is essential for a normal function of regulatory T cells.
As a consequence, these patients lack the tolerance-
inducing regulatory T-cells. The phenotype is charac-
terized by an eczematous rash, the early onset of
multiple autoendocrinopathies such as type-1 diabetes
and highly elevated IgE levels.59
In patients with eosinophilia and elevated serum
IgE levels, parasite infections should be considered as
a differential.
13.4 Prevention
13.4.1 Primary Prevention
(“Fighting the Cause”)
Primary prevention strategies are meant for those who
are not yet affected. This can be achieved either by
avoiding known risks or by promoting “health-sustain-
ing” conditions. In the context of preventing AE, the
main strategy has been to avoid exposure to potent
allergens (e.g., cat as a major indoor allergen and milk
as a prominent food allergen)3 as well as other known
risk factors such as cigarette smoke.60
The most direct approach of dietary allergen avoid-
ance is breast-feeding. European61 and American62 guide-
lines recommend 4–6 months of exclusive breast-feeding
in children at risk (with a first degree relative suffering
from an allergic disease). If breast-feeding is not possible,
the same guidelines recommend using hydrolyzed cow’s
milk formulas. There is only little evidence that delaying
the introduction of complementary foods beyond the age
of 6 months prevents the occurring of atopic disease.62
Elimination diets impose significant harm to small infants
13  Diagnosis and Prevention of Atopic Eczema
by withholding essential dietary nutrients. A thorough
allergologic work-up is a “must” before recommending
elimination diets to parents and food-challenges are
needed in cases of doubt. Beyond the age of 3, food
allergy is generally outgrown and elimination diets are
usually not needed in adolescent or adult AE.63, 64
Dietary restrictions in pregnancy to protect the fetus
and for the lactating mother had never been recom-
mended in the European guidelines61 and, due to the
lack of evidence, have also been abandoned in the
2008 American guidelines.62
The situation is more complex for nonfood allergens.
While the avoidance of cats seem to reduce the arising
of allergic asthma,65, 66 primary prevention from house
dust mite exposure does not prevent the arising of
allergy because children living at high altitudes – where
there are practically no house dust mites – develop aller-
gies in the same way as those in the lowlands.67
The second aspect of primary prevention, promot-
ing “health-sustaining conditions,” does not seem to be
met by what is called the Western lifestyle.68 Children
growing up under more natural anthroposophical life-
style (e.g., avoidance of vaccination and conventional
medication, consumption of more traditional food)
within Western societies have a lower prevalence of AE
and allergic asthma than controls.69 Another protective
factor is early attendance at daycare facilities which has
been attributed as a surrogate marker for more episodes
of viral infections.3 Growing up among livestock farm-
ing is an even stronger preventive environment.72 The
change of living conditions when migrating from a
country with a low prevalence of allergies to a highly
developed country with a high prevalence of allergies
increases the risk of atopic diseases.70 De-worming of
Gabonese school children led to a higher skin prick
test-reactivity to house dust mites.71
These observations have been placed in the context
of the “hygiene hypothesis”; resulting in another active
intervention approach. Children with a high coloniza-
tion of commensal and hardly pathogenic germs such
as Lactobacilli, Bifidobacteria and Mycobacteria have
a low rate of atopic diseases. Alimentation with the
addition of these bacteria in the form of “probiotics”
led to a reduction of allergic asthma, rhinoconjunctivi-
tis73, 74 and AE.75 However, most of these data come
from one group and could not be reproduced suffi-
ciently elsewhere. It is possible that components of
“probiotics” such as CpG motifs will be safer, better
defined, and have stronger effects in the near future.
143
For a prevention of allergic sensitization, preventive
allergen vaccinations in nonsensitized infants were pro-
posed before a sensitization occurs, in analogy to preven-
tive vaccination for viral diseases.76 Valenta’s group
demonstrated that they could induce allergy-protecting
“blocking IgG” antibodies with a genetically modified
birch protein that was unable to induce the potentially
“anaphylactogenic IgE” antibodies.77 They argue that a
preventive allergy vaccination to the most common
type-1 allergens could be useful to prevent allergies in all
newborns. However, type-1 allergy causes significant
morbidity but hardly any mortality. Hence, the necessity
to prevent type-1 allergy has a much lower clinical prior-
ity than the prevention of potentially life-threatening
viral infectious like measles. Currently, the medical com-
munity is judging the benefit–risk ratio of a broad allergy
vaccination in not-yet allergic infants as an unfavorable
one. Maybe this will change sometime in the future.
In contrast to the very clear recommendations con-
cerning breast-feeding and using hydrolyzed cow’s
milk formulas, all other data on primary prevention
strategies are much less clear and the evidence was not
validated high enough to include any of these possible
intervention methods into the joint American/European
PRACTALL guidelines.63, 64
13.4.2 Secondary Prevention
(“Preventing Disease
Progression”)
Only a few possibilities have been tested to stop dis-
ease progression in already sensitized individuals. It
was shown convincingly that specific immunotherapy
(allergy shots) can stop disease progression, reduce the
morbidity of allergic asthma and rhinoconjunctivitis,
and reduce the acquisition of new allergies.78, 79
Sublingual immunotherapy seems to work in the same
way although it has a weaker effect. In contrast,
patients with AE did not benefit from specific immu-
notherapy and, until recently, specific immunotherapy
was not recommended in patients with AE. Two recent
studies came up showing a reduction of AE-severity
after treating eczema patients sensitized to house dust
mite with specific immunotherapy.80, 81
For patients suffering from AE and concomitant
allergic rhinoconjunctivitis and/or asthma, the situation
is clear. They should undergo specific immunotherapy
144
for their rhinoconjunctivitis and/or asthma but must be
informed that the effect of the specific immunotherapy
on AE is yet not clear. For patients with AE and a sensi-
tization to house dust mite and no other atopic diseases
more data are needed before specific immunotherapy
can be recommended unequivocally.
13.4.3 Tertiary Prevention
(“Preventing Complications
and Permanent Disabilities”)
The treatment of patients with chronic AE is challeng-
ing. A stepwise approach depending on the symptom
severity was developed by a joint American/European
initiative endorsing members of the American Academy
of Immunology (AAAI) and the European Academy of
Allergy and Immunology (EAACI) called PRACTALL
for “practical allergy” (Fig. 13.2).63, 64
13.4.3.1 Topical Therapy
Skin Care
Dry skin is a prominent feature of AE. Hence, the
regular use of emollients 2 times a day is the basic
treatment for AE patients.50, 56 Emollients should be
Intensity of disease
Fig. 13.2  Stepwise
Step 1
management of patients with
atopic eczema (AE)
according to the joint
American/European
PRACTALL guidelines63,64 AE = atopic eczema, TCI = topical calcineurin inhibitor, TCS = topical corticosteroid,* = > 2 years
S. Wöhrl
applied continuously even if the patient is currently
in remission for the prevention of relapses.63, 64
Addition of low concentrations of urea (up to 4%)
can increase the rehydrating effect. “Topical emol-
lients are preferentially applied directly after a bath
or shower, when the skin is still slightly humid, after
gentle drying.”56 Skin hydration can be ameliorated
by using bath oils. Hot water, especially showering,
and swimming in water with high chlorine concentra-
tions worsens the xerosis in the same way as alcohol
used for disinfection.
The lack of ceramides is an important factor in the
increased transepidermal water loss of atopic skin.
New emollients with physiological ceramide concen-
tration (e.g., Atopiclair®, Sinclair) have shown some
promising effect by increasing the rehydrating effect in
patients with mild-to-moderate AE.82
Detergents such as the ones used in soaps should be
replaced by synthetic wash syndets (synthetic deter-
gents) with a neutral or mild acidic pH 6.0–5.5.63, 64
Dry skin is prone to micro-fissures, easing the entry of
bacteria. Wet dressings can help in treating severely
affected lesions.47
Rough clothing or wool is known to cause irritation
and should be avoided.63, 64 Activities leading to
increased perspiration like some sports can exacerbate
AE. Cigarette smoke is another known irritant. Further
hints for counseling AE patients on the avoidance of
nonspecific irritants can be found in Table 13.3.56
Recalcitrant, Severe AE
Step 4
Systemic therapy
e.g. cyclosporine, phototherapy
Step 3
Moderate to Severe AE
*
Mid-high potency TCS and/or TCI
Mild to Moderate AE
Step 2
*
Low to mind potency TCS and/or TCI
Dry Skin only
Basic treatment: skin hydration, emollients, avoidance of
irritants, identification and avoidance of specific triggers
13  Diagnosis and Prevention of Atopic Eczema 145

Table 13.3  List for counseling AE patients56

Clothing: avoid skin contact with irritating fibers (wool, large-fiber textiles); do not use tight and too warm clothing to avoid
excessive sweating
Tobacco: avoid exposure
Cool temperature in the bedroom; avoid too many bed covers
Increase emollient use with cold weather
Vaccines: normal schedule in noninvolved skin, including egg-allergic patients
Sun exposure: no specific restriction. Usually helpful because of improvement of epidermal barrier. Encourage summer holidays
at high altitude or at beach resorts
Physical exercise, sports: no restriction. If sweating induces flares of AE, progressive adaptation to exercise. Shower and
emollients after swimming pool
Allergy:
Food allergens
Maintain breast-feeding until 4–6 months if possible or use hydrolyzed formula and delay introduction of solid foods
until the seventh month. Avoid foods possibly containing peanut (marked “vegetal fat”). Otherwise normal diet, unless
an allergy workup has proven the need to exclude a specific food
Indoor aeroallergens
House dust mites
Use adequate ventilation of housing. Keep the rooms well-aerated even in winter
Avoid wall-to-wall carpeting
Remove dust with a wet sponge
Avoid soft toys in bed (cot), except washable ones
Wash bedsheets at a temperature higher than 55°C every 10 days
Use bed and pillow encasings
Furred pets
Advise to avoid preventively; if allergy is demonstrated, be firm on avoidance measures

Topical Corticosteroids
Although nearly all published guidelines consider
topical corticosteroids (TCS) as the first-line treat-
ment for AE, there is a lack of literature demonstrat-
ing the efficacy of this recommendation.83 TCS are
grouped according to their potency, which should be
known to their prescribers56: group I: mild; group II:
moderate; group III and IV: potent to very potent.
Because side effects of TCS such as striae, telangi-
ectasias, or atrophy are directly related to their
strength, very potent TCS should only be used for a
very short time and not on the face or intertriginous
areas.47 Systemic resorption of TCS has to be kept in
mind in children of less than 2 years and in patients
with severe flares.
Using TCS twice a day does not improve efficacy
over a once-a-day regimen.84 Interestingly, the type of
corticosteroid used does not seem to be of much impor-
tance in terms of efficacy.83 TCS are the treatment of
choice for acute flares.83 Once control over the current
flare has been reached, some authors proposed that a
twice-weekly application on skin sites prone to relapse
can help to maintain long-term control.85 Recently, the
term “proactive therapy” has been introduced for this
preventive treatment concept and studies were per-
formed with some corticosteroids and the topical cal-
cineurin inhibitor tacrolimus.86
Topical Calcineurin Inhibitors
In the United States and Europe, pimecrolimus (Elidel®,
Novartis) cream (1%) and tacrolimus (Protopic®,
Astellas) ointment (0.03%) are approved for the treat-
ment of AE in children of more than 2 years and of
adults. Tacrolimus ointment (0.1%) is only approved
for use in adults.63, 64 Both drugs have shown their effi-
cacy in numerous studies.83 The clinical potency of
146
tacrolimus is comparable with a TCS of intermediate
activity87 while pimecrolimus is less active.88 The most
observed side effect of both is a transient, mild, burn-
ing sensation on the application site.56
Since the United States Food and Drug Adminis­
tration (FDA) issued a “black box warning” on March
tenth 2005 concerning the safety of the topical cal-
cineurin inhibitors because of a lack of long-term
safety data,89 these valuable alternatives to TCS have
been labeled as second-line therapy and their use is
not recommended in infants younger than the age
of 2. Many clinicians found the FDA warning over-
cautious and statements on the safety have been
issued in response to the warning by multiple scien-
tific societies. For example, the American Academy
of Dermatology (AAD) states that “topical calcineu-
rin inhibitors remain available for patients with
atopic dermatitis.”90 Recent literature published after
the FDA warning indicates that the overall safety
profile of both drugs is still excellent even after long-
term use.91,92
13.4.3.2 UV Light Therapy
The treatment of AE with UV light is a well-estab-
lished standard second-line therapy.63, 64 A combination
with TCS for the treatment of acute flares is possible.
All treatment regimens have been used: broadband
UVB (280–320 nm), narrow-band UVB (311–313 nm),
UVA (320–400 nm), UVA1 (340–400 nm), PUVA, and
Balneo-PUVA.56 Erythema and inflammation are lim-
iting to this method. Due to the unknown long-term
safety profile, phototherapy should be restricted to
patients of 12 years and above.63, 64
13.4.3.3 Antimicrobial Therapy
As already mentioned above (see Sect. 13.2.4.2), the
atopic skin tends to be over-colonized by microbes like
Staphylococci and some fungi.
Topical
The use of “intelligent clothing” consisting of silver-
coated fabrics and specially coated silk textiles with anti-
microbial have shown some promising effect in
S. Wöhrl
preliminary studies.93 The PRACTALL guidelines rec-
ommend the use of chlorhexidine or triclosan to reduce
the microbial load.63, 64 The use of topical antibiotics like
erythromycin and fusidic acid has increased the abun-
dance of resistant Staphylococci. Therefore, topical anti-
biotic therapy should not be extended over more than 2
weeks.63, 64
Systemic
Severe exacerbations with widespread bacterial infec-
tion need a systemic antibiotic therapy. Usually, oral
therapy with penicillinase-resistant penicillins or first or
second generation cephalosporins for 7–10 days is suf-
ficient. Clindamycin and fusidic acid are alternatives.
Acute eczema herpeticum is a dermatological emer-
gency and hospitalization should be considered. Neck
stiffness is a clue to meningeal involvement and lum-
bar puncture should be performed to exclude herpes
meningitis. Acute eczema herpeticum should be treated
with intravenous acyclovir.94 For AE patients with
recurrent eczema herpeticum a continuous suppression
therapy with acyclovir or valacyclovir can reduce the
frequency of episodes and should be recommended to
these patients.94
Fungal infection is often found in patients with
severe AE. However, it is yet not clear whether sys-
temic antimycotic treatment reduces symptom severity
and is not recommended.63, 64
13.4.3.4 Dietary Restrictions
As mentioned above (allergy), dietary restrictions in
children should only be recommended when food
allergy has been proven by meaningful methods (see
Sect. 13.3.3). Hints on counseling patients with proven
allergies are found in Table 13.3.56
13.4.3.5 Antipruritic Treatment
Topical polidocanol at 1%, although known as a weak
contact sensitizer, can be added to emollients and has a
mild antipruritic effect. The pruritus of AE patients
typically exacerbates at night. Hence, sleeplessness is
a common problem. The treatment of choice is adju-
vant sedation with first-generation antihistamines that
13  Diagnosis and Prevention of Atopic Eczema
are capable of crossing the blood–brain barrier and
sedating central arousal functions mediated by hista-
mine.50 Typical drugs are diphenhydramine and
hydroxycine.95 Both drugs are available for children
and in liquid form.
Doxepin is a tricyclic antidepressant with a pro-
nounced antagonistic effect on histamine receptors. It
is a strong sedating drug and another option for treat-
ing sleep disturbances. It is used at a dose of 10 mg for
pediatric and 25 mg for adult AE patients.95 Melatonin
has also been suggested for mild cases.95
13.4.3.6 Systemic Immunosuppression
Cyclosporine
Cyclosporine A is a calcineurin inhibitor functioning
in the same way as the topical immunomodulators.
Treatment with cyclosporine leads to a reduction of the
T-cell activating IL-2 and IFN-g (gamma) cytokines. In
fact, it is a very potent drug for the treatment of AE and
its clinical effectiveness has been demonstrated in
numerous studies for children and adults with an excel-
lent level of evidence.96 It is a registered therapy for the
treatment of AE and is recommended as first option for
patients with AE refractory to conventional treatment.97
The treatment can either be based on short-term high
dose (3–5  mg/kg body weight) or on long-term low
dose (2.5 mg/kg body weight) regimens.63, 64 The nar-
row therapeutic index and the known side effects such
as renal toxicity or elevation of the blood pressure limit
this therapy to severe cases.
Malignancies have been reported after high-dose,
long-term treatment in transplant patients. A recent
review on the long-term safety data of dermatologic
patients revealed a higher risk for the development of
basal cell carcinoma but not of other tumors.98 The
authors conclude that due to the overall beneficial ben-
efit–risk ratio, cyclosporine can still be used at the lower
dermatologic doses of 3–5 mg/kg body weight.98
Azathioprine
Azathioprine at 1–3 mg/kg body weight has some tra-
dition as off-label therapy for recalcitrant AE.56 The
onset of action is rather slow. Myelosuppression, hepa-
totoxicity, and induction of skin malignancies, among
147
others, are relevant side effects. Azathioprine is metab-
olized by the thiopurine methyltransferase. Around
11.5% of the population have a reduced or no activity
in this enzyme caused mostly by three mutations.99
Since this enzyme deficiency causes most toxicities,
enzymatic or genetic testing must be performed before
starting this therapy.99
Other Immunosuppression
Different other immunosuppressive modalities have
been tried for the treatment AE: mycophenolate mofetil
at 2  g/day has a better security profile than azathio-
prine but larger randomized trials are still missing.56
Systemic corticosteroids are usually avoided because
of the pronounced rebound effect in AE patients.
Although a short-term course during an acute flare
might be useful in some cases, a long-term treatment
should be avoided especially in children due to the
problematic side-effect profile (osteoporosis, growth
retardation, diabetes, cataracts). The so-called biologi-
cals that have been so valuable for the treatment of
psoriasis have been disappointing when tried anecdot-
ally in AE and currently have no place in the treatment
of atopic skin.100
13.4.3.7 Nonpharmacological Intervention
Strategies
The goal of patient education is for patients to accept
their diagnosis of AE, to increase their knowledge of
the disease, and to reduce doctor shopping. Hints for
counseling AE patients are found in Table 13.3.56 Other
guidelines from the UK regarding counseling of AE
patients are available online.101
One excellently designed German study showed
that an educational intervention (6 weekly standard-
ized group sessions led by a multidisciplinary team
consisting of dermatologists or pediatricians, psychol-
ogists, and dieticians who had undergone 40 h of spe-
cial training) resulted in a reduction of objective
eczema as well as subjective severity indexes when
compared with a nonintervention control group.102
One American guideline covers recommendations
on psychological approaches,83 while such are lacking
in other guidelines.50, 56, 63, 64 Behavior modification
techniques and relaxation techniques showed some
148
benefit in reducing scratching, although the data are
contradictive.103
A recent Cochrane review104 concludes that the level
of evidence for the effectiveness for educational and
psychological interventions in AE is low due to the
small number and the inferior design of existing studies
except for the one German study mentioned above.102
References
  1. Novak N, Bieber T, et  al Immune mechanisms leading
to atopic dermatitis. J Allergy Clin Immunol. 2003;112(6
suppl):S128–S139
  2. Johansson SG, Bieber T, et  al Revised nomenclature for
allergy for global use: Report of the Nomenclature Review
Committee of the World Allergy Organization, October
2003. J Allergy Clin Immunol. 2004;113(5):832–836
  3. Hamelmann E, Beyer K, et al Primary prevention of allergy:
avoiding risk or providing protection? Clin Exp Allergy.
2008;38(2):233–245
  4. Illi S, von Mutius E, et al The natural course of atopic der-
matitis from birth to age 7 years and the association with
asthma. J Allergy Clin Immunol. 2004;113(5):925–931
  5. Asher MI, Montefort S, et al Worldwide time trends in the
prevalence of symptoms of asthma, allergic rhinoconjuncti-
vitis, and eczema in childhood: ISAAC phases one and three
repeat multicountry cross-sectional surveys. Lancet. 2006;
368(9537):733–743
  6. Van Eerdewegh P, Little RD, et  al Association of the
ADAM33 gene with asthma and bronchial hyperresponsive-
ness. Nature. 2002;418(6896):426–430
  7. Prescott SL. Allergy: the price we pay for cleaner living?
Ann Allergy Asthma Immunol. 2003;90(6 suppl 3):64–70
  8. Liu AH. Hygiene theory and allergy and asthma prevention.
Paediatr Perinat Epidemiol. 2007;21(suppl 3):2–7
  9. Ring J, Krämer U, et al A critical approach to the hygiene
hypothesis. Clin Exp Allergy Rev. 2004;4(suppl 2):40–44
10. Jovanovic S, Felder-Kennel A, et  al Exposition und
Sensibilisierung gegenüber Milben- und Katzenallergenen
bei Kindern in Baden-Württemberg. Gesundheitswesen.
2003;65(7):457–463
11. Cork M, Murphy R, et  al The rising prevalence of atopic
eczema and environmental trauma to the skin. Dermatol
Pract. 2002;10(3):22–26
12. Cork MJ, Robinson DA, et al New perspectives on epidermal
barrier dysfunction in atopic dermatitis: gene-environment
interactions. J Allergy Clin Immunol. 2006;118(1):3–21
13. Elias PM. Epidermal lipids, barrier function, and desquama-
tion. J Invest Dermatol. 1983;80 suppl:44s–49s
14. Taïeb A. Hypothesis: from epidermal barrier dysfunction to
atopic disorders. Contact Derm. 1999;41(4):177–180
15. Holleran WM, Takagi Y, et  al Epidermal sphingolipids:
metabolism, function, and roles in skin disorders. FEBS Lett.
2006;580(23):5456–5466
16. Chiou YB, Blume-Peytavi U. Stratum corneum maturation.
Skin Pharmacol Physiol. 2004;17(2):57–66
S. Wöhrl
17. Palmer CN, Irvine AD, et al Common loss-of-function vari-
ants of the epidermal barrier protein filaggrin are a major
predisposing factor for atopic dermatitis. Nat Genet.
2006;38(4):441–446
18. Baurecht H, Irvine AD, et al Toward a major risk factor for
atopic eczema: meta-analysis of filaggrin polymorphism
data. J Allergy Clin Immunol. 2007;120:1406–1412
19. Lebman DA, Coffman RL. Interleukin 4 causes isotype
switching to IgE in T cell-stimulated clonal B cell cultures.
J Exp Med. 1988;168(3):853–862
20. Maintz L, Novak N. Getting more and more complex: the
pathophysiology of atopic eczema. Eur J Dermatol. 2007;
17(4):267–283
21. Hamid Q, Boguniewicz M, et al Differential in situ cytokine
gene expression in acute versus chronic atopic dermatitis.
J Clin Invest. 1994;94(2):870–876
22. Larché M, Akdis CA, et al Immunological mechanisms of
allergen-specific immunotherapy. Nat Rev Immunol.
2006;6(10):761–771
23. Verhagen J, Akdis M, et  al Absence of T-regulatory cell
expression and function in atopic dermatitis skin. J Allergy
Clin Immunol. 2006;117(1):176–183
24. Sampson HA. Update on food allergy. J Allergy Clin
Immunol. 2004;113(5):805–819; quiz 820
25. Scalabrin DM, Bavbek S, et al Use of specific IgE in assessing
the relevance of fungal and dust mite allergens to atopic der-
matitis: a comparison with asthmatic and nonasthmatic control
subjects. J Allergy Clin Immunol. 1999; 104(6):1273–1279
26. Werfel T, Ballmer-Weber B, et al Eczematous reactions to
food in atopic eczema: position paper of the EAACI and
GA²LEN. Allergy. 2007;62(7):723–728
27. Mothes N, Niggemann B, et al The cradle of IgE autoreac-
tivity in atopic eczema lies in early infancy. J Allergy Clin
Immunol. 2005;116(3):706–709
28. Scheynius A, Johansson C, et al Atopic eczema/dermatitis
syndrome and Malassezia. Int Arch Allergy Immunol. 2002;
127(3):161–169
29. Greaves MW. Recent advances in pathophysiology and cur-
rent management of itch. Ann Acad Med Singap. 2007;36(9):
788–792
30. Schmid-Ott G, Jaeger B, et  al Different expression of
cytokine and membrane molecules by circulating lympho-
cytes on acute mental stress in patients with atopic dermati-
tis in comparison with healthy controls. J Allergy Clin
Immunol. 2001;108(3):455–462
31. Rukwied R, Lischetzki G, et  al Mast cell mediators other
than histamine induce pruritus in atopic dermatitis patients:
a dermal microdialysis study. Br J Dermatol. 2000;142(6):
1114–1120
32. Badertscher K, Bronnimann M, et al Mast cell chymase is
increased in chronic atopic dermatitis but not in psoriasis.
Arch Dermatol Res. 2005;296(10):503–506
33. Järvikallio A, Harvima IT, et al Mast cells, nerves and neu-
ropeptides in atopic dermatitis and nummular eczema. Arch
Dermatol Res. 2003;295(1):2–7
34. Raap U, Werfel T, et al Circulating levels of brain-derived neu-
rotrophic factor correlate with disease severity in the intrinsic
type of atopic dermatitis. Allergy. 2006;61(12): 1416–1418
35. Dillon SR, Sprecher C, et al Interleukin 31, a cytokine pro-
duced by activated T cells, induces dermatitis in mice. Nat
Immunol. 2004;5(7):752–760
13  Diagnosis and Prevention of Atopic Eczema
36. Bilsborough J, Leung DY, et al IL-31 is associated with cuta-
neous lymphocyte antigen-positive skin homing T cells in
patients with atopic dermatitis. J Allergy Clin Immunol.
2006;117(2):418–425
37. Abeck D, Mempel M. Kutane Staphylococcus aureus
Besiedelung des atopischen Ekzems. Hautarzt. 1998;49(12):
902–906
38. Bogaert D, van Belkum A, et al Colonisation by Streptococcus
pneumoniae and Staphylococcus aureus in healthy children.
Lancet. 2004;363(9424):1871–1872
39. Leyden JJ, Marples RR, et al Staphylococcus aureus in the
lesions of atopic dermatitis. Br J Dermatol. 1974;90(5):
525–530
40. Novak N, Bieber T. Pathogenese des atopischen Ekzems.
JDDG J Ger Soc Dermatol. 2005;3(12):994–1005
41. Bunikowski R, Mielke M, et al Prevalence and role of serum
IgE antibodies to the Staphylococcus aureus-derived
superantigens SEA and SEB in children with atopic derma-
titis. J Allergy Clin Immunol. 1999;103(1 Pt 1):119–124
42. Sonkoly E, Muller A, et al IL-31: a new link between T cells
and pruritus in atopic skin inflammation. J Allergy Clin
Immunol. 2006;117(2):411–417
43. Ong PY, Ohtake T, et al Endogenous antimicrobial peptides
and skin infections in atopic dermatitis. N Engl J Med.
2002;347(15):1151–1160
44. Howell MD, Wollenberg A, et  al Cathelicidin deficiency
predisposes to eczema herpeticum. J Allergy Clin Immunol.
2006;117(4):836–841
45. Schudel P, Wüthrich B. Klinische Verlaufsbeobachtungen
bei Neurodermitis atopica nach dem Kleinkindesalter. Eine
katamnestische Untersuchung anhand von 121 Fällen. H±G
Zeitschrift für Hautkrankheiten. 1985;60(6):479–486
46. Hanifin J, Rajka G. Diagnostic features of atopic dermatitis.
Acta Derm Venereol (Stockh). 1980;92 suppl:44s–47s.
47. Leung DY, Bieber T. Atopic dermatitis. Lancet. 2003;
361(9352):151–160
48. Williams HC, Burney PG, et al The U.K. Working Party’s
Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a
minimum set of discriminators for atopic dermatitis. Br J
Dermatol. 1994;131(3):383–396
49. Jøhnke H, Vach W, et al A comparison between criteria for
diagnosing atopic eczema in infants. Br J Dermatol. 2005;
153(2):352–358
50. Lewis-Jones S, Mugglestone MA. Management of atopic
eczema in children aged up to 12 years: summary of NICE
guidance. Bmj. 2007;335(7632):1263–1264
51. Turjanmaa K, Darsow U, et  al EAACI/GA²LEN position
paper: present status of the atopy patch test. Allergy.
2006;61(12):1377–1384
52. Berni Canani R, Ruotolo S, et al Diagnostic accuracy of the
atopy patch test in children with food allergy-related gastro-
intestinal symptoms. Allergy. 2007;62(7):738–743
53. Mehl A, Rolinck-Werninghaus C, et al The atopy patch test in
the diagnostic workup of suspected food-related symptoms in
children. J Allergy Clin Immunol. 2006; 118(4): 923–929
54. Niggemann B, Gruber C. Unproven diagnostic procedures in
IgE-mediated allergic diseases. Allergy. 2004;59(8):
806–808
55. Stapel SO, Asero R, et al Testing for IgG4 against foods is
not recommended as a diagnostic tool: EAACI task force
report. Allergy. 2008;63(7):793–796
149
56. Darsow U, Lübbe J, et  al Position paper on diagnosis and
treatment of atopic dermatitis. J Eur Acad Dermatol
Venereol. 2005;19(3):286–295
57. Smith FJ, Irvine AD, et al Loss-of-function mutations in the
gene encoding filaggrin cause ichthyosis vulgaris. Nat
Genet. 2006;38(3):337–342
58. Lin SP, Huang SY, et al Netherton syndrome: mutation anal-
ysis of two Taiwanese families. Arch Dermatol Res.
2007;299(3):145–150
59. Torgerson TR, Ochs HD. Immune dysregulation, polyendo-
crinopathy, enteropathy, X-linked: forkhead box protein 3
mutations and lack of regulatory T cells. J Allergy Clin
Immunol. 2007;120(4):744–750
60. Lannerö E, Wickman M, et  al Maternal smoking during
pregnancy increases the risk of recurrent wheezing during
the first years of life (BAMSE). Respir Res. 2006;7:3
61. Muraro A, Dreborg S, et  al Dietary prevention of allergic
diseases in infants and small children. Part III: critical review
of published peer-reviewed observational and interventional
studies and final recommendations. Pediatr Allergy Immunol.
2004;15(4):291–307
62. Greer FR, Sicherer SH, et al Effects of early nutritional inter-
ventions on the development of atopic disease in infants and
children: the role of maternal dietary restriction, breastfeeding,
timing of introduction of complementary foods, and hydro-
lyzed formulas. Pediatrics. 2008;121(1):183–191
63. Akdis CA, Akdis M, et al Diagnosis and treatment of atopic
dermatitis in children and adults: European Academy of
Allergology and Clinical Immunology/American Academy
of Allergy, Asthma and Immunology/PRACTALL Consensus
Report. J Allergy Clin Immunol. 2006;118(1):152–169
64. Akdis CA, Akdis M, et al Diagnosis and treatment of atopic
dermatitis in children and adults: European Academy of
Allergology and Clinical Immunology/American Academy
of Allergy, Asthma and Immunology/PRACTALL Consensus
Report. Allergy. 2006;61(8):969–987
65. Lowe LA, Woodcock A, et al Lung function at age 3 years:
effect of pet ownership and exposure to indoor allergens.
Arch Pediatr Adolesc Med. 2004;158(10):996–1001
66. Svanes C, Zock JP, et  al Do asthma and allergy influence
subsequent pet keeping? An analysis of childhood and adult-
hood. J Allergy Clin Immunol. 2006;118(3):691–698
67. Sporik R, Ingram JM, et al Association of asthma with serum
IgE and skin test reactivity to allergens among children liv-
ing at high altitude. Tickling the dragon’s breath. Am J
Respir Crit Care Med. 1995;151(5):1388–1392
68. von Mutius E, Weiland SK, et  al Increasing prevalence of
hay fever and atopy among children in Leipzig, East
Germany. Lancet. 1998;351(9106):862–866
69. Flöistrup H, Swartz J, et al Allergic disease and sensitization
in Steiner school children. J Allergy Clin Immunol.
2006;117(1):59–66
70. Ventura MT, Munno G, et al Allergy, asthma and markers of
infections among Albanian migrants to Southern Italy.
Allergy. 2004;59(6):632–636
71. van den Biggelaar AH, Rodrigues LC, et al Long-term treat-
ment of intestinal helminths increases mite skin-test reactivity in
Gabonese schoolchildren. J Infect Dis. 2004;189(5): 892–900
72. Flood JM, Weinstock HS, et  al Neurosyphilis during the
AIDS epidemic, San Francisco, 1985–1992. J Infect Dis.
1998;177(4):931–940
150
73. Kalliomaki M, Salminen S, et al Probiotics in primary pre-
vention of atopic disease: a randomised placebo-controlled
trial. Lancet. 2001;357(9262):1076–1079
74. Kalliomaki M, Salminen S, et al Probiotics and prevention
of atopic disease: 4-year follow-up of a randomised placebo-
controlled trial. Lancet. 2003;361(9372):1869–1871
75. Kalliomaki M, Salminen S, et al Probiotics during the first 7
years of life: a cumulative risk reduction of eczema in a ran-
domized, placebo-controlled trial. J Allergy Clin Immunol.
2007;119(4):1019–1021
76. Niederberger V, Valenta R. Molecular approaches for new vac-
cines against allergy. Expert Rev Vaccines. 2006;5(1):103–110
77. Niederberger V, Horak F, et al Vaccination with genetically
engineered allergens prevents progression of allergic dis-
ease. Proc Natl Acad Sci USA. 2004;101(suppl 2):
14677–14682
78. Niggemann B, Jacobsen L, et al Five-year follow-up on the
PAT study: specific immunotherapy and long-term preven-
tion of asthma in children. Allergy. 2006;61(7):855–859
79. Jacobsen L, Niggemann B, et al Specific immunotherapy has
long-term preventive effect of seasonal and perennial asthma:
10-year follow-up on the PAT study. Allergy. 2007;62(8):
943–948
80. Bussmann C, Maintz L, et  al Clinical improvement and
immunological changes in atopic dermatitis patients under-
going subcutaneous immunotherapy with a house dust mite
allergoid: a pilot study. Clin Exp Allergy. 2007;37(9):
1277–1285
81. Werfel T, Breuer K, et  al Usefulness of specific immuno-
therapy in patients with atopic dermatitis and allergic sensi-
tization to house dust mites: a multi-centre, randomized,
dose-response study. Allergy. 2006;61(2):202–205
82. Abramovits W, Boguniewicz M. A multicenter, randomized,
vehicle-controlled clinical study to examine the efficacy and
safety of MAS063DP (Atopiclair) in the management of
mild to moderate atopic dermatitis in adults. J Drugs
Dermatol. 2006;5(3):236–244
83. Hanifin JM, Cooper KD, et al Guidelines of care for atopic
dermatitis, developed in accordance with the American
Academy of Dermatology (AAD)/American Academy of
Dermatology Association “Administrative Regulations for
Evidence-Based Clinical Practice Guidelines”. J Am Acad
Dermatol. 2004;50(3):391–404
  84. Hoare C, Li Wan Po A, et al Systematic review of treatments
for atopic eczema. Health Technol Assess. 2000;4(37):1–191
  85. Van Der Meer JB, Glazenburg EJ, et al The management of
moderate to severe atopic dermatitis in adults with topical
fluticasone propionate. The Netherlands Adult Atopic
Dermatitis Study Group. Br J Dermatol. 1999;140(6):
1114–1121
  86. Wollenberg A, Bieber T. Proactive therapy of atopic derma-
titis – an emerging concept. Allergy. 2009;64(2):276–278
  87. Ashcroft DM, Dimmock P, et al Efficacy and tolerability of
topical pimecrolimus and tacrolimus in the treatment of
atopic dermatitis: meta-analysis of randomised controlled
trials. BMJ. 2005;330(7490):516
S. Wöhrl
  88. Luger T, Van Leent EJ, et al SDZ ASM 981: an emerging
safe and effective treatment for atopic dermatitis. Br J
Dermatol. 2001;144(4):788–794
  89. Thaçi D, Salgo R. The topical calcineurin inhibitor pime-
crolimus in atopic dermatitis: a safety update. Acta
Dermatovenerol Alp Panonica Adriat. 2007;16(2):58,
60–62
  90. Berger TG, Duvic M, et al The use of topical calcineurin
inhibitors in dermatology: safety concerns. Report of the
American Academy of Dermatology Association Task
Force. J Am Acad Dermatol. 2006;54(5):818–823
  91. Remitz A, Harper J, et al Long-term safety and efficacy of
tacrolimus ointment for the treatment of atopic dermatitis
in children. Acta Derm Venereol. 2007;87(1):54–61
  92. Ring J, Abraham A, et  al Control of atopic eczema with
pimecrolimus cream 1% under daily practice conditions:
results of a >2000 patient study. J Eur Acad Dermatol
Venereol. 2008;22(2):195–203
  93. Ricci G, Patrizi A, et al Use of textiles in atopic dermatitis:
care of atopic dermatitis. Curr Probl Dermatol.
2006;33:127–143
  94. Rerinck HC, Kamann S, et  al Eczema herpeticum:
Pathogenese und Therapie. Hautarzt. 2006;57(7):586–591
  95. Kelsay K. Management of sleep disturbance associated
with atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):
198–201
  96. Schmitt J, Schmitt N, et al Cyclosporin in the treatment of
patients with atopic eczema – a systematic review and
meta-analysis. J Eur Acad Dermatol Venereol. 2007;21(5):
606–619
  97. Schmitt J, Schakel K, et  al Systemic treatment of severe
atopic eczema: a systematic review. Acta Derm Venereol.
2007;87(2):100–111
  98. Behnam SM, Behnam SE, et  al Review of cyclosporine
immunosuppressive safety data in dermatology patients after
two decades of use. J Drugs Dermatol. 2005;4(2): 189–194
  99. Wise M, Callen JP. Azathioprine: a guide for the manage-
ment of dermatology patients. Dermatol Ther. 2007;
20(4):206–215
100. Heymann WR. Antipsoriatic biologic agents for the treat-
ment of atopic dermatitis. J Am Acad Dermatol. 2007;56(5):
854–855
101. National Institute for Health and Clinical Excellence. NICE
guidance. At: <http://www.nice.org.uk/search/searchresults.
jsp?keywords=eczema&searchType=all>; 2009 Accessed
04.04.09
102. Staab D, Diepgen TL, et al Age related, structured educa-
tional programmes for the management of atopic dermatitis
in children and adolescents: multicentre, randomised con-
trolled trial. BMJ. 2006;332(7547):933–938
103. Chida Y, Steptoe A, et al The effects of psychological inter-
vention on atopic dermatitis. A systematic review and
meta-analysis. Int Arch Allergy Immunol. 2007;144(1):1–9
104. Ersser SJ, Latter S, et  al Psychological and educational
interventions for atopic eczema in children. Cochrane
Database Syst Rev. 2007;(3):CD004054
 Prevention of Psoriasis
14
Gwynn Coatney and Robert A. Norman

14.1 Introduction stem cells of the innermost or basal layer) upwards to

the most superficial layer of the epidermis, the stratum
corneum. In psoriasis this process is much faster, taking
Psoriasis is one of the most common skin diseases and
only 3–5 days to complete the cycle. The hyperprolif-
it affects millions of people all over the world. It is
eration of these cells is caused by an inflammatory
usually chronic in nature with onset and flare-ups being
response in the immune system. It is still unclear what
unpredictable. The disease course ranges from mild
causes this response in psoriasis, but it is known that the
forms consisting of annoying symptomatology of itchy
immune system erroneously activates T cells. T cells
dry skin and unsightly scaling plaques to extreme cases
then activate inflammatory mediators, or cytokines like
that can induce disfigurement, prolonged suffering,
tumor necrosis factor-alpha (TNF-a), to trigger the
and systemic manifestations such as arthritis and even
increased proliferation of the epithelial cells.11, 24
an increased mortality. Psoriasis is very costly to treat
and treatment itself can be a very time-consuming
commitment. Some of the newest treatments can cost
up to $25,000 a year and most treatments involve 14.1.2 Prevalence/Incidence
months of intensive treatment regimens.13 In general,
psoriasis is a major cause of social and physical dis-
Current estimates show that 2–3% of the world popula-
comfort that can also become a serious burden finan-
tion is affected by psoriasis. Up to seven million people
cially for patients affected by this inflammatory
in the United States have this common cutaneous dis-
disease. Due to the widespread affliction and the severe
ease. It is also estimated that 150,000–200,000 new
nature of psoriasis special attention should be focused
cases are diagnosed each year in the US. Psoriasis
on preventing the disease.
equally affects the male and female genders. There is a
lower incidence of psoriasis seen in people with darker
skin – Africans, Asians, and Inuits, and the disease is
14.1.1 Pathogenesis very rarely seen in North and South American
Indians.11, 17, 24
Psoriasis is an immune-mediated inflammatory disor-
der, in which epithelial cells have an increased produc-
tion and turnover rate. Normal skin takes almost a 14.1.3 Onset
month to cycle from newly formed keratinocytes (from
The peak age of onset of psoriasis usually occurs in
people in their third decade of life, but it can present
anywhere from the neonatal period to people in their
G. Coatney (*)
Department of Family Medicine, University of Medicine
70s. When the disease presents early in life it is more
and Dentistry of New Jersey, Stratford, NJ, USA likely to develop into a more severe form and become
e-mail: gcoatney@hotmail.com chronic in nature.24

R. A. Norman (ed.), Preventive Dermatology, 151

DOI: 10.1007/978-1-84996-021-2_14, © Springer-Verlag London Limited 2010
152 G. Coatney and R. A. Norman

14.1.4 Severity/Types/Distribution Pustular psoriasis has two subtypes, palmoplantar

and generalized acute pustular psoriasis. Cases of pus-
tular psoriasis are much less frequently seen than the
There are two major classifications of psoriasis, psoria-
psoriasis vulgaris types. Palmoplantar psoriasis usu-
sis vulgaris and pustular psoriasis (Table 14.1). Psoriasis
ally appears later in life and has a higher incidence
vulgaris includes the acute guttate, chronic plaque,
females, a ratio of almost 4:1. Palmoplantar pustulosis
inverse and palmoplantar subtypes. Characteristically,
is a chronic condition where pustules in different stages
these different types range from eruptive and inflam-
of evolution and healing appear in groups only on the
matory lesions to chronic and lichenified. Guttate pso-
palms and soles of the hands and feet. Relapse and
riasis is seen in about 2% of all psoriasis cases and
recurrence of the disorder is common. Generalized
consists of small erythematous lesions that appear
acute pustular psoriasis can be a dermatologic emer-
acutely. This subtype of psoriasis vulgaris can sponta-
gency. In this subtype the skin becomes diffusely ery-
neously resolve without treatment. Guttate psoriasis
thematous and pustules appear in clusters within hours
has a generalized distribution with the majority of
of initial onset. This condition is usually accompanied
lesions appearing on the trunk. A common presentation
by fever, malaise and generalized weakness.
of guttate psoriasis occurs after an infection like strep-
About 10% of those diagnosed with psoriasis are also
tococcal pharyngitis. The lesions appear diffusely on
diagnosed with psoriatic arthritis. The age of onset for
the skin, much like an exanthem-type rash. Plaque pso-
psoriatic arthritis is 10–15 years later in life, averaging in
riasis is usually chronic in nature and is the most com-
the mid-30s. Psoriatic arthritis is most often found in the
mon type of psoriasis. Clinically, this subtype exhibits
hands and feet, resulting in “sausage” digits, but can also
the classic lesions that most people associate with pso-
affect larger joints. Finger and toenails are involved in
riasis. They are sharply demarcated, salmon pink to ery-
25% of psoriatic cases in general, and have a high corre-
thematous in color and have a loose silvery white scale.
lation with psoriatic arthritis. Clinically the nail may
Lesions are classically concentrated on the elbows,
include pitting, hyperpigmented spots under the nail plate
knees, over the sacrum, on the scalp, and on the palms
and hyperkeratotic changes of the nail itself. 11, 24
and soles of the hands and feet. The face and neck are
rarely involved. These plaques are generally bilateral
and symmetric. Inverse type of psoriasis chronically
affects the skin-fold areas of the body including the 14.1.5 Genetics
groin region, under the breasts, and the axillae. These
areas are moist, giving the psoriatic plaques a different Immunological factors contribute to the pathophysiol-
appearance than seen in the classic presentation. The ogy of psoriasis, but it is unknown whether psoriasis is
thick, scaly plaques are replaced with bright red and fis- caused by an immune system dysfunction or by genetic
sured lesions. The plaques of the palmoplantar type of defects found in keratinocytes of the epidermis.1 Many
psoriasis are distributed only on the palms and soles and studies suggest that there is a genetic predisposition
usually demonstrate more hyperkeratotic and scaling for psoriasis. The Lomholt study conducted on the
type lesions.8 Faroe Islands of Denmark found that 91% of those

Table 14.1  Types of psoriasis

Psoriasis vulgaris subtypes Pustular subtypes
Subtypes Acute guttate Chronic plaque Inverse Palmo-plantar Generalized acute Palmo-plantar
pustular

Onset/duration Acute Chronic Sub-acute to chronic Chronic Acute Chronic

Distribution Diffuse, but mainly Bilateral, symmetric, In skin folds, under Palms of hands, Generalized and Palms and soles
pattern on the trunk elbows, knees, breast, groin, soles of diffuse
scalp, sacrum axillae feet

Characteristics Erythematous, small, Salmon pink with a Bright red, fissured Scaly-crusted, Base is erythematous Pustules are arranged
round-oval in silvery scale, thick, thick with overlying in groups in
shape sharply demarcated clusters of different stages
pustules of healing
14  Prevention of Psoriasis
questioned with psoriasis had at least one first- or
­second-degree relative who were also inflicted with the
disease.18, 23 Over 5,000 study subjects with psoriasis
had family members also affected by the disease in a
study done by Farber and Nall.4, 23 A study by Kavli
showed that the prevalence of psoriasis increases with
the number of relatives with the same disease.14, 23 Twin
studies have been performed revealing that the herita-
bility of psoriasis was estimated to be as high as
60–90%.2, 23 When one parent has psoriasis 8% of the
offspring will develop the disease. When both parents
have psoriasis 41% of their children will also have the
disease. Psoriasis is inherited as a polygenic trait in
which disease types, severity, and degree of skin
involvement depends on several different alleles found
on different genes. The human leukocyte antigen
(HLA) types most frequently associated with psoriasis
are HLA-B13, -B17, Bw57, and Cw6. Nearly half the
patients with psoriatic arthritis will have HLA-B27,
which is most commonly associated with ankylosing
spondylitis.24
14.2 Risk Factors/Triggers
Most triggers for psoriasis are immunologic in nature.
Physical trauma like harsh rubbing of the epidermis or
scratching can elicit the lesions, known as Koebner’s
phenomenon. Infections have been known to precipi-
tate outbreaks of psoriasis. For example, the first lesion
of psoriasis can show up after a streptococcal infec-
tion. This is most often seen in the guttate type of pso-
riasis, and in children. Stress is an important risk factor
causing flares in up to 40% of adults and children. In
the Farber and Nall study one-third of the 5,600 pso-
riasis patients studied reported that stress or worry
induced new areas of affected skin.4, 23
Certain types of drugs have been associated with
the onset and exacerbation of psoriasis. The most stud-
ied include beta blockers, calcium channel blockers,
lithium, NSAIDs, and antimalarial medications.
Smoking cigarettes and drinking alcohol have a
strong correlation with psoriasis. Combining the results
of two studies performed in Germany, current smokers
have a higher prevalence rate of psoriasis, when com-
pared to those who have quit smoking or who have
never smoked. The results indicating positive histories
of both smoking and psoriasis were 3.8 vs. 2.7 and
153
2.8% respectively. One of these studies also showed
that participants that drank more than 20 g of alcohol a
day had a prevalence of psoriasis of 4.7%.23 More spe-
cifically, 4.8% of the participants who drank a daily
beer also had psoriasis, and of those who admitted to
drinking at least three glasses of wine a week 6.4%
also had the disease. The dermatology clinics of the
University of Utah enrolled patients in the Utah
Psoriasis Initiative (UPI), which studied the impact of
smoking and obesity on psoriasis. Of the patients stud-
ied 37% admitted being current smokers. The preva-
lence of smoking in the UPI was higher than the
general Utah population, which is 13%. It was also
higher than in the nonpsoriatic population of Utah of
which 25% are smokers.9
In the two separate research pursuits of Naldi and
Kavli evidence was found that lack of a balanced diet
or being deficient in certain vitamins and minerals are
risk factors for psoriasis. Proper nutrition in general is
important for a person’s overall health and mainte-
nance of immune system function. People who have a
low consumption of fruit and vegetables, especially
carrots, tomatoes or Beta carotene are more likely to
have psoriasis.20, 14
14.2.1 Disease Associations
There are many diseases associated with psoriasis.
Some of the more common disorders include hyper-
tension, cardiovascular diseases, obesity, inflammatory
bowel disorders, depression, and cancer.15, 16
Those who are overweight and obese or who have
an increased body mass index (BMI) have been shown
to have a higher incidence of psoriasis.20 Looking again
at the UPI, the percentage of patients that were obese
and had psoriasis was double the number compared to
the general Utah population that was obese and with-
out psoriasis. This study found that the majority of
their participants were of normal weight at the time of
onset or diagnosis of psoriasis and transitioned into
being obese. This suggests that obesity is not a risk
factor for psoriasis, but a result of the disease.9
There is a strong relationship between Crohn’s dis-
ease and psoriasis. This may be due to a common fac-
tor between inflammatory bowel disease and psoriasis;
they both have increased levels of the inflammatory
cytokine, tumor necrosis factor-a.19
154
Multiple television ads portray people with psoriasis
and their embarrassment about their skin’s appearance.
Over the years many writers and poets have written
about the disease and how it has a negative effect on their
lives. It has long been known that psoriasis has a link to
psychosocial disorders and decreased self-esteem.22 An
Italian study done in 2006 sent questionnaires to patients
who were diagnosed with psoriasis. The goal of this
study was to assess the degree of depressive symptoma-
tology in psoriasis patients. A total of 2,391 people par-
ticipated and it was found that 62% of those polled
admitted to symptoms of depression.3
A retrospective survey has shown the correlation of
psoriasis and cancer. The percentage of subjects of
this study with no cancer history was 3.3% compared
with 9.4% of the participants who had a positive can-
cer history. These results were obtained after control-
ling age, gender, and alcohol or tobacco use. Many
studies have concluded that patients with psoriasis are
at an increased risk for developing a specific type of
cancer, lymphoma.23, 5
Patients with psoriasis have an increased morbidity
and mortality rate. A cohort study done by Dr. Gelfand
and his colleagues used the United Kingdom’s general
practice research database (GPRD) to follow patients
with psoriasis over a 15-year period. They compared
three groups of patients. The first included over
130,000 patients with mild psoriasis, the second group
was comprised of almost 4,000 patients with severe
psoriasis, and the third group was considered the con-
trol group, patients not diagnosed with psoriasis. This
last group included 5 times as many patients as the first
two groups combined. To differentiate between mild
and severe psoriasis the researchers classified the mild
group as patients that had the diagnosis of psoriasis,
but had no history of systemic therapy. Conversely the
severe group was classified as patients with the diag-
nosis of psoriasis and also with history of being treated
with systemic therapy. One objective of this study was
to determine whether psoriasis is an independent risk
factor for myocardial infarction (MI). Adjustments
were made to the study regarding major cardiovascular
risk factors such as hypertension, diabetes mellitus,
hyperlipidemia, age, sex, smoking history, family his-
tory of MI, BMI, or previous personal history of MI.
The incidence of MI for the control group and the mild
psoriasis group was about 2%. The incidence of MI in
the severe psoriasis group was 2.9%. Relative risk was
also measured according to age. For a 30-year-old
G. Coatney and R. A. Norman
patient the relative risk for MI is 1.29 for mild psoria-
sis and 3.10 for severe psoriasis. The relative risk for
MI in a 60-year-old is 1.08 for mild and 1.36 for severe
psoriasis. This same study found that the group of
patients with severe psoriasis had a death rate almost
double of the control group. This ratio even persisted
after controlling other comorbidities linked to mortal-
ity from the equation, including smoking status, BMI,
heart disease, AIDs, cancer, renal disease, and others.
An interesting observation showed that there was no
significant difference when comparing the death rate
of the group with mild psoriasis to the group without
psoriasis. On average, patients with severe psoriasis
died 3–4 years earlier than patients not diagnosed with
and treated for the severe form of the disease.6, 7
14.3 Treatments
Psoriasis is a chronic and recurrent disease that requires
appropriate care and often includes systematic treat-
ment.12 A recent survey from the National Psoriasis
Foundation polled 1,657 participants diagnosed with
severe or moderate psoriasis to assess their level of
treatment. This study found that almost 40% of those
surveyed are currently receiving no treatment at all for
their condition. In opposition, one quarter of those
questioned with severe psoriasis were receiving either
systemic therapy or phototherapy and 35% are being
treated with only topical therapy (Table 14.2).10, 21
14.3.1 Topicals
One of the longest treatments in use is Anthralin, a
synthetic form of chrysarobin, which is a chemical
compound found in the bark of the Araroba tree of
South America. It can be a good treatment choice for
the plaque type of psoriasis.
Dovonex is a synthetic form of vitamin D3 which
treats psoriasis by decreasing the rate of keratinocyte
proliferation. It does not treat the inflammation aspect
of the disease but it decreases the surface area of the
lesions and helps in removing the scale. A scalp solu-
tion of Dovonex is also available. Recommendations
say to apply the solution at night and wear a shower
cap to bed. The solution can then be washed out in the
14  Prevention of Psoriasis 155

Table 14.2  Overview of treatments

Treatment Examples Treatment for Use in conjunction Common side effects
with
Topicals Anthralin, Dovonex, Mild-to-moderate plaque Topical steroids, Anthralin can stain the skin,
Taclonex, Tazorac psoriasis, scalp phototherapy or oral Dovonex, Taclonex, and
medications used to Tazorac can cause skin
treat psoriasis irritation
Phototherapy UVB treatment, Mild-to-moderate plaque May be used together or Redness/sunburn, irritated
PUVA treatment psoriasis, vitiligo alternate with skin, blistering. Psoralen
with Psoralen topicals, orals, or can cause nausea
biologics, but avoid
with Taclonex and
Tazorac
Oral systemics Cyclosporine, Moderate-to-severe Topical medications like Possibility of organ damage,
Soriatane, psoriasis, Dovonex most commonly the
Methotrexate Cyclosporine is good kidneys or liver
to treat nail involve-
ment, Methotrexate
can also treat psoriatic
arthritis
Biologics Amevive, Enbrel, Moderate to severe plaque Can be used alterna- Nausea, itching, chills, sore
Humira, Remicade psoriasis, those who tively with throat, dizziness, injection
did not clear with phototherapy and site irritation, headache,
other treatments. oral medications like cough
Enbrel, Humira and Methotrexate
Remicade can also be
used to treat psoriatic
arthritis

morning. This cream or ointment has been shown to be
safe and effective when used in combination with topi-
cal steroids and systemic treatments to combat more
severe cases of psoriasis. Dovonex has also been shown
to increase the effectiveness of phototherapy treat-
ments when applied after the UV ray treatment.
Another topical treatment option is Taclonex, which
is a combination of the same active ingredient found in
Dovonex and a steroid. There is also a formulation that
can be used on the scalp.
Tazorac is a topical therapy used for plaque psoria-
sis. It is a topical retinoid, or vitamin A derivative.
Tazorac comes in two forms, gel and cream and each
has two strengths, 0.05 and 0.1%. The gel is clear and
fast-drying and the cream has a moisturizer that makes
it a good choice for patients with drier, more sensitive
skin. Both formulations work to slow the rapid prolif-
eration of the epithelial cells. Tazorac can be combined
with steroids to promote faster clearing time and can
also reduce skin irritation and redness. Combining
Tazorac with phototherapy has also been shown to get
better results than using either treatment alone.
Topical steroids can be a great aid in the treatment
of psoriasis. They can be used in combination with
most other topical treatments but are not effective
when used alone. They can help achieve the goal of
clearing the psoriasis lesions at a faster rate. Their anti-
inflammatory capabilities help reduce side effects of
the medications, including irritation, itching, and red-
ness. For resistant psoriasis plaques intralesional injec-
tions of steroids may be a good option.21
14.3.2 Systemic Therapy
Systemic therapy for psoriasis is usually reserved for
moderate-to-severe psoriasis or for patients who have
failed to become clear with topical or phototherapy
treatment.
Cyclosporine, or Neoral, is an immune-suppressant.
Its mechanism of action works to inhibit T cells. It is
taken every day in either pill or liquid form. Good
­outcomes have been achieved when combining
156
Cyclosporine and Dovonex topical therapy. By using
both medications the dosage of Cyclosporine can be
lowered and thus decreases potential side effects
caused by high doses or chronic use of Cyclosporine.
The only oral retinoid approved for the treatment of
psoriasis is called Soriatane. It is a synthetic form of
vitamin A. Soriatane is a good treatment for the plaque,
guttate, pustular and palmoplantar types of psoriasis.
Oral retinoids like Soriatane result in clearer skin by
modifying how keratinocytes multiply and the rate at
which they divide and shed. Soriatane is taken once
daily in pill form. It can be used in combination with
Dovonex and has had great results when used in con-
junction with phototherapy.
Methotrexate is another common oral systemic
medication used to treat psoriasis. It is a medication
that has been used to treat cancer since the 1950s and
20 years later was approved to treat psoriasis.
Methotrexate is effective in treating psoriasis because
the medication decreases epithelial cell growth. Unlike
Cyclosporine and Soriatane, Methotrexate can also be
used to treat psoriatic arthritis. Methotrexate is admin-
istered once a week either in pill or liquid form, or by
injection. After the clearance of psoriasis lesions is
obtained the dosage is tapered. Some patients may
require a maintenance dose to prevent relapse.21
14.3.3 Biologics
Biologics are the newest treatments for psoriasis and
psoriatic arthritis. The name for this group of medica-
tions is fitting, because these formulations are derived
from human or animal proteins, not chemicals or syn-
thetic compounds. Biologics are different from other
psoriasis treatments because they are designed to
work in the immune system; their goal is to block the
disease in the early developmental stages. Biologics
do this by targeting the overactive immune cells in the
body. Some concentrate on T cells by preventing their
activation or by stopping their migration in the
immune response. Other biologic treatments bind to
TNF-a and prevent it from initiating the proliferation
of keratinocytes.
Amevive and Raptiva are two of the biologic prepa-
rations that work by blocking the activation of T cells,
thereby decreasing inflammation and halting the immune
response before TNF-a cells can cause rapid growth
G. Coatney and R. A. Norman
and turnover of epithelial cells. Amevive and Raptiva
are FDA-approved for the treatment of moderate-to-
severe plaque psoriasis in adults, but not psoriatic arthri-
tis. Patients receiving Amevive receive an intramuscular
shot at their doctor’s office weekly for at least 12 weeks.
If the goal of 75% clearance is not achieved a second
12 week course can be instituted. Raptiva can be self-
injected by patients on a weekly basis.
The mechanism of action for Enbrel, Humira and
Remicade consists of blocking TNF-a and interrupt-
ing the inflammatory cycle of psoriasis and psoriatic
arthritis. Patients using Enbrel give themselves a sub-
cutaneous injection once or twice weekly, those using
Humira also inject subcutaneously, but only every
other week. Remicade is given in a doctor’s office and
the treatment includes three separate 2-h infusions dur-
ing the first 6 weeks of treatment. Every 8 weeks fol-
lowing another infusion is given. Enbrel, Humira, and
Remicade are currently approved to treat moderate-to-
severe plaque psoriasis and psoriatic arthritis in adults.
They are also being used to treat rheumatoid arthritis,
juvenile rheumatoid arthritis, and ankylosing spon-
dylitis. Remicade is also approved for the treatment of
Crohn’s disease and ulcerative colitis. In the future
Enbrel may be approved to treat psoriasis in children
as well as adults.21
14.3.4 Phototherapy
Natural sunlight contains ultraviolet light bands A–C.
Most ultraviolet light is absorbed by the earth’s atmo-
sphere, with mostly UVA reaching the earth’s surface.
UVB light can be beneficial to our skin in small doses
by initiating vitamin D synthesis. Too much UVB
exposure can be harmful by causing sunburn in human
skin. UV treatments are being used in a controlled set-
ting at dermatology offices to treat dermatologic con-
ditions such as psoriasis and vitiligo. Many offices
have stand-up units that emit the artificial rays and
some have smaller handheld devices to treat localized
areas. Exposure time starts at a few seconds and can be
increased to 25 or 30  min increments. Phototherapy
treatments are usually scheduled 3 times a week.
Treatment times depend on the patient’s skin type and
the skin’s ability to respond to the treatment and are
gradually increased as the treatment progresses until
clearing of the psoriasis lesions is achieved.
14  Prevention of Psoriasis
UVB phototherapy can be useful in treating psoria-
sis when supplied at a set length on a regular schedule.
Broadband UVB treatment uses a wider range of UV
wavelengths and the narrowband type of treatment
uses a more specific range to treat psoriasis. Narrowband
UVB has been shown to clear psoriasis faster and can
achieve the treatment goal with less exposure time and
with fewer treatments than broadband UVB. Unlike
PUVA treatment, UVB can be used on adults as well as
children.
PUVA is a type of phototherapy treatment that com-
bines Psoralen and ultraviolet light A. Psoralen is a
light-sensitizing medication and represents the “P” in
the acronym. It comes in a pill form and a topical form.
UVA is ineffective to treat psoriasis by itself, but when
combined with Psoralen in PUVA therapy it can clear
up to 85% of patients. PUVA works by slowing down
the increased cell production. This treatment has most
patients cleared by 25 treatments and has a good
chance of inducing remissions. PUVA is a good treat-
ment for moderate to severe cases.21
14.4 Prevention
14.4.1 Avoid Risk Factors/Triggers
Patients diagnosed with psoriasis or with a family his-
tory of the disease should avoid certain risk factors.
Cold or dry climates can worsen symptoms and increase
the severity of psoriasis. Avoid scratching and picking
at the skin. Epidermal injuries or mechanical trauma
such as cuts or scratches of the skin can invoke
Koebner’s phenomenon. In this event, psoriasis lesions
appear on the skin at sites of induced trauma. Although
it may sound almost impossible, psoriasis patients
should be encouraged to avoid stress and anxiety. They
may wish to consider learning meditation techniques,
yoga, or participate in regular exercise in order to
reduce stress and anxiety. Infections can induce types
of psoriasis or flares. Regular office visits and antibi-
otic treatment when indicated can reduce occurrences.
Certain medications can also trigger psoriasis;
therefore these medications should be avoided if pos-
sible. Potential patients should consult a physician
before beginning any new medications that may induce
psoriasis. Alcohol should be limited to two drinks a
day for a man or one drink for a woman. People with a
157
family history of psoriasis or a current diagnosis should
quit smoking. According to studies, people who use
tobacco are much more likely to develop psoriasis.
Smoking has also been linked to making psoriasis out-
breaks more severe and symptoms last longer.9
14.4.2 Diet
Multiple studies have shown that psoriasis can actually
cause nutritional deficiencies in protein, iron, and
folate. It has also been noted that gaining weight can
cause flares or can worsen symptoms or psoriasis.
Therefore, a low-fat diet with high protein content
and green leafy vegetables can help prevent psoriasis
flares. Eliminating or limiting caffeinated beverages
and foods with high gluten content may reduce
outbreaks.20, 21
14.4.3 Side Effects of Treatments
Anthralin cream can stain surrounding unaffected skin
and hair a brownish color. To prevent this adverse
effect rub this medication only on areas of psoriasis
and wipe excess cream away. Occlusive dressings
should be used to prevent stains on clothing or bed lin-
ens. Patients with light hair should use caution if using
Anthralin to treat scalp psoriasis because of the stain-
ing quality of the medication.
Dovonex has no major side effects when used cor-
rectly. The most common adverse reaction is skin irri-
tation. To prevent this Dovonex can be mixed with
petroleum jelly in increasing potencies until the skin
becomes adjusted to the medication.
As with any topical steroid Taclonex should only be
applied to any area of the skin for up to 4 weeks. It
should also be omitted from use in the axillae, groin
area, or face as there is increased sensitivity in those
areas. The overuse of this medication can cause atro-
phy of the epidermis. Increased sun exposure should
be limited when using this medication; therefore, no
phototherapy treatment should be instituted to avoid
unwanted side effects.
The most common side effect from using Tazorac
is skin irritation. The best way to prevent this effect is
to spot test the medication on a small area of skin
158
before using on all the affected areas. Tazorac can
make your skin more susceptible to sunburn. To avoid
the adverse effects of using the medication in the sun
the patients should be instructed to wear sunscreen or
protective clothing when sun exposure is expected.
Another option would be to wear the cream at night
and wash it off in the morning before spending a day
out in the sun.
Topical steroids can be great assets when treating
psoriasis but those using topical steroids should be
advised of the many possible adverse effects. The ste-
roid strength should be chosen carefully by the treating
physician, using low strengths on the face and groin,
and the most potent on thick skin like elbows and
knees. Overuse of steroids can cause skin to thin or
change pigmentation. Topical steroids have also been
known to induce acne. Psoriasis lesions may even
become worse if steroid treatment suddenly ceases. It
is recommended to slowly taper steroids when plan-
ning to discontinue use. Topical steroids, especially
the more potent types should be avoided around the
eyes. Cataracts and glaucoma can present after pro-
longed steroid exposure to the eyelids and skin around
the orbit. Intralesional injections have few side effects
if used sparingly and only on a few resistant lesions.
Be careful not to inject the same area repeatedly which
could lead to skin atrophy at the injection site and can
even result in divots in the skin. To prevent these effects
the treatment regimen involving steroids should be
explained to patients. Patients should have regular vis-
its to their dermatologist in order to closely monitor
the frequency and duration of steroid use.21
14.4.4 Systemic Therapy:
Oral Medications
Patients that are immunocompromised (HIV, history
of malignancy, current radiation treatment, etc.), or
those with hypertension or renal disease should not
take Cyclosporine. To prevent side effects seen with
Cyclosporine patients should be encouraged to have
their blood pressure and kidney functions closely
monitored while taking this medication. Before start-
ing patients on this medication physicians should
obtain a detailed list of medications and supplements
the patient is taking as there are many cross-reactions
G. Coatney and R. A. Norman
with Cyclosporine. Patients should also avoid eating
grapefruit or drinking grapefruit juice, because it
decreases the excretion of the drug leading to increased
levels of Cyclosporine in the blood. Conversely
St. John’s wort can decrease Cyclosporine levels in the
blood so it should also be avoided.
A good medical history and exam should be
obtained before starting a patient on Methotrexate. To
prevent side effects the patient should have no history
or current illness including blood disorders, anemia,
peptic ulcers, any significant liver or kidney abnormal-
ities, or excessive alcohol use. A close calculation of
the total dosage amount should be recorded each time
the patient has a doctor’s visit. Once the cumulative
dose exceeds 1.5 g there is an increased risk for irre-
versible liver damage. NSAIDs and medications con-
taining sulfa should be avoided in patients taking
Methotrexate to prevent harmful side effects.
Common side effects in Cyclosporine and Soriatane
include bleeding or sensitive gums, changes in lipid
levels in the blood, hair loss or excessive hair growth,
and joint and muscle pains to name a few. These
adverse reactions disappear when the medication dos-
ages are lowered or stopped all together.
Soriatane and Methotrexate are known teratogenic
drugs. They should be avoided at all costs in pregnant
women or those who may become pregnant to prevent
birth defects in the developing fetus. Women of child-
bearing age can prevent the chance of harmful side effects
to the fetus by getting regular pregnancy tests and remain-
ing on two types of contraceptives during ­treatment.
Cyclosporine is usually contraindicated in ­pregnant or
breast-feeding women, but in cases of ­pustular psoriasis
where the patient’s life is threatened Cyclosporine may
be the treatment of choice compared to the other options
of Soriatane and Methotrexate.21
14.4.5 Prevention of Biologics
Side Effects
All of the biologics are administered by injection.
Irritation, pain, and inflammation at the site of injection
are common side effects but these reactions have been
proven to decrease after the initial dose. Other common
side effects include sore throat, cough, nausea, head-
ache, dizziness, and abdominal pain. To prevent patients
14  Prevention of Psoriasis
from discontinuing treatment on their own due to
adverse effects educate them on these potential side
effects and how they will most likely decrease and
cease if continuing to use the medication as directed.
Biologics are still relatively new treatments for psoria-
sis. Long-term side effects are still being evaluated.
Because Amevive decreases the body’s immune
response, people with a history of malignancy, recur-
rent infections, or in an immunocompromised state
(HIV) should not use this medication. Amevive
decreases the amount of T cells in the body, even
though patients with psoriasis have an increased
amount of T cells some patients can exhibit lymphope-
nia. Weekly CBCs should be drawn to monitor white
blood cell counts to prevent levels from dropping to
dangerously low levels.
Patients with any active infection or history of
recurrent infections should not use Enbrel, Humira, or
Remicade. Those who have a history of multiple scle-
rosis or congestive heart failure should also not use
these medications. A PPD skin test should be per-
formed on patients before initiating treatment to rule
out latent tuberculosis.21
14.4.6 Prevention of Phototherapy
Adverse Effects
Prevention of UVB treatment side effects is simple.
Before UV exposure, apply sunscreen to the areas
that are free of psoriasis lesions. Patients should also
avoid UV exposure in sensitive areas such as the
groin and face and neck. As there are many prescrip-
tion and over-the-counter medications that increase
UV sensitivity patients should provide a detailed list
of all medications and supplements they take on a
regular basis to their dermatologist. Many UVB and
PUVA therapy patients experience remission of their
disease, but some patients may need to continue with
a maintenance regimen to prevent relapse of psoria-
sis. The maintenance regimen could be once a week
to once a month depending on how severe the case of
psoriasis.
Oral Psoralen can cause nausea, pruritus, and ery-
thema. To prevent these side effects patients should
consider drinking ginger ale or eating at the same time
the pill is taken for the nausea, and take a mild
159
antihistamine to alleviate itching. If the adverse effects
are unbearable the switch to topical Psoralen should be
considered. Patients that have participated in more
than 150 phototherapy treatments are at an increased
risk for sun-induced keratoses and nonmelanoma skin
cancers. These patients should have an annual full-
body exam, even after phototherapy has stopped, per-
formed by a dermatologist to catch and treat any
precancerous lesions. To prevent cataracts and any
other eye problems, UVA-blocking sunglasses should
be worn for at least 12  h after taking Psoralen when
going out in the sun. To help avoid risks associated
with increased UVA exposure the number of treat-
ments should be kept to a minimum. This can be
achieved by combining phototherapy with other treat-
ments. Anthralin or topical steroids can be added to
treat persistent lesions. Dovonex can also be used in
combination with UVA therapy, but needs to be applied
after phototherapy because UVA can inactivate this
medication.21
14.5 Conclusion
There is no cure for psoriasis but there are many ways
to prevent the initial onset or exacerbations of the
disease. Health education is an important aspect of
psoriatic prevention and treatment. Patients should
be informed about risk factors associated with psori-
asis and about potential side effects associated with
specific treatments. As stated earlier, psoriasis has a
genetic link, and therefore may be unpreventable for
some people. Those who have a family history of the
disorder should pay special attention to their health
in general, and to the health of their skin in particular
in order to prevent initial psoriasis outbreaks or flares
of previous incidents of the disease. For patients
already suffering from the disease the treatment goal
is to prevent exacerbations and flares to achieve the
longest possible remission. Since the severity of
­psoriasis varies so much from case to case it is
­imperative to monitor it as closely as possible by
maintaining regular appointments with primary care
physicians or dermatologists. If prevention of the ini-
tial onset of psoriasis or preventing exacerbations of
the disease is achieved a greater quality of life can be
maintained.
160
References
  1. Atochina O, Harn D. Prevention of psoriasis-like lesions
development in fsn/fsn mice by helminth glycans. Exp
Dermatol. 2006;15:461–468
  2. Elder J, Nair R, Guo S, et al The genetics of psoriasis. Arch
Dermatol. 1994;130:216–224
  3. Esposito M, Saraceno R, Giunta A, et al An Italian study on
psoriasis and depression. Dermatology. 2006;212:123–127
  4. Farber E, Nall M. The natural history of psoriasis in 5,600
patients. Dermatologica. 1974;148:1–18
  5. Gelfand JM, Berlin J, Van Voorhees A, et  al Lymphoma
rates are low but increased in patients with psoriasis. Arch
Dermatol. 2003;139:1425–1429
  6. Gelfand JM, Neimann AL, Shin DB, et al Risk of myocar-
dial infarction in patients with psoriasis. JAMA. 2006;296:
1735–1741
  7. Gelfand JM, Troxel AB, Lewis JD, et al The risk of mortality
in patients with psoriasis: results from a population-based
study. Arch Dermatol. 2007;143(12):1493–1499
  8. Glade CP, Van Erp PEJ, Werner-Schlenzka H, et al A clinical
flow cytometric model to study remission and relapse in pso-
riasis. Acta Derm Venereol. 1998;78:180–185
  9. Herron MD, Hinckley M, Hoffman MS, et al Impact of obe-
sity and smoking on psoriasis presentation and management.
Arch Dermatol. 2005;141:1527–1534
10. Horn EJ, Fox KM, Patel V, et al Are patients with psoriasis
undertreated? Results of National Psoriasis Foundation sur-
vey. J Am Acad Dermatol. 2007;57:957–962
11. James WD, Berger TG, Elston DM. Andrews’ diseases of the
skin. Clinical dermatology. Philadelphia: Saunders Elsevier;
2006
12. Jankowiak B, Krajewska-Kulak E, Van Damme-Ostapowicz
K, et al The need for health education among patients with
psoriasis. Dermatol Nurs. 2004;16:439–441
G. Coatney and R. A. Norman
13. Javitz H, Ward M, Farber E, et al The direct cost of care for
psoriasis and psoriatic arthritis in the United States. J Am
Acad Dermatol. 2002;46:850–860
14. Kavli G, Forde O, Arnesen E, et al Psoriasis: familial predis-
position and environmental factors. Br Med J. 1985; 291:
999–1000
15. Kimball AB, Gladman D, Gelfand JM, et al National psoria-
sis foundation clinical consensus on psoriasis comorbidities
and recommendations for screening. J Am Acad Dermatol.
2008;58:1031–1042
16. Kimball AB, Robinson D Jr, Wu Y, et al Cardiovascular dis-
ease and risk factors among psoriasis patients in two US
healthcare databases, 2001–2002. Dermatology. 2008;217:
27–37
17. Lindegard B. Diseases associated with psoriasis in a general
population of 159, 200 middle-aged, urban, native Swedes.
Dermatologica. 1986;172:298–304
18. Lumholt G. Psoriasis: Prevalence, Spontaneous Course and
Genetics- A Census study on the Prevalence of Skin Disease
on the Faroer Islands. Copenhagen: GEC, GAD; 1963
19. Najarian DJ, Gottlieb AB. Connections between psoriasis
and Crohn’s disease. J Am Acad Dermatol. 2003;48:
805–821
20. Naldi L, Patrazzini F, Peli L, et al Dietary factors and the risk
of psoriasis: results of and Italian case-control study. Br J
Dermatol. 1996;134:101–106
21. National Psoriasis Foundation, Psoriasis Overview and
Treatment, November 2008. URL <http://www.psoriasis.org>
22. Rapp SR, Feldman SR, Exum ML, et al Psoriasis causes as
much disability as other major medical diseases. J Am Acad
Dermatol. 1999;41:401–407
23. Schafer T. Epidemiology of psoriasis. Dermatology. 2006;
212:327–337
24. Wolff K, Johnson RA, Suurmond D. Fitzpatrick’s Color
Atlas and Synopsis of Clinical Dermatology. New York:
McGraw-Hill; 2005
 Sports Dermatology: Prevention
Brian B. Adams
The four main categories of skin conditions that afflict
the athlete include infections, trauma, inflammation,
and encounters with the environment. Knowledge of
the etiology of cutaneous skin problems of athletes
helps the clinician best formulate a prevention plan.
Most of the skin ailments that sideline athletes can be
prevented through proper disqualification, appropriate
use of equipment, and selective use of pharmacologic
agents.
15.1 Infections
The four main types of infections that affect the athlete
are bacteria, fungi, viruses, and parasites. In general,
parasitic infestations play a relatively small role in
sports dermatology. However, all contact athletes need
screening before practice and competition to ensure
that infestations with lice and scabies do not cause
epidemics.
15.1.1 General Prevention Techniques
Some athletes are particularly susceptible to infec-
tions because of intense and prolonged skin-to-skin
contact and trauma, inherent to athletic activity, which
disturbs the normal epidermal barrier and allows for
microorganism penetration. Sweating provides an
B. B. Adams
Department of Dermatology, University of Cincinnati,
Cincinnati, OH, USA
e-mail: brianadams@pol.net
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_15, © Springer-Verlag London Limited 2010
15
ideal microenvironment (warm and moist) for micro-
organism growth. Finally, athletes transmit infections
among team competitors through sharing equipment
(Table 15.1).
Basic prevention principles for athletes include
modifying these risk factors (Table  15.2). No athlete
should share towels, pads (shoulder, knee, elbow),
helmets, hats, gloves, sweatbands, clothing, footwear,
or razors. Athletic trainers should also be careful to
ensure that they do not cross-contaminate any commu-
nal source. For example, once a trainer dips a tongue
depressor into a jar of gel and applies it to an athlete,
that depressor must be discarded. Any subsequent
applicator that gets dipped into that container must be
clean though not necessarily sterile.
Athletes should always consider placing a barrier
between their skin and the athletic environment. During
practice and competition (if allowed) athletes who
anticipate prolonged and intense skin-to-skin contact
with competitors should wear synthetic moisture-wick-
ing clothing to cover exposed areas. Loose-fitting cloth-
ing made of this fabric keeps the athletes cool and their
skin dry while creating a physical barrier between them-
selves and potentially infectious competitors. Athletes
should also wear synthetic moisture-wicking socks at
all times. The feet of athletes become warm and moist
as a result of their athletic activity and experience occlu-
sion by athletic footwear, which further exacerbates the
risk of infection of tinea pedis (Table 15.3).1
Athletes should never go barefoot on the locker
room or shower floors. Poolside is equally infectious
and athletes should always wear sandals in these situa-
tions. One group of investigators cultured dermato-
phytes each time they examined the pool and locker
room floors every other week for a year.2 Additionally,
once experiencing a traumatic break in their skin, the
athlete should carefully bandage the area.
161
162 B. B. Adams

Table  15.1  Evidence for transmission of Staphylococcus by Table  15.2  Prevention techniques to avoid skin infection
fomites epidemics
Equipment type Epidemic study Level of evidence Frequent, if not daily, skin checks by athletes and trainers
Fencing sensor wires MMWR, 2003 + Daily showers immediately after practices or competition
Whirlpools Kazakova + Routine antibacterial soap use in the showers
Begier +++ Frequent hand washing by trainers and affected athletes
Bartlett +++ Universal availability of alcohol-based, waterless, soap
cleansers
Seidenfeld –
Regular laundering of equipment and clothing
Lindenmayer –
Mandatory no sharing policy for equipment and personal
Weights Kazakova +
items
Sharing towels Kazakova +
Required personal towels
Begier –
Meticulous covering of all wounds
Seidenfeld –
Use of protective gloves when using weight-lifting
Sosin – equipment
Lindenmayer – Universal sandal usage in the locker room and showers
Sharing equipment Begier – Periodic formal education for the athletes, coaches, and
trainers
Seidenfeld –
From Adams.1 With permission from Springer Science and
Sosin – Business Media LLC
Lindenmayer –
Table  15.3  Preventative measures for tinea pedis and tinea
Tape sharing Seidenfeld –
ungium
Elbow pad use Sosin +++ Synthetic moisture-wicking socks
Seidenfeld ++ Immediate showers after sporting activity
Bartlett +++ Sandals or other footwear while in shower and locker room
or pool deck
Athletic tape use Sosin +++
Thorough feet washing
Bartlett +++
Regular cleaning of shower, locker room, and pool floors
Skin lubricants use Bartlett +++
“–” no statistical association Daily application of antifungal cream to feet
“+” suggested link From Adams.1 With permission from Springer Science and
“++” increased risk but not statistically significant Business Media LLC
“+++” statistically significant increased risk
From Adams.1 With permission from Springer Science and Athletes, coaches, and trainers must together ensure
Business Media LLC timely diagnosis and prompt therapy of skin infec-
tions; daily skin examinations of athletes who experi-
ence intense skin-to-skin contact are mandatory. Often,
Appropriate cleansing remains a cornerstone of a medley of clinicians care for athletes on the high
infection control among sports teams. Immediately after school level and coordination of care can be difficult.
practice or competition, athletes should shower with One study demonstrated the untoward effects of hav-
antibacterial soap. Athletes and trainers should liberally ing wrestlers return to wrestling before their communi-
and frequently use soapless cleansers with moisturiz- cable skin disease was adequately treated.3 This study
ers while in the training room. It is vital that athletic demonstrated that a series of wrestlers were incorrectly
trainers use these cleansers between caring for sepa- diagnosed and treated for herpes gladiatorum when in
rate athletes. Salient and judicious placement of these fact they actually had impetigo (70%), tinea corporis
cleansers in the training room help ensures its use. gladiatorum (10%), and eczema (10%). Eighty percent
15  Sports Dermatology: Prevention
of these sidelined wrestlers returned to wrestling with-
out proper treatment for their bacterial and fungal
eruptions and 10% (eczema) of the benched athletes
had no infection at all.3 Specific National Collegiate
Athletic Association (NCAA) guidelines exist that
assist clinicians in the disposition of infected athletes.
Adherence to these guidelines can prevent epidemics.
15.1.2 Specific Prevention Techniques
While these general methods significantly decrease the
incidence of skin infections in athletes, specific recom-
mendations exist for each unique condition. Herpes
simplex virus causes two different types of skin condi-
tions in athletes. First, in outdoor athletes, the ultravio-
let rays (both direct and reflected) can activate herpes
labialis. One double-blind placebo controlled study of
skiers demonstrated that 71% of those using placebo
lip balm developed herpes labialis; no skiers assigned
to use sunscreen on their lips developed herpes labia-
lis.4 Another study demonstrated that skiers that took
valacyclovir 400  mg twice daily starting 12 h before
skiing experienced significantly fewer outbreaks of
herpes labialis.5
Herpes simplex virus (specifically HSV-1) also
causes epidemics in wrestlers (Fig. 15.1). To address
these epidemics, one research team examined the
Fig. 15.1  Herpes gladiatorum of the ear (From Adams.1 With
permission from Springer Science and Business Media LLC)
163
effectiveness of season-long pharmacological prophy-
laxis.6 This double-blind placebo controlled study had
four distinct groups. The first section represented wres-
tlers whose initial herpes lesion occurred more than 2
years prior; half of these individuals took placebo and
half took 500 mg of valacyclovir. None of the athletes
who took valacyclovir in this section developed herpes
while 33% of the wrestlers who took placebo devel-
oped herpes. The second section represented athletes
who had first had a history of herpes less than 2 years
prior to the start of the study. The athletes who took
valacyclovir developed herpes 21% of the time whereas
33% of those athletes who had placebo developed her-
pes. Though differences among groups do not exist
upon close statistical analysis, season-long prophy-
laxis with 1 g of valacyclovir seems prudent and allows
maximal athletic participation.
Methicillin resistant Staphylococcus aureus (MRSA)
has caused many epidemics in athletes at many ability
levels. Athletes with positive skin cultures for MRSA
need to also have their nares swabbed for culture.
Mupirocin 2% applied twice daily to the nares for 1
week significantly decreases nasal carriage. This pro-
cess should be repeated twice per year to decrease the
athlete’s staphylococcal carriage.1 In repeated cutane-
ous disease, clinicians should also consider the peria-
nal, groin, and axillae regions as possible sites of
staphylococcal colonization. The same mupirocin 2%
application process for the nares works also for the
perianal, groin, and axillae areas.
As athletes spend time in the whirlpool while rehab-
bing an injury, they risk developing hot tub folliculitis
caused by Pseudomonas. Whirlpools must be cleaned
routinely and adequately chlorinated to prevent hot tub
folliculitis. The free chlorine level should be at least
0.6  mg/L and the pH kept between 7.2 and 7.8.
Unfortunately, adequate chlorination does not ensure
bacteria-free water. In 16% of Pseudomonas folliculi-
tis epidemics, unfortunately, the chlorination has been
adequate.7,8 Pools with Pseudomonas necessitate a
hyperchlorination with 5 mg/L for 3 days.9
Other bacterial infections that occur in athletes such
as erythrasma (groin and axillae) and pitted keratolysis
(feet) propagate in warm and moist microenvironments
(Fig. 15.2). Wearing synthetic moisture-wicking under-
garments and socks prevent those infections. Some of
these types of socks also possess antimicrobial proper-
ties. Athletes predisposed to pitted keratolysis may
find it helpful to apply aluminum chloride (which is
164
Fig. 15.2  Pitted keratolysis
quite drying) to the soles and interdigitally before
exercising.
Tinea corporis gladiatorum, caused by Trichophyton
tonsurans, causes frequent epidemics among wrestling
teams. Teams and their staff frequently clean the mats
before and after practice, though only one study has
ever documented dermatophyte presence on the mats.10
Two studies have examined pharmacological preven-
tion of tinea corporis gladiatorum. Itraconazole
(400 mg every other week), in an open-label prospec-
tive trial, decreased the incidence from 27 to 0%.11 A
subsequent randomized placebo controlled study of
100 mg of weekly fluconazole significantly decreased
the incidence of tinea corporis gladiatorum.12
As a complication of their skin becoming warm and
sweaty, athletes also frequently develop tinea versi-
color. Prevention of this condition thwarts the persistent
discoloration (either hyperpigmentation or hypopig-
mentation) of the skin that occurs subsequently. Once
per week, athletes can apply selenium sulfide 2.5% to
the predisposed areas and wash off after 15 min.1
While no direct evidence-based medicine exists to
support this specific recommendation, athletes with
recurrent tinea pedis should indefinitely apply topical
antifungal agents to their soles and interdigital regions
on the weekends. This recommendation relates in part
to one study that revealed a decrease in the prevalence
of tinea pedis from 21.5 to 6.9% over 3 years after bath-
ers used an antifungal powder upon leaving the pool.13
Athletes, with recurrent tinea pedis, should consider
obtaining new shoes; one study documented dermato-
phytes in 15% of shoes kept in storage for 1–4 weeks.14
B. B. Adams
Table 15.4  Prevention of friction bullae
Category Method
Equipment Gloves
Shoes Adequately sized toebox
Nonslip insoles
Supple shoes
Unique lacing techniques
Socks Double-layered
Padded
Synthetic moisture-wicking
Topical agents Aluminum chloride
Drying powders
Micronized wax and silicone powder
Petroleum jelly
Tissue adhesives
From Adams.1 With permission from Springer Science and
Business Media LLC
15.2 Trauma
While skin infections can sideline athletes and disrupt
team activities, trauma causes the most common cuta-
neous ailments in athletes. Friction between the ath-
lete’s skin and athletic equipment results in bullae and
occasionally erosions. Depending on location, these
physical disruptions in the skin may result in significant
decrease in athletic ability secondary to pain. The pri-
mary risk factors for the development of bullae include
ill-fitted equipment, moisture, heat, and prolonged
activity. Athletes typically experience friction on their
hands, feet, groin, shoulders, face, and nipples.
Several approaches assuage friction bullae produc-
tion (Table 15.4). First and foremost, athletes need to
wear properly fitted footwear. Shoes that are too small
or too large can result in bullae. Special lacing tech-
niques can ameliorate bullae on the feet by preventing
slippage in shoes that are too large (Fig. 15.3). Slip-
resistant shoe insoles also help prevent bullae by not
allowing the toes to slam into the toe box. Brand new
shoes need to be gradually included into the exercise
regimen. Wearing new shoes for a prolonged period
during intense activity can lead to bullae.
Athletes should also wear synthetic moisture-wick-
ing clothing (including socks); decreasing the degree
of wet clothing and equipment decreases the incidence
of bullae. Before the development of frank bullae, ath-
letes experience warmth in the skin on the affected
area. Some socks have extra padding in these “hot
15  Sports Dermatology: Prevention
Fig. 15.3  (a) Rather than lacing across to the opposite hole, lace
the shoestring through the hole on the same side. (b) Through
each of the loops made by the lacing procedure in (a), lace across
to the opposite side. (c) Finally pull up, out, and tight. This snug-
spots” to decrease bulla formation while other socks
lack seams that can contribute to bulla genesis. Athletes
can also decrease friction by wearing two layers of
synthetic moisture-wicking clothing.
Athletes whose hands come in contact with imple-
ments also can acquire bullae on their hands; gloves
serve to decrease the amount of friction.
Athletes can also apply topical antiperspirants to
these “hot spots” to decrease moisture. In addition,
lubricants applied to these hot spots decrease the coef-
ficient of friction between the skin and the equipment.
These lubricants include cosmetically elegant vehicles
but also cheaper alternatives such as a petroleum jelly.
There remains one caveat to the use of these occlusive
agents. In the short term, the coefficient of friction is
reduced but after about 3  h the occlusive nature of
these agents results in a decrease in transepidermal
water loss and supersaturation of the epidermis. This
excess local moisture thus increases the chance of bul-
lae formation. Commercially available tissue adhesives
also serve to decrease the degree of friction experi-
enced by the epidermis.
165
gly stabilizes the heel and ankle for athletic participation (From
Adams.1 With permission from Springer Science and Business
Media LLC)
Athletes’ skin that chronically experience these fric-
tional forces develops calluses. These callosities occur
in anatomic locations that relate to specific athletic
activities (Table  15.5) and help prevent future bullae.
The same methods that prevent bullae acutely prevent
calluses in the long term.
Other frictional forces result not in bullae but in
painful erosions. Common locations for these erup-
tions include the nipples (runners) and thighs (cyclists).
Prevention of these erosions requires a multifaceted
approach. First, athletes should apply a barrier between
the “hot spots” and the clothing. Petroleum jelly and
multiple commercially available substances decrease
the coefficient of friction thus preventing epidermal
breakdown. Synthetic moisture wicking clothing
(including undergarments) also decrease friction by
adding a layer that will, instead of the skin, experience
the shearing forces and by wicking away moisture
from the skin. Without additional moisture, the epider-
mis is less likely to develop erosions. Runners may
also purchase patches to apply over their nipples to
decrease friction.
166 B. B. Adams

Table 15.5  Sport-specific callosities

Sport Location Etiology
Archery Fourth fingertip Bowstring hand
Baseball Palms Batting
First finger Pitching
Billiards Nondominant, palmar aspect thumb and first finger; Holding the cue
dorsal aspect second finger
Bowling (no holes) Throwing hand, third and fourth fingers Throwing ball
With holes Throwing hand, second, third, and fourth lateral fingers Throwing ball
Canoeing/crew/kayaking/rowing Palms (depends on oar type) Rowing
Cycling Ischial tuberosities Peddling
Dance Distal toes Dancing ballet
Equestrian Fingers and palms Holding on to reins
Fishing Thumb and opposite first finger Reeling in fish
Golf Dominant hand, first finger and opposite palm, and Swinging club
opposite third finger
Gymnastics Palms Horse, parallel bar, rings
In-line skating Legs Pushing off while
skating
Karate/judo Lateral sides of hands and heels Blows, chops, kicks
Tennis (badminton, racquetball, squash) Dominant palm and thumb Swinging racquet
Track and field (discus) Throwing hand, all palmar aspects of fingers except thumb Throwing discus
Shot put Hypothenar eminence Throwing shot
Distance runners Heel (“runner’s bump”) Running
Weightlifters Palms, web spaces between thumb and first fingers Lifting
From Adams.1 With permission from Springer Science and Business Media LLC

These shearing forces when experienced on the sole

Fig. 15.4  Like cyclists and surfers, skaters wearing tight-fitting
skates may develop athletes’ nodules such as seen here on the
medial aspect of the foot
of the foot can cause talon noire. Black heel (or talon
noire) may appear clinically similar to malignant mel-
anoma. Heel cups may help prevent talon noire.
Surfer’s and cyclist’s nodules represent another
sports-related traumatic skin condition (Fig.  15.4).
Surfer’s nodules occur on the knees and feet; protec-
tive padding on these areas prevent the nodules.
Interestingly, cold-water surfers develop surfer’s nod-
ules more frequently than surfers in warm water. While
paddling out to catch waves in cold water, surfers rest
on their board only on their knees and feet; this intense
focal pressure results in nodular formation. Warm
water surfers can lie prone on their board and thus dis-
tribute their weight equally. Cold-water surfers can
decrease the incidence of surfer’s nodules by wearing
wet suits that permit them to lie prone on the board in
15  Sports Dermatology: Prevention
Fig.  15.5  A tight-fitting figure skate resulted in this athlete’s
toenail abnormality
cold water.1 Cyclists develop morphologically similar
nodules in sacrococcygeal area. Properly fitted and
padded seats, along with padded biking shorts, decrease
the incidence of cyclist’s nodules.1
Athlete’s toenail occurs in myriad athletes
(Fig.  15.5). To prevent these nail changes, athletes
need to cut their nails straight across so that the pres-
sure of the toe box distributes equally across the nail.
The shoe’s toe box must allow adequate room. Unique
lacing techniques ensure that the most distal toenails
do not slam into the toe box.
Combined forces (heat, moisture, and friction) cre-
ate acne mechanica in athletes (Fig.  15.6 and
Table 15.6). The focus of prevention for acne mechan-
ica aims to decrease all three factors on the skin.
Athletes must shower immediately after practicing or
competing. The use of mildly abrasive soaps may also
decrease the incidence of acne mechanica. Athletes
can also use keratolytic agents to prevent acne mechan-
ica. Synthetic moisture-wicking clothing keeps the
skin cool and dry and decreases friction. Athletes can
use fragments of this type of clothing to form a barrier
beneath chinstraps, knee pads, and elbow pads.
15.3 Inflammation
Both allergic and irritant contact dermatitis occur in
athletes; their equipment and environment can cause
eruptions (Fig. 15.7 and Table 15.7). Topical medica-
tion and equipment alternatives allow sensitized
167
Fig.  15.6  Acne mechanica (From Adams.1 With permission
from Springer Science and Business Media LLC)
athletes (allergic contact dermatitis) to compete and
practice without incident. If no equipment alternatives
exist, athletes should apply tape, coban wrap, tissue
adhesive, petroleum jelly, or another barrier between
the offending equipment and the skin. Athletes sensi-
tized to poison ivy, poison oak, and poison sumac can
apply bentoquatam (commercially available as
IvyBlock) to their skin to prevent allergic reactions;
these athletes need to apply this medication at least
15 min before going outdoors and reapply every 4 h.1
Irritant contact dermatitis results from a direct toxic
irritation of the skin with some agent in the environ-
ment; an athlete’s own immune system plays little ini-
tial role in the pathogenesis (unlike allergic contact
dermatitis). Athletes decrease their risk for irritant
contact dermatitis by placing a barrier between their
skin and the environmental irritant. Such barriers
include waterproof gloves, wet suits, petroleum jelly,
and clothing to decrease the amount of exposed skin.
168 B. B. Adams

Table 15.6  The location and cause of acne mechanica depending Several types of urticaria occur in athletes. Athletes
on sport can prevent cholinergic urticaria with antihistamines;
Sport Acne location Etiology also a gradual increase in athletic intensity may result
Dancers Trunk Beneath tight leotard in habituation that allows the athlete to participate
Football Chin Chin straps without bouts of urticaria. Cold-urticaria-susceptible
athletes should wear cold weather synthetic moisture-
Shoulders Shoulder pads
wicking clothing; using several layers of such clothing
Upper inner arm Shoulder pad straps maximizes heat retention. Some authors have suggested
Forehead, cheeks Helmet that cyproheptadine hydrochloride best prevents cold
Golfers Lower lateral back Golf bag while carrying it urticaria.15 Athletes with solar urticaria need to apply
broadband blocking water-resistant sunscreen fre-
Hockey Chin Chin straps
quently. The use of sun-protective athletic clothing and
Shoulders Shoulder pads broad-brimmed hats also helps prevent solar urticaria.
Upper inner arm Shoulder pad straps Athletes with severe recalcitrant solar urticaria may
require antimalarial agents or desensitization with
Forehead, cheeks Helmet
ultraviolet radiation. Inert oily substances applied to
Shot putters Neck Shot put before launch the exposed skin in sensitized athletes, prevents the
Tennis Back Heavy warm clothes exceedingly rare condition, aquagenic urticaria.
Weightlifters Upper back Plastic/vinyl bench Some athletes develop exercise-induced anaphy-
cover laxis. A study of 278 athletes reported that over three-
Upper central Weight bar
quarters of those affected identified running as a trigger
chest of their disease.16 Several factors exacerbate exercise-
induced anaphylaxis including extreme temperatures,
Wrestlers Chin, neck peri- Headgear
auricular eating before exercise, and ingesting NSAIDS (non-
Elbows, knees Elbow and kneepads steroidal anti-inflammatory drugs), aspirin, and
From Adams.1 With permission from Springer Science and B-lactam antibiotics (Table 15.8). Some of the notable
Business Media LLC foodstuffs that trigger exercise-induced anaphylaxis
include barley, beans, broccoli, cheese, chicken, eggs,
garlic, grapes, lettuce, peaches, peanuts, rye, shellfish,
tomatoes, and wheat.17 By avoiding these triggers, ath-
letes can mitigate outbreaks. Ketotifen appears to
­prevent exercise-induced anaphylaxis-related angioe-
dema18 and cromolyn mitigates the exercise-induced
anaphylaxis-related respiratory-related symptoms.19
The symptoms of exercise-induced anaphylaxis do not
occur consistently during each athletic activity; how-
ever, athletes with this disorder should never exercise
alone.

Fig.  15.7  Note the linear pattern characteristic of poison ivy.
Also note the black dots in several of the lesions. These dots rep-
resent oxidized uroshiol, the protein responsible for poison ivy
Some irritants will wash away if too much time has not
elapsed.
15.4 Environmental Encounters
Environmental conditions also put athletes at risk to
develop several other dermatologic conditions. Athletes
practice and compete during the peak hours of ultravi-
olet exposure (10 am to 4 pm). Several studies note an
excessive exposure among athletes (Table  15.9). For
instance, in the Tour de Suisse, the cyclists experienced
15  Sports Dermatology: Prevention 169

Table 15.7  The etiologies of the various sports-related types of irritant contact dermatitis
Category Sport Designation Irritant
Playing field Mountaineering Canyoning hands Forces of nature (rocks, water, wind)
Soccer Cement burns Calcium oxide
Swimming Pool dermatitis Halogenated compounds in pool water
Athletes’ implements Basketball Basketball pebble fingers Pebbled nicked ball
Hockey Hockey dermatitis Fiberglass
Injured athletes Pack dermatitis Ammonium nitrate
Board surfers Surf rider’s dermatitis Mixed (board, salt, sand)
Athletes themselves Baseball Baseball pitcher’s friction dermatitis Questionable coarse clothing
Swimming Swimmer’s shoulder Hair stubble
From Adams.1 With permission from Springer Science and Business Media LLC

Table  15.8  Critical history questions to ask the athlete with up to 17 times their MED (the minimal UV dose to
suspected exercise-induced angioedema/anaphylaxis barely cause the skin to be pink).20 Another study
Do you experience EIA flares more frequently when you... revealed that athletes’ sweat reduces, by 40%, the
Exercise in very cold or very hot conditions? amount of ultraviolet exposure required for sunburn.21
Eat certain foods before exercising? Outdoor winter athletes and beach athletes must also
Take aspirin, ibuprofen (or other NSAIDS), or antibiotics endure significant reflectance of the ultraviolet rays.
before exercising? Avoidance of ultraviolet exposure prevents not only
From Adams.1 With permission from Springer Science and the acute effects of the sun (sunburn, bullae, sun poi-
Business Media LLC soning) but also the long-term effects (premature aging,
wrinkles, sun spots) and skin cancer (Table  15.10).
Table 15.9  Sports for which studies have specifically illustrated When possible, athletes should avoid practicing during
reasons for increased ultraviolet damage the peak hours of ultraviolet radiation. Athletes should
Sports Reasons for increased wear water-resistant SPF 30+ sunscreen and reapply
ultraviolet damage frequently with sweating and water exposure.
Triathalon, cycling, baseball, Gross exposure to severe Unfortunately, athletes – despite their obvious
softball, golf level of UV rays increased risk – do not often use sunscreen. In one study,
Skiing, soccer, runners Failure to apply sunscreen 85% of 200 collegiate athletes never used sunscreen.
Outdoor athletes High wind Only 6% of these collegiate athletes used sunscreen at
least 3 of 7 days of the week.22 This same study identi-
Outdoor athletes High temperatures
fied one of the major barriers to athletes’ use of sun-
Outdoor athletes Sweating screen as the lack of access to it. By making sunscreen
Skiing, snowboarding, Reflectance of UV rays readily available in the training rooms of high schools,
swimming
From Adams.1 With permission from Springer Science and Table  15.11  Factors influencing the protection factor of an
Business Media LLC athlete’s clothing
Variable of fabric Effect on protection factor

Table 15.10  Smart sun safety tips for athletes Nylon, wool, silk Relatively increases

Avoid, if possible the sun between 10 am and 3 pm Cotton, rayon, linen Relatively decreases
Apply SPF 30 sunscreen one half hour before practicing in Dark color Increases
outdoor sports
UV absorbers added Increases
Reapply sunscreen often while sweating or swimming
Increasing wetness Decreases
Wear hats
Increasing numbers of Increases
Wear sun-protective clothing washes
From Adams.1 With permission from Springer Science and From Adams.1 With permission from Springer Science and
Business Media LLC Business Media LLC
170
colleges, and professional venues, medical providers
can increase the likelihood of athletes’ sunscreen use.
In addition to sunscreen, athletes should wear hats
and sun-protective clothing. Broad-brimmed hats do
not allow athletes to forego sunscreen use on their face,
however, as sand and snow (two common sporting
activity venues), reflect a great deal of ultraviolet radi-
ation. Experts assign the term UPF to describe the rela-
tive ultraviolet-protective value of clothing. Several
factors of athletic clothing influence ultraviolet protec-
tion (Table  15.11). Nylon, silk, and wool possess
higher sun-protective factors than do other fabric types.
Darker-colored clothes block more ultraviolet rays as
do tighter weave fabrics (though they will be hotter).
The initial launderings of athletic clothing improve its
sun-protection ability. However, in general when an
athlete’s clothing becomes wet (either through sweat-
ing or from the environment) the sun protection ability
of the clothing decreases.1
On the opposite spectrum from the sun and warmth,
frostbite and chilblains can occur in winter sport ath-
letes. To prevent these cold-weather-related ailments,
athletes can layer synthetic moisture-wicking clothing;
outerwear should be waterproof. Winter athletes should
avoid wearing metal jewelry as it conducts heat.
Commercially available warming packets can be placed
in gloves or shoes.
As they practice and compete, athletes also must
endure insect (bees, flies, wasps, yellow jackets, hor-
nets) attacks. Several methods assuage the attack of
these insects. First, athletes should avoid wearing
bright colors. Scented products and shiny jewelry also
attract insects. Second, most arthropod pests have a
specific time of day that they prevail; avoidance of this
time helps prevent arthropod stings. Products contain-
ing 20% (or greater) DEET deter insect bites. Long-
sleeved synthetic moisture-wicking clothing keeps the
athlete cool but also protected from insect bites.
Athletes should also wear sandals in grass to prevent
stepping on one of these insects. Some insects are
social insects and release a pheromone if destroyed;
this pheromone incites all nearby yellow jackets, for
instance, to swarm around the destroyed insect. All
sporting venues should remove trash receptacles from
areas of athlete congregation to prevent stings.1
Insults from insects are not all that athletes must
endure; aquatic athletes who frequent areas where sea
urchins and starfish are prevalent should wear protec-
tive boots. Swimmers who use chlorinated pools,
B. B. Adams
instead of the ocean may develop a condition termed
green hair. Green hair occurs in light haired aquatic ath-
letes exposed to water rich in copper. To prevent green
hair, these athletes should shampoo immediately after
water exposure; shampooing with copper chelating
shampoos also deters the production of green hair.1
15.5 Summary
Knowledge of the etiology of cutaneous skin problems
of athletes reviewed here helps the clinician best for-
mulate a prevention plan. Most of the skin ailments
that sideline athletes can be prevented by following the
guidelines included in this chapter.
References
  1. Adams BB. Sports Dermatology. New York: Springer; 2006
  2. Detandt M, Nolard N. Dermatophytes and swimming pools:
seasonal fluctuations. Mycoses. 1988;31:495–500
  3. Dworkin MS, Shoemaker PC, Spitters C, et al Endemic spread
of herpes simplex virus type I among adolescent wrestlers
and their coaches. Pediatr Infect Dis J. 1999;18:1108–1109
  4. Rooney JF, Bryson Y, Mannix ML, et al Prevention of ultra-
violet-light induced herpes labialis by sunscreen. Lancet.
1991;338:1419–1422
  5. Spruance SL, Hamill ML, Hoge WS, et al Valacyclovir pre-
vents reactivation of herpes simplex labialis in skiers. JAMA.
1988;269:1597–1599
  6. Anderson BJ. The effectiveness of valacyclovir in prevent-
ing reactivation of herpes gladiatorum in wrestlers. Clin J
Sport Med. 1999;9:86–90
  7. Fox AB, Hambrick GW. Recreationally associated Pseudomonas
aeruginosa folliculitis. Arch Dermatol. 1984;120:1304–1307
  8. Spitalny KC, Voot RL, Witherell LE. National survey on
outbreaks associated with whirlpool spas. Am J Public
Health. 1984;74:725–726
  9. Thomas P, Moore M, Bell E, et al Pseudomonas dermatitis asso-
ciated with a swimming pool. JAMA. 1985;253:1156–1159
10. El Fari M, Graser Y, Presber W, et al An epidemic of tinea
corporis caused by Trichophyton tonsurans among children
(wrestlers) in Germany. Mycoses. 2000;43:191–196
11. Hazen PG, Weil ML. Itraconazole in the prevention and
management of dermatophytosis in competitive wrestlers.
J Am Acad Dermatol. 1997;36:481–482
12. Kohl TD, Martin DC, Nemeth R, et al Fluconazole for the
prevention and treatment of tinea gladiatorum. Pediatr Infect
Dis J. 2000;19:717–722
13. Gentles JC, Evans EGV, Jones GR. Control of tinea pedis in
a swimming bath. Br Med J. 1974;2:577–580
15  Sports Dermatology: Prevention
14. Ajello L, Getz ME. Recovery of dermatophytes from shoes
and shower stalls. J Invest Dermatol. 1954;22:17–24
15. Briner WW. Physical allergies and exercise. Sport Med.
1993;15:365–373
16. Shaddick NA, Liang MH, Partridge AJ, et al The natural history
of exercise induced anaphylaxis: survey results from a 10-year
follow-up study. J Allergy Clin Immunol. 1999;104:123–127
17. Adams ES. Identifying and controlling metabolic skin disor-
ders. Phys Sportsmed. 2004;32:29–40
18. Nichols AW. Exercise-induced anaphylaxis and urticaria.
Clin Sports Med. 1992;11:303–312
171
19. Adams BB. Exercise-induced anaphylaxis in a marathon
runner. Int J Dermatol. 2002;41:394–396
20. Moehrle M, Heinrich L, Schmid A, et al Extreme UV expo-
sure of professional cyclists during selected outdoor activi-
ties. Photodermatol Photoimmunol Photomed. 2000;201:
44–45
21. Moehrle M, Koehle W, Dietz K, et al Reduction of minimal
erythema dose by sweating. Photodermatol Photoimmunol
Photomed. 2000;16:260–262
22. Hamant E, Adams BB. Sunscreen use among collegiate ath-
letes. J Am Acad Dermatol. 2005;53:237–241
 Prevention of Cosmetic Problems
Zoe Diana Draelos
Cosmetic problems can be prevented through proper
diagnosis and the use of carefully selected products.
These products typically fall in the over-the-counter
(OTC) realm and can be classified as true cosmetics or
OTC drugs. Products that are considered cosmetics
include moisturizers, lip balms, and shaving prepara-
tions while OTC drugs include sunscreens and antiper-
spirants. This chapter examines the use of these
products in the prevention of cosmetic-related skin dis-
ease including facial eczema, eyelid dermatitis, cheili-
tis, postinflammatory hyperpigmentation, hyperhidrosis,
and acne. These are common cosmetic problems that
can be exacerbated or alleviated based on the derma-
tologist’s ability to correctly recommend prescription
and complimentary nonprescription therapies.
16.1 Facial Eczema
The face is the most complex area of the entire body
because more products are designed for facial use than
any other. The face contains sebaceous, eccrine, and
apocrine glands, as well as keratinized and transitional
skin. The face is also characterized by numerous folli-
cular structures in the form of pigmented terminal hairs
in the eyebrows, eyelashes, and male beard combined
with white fine downy vellus hairs over the rest of the
face. These follicular structures are the transition
between the skin on the surface of the face and the fol-
licular ostia associated with the follicle and sebaceous
Z. D. Draelos  from the environment, unless the ambient humidity is
Department of Dermatology, Duke University School
of Medicine, 2444 North Main Street, High Point,
Durham, North Carolina NC 27262
e-mail: zdraelos@northstate.net
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_16, © Springer-Verlag London Limited 2010
16
glands. This skin cannot be reached by traditional cos-
metics and skin care products, but irritant or allergic
reactions that occur at the skin surface can impact this
follicular lining. Thus, moisturizer and cleanser for-
mulations for the face must be hypoallergenic, non-
comedogenic, and nonacnegenic, since the face is
capable of all these reaction patterns.
16.1.1 Facial Moisturizers
Facial moisturizers are the most important cosmetic in
the prevention of facial eczema. These moisturizers
attempt to mimic the effect of sebum and the intercel-
lular lipids composed of sphingolipids, free sterols,
and free fatty acids. They intend to provide an environ-
ment allowing healing of the stratum corneum barrier
by replacement of the corneocytes and the intercellular
lipids. Yet, the moisturizing substances must not
occlude the sweat ducts, or miliaria will result; must
not produce irritation at the follicular ostia, or an acne-
iform eruption will result; and must not initiate come-
donal formation.
Moisturizers are used to heal barrier-damaged skin
by minimizing transepidermal water loss (TEWL) and
creating an environment optimal for healing. There are
three categories of substances that can be combined to
enhance the water content of the skin, which include
occlusives, humectants, and hydrocolloids (Table 16.1).
Occlusives are oily substances that retard TEWL by
placing an oil slick over the skin surface, while humec-
tants are substances that attract water to the skin, not
70%, but rather from the inner layers of the skin.
Humectants draw water from the viable dermis into the
viable epidermis and then from the nonviable epidermis
173
174 Z. D. Draelos

Table 16.1  Facial moisturizer categories

Moisturizer category Ingredients Skin effect
Occlusive Petrolatum, mineral oil, cetyl alcohol, dimethicone, Prevent water evaporation from skin,
cyclomethicone, soybean oil, lanolin, shea butter, smooth desquamating corneo-
cocoa butter, sesame oil, borage oil, all vegetable cytes, place protective film over
oils nerve endings to alleviate itch,
add skin shine
Humectant Glycerin, hyaluronic acid, sodium PCA, sorbitol, Act as a sponge to hold water within
propylene glycol, vitamins, gelatin the skin enabling hydration
Hydrocolloid Proteins, hyaluronic acid, colloidal oatmeal Create a physical barrier to water
evaporation from the skin

into the stratum corneum. Lastly, hydrocolloids are
physically large substances, which cover the skin, thus
retarding TEWL.
The best moisturizers to prevent facial eczema com-
bine occlusive and humectant ingredients to combine
the benefit of both categories. For example, a well-for-
mulated moisturizer might contain petrolatum, mineral
oil, and dimethicone as occlusive agents. Petrolatum is
the synthetic substance most like the natural intercel-
lular lipids, but too high a concentration will yield a
sticky, greasy ointment. The aesthetics of petrolatum
can be improved by adding dimethicone, also able to
occlude water loss, but allowing a reduction in the pet-
rolatum concentration and a thinner, more acceptable
formulation. Mineral oil is not quite as greasy as petro-
latum, but still an excellent barrier repair agent that
further improves the ability of the moisturizer to spread,
yielding enhanced aesthetics. The addition of glycerin
to the formulation will allow water attraction to the
xerotic facial skin from the dermis, speeding hydra-
tion. It is through the careful combination of these
ingredients that facial moisturizers can be constructed
to prevent and heal facial eczema.
16.1.2 Facial Cleansers
The second most important cosmetics for the preven-
tion of facial eczema are cleansers. Facial hygiene is an
important concern; however, the cleanser must normal-
ize the biofilm without damaging the stratum corneum
skin barrier. The biofilm is the thin layer of sebum,
eccrine sweat, apocrine sweat, skin care products, cos-
metics, medications, environmental dirt, bacteria, and
fungus that is present on the facial skin surface. Thus,
a cleanser must remove sebum, p. acnes, other bacteria,
Malassezia, other fungi, and Demodex to maintain the
health of the facial skin. Good facial hygiene is a care-
ful balance between maintaining a healthy biofilm
while preserving the integrity of the barrier by leaving
the intercellular lipids intact and preventing facial
eczema. This can be challenging because cleansers
cannot accurately differentiate between sebum and
intercellular lipids. It is further challenged by the ever-
changing sebum production of the facial glands, which
varies by both age and climate, and the different bacte-
ria with which the body comes in contact.
Cleansers for the face must be selected to maintain
hygiene while preserving the intercellular lipids, which
form the skin barrier. The three major chemical cate-
gories of cleansers are soaps, syndets, and combars,
which can be placed on a variety of cleansing imple-
ments from the hands to a washcloth to a disposable
face cloth (Table 16.2). True soap is a specific type of
cleanser with an alkaline pH of 9–10 created by chemi-
cally reacting a fat and an alkali to create a fatty acid
salt with detergent properties. Soap efficiently removes
both sebum and intercellular lipids making it an excel-
lent general facial cleanser, but a poor choice for dry,
sensitive facial skin. Milder cleansing for normal to
dry facial skin is found in the syndet cleansers, which
contain sodium cocoyl isethionate formulated at a neu-
tral pH of 5.5–7. This more neutral pH removes fewer
intercellular lipids, making it a cleanser suitable for the
prevention of facial xerotic eczema. If the patient has
extremely dry facial skin or tendencies toward eczem-
atous skin conditions, a moisturizing liquid cleanser
that leaves behind a thin layer of petrolatum, dimethi-
cone, or vegetable oils should be selected for preven-
tion of disease recurrence. Finally, extremely dry
sensitive skin should be cleansed with a lipid-free
cleanser, based on sodium laurel lauryl sulfate, for
facial eczema prevention.
16  Prevention of Cosmetic Problems 175

Table 16.2  Cleanser categories

Cleanser category
Soap (Ivory, P &G; pure and
natural, Jergens)
Syndet (Dove, Unilever; Olay Bar,
P & G)
Combar (Dial, Dial Corporation;
Irish Spring, Coast, Colgate-
Palmolive)
Moisturizing body wash (Olay
Ribbons, P & G; Dove
Nutrium, Unilever)
Lipid-free cleanser (Cetaphil,
Galderma; Aquanil, Person
and Covey; CeraVe Cleanser,
Coria)
Formulation
Fatty acid salt, pH 9–10
Synthetic detergent (sodium cocoyl isethionate),
pH 5.5–7
Soap and syndet combined, pH 7–9
Synthetic detergent combined with petrolatum,
dimethicone, and/or vegetable oils
Sodium laurel sulfate with cetyl alcohol and
stearyl alcohol
Appropriate patient selection
Normal-to-oily skin, general
cleansing
Normal-to-dry skin, general cleansing
Triclosan antibacterial useful in
patient with wound infection,
bacterial colonization, or body
odor
Extremely dry skin, similar to
conditioning shampoo, leaves
behind a thin film of occlusive
moisturizers to minimize skin
scaling and roughness
Dry, sensitive skin

16.2 Eyelid Dermatitis from products transferred to the eyelids by the hands.

The eyelid skin also has a paucity of sebaceous glands,
making it a common area of skin dryness. While there
The most sensitive skin on the entire body is located on
are no hairs on the eyelids themselves, the eyelashes
the eyelids. The eyelid skin moves constantly as the
form an interesting transition between the keratinized
eyes open and close, thus it must possess unique
eyelid skin and the cartilage of the tarsal plate giving
mechanical properties. It must be thin enough for rapid
structure to the edge of the eyelid. Tearing from the eye
movement yet strong enough to protect the tender eye
impacts the skin of the eyelid, since wetting and drying
tissues. Eyelid tissue shows the state of health and age
of the eyelid tissues can predispose to dermatitis.
of an individual more rapidly than any other skin of the
The eyelids are also a common source of symptoms
body. When others comment on a tired appearance,
induced by allergies. These symptoms can be itching,
they are usually assessing the appearance of the eyes
stinging, and/or burning. Most persons with these
and the eyelid tissue. When others comment on a sickly
symptoms respond by vigorously rubbing the eyelids.
appearance, they are also assessing the appearance of
This can cause mechanical damage to the eyelid skin
the eyes and the eyelid tissue. The eyelid skin appears
from minor trauma resulting in sloughing of portions
to age quickly resulting in the presence of redundant
of the protective stratum corneum to major trauma
upper eyelid tissue and lower eyelid bags. The redun-
resulting in small tears in the skin. Most of the skin on
dant upper eyelid tissue is due to loss of facial fat,
the body responds by thickening when rubbed. Eyelid
cumulative collagen loss in the eyelid skin from UV
skin will also thicken, but this predisposes to decreased
exposure, and the effect of gravity pulling down the
functioning and worsening of the symptoms.
upper eyelid skin. Lower eyelid bags are also due to
the effect UV damage and gravity, but edema or swell-
ing may also contribute. This edema may be due to
retained body fluids or the release of histamine from
inhaled allergens. All of these factors contribute to the 16.2.1 Eyelid Cosmetics
complexity of the eyelid skin.
The eyelids are the thinnest skin on the body; hence Eyelids are also a common site for cosmetic adorn-
the eyelids are the most common site for irritant con- ment. There are more individual colored cosmetics for
tact dermatitis and allergic contact dermatitis, either the eyelid area than any other body area to include
from products that are directly applied to the eyelids or mascara, eyeliner, eye shadow, and eyebrow pencil.
176
These cosmetics and the products used to remove them
can be a source of both allergic and irritant contact der-
matitis. The most common cause of cosmetic eyelid
dermatitis is the use of light-reflective pigments in eye
shadow powders or creams. Mica, bismuth oxychlo-
ride, fish scale, and ground minerals are used to create
the iridescent appearance of the cosmetic when applied
to the eyelid skin. These small particles can create irri-
tation when placed on sensitive eyelid skin, resulting in
an irritant contact dermatitis. Cosmetic-induced eyelid
dermatitis can be prevented by selecting matte finish
eyelid cosmetics without the light-reflective particles.
16.2.2 Eyelid Moisturizers
The most common cause of eyelid dermatitis is barrier
disruption from xerotic eczema. Since the eyelid is
relatively poor in oil glands, dry eyelid skin is fre-
quently seen due to overly aggressive removal of lip-
ids. This may be due to the use of a strong cleanser or
products designed to solubilize oil-based waterproof
cosmetics, such as mascara and eyeliner. Anything that
damages the intercellular lipids or the corneocytes will
result in eyelid eczema. Thus, eyelid hygiene must
achieve a careful balance between the removal of
excess sebum and old cosmetics to prevent eyelash
infections and seborrheic blepharitis, while preventing
damage to the intercellular lipids and ensuing eyelid
eczema. Moisturizers for the eye area should be com-
posed of occlusive substances that have minimal
chance for allergic or irritant reactions, reduced ability
to enter the eye, and excellent moisturizing properties
(CeraVe, Coria).
16.2.3 Eyelid Cleansers
The use of eyelid moisturizers should be complemented
by the formulation of cleansers designed to maintain
the biofilm around the eye area. Cleansing of the eyelid
tissue is indeed a delicate task. Typically, the skin
should be handled very gently, due to its thin nature,
and cleansing should remove excess sebum while pre-
serving the intercellular lipids. Lipid-free cleansers
(Table 16.2) are excellent to prevent eyelid dermatitis.
If more aggressive cleansing is required, such as pro-
vided by a foaming face wash (Olay Foaming Face
Z. D. Draelos
Wash, P & G) an appropriate moisturizer must be
selected that will provide an environment for healing
while the intercellular lipids are resynthesized (Cetaphil
Cream, Galderma).
16.3 Cheilitis
Inflammation of the lip tissues, known as cheilitis, can
be related to a variety of causes including lip-licking,
irritant contact dermatitis, allergic contact dermatitis,
actinic damage, and eczema. Cheilitis is a condition
that combines both medical and cosmetic treatments,
since lip balms and lipsticks may be an important part
of disease prevention, or in some cases, the cause of
the cheilitis.
Cheilitis is basically an inflammation of the lips.
This inflammation may be due to defective cellular
repair from actinic damage, which leads to leukoplakia
and chronic lip peeling. This is perhaps the most com-
mon cause of cheilitis in men. Alternatively, cheilitis
may be due to an allergic reaction to cosmetics. The
most common culprit is castor oil, which is found in
the majority of lipsticks. Irritation from medications or
lip-licking may also contribute. The irritation may be
due to retinoids applied elsewhere on the face migrat-
ing to the lips or maceration from repeated wetting and
drying of the lips. Lastly, there may be individuals who
have defective oil production from the tiny oil glands
found on the periphery of the lip where the transitional
mucosa meets the keratinized skin. These sebaceous
glands, also known as Fordyce spots, appear as yellow
dots within the red vermillion. These individuals could
be viewed as having a type of lip eczema.
16.3.1 Xerotic Cheilitis
In the female patient, lipsticks can be used to prevent
and treat xerotic cheilitis. Lipsticks are mixtures of
waxes, oils, and pigments in varying concentration to
yield the characteristics of the final product. A moistur-
izing lipstick designed to prevent cheilitis should con-
tain a high concentration of waxes combined with
some oils to create an environment optimal for mainte-
nance of the transitional lip barrier. The waxes com-
monly incorporated into lipstick formulations are white
beeswax, candelilla wax, carnauba wax, ozokerite wax,
16  Prevention of Cosmetic Problems 177

lanolin wax, ceresin wax, and other synthetic waxes.
Usually, lipsticks contain a combination of these waxes
carefully selected and blended to achieve the desired
melting point. Oils are then selected (i.e., castor oil,
white mineral oil, lanolin oil, hydrogenated vegetable
oils) to form a film suitable for application to the lips.
The oils provide emolliency in the lipstick, making the
lips feel smooth and soft.
Lip balms can also be used in the treatment and pre-
vention of cheilitis. They can be viewed as moisturizers
for the lips without the pigments contained in the previ-
ously discussed lipsticks. Lip balms are designed to
reduce TEWL creating an environment optimal for lip
healing. The best prevention for xerotic cheilitis is the
use of lip balm at night prior to bed (Lip Moisture
SPF15, Neutrogena). The lips are at rest at night and the
lip balm the greatest effect when applied at this time.
16.3.2 Allergic Contact Cheilitis
Allergic contact dermatitis is also a cause of cheilitis,
which can be difficult to diagnose. Several ingredi-
ents unique to lipstick formulation can cause allergic
contact dermatitis in the sensitized patient.1 Castor
oil, found in almost all lipsticks due to its excellent
ability to dissolve bromo acid dyes, is a cause of aller-
gic contact lip cheilitis.2–4 Another common lipstick
sensitizer is the bromo acid dyes, one of which is
eosin (D and C Red No. 21).5 Eosin is used in the
indelible red lipsticks designed to stain the lips and
extend the amount of time color remains on the lips.
Many long-wearing lip products contain this allergen.
In addition to causing allergic contact dermatitis, the
bromo acid dyes may also cause irritant contact der-
matitis and worsen lip dryness. Other ingredients in
lipstick that may cause allergic contact dermatitis
include: ricinoleic acid,6 benzoic acid,7 lithol rubine
BCA (Pigment Red 57–1),8 microcrystalline wax,9
oxybenzone,10 propyl gallate,11 and C18 aliphatic
compounds.12
16.4 Postinflammatory
Hyperpigmentation
Postinflammatory hyperpigmentation is a common cos-
metic problem of the entire body that is best prevented
rather than treated. The prevention of postinflammatory
hyperpigmentation may be difficult, especially in
Fitzpatrick skin types III and higher. This unsightly pig-
mentation can occur after casual or deliberate sun expo-
sure, unintended injury to the skin, or following skin
surgery. A successful treatment must remove existing
pigment from the skin, shut down the manufacture of
melanin, and prevent the transfer of existing melanin to
the melanosomes. Currently, there is no topical pre-
scription or OTC product that achieves these three goals.
The following discussion divides the prevention and
treatment of postinflammatory hyperpigmentation into
the prescription pigment-lightening agents such as hyd-
roquinone mequinol, tretinoin, and azelaic acid
(Table  16.3); and the botanical OTC agents such as
ascorbic acid, licorice extract, alpha lipoic acid, kojic
acid, aleosin, and arbutin. There is no doubt that the pre-
scription products are more effective than the botanical
derivatives, but both are discussed for completeness.

Table 16.3  Skin-lightening ingredients for postinflammatory hyperpigmentation

Skin-lightening ingredient Effect on melanogenesis Relative efficacy
Hydroquinone Inhibits tyrosinase by interfering with copper binding Highest
reducing conversion of dihydroxyphenylanlanine
(DOPA) to melanin
Azelaic acid Inhibits tyrosinase by interfering with copper binding Moderate
reducing conversion of DOPA to melanin
Kojic acid Inhibits tyrosinase by interfering with copper binding Moderate
reducing conversion of DOPA to melanin
Arbutin Decreases tyrosinase activity without affecting Moderate
messenger RNA expression
Liquirtin Increases melanin granule dispersion Low
Vitamin C Interacts with copper ions to reduce dopaquinone and Low
blocks dihydrochinindol-2-carboxyl acid oxidation
178
16.4.1 Prescription Hyperpigmentation
Topical Agents
16.4.1.1 Hydroquinone
The gold standard for hyperpigmentation therapy in
the United States remains hydroquinone. This sub-
stance is actually quite controversial, having been
removed from the OTC markets in Europe and Asia.
Concern arose because oral hydroquinone has been
reported to cause cancer in mice fed large amounts of
the substance. While oral consumption probably is not
related to topical application, hydroquinone remains
controversial because it actually is toxic to melano-
cytes. Hydroquinone, a phenolic compound chemi-
cally known as 1,4 dihydroxybenzene, functions by
inhibiting the enzymatic oxidation of tyrosine and phe-
nol oxidases. It covalently binds to histidine or inter-
acts with copper at the active site of tyrosinase. It also
inhibits RNA and DNA synthesis and may alter mel-
anosome formation, thus selectively damaging mel-
anocytes. These activities suppress the melanocyte
metabolic processes inducing gradual decrease of mel-
anin pigment production.13
Hydroquinone is available in both the OTC and pre-
scription markets in the US. The maximum concentra-
tion in OTC formulations is 2% while most prescription
formulations are 4%. It is possible to compound hyd-
roquinone creams as high as 8%, but the formulations
are unstable with rapid oxidation represented by
browning of the product. In all formulations, hydro-
quinone is unstable, turning brown upon contact with
air. Once the hydroquinone has oxidized, it is no lon-
ger active and should be discarded.
Prescription hydroquinone formulations have tried
to increase the potency of formulations by adding pen-
etration enhancers such as glycolic acid, sunscreens,
and tretinoin as a supplemental pigment lightening
agent. Other prescription formulations have added
microsponges to create time delivery of hydroquinone
to the skin while others have placed the hydroquinone
in a special canister dispenser.
The initiation of hydroquinone prior to elective cos-
metic surgery is the best preventative for minimizing and
possibly eliminating postinflammatory hyperpigmenta-
tion. Hydroquinone can be used to decrease pigment pro-
duction prior to the skin surgery that will ultimately drive
pigment production.
Z. D. Draelos
16.4.1.2 Mequinol
Mequinol is the newest prescription skin-lightening agent
approved in the US. It has also received approval in
Europe. It is chemically known as 4-hydroxyanisole.
Other names include methoxyphenol, hydroquinone
monomethyl ether, and p-hydroxyanisole. Mequinol is
available in the US in a 2% concentration and is commer-
cially marketed as a prescription skin lightener in combi-
nation with 0.01% tretinoin as a penetration enhancer and
vitamin C, in the form of ascorbic acid and ascorbyl
palmitate, to enhance skin lightening. These active agents
are dissolved in an ethyl alcohol vehicle. The exact mech-
anism of action accounting for the skin-lightening prop-
erties of mequinol is unknown; however, it is a substrate
for tyrosinase, thereby acting as a competitive inhibitor in
the formation of melanin precursors. It does not damage
the melanocyte as does hydroquinone.
Mequinol can be irritating to the skin and cause
hyperpigmentation in persons with sensitive skin. Prior
to picking this ingredient for the prevention of postin-
flammatory hyperpigmentation, a small test site should
be selected to daily application for 2 weeks. If no skin
darkening occurs, the mequinol may be suitable for the
prevention of postinflammatory hyperpigmentation. It
may actually be the 0.01% tretinoin that is the irritant
in the presently available commercial mequinol for-
mulation, rather than the mequinol itself (Solage, bar-
rier therapeutics).
16.4.1.3 Tretinoin
Topical tretinoin is used alone and in combination with
hydroquinone as prescription pigment lightening treat-
ment. Tretinoin has an effect on skin pigmentation as
seen by a decrease in cutaneous freckling and lenti-
genes.14 It is the irregular grouping and activation of
melanocytes that accounts for the dyspigmentation
associated with photoaging,15 but normalization of this
change has been histologically demonstrated with retin-
oids.16 While this effect is more dramatic with topical
tretinoin, topical retinol has been thought to provide
similar effects as a cosmeceutical. For persons with
difficult-to-manage postinflammatory hyperpigmenta-
tion, tretinoin can be combined with hydroquinone and
a topical corticosteroid, to reduce inflammation, in a
presently marketed combination formulation (TriLuma,
Galderma).
16  Prevention of Cosmetic Problems
16.4.1.4 Azelaic Acid
Azelaic acid is available currently as a 15% gel
approved in the US for the treatment of rosacea
(Finacea, Intendis). It is a 9-carbon dicarboxylic acid
obtained from cultures of Pityrosporum ovale that may
be a treatment alternative for individuals allergic to
hydroquinone. Although its lightening effects are mild,
several large studies done with a diverse ethnic back-
ground population have compared its efficacy to that of
hydroquinone.17,18 It too interferes with tyrosinase
activity, but may also interfere with DNA synthesis. It
appears to have a specificity for abnormal melanocytes
and for this reason has been used to suppress the pro-
gression of lentigo maligna to lentigo maligna mela-
noma. Azelaic acid may be an alternative to the
previously mentioned prescription formulations in per-
sons with sensitive skin or an allergy to other pigment
lightening ingredients for the prevention of postinflam-
matory hyperpigmentation.
16.4.2 Nonprescription
Hyperpigmentation Topical
Agents
There are a variety of nonprescription topical agents
that are available in cosmeceuticals and cosmetics to
prevent postinflammatory hyperpigmentation. None of
these ingredients are as efficacious as hydroquinone;
however, they are considered safe for use both in the
US and worldwide.
16.4.2.1 Ascorbic Acid
Ascorbic acid, also known as vitamin C, is used in the
treatment and prevention of postinflammatory hyper-
pigmentation. It interrupts the production of melano-
genesis by interacting with copper ions to reduce
dopaquinone and blocking dihydrochinindol-2-car-
boxyl acid oxidation.19 Ascorbic acid, an antioxidant,
is rapidly oxidized when exposed to air and is of lim-
ited stability. High concentrations of ascorbic acid
must be used with caution as the low pH can be irritat-
ing to the skin actually precipitating postinflammatory
hyperpigmentation.
179
16.4.2.2 Licorice Extract
Licorice extracts are being used as topical anti-inflam-
matories to decrease skin hyperpigmentation. The
active agents are known as liquiritin and isoliquertin,
which are glycosides containing flavenoids.20 Liquiritin
induces skin lightening by dispersing melanin. It is
typically applied to the skin in a dose of 1  g/day for
4 weeks to see a clinical result. Irritation is fortunately
not a side effect.
16.4.2.3 Alpha Lipoic Acid
Alpha lipoic acid is found in a variety of antiaging cos-
meceuticals to function as an antioxidant, but it may
also have very limited value in postinflammatory hyper-
pigmentation. It is a disulfide derivative of octanoic
acid that is able to inhibit tyrosinase. However, it is a
large molecule and cutaneous penetration to the level
of the melanocyte is challenging.
16.4.2.4 Kojic Acid
Kojic acid, chemically known as 5-hydroxymethyl-4H-
pyrane-4-one, is one of the most popular cosmeceuti-
cal skin-lightening agents found in cosmetic counter
skin-lightening creams distributed worldwide. It is a
hydrophilic fungal derivative obtained from Aspergillus
and Penicillium species. It is the most popular agent
employed in the Orient for the treatment of melasma.21
Some studies indicate that kojic acid is equivalent to
hydroquinone in pigment-lightening ability.22 The
activity of kojic acid is attributed to its ability to pre-
vent tyrosinase activity by binding to copper. It may be
useful in postinflammatory hyperpigmentation.
16.4.2.5 Aleosin
Aleosin is a low-molecular-weight glycoprotein obtained
from the aloe vera plant. It is a natural hydroxymethyl-
chromone functioning to inhibit tyrosinase by competi-
tive inhibition at the dihydroxyphenylanlanine (DOPA)
oxidation site.23, 24 In contrast to hydroquinone, it shows
no cell cytotoxicity; however, it has a limited ability to
penetrate the skin due to its hydrophilic nature. It is
180 Z. D. Draelos

sometimes mixed with arbutin to enhance its skin-­ are the PABA derivatives, salicylates, and cinnamates;
lightening abilities. substances that absorb both UVB and UVA are tita-
nium dioxide and zinc oxide. Most quality sunscreens
to prevent postinflammatory hyperpigmentation com-
16.4.2.6 Arbutin bine these ingredients to yield a product with excellent
photoprotection that is cosmetically elegant.
Arbutin is obtained from the leaves of the vaccinicum
vitis-idaca and other related plants. It is a naturally
occurring gluconopyranoside that causes decreased 16.4.3.1 UVA Filters and Prevention of
tyrosinase activity without affecting messenger RNA Tanning Response
expression25. It also inhibits melanosome maturation.
Arbutin is not toxic to melanocytes and is used in a The UVA absorbers are most important in the preven-
variety of pigment-lightening preparations in Japan at tion of postinflammatory hyperpigmentation. UVA
concentrations of 3%. Higher concentrations are more absorbers can be divided into organic and inorganic
efficacious than lower concentrations, but a paradoxi- subgroups. The organic subgroup undergoes a chemi-
cal pigment darkening and postinflammatory hyper- cal reaction, known as resonance delocalization, to
pigmentation may occur. transform the UVA energy into heat. The main organic
UVA absorber in sunscreens that prevent postinflam-
matory hyperpigmentation is avobenzone. Avobenzone
must be combined with other organic filters because it
16.4.3 Sunscreens is rapidly degraded by UV exposure. Almost 36% of
the avobenzone in a sunscreen formulation becomes
chemically inactive on initial exposure. Thus, avoben-
Sunscreens are another product category that can be
zone is combined with oxybenzone and octocrylene to
used to prevent postinflammatory hyperpigmentation
enhance its photostability. Other UVA organic filters,
by minimizing the pigmenting effect of ultraviolet
such as the anthranilates (menthyl anthranilate), can be
(UV) radiation. Sunscreens are designed to absorb
added as secondary agents.
UVA radiation (320–360 nm), accounting for pigmen-
However, some of the most effective UVA photo-
tation, and UVB radiation (290–320 nm), accounting
protectants are the organic filters zinc oxide and tita-
for sunburn. Table  16.4 summarizes the more com-
nium dioxide. These white powders primarily reflect
monly used UVA and UVB filters. The primary UVA
UVA radiation, but may also absorb a small amount.
absorbers on this list are the benzophenones, anthrali-
They also reflect UVB radiation. Zinc oxide is avail-
nates, and avobenzone. The primary UVB absorbers
able as a microfine powder, but it cannot be used in
high concentration due to the white-skin appearance
Table 16.4  Cosmeceutical sunscreens created. Typically, zinc oxide is only used in concen-
Sunscreen Spectrum of Ingredients trations of 2% or less for this reason. The newer nano-
categories protection particle zinc oxide is transparent, but very controversial.
Organic UVB filters 290–320 nm Octyl methoxy The controversy revolves around the ability of nano-
cinnamate, particle zinc oxide to penetrate the skin and create a
ocytocrylene,
octyl salicylate
permanent nonreactive dermal reservoir. The safety of
this reservoir is unknown at this writing, leading the
Organic UVA filters 320–360 nm Ecamsule,
cosmetics industry to voluntarily refrain from use of
avobenzone,
oxybenzone, this material until a better understanding of its skin
menthyl effects can be obtained.
anthranilate Titanium dioxide is typically used in a larger parti-
Inorganic UVB/ Total reflection Zinc oxide, cle size than zinc oxide. The term micronized is used
UVA filters of all titanium to describe these particles because they are of many
radiation dioxide different sizes as compared to the even size of microfine
16  Prevention of Cosmetic Problems 181

particles. The microfine formulations produce less skin Water resistance is predicated on the fact that water
whitening than the micronized formulations. Both par- soluble and oil-soluble substances do not mix. Thus, if
ticulates are often silicone-coated to decrease the gen- a sunscreen is predominantly oil, with minimal water,
eration of secondary oxygen radicals when struck by it will not dissolve in the presence of water or perspira-
UV radiation. Thus, the most effective inorganic sun- tion. However, oil-dominant sunscreens are greasy and
screens for preventing postinflammatory hyperpig- sticky, imparting poor aesthetics. This has led to devel-
mentation are zinc oxide and titanium dioxide while opment of silicone-based sunscreens, since silicone is
the most effective organic sunscreen is stabilized an oil that is not greasy or sticky and has excellent
avobenzone. However, the sunscreen filter is just as water-resistant properties.
important as the ability of the sunscreen to stay on the Another method of imparting water resistance to a
skin preventing postinflammatory hyperpigmentation. sunscreen is to alter or eliminate the emulsifier. The
emulsifier allows water and oil-soluble ingredients to
coexist as one continuous phase. Unfortunately, the
16.4.3.2 Sunscreen Longevity sunscreen emulsifier will also allow perspiration or
swimming pool water to mix with the oily ingredients,
Providing superior longevity of the sunscreen film on facilitating removal. This has led to the development
the skin surface and preventing postinflammatory of acrylate cross polymers and liquid crystal gels as the
hyperpigmentation can be accomplished by imparting vehicle without an emulsifier. This increases the lon-
water-resistant characteristics, since sweat, humidity, gevity of the sunscreen, an important consideration on
and a moist environment are the three most common areas such as the face that are prone to pigmentation
factors that result in sunscreen failure (Table  16.5). following surgery.
The last method used to confer sunscreen longevity
in a moist environment is predicated on creating a film
Table 16.5  Water-resistant sunscreens
resistant to water removal. This can be accomplished
Chemical technology Mechanism of efficacy with phospholipids, structurally similar to natural
sebum, that create a thin oily film on the skin. Polymers
Water-in-oil emulsions Oil is the main ingredient
and resists removal by can also be used to create a thin water-resistant film on
water the skin surface.
Silicones Hydrophobic oily liquid that
resists removal by water
and forms film over skin 16.4.3.3 SPF and Sunscreen Efficacy
surface
Acrylate crosspolymer No emulsifier required Another important consideration in sunscreen efficacy
which prevents water
from dissolving the
is the amount of photoprotection afforded by the prod-
sunscreen, used in uct. It has been traditionally thought that a sunscreen
titanium dioxide with an SPF of 15 was sufficient. Recently, newer sun-
preparations screen formulations have been introduced with higher
Liquid crystal gels Hydrophobic emulsifiers SPF ratings, providing added benefits. While an SPF
used that resist water, of 15 was thought to be sufficient for the prevention of
used in titanium dioxide
sunburn, it is not optimal for protection against postin-
preparations
flammatory hyperpigmentation. A higher SPF cannot
Phospholipid emulsifiers Substances engineered to be achieved without providing additional UVA photo-
mimic natural sebum
(potassium cetyl protection. At present, no rating system exists for the
phosphate) with UVA qualities of a sunscreen.
water-resistant properties In summary, a sunscreen to prevent postinflamma-
Film forming polymers Thin polymer film formed tory hyperpigmentation should contain broad-spectrum
over the skin with UVA photoprotective ingredients, water-resistant qual-
inherent water resistance ities, and a high SPF.
182
16.5 Hyperhidrosis
Another common cosmetic problem is unwanted axil-
lary perspiration. Clearly, the biggest advance in the
treatment of this condition is the injection of botulinum
toxin, which produces dramatic long-term sweat reduc-
tion. Yet antiperspirants remain a viable effective alter-
native in some patients. Antiperspirants can even be
combined with botulinum toxin to prolong or increase
the effect.
Antiperspirants function to reduce both apocrine
and eccrine sweat. Eccrine sweat is a clear, odorless
fluid of pH 4–6.8 composed of 98–99% water, sodium
chloride, lower fatty acids, lactic acid, citric acid,
ascorbic acid, urea, and uric acid. Apocrine sweat is a
turbid, viscous, odorless fluid of pH 6–7.5 that has
high content water, in addition to protein, carbohydrate
waste materials, and sodium chloride. The amount of
eccrine perspiration is much greater than the amount
of apocrine perspiration. An effective antiperspirant
must reduce both types of perspiration.
16.5.1 Antiperspirant Mechanism
of Action
To reduce axillary hyperhidrosis, the antiperspirant
must reach some 25,000 eccrine glands and coagulate
the sweat duct protein. Antiperspirants contain metal
salts that alter intraductal keratin fibrils to cause eccrine
duct closure and formation of a horny plug, which
obstructs sweat flow to the skin surface.26 The plug is
formed by aluminum and zirconium metal salts.27 The
original antiperspirant formulation was a 25% solution
of aluminum chloride hexahydrate in distilled water,
but it was extremely irritating.28 More modern antiper-
spirant formulations contain aluminum chloride, alu-
minum chlorohydrate, aluminum zirconium
chlorohydrate, and buffered aluminum sulfate.29 These
metals provide a better balance between efficacy and
skin irritation.
An effective antiperspirant must reduce sweat by at
least 20% as mandated by the FDA, since antiperspi-
rants are regulated as OTC drugs. Antiperspirants
labeled as highly effective must reduce sweat by at least
30%. The antiperspirant must create a long-lasting plug
Z. D. Draelos
in the sweat duct ostia quickly. This is best accom-
plished by evenly spreading the antiperspirant in
the axillary vault. If the antiperspirant does not touch
the sweat duct, it will not work. The active agent in the
newer antiperspirants is aluminum-zirconium tetra-
chlorohydrex-gly complex. This complex can reduce
axillary perspiration by 40–60%. These aluminum salts
have an acidic pH of 3.0–4.2.30 Irritation is reduced by
incorporating skin conditioning agents, such as dime-
thicone or cyclomethicone, into the formulation. The
silicone imparts skin soothing properties to the skin
irritated by the antiperspirant ingredients.
16.5.2 Optimizing Antiperspirant Efficacy
Antiperspirants can fail to control hyperhidrosis for
many reasons. The most common reason is use of a
poor formulation that does not contain an optimal
active ingredient mix and appropriate vehicle construc-
tion to deliver results. Antiperspirants also fail because
an even film cannot be obtained that covers the entire
armpit. The antiperspirant must be in contact with each
and every eccrine and apocrine duct in the armpit to
work. Thus, the applicator should be domed to fit into
the axilla and dispense a thick even film of product.
The film must be somewhat water-resistant or it will be
rinsed away by perspiration before the plug can be
formed in the ducts. For this reason, the armpit should
be dry when the product is applied. Many dermatolo-
gists recommend that patients apply an OTC or pre-
scription antiperspirant and then occlude the armpit
with plastic wrap. If the patient sweats profusely under
the occlusion, the perspiration may wash away the
active ingredients before a plug can be formed. Thus,
the occlusion may decrease the efficacy of the antiper-
spirant rather than increase efficacy due to enhanced
penetration.
Another possible cause for antiperspirant failure is
inconsistent application. Compliance is important to
achieve optimal results. It takes about 10 days of anti-
perspirant application for the complete plug to be formed
in the sweat duct. If the patient decides after 3 days of
application that the antiperspirant has not worked suffi-
ciently, they have not given the product an adequate
trial. Furthermore, the plug is completely gone 14 days
after the last application. Continuous daily application
16  Prevention of Cosmetic Problems
is necessary to achieve and maintain the sweat reduction
effect.
Another consideration is the depth of the plug within
the sweat duct. Plugs that are more deeply placed in the
sweat gland will provide better sweat reduction than
those that are superficially situated. If the plug is very
close to the surface, it is possible that it can be removed
by the rubbing of clothing or shaving. Patients who
complain that antiperspirants do not work may wish to
wear loose fitting clothing around the armpits and use
only light razor pressure when shaving the armpits.
The deepest plugs are created by prescription alumi-
num chloride solutions, but these formulations must be
used carefully as they can irritate skin and ruin natural
fabrics, such as rayon, cotton, and silk. More superfi-
cial plugs are created by OTC antiperspirants contain-
ing aluminum chlorohydrate. Intermediate depth plugs
are created by OTC antiperspirants containing alumi-
num zirconium chlorohydrate.
Optimizing antiperspirant efficacy requires the use
of a well-formulated product that is consistently applied
to the entire armpit as a thin film. One of the newer
formulations uses aluminum-zirconium tetrachlorohy-
drex-gly complex, which has good efficacy with mini-
mal skin irritation (Secret Platinum, P & G). This
irritation is further reduced by the presence of dimethi-
cone in the vehicle, which also provides for easy spread-
ability of a thin water-resistant film. Efficacy can be
further enhanced by applying the antiperspirant twice
daily. The bedtime application is actually more impor-
tant than the morning application because the body is at
rest and sweating reduced. The reduced sweating
decreases the removal of the antiperspirant from the
armpit and allows the active ingredient to remain in
contact with the skin longer creating a stronger plug.
Thus, antiperspirants can be optimized to provide pre-
vention for the cosmetic problem of hyperhidrosis.
16.6 Acne
Perhaps the most bothersome cosmetic problem to pre-
vent is acne. Many skin care products have been accused
of causing or worsening acne. Is there a true cause-and-
effect relationship between skin care or cosmetic prod-
uct use and the onset of acne? Sometimes this is difficult
to ascertain. The final topic of discussion in this chapter
183
addresses the issue of acne cosmetica, a term used to
describe acne caused by the application of topical
products.
16.6.1 Acne Cosmetica
Acne cosmetica is a concept that was developed many
years ago when there was concern that cosmetics could
indeed cause comedones formation. The issue of come-
dogenicity in relation to cosmetics arose in 1972 when
Kligman and Mills described a low-grade acne charac-
terized by closed comedones on the cheeks of women
ages 20–25.31 Many of these women had not experienced
adolescent acne. The authors proposed that substances
present in cosmetic products induced the formation of
closed comedones and, in some cases, a papulopustular
eruption. Presently, personal conversations with Dr.
Kligman indicate that he no longer believes currently
marketed cosmetics cause comedones formation, yet
acne related to cosmetics remains a problem.
Lists remain in the literature of ingredients that sup-
posedly cause acne, yet it is practically impossible to find
formulations devoid of these substances. The list con-
tains some of the most effective emollients (octyl stear-
ate, isocetyl stearate), detergents (sodium lauryl sulfate),
occlusive moisturizers (mineral oil, petrolatum, sesame
oil, cocoa butter), and emulsifiers found in the cosmetic
industry.32 A product line that excluded all these ingredi-
ents would exhibit poor efficacy and aesthetics.
The skin care industry has developed the nomencla-
ture of noncomedogenic and nonacnegenic to assure the
consumer that the product does not cause acne; how-
ever, these claims carry no scientific validity as they are
strictly for marketing purposes. The claims were devel-
oped to create a new consumer image for cosmetic lines
designed to minimize acne. While testing is not required
to make these claims, most large companies voluntarily
will use established industry tests to ensure product
safety and substantiate their claims.
Many manufacturers, however, make noncomedo-
genic and nonacnegenic claims based on the safety
profiles of the individual ingredients in the formula-
tion. This is inaccurate. Noncomedogenic and non-
acnegenic claims should be made based on clinical
testing of the finished formulation. There are several
established methods of testing cosmetic products.
184 Z. D. Draelos

16.6.2 Comedogenicity Testing for purchase in industrial and cosmetic grades.

Industrial grade mineral is used as a machine lubricant
and may be contaminated with tar by-products, which
Comedogeniticity testing is typically carried out on
are comedogenic. However, cosmetic grade mineral
either the rabbit ear or the human upper back. Rabbit
oil is certified pure by the supplier and is noncomedo-
ear testing is forbidden in the European Union and has
genic. No quality cosmetic company would use indus-
been largely abandoned in the US as most companies
trial grade mineral oil in their products.
wish to advertise that their products do not involve ani-
Most of the ingredients of old that were considered
mal testing. Human testing is conducted on the upper
comedogenic were derived from petroleum distillates.
back of individuals who have demonstrated the ability
It is well-known in dermatology that tar is comedo-
to form comedones. This is confirmed by performing a
genic. If a raw material is contaminated with tar, it may
cyanoacrylate biopsy on the upper back of volunteers.
cause comedones formation. With new mass spectros-
The biopsy is obtained by placing cyanoacrylate glue
copy and better control on the manufacture of cosmetic
on a microscope slide and allowing the acrylate to
materials, by-product contamination is rare. Most cos-
polymerize, adhering the stratum corneum to the glass
metic companies require purity testing from their sup-
slide. The slide is then peeled from the upper back and
pliers and then retest shipments of raw materials for
a thin layer of stratum corneum along with follicular
purity in their own laboratories. The risk of ruining a
contents is removed. The number of comedonal plugs
good reputation based on a poor-quality raw material
removed is counted and should be at least ten to pro-
is too great in today’s competitive market. The old lists
vide an adequate sample size. The cosmetic for come-
of comedogenic substances probably need to be retired
dogenicity testing is applied to the upper back under
in the modern marketplace.
occlusion Monday through Friday for 2 weeks.
At the end of the testing period, the cyanoacrylate
biopsy is repeated. One negative control patch is
applied with no cosmetic and one positive control 16.6.4 Acneiform Eruptions
patch is applied with coal tar. The final counts are and Cosmetics
obtained by viewing the slide upside down with a low
magnification microscope and counting in a 1-cm
Acnegenicity must be distinguished from comedoge-
squared field. If the number of comedonal plugs
nicity. While comedogenicity is rare, acnegenicity is
increases as compared to baseline, the cosmetic is con-
much more common from skin care products.
sidered comedogenic. If the number of comedonal
Comedogenicity results in the formation of comedones
plugs remains the same or decreases, the cosmetic can
while acnegenicity results in the formation of inflam-
be labeled noncomedogenic. This type of human test-
matory perifollicular papules. These papules may rep-
ing is safe and appears to accurately predict the come-
resent true acne with the involvement of the sebaceous
dogenic potential of a cosmetic.
gland or may simply represent a perifollicular acnei-
form eruption, which is undoubtedly more common.
Many patients note the occurrence of “breakouts”
16.6.3 Comedogenic Ingredients following the use of moisturizers, facial foundations,
sunscreens, etc. These patients typically present with
There are many frequently used cosmetic ingredients perifollicular papules and pustules in a random distribu-
that have been associated with comedones formation. tion over the face. This eruption appears within 24–48 h
Perhaps mineral oil is the most common. Several cos- after wearing the facial product. This is insufficient time
metic lines have been founded on the premise that for true acne to develop as evidenced by follicular rup-
mineral oil is a “bad” ingredient and avoidance of this ture. However, it is sufficient time for an irritant contact
material creates a “good” facial cosmetic. Mineral oil dermatitis to develop. Most liquid formulations contain
is a lightweight, inexpensive oil that is odorless and an emulsifier that allows the oily and water-soluble
tasteless. Mineral oil may have been comedogenic in ingredients to coexist in one continuous phase. These
the past, but in current forms used in cosmetic formu- emulsifiers can also emulsify sebum and create perifol-
lations it is not comedogenic. Mineral oil is available licular irritation. Most companies test their product for
16  Prevention of Cosmetic Problems
acnegenicity for this reason. The tests usually involve
an in-use test where volunteers use the product for 12
weeks with every 4-week evaluation by a dermatolo-
gist. All adverse reactions are recorded. If these perifol-
licular eruptions do not occur, the product can then
accurately claim the formulation to be nonacnegenic.
Persons who are prone to acneiform eruptions
should prevent cosmetic problems by use-testing a
new cosmetic or skin care product inside the elbow for
five consecutive nights. If no problems arise, the prod-
uct can then be applied to an area lateral to the eye for
five consecutive nights. If no problems present, the
product can be applied to the entire face. This type of
testing can best prevent a total facial eruption.
16.7 Summary
This chapter has discussed prevention of the common
cosmetic problems including facial eczema, eyelid
dermatitis, cheilitis, postinflammatory hyperpigmenta-
tion, hyperhidrosis, and acne. The proper selection of
skin care products can aid in prevention. Adequate
treatment of these conditions is best addressed through
the use of pharmaceuticals in conjunction with OTC
drugs, such as sunscreens and antiperspirants, along
with the use of skin care products, such as moisturiz-
ers, skin-lightening agents, and cleansers. A complete
understanding of cosmetic problems involves under-
standing all the product categories available for thera-
peutic intervention.
References
  1. Sulzgerger MD, Boodman J, Byrne LA, Mallozzi ED.
Acquired specific hypersensitivity to simple chemicals.
Cheilitis with special reference to sensitivity to lipsticks.
Arch Dermatol. 1938;37:597–615
  2. Sai S. Lipstick dermatitis caused by castor oil. Contact
Derm. 1983;9:75
  3. Brandle I, Boujnah-Khouadja A, Foussereau J. Allergy to
castor oil. Contact Derm. 1983;9:424–425
  4. Andersen KE, Neilsen R. Lipstick dermatitis related to cas-
tor oil. Contact Derm. 1984;11:253–254
  5. Calan CD. Allergic sensitivity to eosin. Acta Allergol.
1959;13:493–499
  6. Sai S. Lipstick dermatitis caused by ricinoleic acid. Contact
Derm. 1983;9:524
185
  7. Calnan CD. Amyldimethylamino benzoic acid causing lip-
stick dermatitis. Contact Derm. 1980;6:233
  8. Hayakawa R, Fujimoto Y, Kaniwa M. Allergic pigmented
lip dermatitis from lithol rubine BCA. Am J Contact Derm.
1994;5:34–37
  9. Darko E, Osmundsen PE. Allergic contact dermatitis to lip-
care lipstick. Contact Derm. 1984;11:46
10. Aguirre A, Izu R, Gardeazabal J, et al Allergic contact cheil-
itis from a lipstick containing oxybenzone. Contact Derm.
1992;27:267–268
11. Cronin E. Lipstick dermatitis due to propyl gallate. Contact
Derm. 1980;6:213–214
12. Hayakawa R, Matsunaga K, Suzuki M, et al Lipstick derma-
titis due to C18 aliphatic compounds. Contact Derm.
1987;16:215–219
13. Halder RM, Richards GM. Management of dischromias in
ethnic skin. Dermatol Ther. 2004;17:151–157
14. Weinstein GD, Nigra TP, Pochi PE, et al Topical tretinoin for
treatment of photodamaged skin. Arch Dermatol.
1991;127:659–665
15. Gilchrest BA, Blog FB, Szabo G. Effects of aging and
chronic sun exposure on melanocytes in human skin. J Invest
Dermatol. 1979;73:141–143
16. Bhawan J, Serva AG, Nehal K, et al Effects of tretinoin on
photodamaged skin a histologic study. Arch Dermatol.
1991;127:666–672
17. Fitton A, Goa KL. Azelaic acid. a review of its pharmaco-
logical properties and therapeutic efficacy in acne and hyper-
pigmentary skin disorders. Drugs. 1991;5:780–798
18. Balina LM, Graupe K. treatment of melasma. 20% azelaic
acid versus 4% hydroquinone cream. Int J Dermatol.
1991;30(12):893–895
19. Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. A
double blind randomized trial of 5% ascorbic acid vs. 4%
hydroquinone in melasma. Int J Dermatol. 2004;
43(8):604–607
20. Amer M, Metwalli M. Topical Liquiritin improves melasma.
Int J Dermatol. 2000;39(4):299–301
21. Lim JT. Treatment of melasma using kojic acid in a gel con-
taining hydroquinone and glycolic acid. Derm Surg.
1999;25:282–284
22. Garcia A, Fulton JE Jr. The combination of glycolic acid and
hydroquinone or kojic acid for the treatment of melasma and
related conditions. Dermatol Surg. 1996;22(5):443–447
23. Choi S, Lee SK, Kim JE, et al Aloesin inhibits hyperpigmen-
tation induced by UV radiation. Clin Exp Dermatol.
2002;27:513–515
24. Jones K, Hughes J, Hong M, et al Modulation of melanogen-
esis by aloesin: a competitive inhibitor of tyrosinase. Pigment
Cell Res. 2002;15:335–340
25. Hori I, Nihei K, Kubo I. Structural criteria for depigmenting
mechanism of arbutin. Phytother Res. 2004;18:475–469
26. Shelley WB, Hurley HJ Jr. Studies on topical antiperspirant
control of axillary hyperhidrosis. Acta Derm Venereol.
1975;55:241–260
27. Jass HE. Rationale of formulations of deodorants and anti-
perspirants. In: Frost P, Horwitz SN, eds. Principles of
Cosmetics for the Dermatologist. St. Louis: CV Mosby;
1982:98–104
28. Emery IK. Antiperspirants and deodorants. Cutis. 1987;
39:531–532
186
29. Morton JJP, Palazzolo MJ. Antiperspirants. In: Whittam JH,
ed. Cosmetic Safety: A Primer for Cosmetic Scientists. New
York: Marcel Dekker; 1987:221–263
30. Calogero AV. Antiperspirant and deodorant formulation.
Cosmet Toilet. 1992;107:63–69
Z. D. Draelos
31. Kligman AM, Mills OH. Acne cosmetica. Arch Dermatol.
1972;106:843
32. Fulton JE, Pay SR, Fulton JE. Comedogenicity of current
therapeutic products, cosmetics, and ingredients in the rabbit
ear. J Am Acad Dermatol. 1984;10:96–105
 Nutrition, Vitamins, and Supplements
Evangeline B. Handog and Trisha C. Crisostomo
Everyone has the right to a standard of living adequate for the health and well-being of himself and
his family, including food.
Adequate nutrition is essential for health and for the man-
agement of disease. From the earliest stages of life until
old age, proper food and good nutrition is fundamental
for survival, physical growth, mental development, per-
formance and productivity, health and well-being.
The right to food and nutrition, and the right to be
free from hunger and malnutrition are international
human rights being promoted by the World Health
Organization (WHO) and other intergovernmental
organizations since 1948. In the Rome Declaration
on World Food Security (World Food Summit, 1996),
heads of state and governments reaffirmed “the right
of everyone to have access to safe and nutritious
food, consistent with the right to adequate food and
the fundamental right of everyone to be free from
hunger.”1
The various nutrients, vitamins, and minerals
can be acquired through a balanced diet, but more
often than not, supplements are needed to maintain
this equilibrium and prevent malnutrition. In 2000,
WHO reported 150 million children less than
5 years old having protein–energy malnutrition, but
this figure is slowly decreasing. It is distressing to
note that WHO also reported 49% of the 10.7 mil-
lion deaths among children less than 5  years old
E. B. Handog (*)
Section of Dermatology, Research Institute for Tropical
Medicine, Department of Health, Muntinlupa, Alabang,
Philippines
e-mail: handogmd@pacific.net.ph
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_17, © Springer-Verlag London Limited 2010
17
Universal Declaration of Human Rights
each year in the developing world are associated
with malnutrition.1
Malnutrition is most commonly caused by a defi-
ciency in nutrients. It may be caused by insufficient
ingestion, abnormal absorption or inadequate utiliza-
tion of nutrients. However, it may also be caused by an
intake excess. WHO reports an emerging epidemic of
obesity. Three hundred million adults are diagnosed
with obesity, 17.6 million of which are children in
developing countries.1
Nutritional diseases may present initially or eventu-
ally with cutaneous signs and symptoms. This chapter
aims to describe the common nutritional disorders
encountered by dermatologists and how to prevent
them.
17.1 Definition
17.1.1 Nutrition
Nutrition is the process by which a living being takes
in substances such as food and nutrients and uses them
for life, growth, and the preservation of health.2
Nutrients are substances not synthesized by the body
in enough amounts and thus must be supplemented by
the diet. These include proteins, fats, carbohydrates,
vitamins, minerals, and water. The required amounts
of each essential nutrient differ according to the age
and physiologic state of the individual.3
187
188
Table 17.1  Body mass index (BMI) classification
BMI (kg/m2) Classification
<18.5 Underweight
18.5–24.9 Normal
25.0–29.9 Overweight
30.0–39.9 Obese
>40 Morbidly obese
BMI = weight (kilograms)/[height(meters)]2
17.1.2 Body Mass Index
Body mass index (BMI) is computed by dividing the
person’s weight in kilograms by the square of his
height in meters. A BMI within the range of 18.5–
24.9 kg/m2 is normal, a BMI of 25.0–29.9 kg/m2 is cat-
egorized as overweight, a BMI of 30.0–39.9 kg/m2 is
considered obesity and a BMI of >40 kg/m2 is morbid
obesity. WHO suggests that a BMI over 25 is respon-
sible for 64% of male and 77% of female cases of
noninsulin-dependent diabetes mellitus (NIDDM). A
BMI below 18.5 is considered underweight. BMI mea-
surement is a very quick and simple way of assessing
malnutrition, but it does not reflect differences in frame
size.4 Table  17.1 summarizes the BMI value and its
corresponding classification.
17.1.3 Degrees of Malnutrition
and Treatment
17.1.3.1 Protein–Energy Malnutrition
A lack of intake of protein and energy causes loss of
both body mass and adipose tissue, although both may
not be necessarily found in a given individual. This
disorder is found in conditions wherein the socioeco-
nomic factors limit the quantity and quality of food.
The problem is heightened when energy intake is
insufficient so that the dietary proteins are utilized as
fuel rather than for the synthesis of body protein.5
Protein–energy malnutrition may occur in adults. The
most observable change is the loss of subcutaneous fat
from prominent deposits. The skin turns dry and rough
and loses its elasticity. Follicles become more promi-
nent. Follicular hyperkeratosis ensues, giving the skin
texture similar to a nutmeg grater. Brown pigmentation
E. B. Handog and T. C. Crisostomo
develops around the oral, orbital, and malar areas.
Patients with acne observe that this condition disappears,
yet lesions resume when nutrition is restored. Hair
growth is slow. It falls out prematurely and turns gray.
Nail growth is impeded. Bacterial infections such as
furunculosis, impetigo, skin ulcers, and sores are com-
mon due to associated unsanitary environment.2
Malnourished children from developing countries
may present with either of two conditions. The first is
marasmus, which in Greek means “wasting.” It is a pro-
longed deficiency of protein and calories, and is a major
contributing factor to mortality in infancy and early
childhood. It is usually caused by weaning problems
due to disease, poor hygiene, poverty, and cultural fac-
tors. Symptoms include dry, wrinkled loose skin due to
a marked loss of subcutaneous fat. The loss of fat pads
in the buccal area brings about the “monkey facies.”
Hair is thin, grows slowly, and easily falls out or breaks.
Nails may be fissured and nail growth is retarded. There
is no edema or dermatosis in this condition.2
The second condition is kwashiorkor, which in Ghana
language literally means “the first child gets when the
second is on the way.” It is a severe deficiency in protein,
usually occurring when the child is weaned onto a starchy
diet. Changes in pigmentation may be found around the
perioral area, the lower extremities, and around previous
wounds, ulcerations, and other injuries. In children with
fair skin, depigmentation starts with blanchable erythema
evolving into small, dusky purple patches that do not
blanch. In children with dark-skinned complexion,
depigmentation is more obvious, evolving into waxy
“enamel paint” spots on the trunk, diaper area, trochant-
ers, knees, and ankles. The lesions have sharp edges and
are elevated. Large areas of erosions that resemble “flaky
paint” or “crazy paving” are seen in severe cases. Linear
fissures can be found around the pinna, popliteal, antecu-
bital and axillary areas, interdigits, in the center of the
lips, and at the edge of the foreskin of the penile shaft.
These lesions are brought about by intermittent tension.
The skin is easily damaged; therefore, care must be
taken to avoid acute trauma and chronic pressure inju-
ries in bedridden children. Hair findings show the “flag
sign,” wherein there are alternating bands of dark and
pale hair. These bands reflect the alternating periods of
adequate and inadequate nutrition.2
Protein–energy malnutrition rarely occurs alone.
Concomitant nutritional deficiencies commonly seen
include deficits in folic acid, thiamine, riboflavin, nico-
tinic acid, pyridoxine, and vitamin A.
17  Nutrition, Vitamins, and Supplements 189

17.1.3.2 Obesity coined by Funk in the early 1900s which came from

two words: “amine,” which was the chemical that he
Malnutrition may also be due to excess in nutrients. was able to isolate from rice polishings, which he
Obesity may be seen as an interplay of environmental believed to preserve life, “vita.” He further went on to
and genetic factors. It is a condition wherein there is an define avitaminosis and deficiency disorders.7
excess of adipose tissue. This term is not analogous to
being overweight, for the reason that muscular indi-
viduals may exceed their ideal weight for height with-
out having an excess of adipose tissue. Aside from the 17.2.2 Recommended Dietary Allowance
BMI, we may measure adiposity by skin-fold thickness
(anthropometry), underwater weighing (densitometry),
The recommended dietary allowances or recommended
or getting the waist-to-hip ratio, wherein abnormal val-
daily allowances (RDA) are based on the evaluation of
ues would be >0.9 for women and >1.0 in men.6
the Food and Nutrition Board of the National Research
Body fat and fat distribution are affected by gender,
Council on the correct amount of essential nutrients
age, degree of physical activity, and a number of drugs
sufficient to meet the needs of a healthy individual. It
such as phenothiazines, antidepressants, antiepileptics,
is defined as the average daily dietary intake level that
and steroids. Body fat increases with age in both men
is sufficient to meet the nutrient requirements of nearly
and women.6
all healthy individuals of a specific sex, age, life stage,
The WHO reports that obesity in school children is
or physiologic condition (pregnancy or lactation).3
estimated at 10% in industrialized countries such as
RDAs are based on many types of evidence on nutri-
Japan, US, and some countries in the European conti-
ents, including replacement studies in persons with
nent. Overweight and obesity during childhood lead to
deficiency, biochemical assessments of function in
an increased risk of becoming overweight and obese in
relation to intake, epidemiologic studies, and extrapo-
adulthood, as well as an increased prevalence of obe-
lation of data from animal experiments. The objective
sity-related disorders.1
of these recommendations is to provide a safety factor
In adults, the prevalence of obesity is 10–25% in
appropriate to each nutrient by exceeding the actual
most countries of Western Europe, 20–25% in some
requirements of most individuals.8
countries in the Americas, up to 40% in some coun-
Water-soluble vitamins include the vitamin B-complex
tries in Eastern Europe, and more than 50% in some
and vitamin C (Tables 17.2 and 17.3). Fat-soluble vitamins
countries in the Western Pacific.1
include vitamins A, D, E, and K (Tables 17.4 and 17.5). A
With obesity, there is an increased risk of hyperten-
balanced diet will ensure an individual of both water-solu-
sion, cardiovascular disease, diabetes, gall bladder
ble and fat-soluble vitamins (Tables 17.6 and 17.7).
­disease, sleep apnea, and osteoarthritis. Cutaneous
man­ifestations associated with obesity include inter-
trigo due to friction between excessive fat folds, striae,
and acrochordons. Acanthosis nigricans is character-
17.2.3 Hypervitaminosis/
ized by a gray–brown velvety plaque found on the
face, inner thighs, antecubital and popliteal fossae, Hypovitaminosis
umbilicus, and perianal area.2
17.2.3.1 Vitamin A

17.2 Vitamins Vitamin A consists of all naturally occurring active

17.2.1 Definition
Vitamins are organic compounds that cannot be syn-
thesized by humans and therefore must be ingested to
prevent metabolic disorders. The term “vitamine” was
forms, which include retinol and retinyl esters, and the
carotenoids. This fat-soluble vitamin is essential for
normal epithelial proliferation, keratinization, and the
transduction of visual images by the retina.9
The major causes of vitamin A deficiency are inad-
equate diet, malabsorption of fat and liver disease. It
can be assessed by taking the serum retinol level.2
190 E. B. Handog and T. C. Crisostomo

Table  17.2  Recommended dietary allowances (RDA) of water-soluble vitamins for children (modified from dietary reference
intakes of the Food and Nutrition Board of the National Research Council)
Life-stage Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B6 Vitamin B12 Folate Vitamin C Vitamin
group (thiamin) (riboflavin) (niacin) (pantothenic (pyridoxine) (cyanocobala- mg/ (ascorbic H (biotin)
mg/day mg/day mg/day acid) mg/day mg/day min) mg/day day acid) mg/day mg/day
Infants
0–6 months 0.2 0.3  2 1.7 0.1 0.4   65 40  5
7–12 months 0.3 0.4  4 1.8 0.3 0.5   80 50  6
Children
1–3 years 0.5 0.5  6 2 0.5 0.9 150 15  8
4–6 years 0.6 0.6  8 3 0.6 1.2 200 25 12
Males
9–13 years 0.9 0.9 12 4 1.0 1.8 300 45 20
14–18 years 1.2 1.3 16 5 1.3 2.4 400 75 25
Females
9–13 years 0.9 0.9 12 4 1.0 1.8 300 45 20
14–18 years 1.0 1.0 14 5 1.2 2.4 400 65 25

Vitamin A deficiency may have ocular manifesta-
tions such as night blindness and diseases of the con-
junctiva, sclera and cornea, such as xerosis conjunctivae,
Bitot spots, xerosis corneae, and keratomalacia.
Cutaneous manifestations include dermomalacia where
in the large areas of the body have dry, wrinkled skin
covered with fine scales. Phrynoderma or “toad skin”
is a type of follicular hyperkeratosis which is also seen
in vitamin A deficiency. Lesions may present as flesh-
colored or hyperpigmented filiform, conical or large
papules with large horny centers usually seen on the
elbows and knees.2
WHO has strategies for controlling vitamin A defi-
ciency which aim to provide an adequate intake through

Table 17.3  RDA of water-soluble vitamins for adults (modified from dietary reference intakes of the Food and Nutrition Board of
the National Research Council)
Life-stage Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B6 Vitamin B12 Folate Vitamin C Vitamin H
group (thiamin) (riboflavin) (niacin) mg/ (pantothenic (pyridoxine) (cyanocobala- mg/day (ascorbic (biotin)
mg/day mg/day day acid) mg/day mg/day min) mg/day acid) mg/day mg/day
Males
19–30 years 1.2 1.3 16 5 1.3 2.4 400   90 30
31–50 years 1.2 1.3 16 5 1.3 2.4 400   90 30
50–70 years 1.2 1.3 16 5 1.7 2.4 400   90 30
>70 years 1.2 1.3 16 5 1.7 2.4 400   90 30
Females
19–30 years 1.1 1.1 14 5 1.3 2.4 400   75 30
31–50 years 1.1 1.1 14 5 1.3 2.4 400   75 30
50–70 years 1.1 1.1 14 5 1.5 2.4 400   75 30
>70 years 1.1 1.1 14 5 1.5 2.4 400   75 30
Pregnancy
<18 years 1.4 1.4 18 6 1.9 2.6 600   80 30
19–30 years 1.4 1.4 18 6 1.9 2.6 600   85 30
31–50 years 1.4 1.4 18 6 1.9 2.6 600   85 30
Lactation
<18 years 1.4 1.4 17 7 2.0 2.8 500 115 35
19–30 years 1.4 1.4 17 7 2.0 2.8 500 120 35
31–50 years 1.4 1.4 17 7 2.0 2.8 500 120 35
17  Nutrition, Vitamins, and Supplements 191

Table 17.4  RDA of fat-soluble vitamins for children (modified Table  17.6  Common food sources of water-soluble vitamins
from dietary reference intakes of the Food and Nutrition Board (modified from dietary reference intakes of the Food and
of the National Research Council) Nutrition Board of the National Research Council)
Life-stage Vitamin A Vitamin D Vitamin E Vitamin K Vitamin Food Source
group (mg/day) (mg/day) (mg/day) (mg/day)
Vitamin B1 Enriched, fortified, or whole-grain
Infants (thiamin) products; bread and bread
0–6 months 400 5  4 2.0 products, mixed foods whose
7–12 months 500 5  5 2.5 main ingredient is grain, and
ready-to-eat cereals
Children
1–3 years 300 5  6 30 Vitamin B2 Organ meats, milk, bread products,
4–6 years 400 5  7 55 (riboflavin) and fortified cereals

Males Vitamin B3 Meat, fish, poultry, enriched and

(niacin) whole-grain breads and bread
9–13 years 600 5 11 60
products, fortified ready-to-eat
14–18 years 900 5 15 75
cereals
Females
Vitamin B5 Chicken, beef, potatoes, oats,
9–13 years 600 5 11 60 (pantothenic acid) cereals, tomato products, liver,
14–18 years 700 5 15 75 kidney, yeast, egg yolk, broccoli,
whole grains
Vitamin B6 Fortified cereals, organ meats,
(pyridoxine) fortified soy-based meat
a combination of dietary improvement including breast- substitutes
feeding, supplementation, and food fortification.1 Vitamin B12 Fortified cereals, meat, fish, poultry
Acute vitamin A intoxication may occur after inges- (cyanocobalamin)
tion of 500,000 IU or greater by adults or proportional Folate Enriched cereal grains, dark leafy
amounts by children (over 100 times the RDA). Symptoms vegetables, enriched and
whole-grain breads and bread
products, fortified ready-to-eat
cereals
Table  17.5  RDA of fat-soluble vitamins for adults (modified Vitamin C Citrus fruits, tomatoes, tomato juice,
from dietary reference intakes of the Food and Nutrition Board (ascorbic acid) potatoes, brussels sprouts,
of the National Research Council) cauliflower, broccoli, strawber-
Life-stage Vitamin A Vitamin D Vitamin E Vitamin K ries, cabbage, and spinach
group (mg/day) (mg/day) (mg/day) (mg/day) Vitamin H (biotin) Liver and smaller amounts in fruits
Males and meats
19–30 years 900  5 15 120
31–50 years 900  5 15 120
50–70 years 900 10 15 120 Table  17.7  Common food sources of fat-soluble vitamins
>70 years 900 15 15 120 (modified from dietary reference intakes of the Food and
Females Nutrition Board of the National Research Council)
19–30 years 700  5 15   90 Vitamin Food Source
31–50 years 700  5 15   90 Vitamin A Liver, dairy products, fish, darkly colored
50–70 years 700 10 15   90 fruits, and leafy vegetables
>70 years 700 15 15   90
Vitamin D Fish liver oils, flesh of fatty fish, liver and fat
Pregnancy from seals and polar bears, eggs from hens
<18 years 750  5 15   75 that have been fed vitamin D, fortified milk
19–30 years 770  5 15   90 products, and fortified cereals
31–50 years 770  5 15   90 Vitamin E Vegetable oils, unprocessed cereal grains, nuts,
Lactation fruits, vegetables, meats
<18 years 1,200  5 19   75 Vitamin K Green vegetables (collards, spinach, salad
19–30 years 1,300  5 19   90 greens, broccoli), brussels sprouts,
31–50 years 1,300  5 19   90 cabbage, plant oils, and margarine
192
include skin desquamation, abdominal pain, nausea,
vomiting, and muscle weakness. Chronic intoxication
occurs after intake of 50,000 IU/day for several months.
Symptoms include desquamation, pruritus, facial derma-
titis, dryness of the mucous membranes, erythema, brittle
nails, cheilitis, and alopecia, which are reversible upon
cessation of overdosing.2
17.2.3.2 B Vitamins
Vitamin B1 (thiamine) deficiency may present as
either of two conditions. Beri-beri is commonly found
in Asians and presents with symptoms of fatigue,
peripheral neuropathy, polyneuritis, heart failure,
edema, angular stomatitis, and glossitis. Wernicke-
Korsakoff syndrome presents as thiamine deficiency
with symptoms of apathy, loss of memory, and con-
fabulations. A deficiency in this vitamin may be asso-
ciated with other B-complex vitamin and folate
deficiency.2
A deficiency in riboflavin or vitamin B2 may result
in glossitis, angular stomatitis or perlèche, cheilosis of
vertical fissures of the lip, and lesions resembling seb-
orrheic dermatitis distributed along the nasolabial
folds, cheeks, forehead, and postauricular area.2
Pellagra is the deficiency in vitamin B3 or niacin
and is characterized by the triad of dermatitis, diar-
rhea, and dementia. Cutaneous symptoms are found
on areas that are exposed to the sun or localized pres-
sure. It begins as erythema of the dorsal aspect of both
hands with associated pruritius, burning, and edema.
Vesicles may appear, coalesce to form bullae then
burst. Dry brown scales may form. These scales are
thicker and larger on the face, and may evolve into
pustules. These lesions may become hard, rough,
cracked, blackish, and brittle. Painful fissures develop
in the palms and digits. In severe cases, the skin is
covered with scales and blackish crusts due to hemor-
rhages. Lesions on the upper extremities may follow a
“glove” or “gauntlet” distribution, while lesions on
the lower extremities do not exceed the proximal mal-
leoli, giving a “boot” distribution. On the face, lesions
are usually found on the nose, forehead, cheeks, and
chin giving a “butterfly” appearance. Lesions on the
neck seen as a broad band encircling the neck are
known as the Casal’s necklace.2
There have been no reported cutaneous changes in
humans deficient in vitamin B5 or pantothenic acid.2
E. B. Handog and T. C. Crisostomo
Vitamin B6 (Pyridoxine) deficiency reveals sebor-
rhea-like lesions on the face, scalp, neck, shoulders,
buttocks, and perineum. Similar to riboflavin defi-
ciency, one may also find angular stomatitis, cheilo-
sis, and glossitis. Other symptoms include anorexia,
nausea, vomiting, and neurologic findings such as
hyperesthesia, ascending paresthesia, altered vibra-
tion and position sense, and hypoactive deep tendon
reflexes.2
Cutaneous findings of a deficiency in cyanocobala-
min or vitamin B12 include generalized hyperpig-
mented macules and patches found on flexural areas,
palmar creases, soles, knuckles, and oral mucosa. Nail
plates may also develop longitudinal, hyperpigmented
streaks. Individuals with this deficiency may also pres-
ent with graying of hair and a beefy red tongue.2
Cutaneous changes due to a deficiency in folic acid
are rare but it has been reported to cause scaly papules
and plaques on the face, trunk and extensor aspects of
the extremities, stomatitis, and glossitis. Megaloblastic
anemia is found in individuals deficient in folic acid.
When treating this deficiency, it is important to check
for a concomitant deficiency in vitamin B12. If this is
overlooked, treatment with folate supplements will
improve the anemia, but can progress to neurologic
damage due to the cyanocobalamin deficiency.2
Biotin, also known as vitamin H, is found in the
diet, but is also synthesized by bacteria found in the
human intestines. A deficiency in this vitamin may
either be acquired or inborn. An acquired deficiency is
commonly caused by an excessive intake of the avidin-
containing egg whites, which blocks the absorption of
biotin. Symptoms include fine desquamation on the
extremities, periorificial eczema, alopecia, pallor and
atrophy of the tongue. Inborn deficiencies of the
enzymes holocarboxylase synthetase or biotinidase
may cause biotin deficiency due to malabsorption and
ineffective metabolism. Symptoms include a general-
ized erythematous scaly rash similar to ichthyosis or
seborrheic dermatitis, alopecia of the scalp, eyebrows
and eyelashes, absence of lanugo hair. Corneal ulcers
and keratoconjunctivitis may develop.2
17.2.3.3 Vitamin C
Ascorbic acid, ascorbate, or vitamin C is a water-
soluble vitamin most commonly found in citrus fruits
and green vegetables. It is critical in wound healing
17  Nutrition, Vitamins, and Supplements
due to its important role in collagen synthesis. It also
has a role in regenerating active vitamin E and increases
cholesterol excretion.10
Scurvy or the deficiency in the intake of vitamin C
begins with symptoms of follicular hyperkeratosis and
the appearance of corkscrew hairs. Perifollicular pur-
pura then ensues, seen commonly on the lower extrem-
ities. There is poor wound healing and old scars may
break down. Other associated symptoms include edema
of the lower extremities and gingival necrosis. Marginal
deficiencies increase the risk of cancer, cardiovascular
disease, hypertension, decreased immunity, diabetes
and cataracts.2
An increased intake of vitamin C may cause dose-
dependent symptoms. An intake of greater than 1 g/day
may cause an increase in oxalate excretion. Those tak-
ing 2 g/day may produce kidney stones in some cases.
Doses greater than 2 g/day may cause diarrhea, nau-
sea, stomach cramping, excess urination, and skin
rashes.11
17.2.3.4 Vitamin D
Vitamin D is a steroid hormone which is important in
calcium regulation and tissue growth and differentiation,
including the skin. It comprises a number of related mol-
ecules, wherein only a few can be ingested, namely,
vitamin D2 (ergocalciferol) and vitamin D3 (cholecalcif-
erol). A deficiency of this vitamin may cause an abnor-
mality in the absorption and transport of calcium into
the bone. An acquired deficiency of this vitamin is
caused by inadequate diet, malabsorption, or a decreased
exposure to ultraviolet B (UVB) radiation. Symptoms
include osteomalacia, muscle weakness, and alopecia.
Chronic ingestion of excessive amounts of vitamin D
(50,000–100,000 U/day) may produce hypervitaminosis
D with symptoms such as weakness, lethargy, headache,
nausea and polyuria, and metastatic calcification.12
17.2.3.5 Vitamin E
Vitamin E is a group of eight fat-soluble compounds,
with a-tocopherol as the only active form found in
humans. Deficiency of this vitamin is rare and occurs
in individuals with chronic liver disease and fat mal-
absorption syndromes such as celiac disease and ­cystic
fibrosis. Symptoms include nerve damage, lethargy,
193
apathy, inability to concentrate, staggering gait, low
thyroid hormone levels, decrease immune response,
and anemia. Marginal deficiency in vitamin E is more
common and is associated with an increased risk of
cardiovascular disease and cancer. Vitamin E toxicity
will cause adverse effects such as increased risk of
bleeding, diarrhea, abdominal pain, fatigue, reduced
immunity, and transiently raised blood pressure.13
17.2.3.6 Vitamin K
Vitamin K deficiency causes hemorrhage due to an
abnormal coagulation. This may occur in any part of
the body, but this may manifest cutaneously as pur-
pura. The confirmatory test that can be requested is a
prothrombin time measurement.2
17.3 Supplements
17.3.1 Antioxidants
Two types of chemical reactions occur widely in
nature, namely oxidation and reduction. Oxidation
involves the loss of electrons, while reduction is the
gain of electrons. Oxidation and reduction reactions
always occur together. Highly reactive molecules can
oxidize molecules that were formerly stable causing
them to become unstable species, such as free radicals.
A free radical is defined as a chemical with an unpaired
electron that can be neutral, positively charged, or neg-
atively charged. Therefore, without antioxidants, a
single free radical can cause damage to numerous mol-
ecules. However, despite the actions of antioxidant
nutrients, some oxidative damage will still occur, and
accumulation of this damage throughout life is believed
to be a major factor in aging and disease.13
An antioxidant is any substance that significantly
decreases the adverse effects of reactive species, such
as reactive oxygen and nitrogen species, on the normal
physiological function in humans.14
Human cells, most especially those found in the
epidermis, possess an efficient antioxidant system,
including enzymatic and nonenzymatic reductants,
that deactivate reactive oxygen species (ROS) and
reduce oxidized molecules such as lipid peroxides.14
194 E. B. Handog and T. C. Crisostomo

Fig. 17.1  Interacting network Membrane ROO° ROOH

of nonenzymatic endogenous Radicals
PUFAs RO° ROH
antioxidants

-Tocopherol Vitamin E -Tocopheroxyl−

-Tocolniend
Cycle -Tocolnienoxyl−

Dehydro- Vitamin C Ascorbale

ascorbale Cycle

Dihydrolipoic acid Thiol Alpha-lipoic acid

Cycle
Reduced Giutalnione Oxidised Giutalnione
(GSH) (GSSG)

NAD(P)*H* GSH Reductase NAD(P)H

17.3.1.1 Endogenous Antioxidants of NF-B activation and inhibition of tyrosinase activity

Endogenous antioxidants are those found inherently in
the epidermis, using either enzymatic and nonenzy-
matic reductants deactivating the ROS and reducing
oxidized molecules. These include tocopherols (vita-
min E) and ascorbic acid (vitamin C).14
The main advantage of endogenous antioxidants is
their low toxicity potential since they are innate com-
ponents of the organism (Fig. 17.1).14
Alpha-Lipoic Acid
Lipoic acid is a very powerful antioxidant due to its being
both aqueous and lipid-soluble, its anti-inflammatory
activity, and its easy penetrability in the skin when topi-
cally applied due to it being a small, stable molecule.15
Its mechanism of action of preventing UV-induced
photo-oxidative damage is due to the down-modulation
by chelating the copper ions.
Coenzyme Q10
Coenzyme Q10 (CoQ10) is a powerful free radical inhib-
itor that acts on hindering lipid peroxidases from forming
plasma membranes. It also has a very important role in
cellular energy production and works in  the mitochon-
drial adenosine triphosphate (ATP) energy-producing
pathway of the cell. It may also play a role in preventing
oxidative stress-induced cellular apoptosis since it is in
the mitochondria where the final apoptotic signal is dis-
patched. It is reported that oral CoQ10 improves cellular
energy production while topical CoQ10 is shown to
inhibit collagenase expression in UV-irradiated human
fibroblasts.15 It can regenerate reduced tocopherol 3 to 30
times greater than tocopherol within membranes.
17  Nutrition, Vitamins, and Supplements 195

Glutathione naturally occurring organic acids that are often referred

The glutathione system, also called the “master anti-
oxidant,” is our first line of defense against peroxida-
tion in the body. The liver contains the greatest amount
while the heart and muscles show lower quantities. It is
found both in the epidermis and the dermis, particu-
larly within the fibroblasts. Glutathione peroxidase is a
major detoxifier of hydrogen peroxide in the cyto-
plasm, along with catalase.10
17.3.1.2 Exogenous Antioxidants
to as fruit acids because they are found mostly in citrus
fruits, apples, and grapes (Table 17.8).
Anapsos
Anapsos comes form the tropical fern P. leucotomos,
which has in  vitro antioxidant and immunomodulating
properties. It has been used in the treatment of psoriasis
and vitiligo. It is shown to inhibit lipid peroxidation, ROS
formation, phototoxicity, and acute sunburn in humans
in vivo following acute ultraviolet (UV) light exposure.14

An immense inflammation can overpower the antioxi- Isoflavone Genistein

dant defense system of the skin and lead to tissue
destruction, thus the use of exogenous antioxidants, Genistein is a soy derivative which has been reported to
both topical and systemic. These include a-hydroxy have antioxidant, anticarcinogenesis, particularly breast
acids (AHAs) and the various plant antioxidants such and prostate cancers, and estrogen-like properties, thus
as anapsos, silymarin, soybeans, and tea. They are improving the skin condition of postmenopausal
women. Its action is in the protection of oxidative and
Table 17.8  Common food sources of exogenous antioxidants
Antioxidant Food Source
photodynamically damaged DNA and downregulation
of UVB-activated signal transduction cascade.16
Carotenoids
Beta-carotene Carrots, various fruits
Lutein, zeaxanthin Kale, collards, spinach, corn, eggs,
citrus Procyanidins
Lycopene Tomatoes and processed tomato
products The seeds of red grapes are the richest source of pro-
Flavonoids cyanidins. Similar to polyphenols, it has antioxidant
Anthocyanidins Berries, cherries, red grapes properties and is shown to inhibit lipid peroxidation.15
Flavanols (catechins, Tea, cocoa, chocolate, apples,
epicatechins, grapes
procyanidins)
Flavanones Citrus foods
Flavonols Onions, apples, tea, broccoli 17.3.1.3 Botanical Antioxidants
Proanthocyanidins Cranberries, cocoa, apples,
strawberries, grapes, wine,
All plants protect themselves from oxidation following
peanuts, cinnamon
UV exposure in the outdoor environment. They work
Isothiocyanates by quenching singlet oxygen and ROS. Most of these
Sulforaphane Cauliflower, broccoli, broccoli
botanical antioxidants can be classified as flavonoids,
sprouts, cabbage, kale,
horseradish carotenoids, and polyphenols.17
Phenols
Caffeic acid, ferulic Apples, pears, citrus fruits, some
acid vegetables Chamomile
Sulfides/thiols
Diallyl sulfide, allyl Garlic, onions, leeks, scallions Chamomile or Matricaria recutita inhibits UVB-
methyl trisulfide induced pigmentation by avoiding ET-1-induced DNA
Dithiolthiones Cruciferous vegetables (broccoli, synthesis. Its main ingredient is a-bisabolol. It has
cabbage, bok choy, collards) antiallergic, antineoplastic, and analgesic properties.
Whole grains Cereal grains Studies have shown that it has antimicrobial effects
196
against Staphylococcus sp. and Candida sp. It has also
been shown to promote wound healing and exhibit
anti-inflammatory activity.18
Curcumin
Curcumin is a polyphenol antioxidant extracted from
the tumeric root. Its effect has been shown to be greater
than that of vitamin E. Tetrahydrocurcumin is added to
cosmetic products and functions as an antioxidant. It
prevents the lipids from the moisturizer from becom-
ing rancid.17
Echinacea
Echinacea contains polysaccharides and glycoproteins,
flavonoids, caffeic and ferulic acid derivatives, volatile
oils, alkamides, polyenes, and pyrrolizine alkaloids
which stimulate immunity and protect collagen.18
Garlic
Garlic has potent antimicrobial and antioxidant activ-
ity primarily due to alkylcysteine sulfoxides, specifi-
cally alliin. Other components include polysaccharides,
saponins, and vitamins A, B2, and C. It also stimulates
immunity and has anti-yeast activity.18
Gingko Biloba
Gingko biloba contains unique polyphenols such as
terpenoids, flavonoids, and flavonol glycosides that
have anti-inflammatory effects that have been linked to
anti-radical and anti-lipoperoxidant effects in experi-
mental fibroblast models. There is increased collagen
and extracellular fibronectin as demonstrated by radio-
isotope assay.17
Green Tea
Polyphenols can be found in tea (Camellia sinensis)
and is produced during the tea leaf processing. Green
tea contains predominantly monomeric polyphenol
catechins, whereas black tea contains polymeric
E. B. Handog and T. C. Crisostomo
polyphenols. In humans, polyphenols has been shown
to inhibit UV-induced erythema and inflammation.14
Licorice
The roots of the licorice plant contain saponosides
(glycyrrhizine) which serve as an emollient, flavonoids
which are antioxidants, and glycyrrhetinic and gly-
cyrrhizinic acids which have anti-inflammatory and
wound healing effects. Glabridin is the main ingredi-
ent of licorice extract. It inhibits tyrosinase activity
in vitro without affecting DNA synthesis.
Pycnogenol
Pycnogenol is derived from the bark of the French
maritime pine (Pinus pinaster). It is several times more
powerful than vitamins C and E. It recycles vitamin C,
regenerates vitamin E, and increases the endogenous
antioxidant enzyme system. Its active ingredient is
proanthocyanidin.17
Resveratrol
Resveratrol is a phytoalexin found in grape seeds and
Mulberry tree (Morus alba). It has anti-inflammatory
effects and inhibits cyclooxygenase and hydroperoxi-
dase functions.19
Silymarin
Silymarin comes from the extract of the thistle Silybum
marianum and has been used in the treatment of liver
diseases due to its powerful antioxidant properties. It
has been reported to inhibit the actions of UV radiation
on living cells, and thus is a potential topical reagent in
preventing and treating photodamage.14
Soybean
Soybean milk extracts has been shown to reduce the
melanin deposition within the swine epidermis. It pre-
vents UVB-induced pigmentation in  vivo, similar to
soybean trypsin inhibitor STI.20
Table 17.9  RDA of minerals for children (modified from dietary reference intakes of the Food and Nutrition Board of the National Research Council)
Life-stage Calcium Chromium Copper Fluoride Iodine Iron Magnesium Manganese Molybdenum Phosphorus Selenium Zinc
group (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day)
17  Nutrition, Vitamins, and Supplements

Infants
0−6 months 210 0.2 200 0.01 110 0.27 30 0.003 2 100 15 2
7−12 months 270 5.5 220 0.5 130 11 75 0.6 3 275 20 3
Children
1−3 years 500 11 340 0.7 90 7 80 1.2 17 460 20 3
4−8 years 800 15 440 1 90 10 130 1.5 22 500 30 5
Males
9−13 years 1,300 25 700 2 120 8 240 1.9 34 1,250 40 8
14−18 years 1,300 35 890 3 150 11 410 2.2 43 1,250 55 11
Females
9−13 years 1,300 21 700 2 120 8 240 1.6 34 1,250 40 8
14−18 years 1,300 24 890 3 150 15 360 1.6 43 1,250 55 9
197
 198

Table 17.10  RDA of minerals for adults (modified from dietary reference intakes of the Food and Nutrition Board of the National Research Council)
Life-stage Calcium Chromium Copper Fluoride Iodine Iron Magnesium Manganese Molybdenum Phosphorus Selenium Zinc
group (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day) (mg/day)
Males
19−30 years 1,000 35 900 4 150 8 400 2.3 45 700 55 11
31–50 years 1,000 35 900 4 150 8 420 2.3 45 700 55 11
50–70 years 1,200 30 900 4 150 8 420 2.3 45 700 55 11
>70 years 1,200 30 900 4 150 8 420 2.3 45 700 55 11
Females
19−30 years 1,000 25 900 3 150 18 310 1.8 45 700 55 8
31–50 years 1,000 25 900 3 150 18 320 1.8 45 700 55 8
50–70 years 1,200 20 900 3 150 8 320 1.8 45 700 55 8
>70 years 1,200 20 900 3 150 8 320 1.8 45 700 55 8
Pregnancy
£18 years 1,300 29 1,000 3 220 27 400 2.0 50 1,250 60 12
19–30 years 1,000 30 1,000 3 220 27 350 2.0 50 700 60 11
31–50 years 1,000 30 1,000 3 220 27 360 2.0 50 700 60 11
Lactation
£18 years 1,300 44 1,300 3 290 10 360 2.6 50 1,250 70 13
19–30 years 1,000 45 1,300 3 290 9 310 2.6 50 700 70 12
31−50 years 1,000 45 1,300 3 290 9 320 2.6 50 700 70 12
E. B. Handog and T. C. Crisostomo
17  Nutrition, Vitamins, and Supplements
Table 17.11  Common food sources of minerals
Mineral Food Source
Calcium Almonds, figs, beans, carrots, pecans,
raisins, brown rice, apricots, garlic,
dates, spinach, sesame seeds, brazil
nuts, cashews, papaya, avocados,
celery
Chromium Brewer’s yeast, clams, cheese, corn oil,
whole grains
Copper Soy beans, brazil nuts, bone meal, raisins,
legumes, seafoods, black strap molasses
Iodine Kelp, dulse, beets, celery, lettuce, irish
moss, grapes, mushrooms, oranges
Iron Kelp, raisins, figs, beets, soy beans, bananas,
asparagus, carrots, cucumbers, sunflower
seeds, parsley, grapes, watercress
Magnesium Honey, almonds, tuna, kelp, pineapple,
pecans, green vegetables
Manganese Celery, bananas, beets, egg yolks, bran,
walnuts, pineapples, asparagus, whole
grains, leafy green vegetables
Phosphorus Mushrooms, cashews, oats, beans, squash,
pecans, carrots, almonds
Potassium Spinach, apples, tomatoes, strawberries,
bananas, lemons, figs, celery, mush-
rooms, oranges, papaya, pecans, raisins,
pineapple, rice, cucumbers, brussels
sprouts
Selenium Brazil nuts, meats, tuna, plant foods
Sodium Turnips, raw milk, cheese, wheat germ,
cucumbers, beets, string beans, seafoods,
lima beans, okra, pumpkins
Sulfur Bran, cheese, eggs, cauliflower, nuts, onions,
broccoli, fish, wheat germ, cucumbers,
turnips, corn
Zinc Mushrooms, liver, seafoods, soy beans,
sunflower seeds, brewer’s yeast
17.3.2 Minerals
17.3.2.1 Recommended Dietary Allowances
The RDA of minerals differ according to life-stage
group (Tables 17.9 and 17.10). These mineral nutrients
can be acquired through a balanced intake of the fol-
lowing common food sources (Table 17.11).
199
17.3.2.2 Calcium
In an adult, there is approximately 1–2 kg of calcium
present in the body, 99% of which is found in the skel-
etal system. RDA ranges from 1,000 to 1,200 mg/day.
However, some individuals increase their oral supple-
mentation to 1,500–2,000 mg/day to prevent osteopo-
rosis. A feedback mechanism exists to regulate
hormonal regulation of intestinal absorption of cal-
cium, resulting in an almost constant daily net calcium
absorption of approximately 200–400 mg/day.12
An inadequate intake of calcium during growth may
increase the risk of osteoporosis later in life. Osteoporosis
is defined as a reduction of bone mass or density, char-
acterized by a decrease in bone strength. In taking cal-
cium supplements, it should be taken in doses <600 mg
at a time, as the calcium absorption fraction decreases
at higher doses. Calcium supplements should be com-
puted based on the elemental calcium content, and not
the weight of the calcium salt. Calcium carbonate is
best taken with food since it requires acid for solubility.
Calcium citrate can be taken at any time. Although side
effects from calcium supplements are rare, individuals
with a history of kidney stones should have a 24-h urine
calcium determination before starting calcium to avoid
hypercalciuria.12
17.3.2.3 Copper
Copper plays an integral role in iron metabolism, mela-
nin synthesis, and central nervous system function.
Deficiency of this mineral is rare, although it may be
found in premature infants who are fed mild diets and in
infants with malabsorption. Patients with malabsorptive
diseases and nephritic syndrome and in patients treated
for Wilson’s disease with chronic high doses of oral zinc,
which can interfere with copper absorption, may acquire
copper deficiency anemia. Menkes kinky hair syndrome,
a cross-linked metabolic disease of copper metabolism
presents with symptoms such as mental retardation,
hypocupremia, and decreased circulating ceruloplasmin.
Children diagnosed with this disease often die within 5
years due to dissecting aneurysms or cardiac rupture.11
Copper deficiency is diagnosed by a finding of low
serum levels of copper (<65 mg/dL) and low cerulo-
plasmin levels (<18 mg/dL).11
200
Copper toxicity can, in severe cases, cause kidney
failure, liver failure, and coma. In Wilson’s disease,
mutations in the copper-transporting ATP7B gene lead
to accumulation of copper in the liver and brain.
However, low blood levels of copper are detected due
to decreased ceruloplasmin.11
17.3.2.4 Iron
Chronic iron deficiency may manifest as anemia, ­glossitis,
cheilosis, koilonychia, and hair loss. Hemosiderosis or
chronic excess intake of iron would cause a bronze pig-
mentation of the skin, cirrhosis of the liver, diabetes mel-
litus, cardiomyopathy, and an increased risk in porphyria
cutanea tarda.2
17.3.2.5 Selenium
The mineral selenium is necessary for the function of
glutathione peroxidase, an antioxidant enzyme. A defi-
ciency in selenium causes cardiomyopathy, muscle
pain and weakness, nail changes similar to Terry’s
nails (found in patients with hepatic cirrhosis), dys-
chromotrichia, and macrocytosis. Selenium poisoning
can occur after ingestion of water containing large
amounts of the metal. Acute selenium intoxication
may cause cutaneous findings such as alopecia, parony-
chia, possible nail loss, and reddish pigmentation of
the nails, hair, and teeth.2
17.3.2.6 Zinc
Zinc is essential for the formation and function of the
immune system. It plays a role in the sense of taste and
in wound healing.
Acrodermatitis enterohepatica is an autosomal
recessive disease that may cause zinc deficiency due to
a defect in zinc absorption. The initial manifestations
are usually seen when an infant is weaned from human
to cow’s milk. Hallmark features include dermatitis,
diarrhea, and alopecia.21
Toxicity may be caused by inhalation, oral inges-
tion, or intravenous administration. Inhalation of zinc
oxide fumes by welders leads to a condition called
metal-fume fever or brass chills, with symptoms such
as fever, chills, excessive salivation, headaches, cough,
E. B. Handog and T. C. Crisostomo
and leukocytosis. Contamination of dialysis fluids with
zinc from the adhesive on the dialysis coils or from
galvanized pipes may also cause zinc toxicity with
symptoms such as anemia, fever, and central nervous
system disturbances.22
17.4 Conclusion
An excess or deficiency in certain vitamins and miner-
als may manifest characteristically in the skin. The
“toad skin” appearance found in hypovitaminosis A,
the Casal’s necklace in hypovitaminosis B3, and the
perifollicular purpura found in scurvy are just a few
examples of distinctive dermatologic manifestations.
Armed with the knowledge of this chapter, if one is to
be presented with a patient with these symptoms, a
diagnosis is very hard to miss.
The WHO, together with the different health sec-
tors and their national programs, has come up with a
global strategy to fight malnutrition. However, preven-
tion is always superior to cure. A well-balanced diet,
along with the various supplements available in the
market, will ensure a healthy individual.
Our vision is of a world where people everywhere, at every age,
enjoy a high level of nutritional well-being, free from all forms
of hunger and malnutrition.
World Health Organization
References
  1. World Health Organization. Nutrition for Health and
Development: A global agenda for combating malnutrition.
World Health Organization; 2000. http:/whqlibdoc.who.int/
hq/2000/WHO_NHD_00.6.pdf; 2007 Accessed 11.12.07
  2. Nieves D, Goldsmith L. Cutaneous changes in nutritional
disease. In: Freedberg I, Eisen A, Wolff K, et  al, eds.
Fitzpatrick’s Dermatology in General Medicine. 6th ed.
New York: McGraw-Hill; 2003
  3. Dwyer J. Nutritional requirements and dietary assessment.
In: Kasper D, Braunwald E, Fauci A, et al, eds. Harrison’s
Principles of Internal Medicine. 16th ed. New York:
McGraw-Hill; 2005
  4. Denke M, Wilson J. Assessment of nutritional status. In:
Fauci A, Braunwald E, Isselbacher K, et al, eds. Harrison’s
Principles of Internal Medicine. 14th ed. New York:
McGraw-Hill; 1998
17  Nutrition, Vitamins, and Supplements
  5. Denke M, Wilson J. Protein and energy malnutrition. In:
Fauci A, Braunwald E, Isselbacher K, et al, eds. Harrison’s
Principles of Internal Medicine. 14th ed. New York:
McGraw-Hill; 1998
  6. Flier J, Maratos-Flier E. Obesity. In: Kasper D, Braunwald
E, Fauci A, et  al, eds. Harrison’s Principles of Internal
Medicine. 16th ed. New York: McGraw-Hill; 2005
  7. Bereston E. Vitamins in dermatology. A J Clin Nutr.
1954;2(2):133–139
  8. Denke M, Wilson J. Nutrition and nutritional requirements.
In: Fauci A, Braunwald E, Isselbacher K, et  al, eds.
Harrison’s Principles of Internal Medicine. 14th ed. New
York: McGraw-Hill; 1998
  9. Meyers D, Maloley P, Weeks D. Safety of antioxidant vita-
mins. Arch Int Med. 1996;156(9):925–935
10. Pugliese P. The skin’s antioxidant systems. Dermatol Nurs.
1998;10(6):401–416
11. Russell R. Vitamin and trace mineral deficiency and excess.
In: Kasper D, Braunwald E, Fauci A, et al, eds. Harrison’s
Principles of Internal Medicine. 16th ed. New York:
McGraw-Hill; 2005
12. Bringhurst FR, Demay M, Krane S. Bone and mineral
metabolism in health and disease. In: Kasper D, Braunwald
E, Fauci A, et  al, eds. Harrison’s Principles of Internal
Medicine. 16th ed. New York: McGraw-Hill; 2005
13. Quiroga R. Anti-aging medicine as it relates to dermatology. In:
Burgess C, ed. Cosmetic Dermatology. Berlin: Springer; 2005
201
14. Sorg O, Antille C, Saurat J. Retinoids, other topical vita-
mins, and antioxidants. In: Rigel D, Weiss R, Lim H, et al,
eds. Photoaging. New York: Marcel Dekker; 2004
15. Graf J. Anti-aging skin care ingredient technologies. In:
Burgess C, ed. Cosmetic Dermatology. Berlin: Springer; 2005
16. Wei H, Saladi R, Yuhun L, et al Isoflavone genistein: photo-
protection and clinical implications in dermatology. J Nutr.
2003;133:3811S–3819S
17. Draelos ZD. Cosmeceutical botanicals: part 1. In: Draelos
ZD, ed. Cosmeceuticals. Philadelphia: Elsevier Saunders;
2005
18. Thornfeldt C. Cosmeceutical botanicals: part 2. In: Draelos ZD,
ed. Cosmeceuticals. Philadelphia: Elsevier Saunders; 2005
19. Jang M, et al Cancer chemopreventive activity of resveratrol, a
natural product derived from grapes. Science. 1997;275(5297):
218–220
20. Paine C, et al An alternative approach to depigmentation by
soybean extracts via inhibition of the PAR-2 pathway. J
Invest Dermatol. 2001;116(4):587–595
21. Neldner K. Acrodermatitis enterohepathica and other zinc-
deficiency disorders. In: Freedberg I, Eisen A, Wolff K, et al,
eds. Fitzpatrick’s Dermatology in General Medicine. 6th ed.
New York: McGraw-Hill; 2003
22. Falchuk K. Disturbances in trace elements. In: Fauci A,
Braunwald E, Isselbacher K, et al, eds. Harrison’s Principles
of Internal Medicine. 14th ed. New York: McGraw-Hill;
1998
 Part
III
Sexually Transmitted Diseases, Viral
Diseases, and Vaccines
 Vaccines for Viral Diseases
18
Ivan D. Camacho and Brian Berman

Vaccination against viral agents has considerably alle- antigen-matched infected cells by CD8+ T lympho-
viated the burden associated with viral diseases and cytes. CD4+ T lymphocytes present antigens to B-cells
has saved millions of lives worldwide. Global vaccina- resulting in long-lasting immunity, even without anti-
tion eradicated diseases like polio and other vaccines body test results.1
have led to a significant decline in infection rates and
related complications of viral diseases. Important cri-
teria for a disease to be susceptible of global elimina-
tion are that the disease is specific to humans and that 18.1 Paramyxoviruses
there are no animal reservoirs for the infection.
Three types or viral vaccines are currently Paramyxoviruses encompass a heterogeneous family
available: of RNA viruses including measles virus, mumps virus,
parainfluenza virus, and respiratory syncytial virus.
• Attenuated live viral vaccines: these vaccines con-
Vaccination for measles, mumps, and rubella is
tain viruses that have been modified to produce an
typically given in combination in the MMR vaccine,
immune response without causing the disease. A
providing efficacious immunity with fewer immuniza-
risk of mutation to a pathogenic form is possible.
tions and to a large target population. MMR is part of
These include measles, mumps, oral polio, rubella,
the US centers for disease control and prevention
varicella, and yellow fever.
(CDC) Recommended Immunization Schedule. MMR
• Killed viral vaccines: these vaccines contain viral
is a live attenuated virus vaccine that is provided as a
particles that have been deactivated, causing an
first dose for children 12–18 months of age and a sec-
immune reaction but not an infection. These include
ond dose for children 4–6 years of age. Second doses
influenza, rabies, Japanese encephalitis, etc.
may be given to adolescents ages 11–18 (if not received
• Recombinant antigens: specific immunogenic viral
before) and adults that were either recently exposed to
proteins are subtracted to induce antibody forma-
measles, previously vaccinated with killed measles
tion against that virus. The hepatitis B vaccine is
vaccine, healthcare workers, or international travelers.
one example of this kind of vaccine.
MMR should not be administered to immunocompro-
The efficacy of a vaccine is measured by the length of mised patients, patients with allergy to neomycin, and
immunity and the percentage of vaccinated individuals pregnant women. Pregnancy should be avoided in the
displaying immunity. Vaccines stimulate the produc- following 4 weeks to an immunization.2
tion of IgG and IgA secretory antibodies by B-cell
lymphocytes and the elimination of human leukocyte

18.1.1 Measles (Rubeola)

I. D. Camacho (*)
Department of Dermatology and Cutaneous Surgery,
University of Miami, Miami, FL, USA
e-mail: icamacho2@med.miami.edu
Measles virus is a highly contagious airborne virus
that causes the typical prodrome of fever, malaise, con-
junctivitis, photophobia and cough, followed 48 h later

R. A. Norman (ed.), Preventive Dermatology, 205

DOI: 10.1007/978-1-84996-021-2_18, © Springer-Verlag London Limited 2010
206
by a characteristic maculopapular rash. About 75% of
household contacts to infected patients will develop
the disease. Measles virus is related to orthomyxovi-
ruses, which cause mumps and influenza, but is not
related to togaviruses, which cause German measles or
rubella. Since humans are the only reservoir to the
infection, global eradication of measles is feasible,
with a goal date of 2010.
The measles vaccine is produced by culturing the
Moraten virus strain in chick embryo cells. Vaccination
produces 95–99% serologic evidence of immunity after
two doses of vaccine and life-long immunity.3 The vac-
cination produces a mild noncontagious infection, with
occasional fever (15%) and a transient viral exanthem.
Encephalitis and subacute sclerosing panencephalitis
are rare adverse effects.4 In the last decade, an aero-
solized measles vaccine has been administered, provid-
ing superior immunogenicity and fewer side effects.5
18.1.2 Mumps
Live attenuated mumps vaccine produces a mild, non-
communicable infection, providing 93–97% of sero-
logical evidence of immunity after one vaccination.
However, the duration of the immunity is not clear,
with efficacy rates ranging from 75 to 95% as demon-
strated during outbreaks. Low-grade fever, mild paro-
titis, and a viral exanthema are the most common side
effects.6,7
18.1.3 Rubella (German Measles)
The rubella vaccine is grown in human diploid fibro-
blast cell cultures, producing high antibody titers in
97% of immunized individuals and lifelong protec-
tion.8 Arthritis is a common side effect in adults (40%),
followed by fever, lymphadenopathy, and a viral exan-
thema (15%).
18.2 Human Herpes Viruses
Herpesviruses comprise eight types of viruses that are
known to be pathogenic in humans.
I. D. Camacho and B. Berman
Herpes simplex virus type 1 (HSV-1) is one of the
most prevalent viruses, causing oral and perioral gingi-
vostomatitis, and the most common type of herpesvi-
rus infections. Although several topical and systemic
antiviral medications are routinely used for treatment
and prophylaxis of HSV-1 infections, no successful
vaccines have been developed. Herpes simplex virus 2
(HSV-2) is generally a cause of herpetic genital lesions,
although oral lesions have been reported. Epstein–Barr
virus (HSV-4) is associated with multiple presenta-
tions, including infectious mononucleosis, Burkitt’s
lymphoma in African children, nasopharyngeal carci-
noma in Asian populations, and oral hairy leukoplakia.
Cytomegalovirus (HSV-5) may present as sialadenop-
athy in immunocompetent individuals, birth defects in
infected fetuses, and stomatitis in immunosuppressed
patients. Human herpesvirus type 6 (HSV-6) is the
cause of exanthema subitum (roseola infantum).
Herpes virus type 8 (HSV-8 or Kaposi’s sarcoma-
related herpes virus [KSHV]) is the etiologic agent for
Kaposi’s sarcoma in patients with AIDS. HSV-8 has
also been associated with primary effusion lymphoma
and multicentric Castelman’s disease, both encoun-
tered in HIV-positive patients, as well as myeloma
multiple and lymphoproliferative disorders. From this
group of viruses, only the varicella zoster virus (VZV)
(HSV-3) has an approved vaccine available.
18.2.1 Varicella Zoster Virus (HSV-3)
VZV is an enveloped double-stranded DNA virus that
causes varicella (chicken pox) as a primary infection and
presents in the form of herpes zoster (shingles) as a reac-
tivation of a latent VZV in the sensory ganglia of previ-
ously infected individuals. VZV is an airborne pathogen
and the virus also sheds from infected vesicles.
The varicella vaccine was developed using a live-
attenuated Oka strain varicella virus, and was approved
for use in 1995, proving to be safe, effective, and
reducing the rate of infection by 60–90%.9 Varicella
vaccination is currently recommended for all people at
high risk for exposure who do not have a reliable his-
tory of varicella infection or serological evidence of
VZV infection, including healthcare workers, those
who live or work in environments where transmission
is likely (corrections, military bases, daycare centers,
colleges, etc.), women wanting to become pregnant,
18  Vaccines for Viral Diseases
and international travelers. Susceptible children may
be vaccinated after 12 months of age; susceptible indi-
viduals over 13 years of age should receive two doses,
at least 4 weeks apart. The varicella vaccine is con-
traindicated in pregnant women and pregnancy should
be avoided for 4 weeks after immunization. The live
attenuated Oka strain varicella vaccine does not effec-
tively prevent herpes zoster or postherpetic neuralgia
because it does not provide enough antigenic load to
enhance the cell-mediated immune response to VZV.
A herpes zoster live vaccine (Zostavax, Merck)
developed to reduce the manifestation of shingles and
its complications was approved by the FDA in 2006,
for use in patients over 60 years of age. The zoster vac-
cine contains 18,700–60,000 plaque-forming units of
virus and is estimated to be 14 times more potent than
the varicella vaccine. The vaccine proved to be safe
and efficacious in reducing the morbidity in immuno-
competent elderly patients. The vaccine reduced the
incidence of herpes zoster by more than 50% and
reduced pain and discomfort of affected individuals by
61.1%, compared to the placebo group. The incidence
of postherpetic neuralgia decreased by 66.5%, and the
severity and duration of pain in those who develop the
disease was 61% less than the control group.10
Erythema, swelling, and pain at the injection site are
the most common side effects. Varicella-like rashes
may also develop. The live attenuated vaccine is con-
traindicated in immunocompromised patients and is
given as a single subcutaneous dose. Further studies on
long-term effectiveness and cost-effectiveness will
provide important information for the extended use of
this vaccine.
Although the effect of the zoster vaccine on the
incidence of herpes zoster was less among individuals
over 70-years old compared to individuals with ages
ranging from 60 to 69 years (65.5 vs. 55.4%) the effect
of the vaccine on the severity of illness and the devel-
opment of postherpetic neuralgia was greater among
the older age group (66.8 vs. 65.7%).11
18.3 Human Papillomavirus
Human papillomavirus (HPV) is a nonencapsulated,
double-stranded DNA virus that affects the skin and
mucoses, and is the cause of common diseases such as
cervical neoplasia and anogenital warts. In the US,
207
over six million cases of HPV infection are docu-
mented each year, and approximately 50% of people
will carry HPV at some point in their life. Two distinct
groups have been identified: oncogenic stains and non-
oncogenic strains. Fifteen HPV types are considered
high risk for cervical cancer, types 16 and 18 being the
most common, accounting for about 70% of cervical
cancers in women. HPV types 6 and 11 cause more
than 90% of anogenital warts. Vaccination prevention
with a vaccine could be 90%.12
A HPV quadrivalent vaccine (Gardasil, Merck)
against the most prevalent high-risk HPV types was
approved by the FDA to reduce the incidence of cervi-
cal, vaginal and vulvar cancer, and anogenital warts.
This vaccine contains recombinant HPV type-specific
virus-like particles made of L1 capsid protein of types
6, 11, 16, and 18. The vaccine has proven to be suc-
cessful in the prevention of cervical cancer and genital
warts by 90% in the vaccine group when compared
with placebo.13
This vaccine is FDA-approved for use in females
9–26 years of age, and a priority review was announced
to extend the potential use to women aged 27 through
45. The vaccine should be given to patients in the
approved ages even if they are already carries of other
HPV types or have suffered HPV disease. The vaccine
is given intramuscularly, at days 1, 60, and 180, cov-
ered by most health insurance plans or may be pro-
vided through a patient assistance program. Pain,
swelling, and local erythema at the site of injection are
the most common adverse reactions.
Many experts believe that boys and young men as
well as immunosuppressed organ transplant recipients
and HIV-positive individuals may benefit from HPV
vaccination, protecting themselves against anogenital
warts, penile, and anal carcinomas. The European
Commission approved the use of this vaccine in males
ages 9–15 in an effort to decrease the incidence of
genital warts, penile and anal cancers, and reduce cer-
vical cancer in sexual contacts of these individuals.
The effectiveness of vaccination in males still needs
further investigation.
A bivalent prophylactic vaccine containing virus-
like particles of HPV 16 and 18 was also investigated,
showing good efficacy against HPV infection (91.6%),
but requires further investigation regarding its duration
of protective effects and administration standards.14
However, virus-like particle HPV vaccines failed to
improve the rate of viral clearance in women already
208
infected with HPV types 16 and 18, and should not be
used to treat the infection.15
Therapeutic vaccines in which induced enhanced
cell-mediated immunity produces lesion regression
have been studied, showing lack of efficacy in human
trials for the treatment of genital warts but some prom-
ising results in a patient with metastatic cervical can-
cer.16,17 Further trials will explore other therapeutic
vaccination strategies to include multiple HPV types
and using different antigens.18
18.4 Poxviruses
Poxviruses are an extensive family of viruses that
include molluscipoxvirus (molluscum contagiosum
virus), orthopoxvirus (vaccinia), parapoxvirus (orf),
pseudocowpox, yatapoxvirus (tanapox), and cowpox
virus, the causing agent of smallpox (variola) and the
only virus in this group with an approved vaccine.
18.4.1 Cowpox (Smallpox: Variola)
The smallpox vaccine was the first human vaccine,
created by Edward Jenner in 1796, becoming the
model for success of viral vaccines. Smallpox was
finally eradicated worldwide in 1977 and just over the
past years became a concern that it could be used for
bioterrorist purposes since it is highly contagious and
has a high mortality rate. Smallpox is an airborne and
fomite transmitted virus from active skin lesions, and
characteristically presents with a febrile prodrome fol-
lowed by a deep-seated papulo-vesicular rash with
subsequent pustule and scab formation.
The smallpox vaccine is a suspended live vaccine
derived from the vaccinia virus, similar to the cowpox
virus. Although this vaccine is not routinely adminis-
tered, it is provided to US military personnel and
reserves are maintained in case of a bioterrorist out-
break. Pustule formation, local erythema, and pain are
common adverse effects, but in the new era of smallpox
vaccination other side effects such as erythema multi-
forme-like rashes and urticarial hypersensitivity reac-
tions have been seen.19 Postvaccinal encephalomyelitis
and death have occurred. Generalized vaccinia is also
rare reported complication of smallpox vaccination.20
I. D. Camacho and B. Berman
Some physicians are not familiar with the estimated
rate of death related to smallpox vaccination (1 in
1,000,000), and vaccination contraindications such as
myocardial infarction, angina, congestive heart failure,
steroid eye drop use, and the nonemergency vaccina-
tion of those younger than age 18.21 Coadministration
of smallpox vaccine with vaccine immune-globulin
(VIG) decreases the severity of smallpox in exposed
individuals, if administered within 4 days of known
exposure.
The development of recombinant vaccines will
result in good immunity with fewer complications. A
second-generation smallpox vaccine (ACAM2000)
was approved in 2007 by the FDA for the inoculation
of people at high risk of exposure to smallpox and
could be used to protect individuals and populations
during a bioterrorist attack.
References
  1. Plotkin SA. Immunologic correlates of protection induced
by vaccination. Pediatr Infect Dis J. 2001;20(1):63–75
  2. Watson JC, Hadler SC, Dykewicz CA, et al Measles, mumps,
and rubella – vaccine use and strategies for elimination of
measles, rubella, and congenital rubella syndrome and con-
trol of mumps: recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR Recomm Rep.
1998;47(RR-8):1–57
  3. Watson JC, Pearson JA, Markowitz LE, et al An evaluation
of measles revaccination among school-entry-aged children.
Pediatrics. 1996;97(5):613–618
  4. Peltola H, Heinonen OP. Frequency of true adverse reactions
to measles-mumps-rubella vaccine. A double-blind placebo-
controlled trial in twins. Lancet. 1986;1(8487):939–942
  5. Bennett JV, Fernandez de Castro J, Valdespino-Gomez JL,
et  al Aerosolized measles and measles-rubella vaccines
induce better measles antibody booster responses than
injected vaccines: randomized trials in Mexican schoolchil-
dren. Bull World Health Organ. 2002;80(10):806–812
  6. Kim-Farley R, Bart S, Stetler H, et al Clinical mumps vac-
cine efficacy. Am J Epidemiol. 1985;121(4):593–597
  7. Hersh BS, Fine PE, Kent WK, et  al Mumps outbreak in a
highly vaccinated population. J Pediatr. 1991;119(2):187–193
  8. Chu SY, Bernier RH, Stewart JA, et al Rubella antibody per-
sistence after immunization. Sixteen-year follow-up in the
Hawaiian Islands. JAMA. 1988;259(21):3133–3136
  9. Vázquez M, LaRussa PS, Gershon AA, et al Effectiveness
over time of varicella vaccine. JAMA. 2004;291(7):851–855
10. Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the
prevention of herpes zoster. N Engl J Med. 2007;356(13):
1338–1343
11. Oxman MN, Levin MJ, Johnson GR, et  al Shingles
Prevention Study Group. A vaccine to prevent herpes zoster
18  Vaccines for Viral Diseases
and postherpetic neuralgia in older adults. N Engl J Med.
2005;352(22):2271–2284
12. Muñoz N, Bosch FX, de Sanjosé S, et  al International
Agency for Research on Cancer Multicenter Cervical Cancer
Study Group. Epidemiologic classification of human papil-
lomavirus types associated with cervical cancer. N Engl J
Med. 2003;348(6):518–527
13. Villa LL, Costa RL, Petta CA, et al Prophylactic quadriva-
lent human papillomavirus (types 6, 11, 16, and 18) L1
virus-like particle vaccine in young women: a randomised
double-blind placebo-controlled multicentre phase II effi-
cacy trial. Lancet Oncol. 2005;6(5):271–278
14. Harper DM, Franco EL, Wheeler C, et al GlaxoSmithKline
HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-
like particle vaccine in prevention of infection with human
papillomavirus types 16 and 18 in young women: a ran-
domised controlled trial. Lancet. 2004;364(9447):1757–1765
15. Hildesheim A, Herrero R, Wacholder S, et al Effect of human
papillomavirus 16/18 L1 viruslike particle vaccine among
young women with preexisting infection: a randomized trial.
JAMA. 2007;298(7):743–753
209
16. Santin AD, Bellone S, Gokden M, et  al Vaccination with
HPV-18 E7-pulsed dendritic cells in a patient with metastatic
cervical cancer. N Engl J Med. 2002;346(22):1752–1753
17. Vandepapeliere P, Barrasso R, Meijer CJ, et al Randomized
controlled trial of an adjuvanted human papillomavirus
(HPV) type 6 L2E7 vaccine: infection of external anogenital
warts with multiple HPV types and failure of therapeutic
vaccination. J Infect Dis. 2005;192(12):2099–2107
18. Urman CO, Gottlieb AB. New viral vaccines for dermato-
logic disease. J Am Acad Dermatol. 2008;58(3):361–370
19. Bessinger GT, Smith SB, Olivere JW, James BL. Benign
hypersensitivity reactions to smallpox vaccine. Int J Dermatol.
2007;46(5):460–465
20. Lewis FS, Norton SA, Bradshaw RD, et al Analysis of cases
reported as generalized vaccinia during the US military
smallpox vaccination program, December 2002 to December
2004. J Am Acad Dermatol. 2006;55(1):23–31
21. Dellavalle RP, Heilig LF, Francis SO, et al What dermatolo-
gists do not know about smallpox vaccination: results from a
worldwide electronic survey. J Invest Dermatol. 2006;126(5):
986–989
 Prevention of Sexually Transmitted
Diseases from Office to Globe 19
Kim K. Dernovsek

19.1 Introduction patients by diseases that could have been prevented by

different choices. Ultimately, I came full circle in my
own thinking, from my early venereal-disease–clinic
My interest in prevention of sexually transmitted dis-
years of “see ’em and treat ’em,” to becoming an advo-
eases (STDs) was borne out of my own frustration in
cate for primary prevention via behavior change.
managing the maladies of my dermatologic patients
Certainly there are few physicians who want to
over the last 25 years. As they suffered the conse-
manage STDs and the complexities of coinfections,
quences of what they had understood would be “safe”
reportability, contact tracking, and the coincidental
sex, via condom use, I began to contemplate that strat-
emotional overlay. It follows that the dermatologist
egy. “Safe sex” originated in the early 1980s as the
who is least interested in managing STDs would be
“buzz-word” for promotion of condom use to high-risk
most interested in encouraging prevention, lest a
population groups to prevent sexual transmission of
patient with an STD show up for a clinic appointment.
HIV/AIDS. Since condoms doubled as barrier contra-
Surely, practicing physicians everywhere would unani-
ceptive devices, it was not long before “safe sex”
mously concur that prevention of STDs would be a
became the prevention strategy of the era. With the use
goal worth achieving for patients and doctors alike.
of a simple “prophylactic” device, the condom, adults
How to really prevent the now-myriad STDs has
and teens alike could, in theory, prevent both HIV trans-
become increasingly complex with vaccines, palliative
mission and pregnancy. They could be “safe” in their
treatment, condoms, etc. Is it any wonder that there is
sexual practices. In the 1980s and 1990s, it became cus-
a grassroots movement toward a holistic approach of
tomary for physicians to caution patients to “practice
utter simplicity? Yet the generations since the 1960s
safe sex.” Then, during the late 1990s, as rising rates of
are quick to dismiss the concept of true primary pre-
chronic, viral, skin-to-skin transmitted STDs became
vention, via behavior change, labeling it as religious or
an increasingly widespread public health problem, the
political ideology or simply calling it “unrealistic.”
medical literature quietly transitioned to the more accu-
What is realistic is that the patients of this millennium
rate description, “safer” sex. Yet “safe sex,” long writ-
are concerned about their health. They want healthy
ten into classroom curricula and medical pamphlets,
skin, healthy genitalia, healthy reproductive tracts, and
was in its second-generation as the prevention strategy
they want to live. They don’t want to die of an STD.
for the general public. It was not until one of those peo-
The scientific evidence establishes the failure of the
ple got a sexually transmitted disease (STD) and ended
condom “risk reduction” approach used over the last
up as a patient that the idea that “sex” was not really
25 years and the data support that people can change
“safe” had become a reality for that patient and doctor.
their sexual behavior to healthy lifestyles, i.e., primary
I began to feel the havoc wreaked in the lives of my
prevention via “risk avoidance.” In this chapter I present
the magnitude of the problem, the failure of the past
paradigm, the current trends in sexual behavior, a
K. K. Dernovsek
directive counseling approach to patients in the office,
Departments of Dermatology and Family Medicine, University
of Colorado Health Sciences Center, Pueblo, CO, USA and a low-cost vision for health based on the world’s
e-mail: kdernovsek@gmail.com best success against HIV to date. There is no other area

R. A. Norman (ed.), Preventive Dermatology, 211

DOI: 10.1007/978-1-84996-021-2_19, © Springer-Verlag London Limited 2010
212
of public health where we as physicians might, with
such a simple approach, have a positive impact and save
lives. Whether in the office caring for individual patients,
or whether in implementing a new public health para-
digm in our local community or around the globe, the
opportunity exists for all physicians and healthcare pro-
viders to play a role. The vision is to put an end to the
suffering and death from STDs the world over by moti-
vating patients to choose healthy sexual lifestyles.
19.2 The Magnitude of the Problem
of STDs
The possible adverse consequences of sexual inter-
course are varied and well-documented in the litera-
ture and include in excess of 25 sexually transmitted
infections.1 More than 65 million people in the United
States alone are living with an incurable STD2 and the
financial burden of management of STDs is at an esti-
mated cost to our healthcare system of 17 billion dol-
lars annually.1
Dermatologists diagnose and treat lice, molluscum
contagiosum, and scabies, all of which can be trans-
mitted by sexual activity and yet are so readily trans-
mitted that nonsexual skin-to-skin contact is their most
common presentation. Such skin-to-skin transmission
is well-understood by dermatologists who are likewise
the experts for diagnosing the manifestations of lym-
phogranuloma venereum (LGV), syphilis, granuloma
inquinale, chancroid, herpes simplex virus (HSV), and
genital warts from human papilloma virus (HPV).
Physicians may be called upon to manage long-term
sequelae such as pelvic inflammatory disease and
infertility caused by gonorrhea or chronic asymptom-
atic chlamydia infection. Sexually acquired hepatitis
(A, B, or C) can induce serious morbidity via chronic
active hepatitis leading to cirrhosis or resulting in liver
transplantation. Patients can die from HIV/AIDS or
HPV-induced cervical or penile cancer and will at the
least require ongoing medical care.
Due to the chronicity, pathology, and impairment of
function caused by most sexually transmitted infec-
tions, the intentional use of the traditional terminology,
STDs is warranted. Euphemistic deviation from this
descriptive nomenclature is misleading to patient and
doctor alike. A sexually transmitted infection can be
treated and sometimes cured; such that the anatomical
K. K. Dernovsek
area involved can be returned to normalcy. However, a
return to normal is certainly not possible for those suf-
fering from venereal infections which are either
chronic, intermittently recurring, or cause permanent
pathologic damage to the involved tissues and hence
by definition, are diseases, which are transmitted sexu-
ally, i.e., STDs.
At particular risk are current and future generations of
youth since 48% of the 18.9 million new cases occurring
annually are in sexually active young people aged 15–24
years.3 It is known that young women are biologically
more susceptible to chlamydia, gonorrhea, and HIV
infections.2 This is due to the ectropion of the adolescent
cervix, in which there is exposed columnar epithelium
for which chlamydia and gonorrhea have a predilection.4
The squamous-columnar cell junction is likewise more
exposed in the adolescent cervix, making this metaplas-
tic transformation zone more susceptible to HPV infec-
tion.5 Unequivocally, STDs pose a more serious health
threats to our adolescent patients, whom we diagnose
and treat, yet in the case of the viral STDs, cannot cure.
Two of these, HSV II (progenitalis) and HPV (genital
warts) are seen so regularly in dermatologic office prac-
tice so as to warrant more detailed discussion.
19.3 Dermatologic Perspective
on Herpes Simplex Virus
Genital herpes (HSV I or HSV II) is most commonly
caused by HSV II, which is also known to be a potent
facilitator of sexual transmission of HIV infection.6
Genital herpes is a recurrent, lifelong viral infection7
affecting at least 50 million Americans age 12 years
and older.7 Ninety percent of these patients are unaware
of their status8 due to asymptomatic intervals between
herpes outbreaks and/or undetected signs of lesions
especially when hidden on mucosal surfaces of the
vagina, cervix, or anus. The virus can be detected in
genital secretions of most HSV-II seropositive patients
who give no history of having genital herpes9; such
asymptomatic cutaneous viral shedding likely contrib-
utes to the ease with which HSV-II is transmitted. No
effective vaccine exits, intermittent or suppressive
antiviral treatment does not eradicate the organism
from secretions or lesions, nor does condom use fully
protect. This is because both HSV-1 and HSV-2 are
transmitted through direct contact: kissing, sexual
19  Prevention of Sexually Transmitted Diseases from Office to Globe
contact (vaginal, oral, or anal sex), or skin-to-skin con-
tact and can be transmitted with or without the pres-
ence of sores or other symptoms.6
While our nondermatologic colleagues may be baf-
fled by herpes gladiatorum or herpetic whitlow, derma-
tologists understand the ease of skin-to-skin transmission
where pressure, rubbing, or even simple contact is
involved. This is true especially with direct droplet
transmission of the infectious agent and enhanced
where skin barrier alteration via erosion or microscopic
fissure from xerosis exists. In the simplest of terms,
there is no dermatologist who would with ungloved fin-
ger knowingly touch a herpetic vesicle, a syphilitic
chancre, the rash of secondary syphilis, or the sore or
drainage of chancroid or lymphogranuloma venereum
(LGV). Indeed, most dermatologists would likely
glove-up to do diagnostic scrapings of scabies or to
curette lesions of molluscum contagiosum, even in the
years predating “universal precautions.”
According to the National Health and Nutrition
Examinations Survey (NHANES), which is the key
American ongoing population-based study, the HSV II
seroprevalence rates rose 30% from 1976 to 1994.8 It is
during this same period of time that a societal liberaliza-
tion of sexual mores and wide promotion of the “safe”
sex condom strategy in clinics and schools was ongoing.
In more recent times, alternative sexual practices are
changing the natural history of genital herpes infections
which had traditionally been HSV II in type. Up to 50%
of first-episode genital herpes is HSV-110 with oral sex
the most likely source, from shedding in the mouth.11 A
review of Herpes genital isolates showed that HSV I
increased from 31% in 1993 to 78% in 2001, with HSV
I having become the most common cause of new genital
herpes on a Midwestern college campus.10
On a positive note, from 1999 to 2004, there has
been a downward trend in HSV II seroprevalence rate
toward 17%.12 Interestingly, this correlates time-wise
with implementation of the Sect. 510 Title V abstinence
education initiative in 1999 when abstinence was
increasingly emphasized in character-based, sex educa-
tion school curriculae.13 Simultaneously during these
same years there has been a counter-cultural backlash
toward “virginity” among the youth themselves.14
Condom use had also gone up during this period of
time however this is of uncertain significance due to
the theoretical offset of “risk compensation.” Risk
compensation is the increase in the actual risky behav-
ior (i.e., sexual intercourse) due to the perception of
213
being at reduced risk (i.e., via condom use), which
thereby paradoxically increases the frequency of the
risky behavior (i.e., sexual intercourse).
What is known with certainty is that HSV II sero-
prevalence rates are higher if intercourse is initiated
under 18 years of age at 21.1% compared to 18 years
of age and older at 14.3%.12 HSV II seroprevalence
rates are also higher if there is a greater number of life-
time partners. For example, HSV II seroprevalence is
39.9% if more than 50 partners, 20.8% if five to nine
partners, and 3.8% with only one lifetime partner.12
Therefore, delay of sexual debut and limitation of life-
time partners is paramount to a successful genital her-
pes prevention strategy.
19.4 Dermatologic Perspective
on Human Papilloma Virus
The second STD that dermatologists frequently manage
is HPV infection, in particular, genital warts, which can
be found in 1.5–13% of sexually active adults, depen-
dent on the population group studied.2 Any clinician has
experienced the time-consuming agony of the patient
newly diagnosed with either Herpes II or HPV (genital
warts). It is not unusual for those newly diagnosed with
genital warts to experience disclosure anxiety, relation-
ship breakdown, depression, and fears about recurrence
and transmission,15 ,16 and to reduce numbers of partners
(14%), use a condom (41%), or abstain from sexual
intercourse (26%).15 Fortunately our patients can be
reassured that 90% of genital warts are caused by non-
carcinogenic HPV types 6 and 11, although carcinogenic
HPV types 16, 18, 31, 33, and 35 are found occasionally
and have been associated with cervical neoplasia in
females and squamous cell carcinoma in situ, bowenoid
papulosis, erythroplasia of Queyrat and Bowen’s dis-
ease, and squamous cell carcinoma of the anogenital and
head and neck region in males and females.17
19.5 Gynecologic Perspective
on Human Papilloma Virus
Our gynecology and primary care colleagues regularly
encounter subclinical genital HPV infection since 5.5
million such new cases occur annually and it is
214
estimated that 20 million people are currently infected,
with the prevalence ranging from 28 to 46% in women
under age 26.2 Due to the ubiquitous nature of HPV
genital infection in our sexually active patients, it
behooves us as dermatologists to fully understand its
natural history so as to correctly counsel patients in
prevention. Regarding the natural history of subclini-
cal genital HPV infection, it is reported that among
sexually active college women, 26% of 608 studied
were already infected at outset. Forty-three percent
became infected over 3 years with 9% of them remain-
ing infected at 2 years.18 In another investigation,
19.7% of 553 enrolled were already infected at outset
and 38.8% of the remaining 444 became infected over
2 years.19 It is from these studies that we understand
that at least 90% of subclinical HPV infections sponta-
neously clear. Nevertheless, persistent infection with a
high-risk HPV type for at least 6 months is associated
with the risk of developing a squamous intraepithelial
lesion.18 It is known that 95% of cervical cancer is
associated with 8 types of HPV16, 18 and that HPV 16
alone accounts for over 50% of cervical cancers and
high-grade dysplasias.20
From a public health concern, it is the potential car-
cinogenicity of subclinical genital HPV infection that
sets it apart from genital herpes infection. Unfortunately,
just as treatment for visible herpetic blisters does not
prevent future viral shedding, likewise treatment of
visible genital warts possibly reduces, but does not
eradicate HPV infectivity. Our dermatologic aim is
always to remove the visible genital warts, destruc-
tively, surgically, or via a topical immune modulator.
Yet it remains unclear whether reduction of HPV DNA
in genital tissue impacts future transmission.17
Both HSV II and HPV have been generally rising in
prevalence over the last 30 years despite widespread
and increasing condom use by adolescents documented
over the 14 years from 1991 to 2005.21 While this may
be due to “risk compensation,” (above), the inadequacy
of condoms to protect uncovered skin during skin-to-
skin transmission is the most likely explanation. The
herpes lesion may occur on skin that is not covered by
the condom or may be transmitted either when visibly
present or during asymptomatic periods of viral shed-
ding. In 2001 a panel of 28 experts reviewed 138
papers and concluded that there was no epidemiologic
evidence that condom use reduced the risk of HPV
transmission although they “might afford some protec-
tion.”22 The center for disease control and prevention
K. K. Dernovsek
(CDCP) reported that prevention of genital HPV infec-
tion involved (1) refraining from any genital contact
with another, (2) long-term mutual monogamy, (3)
reduction in the number of partners and careful partner
selection, and (4) that the available scientific evidence
was not sufficient to recommend condoms as a primary
prevention strategy.23 In a recent study of newly sexu-
ally active college women, when partners used con-
doms consistently and correctly, there was a 70%
reduction in HPV infection.24 The discerning reader
will recognize the terms consistently and correctly as
significant detractors from these results (see Sect. 19.8).
A CDCP publication for clinicians, in discussion of the
use of condoms for decreasing efficiency of transmis-
sion of HPV, states that infections can happen in the
scrotum, vulva, or perianus areas unprotected by a
condom.25
19.6 The HPV Vaccine
An HPV vaccine that targets HPV 16, 18, 6, and 11
was developed and licensed by the Food and Drug
Administration (FDA) in 2006. HPV 16 and 18 cause
up to 70% of CIN II/III and anogenital cancer and
HPV 6 and 11 cause up to 90% genital warts.26 The
vaccine, made from noninfectious HPV-like particles,
was tested in thousands of 9–26 year-olds and found
to be safe with no serious side effects.27 Pain at the
injection site occurs in 80%, site redness or swelling
in 20%, fever (100°F) in 10%, site itching in 3%, and
fever (102°F) in 2%.28 These side effects and fainting
comprise most of the adverse events reports on the
vaccine. The serious reports (7%) have included
Guillain-Barre Syndrome, blood clots, and 39 deaths,
although careful analysis by experts has not found a
pattern suggestive of causation by the vaccine.29 The
vaccine has nearly 100% efficacy against HPV 16,
18, 6, and 11 of at least 5 years duration with no wan-
ing immunity.27 It is recommended for 11–26 year-
old nonpregnant females and contraindicated in
yeast-allergic patients.27 Administered in a series of
three injections, the total cost is $375.30 The cost-
effectiveness for HPV 16 and 18 vaccination of
12-year-old girls is estimated at $43,600 per quality
adjusted life year (QALY) and cost of extension of
vaccination to older girls and women is not cost-
effective.31 Since the vaccine is effective only against
19  Prevention of Sexually Transmitted Diseases from Office to Globe
carcinogenic HPV types 16 and 18, women remain
unprotected against 30% of cervical cancer and pre-
immunization counseling is to include a recommen-
dation for continued Pap testing after vaccine
administration. Additionally, vaccine providers should
notify vaccinated females that “they should continue
to practice abstinence or protective sexual behaviors
(i.e., condom use), since the vaccine will not prevent
other sexually transmitted infections.”27
Less than a year after FDA approval of the HPV
vaccine, the governor of Texas made it mandatory, pro-
voking widespread public concern that later resulted in
overturn of this decision. The state of Virginia has
made the vaccine mandatory, but with very generous
opt-out provisions. Salmon et al, in a Lancet publica-
tion expressed concern that generous religious and
conscientious exemptions to the HPV vaccine could
cause legislators to extend the same to other childhood
vaccinations, which would then be detrimental to the
public’s health.32 A 2007 Journal of the American
Medical Association (AMA) editorial stated: “Given
that the overall prevalence of HPV types (16 and 18)
associated with cervical cancer is relatively low
(2.3%)33 and that the long-term effects are unknown, it
is unwise to require a young girl with a very low life-
time risk of cervical cancer to be vaccinated without
her assent and her parent’s consent.”34 A New England
Journal of Medicine editorial,35 in commenting on a
large study of the quadrivalent HPV vaccine in pre-
venting high-grade cervical lesions,36 raised concerns
that evidence was insufficient to infer the effectiveness
of vaccination in prevention of CIN III or adenocarci-
noma in situ and “… a cautious approach may be war-
ranted in light of important unanswered questions
about overall vaccine effectiveness, duration of protec-
tion, and adverse effects that may emerge over time.”
A more recent NEJM editorial raised further reasons
for caution, including whether vaccinated women will
be less likely to pursue cervical cancer screening and
whether other HPV strains will emerge as significant
oncogenic serotypes.37 The American Cancer Society,
citing probable diminished vaccine efficacy as the
number of lifetime sexual partners increases, does not
recommend universal vaccination among women
between 18 and 26 years of age.38 Lastly, general ques-
tions have been raised about the applicability of the
traditional compulsory vaccination paradigm to vacci-
nation against HPV. HPV is not a highly infectious air-
borne disease. There is a cost to society at a loss of
215
something else.34 Finally, does the patient (parent)
retain the right to decline a prevention modality that by
one’s own behavior and by regular cervical cancer
screening can be prevented?
19.7 Prevention of Cervical Cancer
here and Abroad
In the United States it is estimated that there were
11,270 cases and 4,070 deaths from cervical cancer
during 2009.39 Since 95% of cervical cancer is caused
by asymptomatic carcinogenic HPV present on the
cervix longer than 6 months, it seems to follow that
primary prevention of genital HPV infection be the
method of preventing cervical cancer. “However, in
populations that are screened regularly, as is typical in
the U.S., cervical cancer develops rarely in women,
even with persistent HPV infection. This is because
women with high-grade precursor lesions are usually
identified through cytologic screening, and the devel-
opment of cancer can be prevented through early
detection and treatment.”25 Since most cervical precan-
cers develop slowly, nearly all cases can be prevented
if a woman is screened regularly.39 Four separate stud-
ies of women who were diagnosed with cervical can-
cer showed that 28.540 and 30.1%41 had never had a
Pap test and 5342 and 56%43 had not had a Pap test
within the 3 years prior to diagnosis. The CDCP sum-
marizes that “The single most important factor associ-
ated with invasive cervical cancer is the factor of never
or rarely being screened for cervical cancer.”25
Underscoring the role of preventive cervical screen-
ing it is noted that prior to PAP testing programs in the
USA, the cervical cancer incidence per 100,000 was
38.0 whereas current rates in developed countries are
less than 14.5.44 Globally, cervical cancer killed 274,000
women in 2002 and age-standardized incidence rates
per 100,000 were highest in Southern Africa at 38.2
and Eastern Africa at 42.7.44 These sobering statistics
emphasize the role of cervical Pap testing in prevention
of cervical cancer and the effect of the asymptomatic
progression of a long-term infection with a carcino-
genic HPV subtype in settings where screening is
unavailable. It is unlikely that the HPV vaccine will
ever be a feasible prevention modality in the develop-
ing world countries that need it most due to high cost
($375)30 and required administration as a series of three
216
injections widely separated over time. Fortunately for
countries where vaccines and Pap testing are unlikely
to ever reach the masses, there remains a low-cost strat-
egy, one in fact recommended by the CDCP, which
states: “The surest way to prevent HPV infection is to
abstain from any genital contact, including nonpenetra-
tive intimate contact of the genital area.”25
19.8 The Failure of the
Condom Strategy
To interpret the literature on condoms and determine
their role in prevention of STDs from office (individ-
ual) to globe (public health), the first step is to review
the mechanism of action of the condom. The condom
is a latex sheath that covers the penile shaft and glans
penis with a receptacle at the tip to contain ejaculate
and which must be applied by a human being, during a
state of sexual arousal, to the erect penis. By design, a
condom is a barrier to transmission of ejaculate con-
taining sperm, i.e., a contraceptive device. The con-
dom therefore is mechanically suited for protection
against those pathogens known to be delivered via
ejaculate: HIV, gonorrhea, and syphilis. The condom
in theory provides at least some protection against
those organisms that could be present in ejaculate, on
the penile shaft/glans, or against any infectious organ-
isms that might present in the recipient. Therefore con-
doms theoretically have the potential to be useful
protecting against HSV I and II, Herpes, HPV, chla-
mydia, and any infectious lesion or organism covered
by the condom. However, numerous STDs are or can
be transmitted by skin-to-skin contact and the condom
does not cover all of the potentially infected skin. So
even at very best, “perfect and always” use of the con-
dom, the condom by design will never protect against
all STDs in real life.
How are condoms assessed as prophylactic devices?
The FDA regulates manufacturer’s pre- and postmarket
compliance with industry standards of testing condom
lots via the “water leak” and “air-burst” tests prior to
sale. The air-burst test examines strength to resist
breakage during use and the water leak test specifies
that the average defect rate should not exceed four leak-
ing condoms per 1,000, although industry standards are
more stringent at 1 per 400, with the FDA draft regula-
tions now recommending the same.45
K. K. Dernovsek
The water leak test, “under ideal conditions, is able
to detect a hole 3 mm in diameter, but, in practice, the
sensitivity (diameter of the smallest hole reliably
detectable) is approximately 15 mm.”46 The normal
human sperm has a width range of 2.5–3.5 mm (microns,
i.e., 2,500 nm) and a length range of 4–5 mm.47 Since
sexually transmitted viruses vary in diameter from
0.04 to 0.15 mm,48 a conservative, sensitive test of con-
doms was developed to further evaluate condoms
already purchased through retail distributors (and
thereby presumably having passed the water leak
test).48 This virus penetration assay was used to evalu-
ate a broad range of condom types and brands and
found that 2.6% of latex condoms allowed some virus
penetration of particle size 0.032 mm.48 By compari-
son, the size of HPV is 0.060 mm.49 Hepatitis B is
0.040 mm, HIV is 0.10 mm, Herpes simplex is 0.14 mm.42
However, the relative importance of holes is related to
the volume of semen that contains an “infectious dose”
of the given STD and it has been concluded that “for
infectious agents with low titer and low infectivity
(such as HIV), leakage through pores too small to be
detected by the water leak test is not the primary public
health risk of condom use.”50
In addition to virus titer, it is known that transmis-
sion through a small hole also depends upon transcon-
dom pressure, time for passage, viscosity of the carrier
fluid, and condom thickness.48 Fluid flow is the most
important determinant of viral passage through a
hole.22 It has been demonstrated that (1) there is a
“strong dependence of virus penetration on hole diam-
eter,” such that virus penetrations varied over four to
five orders of magnitude, whereas the hole size varied
over one (from 2 to 21.5 mm), i.e., roughly correlating
with the Poiseuille equation of fluid flow through a
cylindrical hole varying as the hole diameter to the
forth power and that (2) most virus penetration is com-
plete or nearly complete by 2 min.51 Results from the
laboratory tests were applied to determine the hypo-
thetical relative risk of exposure to semen as a function
of semen volume attributable to various independent
condom use events and it was concluded that the data
showed condoms to be a highly effective barrier to
transmission of particles of similar size to those of the
smallest STD viruses; with a strong probability of con-
dom effectiveness when used correctly, where the eti-
ology of STD transmission is linked to containment of
preejaculate and seminal fluids or barrier coverage
of lesions of the penis and there is no slippage or
19  Prevention of Sexually Transmitted Diseases from Office to Globe
breakage. It was additionally noted however that for
many STDs the risk of infection might not be propor-
tional to exposure to a volume of semen and that esti-
mation of risk requires further extrapolation because it
depends also on the concentration, infectivity, and
mode of transmission of the specific STD.22 Thus it
can be summarized that even if minute leakage of
viral-sized particles occurs,48 condoms do protect
against STDs and in a controlled laboratory setting,
transmission of infection is highly unlikely.19, 42
Such laboratory testing is for efficacy, i.e., the
improvement, achieved in a desired health outcome in
a research setting in expert hands under ideal condi-
tions. To achieve something close to efficacious use of
the condom in actual life, “perfect use” must be
achieved: i.e., use of the condom 100% of the time and
100% correctly each time of use. Unfortunately, in
“real life,” the condom often fails to protect.52–56 That is
because in actuality the best that can be achieved is
“typical” use of the condom, which includes using the
condom “some,” “most,” or “all” of the time and using
it both correctly and incorrectly. Hence it is effective-
ness, i.e., the amount of improvement in the health out-
come in actual life with typical implementation, which
is clinically applicable.
Condoms are known to fail in protection against
pregnancy at a rate of 14%52 and in protection at vari-
able rates against ejaculate-delivered pathogens, the
specific purpose for which they were designed.45,46,48
Failure can occur due to “method” or “user” failure or
both. “Method” failure occurs when the condom itself,
as a device, fails. Types of “method” failure would result
from defects incurred during manufacture or improper
storage, and could include leakage or breakage during
intercourse or withdrawal, or slippage during inter-
course, either partially or completely.53, 55, 57–60
“User” failure refers to the condom being used
incorrectly and represents the human component, i.e.,
one’s (in)ability to comply with proper use during
arousal and sexual intercourse. Examples of “user”
failure include genital contact before condom applica-
tion61 (preejaculatory secretions can contain both
infectious pathogens and sperm), flipping condom
over after initial application (noting the condom to be
applied “upside-down” so that when turned over con-
tact with preejaculatory secretions on the now-exposed
condom surface occurs), holes poked in condom (fin-
gernails or jewelry from piercings), use of oil-based
lubricants (known to weaken condom strength),
217
improper positioning of condom, not holding on to
condom during withdrawal resulting in ejaculate spill-
age and not withdrawing while penis erect (falling
asleep after intercourse).53,62
To approach laboratory-setting efficacy of condoms
in real life, “perfect condom use” (i.e.,“always” (con-
sistently) and “correctly” with each use), would need
to be achieved. What scientific evidence exists for
one’s ability to achieve perfect use in real life? In one
study of college-educated males with an average of
more than 5 years of condom experience who were
“consistent, 100%” condom users, it was found that
altogether at least 13% of condom uses had resulted in
exposure to risks of unprotected intercourse due to
breakage, slippage, or failure to use condoms through-
out intercourse. This calculated to 33% of the consis-
tent condom users having been exposed to risks of
disease or pregnancy in the prior month.62 Similarly, of
186 females aged 15–21, who had reported vaginal sex
in the past 14 days and who were self-described con-
sistent (100%) condom users, 34% were found to have
sperm present in vaginal fluid via Y-chromosome poly-
merase chain reaction assay.63 In a study of the value of
consistent condom use in adolescent females, 17.8%
acquired at least one STD (chlamydia, trichomoniasis,
gonorrhea) despite consistent (100%) condom use.64
Lastly, in a study of HIV serodiscordant heterosexual
couples, in which 171 always used condoms, three
seroconversions occurred over 24 months (1.1% inci-
dence rate).65 Therefore, either method (device) or user
failure (incorrect use) must have occurred in order for
seroconversion to HIV positivity to have taken place
for any of them.
On a lighter note, a personal observation of an aca-
demically embarrassing demonstration of the com-
plexities of correct condom use is recalled from the
AIDS and STD Symposium of the 2002 American
Academy of Dermatology meeting. The speaker was
explaining how teens are taught in school programs to
correctly use condoms by ordering steps known to be
necessary for correct condom usage. To press the point
he ordered dermatologists from the audience to the
front, divided them into two groups and gave them
each a card with a “step” in the condom use process, to
put in proper order. In competition against their col-
leagues, the dermatologists, presumably both intelli-
gent and manually adroit, appeared to have a great deal
of difficulty ordering the steps. Ultimately each group
came up with a different order of steps. In the comedy
218
that ensued, it was never confirmed whether either
group had correctly ordered the steps involved in using
a condom. Since each group came up with a different
order of steps, what can be concluded is that one of the
groups of physicians was wrong.
The fact remains that despite years of condom public
education, people still fail to use condoms correctly.
What does the evidence show about whether people are
able to use condoms “always,” i.e., “consistently?”
Three studies are concerning that, for whatever reason,
people don’t or won’t or can’t use condoms consistently.
First, among a nationally representative sample of
unmarried sexually experienced females aged 15–44
years who stated they “used condoms” for disease pre-
vention, only 18.5% always used condoms.66 Second,
we know that among Herpes discordant couples, despite
counseling to always use a condom (11 visits during 18
months), and in a vaccine trial where it was not known
whether the seronegative partner had received the HSV
subunit vaccine or a placebo, that only 8% “always
used” a condom and 15.5% used a condom for 51–99%
of sex acts.67 In a parallel clinical trial of an HSV-2 vac-
cine subsequently found to be ineffective, 13% “always
used” a condom and 16% used a condom for 76–99% of
sexual acts, despite the counseling protocol described
above and provision of free condoms at the 11 study vis-
its.68 Lastly is a prospective study, done prior to the
development of effective antiretroviral therapy, of HIV-
negative subjects whose only risk of HIV infection was
a stable heterosexual relationship with an HIV-infected
partner. Every 6 months the subjects were interviewed,
tested for HIV, and counseled about safe sexual prac-
tices and despite the knowledge that they were at risk for
a fatal disease, only 48.4% of these HIV discordant cou-
ples “always” used a condom.69
In addition to the problems of correct and consistent
use of condoms outlined above, there are additional
factors influencing condom failure in the real-life set-
ting. The adequacy of protection against STDs will
depend on the degree of infectivity of the particular
STD, the prevalence of the STD in the community, the
number of acts of intercourse, the user’s prior experi-
ence with condoms, the age and sex of the individual,
the natural immunity of the individual, and whether
lesions of other STDs are present.70 Earlier in the chap-
ter was described the discouraging conclusions reported
by three government agencies on the existing scientific
evidence for condom effectiveness in preventing HPV.
Equally discouraging are the experts’ conclusions
K. K. Dernovsek
regarding prevention of other STDs. Regarding chla-
mydia, gonorrhea in women, and trichomoniasis they
concluded that the available epidemiologic literature
does not allow an accurate assessment of the degree of
potential protection.22 Regarding genital herpes, syphi-
lis, and chancroid they stated that the data were insuf-
ficient to draw meaningful conclusions about the
effectiveness of the latex male condom to reduce the
risk of transmission.22 The data were clear regarding
the “strong evidence” for the effectiveness of condoms
for reducing sexually transmitted gonorrhea for men
and HIV/AIDS: that with HIV/AIDS, consistent con-
dom use decreased the risk of HIV/AIDS transmission
by approximately 85%.22 In the more recent Sexually
Transmitted Diseases Treatment Guidelines 2006, the
CDCP states that “HIV-negative partners in heterosex-
ual serodiscordant relationships in which condoms
were consistently used were 80% less likely to become
HIV-infected compared with persons in similar rela-
tionships in which condoms were not used.”71
The scientific evidence has supported cautions
offered during the early years of AIDS prevention strat-
egy development. For example, Judson, et  al. who in
1989 stated after describing the factors related to con-
dom effectiveness: “Thus it would seem prudent not to
place excessive reliance on latex condoms alone for
prevention of sexually transmitted infections.”55 In
1994, d’Oro et al. reviewed barrier methods in preven-
tion of STDs and concluded, “A consistent and strong
protection may well be acceptable for treatable diseases
and rare exposures, but a similar protection is clearly
not satisfactory for frequent exposures and, particularly,
serious or severe diseases.”56 Certainly there is no other
fatal disease where it is acceptable public health policy
to widely and primarily promote, around the globe, to
young and old alike, a risk reduction modality in which
the chance of becoming infected still remains 20%, at
the universal exclusion of a risk avoidance strategy in
which the chance of infection is 0%.
We have assumed that our patients cannot abstain
from sex even though we understand that sex is not a
mandatory biologic reflex like micturation, defecation,
or sleep. We must consider the possibility that our own
bias based on personal life experience has skewed our
medical approach. Perhaps when we do not or have not
modeled the proposed sexual behavior change, it
becomes more uncomfortable for us to endorse and/or
recommend it. Nevertheless we are ethically obligated
to give our patients the best medical recommendation
19  Prevention of Sexually Transmitted Diseases from Office to Globe
for health preservation. Therefore, for the health of our
patients, is it time to rethink our STD prevention strat-
egy from office to globe?
19.9 Defining Terminology:
Safe Sex, Sex, and Abstinence
Although the medical literature currently refers to the
condom method as “safer” sex, confusion over what peo-
ple understand to be “safe” has prevailed. This is exem-
plified by varied verbiage describing condom effectiveness
on packaging, such as, “safer sex, give protection, pro-
tect, are highly effective, effective, may help, will help,
can reduce the risk, will reduce the risk and significantly
reduce the risk.”72 As a result, directed by Public Law
106–554, the FDA proposed rules in 2005 to designate a
special controls guidance document with labeling recom-
mendations for latex condoms. The FDA concluded that
condoms reduce the overall risk of STD transmission
although the degree of risk reduction for different types
of STDs varies with their routes of transmission. The
FDA now proposes that labeling consistently utilize the
terminology, “sexually transmitted diseases” and address
incorrect and inconsistent use which “undermines” con-
dom effectiveness. The FDA also proposes that labeling
address the limited benefits and risks presented by N-9
spermicidal lubricant since frequent use can cause
mucosal irritation, which may increase the risk of trans-
mission of HIV.73
Twenty-plus years of the “safe sex” paradigm have
resulted in terminology confusion for youth. In a 2000
survey of 12–17 year olds, 88% reported having heard
the expression “safe sex,” yet when asked to specify
which behavior(s) they considered safe, 86% said not
having sex/abstinence was “safe sex,” 72% said “safe
sex” was using a condom, 46% said birth control pills
were “safe sex” and 21% said oral sex was “safe sex.”74
Regarding the practice of oral sex, specifically, a 2003
survey of 15–17 year olds revealed that 46% thought
oral sex was “not as big of a deal” as sexual intercourse.
Thirty-nine percent considered oral sex “safer sex” and
19% did not know you could get an STD through oral
sex.75 These misconceptions exist despite clearly listing
as “can be transmitted by oral sex” in a 2000 CDCP fact
sheet: HIV, herpes, syphilis, gonorrhea, HPV, intestinal
parasites (amebiasis), and hepatitis A.76 It is not clear to
teens that oral sex is a form of sexual intercourse. In the
219
youth surveys, 63% said they had “never had sex” but
13% of those had had oral sex.75 It is therefore para-
mount that we retain a precise definition: Sexual inter-
course is the stimulation of a partner to orgasm via
vaginal, oral, anal, nongenital activity, i.e., mutual mas-
turbation.77 As we communicate with clarity the correct
definition of sexual intercourse, then our patients (who
are themselves, community members, teachers, parents
and teens) can correctly counsel that it follows that
abstinence is by definition, abstinence from all forms of
sexual intercourse. Adding an appropriate endpoint to
abstinence makes it clear that “abstinence” is not just
until the next Saturday night date, but that it is a life-
style to be continued until a certain predefined time.
Thus derives the terminology, “lifestyle abstinence,”78
that being a lifestyle of abstaining from all sexual activ-
ity until marriage, i.e., selection of lifelong faithful
partner, i.e., until sustained mutual monogamy.
“Lifestyle abstinence” as a lifestyle choice will
ensure freedom from all sexually transmitted diseases
as will sustained mutual monogamy in the case where
both  partners have abstained until this relationship.
Encouraging these health-preserving behaviors is in
keeping with most global societal standards. Our patients
deserve to understand the health risk that exists with the
lifestyle of “serial monogamy,” i.e., monogamy for some
period of time followed by termination of that relation-
ship followed by monogamy for another period of time
with a different individual, and so forth. With each new
monogamous relationship, that new partner brings with
them a past sexual health history that may not be healthy.
If the periods of serial monogamy are each of brief dura-
tion then the risk to the health of the individual may not
be much improved over networks of concurrent sexual
partners. This latter category of sexual lifestyle, whether
called concurrency, polygamy, prostitution, sex work,
promiscuity, or guised in slang terms of “hooking up,”
“anonymous partnering,” or “friends with benefits” are
all highly risky sexual lifestyles for both the individual
and for the health of the society (Fig. 19.1).
19.10 STD Prevention in the Office:
Recommended Guidelines
The medical and scientific practice guidelines clearly
recommend counsel regarding behavior change in pre-
vention of STDs and their sequelae. In response to the
220
Sexual Lifestyle Choices
Abstinence Mutual
(Celibacy) Monogamy
Concurrency
Polygamy
Promiscuity
Anonymous Partnering
Hooking-up Serial Monogamy
Fig. 19.1  There is no risk of contracting a sexually transmitted
disease (STD) in lifestyle abstinence or sustained mutual monog-
amy with an uninfected partner but with each new sexual part-
ner, who may be an asymptomatic STD carrier due to past or
current sexual relationships, STD risk occurs and is highest with
multiple sexual partners. Adapted from a video by Stephen J.
Genuis, courtesy Stephen J. Genuis
growing health threats of STDs for our adolescent
patients and to assist primary care physicians and other
health providers to make preventive services a greater
component of their clinical practice, the AMA
Guidelines for Adolescent Preventive Services (1997)
first recommended that annual “health guidance”
regarding responsible sexual behavior include “coun-
seling that abstinence from sexual intercourse is the
most effective way to prevent pregnancy and STDs,
including HIV infection.”79 The CDCP state in both the
2002 and the 2006 Guidelines for Treatment of STDs
that “the most reliable way to avoid transmission of
STDs is to abstain from sexual intercourse (i.e., oral,
vaginal, or anal sex) or to be in a long-term, mutually
monogamous relationship with an uninfected part-
ner.”80,81 The guidelines further state that “counseling
that encourages abstinence from sexual intercourse is
crucial … for persons who wish to avoid the possible
consequences of sexual intercourse (e.g., STD/HIV and
unintended pregnancy).”80,81 A 2005 clinical report from
the Committee on Adolescence, American Academy of
Pediatrics (AAP), makes as the first, and presumably
primary, recommendation to pediatricians the follow-
ing: “Encourage adolescents to postpone early sexual
activity and encourage parents to educate their children
and adolescents about sexual development, responsible
sexuality, decision-making, and values.”82
Nevertheless, adolescents are not routinely being
encouraged by physicians to postpone early sexual
K. K. Dernovsek
activity since only 42.8% females and 26.4% males
indicated having discussed STD, HIV, or pregnancy pre-
vention at a healthcare visit in the preceding year83 and
counseling in HIV/STD transmission has been reported
to occur in only 6.2% of well visits.84 Barriers to sexual
history taking were reported to be difficulties asking
sexual history questions, fear of offending patients, and
lack of time in more than half of physicians surveyed.85
Even in the less sensitive realm of counseling young
patients in smoking cessation, the perception that coun-
seling is time-consuming and the fear that the parent
would be angered were reported as perceived barriers to
counseling by over 50% of physicians surveyed.86
19.11 STD Prevention in the Office:
A Directive Approach
Within my own community private practice of derma-
tology, I examined the validity of two perceived barri-
ers to abstinence counseling (fear of offending and
perception of inadequate time) by observing whether
the physician–patient relationship is adversely affected,
as assessed by frequency of return for care. I addition-
ally determined whether abstinence counseling is time-
consuming by observing its effect on usual scheduling
patterns. Due to the broad implications in the area of
physician health maintenance counseling, adolescent
sexual health, and our role as dermatologists in this
realm, I report my findings within this chapter.
My solo private practice is one of four dermatology
practices (all of which are open to new patients [NPs])
in Pueblo County, Colorado (population 141,47287).
The study practice has a payer mix of managed care,
preferred provider organizations, private pay, Medicaid,
and indigent community clinic patients. Ethnicity was
estimated by my observation to be 77% Caucasian,
22% Hispanic, <1% African American, and <1% other.
The county served is 57.7% Caucasian, 38% Hispanic,
1.9% African American, and 2.3% other.87 Ethnicity
breakdown and description of payer mix are provided
for ease of evaluating applicability of results to other
communities and to demonstrate that the practice
draws widely from the community. Scheduling allots
NPs 20 or 30 min (physician referral) and established
patients (FUs) 10 (acne or postoperative) or 15  min.
Scheduling is done by the same staff member who has
performed in this capacity since 1993.
19  Prevention of Sexually Transmitted Diseases from Office to Globe
I undertook to initiate medical guideline recom-
mended abstinence counsel to all youth in my practice
and then observe whether return to the office was
inhibited by such abstinence counseling beginning on
01 Nov 1998 and continuing to 01 Jan 2001. During
this time male and female NPs and FUs, aged 13–19,
nonrandomized, regardless of reason for visit, were
counseled by me. The NP and FU control groups con-
sisted of the cohorts of male and female patients aged
13–19 not instructed in abstinence in the immediate
10-months prior to the study, January through October
of 1998. Analysis showed the control and abstinence-
counseled groups to be age and gender matched.
The physician counseling style was concerned,
casual, simple, and brief, allowing silence for patient
response. After forewarning that an unexpected topic
would be initiated, “This has nothing to do with the
reason for your visit, but is also important for your
health,” counseling in the style of asking, informing,
and advising began: While handing an abstinence
pamphlet88 I asked, “Have you ever heard of absti-
nence?” Physician silence followed. Then “lifestyle
abstinence”78 was defined as a lifestyle choice requir-
ing restraint from all forms of sexual intercourse until
selection of lifelong partner. Third, the patient was
advised that lifestyle abstinence could be initiated
despite past or current behavior, thereby preventing
disease transmission and ensuring health preservation.
Physician silence followed. Throughout, counseling
was adapted according to patient response (Fig. 19.2).
If a patient confirmed abstinence/virginity, this was
reinforced by physician’s affirmation of this behavior
as “healthiest,” sustained abstinence was encouraged
and the patient was enlisted to advise peers and pass
the pamphlet on. If a patient declared sexual activity,
counseling was modified to risk reduction via an
“informed condom recommendation,” hereby strictly
defined: First, informing the patient of condom inade-
quacy in complete protection against all STDs. Second,
recommending condom usage as the next best alterna-
tive to lifestyle abstinence. Third, advising that life-
style abstinence could be resumed, variously termed
by peers as renewed-, recycled-, or secondary virgin-
ity. Fourth, the option of conversion of the relationship
to lifelong monogamy was raised for the patient’s
consideration.
If there was no verbal response, didactic directive
education began with one of the following, “A lot of
kids don’t realize that … condoms don’t fully protect
221
them against diseases22, 23, 78 … one in five people over
age 12 already have genital herpes8 or HPV89 … der-
matologists have to treat STDs … even their skin doc-
tor wants them to stay healthy … that this is a message
for boys and girls” ending with, “I don’t want my
patients to say that I never warned them about STDs
and how to prevent them. Now is the time for you to
decide where you will stand in this matter.”
The patient and/or parent response to lifestyle absti-
nence counseling was observed and whether the patient
returned for care was determined. A return was recom-
mended only as warranted by the patient’s medical
condition and the adolescent received medical counsel
and treatment regardless of presence or absence of the
parent; as per the standard of care for the practice.
Counsel in sexual abstinence, specifically, is as recom-
mended by both the CDCP80,81 and the AAP82; it is pri-
mary prevention (risk elimination) counsel of universal
benefit and therefore no patients were intentionally
excluded. Finally, the rate of return to the practice was
not calculated for either control or observed cohort
until the observation was complete.
Results of in-office adolescent abstinence counsel
revealed that 135 new and established patients were
counseled. Lifestyle abstinence counseling did not
require schedule alteration; hence the observation was
not terminated prematurely as had been intended if the
physician schedule could not be maintained. In all
51.9% NPs (61.5% females, 42.9% males) not
instructed in abstinence returned compared to 69.7%
NPs (75.0% females, 64.7% males) who were instructed,
(P = 0.151, P = 0.473, P = 0.206); 74.5% FUs (75.9%
females, 72.7% males) not instructed in abstinence
returned compared to 78.3% FUs (80.6% females,
75.8% males) who were instructed, (P = 0.667,
P = 0.764, P = 1.00). Statistical analysis (Fisher’s Exact
Test, 2-sided) failed to detect a significant difference in
population groups, indicating that the abstinence-
counseled patients (NPs, FUs, males, females) were at
least as likely to return as those who had not been
counseled (Fig. 19.3).
Ninety-seven percent (131/135) of patient responses
varied from neutral to positive; 12% (16/135) of patient
responses were so positive as to result in role reversal
with the patient enumerating reasons for abstinence
until marriage with four describing renewed virginity
and 12 intending to “stay virgins.” Three percent (4/135)
of the responses were categorized as negative: All were
parents who questioned the “reality” of abstinence.
222 K. K. Dernovsek

Counseling style: Concerned, Casual, Simple, Brief, Didactic, Directive Silence allows
response. Adapt counsel to response

FEMALES
Medication Review: Hormonal Contraceptive (BCP)? MALES
“This has nothing to do with
the reason for your visit, but
On BCP it is also important for your
“Did you know that there is no NO BCP health…”
protection from BCP against STDs?”

Asking: “Have you ever

Uses Not Therapeutic Clarify: “…not heard of abstinence?”
condoms aware BCP sexually active or
also (Not for sexually active and not “Too late “You bet, I’m
contraception) on BCP?” for me.” all for it.”

Clarify: Sexually Not Sexually Not sexually

“…meaning, active sexually active active
that you could active
get pregnant?”

“I guess Not sexually Patient confirms

so.” active abstinence/virginity
Physician Reinforcement
Affirm Behavior as
healthiest
Encourage Sustained
abstinence
Enlist Patient to advise
peers, “pass pamphlet on”
Patient declares sexual activity:
Modify to risk reduction
“Informed Condom Recommendation”
(strictly defined)
Inform of condom inadequacy for complete The Silent Patient…
protection against all STDs Respect Modesty. Give
Recommend condoms as “next best” to abstinence Pamphlet. Inform.
Advise resumption of abstinence: “Renewed-, Advise.
Recycled-, Secondary Virginity”
Consider conversion of the relationship to life-long
monogamy
Informing:
Lifestyle Abstinence78
Restraint from all forms of
Didactic Directive Education
sexual intercourse until
“A lot of kids don’t realize that…”
Condoms don’t fully protect them against diseases22, 23, 64, 65 selection of lifelong partner
1 in 5 people over age 12 already have genital herpes8 or HPV2 Give abstinence pamphlet 88
Dermatologists have to treat STDs
Even their skin doctor wants them to stay healthy
Advising:
This is a message for boys and girls
Abstinence can be started
ending with regardless of past/current
“I don’t want my patients to say that I never warned them about behavior to prevent STDs and
STDs and how to prevent them. Now is the time for you to decide stay healthy.
where you will stand.”

Fig. 19.2  Algorithm for sexual abstinence counsel of the adolescent

19  Prevention of Sexually Transmitted Diseases from Office to Globe 223

However, two of four parents were immediately chal- This in-office observation is limited firstly by failure
lenged by the adolescent patient who defended absti- to enumerate observations; for example, the parental
nence: One countered, “Mom, chastity is cool!” Another silently mouthed, “thank you” response predominated,
muttered, “My mother needs your lessons.” Two patients yet frequency was not recorded. Secondly, 24 NPs and
were on oral contraceptives at the next visit: evidence of 22 FUs, i.e., 25% (46/181) of patients in the abstinence-
their commitment to sexual activity, but also evidence counseled population were not counseled due to severity
that the physician–patient relationship was not adversely of illness, psychiatric disorder, mental retardation, cur-
affected by the patient’s knowledge that the physician rent pregnancy, and if already on birth control, received
recommended sexual abstinence as ideal. A separate an “informed condom recommendation.” Thirdly, other
patient returned for an STD examination, newly moti- barriers to lifestyle abstinence counseling may exist,
vated to address health risks of prior sexual activity. including inadequate physician knowledge; the physi-
This observation undertaken in a general practice of cian is encouraged to review the myriad STDs, their
dermatology shows that new and established patients consequences, and the scientific evidence on condom
counseled in lifestyle abstinence were at least as likely effectiveness (or lack thereof) for STD prevention.22,23
as those who had not been counseled to return for care, Finally, no attempt is made to determine whether the
apparently not inhibited by the abstinence instruction. patients followed the lifestyle abstinence counsel given;
Furthermore, from 01 Jan 2001 through 01 Jan 2004, a follow-up survey is under consideration.
since most FUs had already been counseled, this phy- This clinical observation of correct counsel of
sician continued to counsel NPs (n = 32, 47% males, youth in abstinence per guideline recommendations
average age 15.3 years; 53% females, average age 15.6 has shown that the physician need not fear offending
years); 62.5% (20/32) returned. Statistical analysis the patient or disrupting the schedule when providing
(Fisher’s exact test, 2-sided) of this group compared to lifestyle abstinence counseling, even in a dermatology
the original control group fails to detect a significant practice, where the advice was somewhat unexpected.
difference in population groups (P = 0.440), again indi- Explanation of the relationship between the skin and
cating that the abstinence-counseled patients were at STDs actually facilitated patient and parent educa-
least as likely to return as those who had not been tion, since (1) it is no longer commonly known that
counseled (Fig. 19.3). This physician continues coun- until 1955, ours was the specialty of dermatology and
seling in lifestyle abstinence, time-efficiently, with syphilology and (2) patients and their parents were
unaltered scheduling to this date. seldom aware that condoms do not fully protect from

FU Females FU Males FU Total NP Females NP Males NP Total

100

90
Returning for Continued Care (%)

80

70

60

50

40 80.6 78.3
75.9 72.7 75.8 74.5 75
69.7
61.5 64.7 62.5
30
51.9
20 42.9

Fig. 19.3  The percentage of 10

new (NP) and established
(FU) male and female 0

adolescent patients (aged

ed

51
0
ed
ed

67

ed
64

40
ed
ed

73

06
.0

ct

.1
ct
ct

.6

ct
.7

.4
ct
ct

.4
1

.2

13–19) returning for care:

ru
ru
ru

tru

P=
P=

P=
P=

tru

P=
ru

P=

P=
st
st
st

st

ns
ns

ed
ed

ed

In
ed

in
in

4
ed
in

ed

comparison of those who

i

/0
i

ct
ct

ct

ot
ct

ot
ot

ot
ot
ot

ct

ct

-1
ru
ru

ru
ru

N
N
N

N
N
ru
N

ru

01

received sexual abstinence

st
st

st
st

st

st

1/
In
In

In
In

In

In

ed

counseling with those who

ct
ru
st

did not
In
224
the skin-to-skin transmission of HSV90 and HPV.23
Educating that lifestyle abstinence is “restraint from
all forms of sexual intercourse until selection of life-
long partner” is important because disease transmis-
sion also occurs with nontraditional forms of sexual
intercourse and adolescents who abstain for the lon-
gest periods of time will be at least risk. For these
reasons, dermatologists and other physicians caring
for adolescents can be encouraged to incorporate life-
style abstinence counseling in health maintenance
advice alongside skin cancer prevention instruction.
19.12 STD Prevention:
Trends and Expectations
Aligned with the AMA,79 CDCP,80,81 and AAP82 rec-
ommendations, 91–95% adults and 92–94% adoles-
cents surveyed annually from 2001 to 2004 agree that
it is important for teens to be given “a strong message
from society to abstain from sex until they are at least
out of high school.”91–95 The community physician
likely recognizes the importance of such a message
since survey has shown that 49% of people with an
STD had gone to a private practice for treatment.96
Furthermore, sexual abstinence counseling may be
most effective if done specifically by the physician
since patients who received physician advice on other
topics, such as diet and exercise were significantly
more likely to engage in risk reduction activities97 and
when physicians provide brief simple advice on smok-
ing cessation there is a small but significant increase in
cessation rates.98 Primary care and pediatrics practices,
where health maintenance advice for the adolescent is
expected, can be encouraged to include lifestyle absti-
nence counseling alongside routine counsel against
tobacco, drinking, illicit drug use, and promotion of
exercise and healthy diet. However, since childhood
immunizations are completed at age 12,99 the primary
care provider may have fewer opportunities to advise
the adolescent than the dermatologist.
Ramsay et al. reported in 1986 that both dermatolo-
gists and dermatology training program directors over-
whelmingly supported an increase in dermatology’s
role in the treatment of sexually transmitted disease
and in public awareness of our interest and ability.100
More than 20 years later it is expected that dermatolo-
gists, who understand skin-to-skin transmission of
K. K. Dernovsek
disease and still regularly treat genital HSV, genital
warts and other STDs, are sufficiently motivated to pre-
vent these infections and will assume a leadership role
as physicians in educating adolescent patients, of whom
they have many. In 1997, a panel addressed the “hidden
epidemic” of STDs and called for private sector organi-
zations and for clinicians to assume more leadership in
and responsibility for STD prevention especially among
adolescents.1 For example, if dermatology, as a spe-
cialty, were to publish a pamphlet for facilitation of
youth counsel in abstinence by dermatologists and pri-
mary care physicians alike, we might positively impact
the sexual health of untold numbers of adolescent
patients. This opportunity for prevention is certainly
more desirable than the necessity of treatment.
Lowell A. Goldsmith, MD, the Clarence S.
Livingood, MD lecturer, said in his address at the
national meeting of the American Academy of
Dermatology in 2001 that dermatologists should have
a goal to think about health promotion every day and
to promote the concept to their patients. Aligned with
that vision, there is a daily opportunity to reduce mor-
bidity and mortality by encouraging adolescent
patients toward the healthiest sexual behavior. Yet, in
a 2004 survey of clinicians, 91% of whom agreed that
abstinence was a highly effective method for preven-
tion of HPV infection acquisition, only 54% recom-
mended abstinence to their adolescent patients.101 It
appears that we are reluctant to counsel abstinence to
our adolescent patients perhaps because we hold little
hope that they might choose it. The evidence shows
otherwise: the Youth Risk Behavior Surveys showed a
reversal from 1991 to 2001 in what had been in prior
years, elevating trends of teen sexual experience (“ever
having had sexual intercourse”),102 and in both 2007
and 2005, 52–53% of high school students described
themselves as not yet having experienced first sexual
intercourse.103,104 Surveys in 2003 of slightly younger
adolescents, aged 15–17, revealed 63105 and 67%106
had never had sexual intercourse.
Dermatologists have the expertise in STDs and see
adolescents regularly as patients and thus are ideally
situated to correctly counsel them. Even if the absti-
nence counsel were followed only temporarily, post-
ponement of sexual activity would reduce the number
of lifetime partners, in turn reducing the risk of STD
acquisition. On the other hand, if the lifestyle absti-
nence counsel were heeded, it would positively impact
that patient’s health for a lifetime.
19  Prevention of Sexually Transmitted Diseases from Office to Globe
19.13 Sexual Behavior
Change Yields Health
Is there evidence that people can change sexual behav-
ior with a resultant improvement in health? The answer
is found in the story of Uganda. This sub-Saharan
African nation reversed what had been the highest
rates of HIV/AIDS in the world – and did so without
Western world public health direction. Ugandan lead-
ership inspired culturally appropriate sexual behavior
change as the means by which to save lives, their cul-
ture, and their youth. What followed was a dramatic
drop in HIV prevalence rates, as was said in 2003, and
still holds true today: “… Uganda has experienced the
most significant decline in HIV prevalence of any
country in the world…”107 Without a doubt, what hap-
pened in Uganda, at an estimated cost of only$1.80
per adult per year over a 10-year period (1989–
1998)108 is the greatest public health achievement of
this millennium. The scientific evidence demonstrat-
ing population level risk-avoidance behavior change
which in turn resulted in reduced HIV prevalence rates
should irrefutably and without delay shift global pub-
lic health strategy in the fight against AIDS. The
Ugandan strategy is a low-cost model with potential
for eradicating global AIDS if other countries can
implement similar risk-elimination behavior change.
During the years from 1986 to 2001 the dramatic
drop in HIV prevalence was observed in Uganda while
simultaneously elsewhere in sub-Saharan Africa the
HIV prevalence was rising.109 This remarkable anomaly
was first reported in 2002, in a landmark presentation
to USAID in which the authors reported that “The most
important determinant of the reduction in HIV inci-
dence in Uganda appears to be a decrease in multiple
sexual partnerships and networks.” They further con-
cluded that “The effect of HIV prevention interventions
in Uganda (particularly partner reduction) during the
past decade appears to have had a similar impact as a
potential medical vaccine of 80% efficacy.”108
Most notable was that this strategy was a conceptu-
ally simple, financially achievable, culturally appropri-
ate indigenous response incorporating broad-sector
community involvement under presidential leadership.
The Ugandan president, Yoweri Museveni had entered
office in 1986 and found a high percentage of the mili-
tary infected with HIV. In those tenuous years immedi-
ately following the regimes of Idi Amin and Milton
Obote, and until about 1995, Uganda was without
225
Western world influences on public health strategy
development. President Museveni encouraged Ugandan
community leaders in medicine, religion, media, and
education to work together toward the goal of prevent-
ing AIDS, in order to save Uganda. He and First Lady
Janet Museveni (who was to became a key youth moti-
vator via the Uganda Youth Forum) heightened aware-
ness about AIDS, dispelled myths about its cause, and
warned people that AIDS caused death, but that AIDS
could be stopped. AIDS was a danger to Uganda’s sur-
vival, so appropriate to African context, they sent out
an “alarm” to “call” to all Ugandans that, by their own
sexual behavior of abstaining from sexual activity and
being faithful in marriage, they could completely avoid
death from AIDS.110 This homegrown public health
campaign was disseminated widely in schools, from
pulpits and taken up by the media and performing arts.
It was culturally appropriate and easily understood by
an African agrarian population. For example, the idea
of sticking only to one partner was called “zero graz-
ing.” This concept was easily understood by rural peo-
ple via communication of a metaphor that made sense
to them: “You tether your animal around a tree, and it
can only feed where it is tethered.”111 The First Lady
encouraged youth to abstain at every opportunity, stat-
ing about her efforts, “Young people must be taught the
virtues of abstinence, self-control and postponement of
pleasure and sometimes sacrifice” and teaching them a
different lifestyle “will ensure their survival.”112
When the Ugandan success was summarized to
USAID in 2002, it described the “matter-of-fact,” inspi-
rational approach used by President Museveni and thou-
sands of community, religious, and government leaders
who encouraged “delayed sexual activity, abstaining,
being faithful, ‘zero grazing’ and using condoms
(roughly in that order).”108 As Mrs. Museveni herself has
noted, the condom message was targeted to adults who
were “already infected with HIV” or were “set in their
ways” and unlikely to change their risky behaviors.110
Uganda’s unique strategy had been under scientific scru-
tiny since the late 1990s by WHO and other organiza-
tions and was sometimes “conveniently” abbreviated
ABC although “Uganda did in fact emphasize A (absti-
nence) and B (being faithful) before advising C (con-
doms).”113 In other words, the elements of the abbreviation
were not equivalent; “their rank order reflects the prior-
ity in which they arguably ought to be considered, since
it is a basic public health maxim that avoiding a risk is
inherently better than reducing a risk.”113
226
Others have likewise concluded that the emphasis
was on A and B, abstinence and being faithful: “con-
doms were a minor component of the original strat-
egy.”114 It is reported that prior to 1995 in Uganda there
were “few” condoms available in 1987, 15 million in
1989, 12 million in 1991, 10 million in 1992, and 22
million in 1993.115 Given 4,548,701 men over age 15 in
Uganda in 1990116 it can be calculated that at best, prior
to 1995, each Ugandan man had two to five condoms
in a year that he had any condoms at all.
In fact, condom distribution by the Ministry of
Health did not begin until the early to mid-1990s and
condom sales did not reach substantial levels until the
later 1990s when Population Services International
began its more successful condom sales program in
1997.117 During this time of limited condom availability,
the data show that HIV prevalence nationally among
pregnant women had peaked in 1991 at 21.1% and
already by 1998 had declined to 9.7% (a decline of 54%
apparent in both rural and urban settings) (Fig. 19.4).114
It has been concluded that “nearly all of the decline
in HIV incidence (and much of the decline in preva-
lence) had already occurred by 1995” in response to
social acceptance of the sexual behavior change mes-
sages of abstinence and faithfulness.117 The role of pri-
mary risk avoidance behavior change (reflective of the
A, Abstinence) is substantiated by analysis of Ugandan
population-based surveys of HIV behavioral risk indi-
cators between 1989 and 1995 which show increase in
the age of sexual debut in all youth aged 15–24 except
40
35
30
HIV prevalence (%)
25
20
Fig. 19.4  HIV prevalence
rates (%) in pregnant 15
women surveyed at
antenatal sentinel surveil- 10
lance sites in Uganda in
urban Kampala, other urban
5
sentinel sites, and rural sites
from 1985 to 2001. Adapted
from Stoneburner.114 Used 0
with permission
K. K. Dernovsek
rural females,114 who traditionally marry young, such
that their age of sexual debut remained unchanged
(Fig. 19.5). Partner reduction (reflective of the B, Be
faithful) is demonstrated by a 60% reduction in per-
sons reporting casual sexual partnerships in the previ-
ous year in all population groups studied. (male and
female, urban, and rural) (Fig. 19.5). The authors con-
clude that “HIV reductions in Uganda resulted from
public-health interventions that triggered a social pro-
cess of risk avoidance manifested by radical changes
in sexual behavior.”114
Given the historical and scientific data, it is not sur-
prising that there are Ugandans who reflect that their
success would have been more aptly called “AB,” write
out the abbreviation as ABc while vocalizing, “AB,
little c” (personal communications and observations.
Dernovsek, KK. Mbarara and Kampala, Uganda, 1–31
Oct 2003), or say it was simply, “AB-Stop!” or “AB-Full
stop!”118 Indeed, in Washington DC (2003), the Uganda
Youth Forum Coordinator wrote out, “Abstinence and
Being faithful are the best Choices.”119 In federal testi-
mony, Edward C. Green, PhD, Senior Research
Scientist with the Harvard Center for Population and
Development Studies, reported concern about a grad-
ual change away from the original endogenously devel-
oped Ugandan strategy toward “medical solutions”
with less emphasis on sexual behavior. He concluded,
“The distinctive Uganda ABC model of the earlier
period, the one developed primarily by Ugandans for
Ugandans, is the one that seems to have worked best,
Kampala
Kampala age 15-19
Kampala age 20-24
Other urban
Rural
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
19  Prevention of Sexually Transmitted Diseases from Office to Globe 227

Fig. 19.5  Changes in the Males non-regular partner

proportion of persons Females non-regular partner

45% Males never sex age 15-24
reporting sex with a
Females never sex age 15-24
nonregular partner in the 40%
previous 12 months and 36%
35%
persons aged 15–24 32%
reporting never having had 30%
sex in Uganda among adult

affirmative response
25%
populations, measured by
population-based behav- 20% 19%
ioral surveys performed in 17%
15% 14%
1989 and in 1995, by sex 12%
and population characteris- 10%
tics. Adapted from 6%
5%
5%
Stoneburner.114 Used with
permission 0%
1989 1995 1989 1995

Urban Rural

and is the one that has most to teach the rest of the
world.”120 It is no wonder, with increasing condom
social marketing117 to the general population, including
youth, that Ugandans should feel frustrated to the point
of staging abstinence marches and rallies to “stop
abstinence stigma” (personal communication from
participant, Oct 2006, Kampala Uganda), finding it
counterproductive that the Western world promotes
condoms in their country instead of supporting what
the evidence showed was successful: their own grass-
roots AB method of primary behavior change.
19.14 Preventing STDs:
The New Global Paradigm
During the last 25 years, a risk-reduction, condom/
safe/safer sex public health paradigm has been applied
broadly, including to youth, in the United States and
around the globe. The evidence reported herein indi-
cates that both, youth in the United States and the gen-
eralized population of Uganda, Africa are capable of
risk-avoidance via abstinence, lifetime monogamy
(being faithful), and/or motivated toward those life-
styles for personal/social/health reasons. The numbers
of STDs, the serious health consequences, the variable
effectiveness of existing prevention parameters (con-
doms, vaccines, microbiocides, treatment) has compli-
cated individual patient management and inevitably
will overwhelm an already overburdened healthcare
system, especially at the global level.
We stand at a crossroads in public health paradigm
that could alter forever the survival of the inhabitants
of sub-Saharan Africa, (i.e., the black race), and those
human beings in all areas in the world facing the AIDS
pandemic. The grim statistics indicate that every 8 sec-
onds a person is infected with HIV somewhere in the
world. This equates to 6,800 new infections per day.
Sixty-eight percent of the 33.2 million people with
HIV live in Sub-Saharan Africa.121 It has been a num-
ber of years since the HIV prevalence in Uganda
reached its low in 2001 at 5% and was reported to the
world in 2003. At last survey in 2007, Ugandan HIV
prevalence was holding at 5.4%.122 What role increas-
ing condom social marketing, occurring over the objec-
tions of the Ugandans themselves, will have on their
success is yet to be observed.
Hearst and Chen have shown graphically that in
Cameroon, Kenya, and Botswana, from 1990 to 2001,
“urban and rural HIV prevalence have gone up right
along with condom sales.”123 Likewise, from 1989 to
2000, South Africa, Botswana and Zimbabwe, had the
highest rates of condom availability (seven to ten con-
doms per year per man) yet had the highest HIV preva-
lence rates, ranging from 20 to 36%.124 While causality
is unproven, there likewise “is no evidence at the
national level in Africa that more condoms have
resulted in less AIDS.”124 In 2005, Kajubi et al. reported
that gains in condom use by Ugandan men in a con-
dom promotion program seemed to have been offset
by increases in the number of sex partners.125 This phe-
nomenon of “risk compensation” (discussed in Sect.
19.3) refers to the perception of reduced risk being
228
compensated for by a paradoxical increase in risky
behavior. In a 2006 commentary published in British
Medical Journal, the authors questioned whether vac-
cines, microbicides, and male circumcision could be
compensated for by an increase in risky behavior and
thus concluded that with regard to HIV prevention,
“successful approaches to change behavior must be
studied, adapted, and applied with at least the same
vigor as the promising host of technological innova-
tions under development.”126
Time is short as we confront the most serious of all
STDs in the global AIDS pandemic. The UNAIDS/
WHO 2006 AIDS Epidemic Report challenges all of
us who counsel youth: “The future course of the
world’s HIV epidemics hinges in many respects on
the behaviors young people adopt or maintain, and the
contextual factors that affect those choices.”127 If we
take aim with a goal to prevent all STDs, especially in
youth, we need to move quickly and, following the
example set by Uganda, align with the same risk avoid-
ance message.
The available scientific evidence supports that the
risk-reduction, “safe/safer sex” or “vaccinate, con-
domize and treat” paradigm was and is not enough.
Also established is that the risk-avoidance, Absti­
nence/Be faithful paradigm is both “realistic” and
effective and it is consistent with existing medical
guidelines. It is an “umbrella approach,” that is best
suited to protect vast numbers of people from all
STDs whether in-office or around the globe. Subset
at-risk populations can be targeted specifically to
their risk behavior but always with the goal of mov-
ing them toward the healthiest behavior, no different
than what a physician would do in the office with an
individual patient. The Ugandan model has demon-
strated that behavior can be changed, that sexual
behavior can be changed, that health can be preserved
and that lives can be saved. Dermatologists/venere-
ologists, other physicians, scientists, and leaders,
capable of capturing this vision and willing to learn
from a developing nation, should be given the lead to
establish risk-avoidance strategies worldwide. The
Ugandan success model is low cost and simple but
requires that community leaders get “on the same
page” with a single, clear message that Abstinence
and Being faithful are the best Choices. That is what
the scientific evidence indicates needs to be done for
the health of all people around the globe. There is no
time to lose.
K. K. Dernovsek
References
  1. Executive summary, committee on prevention and control of
sexually transmitted diseases. Institute of medicine. In: Eng
TR, Butler WT, eds. The Hidden Epidemic: Confronting
Sexually Transmitted Disease. Washington, DC: National
Academy; 1997:1–17
  2. Centers for Disease Control and Prevention. Tracking the
hidden epidemics 2000. Available at: http://www.cdc.gov/
std/Trends2000/Trends2000.pdf; 2009 Accessed 29.05.09
  3. Weinstock H, Berman S, Cates W Jr. Sexually transmitted
diseases among American youth: incidence and preva-
lence estimates, 2000. Perspect Sex Reprod Health. 2004;
36(1):6–10
  4. Neinstein LS. Adolescent Health Care: A Practical Guide.
4th ed. Philadelphia: Lippincott Williams and Wilkins;
2002
  5. Kahn JA, Hillard PA. Human papillomavirus and cervical
cytology in adolescents. Adolesc Med Clin. 2004;15:
301–321
  6. Corey L, Handsfield HH. Genital herpes and public health:
addressing a global problem. JAMA. 2000;283(6):791–794
  7. Centers for Disease Control and Prevention. Sexually trans-
mitted diseases treatment guidelines 2006. MMWR
2006:55(No. RR-11):16
  8. Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ,
Aral SO, Lee FK, St Louis ME. Herpes simplex virus type 2
in the United States, 1976 to 1994. N Engl J Med.
1997;337(16): 1105–1111
  9. Wald A, Zeh J, Selke S, et al Reactivation of genital herpes
simplex virus type 2 infection in asymptomatic seropositive
persons. N Engl J Med. 2000;342(12):844–850
10. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of
herpes simplex virus type 1 as a cause of genital herpes
infection in college students. Sex Transm Dis. 2003;30 (10):
797–800
11. Tyring SK. Drugs with antiviral activity in clinical dermatol-
ogy. Dialogues in Dermatology. 1998 Jul;42(4)
12. Xu F, Sternberg MR, Kottiri BJ, et al Trends in herpes sim-
plex virus type 1 and type 2 seroprevalence in the United
States. JAMA. 2006;296(8):964–973
13. Sonfield A, Gold RB. States’ implementation of the Section
510 abstinence education program, FY 1999. Fam Plann
Perspect. 2001;33(4):166–171
14. Ali L, Scelfo J. Choosing virginity. Newsweek. 2002;140(24):
60–64, 66
15. Maw RD, Reitano M, Roy M. An international survey of
patients with genital warts: perceptions regarding treatment
and impact on lifestyle. Int J STD AIDS. 1998;9(10):571–578
16. Reitano M. Counseling patients with genital warts. Am
J Med. 1997;102(5A):38–43. Review
17. Centers for Disease Control and Prevention. Sexually trans-
mitted diseases treatment guidelines 2006. MMWR 2006;
55[No.RR-11]63. Available at: http://www.cdc.gov/std/
treatment/2006/rr5511.pdf; 2009 Accessed 27.05.09
18. Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD.
Natural history of cervicovaginal papillomavirus infection in
young women. N Engl J Med. 1998;338(7):423–428
19. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB,
Koutsky LA. Genital human papillomavirus infection:
19  Prevention of Sexually Transmitted Diseases from Office to Globe
i­ncidence and risk factors in a cohort of female university
students. Am J Epidemiol. 2003;157(3):218–226
20. Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué
X, Shah KV, Snijders PJ, Meijer CJ, International Agency
for Research on Cancer Multicenter Cervical Cancer Study
Group. Epidemiologic classification of human papillomavi-
rus types associated with cervical cancer. N Engl J Med.
2003;348(6):518–527
21. Centers for Disease Control and Prevention. Youth risk
behavior surveillance-United States, 2005. MMWR 2006;55
(No.SS–05)
22. National Institute of Allergy and Infectious Diseases,
Workshop Summary: Scientific Evidence on Condom Effec­
tiveness for Sexually Transmitted Disease (STD) Prevention,
July 20, 2001. Available at: http://www3.niaid.nih.gov/
about/organization/dmid/PDF/condomReport.pdf; 2009
Accessed 29.05.09
23. Centers for Disease Control and Prevention, Report to
Congress: Prevention of genital human papillomavirus
infection. Jan 2004. Available at: http://www.cdc.
gov/std/HPV/2004HPV%20Report.pdf; 2009 Accessed
27.05.09
24. Winer RL, et al Condom use and the risk of genital human
papillomavirus infection in young women. N Engl J Med.
2006;354(25):2645–2654
25. Centers for Disease Control and Prevention, Human
Papilloma Virus: HPV information for clinicians. April
2007. Available at: http://www.cdc.gov/std/HPV/hpv-
clinicians-brochure.htm; 2009 Accessed 27.05.09
26. Unger ER, Barr E. Human papillomavirus and cervical can-
cer, conference summary. Emerg Infect Dis 2004 Nov.
Available at: http://www.cdc.gov/ncidod/EID/v0110n011/
04–0623_09.htm; 2009 Accessed 27.05.09
27. Centers for Disease Control and Prevention, HPV Vaccine
Information for Clinicians. June 26, 2008. Available at:
http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-
hcp.htm; 2009 Accessed 27.05.09
28. Centers for Disease Control and Prevention, Vaccine infor-
mation statement (interim) human papillomavirus (HPV)
Vaccine. 2007 Feb 2. Available at: http://www.cdc.gov/vac-
cines/pubs/vis/default.htm#hpv; 2009 Accessed 27.05.09
29. Centers for Disease Control and Prevention, Reports of
Health Concerns Following HPV Vaccination. 2009 June 10.
Available at: http://www.cdc.gov/print.do?url=http%3A%2
F%2Fwww.cdc.gov%2Fvaccinesafety%2Fvaers%2Fgardasi
l.htm; 2009 Accessed 29.06.09
30. Centers for Disease Control and Prevention, HPV vaccine
information for young women. June 26, 2008. Available at:
http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-young-
women.htm#hpvvac4; 2009 Accessed 01.06.09
31. Kim JJ, Goldie SJ. Health and Economic Implications of
HPV Vaccination in the United States. N Engl J Med. 2008;
359(8):821–832
32. Salmon DA, Teret SP, MacIntyre CR, Salisbury D, Burgess
MA, Halsey NA. Compulsory vaccination and conscientious
or philosophical exemptions: past, present, and future.
Lancet. 2006;367(9508):436–442
33. Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC,
Patel SS, Markowitz LE. Prevalence of HPV infection
among females in the United States. JAMA. 2007;297:
813–819. Erratum JAMA 2007;298(2):178
229
34. Gostin LO, DeAngelis CD. Mandatory HPV vaccination:
public health vs private wealth. JAMA. 2007;297(17):1921–
1923. Erratum JAMA 2007;298(2):178
35. Sawaya GF, Smith-McCune K. HPV vaccination – more
answers, more questions. N Engl J Med. 2007;356(19):
1991–1993
36. The FUTURE II Study Group. Quadrivalent vaccine against
human papillomavirus to prevent high-grade cervical lesions.
N Engl J Med. 2007;356:1915–1927
37. Haug CJ. Human papillomavirus vaccination – reasons for
caution. N Engl J Med. 2008;359(8):861–862
38. Saslow D, Castle PE, Cox JT, et al American Cancer Society
guideline for human papillomavirus (HPV) vaccine use to
prevent cervical cancer and its precursors. CA Cancer J Clin.
2007;57:7–28
39. American Cancer Society. Cancer Facts and Figures 2009.
Atlanta: American Cancer Society;2009. Available at: http://
www.cancer.org/docroot/STT/STT_0.asp; 2009 Accessed
29.05.09
40. Janerich DT, Hadjimichael O, Schwartz PE, et  al The
screening histories of women with invasive cervical
cancer, Connecticut. Am J Public Health. 1995;85(6):
791–794
41. Stuart GC, McGregor SE, Duggan MA, Nation JG. Review
of the screening history of Alberta women with invasive cer-
vical cancer. CMAJ. 1997;157(5):513–519
42. Sung HY, Kearney KA, Miller M, Kinney W, Sawaya GF,
Hiatt RA. Papanicolaou smear history and diagnosis of inva-
sive cervical carcinoma among members of a large prepaid
health plan. Cancer. 2000;88(10):2283–2289
43. Leyden WA, Manos MM, Geiger AM, et al Cervical cancer
in women with comprehensive health care access: attribut-
able factors in the screening process. J Natl Cancer Inst.
2005;97(9):675–683
44. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statis-
tics, 2002. CA Cancer J Clin. 2005;55:74–108
45. Department of Health and Human Services. Food and Drug
Administration Docket No. 02D-0103. Draft revised com-
pliance policy guide; male condom defects; availability. Fed
Regist. 2002;67(61):15213–15214
46. Herman BA, Carey RF. Validation of a corona discharge
technique to test male latex condoms for pinhole defects.
J Test Eval. 1999;27(1):3–6
47. World Health Organization. WHO Laboratory Manual for
the Examination of Human Semen and Sperm-Cervical
Mucus Interaction. 4th ed. Cambridge University Press, UK;
New York, NY; 1999:19–21
48. Lytle CD, Routson LB, Seaborn GB, Dixon LG, Bushar HF.
Cyr WH.An in vitro evaluation of condoms as barriers to a
small virus. Sex Transm Dis. 1997;24(3):161–164
49. Modis Y, Trus BL, Harrison SC. Atomic model of the papil-
lomavirus capsid. EMBO J. 2002;21(18):4754–4762
50. Carey RF, Lytle CD, Cyr WH. Implications of laboratory
tests of condom integrity. Sex Transm Dis. 1999;26(4):
216–220
51. Lytle CD, Duff JE, Fleharty B, Bidinger RL, Cyr WH. A
sensitive method for evaluating condoms as barriers. J AOAC
Int. 1997;80(2):319–324
52. Fu H, Darroch JE, Haas T, Ranjit N. Contraceptive failure
rates: new estimates from the 1995 National Survey of
Family Growth. Fam Plann Perspect. 1999;31(2):56–63
230
53. Morris BA. How safe are safes? Efficacy and effectiveness
of condoms in preventing STDs. Can Fam Physician.
1993;39:819–822, 827. Review
54. Cates W Jr, Stone KM. Family planning, sexually transmit-
ted diseases and contraceptive choice: a literature update –
Part I. Fam Plann Perspect. 1992;24(2):75–84. Review
55. Judson FN, Ehret JM, Bodin GF, Levin MJ, Rietmeijer CA.
In vitro evaluations of condoms with and without nonoxynol
9 as physical and chemical barriers against chlamydia tra-
chomatis, herpes simplex virus type 2 and human immuno-
deficiency virus. Sex Transm Dis. 1989;16(2):51–56
56. D’Oro LC, Parazzini F, Naldi L, La Vecchia C. Barrier methods
of contraception, spermicides, and sexually transmitted dis-
eases: a review. Genitourin Med. 1994;70(6):410–417. Review
57. Grady WR, Tanfer K. Condom breakage and slippage among
men in the United States. Fam Plann Perspect. 1994;26
(3):107–112
58. Trussel J, Warner DL, Hatcher RA. Condom slippage and
breakage rates. Fam Plann Perspect. 1992;24(1):20–23
59. Trussel J, Warner DL, Hatcher RA. Condom performance
during vaginal intercourse: comparison of Trojan-Enz and
Tactylon condoms. Contraception. 1992;45(1):11–19
60. Macaluso M, Kelaghan J, Artz L, et al Mechanical failure of
the latex condom in a cohort of women at high STD risk. Sex
Transm Dis. 1999;26(8):450–458
61. Darrow WW. Condom use and use-effectiveness in high-risk
populations. Sex Transm Dis. 1989;16(3):157–160
62. Warner L, Clay-Warner J, Boles J, Williamson J. Assessing
condom use practices. Implications for evaluating method
and user effectiveness. Sex Transm Dis. 1998;25(6):273–277
63. Rose E, et al The validity of teens’ and young adults’ self-
reported condom use. Arch Pediatr Adolesc Med. 2009;
163(1):61–64
64. Crosby RA, DiClemente RJ, Wingood GM, Lang D,
Harrington KF. Value of consistent condom use: a study of
sexually transmitted disease prevention among African
American adolescent females. Am J Public Health. 2003;93
(6):901–902
65. Saracco A, et al Man-to-woman sexual transmission of HIV:
longitudinal study of 343 steady partners of infected men.
J Acquir Immune Defic Syndr. 1993;6(5):497–502
66. Anderson JE, Brackbill R, Mosher WD. Condom use for
disease prevention among unmarried U.S. women. Fam
Plann Perspect. 1996;28(1):25–28
67. Wald A, Langenberg AG, Link K, et al Effect of condoms on
reducing the transmission of herpes simplex virus type 2
from men to women. JAMA. 2001;285(24):3100–3106
68. Wald A, Langenberg AG, Krantz E, et  al The relationship
between condom use and herpes simplex virus acquisition.
Ann Intern Med. 2005;143(10):707–713
69. de Vincenzi I, European Study Group on Heterosexual
Transmission of HIV. A longitudinal study of human immu-
nodeficiency virus transmission by heterosexual partners.
European Study Group on Heterosexual Transmission of
HIV. N Engl J Med. 1994;331(6):341–346
70. Fitch JT, Stine C, Hager WD, Mann J, Adam MB, McIlhaney
J. Condom effectiveness: factors that influence risk reduc-
tion. Sex Transm Dis. 2002;29(12):811–817
71. Centers for Disease Control and Prevention. Sexually trans-
mitted diseases treatment guidelines 2006. MMWR 2006;
55(No. RR-11):4
K. K. Dernovsek
72. Medical Institute of Sexual Health, conference on sexual
health in the 21st Century. Fitch JT, oral presentation 2000
Nov; San Antonio TX
73. Department of Health and Human Services. Food and Drug
Administration Docket No. 2004N-0556. Designation of spe-
cial control for condom and condom with spermicidal lubri-
cant; proposed rule. Fed Regist. 2005;70(218):69102–69118
74. A series of national surveys of teens about sex:safer sex, con-
doms and “the pill.” 2000 Nov. Menlo Park, CA: Kaiser Family
Foundation. Available at: http://www.kff.org/youthhivstds/
20001127b-index.cfm; 2009 Accessed 27.05.09
75. National survey of adolescents and young adults: sexual
health knowledge, attitudes and experiences 2003 May 19.
Kaiser Family Foundation. Available at: http://www.kff.org/
youthhivstds/3218-index.cfm; 2009 Accessed 27.05.09
76. Centers for Disease Control and Prevention. Preventing the
sexual transmission of HIV, the virus that causes AIDS. Dec
2000. Available at: www.cdc.gov/hiv/resources/factsheets/
pdf/oralsex.pdf; 2009 Accessed 27.05.09
77. Dernovsek KK. Sex, Teens and the dermatologist: recognize
your role in preventing the spread of STDs. Practical
Dermatology. Dec 2004
78. Dernovsek KK. Teens and STDs: a new message for a
healthy millennium. School Health Reporter; spring 2003:
1–3. Available at: http://www.thechildrenshospital.org/
news/publications/school_health_reporter/2003/std.aspx;
2009 Accessed 27.05.09
79. American Medical Association. Guidelines for Adolescent
Preventive Services (GAPS) Recommendations Monograph.
Chicago, Il:1997:4. Available at: http://www.ama-assn.org/
ama/upload/mm/39/gapsmono.pdf; 2009 Accessed 27.05.09
80. Centers for Disease Control and Prevention. Sexually trans-
mitted diseases treatment guidelines 2002. MMWR 2002;
51(No. RR-6):2. Available at: http://www.cdc.gov/STD/
treatment/TOC2002TG.htm; 2009 Accessed 27.05.09
81. Centers for Disease Control and Prevention. Sexually trans-
mitted diseases treatment guidelines 2006. MMWR 2006;
55[No.RR-11]3. Available at: http://www.cdc.gov/std/treat-
ment/2006/rr5511.pdf; 2009 Accessed 27.05.09
82. Klein JD; Committee on Adolescence. Adolescent preg-
nancy: current trends and issues. Pediatrics. 2005;116;
291–286. Available at: http://pediatrics.aappublications.org/
cgi/content/full/116/1/281; 2009 Accessed 27.05.09
83. Burstein GP, Lowry R, Klein JD, Santelli JS. Missed opportuni-
ties for sexually transmitted diseases, human immunodeficiency
virus, and pregnancy prevention services during adolescent
health supervision visits. Pediatrics. 2003; 111: 996–1001
84. Rand CM, Auinger P, Klein JD, Weitzman M. Preventive
counseling at adolescent ambulatory visits. J Adolesc Health.
2005;37:87–93
85. Haley N, Maheux B, Rivard M, Gervais A. Sexual health
risk assessment and counseling in primary care: how involved
are general practitioners and obstetrician-gynecologists?
Am J Public Health. 1999;89(6):899–902
86. Kaplan CP, Perez-Stable EJ, Feutes-Afflick E, Gildengorin V,
Millstein S, Juarez-Reyes M. Smoking cessation counseling with
young patients. Arch Pediatr Adolesc Med. 2004; 158:83–90
87. U.S. Census Bureau: State and County QuickFacts. Data
derived from Population Estimates, 2000 Census of
Population and Housing. Available at: http://quickfacts.cen-
sus.gov/qfd/states/08/08101.html; 2009 Accessed 27.05.09
19  Prevention of Sexually Transmitted Diseases from Office to Globe
  88. Abstinence because. Austin, Texas:The Medical Institute
for Sexual Health
  89. Koutsky L. Epidemiology of genital human papillomavirus
infection. Am J Med. 1997;102(5A):3–8
  90. Whitley RF, Gnann JW. Herpes simplex virus. In: Tyring S,
Yen-Moore A, eds. Mucocutaneous Manifestations of Viral
Diseases. 1st ed. New York, NY: Marcel Dekker; 2002:103
  91. With One Voice: America’s adults and teens sound off
about teen pregnancy. Washington, DC: National Campaign
to Prevent Teen Pregnancy. April 2001. Available at: http://
www.teenpregnancy.org/resources/data/pdf/chrtbook.pdf;
2009 Accessed 27.05.09
  92. With One Voice: America’s adults and teens sound off
about teen pregnancy. Washington, DC: National Campaign
to Prevent Teen Pregnancy. December 2002. Available at:
http://www.teenpregnancy.org/resources/data/pdf/
WOV2002_fulltext.pdf; 2009 Accessed 27.05.09
  93. With One Voice 2003: America’s adults and teens sound off
about teen pregnancy. Washington, DC: National Campaign
to prevent Teen Pregnancy. December 2003. Available at:
http://www.teenpregnancy.org/resources/data/pdf/
wov2003.pdf; 2009 Accessed 27.05.09
  94. Albert B. With One Voice 2004: America’s adults and teens
sound off about teen pregnancy. Washington, DC: National
Campaign to Prevent Teen Pregnancy. December 2004.
Available at: http://www.teenpregnancy.org/resources/data/
pdf/WOV2004.pdf; 2009 Accessed 27.05.09
  95. Albert B. With One Voice 2007: America’s adults and
teens sound off about teen pregnancy. Washington, DC:
National Campaign to Prevent Teen Pregnancy. February
2007. Available at: http://www.teenpregnancy.org/product/
pdf/6_9_2007_15_17_14WOV2007_fulltext.pdf; 2009
Accessed 27.05.09
  96. Brackbill RM, Sternberg MR, Fishbein M. Where do peo-
ple go for treatment of sexually transmitted diseases? Fam
Plann Perspect. 1999;31(1):10–15
  97. Center for Disease Control and Prevention. Physician
advice and individual behavior about cardiovascular dis-
ease risk reduction B seven states and Puerto Rico, 1997.
MMWR. 1999;48:74–77
  98. Lancaster T, Stead LF. Physician advice for smoking cessa-
tion. The Cochrane Database of Systemic Reviews 2005;3
  99. Center for Disease Control and Prevention. Recommended
Immunization Schedules for persons aged 0 through 18
years – United States, 2009. MMWR 1–2–09;57(51&52);Q-
1-Q-4. Available at: http://www.cdc.gov/mmwR/preview/
mmwrhtml/mm5751a5.htm; 2009 Accessed 29.05.09
100. Ramsay DL, Weiss R, Brademas ME. Margolies, R.
National survey of dermatologists and residency training
program directors on dermatology’s role in treating sexually
transmitted diseases. J Am Acad Dermatol. 1986;14
(3):527–531
101. Centers for Disease Control and Prevention. STD-Prevention
Counseling Practices and Human Papillomavirus Opinions
Among Clinicians with Adolescent Patients – United States,
2004. MMWR 2006;55(41)1117–1120. Available at: http://
www.cdc.gov/mmwr/preview/mmwrhtml/mm5541a1.htm;
2009 Accessed 27.05.09
102. Center for Disease Control and Prevention. Trends in
Sexual Risk Behaviors Among High School Students –
United States, 1991–2001. MMWR 9–27–02 /51(38);
231
856–859. Available at: http://www.cdc.gov/mmwr/preview/
mmwrhtml/mm5138a2.htm; 2009 Accessed 27.05.09
103. Center for Disease Control and Prevention. Youth risk
behavior surveillance-United States, 2007. MMWR6-6-
08/58(SS-4);1. Available http://www.cdc.gov/mmwr/PDF/
ss/ss5704.pdf Accessed December 5, 2009
104. Center for Disease Control and Prevention. Trends in
HIV-related risk behaviors among high school students –
United States, 1991–2005. MMWR 8–11–06/ /55(31);
851–4. Available at: http://www.cdc.gov/mmwr/preview/
mmwrhtml/mm5531a4.htm; 2009 Accessed 27.05.09
105. National Survey of Adolescents and Young Adults: Sexual
Health Knowledge, Attitudes and Experiences. 2003.
Menlo Park, CA: Kaiser Family Foundation. Available
at: http://www.kff.org/youthhivstds/3218-index.cfm; 2009
Accessed 27.05.09
106. A Series of National Surveys of Teens About Sex: Virginity
and the First Time. Menlo Park, CA: Kaiser Family
Foundation. October 2003. Available at: http://www.kff.
org/entpartnerships/3368-index.cfm; 2009 Accessed 27.05.09
107. U.S. Agency for International Development. Green
EC. Faith-based organizations:contributions to HIV preven-
tion. Sep 2003. Available at: http://www1.usaid.gov/our_
work/global_health/aids/TechAreas/community/fbo.pdf;
2009 Accessed 29.05.09
108. U.S. Agency for International Development. Hogle JA, Green
E, Nantulya V, Soneburner R, Stover J. What happened in
Uganda? Declining HIV prevalence, behavior change, and
the national response. Sep 2002. Available at: http://www.
usaid.gov/our_work/global_health/aids/Countries/africa/
uganda_report.pdf; 2009 Accessed 27.05.09
109. World Health Organization/ UNAIDS. HIV/AIDS in sub-
Saharan Africa, July 2002. Slide #SSA-5. Available at:
www.who.int/hiv/facts/en/Sub-SaharanAfrica.ppt; 2009
Accessed 29.05.09
110. Address by Her Excellency Janet K. Museveni, First Lady
of the Republic of Uganda. “Common Ground: A Shared
Vision for Health” Conference hosted by Medical Institute
for Sexual Health. Washington DC June 17–19 2004.
Available at: http://uceglobal.org/pdf/mrsMuseveniAddress.
pdf; 2009 Accessed 27.05.09
111. Allen A. “Uganda vs condoms.” The New Republic. May
27, 2002
112. Address by Her Excellency Janet K. Museveni, First Lady
of the Republic of Uganda. Samaritan’s Purse “Prescription
for Hope” conference on HIV/AIDS. February 20, 2002 in
Washington, D.C Accessed at http://www.usinfo.state.gov/
topical/global/hiv/02022710.htm. No longer available
113. Green EC, Herling A. The ABC approach to preventing the
sexual transmission of HIV: common questions and answers.
Mclean VA: Christian Connections for International Health
and Medical Service Corporation International, 2007
114. Stoneburner RL, Low-Beer D. Population-level HIV
declines and behavioral risk avoidance in Uganda. Science.
2004;304:714–717
115. Success in Uganda: An Overview of Uganda’s Campaign
to Change Sexual Behaviors and Decrease HIV Prevalence
1986–1995 Douglas Kirby ETR Assoc. 9/2008
116. Available at: http://www.nationmaster.com/red/graph/peo_
pop-people-population&date=1990&ob=ws and http://
www.nationmaster.com/graph/peo_pop_age_014_of_tot-
232
population-ages-0-14-total&date=1990 and http://www.
nationmaster.com/red/graph/peo_pop_fem_of_tot-
people-population-female-of-total&date=1990&ob=ws;
2009 Accessed 29.05.09
117. Green EC, Halperin DT, Nantulya V, Hogle JA. Uganda’s
HIV prevention success: the role of sexual behavior change
and the national response. AIDS Behav. 2006;10(4):
335–346
118. Ssempa M. Presentation at the International Leadership
Conference sponsored by the National Abstinence Clearing­
house. Kansas City KS. Jun 8, 2006
119. Bampata EK. Presentation at “HIV/AIDS Prevention for
Young People in Developing Countries,” a conference
sponsored by USAID Office of HIV/AIDS, Institute for
Youth Development, YouthNet/Family Health International.
24 July 2003. Washington DC
120. Green EC. Senior Research Scientist. Harvard Center for
Population and Development Studies. Testimony before the
African subcommittee U.S. Senate. Available at: foreign.
senate.gov/testimony/2003/GreenTestimony030519.pdf;
2008 Accessed 18.05.09
121. Joint United Nations Programme on HIV/AIDS (UNAIDS)
and World Health Organization (WHO) AIDS Epidemic
update December 2007. Available at: http://data.unaids.
K. K. Dernovsek
org/pub/EPISlides/2007/2007_epiupdate_en.pdf; 2009
Accessed 27.05.09
122. UNAIDS/WHO Epidemiologic Fact Sheet on HIV and
AIDS, October 2008 Update, Uganda. Available at: http://
who.int/globalatlas/predefinedReports/EFS2008/full/
EFS2008_UG.pdf; 2009 Accessed 27.05.09
123. Hearst N, Chen S. Condom promotion for AIDS preven-
tion in the developing world: is it working? Evidence
That Demands Action. Austin TX: The Medical Institute
2004
124. Green EC. Moving toward evidence-based AIDS preven-
tion. Evidence That Demands Action. Austin TX: The
Medical Institute 2004
125. Kajubi P, et  al Increasing condom use without reducing
HIV risk: results of a controlled community trial in Uganda.
J Acq Immune Defic Syndr. 2005;40(1):77–82
126. Cassell MM, Halperin DT, Shelton JD, Stanton D. Risk
compensation: the Achilles’ heel of innovations in HIV
prevention? BMJ. 2006;332:605–607
127. Joint United Nations Programme on HIV/AIDS (UNAIDS)
and World Health Organization (WHO) AIDS Epidemic
Update. December 2006. Available at: http://data.unaids.
o rg / p u b / E p i R e p o r t / 2 0 0 6 / 0 3 - I n t r o d u c t i o n - 2 0 0 6 _
EpiUpdate_eng.pdf; 2009 Accessed 27.05.09
 Current Vaccinations in Dermatology
Kamaldeep Singh and Robert A. Norman
20.1 Introduction
Vaccines have been called medicine’s greatest life sav-
ers. They have helped eradicate vexing diseases such
as smallpox and effectively prevented diseases such as
rubella and rubeola. In the present medical landscape
vaccinations occupy enormous ground and from first
world nations to third world countries they have
become part of government policies and legislation to
prevent disease. One does not need to study the count-
less studies and trials that focus on disease reduction
from the use of vaccines, but only to go back in history
and see the triumph of vaccines over horrific diseases
such as polio and tetanus. Edward Jenner would have
never envisioned that his use of cowpox to prevent
smallpox would have such a paramount impact on
medicine. Although the idea behind vaccinating is
older than Jenner and records of inoculations can be
found as far back as a millennium before Jenner’s time,
history credits him as being the father of vaccine
because his vaccine was safer than inoculation.
Edward Jenner’s vaccine was also the first against a
disease with cutaneous manifestations and since then
many vaccines have been developed including the ones
that prevent against diseases with cutaneous compo-
nents such as measles, mumps, and rubella and more
recently diseases caused by varicella zoster virus (VZV)
and human papilloma virus. The focus of this chapter is
to review the natural history, epidemiology, and diagno-
sis of VZV and HPV and to emphasize vaccination
strategies including the latest CDC guidelines.
K. Singh (*)
Internal Medicine Resident, Stony Brook University Hospital,
Stony Brook, NY, USA
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_20, © Springer-Verlag London Limited 2010
20
20.2 Varicella Zoster Virus
VZV, also known as human herpes 3 (HHV3), is a
human neurotropic virus belonging to the family of
DNA viruses known as herpesviridae. Its single, linear
double-stranded DNA molecule is enclosed within an
icosapentahedral capsid making it very similar to her-
pes simplex virus 1 and 2. The distinguishing factor
that is responsible for each virus’s unique properties is
the lipid envelope consisting of polyamines, lipids, and
glycoproteins that encloses this 162 capsomere capsid.
More specifically, the glycoproteins are responsible
for the distinctive properties of each virus as well as
the antigenic capabilities of eliciting an immune
response in the host. For example, VZV glycoproteins
(gB, gC, gE, gH, gK, gL) correspond with those in the
HSV, but HSV gD is not found in the VZV lipid enve-
lope. VZV puts forth a considerable challenge in terms
of studying the virus for its biological and pathogenic
properties because it only replicates in human cells
and tissues for reasons currently unknown.
20.2.1 Epidemiology
Varicella (chickenpox) and herpes zoster (shingles)
are both caused by VZV. Chickenpox is a very com-
mon childhood illness with peak incidence between 1
and 9 years of age resulting in 90% of the population
having positive serology by adolescence and 100% of
the population being seropositive by the age of 60.
VZV infections are more widespread in winter and
spring seasons and have a tendency of epidemics every
2–5 years. The disease is highly contagious and
spreads from person to person via direct contact with
fluids from vesicles or respiratory inhalation of viral
233
234
fomites. In immunocompetent persons varicella is a
mild-to-moderate illness while immunocompromised
persons can suffer from severe complications includ-
ing death.
Shingles is caused by the reactivation of the latent
VZV. It is a disease most commonly of the elderly and
immunocompromised and incidence increases with
age because of declining immunity. At 60 years of age
incidence is reported between 2.5 and 5% and increases
to 3–6.8% the age of 70 with lifetime risk of 15–30%.
Shingles can also occur in seemingly healthy individu-
als with incidence of 1.2–3.4%. The disease is worri-
some because it poses the potential for severe and
debilitating complications such as herpes opthalmicus,
postherpetic neuralgia, paresis, myelopathy, myocardi-
tis, depression, and others.
20.2.2 Virus Life Cycle
The VZV life cycle consists of three stages, the pri-
mary infection, latent period, and reactivation. The
virus gains access to the host’s peripheral nervous sys-
tem via the mucocutaneous surfaces; it replicates,
spreads, and causes an immune response resulting in
usually self-limiting disease of chickenpox. Thereafter,
the virus enters the axonal endings within the mucocu-
taneous surfaces and travels to the dorsal root ganglia
where it remains latent until reactivation. Latency is
the presence of viral genome without production of the
infective particle. Reactivation occurs in response to
stimulus such as immunosuppression, hormonal
changes, stress, nerve damage, etc. and causes the
virus to once again become active and replicate itself
causing shingles. Latency is once again established
and potential to reactivate remains.
20.2.3 Varicella (Chickenpox)
Mucocutaneous surfaces most susceptible to VZV are
the upper respiratory mucosa and conjunctiva. Upon
entering these surfaces VZV replicates in the regional
lymph nodes for the next 2–4 days, followed by pri-
mary viremia in 4–6 days and then leading to viral rep-
lication in the liver, spleen, and other organs. Secondary
viremia occurs in 14–16 days leading to the
K. Singh and R. A. Norman
dissemination of the virus to the skin and vicera and
producing the typical vesicular lesions. Prodromal
symptoms include fever, malaise, anorexia, and head-
ache. In the United States, universal vaccination policy
against varicella was adopted in 1995 and has led to
significant reduction in morbidity and mortality asso-
ciated with VZV (Table 20.1).
20.2.4 Herpes Zoster (Shingles)
Reactivation of the latent VZV causes herpes zoster or
shingles. The virus that had remained latent inside the
neuronal nucleus maintaining the ability to replicate
reverts to its infectious state. It is not clearly known
why the reactivation happens but the fact that the dis-
ease is more prevalent in the elderly and the immu-
noincompetent leads to the theory that declining
cell-mediated immunity is the culprit. Support for this
theory stems from the experimental evidence that, over
time, even person with apparent immunity to varicella
exhibit T cells with reduced ability to proliferate and
produce VZV-specific interferon gamma when exposed
to VZV antigen in vitro. Fifty percent of the estimated
one million causes of herpes zoster in the United States
occur in individuals aged 50 years or older and 50% of
individuals 85 or older are expected to develop herpes
zoster. Another 300,000 cases occur in the immuno-
compromised with bone marrow transplant recipients
and HIV patients having the highest vulnerability.
In contrast to the primary varicella infection, reacti-
vation tends to occur locally and within dermatomes
where the highest viral load was present during the pri-
mary infection. Most often these sites are the thorax
and the trigeminal distribution of the face. Clear vesic-
ular eruptions appear within a dermatome, becoming
turbid and eventually crusting within 5–10 days.
Preherpetic neuralgia sometimes precedes shingles
and is defined as parasthesias, itching and pain some-
times severe enough to suggest coronary artery isch-
emia or abdominal conditions. The most common and
worrisome complication of the disease is when the
pain and itching, usual concomitants of the eruptions,
become chronic and lead to the condition known
as postherpetic neuralgia. Although self-limiting,
postherpetic neuralgia can be debilitating, often diffi-
cult to treat, and can leave the patient with poor quality
of life leading to social withdrawal and depression.
20  Current Vaccinations in Dermatology
Table 20.1  Summary of the recommendations of the advisory committee on immunization practices for prevention of varicella –
United States, 1996, 1999, and 2007
Category
Routine childhood schedules
Adults and adolescents aged
³13 years
Catch-up vaccination
HIVb-infected persons
Recommendations
1996 1999
One dose at age 12–18 months
Two doses, 4–8 weeks apart
Recommended for susceptible
persons who have close
contact with persons at high
risk for serious complica-
tionsHealth-care workers
Family contacts of immuno-
compromised persons
Should be considered for
susceptible persons at high
risk for exposurePersons
who live or work in
environments in which
transmission of VZV is
likely (e.g., teachers of
young children, childcare
employees, residents and
staff in institutional settings)
Persons who live and work in
environments in which
transmission can occur (e.g.,
college students, inmates
and staff of correctional
institutions, military
personnel)
Nonpregnant women of
childbearing age
International travelers
Is desirable for other suscep-
tible adolescents
One dose for all susceptible
children age 19 months – 12
years (i.e., those with no
history of varicella or
vaccination)
Contraindicated
235
2007
No change Two dosesFirst at age
12–15 months
Second at age 4–6 years
Two doses, 4–8 weeks apart Two doses, 4–8 weeks
apart
No change Recommended for all
adolescents and
adults without
evidence of
immunity
Recommended for susceptible
persons at high risk for expose
or transmissionPersons who
live or work in environments in
with the transmission of VZVa
is likely (e.g., teachers of young
children, daycare employees,
residents and staff in institu-
tional settings)
Persons who live and work in
environments in which
transmission can occur (e.g.,
college students, inmates and
staff of correctional institutions,
military personnel)
Nonpregnant women of childbear-
ing age
International travelers
Adolescents and adults living in
households with children
No change Second dose
recommended for
all persons who
received one dose
previously
Two doses, 3 months apart Two doses, 3 months
apart
Should be considered for asymp- Should be considered
tomatic or mildly symptomatic for HIV-infected
HIV-infected children in CDC children with
immunologic and clinical age-specific CD4+
categories N1 or A1 with T-lymphocyte
age-specific CD4+ percentages ³15%
T-lymphocyte percentages May be considered for
³25% adolescents and
adults with CD4
counts ³200/mL
(continued )
236 K. Singh and R. A. Norman

Table 20.1  (continued)
Category Recommendations
1996 1999 2007
Antenatal screening None None Recommended
prenatal assess-
ment and
postpartum
vaccination
Outbreak control vaccination None Should be considered Recommended
two-dose
vaccination policy
Postexposure vaccination None Recommended within 3–5 days No change
Vaccination requirements None Recommended for children without Recommended for
evidence of immunity attending children attending
childcare centers and entering child-care centers,
elementary school students in all
grade levels, and
Should be considered for middle persons attending
school and junior high school college or other
students without other evidence postsecondary
of immunity educational
institutions
a
Varicella zoster virus
b
Human immunodeficiency virus
From Centers for disease control and prevention. Prevention of varicella. Recommendations of the advisory committee on immuni-
zation practices (ACIP). MMWR 2007; 56(RR-4):3

Various drugs including antivirals and steroids are Contraindications are:

used to treat and reduce the severity of acute herpes
zoster but none can prevent postherpetic neuralgia or
other herpes zoster complications. In 2006, the Food
and Drug Administration (FDA) approved Zostavax, a
live attenuated preparation of VZV. The vaccine has
been shown to boost the recipient’s immunity to VZV
making the reactivation of VZV and development of
herpes zoster less likely. The pivotal Shingles
Prevention Study, on which basis the FDA approved
Zostavax, showed a reduction in the cases of herpes
zoster by half and postherpetic neuralgia by two-thirds
in a sample of 38,000 older adults.
20.2.5 ACIP Provisional
Recommendations
A single dose of herpes zoster vaccine is recommended
for adults 60 years of age and older whether or not they
report a prior episode of herpes zoster. Persons with
chronic medical conditions may be vaccinated unless
contraindications or precautions exist for their condition.
• A history of anaphylactic/anaphylactoid reaction to
gelatin, neomycin, or any other component of the
vaccine
• A history of primary acquired immunodeficiency
states
• On immunosuppressive therapy
• Women of childbearing age, and is not to be admin-
istered to pregnant females
20.3 Human Papilloma Virus
Human papilloma viruses belong to their own family
of viruses known as papillomaviridae. These double-
stranded DNA viruses are species-specific and infect
the skin and mucous membranes of their host. There
are more than 100 types of human papilloma viruses
that have been identified with each type containing
approximately 7,900 base pairs and sharing 90% of
DNA base pair homology with other identified types.
20  Current Vaccinations in Dermatology
Infections with different HPV types result in illness
ranging from clinically silent infections, benign skin
lesions, and malignant cancers. Certain HPV types
associated with squamous intraepithelial lesions and
anogential malignancy including cervical, vaginal, and
vulvar and anal carcinomas prompt tremendous
research effort in order to reduce morbidity and mor-
tality caused by these diseases and to better the treat-
ment and prevention of HPV infections. Types linked
to cervical cancer are classified as either high (16, 18),
intermediate (31, 33, 35, 39, 45, 51, 52, 58) or low risk
(6, 11, 42, 43, 44). Although the high-risk types are
linked to 70% of all cases of cervical cancers not all
infections with types 16 and 18 lead to cervical cancer.
It is the oncogenic potential of different variants of
these high-risk types that determine whether a HPV
infection has a potential to develop into cervical can-
cer. HPV infections are also associated with anal can-
cer and the same high-risk types implicated in cervical
cancer have been identified as the culprits for anal can-
cer. A group of researchers have identified 29 individ-
ual HPV types and 10 HPV groups from anal canal of
homosexual men.
20.3.1 Virus Life Cycle and Pathogenicity
The pathogenicity of HPV is thought to be caused by
proteins E6 and E7 encoded by the HPV DNA. These
proteins are part of six early (E) proteins implicated in
modifying the cell cycle of infected host cells. Once
the HPV virion infects the epithelial tissue through
micro abrasions, it gains access to the nucleus of basal
epithelial cells via several complex transport mecha-
nisms including alpha integrins, laminins, and several
chemical mediators involved in endocytosis within the
cell wall and nuclear membrane. Once inside the host
keratinocyte the HPV lifecycle follows the keratino-
cyte’s differentiation program. The oncogenes E6 and
E7 are thought to modify the function of tumor sup-
pressor gene p53 and retinoblastoma, leaving the kera-
tinocytes cell cycle unchecked. The evidence for
oncogenes E6 and E7’s role in epithelial cancers is
supported by the presence of HPV DNA in tumor biop-
sies and more specifically the expression of E6 and E7
in tumor material. Additionally, E6 and E7 proteins are
required to maintain the malignant phonotype of cervi-
cal carcinoma cell lines.
237
20.3.2 Epidemiology
Currently the bulk of research and emphasis in study-
ing infections caused by human papilloma viruses is
placed on genital tract infections that lead to precan-
cerous or cancerous conditions in healthy individuals
including cervical intraepithelial neoplasia, cervical
cancer, Bowen’s disease, and verrucous carcinoma of
the penis. Other less severe types lead to mostly benign
skin lesions or even clinically silent infections. The
prevalence of anogenital tract HPV infection in the
United States is quite high with an estimated 20 mil-
lion infected individuals. The annual incidence is 5.5
million. Incidence is highest among sexually active
persons and according to some estimates more than
50% of these individuals are expected to be infected
with anogenital HPV infection in their lifetime. With
approximately 9,710 cases of cervical cancer and
3,700 deaths annually the cost related to HPV infec-
tions are enormous to health care. One study based on
a database of cases in Maryland states that the cost of
one HPV-related disease alone (the JORRP) costs
$57,996 per case with annual cost of between $40 mil-
lion and $123 million. Combine this with financial
burden created by other anogenital diseases caused by
HPV infections in both men and women and the dollar
figure grows astounding.
20.3.3 Intervention
The CDC states that by age 50, more than 80% of
American women will have contracted at least one
strain of genital HPV, making them at highest risk of
developing HPV-induced cancers, more specifically
cervical cancer. Fortunately, development of cervical
cancer induced by HPV infection is a slow process
requiring many years, giving physicians an opportu-
nity to screen individuals considered to be at risk for
HPV-induced cervical cancer.
Papanicolaou (pap) testing is a popular screening
test used to detect cervical cytology changes during the
developmental phase of HPV-induced cervical cancer.
Cells from the cervix are smeared onto a slide and
examined under the microscope for presence of precan-
cerous or abnormal cells. The test is 70–80% effective
in detection of abnormal cervical cytology caused by
HPV. Variations of the test are used to increase the
238
sensitivity including liquid-based cytology known as
the thin prep (sensitivity 85–95%), and a pap-HPV
DNA test mainly used for women over the age of 30.
Adjunct testing including the use of colposcopy and
hybrid capture test (the newest FDA-approved method
for detecting high risk HPV DNA) may be used if
abnormal cytology is suspected. The CDC has several
targeted guidelines for routine HPV testing in women to
help detect and prevent HPV-induced cervical cancer.
20.3.4 Vaccine
Cervical cancer is the second leading cause of cancer-
related deaths in women worldwide and nearly all
cases are caused by HPV infections. Although early
detection via pap testing has significantly reduced the
risk of invasive cervical cancer, there still exists con-
siderable risk. In 2006, a prophylactic HPV vaccine
(Gardasil) was approved by the FDA and is currently
being marketed by Merck. The vaccine is based upon
one of the late proteins of the HPV DNA. The L1 pro-
tein is a capsid protein and has the ability to form a
virus-like antigenic particle capable of eliciting an
immune response and production of high levels of neu-
tralizing antibodies. Gardasil protects against the high-
risk type 16 and 18 and types responsible for 90% of
genital warts, 6 and 11.
20.3.5 ACIP Recommendations
20.3.5.1 Routine Vaccination of Females
Aged 11–12 Years
ACIP recommends routine vaccination of females
aged 11–12 years with three doses of quadrivalent
HPV vaccine. The vaccination series can be started as
young as age 9 years.
K. Singh and R. A. Norman
20.3.5.2 Catch-Up Vaccination of Females
Aged 13–26 Years
Vaccination also is recommended for females aged
13–26 years who have not been previously vaccinated
or who have not completed the full series. Ideally, vac-
cine should be administered before potential exposure
to HPV through sexual contact; however, females who
might have already been exposed to HPV should be
vaccinated. Sexually active females who have not been
infected with any of the HPV vaccine types would
receive full benefit from vaccination. Vaccination
would provide less benefit to females if they have
already been infected with one or more of the four vac-
cine HPV types. However, it is not possible for a clini-
cian to assess the extent to which sexually active
persons would benefit from vaccination, and the risk
for HPV infection might continue as long as persons
are sexually active. Pap testing and screening for HPV
DNA or HPV antibody are not needed before vaccina-
tion at any age.
Vaccines for melanoma, nonmelanoma skin cancers
(NMSCs) such as squamous cell and basal cell can-
cers, molluscum contagiosum, common warts, and
chlamydia have been in trial with mixed results.
20.4 Conclusion
Although many of the cutaneous diseases reviewed in
this chapter are self-limiting, they sometimes lead to
serious sequelae. While herpes zoster vaccine,
Zostavax, prevents shingles and related complications,
Gardasil decreases HPV-induced cervical cancer and
genital warts. Although yet to be seen, the universal
vaccination policy against varicella is further set to
decrease the incidence of herpes zoster. The future of
medicine is practicing preventative medicine and we
only need to study the past starting with Edward Jenner
to come to such realization.
 Part
IV
Wounds, Surgery, and
Dermatological Prevention
 Prevention of Skin Infections
21
Dirk M. Elston

21.1 Bacterial Infections a survival advantage to the organism, and it rapidly

replaces other strains of staphylococci. Colonization eas-
ily spreads to close contacts. Those who are colonized
Methicillin-sensitive Staphylococcus aureus accounts
have a high attack rate of clinical infection.7,8
for most cutaneous infections, including wound infec-
Clinical infection with CA-MRSA generally begins
tion (Fig. 21.1), folliculitis (Fig. 21.2), and impetigo.
with folliculitis and rapidly evolves into an abscess
Cutaneous injuries commonly become infected.
(Fig. 21.3). Early in the course of disease, pain is often
Topical antiseptics can reduce the incidence of infec-
severe and out of proportion to physical findings.
tion, but may be contact sensitizers. While topical anti-
Infection commonly begins at sites of minor abrasions
biotics may reduce the overall incidence of infection,
such as turf-burns. In weightlifters, abscesses com-
they may also cause contact dermatitis. Those with a
monly involve the axillae. In women and young chil-
gram-positive spectrum may increase the likelihood
dren, the thighs and buttocks are often involved. Other
that the infecting organism with be gram negative.
common sites of involvement include the neck, back,
Wound care is discussed more thoroughly in the sec-
extremities, nose, and external ear canals.9
tion on prevention of surgical wound infections.
Prevention of cutaneous CA-MRSA infections
Community-acquired methicillin-resistant Staphy­
requires preventive measures to reduce the incidence
lococcus aureus (CA-MRSA) has recently emerged as
of cutaneous injury, elimination of bar soap, policies
an important skin pathogen. CA-MRSA infections have
against sharing of towels, decontamination of mats and
a high attack rate among wrestlers, football players,
equipment, as well as treatment of carriers. Cosmetic
weight lifters, and members of amateur and professional
body shaving is a risk factor for CA-MRSA infection,
sports teams.1–3 Pre-existing cuts or abrasions and shar-
and should be discouraged.10
ing of fomites such as towels and bars of soap are impor-
Sodium hypochlorite (bleach) at a dilution of two
tant risk factors for infection. Nasal carriage is ­associated
tablespoons per bathtub of water can be used to reduce
with sharing of towels and serves as a reservoir for
colonization of eczematous skin lesions, axillae, and
recurrent infection.4 Carriage also occurs in other moist
groin regions. Chlorhexidine gluconate washes can
areas, such as the axillae, groin, and perianal region.
also be effective, although resistance is emerging.11,12
Eczematous skin is commonly colonized. CA-MRSA
Seventy percent ethanol is an effective agent for decon-
has also been isolated from whirlpools and taping gel.5
tamination of mats and equipment.13 The combination
CA-MRSA strains typically contain the type IV staph-
of alcohol and chlorhexidine has also been effective.14
ylococcal chromosomal cassette that codes for methicil-
Triclosan-based hand sterilizers are suitable for use on
lin resistance. Panton-valentine leukocidin (PVL) has
skin and some equipment. As with chlorhexidine, tri-
been identified as a potent virulence factor.6 PVL imparts
closan resistance is emerging.15,16 Mupirocin is com-
monly used for nasal colonization, but resistant strains
are now common and eradication may be achieved in
D. M. Elston
fewer than half of those so treated.17,18 Retapamulin is
Department of Dermatology, Geisinger Medical Center,
Danville, PA, USA a newer alternative, but its effectiveness in this setting
e-mail: dmelston@geisinger.edu must be validated in clinical studies.

R. A. Norman (ed.), Preventive Dermatology, 241

DOI: 10.1007/978-1-84996-021-2_21, © Springer-Verlag London Limited 2010
242
Fig. 21.1  Impetiginized wound
Fig. 21.2  Staphylococcal folliculitis
Group A streptococcal infections complicating
cutaneous injuries can result in impetigo, glomerulo-
nephritis, erysipelas, and lymphangitis.19 Prevention of
streptococcal infections is similar to that for staphylo-
coccal infections.
D. M. Elston
Fig.  21.3  CA-MRSA commonly presents as folliculitis that
rapidly evolves to a painful abscess
Exposure to fresh or salt water is associated with an
increased incidence of skin infection.20 Pseudomonas
infections are associated with exposure to water and
commonly present as folliculitis restricted to covered
or intertriginous areas (hot tub or swimming pool fol-
liculitis). The follicular papules and pustules are typi-
cally more pruritic than tender (Fig.  21.4). Warm
weather or heated water are risk factors for infection,
as free chlorine levels are harder to maintain in the
heat. Both chlorine and bromine treated water can be a
source of infection, as can contaminated plastic, rub-
ber, or natural loofah sponges.21, 22 The implicated
strain is typically type O:11, although types O:1, O:3,
O:8, O:10, and O:16 have also been implicated.23
Most cases of Pseudomonas folliculitis resolve spon-
taneously, although fluoroquinolone treatment may be
required.24 Prevention involves elimination of standing
water and wet sponges, prompt removal of wet bathing
suits, and adequate chlorination. Alter­native water treat-
ments such as ozone ionization have also been used.
21.2 Viral Infections
Herpes infections (Fig. 21.5) may occur through sex-
ual exposure or by any skin-to-skin contact. Infections
are particularly common among wrestlers (herpes
gladiatorum), where attack rates are as high as 34%.25
Ocular involvement can be particularly devastating.
Those with genital lesions should refrain from sexual
activity during outbreaks and should be aware that
asymptomatic shedding occurs. Barrier protection is
only partially effective, but oral prophylaxis with
21  Prevention of Skin Infections
Fig. 21.4  Hot tub folliculitis
acyclovir, valcyclovir, or famciclovir can prevent or
reduce the spread of disease. Abrasive shirts create
potential portals of entry and are a risk factor for her-
pes infections among wrestlers.26 Policies to ban
infected individuals from competition and discourage
abrasive clothing should be enforced.
Blood-borne pathogens can be spread in the health-
care setting, during sexual intercourse, or during com-
petition. Universal precautions should be observed at
all times in healthcare settings. Those with open
wounds should be barred from competition. Minor
wounds may be covered with impermeable adhesive
dressings.
21.3 Fungal Infections
Tinea infection is common among military recruits,
wrestlers, and swimmers.27 Asymptomatic carriers are
common, and fungal spores are easily recovered from
moist surfaces such as the floors around swimming
pool.28,29 There is an inherited susceptibility to
Trichophyton rubrum infection which may be inherited
in an autosomal dominant fashion. Although much of
the population is predisposed to infection, it is not inevi-
table and can certainly be delayed by simple precau-
tions. Those with active tinea should not participate in
243
Fig. 21.5  Herpes simplex virus infection
wrestling matches. Footwear should be worn in locker
rooms and other areas with foot traffic and moist floors.
21.4 Prevention of Surgical
Wound Infections
The incidence of wound infections following cutane-
ous surgery is quite low (just over 1%), the benefits of
routine antibiotic prophylaxis must be carefully
weighed against the cost of treatment, the risks of
adverse drug reactions, and the potential for emergence
of resistant organisms.30
The risk of infection for Mohs surgery is slightly
higher (about 2.5%). For any prolonged surgery, the
risk of infection can be reduced by avoiding buried
suture or allowing the wound to heal by secondary
intention. A single preoperative or intraoperative dose
of antibiotic can also reduce the risk of infection, but
there is no benefit to courses of antibiotic longer than
48 h.31 Many surgeons favor a single dose of a prophy-
lactic antibiotic before surgery on a site such as the
hand where a postoperative infection could be cata-
strophic. An alternative to prophylaxis with a systemic
antibiotic is to add clindamycin to the local anesthetic.32
This results in a reduction in surgical site infection (to
below 1%) with undetectable blood levels and no risk
of contributing to the emergence of resistant organisms.
Clindamycin is also suitable for use in patients with a
history of penicillin allergy. The solution is prepared by
adding 0.15 ml of clindamycin (150 mg/ml) to 50 mg of
lidocaine with 5 ml 8.4% bicarbonate. This results in at
concentration of ­clindamycin of 408 mg/mL.
244 D. M. Elston

Elimination of nasopharyngeal staphylococcal

c­ olonization with chlorhexidine intranasal ointment
and oropharyngeal rinse 4 times daily during the pre-
and postoperative periods reduced the incidence of
nosocomial infections including respiratory infection,
bacteremia, and deep surgical site infections.33 Data on
the use of intranasal mupirocin have generally been
disappointing. Studies are needed to determine if
newer topical antibiotics such as retapamulin will per-
form better.
Postoperative use of a topical antibiotic ointment
results in a small decrease in the incidence of wound
infection at the expense of a significant risk of allergic
contact dermatitis. In a randomized, double-blind trial
of white petrolatum compared to bacitracin ointment,
the infection rate was 1.5% with the former and 0.9%
with the latter.34 Allergic contact dermatitis occurred in
0.9% of those treated with bacitracin. Infections in the
bacitracin group were more likely to be gram negative
infections, and antibiotics needed to treat them were
more expensive. These data make a strong case for the
routine use of white petrolatum postoperatively.

21.5 Prevention of Arthropod-Borne
Infections Fig. 21.6  Rocky mountain spotted fever

Insect bites and stings commonly become infected.
Vector-borne illnesses such as leishmaniasis present
mainly in the skin. Other diseases such as Rocky
Mountain spotted fever (Fig.  21.6) and viral fevers
may present with petechial or hemorrhagic skin lesions.
Avoidance of infested areas as well as consistent use of
repellents and protective clothing can reduce the inci-
dence of infection. Chemoprophylaxis and attention to
screening or mosquito netting is important when trav-
eling. At home, public health measures to reduce mos-
quito and tick populations are important.
In the United States, mosquitoes are vectors for
West Nile fever, St. Louis encephalitis, equine enceph-
alitis, dengue, and malaria. North American ticks carry
Lyme disease, Rocky Mountain spotted fever, ehrli-
chiosis, Colorado tick fever, relapsing fever, tularemia,
and babesiosis. Homeless patients with ectoparasitic
infestation have a high prevalence of infection with
Bartonella quintana, a cause of endocarditis.35–37 Fleas
transmit plague, bacillary angomatosis, and endemic
typhus. Sandflies transmit leishmaniasis. In the United
States, Leishmania mexicana produces chronic crusted
and ulcerative lesions, while L. donovani can produce
subcutaneous nodules.
Primary prevention of vector-borne disease requires
drainage of stagnant water, insecticide spraying pro-
grams, use of repellents, and prompt tick removal.
Secondary prevention can be accomplished with
chemoprophylaxis or early treatment of illness.
Anopheline mosquitoes that carry malaria feed mostly
at night. Transmission is prevented by staying indoors
at night, use of repellents and pyrethroid-impregnated
mosquito netting. Mosquitoes that carry dengue tend
to bite during the day, and repellents and protective
clothing are especially important to prevent transmis-
sion.38,39 Carbon-dioxide–emitting mosquito traps such
are helpful. Chemical attractants such as octenol and
butanone are often used, although some Culex mosqui-
toes are repelled by octenol.40–42
DEET (N,N-diethyl-3-methylbenzamide) is the most
commonly used repellent for the prevention of mos-
quito and sandfly bites. Overall, it has a good safety
21  Prevention of Skin Infections
record, although rare cases of bullous dermatitis,
­anaphylaxis, and toxic encephalopathy have been
reported.43–46 The American Academy of Pediatrics rec-
ommends slow-release products that plateau in efficacy
at concentrations of 30%. Many extended duration
products formulated for children have concentrations of
10% of less. DEET can be applied to exposed skin and
to clothing. The addition of permethrin-treated clothing
increases efficacy against a wide range of biting arthro-
pods.47,48 For those who cannot use DEET, picaridin is a
good alternative. A soybean-oil-based product (Bite
Blocker for Kids) is suitable for those who wish to avoid
chemical repellents. It is not as effective as DEET or
picaridin. Citronella has limited efficacy.49 Neem oil
performs better.50
Permethrin, applied to clothing, has good efficacy
against ticks and chiggers.47,48 The effect lasts through
a number of wash cycles.51 Permethrin can be applied
to clothing, tents, sleeping bags, and mosquito netting.
Although southwest Asian camel ticks are attracted by
permethrin, this phenomenon has not been reported in
North America.52 Exclusion of deer by means of fenc-
ing has been shown to be effective in reducing the
number of disease-carrying ticks.53,54 Feeding stations
can be outfitted to deliver topical acaricides to deer.55–57
Leaf debris should be removed, as ticks are susceptible
to dehydration if they do not have access to a layer of
leaf debris.58,59 Ticks are unlikely to transmit disease if
they are removed promptly.60–62 When removing the
tick, care should be taken not to squeeze it.63 The Tick
Nipper is an inexpensive plastic device that makes tick
removal quite easy.
Fleas can be controlled with lufenuron, a matura-
tion inhibitor that prevents fleas from becoming fertile.
It is marketed in oral and injectable formulations for
both cats and dogs. Fipronil can be applied to pets to
prevent flea and tick infestation.64 Pet owners should
consult a veterinarian for specific recommendations.
References
  1. Cohen PR. Cutaneous community-acquired methicillin-
resistant Staphylococcus aureus infection in participants of
athletic activities. South Med J. 2005;98(6):596–602
  2. Arnold FW, Wojda B. An analysis of a community-acquired
pathogen in a Kentucky community: methicillin-resistant
Staphylococcus aureus. J Ky Med Assoc. 2005;103(5):206–210
245
  3. Centers for Disease Control and Prevention (CDC).
Methicillin-resistant Staphylococcus aureus infections
among competitive sports participants – Colorado,
Indiana, Pennsylvania, and Los Angeles County, 2000–
2003. MMWR Morb Mortal Wkly Rep. 2003;52(33):
793–795
  4. Nguyen DM, Mascola L, Brancoft E. Recurring methicillin-
resistant Staphylococcus aureus infections in a football
team. Emerg Infect Dis. 2005;11(4):526–532
  5. Kazakova SV, Hageman JC, Matava M, et  al A clone of
methicillin-resistant Staphylococcus aureus among profes-
sional football players. N Engl J Med. 2005;352(5):468-475
  6. Carleton HA, Diep BA, Charlebois ED, et  al Community-
adapted methicillin-resistant Staphylococcus aureus (MRSA):
population dynamics of an expanding community reservoir
of MRSA. J Infect Dis. 2004;190(10):1730-1738
  7. Calfee DP, Durbin LJ, Germanson TP, et  al Spread of
­methicillin-resistant Staphylococcus aureus (MRSA) among
household contacts of individuals with nosocomially acquired
MRSA. Infect Control Hosp Epidemiol. 2003;24(6):422–426
  8. Ellis MW, Hospenthal DR, Dooley DP, et al Natural history
of community-acquired methicillin-resistant Staphylococcus
aureus colonization and infection in soldiers. Clin Infect
Dis. 2004;39(7):971–979
  9. Wang J, Barth S, Richardson M, et al An outbreak of methi-
cillin-resistant Staphylococcus aureus cutaneous infection in
a saturation diving facility. Undersea Hyperb Med.
2003;30(4):277–284
10. Begier EM, Frenette K, Barrett NL, et al Connecticut bioter-
rorism field epidemiology response team. A high-morbidity
outbreak of methicillin-resistant Staphylococcus aureus
among players on a college football team, facilitated by cos-
metic body shaving and turf burns. Clin Infect Dis.
2004;39(10):1446–1453
11. Block C, Robenshtok E, Simhon A, et al Evaluation of chlo-
rhexidine and povidone iodine activity against methicillin-
resistant Staphylococcus aureus and vancomycin-resistant
Enterococcus faecalis using a surface test. J Hosp Infect.
2000;46(2):147–152
12. Zhang YH, Liu XY, Zhu LL, et al Study on the resistance of
methicillin-resistant Staphylococcus aureus to iodophor and
chlorhexidine. Zhonghua Liu Xing Bing Xue Za Zhi.
2004;25(3):248–250
13. Suzuki J, Komatsuzawa H, Kozai K, et al In vitro suscepti-
bility of Staphylococcus aureus including MRSA to four
disinfectants. ASDC J Dent Child. 1997;64(4):260–263
14. Kampf G, Jarosch R, Ruden H. Limited effectiveness of
chlorhexidine based hand disinfectants against methicillin-
resistant Staphylococcus aureus (MRSA). J Hosp Infect.
1998;38(4):297–303
15. Brenwald NP, Fraise AP. Triclosan resistance in methicillin-
resistant Staphylococcus aureus (MRSA). J Hosp Infect.
2003;55(2):141–144
16. Bamber AI, Neal TJ. An assessment of triclosan susceptibility
in methicillin-resistant and methicillin-sensitive Staphylococcus
aureus. J Hosp Infect. 1999;41(2):107–109
17. Harbarth S, Dharan S, Liassine N, et  al Randomized, pla-
cebo-controlled, double-blind trial to evaluate the efficacy of
mupirocin for eradicating carriage of methicillin-resistant
Staphylococcus aureus. Antimicrob Agents Chemother.
1999;43(6):1412–1416
246
18. Mulvey MR, MacDougall L, Cholin B, et al Saskatchewan
CA-MRSA Study Group. Community-associated methicil-
lin-resistant Staphylococcus aureus, Canada. Emerg Infect
Dis. 2005;11(6):844–850
19. Falck G. Group A streptococcal infections after indoor asso-
ciation football tournament. Lancet. 1996;347:840
20. Shephard RJ. Science and medicine of canoeing and kayak-
ing. Sports Med. 1987;4:19
21. Penn C, et al Pseudomonas folliculitis: and outbreak associ-
ated with bromine-based disinfectants. Can Dis Wkly Rep.
1990;16:31
22. Zichichi L, Asta G, Noto G. Pseudomonas aeruginosa folli-
culitis after shower/bath exposure. Int J Dermatol. 2000;
39:270–273
23. Maniatis AN, et al Pseudomonas aeruginosa folliculitis due
to non-O:11 serotypes: acquisition through the use of con-
taminated synthetic sponges. Clin Infect Dis. 1995;21:437
24. Rolston KV, et al Pseudomonas aeruginosa infection in can-
cer patients. Cancer Invest. 1992;10:43
25. Belogna EA, et al An outbreak of herpes gladiatorum at a
high school wrestling camp. N Engl J Med. 1991;325:906
26. Strauss RH, et al Abrasive shirts may contribute to herpes
gladiatorum among wrestlers. N Engl J Med. 1989;320:598
27. Adams B. Tinea corporis gladiatorum: a cross-sectional
study. J Am Acad Dermatol. 2000;43:1039–1041
28. Bolanos B. Dermatophyte feet infection among students
enrolled in swimming pool courses at a university pool. Bull
Assoc Med Puerto Rico. 1991;83:181
29. Auger P, et al Epidemiology of tinea pedis in marathon run-
ners: prevalence of occult athlete’s foot. Mycoses. 1993;36:35
30. Whitaker DC, Grande DJ, Johnson SS. Wound infection rate
in dermatologic surgery. J Dermatol Surg Oncol. 1988;14:
525–528
31. Griego RD, Zitelli JA. Intra-incisional prophylactic antibiotics
for dermatologic surgery. Arch Dermatol. 1998;134:688–692
32. Huether MJ, Griego RD, Brodland DG, Zitelli JA.
Clindamycin for intraincisional antibiotic prophylaxis in
dermatologic surgery. Arch Dermatol. 2002;138:1145–1148
33. Segers P, Speekenbrink RG, Ubbink DT, et al Prevention of
nosocomial infection in cardiac surgery by decontamination
of the nasopharynx and oropharynx with chlorhexidine glu-
conate: a randomized controlled trial. JAMA. 2006;296(20):
2460–2466
34. Smack DP, Harrington AC, Dunn C, et  al Infection and
allergy incidence in ambulatory surgery patients using white
petrolatum vs bacitracin ointment. A randomized controlled
trial. JAMA. 1996;276:972–977
35. Guibal F, de La Salmoniere P, Rybojad M, et al High sero-
prevalence to Bartonella Quintana in homeless patients with
cutaneous parasitic infestations in downtown Paris. J Am
Acad Dermatol. 2001;44:219–223
36. Foucault C, Barrau K, Brouqui P, Raoult D. Bartonella quin-
tana bacteremia among homeless People. Clin Infect Dis.
2002;35(6):684–689
37. Raoult D, Foucault C, Brouqui P. Infections in the homeless.
Lancet Infect Dis. 2001;1(2):77–84
38. Coosemans M, Van Gompel A. The principal arthropod vec-
tors of disease. What are the risks of travellers’ to be bitten?
To be infected? Bull Soc Pathol Exotique. 1998;91:467–473
39. Carnevale P. Protection of travelers against biting arthropod
vectors. Bull Soc Pathol Exotique. 1998;91:474–485
D. M. Elston
40. Rueda LM, Harrison BA, Brown JS, et  al Evaluation of
1-octen-3-ol, carbon dioxide, and light as attractants for
mosquitoes associated with two distinct habitats in North
Carolina. J Am Mosq Control Assoc. 2001;17(1):61–66
41. Kline DL. Comparison of two American biophysics mos-
quito traps: the professional and a new counterflow geometry
trap. J Am Mosq Control Assoc. 1999;15(3):276–282
42. Kline DL, Mann MO. Evaluation of butanone, carbon diox-
ide, and 1-octen-3-OL as attractants for mosquitoes associ-
ated with north central Florida bay and cypress swamps.
J Am Mosq Control Assoc. 1998;14(3):289–297
43. Brown M, Hebert AA. Insect repellents: an overview. J Am
Acad Dermatol. 1997;36:243–249
44. Fradin MS. Mosquitoes and mosquito repellents: a clini-
cian’s guide. Ann Intern Med. 1998;128:931–940
45. McKinlay JR, Ross V, Barrett TL. Vesiculobullous reaction
to diethyltoluamide revisted. Cutis. 1998;62:44
46. Miller JD. Anaphylaxis associated with insect repellent.
N Engl J Med. 1982;307:1341–1342
47. Young GD, Evans S. Safety and efficacy of DEET and per-
methrin in the prevention of arthropod attack. Mil Med.
1998;163:324–330
48. Gupta RK, Sweeny AW, Rutledge LC. Effectiveness of con-
trolled-release personal use arthropod repellent and per-
methrin-treated clothing in the field. J Mosq Contr Assoc.
1987;3:556–560
49. Lindsay LR, Surgeoner GA, Heal JD, Gallivan GJ. Evaluation
of the efficacy of 3% citronella candles and 5% citronella
incense for protection against field populations of Aedes
mosquitoes. J Am Mosq Contr Assoc. 1996;12:293–294
50. Caraballo AJ. Mosquito repellent action of Neemos. J Am
Mosq Contr Assoc. 2000;16:45–46
51. Schreck CE, Mount GA, Carlson DA. Wear and wash persis-
tence of permethrin used as a clothing treatment for personal
protection against the lone star tick (Acari: Ixodidae). J Med
Entomol. 1982;19:143–146
52. Fryauff DJ, Shoukry MA, Schreck CE. Stimulation of attach-
ment in the camel tick, Hyalomma dromedarii (Acari:
Ixodidae): the unintended result of sublethal exposure to per-
methrin-impregnated fabric. J Med Entomol. 1994;31:23–29
53. Stafford KC 3rd. Reduced abundance of Ixodes scapularis
(Acari: Ixodidae) with exclusion of deer by electric fencing.
J Med Entomol. 1993;30(6):986–996
54. Daniels TJ, Fish D, Schwartz I. Reduced abundance of
Ixodes scapularis (Acari: Ixodidae) and Lyme disease risk
by deer exclusion. J Med Entomol. 1993;30(6):1043–1049
55. Mount GA, Haile DG, Daniels E. Simulation of manage-
ment strategies for the blacklegged tick (Acari: Ixodidae)
and the Lyme disease spirochete, Borrelia burgdorferi.
J Med Entomol. 1997;34(6):672–683
56. Pound JM, Miller JA, George JE. Efficacy of amitraz applied
to white-tailed deer by the ‘4-poster’ topical treatment device
in controlling free-living lone star ticks (Acari: Ixodidae).
J Med Entomol. 2000;37(6):878–884
57. Solberg VB, Miller JA, Hadfield T, et al Control of Ixodes
scapularis (Acari: Ixodidae) with topical self-application of
permethrin by white-tailed deer inhabiting NASA, Beltsville,
Maryland. J Vector Ecol. 2003;28(1):117–134
58. Strey OF, Teel PD, Longnecker MT, Needham GR. Survival
and water-balance characteristics of unfed Amblyomma cajen-
nense (Acari: Ixodidae). J Med Entomol. 1996;33:63–73
21  Prevention of Skin Infections
59. Slowik TJ, Lane RS. Nymphs of the western black-legged tick
(Ixodes pacificus) collected from tree trunks in woodland-
grass habitat. J Vector Ecol. 2001;26(2):165–171
60. Katavolos P, Armstrong PM, Dawson JE, Telford SR
­3rd. Duration of tick attachment required for transmis-
sion of granulocytic ehrlichiosis. J Infect Dis. 1998;
177(5):1422–1425
61. Berger BW, Johnson RC, Kodner C, Coleman L. Cultivation of
Borrelia burgdorferi from human tick bite sites: a guide to the
risk of infection. J Am Acad Dermatol. 1995;32(2 Pt 1):
184–187
247
62. Piesman J, Mather TN, Sinsky RJ, Spielman A. Duration of
tick attachment and Borrelia burgdorferi transmission.
J Clin Microbiol. 1987;25(3):557–558
63. Piesman J, Dolan MC. Protection against lyme disease spi-
rochete transmission provided by prompt removal of
nymphal Ixodes scapularis (Acari: Ixodidae). Med Entomol.
2002;39(3):509–512
64. Young DR, Arther RG, Davis WL. Evaluation of K9
Advantix vs. Frontline Plus topical treatments to repel brown
dog ticks (Rhipicephalus sanguineus) on dogs. Parasitol
Res. 2003;90(Suppl 3):S116–S118
 Wound Prevention
Cynthia A. Fleck
As the US population ages, the number of persistent
and recurring wounds will continue to rise. Knowledge
of key prevention practices and guidelines will help
save patients from possible pain and suffering, as well
as keep treatment costs to a minimum. Chronic wounds
are caused by a variety of issues. Among the many fac-
tors, the aging process by itself takes its toll, predis-
posing the skin to wounds and other problems such as
xerosis and skin tears. The clinical implications of
aging are numerous and contribute greatly to the inci-
dence and prevalence of wounds. For example, dry,
inelastic skin with larger, more irregular epidermal
cells leads to decreased barrier function.1 Flattening of
the dermal–epidermal junction (rete ridges) has been
observed with the height of the dermal papillae declin-
ing by 55% from the third to ninth decade of life.2 As
the spaces between the well-vascularized dermis and
epidermis increases, several functional changes occur:
• A 30–50% decrease in epidermal turnover rate dur-
ing the 30s–80s.1
• Loss of sub-Q fat reduces protection from injury
from pressure, shear, and friction.
• Decreased sensory perception increases risk of
mechanical forces such as pressure.
A cross-sectional diagram of the changes that occur
during the aging process are illustrated in Fig. 22.1.
Wound prevention in the geriatric patient therefore,
requires a multifaceted approach, considering the eti-
ology of each wound type. Within this chapter, the
C. A. Fleck
The American Academy of Wound Management (AAWM),
Past President, The Association for the Advancement of Wound
Care (AAWC), Past Director, Medline Industries, Inc.,
Vice President, Clinical Marketing, St. Louis, MO, USA
e-mail: cynthiafleck@sbcglobal.net
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_22, © Springer-Verlag London Limited 2010
22
most prevalent wound categories will be described
with practical measures for preventing these trouble-
some wounds, as well as other prevention topics related
to wounds, such as skin care, support surfaces, and
nutrition.
22.1 Venous Insufficiency Ulcers
Venous ulcers, also known as venous hypertension
ulcers or venous insufficiency ulcers are caused by prob-
lems with venous blood return to the heart potentially
produced by nonfunctioning or inadequate calf muscle
pump, incompetent perforator valves, ineffectual valves
in the vein, arteriovenous (AV) fistulas, venous obstruc-
tion, and varicose veins,3 all leading to venous hyperten-
sion as venous blood pools in lower extremities and feet.
Chronic venous disease is most likely the underlying
cause in 80–95% of lower leg ulcers.4,5 The skin is often
firm, indurated and hyperpigmented, or “stained” a
brown or deep color (Fig. 22.2).6
22.1.1 Lower Limb, Calf Pump,
Maintenance Compression,
ABI/TBI, ETC
Some prevention tactics that should be embraced by
individuals with venous insufficiency include:
• Do not smoke.
• Consume adequate nutrition.
• Keep skin clean and well lubricated.
• Elevate the legs above the heart.
• Avoid sitting with the legs crossed.
249
250
Fig. 22.1  (a) Cross-section
of youthful skin;
(b) cross-section of elderly
skin. (Courtesy Medline
Industries, Inc. Used with
permission)
Fig. 22.2  Venous insufficiency ulcer
• Avoid standing for prolonged periods of time.
• Ambulate as tolerated several times a day.
• Take medications as prescribed.
• Use compression therapy as prescribed applying
every morning before rising.
• Take care of your skin.
• Follow-up with the healthcare provider.
• Elevate the foot off the bed while sleeping.
• Exercise the feet and ankles when the legs are
elevated.
• Avoid the use of constrictive clothing.
Patients should undergo a lower-extremity examination,
including determination of circulatory status via appro-
priate diagnostics (duplex imaging, Doppler, Doppler
ultrasonography, air plethysmography, venography),
C. A. Fleck
pedal pulses, skin temperature, venous refill, color
changes, skin changes (edema, hemosiderosis, venous
dermatitis, atrophie blanche, varicose veins, ankle flare,
scars from previous ulcers, tinea, or lipodermatosclero-
sis) and presence of paresthesias. A simple, noninvasive
indirect method to assess arterial flow by comparing
systolic blood pressure in the ankle to brachial pressure
is called an ankle brachial index (ABI).7 It is also known
as the ankle brachial pressure index (ABPI), ankle/arm
index (AAI), and the resting pressure index (RPT). This
measurement provides the best noninvasive approxima-
tion of central systolic pressure.8 The ABI is a screening
test to identify large-vessel peripheral arterial disease
by comparing systolic blood pressures in the ankle to
the higher of the brachial systolic pressures. Its purpose
is to detect large-vessel peripheral arterial disease in
lower extremities,9 determine adequate arterial blood
flow in the lower extremities, and provide documenta-
tion of adequate arterial blood flow in lower extremities
before applying compression therapy.10
If the ABI is higher than 1.3, indicating severe
peripheral vascular disease (PVD), a toe brachial index
(TBI) is recommended.11 This is often true in diabetics
or patients with renal failure where the ABI may not be
properly diagnosed due to calcified vessels not allow-
ing compression. In that case, ABI values will be false
because the blood pressure will be overestimated. Both
examinations compare favorably with angiographic
studies in lower extremity arterial disease (LEAD)
diagnosis.12
Patients with untreated varicosities and/or a history of
deep vein thrombosis are at higher risk for development
22  Wound Prevention
Fig.  22.3  Compression hosiery for lower extremity venous
insufficiency and venous wound prevention
of venous insufficiency wounds. Maintenance compres-
sion with stockings (that are replaced every 3 months to
provide optimal compression) (Fig. 22.3) or other com-
pression devices are the mainstay for prevention of
venous edema and venous related wounds, which tend to
recur frequently. With regard to recurrence, the evidence
is insufficient to support the use of medications such as
anabolic steroids13 or the performance of vein surgery13
to prevent these ulcers. In addition, active treatment of
any varicosities should include attention to one’s weight
and a regular exercise program, as well as an articulated
education plan that includes avoidance of leg crossing,
wearing of constricting garments, etc.
Diabetic/neuropathic wounds are caused by pressure
and/or trauma, secondary to peripheral neuropathy and/or
arterial insufficiency and poor microvascular circulation,
inadequate blood sugar control and/or lack of sensation
(Fig. 22.4). Foot ulcerations are extremely common in the
neuropathic patient. These ulcers often lead to complica-
tions that can result in amputation. Therefore, it is imper-
ative that these wounds be prevented. The following
251
Fig. 22.4  Diabetic ulcer
measures can decrease the potential for developing a dia-
betic/neuropathic wound. These actions should be taught
to the patient and family members to decrease the inci-
dence of developing these wounds:
• Perform daily foot care (inspect the feet, wash and
dry well between toes, wear clean socks that wick
moisture away from the skin and preferably have no
seams or mended areas to irritate or cause
pressure).
• Prevent xerosis of the feet by applying a good-qual-
ity moisturizing cream after drying the feet. Do not
apply it between the toes however, as this could
increase the likelihood of fugal manifestation.
• Avoid soaking the feet.
• Avoid wearing shoes without stockings or socks,
and do not wear sandals with thongs between the
toes.
• Visit a healthcare professional for foot care for toe-
nails, corns, and calluses.
• Avoid over-the-counter medications for corns and
calluses, antiseptic solutions, and adhesive tape.
• Avoid crossing the legs.
• Reduce pressure on bony prominences, especially
on the foot.
• Avoid temperature extremes (cold and hot).
• Avoid external heat sources, including heating pads,
hot water bottles, hydrotherapy, and other hot
surfaces.
252
• Follow-up with a healthcare provider on a routine
basis. Notify the provider immediately if a sore,
blister, cut, or scratch develops.
• Avoid smoking.
• Keep diabetes under control.
• Consider referral to an appropriate dietician or
nutritionist.
• Be aware of poor eyesight and its affect on the over-
all self care of the patient.
Footwear specifics for lower extremity neuropathic
disease as recommended by the Wound, Ostomy and
Continence Nurses Society14 include:
• Avoid friction from ill-fitting shoes.
• Wear well-fitting, therapeutic, customized shoes
that effectively off-load problematic feet and
deformities.
• See a foot wear specialist such as an orthotist or
pedorthist who can choose or manufacture appro-
priate foot wear.
• Follow shoe design recommendations:
• Allow for 0.5 in. of space beyond the longest toe.
• Allow adequate width/depth for toe spread.
• Ensure adequate ball width.
• Check for adequate heel-to-ball fit.
• Shoes should match the shape of the foot.
• Follow shoe fitting recommendations:
• Shoes should be fitted in the afternoon when edema
tends to peak.
• Patients should stand and walk when being fitted
for shoes.
• Socks or stockings that would normally be worn with
the shoes should be worn when fitting new shoes.
• Both feet should be measured and shoes fitted to the
larger foot.
• Wearing of new shoes should be increased gradu-
ally 1–2 h at a time with a routine foot inspection to
check for areas of pressure following each wearing
session.
• Appropriate commercially available shoes include:
–– Made of natural materials such as leather.
–– Have cushioned outer soles and removable inner
liners.
–– Have a deep toe box.
–– Secure with laces or hook-and-loop fasteners.
• Wear orthotic footwear to correct an altered gait or
orthopedic deformities.
• Inspect the inside of shoes every day for foreign
objects, nail points, torn linings, and rough areas.
C. A. Fleck
Patients who used therapeutic footwear showed lower
foot pressures as compared to those who did not. New
ulcer occurrence is significantly higher in those patients
who did not wear therapeutic gear.15 Research also
suggests that only 22% of individuals who own dia-
betic shoes wear them all day as prescribed, although
most wear them periodically.16,17
A multidisciplinary prevention approach is recom-
mended for persons with diabetes, insensate feet, and
peripheral neuropathy.18 Individuals at risk for foot
ulceration (considering loss of protective sensation,
history of previous ulceration or amputation, elevated
plantar pressure, rigid foot deformity, poor diabetes
control [HgA1c > 7%], diabetes of greater than 10
years duration) need to be identified early.18
High-risk individuals should be referred to foot care
specialists for on-going preventative care and lifelong
surveillance.18 A neuropathic foot screening to identify
current foot problems and initiate a prescription for
appropriate prevention measures and treatment, based
on risk category, should be performed at regular inter-
vals.19 It is recommended that a lower extremity ampu-
tation prevention program be undertaken, including
annual foot screening for at-risk individuals, on-going
patient education, assistance with appropriate footwear
selection, patient teaching of daily foot assessment,
and management of simple foot problems.20
22.2 Arterial and Ischemic Ulcers
LEAD is a progressive and persistent disorder affect-
ing about 33% of US seniors (see Fig. 22.5).21 LEAD
is triggered by cholesterol deposits (atherosclerosis),
PVD, and blood clotting disorders (emboli). Insufficient
arterial blood supply to the lower limb leads to full or
partial obstruction of the artery resulting in tissue isch-
emia and ultimately, necrosis.21 Advanced age, hyper-
lipidemia, tobacco use, diabetes mellitus, hypertension,
obesity, inactivity, and a family history of cardiovas-
cular disease predispose one to LEAD.22 LEAD nega-
tively influences individuals, families, and ultimately,
society. Ten to twenty-five percent of individuals with
LEAD progress to critical limb ischemia within 5
years and 3–8% experience limb loss.22 The overall
price to treat lower limb ulcers is approximately $1
billion annually in the US alone, not including the
countless lost work days. In addition, the annual cost
22  Wound Prevention
Fig. 22.5  Arterial ulcer
of LEAD-induced amputations in the United States is
about $5 billion.21 Early diagnosis is often a challenge
due to fewer than 50% of individuals with LEAD
exhibiting typical clinical signs and symptoms con-
nected with LEAD. Therefore, clinicians frequently
use unpredictable assessment techniques for diagnos-
ing disease.21
These wounds may be present in patients with dia-
betes and as mentioned earlier, PVD. It has been esti-
mated that PVD affects 30% of older individuals, ages
55–74.23 Risk factors include high blood pressure, cor-
onary artery disease, age, diabetes, obesity, hyperlipi-
demia, and smoking. The patient will often complain
of pain upon leg elevation and/or nocturnally, and fre-
quently prefer to dangle their legs for optimal blood
flow.24
Patients should be educated on life-style changes to
minimize situations that cause vasoconstriction includ-
ing: avoidance of smoking, exposure to cold, and wear-
ing constricting clothing, as well as how to alleviate
ischemic pain by ambulation or dangling their legs. If
able, the patient with a high-risk of arterial ulcers
and/or compromised arterial blood flow should be
encouraged to ambulate and take part in a regular exer-
cise program.
22.3 Perineal Dermatitis
and Denudation
Perineal or “diaper” dermatitis (Fig. 22.6) is a cutane-
ous eruption in the diaper area caused by frequent and
253
Fig. 22.6  Perineal dermatitis
prolonged use of a diaper or underpad trapping urine
and/or feces close to the skin. It is caused by an inter-
action between several factors:
• Frequent and prolonged skin wetness from occlu-
sion and urine caught close to the skin.
• Friction by movement of the skin against skin, the
diaper, the plastic leg gatherings, or the fastening
tape.
• The presence of fecal enzymes that may cause cuta-
neous irritation coupled with bacterial or yeast
growth in a dark, moist environment on inflamed,
damaged skin.
Perineal dermatitis is common in infants and those
adults who wear basic incontinence products that do
not adequately wick away moisture.25 If this type of
dermatitis is present for longer than 3 days, there is
likely to be secondary Candida albicans infection.26
Generally, perineal dermatitis presents clinically as
bright red, painful erythema with or without papules,
erosions, scale and/or maceration, initially sparing the
skin creases, on the lower abdomen, groin, perineum,
buttocks, labia majora, scrotum, penis, or upper thigh.
Maintaining perineal skin integrity is one of the
biggest challenges in long-term and extended-care set-
tings, where 50–70% of patients suffer from urinary
incontinence.27 Perineal skin injury has been found in
as many as one-third of hospitalized adults.28
Though rarely used in clinical practice, the litera-
ture describes two different assessment tools: the
Perineal Dermatitis Grading Scale and the perirectal
skin assessment tool (PSAT). The PSAT measures the
degree of skin breakdown while the Perineal Dermatitis
254 C. A. Fleck

Grading Scale is more like a wound and skin assess-
ment, specifically targeting location of dermatitis, skin
color and integrity, amount of skin involvement, and
symptoms, such as pain. The scale also includes an
area for a brief description of the skin assessment or
the patient’s symptoms.29
A validated tool developed by Nix can be used to
assess risk for perineal skin damage30 The perineal
assessment tool (PAT) is an instrument that identifies
four determinants of perineal skin breakdown: duration
of irritant, intensity and type of irritant, perineal skin
condition, and contributing factors causing diarrhea.
Each subscale reflects degrees of risk factors. All sub-
scales are rated from one (least risk) to three (most risk).
Each rating has a descriptor and a description of each
level of the scale. Total scores can range from 4 (least
risk) to 12 (most risk). A score between four and six on
the PAT scale is considered a low risk, and a score
between 7 and 12 is considered a high risk (Fig. 22.7).30
This tool may be added to the assessment, along with
the Braden Risk Assessment Score (Fig. 22.8).
The Wound, Ostomy and Continence Nurses
Society guidelines for prevention and management of
pressure ulcers offers these interventions for prevent-
ing perineal dermatitis:
• Establish a bowel and bladder program for patients
with incontinence.
• Avoid excess friction on the skin.
• Cleanse skin gently at each time of soiling with pH-
balanced cleansers.
• Use incontinent skin barriers as needed to protect
and maintain intact skin.
• Select underpads, diapers, or briefs that are absor-
bent to wick incontinence moisture away from the
skin.
• Consider using pouching system or collection
device.31
The use of absorptive and/or occlusive devices has
been identified as a large contributor to the problem of
incontinence-associated dermatitis, leading to wounds.
Prolonged occlusion of the skin under an absorptive
incontinent product for 5 days has been shown to cause
an increased sweat production and compromised bar-
rier function, resulting in increased transepidermal
water loss (TEWL), CO2 emission, and pH; microflora
of the skin undergoes a marked increase in coagulase-
negative staphylococcus.32
Novel disposable underpads that allow air flow
and offer advanced polymer technology provide
super absorbing capacity (absorbing power of three
or more pads) while locking fluid deep within the
pad, keeping the patient’s skin dry for better odor
control and skin care (Fig.  22.9). In addition, the
underpads provide a healthier skin environment,
allowing air flow while acting as a barrier to mois-
ture. They also lower overall costs (reducing the need

PerinealAssessment Tool
P.A.T.
1
Intensity of irritant 3 2
Formed stool
Type and consistency Liquid stool with Soft stool with or without
and/or
of irritant or without urine urine
urine
1
3
Duration of irritant 2 Linen/pad
Linen/pad changes
Amount of time that skin Linen/pad changes changes
at least every 2 hours
is exposed to irritant at least every 4 hours every 8
hours or less
Perinealskin 3 2 1
condition Denuded/eroded with or Erythema/dermatitis with or Clear and
Skin integrity without dermatitis without candidiasis intact
Contributing factors
3 1
Low albumin, antibiotics,
3 or more contributing 2 0-1
tube feeding, or
factors 2 contributing factors contributing
C. Difficile
factor
infection, other

•Score of 4-6 on the PAT scale is considered “low”risk

•Score of 7-12 is considered “high”risk.

Fig. 22.7  Perineal assessment tool (PAT)30

22  Wound Prevention
Patient’s Name _____________________________________
SENSORY PERCEPTION
ability to respond meaning-
fully to pressure-related
discomfort
MOISTURE
degree to which skin is
exposed to moisture
ACTIVITY
degree of physical activity
MOBILITY
ability to change and control
body position
NUTRITION
usual food intake pattern
FRICTION & SHEAR
© Copyright Barbara Braden and Nancy Bergstrom, 1988 All rights reserved
Fig. 22.8  Braden risk assessment score (Copyright Barbara Braden. Used with permission)
Fig. 22.9  Super-absorbent
polymer underpad (Courtesy
Medline Industries, Inc. Used
with permission)
multiple pads, reusable pads and draw sheets) and
make for easier care, as they may be used on regular
or low-air-loss beds.
BRADEN SCALE FOR PREDICTING PRESSURE SORE RISK
Evaluator’s Name________________________________
1. Completely Limited
Unresponsive (does not moan,
flinch, or grasp) to painful
stimuli, due to diminished level of
con-sciousness or sedation.
OR
limited ability to feel
pain over most of body
1. Constantly Moist
Skin is kept moist almost
constantly by perspiration, urine,
etc. Dampness is detected
every time patient is moved or
turned.
1. Bedfast
Confined to bed.
1. Completely Immobile
Does not make even slight
changes in body or extremity
position without assistance
1. Very Poor
Never eats a complete meal.
Rarely eats more than ¹/³ of any
food offered. Eats 2 servings or
less of protein (meat or dairy
products) per day. Takes fluids
poorly. Does not take a liquid
dietary supplement
OR
is NPO and/or maintained on
clear liquids or IV’s for more
than 5 days.
1. Problem
Requires moderate to maximum
assistance in moving. Complete
lifting without sliding against
sheets is impossible. Frequently
slides down in bed or chair,
requiring frequent repositioning
with maximum assistance.
Spasticity, contractures or
agitation leads to almost
constant friction
2. Very Limited
Responds only to painful
stimuli. Cannot communicate
discomfort except by moaning
or restlessness
OR
has a sensory impairment which
limits the ability to feel pain or
discomfort over ½ of body.
2. Very Moist
Skin is often, but not always moist.
Linen must be changed at least
once a shift.
2. Chairfast
Ability to walk severely limited or
non-existent. Cannot bear own
weight and/or must be assisted into
chair or wheelchair.
2. Very Limited
Makes occasional slight changes in
body or extremity position but
unable to make frequent or
significant changes independently.
2. Probably Inadequate
Rarely eats a complete meal and
generally eats only about ½ of any
food offered. Protein intake
includes only 3 servings of meat or
dairy products per day.
Occasionally will take a dietary
supplement.
OR
receives less than optimum amount
of liquid diet or tube feeding
2. Potential Problem
Moves feebly or requires minimum
assistance. During a move skin
probably slides to some extent
against sheets, chair, restraints or
other devices. Maintains relatively
good position in chair or bed most
of the time but occasionally slides
down.
related to friction and shearing forces and chemical
and enzyme irritation from incontinence.33
255
Date of Assessment
3. Slightly Limited 4. No Impairment
Responds to verbal com- Responds to verbal
mands, but cannot always commands. Has no
communicate discomfort or the sensory deficit which would
need to be turned. limit ability to feel or voice
OR pain or discomfort..
has some sensory impairment
which limits ability to feel pain
or discomfort in 1 or 2 extremities.
3. Occasionally Moist: 4. Rarely Moist
Skin is occasionally moist, requiring Skin is usually dry, linen
an extra linen change approximately only requires changing at
once a day. routine intervals.
3. Walks Occasionally 4. Walks Frequently
Walks occasionally during day, but Walks outside room at least
for very short distances, with or twice a day and inside room
without assistance. Spends at least once every two
majority of each shift in bed or chair hours during waking hours
3. Slightly Limited 4. No Limitation
Makes frequent though slight Makes major and frequent
changes in body or extremity changes in position without
position independently. assistance.
3. Adequate 4. Excellent
Eats over half of most meals. Eats Eats most of every meal.
a total of 4 servings of protein Never refuses a meal.
(meat, dairy products per day. Usually eats a total of 4 or
Occasionally will refuse a meal, but more servings of meat and
will usually take a supplement when dairy products.
offered Occasionally eats between
OR meals. Does not require
is on a tube feeding or TPN supplementation.
regimen which probably meets
most of nutritional needs
3. No Apparent Problem
Moves in bed and in chair
independently and has sufficient
muscle strength to lift up
completely during move. Maintains
good position in bed or chair.
Total Score
soft, non-woven topsheet
Soft against skin for increased comfort
Advanced SuperCare absorbent sheet
Thermo-bonded to provide pad integrity
and exceptional skin dryness
AquaShield Film
Traps moisture,providing leakage
protection
Innovative Backsheet
Air permeability means skin comfort
Denudation is a form of partial thickness injury
256
22.4 Maintaining Skin’s Integrity
Skin care is a four-pronged approach with cleansing,
moisturizing, protecting, and now nourishing being
the key steps. The largest organ of the body, the integ-
ument, receives one third of the human body’s car-
diac output, feeding and nourishing it from the
inside.34 Nutrition and antioxidant protection can also
take place endermically with the advent of advanced
skin care products. See Table 22.1 for the hierarchy
or generations of available skin care products.
22.4.1 Cleansing
Cleanser technology has come a long way from merely
cleansing for the removal of sebum, soil, dirt, and bac-
teria to providing mildness, moisture, and now nour-
ishment to the skin in addition to cleaning it. Harsh
soaps and surfactants in cleansers can cause damage to
skin proteins and lipids, inflammation and swelling of
the stratum corneum, and alter lipid rigidity. This leads
to tightness, dryness, barrier damage, irritation, pH
disruption, increased water loss or dehydration of the
skin, and itching.35 Shocking as it may seem, soaps
touted as “natural” and “safe” often have the highest
and, therefore, most damaging pH. For instance, Ivory
soap has a pH of 10.5 and Dial measures in at 10.0.
This simple pH study looked at products commonly
used in nursing homes.36
In order for cleansers to provide skin care benefits,
they must first minimize the damage of surfactants to
skin proteins and lipids. This can be accomplished by
using the least harmful surfactants or, better yet, phos-
pholipids to clean. Phospholipids are ingredients
derived from selected vegetable oils that can bind both
water and fat, providing excellent cleansing and condi-
tioning properties and incredible after-feel due to their
mildness. They contain naturally occurring polyunsat-
urated fatty acids (PUFAs), which can contribute to the
activation of cellular metabolism. They are superior
cleansers that do not strip, dehydrate, or inflame the
epidermis. Cleansers must secondly deposit and deliver
beneficial agents, such as occlusive skin lipids, humec-
tants, amino acids, and vitamins, under wash condi-
tions to improve skin hydration as well as mechanical
and visual properties.
C. A. Fleck
Soap and surfactant detergent-type cleansers can be
damaging and abusive to patients’ skin. Soap strips the
skin of cell-binding lipids and ceramides and makes it
much more vulnerable to assaults of daily living, such
as skin tears. Sodium lauryl sulfate, ammonium lau-
reth sulfate, and sodium laureth sulfate are associated
with irritation and stripping skin lipids, especially
when left on the skin in the “no-rinse” products.
Repeated surfactant use leads to increased skin dehy-
dration and potential damage. Another caveat to con-
sider is to customize bathing according to patient
needs. Daily baths with a bath basin and bar of high
alkaline soap can be extremely detrimental to the
integument.
22.4.2 Hydration
The epidermis contains lipids that play a vital role in
maintaining healthy skin and regulating moisture loss.
With age, the use of detergents and damage, such as
burns or wounds, cause the skin to lose some or all of
its ability to retain moisture. Skin becomes dry and
with this dryness comes skin breakdown.
Skin needs to be protected from the environment to
reduce the effects of aging. To do so, the use of skin
moisturizers and protectants is beneficial. Moisturizers
are complex formulations designed to maintain skin
flexibility, smoothness, and barrier integrity while
maintaining the water content of the skin between
10 and 30%. For skin to appear and function normally,
the water content of the stratum corneum must be at
least 10%. Cells are composed of 70% water. Since
the skin is made up of cells, maintaining a high level
of moisture in the skin is necessary. Skin that is water
deficient, such as thickened skin over the heels, is
often rough to the touch and fissures easily. There are
two means by which to moisturize the skin. One way
is to add back moisture to the skin. The other way is to
block or inhibit TEWL.
Moisture is mandatory for an organ that is in con-
stant motion. Skin hydration is important to maintain
an intact barrier protection. The application of topical
moisturizing and protectant products, coupled with the
use of surfactant-free cleansers, helps reduce dryness
and stop TEWL. In order for moisturizers to work,
they must be coupled with moisture in the form of
water. It either comes from the dermis (internally) or
22  Wound Prevention 257

Table 22.1  Hierarchy of skin care products

Product First-generation products
category
Cleansers Soaps – oldest amphiphilic
cleaning agent, highly
alkaline. Examples include
sodium cocoyl, sodium
tallowate, sodium sterate,
sodium dodycelbenzensul-
foate, sodium cocoate,
sodium palmitate, etc.
Moisturizers Lotions, creams and ointments Lotions, creams and ointments
emollients containing lanolin,
humectants glycerin, mineral oil,
propylene glycol,
petrolatum, cocoa butter,
paraffin, etc
Protectants Creams and ointments
and containing petrolatum,
barriers octyl hydroxysterate, etc
Copyright Cynthia A. Fleck®
Second-generation products
Surfactants – synthetic detergents
such as sodium lauryl sulfate,
tea lauryl sulfate, cocoam-
phocarboxyglaycinate,
disodium oleamido mea
sulfosuccinate, sodium laureth
sulfate, ammonium laureth
sulfate, etc.
containing first-generation
ingredients plus ingredients
such as carbohydrates like aloe
vera, vitamins like retinyl
palmitate (vitamin A),
ergocalcifrol (vitamin D),
glycosaminoglycans such as
hyaluronic acid, polyhydroxy
hydroxy acids, urea, etc.
Creams and ointments containing
dimethicone, allantoin, zinc
oxide, calamine, karaya gum,
etc.
Third-generation products
Phospholipids – mimic the body’s
natural lipid requirements,
ingredients derived from selected
vegetable oils that can bind both
water and fat providing excellent
cleansing and conditioning without
stripping or drying. Examples
include: cocamidoproryl
PG-dimonium phosphate,
linoleamidopropyl PG > dimonium
chloride phosahpte dimethicone,
disodium lauromphodiacetate
Lotions, creams and ointments
containing first- and second-
generaton ingredients plus nutritive
ingredients such as amino acids,
vitamins and cofactors, high-quality
oils and lipids such as shea butter or
grape seed oil, antioxidants such as
hydroytyrosol, advanced silicones
and methylsulfonylmethane
Creams and ointments containing
first- and second-generation
ingredients plus nutritive ingredients
such as amino acids, vitamins and
cofactors, high-quality oils and
lipids such as shea butter or grape
seed oil, antioxidants such as
hydroytyrosol, advanced silicones
and methylsulfonylmethane

externally applied water, such as immediately follow-
ing a bath or shower. The National Eczema Association
for Science and Education recommends sealing in
skin’s moisture with a high-quality moisturizer within
3 min of showering or bathing.
22.4.2.1 Xerosis
Xerosis is dry skin that appears when there is dehydra-
tion of the stratum corneum and is one of the most
common skin conditions to affect the elderly
(Fig. 22.10).37 It is most common in the aged who have
decreased epidermal free-fatty acids, compared to
younger skin. Xerotic skin additionally has a reduced
amino acid content.38 The patient will usually complain
of dryness and itching. The condition is more prevalent
in the lower legs and feet but can occur anywhere on
the body. It also tends to exacerbate in winter months,
and in cold and dry climates or low humidity
conditions.
Moisturizers are primarily intended to help the skin
to function properly in conditions where temperature
and humidity are low and mimic the role of naturally
occurring epidermal lipids. They are sold as creams,
lotions, and in some cases serums. Lotions are the
lightest and provide less protection.
The most important moisturizer, and really the only
true moisturizer, is water. To maintain the water con-
tent of the skin, we can use occlusive ingredients to
keep the moisture from evaporating, such as petrola-
tum or mineral oil, or apply water to the skin and bind
258
Fig.  22.10  Xerosis or dry skin with typical flaky or scaly,
almost transparent appearance
it with humectants (e.g., glycerin, hyaluronic acid, chi-
tosan, beta glucan 1–3), emollients (e.g., shea butter,
avocado butter, cocoa butter), or nonocclusive ingredi-
ents, such as natural oils and silicones. One caveat is
that mineral oil and petrolatum are hydrocarbons and
do not contribute to lipid replacement. Better choices
include high-quality oils like borage oil, olive oil, and
rose hip seed oil.
22.4.3 Skin Protectants
When the skin needs extra protection from inconti-
nence, periwound maceration, wound, stoma, fistula,
or access site drainage or leaking, partial-thickness
wounds, and denudation, barriers provide the answers.
Since incontinence affects 13 million Americans or
about 10–35% of adults and at least half of the 1.5 mil-
lion nursing home residents,39 incontinent dermatitis is
a common skin dilemma that often results when urine
comes in contact with dry, cracked skin. It provides an
excellent environment for the growth of bacteria,
resulting in the production of ammonia. Ammonia
increases the pH of the skin, reducing the acid mantle’s
protective capacity as a bacterial barrier subsequently
presenting the opportunity for chemical irritation by
urine, feces, and excess moisture leading to skin
breakdown.27
Protectants or barriers provide a physical barrier
between the skin and caustic bodily fluids. Ointments
and creams that contain petrolatum are inexpensive
and readily accessible but need to be applied frequently
C. A. Fleck
as they melt off and wash away quickly. They can also
inhibit the absorbency of briefs, under pads, and dress-
ings. An example is A and D Ointment. Products con-
taining zinc oxide stay on the skin longer, providing
better protection. They are thicker and allow the care-
giver to simply “fill in the blanks” when reapplying
after cleansing.
Dimethicone and other silicones provide sophisti-
cated additions in many skin protectants. These ingre-
dients provide long-lasting protection, remaining on
the skin through multiple washings or cleansings. The
percentage of dimethicone cannot be judged by itself
since combinations of various silicones can offer better
protection than just a high percentage of dimethicone
alone.
22.4.4 Skin Nutrition
Maintaining healthy skin is vital to a person’s overall
health. As we age, the skin, like other organs in the
body, begins to function less effectively, and therefore,
special care is required. The use of advanced cleansers
that are gentle and do not strip the skin and moistur-
izers and protectants to defend the skin from dryness
and TEWL is essential. The replacement of soaps with
cleansing lotions and surfactant-free products that
protect skin lipids and aid in skin integrity is also
vital.
There is a new generation of skin care products that
do more than clean, protect, and moisturize. These
advanced skin care products can actually nourish the
skin by providing vital amino acids, vitamins, lipids,
and antioxidants that were developed to protect skin
from breakdown and to minimize the risk of dryness,
decreased skin integrity, and invasion of pathogens.
The products also bring nutrients to the skin that help
restore its protective acid mantle, help reestablish col-
lagen, and help defend against free radical damage
while protecting from stinging and pain. In addition,
they have been shown to decrease the prevalence of
pressure ulcers and skin tears.40 One retrospective,
longitudinal study studied the changes in pressure
ulcer prevalence rates and the economic effect of
introducing a silicone-based dermal nourishing emol-
lient regimen into an existing pressure ulcer proto-
col.41 The results showed a decrease from 17%
incidence rate down to 0% and an average cost
22  Wound Prevention
savings of $6,677 per patient. Think of these third-
generation advanced skin care products as a form of
“corneotherapy,” feeding and nourishing the stratum
corneum.
Key ingredients and nutrients can be applied and
absorbed via the skin to deliver nourishment and pro-
vide healing and health to this vulnerable organ. This
is termed endermic nutrition. Enhancing the skin with
the topical application of amino acids, antioxidants,
and lipids may be the only external way to improve
the health of this vital organ. Nutrients enter the epi-
dermis from the dermis or the stratum corneum.
Advanced skin care products truly address the needs
of the cells, providing the proper nutrients in the cor-
rect forms for the skin to assimilate them, helping pro-
tect the cells against free radical damage while
supplying amino acids that are the main building
blocks of collagen.
22.5 Pressure Ulcers
Pressure ulcers are one of the largest dilemmas facing
long-term care providers and clinicians who care for
geriatric patients. Two thirds of pressure sores occur
in patients older than 70 years of age.42 Pressure ulcer
prevalence is estimated to be around 15% in acute
care, up to 28% in long-term care and up to 29% in
home care.43 Pressure ulcers account for $2.2–3.6 bil-
lion/year in expenditures,44 can cost up to $70,000 to
treat,45 and kill 60,000 people in the US every year.46
Patients inclined to pressure ulcers are at higher risk
of morbidity and mortality, with infection, osteomy-
elitis, and sepsis being the most common major
complications.
Pressure ulcers are any lesions caused by unre-
lieved pressure resulting in damage of underlying
tissue.47
Pressure ulcers have affected us throughout the
ages. Yet, dealing with the general management of
pressure ulcers has only just begun to gain notoriety
among national and worldwide healthcare concerns. In
spite of present attention and development in the areas
of medicine, surgery, nursing care, physical therapy,
and self-care education, pressure ulcers continue to be
a major source of morbidity and mortality. This is
especially true for our elders and for those with
impaired sensation and prolonged immobility.48
259
Fig. 22.11  Pressure ulcer
It is theorized that pressure ulcers are caused by
localized pressure or shear forces that lead to ischemia
and cell death, thus causing skin and tissue breakdown
(Fig. 22.11). Pressure is equal to force, divided by area.
So the greater the surface area of the load, the less pres-
sure exerted. For instance, a sitting individual is at higher
risk of developing a pressure ulcer than a person who is
lying supine. Kosiak proved that tissue compression and
ischemia can lead to tissue destruction and pressure
ulcer formation. He also showed that the amount of
pressure and the duration of the pressure are inversely
proportional.49 For instance, low amounts of pressure
over longer periods of time can be just as detrimental as
high pressure for shorter times (Fig. 22.12).50
22.5.1 Causes
Although prolonged, uninterrupted pressure is the
main cause of pressure ulcers, impaired mobility is
probably the most common reason patients are exposed
to unrelieved pressure. This is common in those who
are neurologically impaired, heavily sedated or anes-
thetized, restrained, demented, or those suffering trau-
matic injury such as a pelvic or femur fracture. These
patients are incapable of assuming the responsibility of
altering their position to relieve pressure. Moreover,
this immobility, if prolonged, leads to muscle and soft
tissue atrophy, decreasing the bulk over which bony
prominences are supported, further increasing the risk
of developing a pressure ulcer.
 260
700
600
Pressure, mm Hg
500
400
300
Unacceptable
200
100
0
Acceptable
2 4 6 8 10 12 14
Hours of continuous pressure
Fig. 22.12  Guidelines for sitting duration. Maximum suggested
pressure/time application over bony prominences50
22.5.2 Heel Pressure Ulcers
The heel presents a problematic source of pressure due
to its bony prominence, especially in the recumbent
individual. Care should be taken to mobilize the immo-
bile, providing good skin care and off-loading with
pressure relief equipment, to the vulnerable heel area.
The heel is one of the most difficult anatomical areas
to address by prevention products.51 Studies have dem-
onstrated that support surface, including special beds,
mattresses, and overlays, do not provide complete
pressure relief in the heel region.52 Be aware of antiem-
bolism stockings, TED hose, and compression devices
as they can camouflage the heels and preclude thor-
ough assessment.
Floating the heels is recommended by many experts
as well as prevention guidelines as the only viable
method to completely alleviate heel pressure and prevent
ulcers.53
22.5.3 Prevention Basics
Healthy individuals with normal sensation, mobility,
and mental faculty usually do not succumb to pressure
ulcers. Feedback, both conscious and unconscious,
from the areas of compression leads us to change our
position. We constantly make micro-movements to
compensate. This shifts the pressure from one area to
another prior to any irreversible ischemic damage to
the tissues. Weight shifting for insensate individuals or
those with poor mobility should take place every
15 min in the seated person and at least every 2 h in the
recumbent individual.54–56
C. A. Fleck
Pressure ulcer prevention encompasses alleviating
the possible causative factors. If we consider that lack
of viable blood flow to the tissue is the main cause of
pressure ulcers, we can further classify that damage
into pressure, shear, friction, moisture and heat and
thus, better support the host. We can also prevent pres-
sure ulcers by managing the following negative effects.
16 18 These prevention recommendations are adapted from
the 1992 agency for healthcare policy and research
(AHCPR), now the Agency for Healthcare Policy and
Research (AHRQ) clinical practice guidelines53 and
the Wound Ostomy and Continence Nurse Association’s
2003 Guidelines for Prevention and Management of
Pressure Ulcers.57
22.5.3.1 Pressure
• Pressure can be lessened by establishing a patient
turning schedule that can be documented. The stan-
dard of care for turning and repositioning is every
2 h in the recumbent individual and every 15 min in
the seated person.
• Use the 30° lateral position in a supine patient
instead of placing a patient side lying at 90°. This
dramatically decreases the peak pressure caused by
the greater trochanter.
• Implement an appropriate pressure-redistribution
support surface to both the seated and recumbent
surfaces that the patient’s body contacts at the first
sign of risk.
• For cushioning a seated client, avoid the use of invalid
rings, “donuts”, rubber rings or any technology that
has a “cut-out” since this can actually increase pres-
sure, especially over bony prominences.
• Limit the time that the patient spends on the com-
mode or bedpan.
• Off-load the heels with a pillow, heel protection
device or wedge.
22.5.3.2 Shear
• Limit the elevation of the head of the bed to 30° or
less.
• Use draw sheets to turn and reposition patients.
• Use the bed’s side rails and consider adding a tra-
peze to the bed frame to optimize mobility and
decrease shear forces.
22  Wound Prevention
• Never perform massage over bony prominences
that have been compressed. This can cause tissue
damage, although there is conflicting information
in the literature.58
22.5.3.3 Miscellaneous
• Apply high-quality moisturizers to the skin to
increase the water content and thus pliability and
strength. Apply moisturizers anytime water comes
in contact with the skin, especially after the bath or
shower. Look for products that allow the skin to
breath while decreasing excessive transepidermal
water loss (e-TEWL).
• Use a skin prepping solution or sealant before using
tape on a patient’s skin.
• Teach the patient and care givers to visually inspect
the skin daily for early detection.
• Encourage proper hydration and nutrition.
• Institute an active or passive range-of-motion routine.
• Calculate a risk assessment score on every patient to
identify those at high risk for development of pres-
sure ulcers (see risk assessment, Braden Scale).
• Apply transparent dressings or skin sealants to pro-
tect the epidermis.
22.5.3.4 Moisture
• Protect the skin from body fluids and drainage by
absorption.
• Decrease baths and address a patient’s need for skin
cleansing individually and by body region.
• Use moisturizing, soap-free cleansers with a neutral
or slightly acidic pH.
• Apply barrier creams that remain in contact with
the skin despite cleaning to offer protection from
incontinence episodes. Good examples of ingredi-
ents include zinc oxide, dimethicone, and other
high-quality silicones. Products containing petrola-
tum-based protectants should be avoided since they
protect for a very short time and do not remain in
contact with the skin.
• Institute a bowel and bladder program that is cus-
tomized to each resident and can be documented.
• Consider the use of some of the newer high-tech
polymer-based incontinent products (briefs, pad,
etc.) and customize to each resident’s needs.
261
22.5.3.5 Seated Dependent
• Avoid uninterrupted sitting.
• Teach the patient to perform a weight shift (stand
up with assist, push-up, bend at the waist, or shift
from side to side) every 15 min.
• If the patient is not able to perform an independent
weight shift, they should be repositioned or put
back to bed once per hour.
• Utilize a high-quality pressure redistribution cush-
ion (high-density foam, air or viscous gel) for all
seated dependent individuals.
Recently, the New Jersey Hospital Association Collabora­
tive achieved a 70% reduction in the incidence of pres-
sure ulcers in 2 years,59 from 18% down to 5%. They
accomplished this by focusing on prevention, develop-
ing, and delivering 2-day sharing and learning sessions
and continuation of best practice.
22.5.4 Support Surfaces
In the pursuit of prevention and management of skin
and tissue breakdown, support surface selection
remains an important decision for the clinician.
Pressure ulcers are caused by a myriad of intrinsic and
extrinsic factors. Support surfaces can have significant
influence over extrinsic factors such as pressure, shear,
friction, moisture, and temperature.60 These factors
directly impact deformation of the soft tissue, blood
flow, tissue ischemia and necrosis, and pressure ulcer
development, especially in the immobile patient. The
manner by which support surfaces manage these
extrinsic factors can be used by clinicians as they select
support surfaces for their patients.
Support surfaces are specialized devices for pres-
sure redistribution designed for management of tissue
loads, microclimate, and/or other therapeutic functions
as adjunctive devices to pressure ulcer prevention.
External pressure, especially over the bony promi-
nences, has been identified as the major etiology in
pressure ulcer development. Additional associated ori-
gins consist of the degree of shear and friction forces
and the further effects of temperature and moisture.
All of these factors can be affected by, and are corre-
lated to, the characteristics of the support surface
selected for an individual.
262
Clinicians typically use the term “pressure” to
reflect normal pressure or interface pressure – the
force per unit area that acts perpendicular to the tissue.
The forces that result in normal pressure on the tissues
are typically due to gravity; body weight is resting on
the supporting surface. With respect to support sur-
faces, this normal loading may be the most significant,
but it is not the only force that impacts tissue
integrity.
Various clinical strategies exist to manage these
extrinsic factors, especially for patients exhibiting the
two greatest risk factors for pressure ulcers, dimin-
ished mobility, and/or lack of sensation. Turning and
repositioning are the most effective ways to counteract
impaired mobility. However, the accepted protocol of
turning and repositioning a patient every 2 h may not
be enough.61 An individualized care plan must be
developed that includes support surfaces as integral
components to prevention and management of pres-
sure ulcers.
Support surfaces choice and selection is one of
many important decisions the clinician and team must
assess, plan, implement, evaluate, and discuss for both
prevention and treatment of pressure ulcers.
22.6 Skin Tears
It is important to mention skin tears, traumatic sores
that tend to occur to some of the same individuals as
pressure ulcers (Fig. 22.13). As the skin ages, the base-
ment membrane (junction between the epidermis and
Fig. 22.13  Skin tear
C. A. Fleck
the dermis) flattens, making it “loose,” thus more prone
to traumatic injury and unintentional separation, in
essence, a skin tear. The anatomy of aging skin makes
skin tears nearly inevitable in the elderly. In addition,
harsh soaps and surfactant cleansers as well as nonnu-
tritional moisturizers and protectants containing hydro-
carbons such as petroleum and mineral oil, which do
not contribute to lipid replacement, further add to the
skin’s vulnerability. Choosing a skin care regime that
replaces soap and harsh surfactant cleansers (detergent
type) with pH balanced mild cleansers and phospho-
lipids cleansers can decrease the incidence of skin
tears, additionally providing overall cost savings and
comfort.
22.7 Nutrition
By far, one of the most incriminating intrinsic risk fac-
tors for the development of pressure ulcers as well as
other wounds is malnutrition. Many studies cite a
strong link between deteriorating nutritional status and
the development and healing of chronic, nonhealing
wounds such as pressure ulcers.62–64 Up to 85% of resi-
dents in nursing homes suffer from malnutrition.65 It is
no wonder that this group of individuals is also at high-
est risk for the development of pressure ulcers.
A nutritional assessment can help the provider iden-
tify whether a patient has nutritional risk factors for
impaired wound healing. When is a nutritional assess-
ment indicated? There are many “red flags” to alert the
provider to potential risk. An obvious one is involun-
tary weight loss and/or a change in the individual’s
appetite. Some not so apparent indicators may include
impaired cognitive patterns, altered communication/
hearing/vision, impaired mood/behavior, and dimin-
ished physical and functional capabilities. A Braden
scale risk-assessment score below the threshold of 18
in older populations can indicate risk for development
of pressure ulcers. This is an assessment that is most
likely already being performed and can serve as an
early warning to initiate further nutritional
investigation.
A nutritional assessment investigates four basic cat-
egories: anthropometric information, biochemical
data, clinical facts, and dietary history66 , and should be
conducted by a registered dietician on every at-risk
individual.
22  Wound Prevention
22.7.1 Biochemical Data
Biochemical data includes laboratory tests, such as
serum albumin, serum prealbumin, serum transferrin,
total lymphocyte count (TLC), and nitrogen balance.
Serum albumin is the major circulating plasma pro-
tein synthesized by the liver. It is an inexpensive blood
test and common indicator of the resident’s protein
stores. Its half life (how long it will take before we see
decreases in lab data) is about 3 weeks, so the blood
you draw from your resident today will indicate their
protein stores from 3 weeks ago. Mild depletion is
considered 3.5  gm/100  mL. Serum albumin below
3.0 gm/dL (hypoalbuminemia) is associated with tis-
sue edema, which further increases risk of pressure
ulcers. Serum albumin levels are often used as an indi-
cator of overall nutrition. Low serum albumin increases
risk of infection, morbidity, and mortality. It impairs or
prevents wound healing and decreases wound tensile
strength.
Serum prealbumin is a more sensitive indicator of
visceral protein status in acute stages of malnutrition.
Its half life is only 2–3 days and can be helpful to eval-
uate the adequacy of nutritional therapy. Mild deple-
tion is <15 mg/dL. Severe depletion is <5 mg/dL. If the
resident has chronic renal failure, prealbumin may be
falsely elevated, since it is eliminated in the kidneys.
Serum transferrin has a half life of a little over a
week and is an indicator of protein stores as well. A
level below 200 mg/dL is considered low. This blood
test may not be useful in the presence of liver disease or
estrogen use, since transferrin levels will be abnormally
high. Also of note, liver disease, burns, cortisone or tes-
tosterone therapy, and chronic infection can lower
serum transferrin levels.
TLC reflects the visceral (contained in the body’s
organs) protein stores of the body and immunity. TLC
is more useful as a screening parameter in noncritical
individuals. A TLC below 2,000 cells/mm3 indicates
an impaired immune system.
Nitrogen balance is also useful for assessment of
protein requirements, since protein is 16% nitrogen.
Nitrogen balance is the difference between nitrogen
intake and output. It helps determine needs for protein
maintenance and anabolism. Accurate measurements
of food and fluid intake over a 24-h period and a 24-h
continuous urine sample are needed. Nitrogen balance
results can be questionable in the presence of renal
disease.
263
22.7.2 Vitamins and Minerals
Many registered dietitians include multivitamin/min-
eral supplements as part of their preventative protocol
for residents at high risk for ulcers or with existing
ulcers. Mega-doses should not be administered with-
out the recommendation of a physician or registered
dietitian. Consider supplementation of a 100% recom-
mended daily allowance (RDA) vitamin/mineral sup-
plement that is automatically incorporated into the
care plan. Supplementation beyond the RDA is not
advised unless the resident has a known deficiency.67
Vitamin and mineral assays are useful to confirm sus-
pected deficiencies. This goes for vitamin C and zinc
as well. Unless the individual has a known deficit, sup-
plementation has not been shown to be of any benefit.
22.8 Prevention and Reimbursement
The centers for medicare and medicaid services (CMS)
issued a new regulation beginning October 2008.
Medicare and Medicaid will no longer provide addi-
tional reimbursement to hospitals for pressure ulcers
that occurred during the patient’s stay.68 CMS believes
pressure ulcers are preventable. Average extra cost for
one pressure ulcer, for one patient in acute care is
$40,000.68 The challenge will be to put the law into
practice without destroying our healthcare system.
Success will be achieved if facilities align policies,
procedures, and personnel to prevent these nosoco-
mial events or hospital acquired conditions (HAC)
from occurring and offer quality patient care. It is rec-
ommended that hospitals ramp up education and pro-
grams to prepare for these changes. This will include
the development of key relationships to provide cost-
effective products and programs to streamline care
and save money. A similar prospective payment sys-
tem has been in place within long-term care (LTC)
since 2004.
22.9 Prevention, Full-Circle
Wound prevention can be equated to the care and
maintenance of inanimate objects or things such as
automobiles or our homes; similar to getting a “tune
264
up” on our automobile or replacing the shingles on a
house. The human body, however, is a living system,
ultimately capable of healing itself and maintaining
the skin barrier function with the proper prevention
measures. Although a complex process, most wounds
can be prevented with the right protocols, products,
personnel, education, and policies and procedures. As
the old adage states, “an ounce of prevention is worth
a pound of cure.” Not only does wound prevention
save facilities and payers time, money and possible
litigation, but ultimately the patient will be spared ache
and anguish, increasing the quality of life.
References
  1. Norman RA, Menendez R. Structure and function of aging
skin. In: Norman RA, ed. Diagnosis of Aging Skin Diseases.
London: Springer; 2008
  2. Baranoski S, Ayello EA, eds. Skin: An Essential Organ,
Chapter 4 in Wound Care Essentials Practice Principles.
Philadelphia, PA: Lippincott Williams and Wilkins; 2004:49
  3. Goldstein DR, et al Differential diagnosis: assessment of the
lower extremity ulcer. Is it arterial, venous, neuropathic?
Wounds. 1998;10:125–131
  4. Rutherford RB. The vascular consultation. In: Rutherford RB,
ed. Vascular Surgery. 4th ed. Philadelphia, PA: WB Saunders;
1995
  5. Young JR. Differential diagnosis of leg ulcers. Cariovasc
Clin. 1983;13(2):171–193
  6. Beylin M. Treating venous stasis ulcers in the lower extrem-
ity. Podiatry Today. 2004;17(10):68–74
  7. Fleck CA. Measuring ankle brachial index. Adv Skin Wound
Care. 2007;20(12):645–649
  8. Vowden K, Vowden P. Doppler and the ABPI: how good is
our understanding? J Wound Care. 2001;10:197–202
  9. Criqui MH, Browner D, Fronek A, et  al Periperal arterial
disease in large vessels is epidemiologically distinct from
small vessel disease. Am J Epidemiol. 1989;129:1110–1119
10. Wound, Ostomy, and Continence Clinical Practice Ostomy
Subcommittee. Ankle Brachial Index: Best Practice for
Clinicians; 2005:1
11. Wound Ostomy Continence Nurses Society. Guidelines for
Management of Wounds in Patients with Lower Extremity
Arterial Disease. Glenview, IL; 2002
12. Criqui M. Systemic atherosclerosis risk and the mandate for
intervention in atherosclerotic peripheral disease. Am J
Cardiol. 2001;88(7B):433–447
13. Nelson EA, Cullum N, Jones J. Compression for preventing
recurrence of venous ulcers. Cochrane Review, The Cochrane
Library, Issue 2; 2003
14. Wound, Ostomy and Continence Nurses Society Guideline
for Management of Wounds in Patients with Lower-Extremity
Neuropathic Disease, WOCN Clinical Practice Guideline
Series number 3. Glenview, IL; 2004
C. A. Fleck
15. Vijay V, Saraswathy G, Gautham A, et  al Effectiveness of
different types of footwear insoles for the diabetic neuro-
pathic foot. A follow-up study. Diabet Care. 2004;27(2):
474–477
16. Knowles EA, Boulton AJM. Do people with diabetes wear
their prescribed footwear? Diabet Med. 1996;13:1064
17. Armstrong DG, Lavery LA, Kimbriel HR, et al Activity pat-
terns of patients with diabetic foot ulcers: patients with
active ulceration may not adhere to a standard pressure off-
loading regimen. Diabet Care. 2003;26:2595–2597
18. American Diabetes Association. Consensus Statement:
Diabetes Care, Consensus Development Conference on
Diabetic Foot Wound Care. Alexandria, VA; 2003
19. Birke JA, Rolfsen RJ. Evaluation of a self-administered sen-
sory testing tool to identify patients at risk of diabetes-related
foot problems. Diabet Care. 1998;21:23–25
20. Birke JA, Patout CA, Foto JG. Factors associated with ulcer-
ation and amputation in the neuropathic foot. J Orthop
Sports Phys Ther. 2000;30(2):91–97
21. Dillingham T, Pezzin L, Mackenzie E. Limb amputation and
limb deficiency. South Med J. 2002;95:875–883
22. Schainfield R. Management of peripheral arterial disease and
intermittent claudication. J Am Board Fam Pract. 2001;14:
443–445
23. Federman DG, Trent J, Frelich C, Deinovic J, Kirsner R. Epide­
miology of peripheral vascular disease: a predictor of systemic
vascular disease. Ostomy Wound Manage. 1998;44:58–66
24. Taylor LM, Porter JM. Natural history and nonoperative
treatment of chronic lower extremity ischemia. In:
Moore WS, ed. Vascular Surgery: A Comprehensive Review.
Philadelphia, PA: W.B. Saunders; 1993
25. Fleck CA. How to avoid perineal skin care problems.
Extended Care Product News. 2004;96(6):1, 13–16
26. Hill MJ. Dermatology Nursing Essentials: A Core
Curriculum. 2nd ed. Pittman, New Jersey: Anthony J. Jannetti
Publication Management; 2003
27. Sibbald RG, Campbell K, Coutts P, Queen D. Intact skin – an
integrity not to be lost. Ost Wound Manag. 2003;49(6):27–41
28. Nix DH. Prevention and treatment of perineal skin break-
down. In: Milne CT, Corbett LQ, Duboc D, eds. Wound
Ostomy and Continence Nursing Secrets. Philadelphia, PA:
Hanley and Belfus; 2003:373–377
29. Storer-Brown D. Perineal dermatitis: can we measure it? Ost
Wound Manag. 1993;39(7):8–30,32
30. Nix DH. Validity and reliability of the perineal assessment
tool (PAT). Ostomy Wound Manag. 2002;48(2):43–49
31. Wound, Ostomy and Continence Nurses Society. Guidelines
for Prevention and Management of Pressure Ulcers. WOCN
Clinical Practice Guidelines Series. Glenview, IL. WOCN
Society; 2003:14
32. Gray M, et al Incontinence-associated dermatitis: a consen-
sus. J WOCN. 2007;314(1):45–54
33. Calhoun JH, et al Diabetic foot ulcers and infections: current
concepts. Adv Skin Wound Care. 2002;15(2):31–42
34. Bryant RA, ed. Acute and Chronic Wounds: Nursing
Management. 2nd ed. St. Louis, MO: Mosby-Yearbook; 2000
35. Ananthapadmanabhan KP, Moore DJ, Subramanyan K,
Misra M, Meyer F. Cleansing without compromise: the
impact of cleansers on the skin barrier and the technology of
mild cleansing. Dermatol Ther. 2004;17(suppl 1):16–25
22  Wound Prevention
36. Lutz J. Cleansing lotions vs bar soap for skin care use.
Presented at the Wound Ostomy and Continence Nurses
Society National Conference; 1998
37. Norman RA. Causes and management of xerosis and pruritis
in the elderly. Ann Long Term Care. 2001;9(12):35–40
38. Fleck CA, McCord D. The dawn of advanced skin care.
Extended Care Product News. 2004;95(5):32, 34–39
39. Fantl JA, Newman DK, Colling J, et al Managing Acute and
Chronic Urinary Incontinence, Clinical Practice Guideline.
Quick Reference Guide for Clinicians, No. 2, 1996 Update.
Rockville, MD: U.S. Department of Health and Human
Services, Public Health Service. Agency for Health Care Policy
and Research. AHCPR Pub. No. 96–0686. March 1996
40. Groom M, Shannon RJ, Chakravarthy D, Fleck CA., An
evaluation of cost and effects of a nutrient-based skin care
program for prevention of skin tears in an extended conva-
lescence center; accepted for publishing, Journal of Wound,
Ostomy and Continence Nursing, in press, 2010
41. Shannon RJ, Coombs M, Chakravarthy D. Reducing
Hospital-Acquired Pressure Ulcers with a Siliconebased
Dermal Nourishing Emollient-Associated Skincare Regimen,
Advances in Skin and Wound Care. 2009;22(10):461–467
42. Revis DR. Decubitus Ulcers, October 2005, eMedicine at
http://www.emedicine.com
43. Cuddigan J, et al, eds. Pressure Ulcers in America: Prevalence,
Incidence and Implications for the Future. Reston, VA:
National Pressure Ulcer Advisory Panel (NPUAP); 2001
44. Beckrich K, Aronovitch S. Hospital acquired pressure ulcers:
a comparison of costs in medical vs. surgical patients. Nurs
Econ. 1999;17(5):263–271
45. Young ZF, Evans A, Davis J. Nosocomial pressure ulcer pre-
vention: a successful project. J Nurs Adm. 2003;33:380–383
46. Allman RM. Pressure ulcers among the elderly. N Engl J
Med. 1989;320(13):850–853
47. National Pressure Ulcer Advisory Panel. Available at: http://
www.npuap.org
48. Abrussezze RS. Early assessment and prevention of pressure
ulcers. In: Lee BY, ed. Chronic Ulcers of the Skin. New
York: McGraw-Hill; 1985:1–9
49. Kosiak M. Etiology and pathology of ischemic ulcers. Arch
Phys Med Rehabil. 1959;40(2):62
50. Reswick J, Rogers J. Experiences at Rancho Los Amigos
Hospital with Devices and Techniques to Prevent Pressure
Sores. Bedsore Biomechanics. London: University Park; 1976
51. Walsh JS, Plonczynski DJ. Evaluation of a protocol for pre-
vention of facility-acquired heel pressure ulcers. JWOCN.
2007;34(2):179
52. Coats-Bennet U. Use of support surfaces in the ICU. Crit
Care Nurs Q. 2002;25:22–32
53. Panel for the Prediction and Prevention of Pressure
Ulcers  in  Adults: Pressure Ulcers in Adults: Prediction
and Prevention. Clinical Practice Guidelines, No. 3 AHCPR
Publication No. 92–0047. Rockville, MD, Agency for
Health  Care Policy and Research, Public Health Service,
265
U.S. Department of Health and Human Services, May
1992
54. Fleck C. Reducing the pressure: methods for effective wound
care management. Contin Care. 2002;3(1):37–42
55. Kosiak M. Etiology of decubitus ulcers. Arch Phys Med
Rehabil. 1961;42(1):19–28
56. Reddy M, Gill SS, Rochon PA. Preventing pressure ulcers: a
systematic review. JAMA. 2006;296(8):974–984
57. Ratliff C, Bryant D. (2003) Guideline for Prevention and
Management of Pressure Ulcers. WOCN Clinical Practice
Guideline Series, No. 2 Wound, Ostomy and Continence
Nurses Society. Available at: http://www.wocn.org
58. Duimel-Peeters I, et  al The Effects of Massage to Prevent
Pressure Ulcers. A Review of the Literature. Ostomy Wound
Manag. 2005;51(4):70–80
59. Holmes A, Edelstein T. Envisioning a world without pres-
sure ulcers. ECPN. 2007;122:24–29
60. Fleck CA, Sprigle S. Support surfaces: tissue integrity,
terms, principles and choice (Chapter 62). In: Krasner D,
Rodeheaver G, Sibbald G, eds. Chronic Wound Care: A
Clinical Sourcebook for Healthcare Professionals. Malvern,
VA, USA. 4th ed. Health Management Publications; 2007
61. Clark M. Repositioning to prevent pressure sores – what is
the evidence? Nurs Stand. 1998;13(3):58–60, 62, 64
62. Breslow R. Nutritional status and dietary intake of patients
with pressure ulcers: review of research literature 1943–
1989. Decubitus. 1991;4:16–21
63. Pinchofsky-Devin G, Kaminski M. The correlation of pres-
sure sores and nutritional status. J Am Geriatr Soc. 1986;37:
173–183
64. Allman RM, Goode PS, Patrick MM, Burst N, Bartolucci AA.
Pressure ulcer risk factors among hospitalized patient with
activity limitation. JAMA. 1995;273:865–870
65. Morley J, Silver A. Nutritional issues in nursing home care.
Ann Intern Med. 1995;123:850–859
66. Flanigan KH. Nutritional aspects of wound healing. Adv
Wound Care. 1997;10(2):48–52
67. Thomas DR. Nutritional factors affecting wound healing.
Ostomy Wound Manag. 1996;42(5):40–48
68. CMS Inpatient PPS Final Rule for FY 2008 available at:
http://www.cms.hhs.gov.AcuteInpatientPPS /downloads/
CMS-1533-FC.pdf
Helpful Websites
Association for the Advancement of Wound Care (AAWC) –
www.aawconline.org
American Academy of Wound Management (AAWM) – www.
aawm.org
Advancing the Practice – www.advancingthepractice.org
Wound, Ostomy and Continence Nurses Association (WOCN) –
www.wocn.org
 Prevention of Surgical Complications
23
Michael R. Hinckley

23.1 Introduction may not realize that numerous other substances can cause
thinning of the blood. Like aspirin, nonsteroidal antiin-
flammatory drugs (NSAIDS) act as platelet inhibitors,
One of the defining characteristics of dermatology is
although in contrast to aspirin, their antiplatelet effect is
wide array of procedures that are performed on the
reversible.1 Other products with antiplatelet effect include
skin. Whether for diagnostic or treatment purposes,
alcohol, fish oil (Omega three polyunsaturated fatty
dermatologic procedures are an important constituent
acids), ginseng, gingko biloba, garlic, ginger, feverfew,
contributing to the personality of this specialty.
vitamin E, and green tea.1–3 As patients may not know of
Dermatologic surgery is one of the most important of
these products’ potential to thin blood, it is prudent to
these procedures and although not common, adverse
specifically ask about the use of these substances. Finding
events can result, which are troublesome both for the
purpura on physical examination can also indicate a clot-
patient and the physician. An appropriate knowledge
ting problem or use of a blood thinner.
of how to prevent such undesirable occurrences is
Some patients can safely discontinue the use of
mandatory for any physician wishing to engage in der-
some blood thinners before cutaneous surgery, and if
matologic surgery. It is hoped that this chapter will
so, they should be told how far in advance to stop the
contribute to this important body of knowledge.
medicine. The antiplatelet effect of some common
blood thinners is shown in Table  23.1.4, 5 Cutaneous
surgery on a patient taking common blood thinners is
23.2 Bleeding considered safe and most reports have shown no
increase of surgical complications.6, 7 Physicians should
be aware that patients taking more than one blood thin-
Bleeding is an unavoidable part of any surgical proce-
ner may be at increased risk of bleeding compared to
dure but a typical dermatologic surgery should involve
those who took only one or no blood thinning agents.8
minimal bleeding. Several steps can be taken preoper-
In any patient with a medical necessity for warfarin,
atively, perioperatively, and postoperatively to decrease
the medication should be continued through surgery.7
the potential of bleeding.
Patients on aspirin that is medically necessary should
The preoperative history should review all medica-
also continue the medication unless the surgery will be
tions and the physician should verbally inquire about any
involving “deep tissue resection or dissection.”7 If sur-
history of abnormal bleeding or use of anticoagulant or
gery is performed on a patient taking warfarin, some
antiplatelet medication. While some patients might be
surgeons request an international normalized ratio
familiar with the blood thinning effects of medicines
(INR) between two and three unless the prescribing
such as warfarin, heparin, aspirin, and clopidogrel, they
physician specifies otherwise.9 One study reported
safety of surgical procedures with INR of less than 3.5
and recommended preoperative testing of INR prefer-
M. R. Hinckley
ably within 24 h of surgery.10
Department of Dermatology, Wake Forest University Baptist
Medical Center, Winston-Salem, NC, USA In the preoperative history, it should also be ascer-
e-mail: mhinckley@wfubmc.edu tained if the patient has any inherited bleeding

R. A. Norman (ed.), Preventive Dermatology, 267

DOI: 10.1007/978-1-84996-021-2_23, © Springer-Verlag London Limited 2010
268
Table 23.1  Duration of blood thinning effect of various agents
(days)
Aspirin 8–10
Warfarin 2–5
Clopidogrel 5 rates have been reported, but one recent publication
disorders. In such patients, a hematology consultation
is warranted to ensure that appropriate measures are
taken to prevent excessive bleeding.11, 12
Perioperatively, the use of the vasoconstrictor epi-
nephrine in the local anesthetic will help decrease
bleeding.13 Moreover, absorption of the anesthetic is
reduced and the risk of toxicity is lessened.13 Methods
of stopping bleeding during surgery include the use of
electrosurgery, electrocautery, pressure, and tying off
vessels. Hydrophilic polymers with potassium salt and
microporous polysaccharide hemispheres are products
that can help with hemostasis.14 Hydrophilic polymers
with potassium salt should only be used on wounds
where second-intention healing will be allowed.14
Postoperatively covering the excision site with a
pressure dressing can theoretically decrease bleeding.
When bleeding does occur after surgery, a hematoma
may form. Evacuation of early hematomas is advised
and even if not treated early, it is still probably best to
evacuate hematomas that are expanding or large and
have become fibrous.1 Observation is acceptable for a
hematoma that is stable and small.1 If control of bleed-
ing has been difficult during performance of a large
multilayered closure or flap, hematoma formation may
be prevented by drain placement.1 If an intraoral hema-
toma forms after surgery on the cheek, it is best to
avoid intervention through the mucosa because of the
risk of forming a fistula to the cheek wound on the
outside.15 Furthermore, involvement of an oral and
maxillofacial surgeon is advisable.15
23.2.1 Key Points
• Be aware of blood thinners patients are using.
• Blood thinners used for primary prevention can be
stopped.
• Do not discontinue medically necessary blood
thinners.
• Evacuate early or expanding hematomas.
M. R. Hinckley
23.3 Infection
Dermatologic surgeons have been fortunate to enjoy a
low incidence of postoperative infection. Different
found an overall infection incidence of 0.7%.16 Patient
risk factors that may affect the rate of infection are
shown in Table 23.2.17, 18 While diabetes and smoking
has been thought to increase infection risk, one study
found no increased risk of infection in diabetics or
smokers.16 Many patient risk factors are chronic and are
difficult to alter immediately prior to surgery, but those
with potential risk factors that can be controlled should
be. Patients with diabetes can work to achieve optimal
blood glucose control and those who use tobacco or
alcohol can be encouraged to decrease the amount
used. Increased rate of infection can also be seen in
skin grafts, ear or lip wedge resections, and in surgery
performed in the groin and below the knee.16 Other fac-
tors that might affect rate of infection include longer
Table 23.2  Some risk factors for infection
Male gender
Advancing age
Immunosuppression
Malnutrition
Diabetes mellitus
Obesity
Peripheral vascular disease
Alcohol use
Tobacco use
Bacterial colonization
Chronic renal insufficiency
Transfusion of blood products during surgery
Concurrent remote infection
Corticosteroid use
Skin grafts
Ear or lip wedge resections
Surgery in the groin and below the knee
Longer surgery duration
Reconstructive procedures
Surgery on the nose, ear, and facial region
23  Prevention of Surgical Complications 269

surgery duration, reconstructive procedures, and ­surgery state that “Antibiotic prophylaxis is reasonable for
on the nose, ear, and facial region.18 Use of prophylac- ­procedures on respiratory tract or infected skin, skin
tic antibiotics should be considered in the proper structures, or musculoskeletal tissue only for patients
scenarios. with underlying cardiac conditions associated with the
Although it might be assumed that the use of sterile highest risk of adverse outcome from IE.”21 That report
gloves during surgery would decrease potential for lists the following conditions:
infection, not all data support this. One report has dem-
• Prosthetic cardiac valve or prosthetic material used
onstrated that the use of nonsterile gloves during Mohs
for cardiac valve repair
micrographic surgery resulted in no increased infec-
• Previous IE
tion rates except in patients who underwent fenestra-
• CHD
tion of cartilage with secondary healing and removal
−− Unrepaired cyanotic CHD, including palliative
of melanomas.19 Another study showed almost no dif-
shunts and conduits.
ference in infection rates in simple excisions with or
−− Completely repaired congenital heart defect with
without sterile glove use (1.7% without sterile gloves,
prosthetic material or device, whether placed by
1.6% with sterile gloves).18 However, this same report
surgery or by catheter intervention, during the
found incidence of infection to be 14.7% when sterile
first 6 months after the procedure.
gloves were not used in excisions with a reconstructive
−− Repaired CHD with residual defects at the site or
procedure and 3.4% with the use of sterile gloves.18
adjacent to the site of a prosthetic patch or pros-
An advisory statement published in 2008 by physi-
thetic device (which inhibit endothelialization).
cians at the Mayo Clinic provides a number of scenar-
• Cardiac transplantation recipients who develop car-
ios where prophylactic antibiotics are appropriate.
diac valvulopathy21
• High risk of surgical site infection: lower extremity,
Another report listed the following noncardiac condi-
especially leg; groin; wedge excisions of the lip or
tions as high risk: orthopedic prosthesis, central ner-
ear; skin flaps on the nose; skin grafts; extensive
vous system (CNS) shunts, and shunt or fistula with
inflammatory skin disease.
nearby or inflamed tissue.17 This same report noted
• Prevention of infective endocarditis: Prosthetic car-
that antibiotic prophylaxis may be appropriate in situ-
diac valve, previous infective endocarditis; cardiac
ations such as closures with high tension, procedures
transplantation recipients who develop cardiac val-
performed on the hand, infected or inflamed skin of a
vulopathy; congenital heart disease (CHD) (unre-
surgical site, when a flap or graft is done on the ear and
paired cyanotic CHD, including palliative shunts
nose, and when several procedures are done at once.17
and conduits, during the first 6 months after com-
If infection would lead to serious consequences such
plete repair of congenital heart defects with pros-
as in immunosuppressed patients, prophylactic antibi-
thetic material or device placed by surgery or
otics for surgery performed in the axillae and mucosal
catheter intervention); repaired congential heart
surfaces are given.17 The American Academy of
disease with residual defects at the site or adjacent
Orthopedic Surgeons website recommends prophylac-
to the site of a prosthetic patch or prosthetic device
tic antibiotics for those who have had a joint replace-
(which inhibit endothelialization).
ment in particular scenarios if a patient is undergoing
• Prevention of hematologic total joint infection:
certain dental and urologic procedures.22, 23 If a patient
The first 2 years following joint replacement; pre-
with a prosthesis is to undergo skin surgery, the derma-
vious prosthetic joint infections, immunocompro-
tologic surgeon might consider the use of preoperative
mised/immunosuppressed patients (inflammatory
antibiotics if the prosthesis was placed within the pre-
arthropathies such as rheumatoid arthritis, sys-
vious 2 years. However, the orthopedic surgeon who
temic lupus erythematosus, drug- or radiation-
placed the prosthesis can be contacted if there is any
induced immunosuppression); insulin-dependent
question.
type I diabetes; HIV infection; malignancy; mal-
Prophylaxis should be timed appropriately to allow
nourishment; hemophilia.20
for adequate accumulation of the antimicrobial in the
The American Heart Association guidelines published coagulum.17 While therapy should be tailored with
in 2007 for infective endocarditis (IE) prophylaxis gram-positive organisms in mind, surgery done in moist
270
areas, below the knees, or on diabetics might also have
a high density of gram-negative organisms.24
When it is determined that antibiotic prophylaxis is
appropriate, different regimens can be employed
depending on the site. For nonoral skin, 2  g of oral
cephalexin or dicloxacillin is given 0.5–1  h prior to
surgery.17 Alternatives for penicillin-allergic patients
are 600  mg of oral clindamycin or 500  mg of oral
azithromycin given 0.5–1 h prior to surgery.17 For nasal
and oral mucosa 2 g of oral amoxicillin or if penicillin-
allergic 600  mg of oral clindamycin, 500  mg of oral
azithromycin, or if nontype one reaction  2  g of oral
cephalexin can be given ½–1  h prior to surgery.17
Unless surgery lasts longer than 6 h, the preoperative
dose could be sufficient for endocarditis and prosthesis
prophylaxis.17 In a patient believed to be at high risk
for infection of a wound, up to 10 days of antibiotics
can be given postoperatively in addition to the preop-
erative dose, twice a day for cephalosporins rather than
4 times a day.17
Preoperative preparation of the surgical site is a
step the surgical staff can take in an effort to decrease
postoperative wound infection. Chlorhexidine glu-
conate and povidone-iodine are antiseptics commonly
employed for skin surgery. While povidone-iodine
has been used as an antimicrobial for many years, it
has a number of disadvantages. It might be inactivated
by blood25 and it can be toxic to human fibroblasts
and thus slow the rate of wound healing.26 Furthermore,
as compared to chlorhexidine, it is more likely to
cause an allergic reaction,27 it is less effective at clear-
ing of microbes,28 and it has less sustained activity
than chlorhexidine.29 Chlorhexidine gluconate can
also be problematic as keratopathy has been reported30
and ototoxicity has been found with its use in animal
studies.31, 32 Thus, this is probably an unwise choice
for cleansing in the auricular region or to prepare the
skin around the eyes. Alcohol has a rapid onset of
action but duration of action is limited.29 An optimal
combination is chlorhexidine gluconate and alcohol,
thus providing the potential for rapid onset and pro-
longed duration of action.29 Surrounding the surgical
site with sterile draping, either disposable or wash-
able, might also help keep the area clean and prevent
infection.
Postoperatively, an antibiotic ointment can be
placed with an overlying dressing. Ointments include
bacitracin, mupirocin, neomycin, erythromycin, poly-
myxin, and combinations of the different topicals.33
M. R. Hinckley
Mupirocin is effective against gram-positive and some
gram-negative organisms and is less likely to cause
contact dermatitis than some other topical antibiotics.33
Neomycin is bactericidal against most gram-negatives
bacteria and against staphylococci but not against
streptococci.33 Neomycin-induced allergic contact der-
matitis has been reported to occur in 1–6% of people.33
Bacitracin is effective against various gram-positive
and gram-negative microbes33 but along with neomy-
cin can cause contact dermatitis.34 Polymyxin is most
effective at killing some gram-negative bacteria, and
when used in combination with other topical antibiot-
ics, the preparation has increased spectrum of activ-
ity.33 Erythromycin 2% ointment has bactericidal
activity against gram-positive bacteria with little risk
of sensitization.35 Silver sulfadiazine is bactericidal
against gram-negative and gram-positive bacteria.33
Retapamulin is a topical antibiotic for the treatment of
impetigo with activity against Streptococcus pyogenes
and Staphylococcus aureus.36
Petrolatum can be used as an alternative to antibi-
otic ointment following surgery. One study was unable
to find a statistically significant difference in the rate of
postoperative infections in patients who had used white
petrolatum vs. bacitracin (2 vs. 0.9%).37 Moreover,
there was no difference in healing that was clinically
significant noted at day 1, 7, or 28.37 No contact derma-
titis was seen in the white petrolatum group.37 In addi-
tion, anaphylaxis to bacitracin has been reported.38
Another study found no statistically significant differ-
ence between petrolatum and gentamycin ointment in
prevention of postoperative suppurative auricular
chondritis.39 Furthermore, inflammatory chondritis
was much more likely in patients who used gentamy-
cin ointment compared to petrolatum.39
In light of the potential for side effects and resis-
tance, as well as the lack of strict guidelines for antibi-
otic use in skin surgery, the need for oral and topical
antibiotics should be determined on a case-by-case
basis.
23.3.1 Key Points
• Infection in dermatologic surgery is low.
• Petrolatum can be safely used on postoperative sites
instead of antibiotic ointment.
• Use antibiotic prophylaxis when appropriate.
23  Prevention of Surgical Complications 271

23.4 Allergic Reactions amide class.45–47 Anesthetics from the ester class are
more likely to cause a reaction than those from the
amide class and this is due to p-aminobenzoic acid, an
Every preoperative medical history should elicit infor-
ester metabolite.27 Patients can experience side effects
mation about drug allergies. Adverse drug reactions
from epinephrine, which is sometimes mixed with
can range from mild annoyances to fatalities. A study
anesthetic and such adverse affects are more likely in
looking at adverse drug events estimated that over
patients with hyperthyroidism, significant cardiac dis-
700,000 people in the United States are treated annu-
ease, who are very anxious or who are taking a nonse-
ally in emergency departments for such events.40 While
lective beta-blocker.48 Such reactions include
few medications are used in conjunction with dermato-
palpitations, tachycardia, tremor, headache, diaphore-
logic surgery, the surgeon should be aware of those that
sis, chest pain, nervousness, light-headedness, and
are most likely to be problematic (Table  23.3).
increased blood pressure.48 If a patient is worried about
Semisynthetic penicillinase-resistant penicillins and
side effects of epinephrine or has a condition that
first-generation cephalosporins are the most common
could result in increased sensitivity to epinephrine, the
antibiotics used for prophylaxis in skin surgery.41
surgeon should discuss the adverse effects of the epi-
Although 0.7–10% claim such an allergy, of these indi-
nephrine with the patient and decide if anesthetic
viduals around 10–30% show a positive IgE-mediated
without epinephrine would be preferable. If epineph-
reaction on skin testing.42 Although cross-reactivity
rine is not used, the surgeon and the patient should
between cephalosporins and penicillin can occur, it is
understand that bleeding will likely be greater and the
probably less than once thought.43 Historically, 10%
duration of the anesthetic effect will probably be
cross-reactivity has been reported, but this number may
shorter.
have resulted from penicillin compounds that were
Perioperative allergic reactions can result from rub-
contaminated with cephalosporins.43 Approximately
ber products (such as latex), acrylates (found in elec-
1–3% of patients can experience an allergic or immune-
trosurgical plates), formaldehyde (formaldehyde gas
mediated reaction to cephalosporins.43 If a patient does
emanating from an open biopsy specimen container),
have a penicillin or cephalosporin allergy and an antibi-
nickel (found in surgical instruments), and suture
otic is warranted, clindamycin can be used as an
(prolene allergy is rare but has been reported).27
alternative.17
Postoperative contact dermatitis can result from
Antiseptics can also cause an allergic reaction in
adhesives and topical antibiotics.27 Both neomycin and
dermatologic surgery. Povidone-iodine-containing
bacitracin were listed among the top ten allergens in a
antiseptics are the most common antiseptics to cause
Mayo Clinic report investigating allergens over a
allergic contact dermatitis.27 Anaphylaxis due to the
5-year period.34 These same two topicals were among
povidone component of povidone-iodine has been
the top ten relevant allergens in an investigation of
reported.44
causes of allergic contact dermatitis in patients with
Local anesthetics used in cutaneous surgery typi-
hand dermatitis.49 Use of these medications may give a
cally belong to the amide class of anesthetics. Allergy
postsurgical wound the appearance of infection when
to local anesthetics is rare, particularly among the
the true issue is contact allergy. Bacitracin-induced
anaphylaxis has been reported.38 Petrolatum can be
considered for use on surgical sites in place of topical
Table 23.3  Potential allergens in a surgical setting antibiotics.
Antibiotics (oral and topical) Adhesive tape can contain colophony, a cause of
Antiseptics contact dermatitis.27 Band-aid Liquid Bandage and
Dermabond contain 2-octyl cyanoacrylate and colo-
Anesthetic
rant,27 and benzalkonium chloride and methylparaben
Latex are also found in Liquid Bandage27; these four sensitiz-
Nickel (surgical instruments) ers can result in allergy.27
Physicians should be aware of patient allergies and
Suture
be able to recognize allergic reactions, which could
Colophony (adhesive tape) result in misdiagnosis of the real problem. For example,
272
if a patient returns to clinic after surgery for suture
removal and the surgical area appears inflamed, the
cause may be a reaction to the topical antibiotic or
tape used postoperatively and not due to infection.
Diagnosing an allergic response as infection could lead
to improper use of antibiotics.
23.4.1 Key Points
• Local anesthetics rarely cause true allergic reactions.
• Potential allergens use in cutaneous surgery include
latex, povidone-iodine, adhesive, suture, antibiotics.
• Inflammation at a surgical site may be secondary to
a topical antibiotic.
23.5 Postoperative Scars,
Pain, and Pruritus
Scarring is an inevitable result of surgery and should
be expected in all cases. While several steps can be
taken to minimize the size and appearance of surgical
scars, during the explanation of the surgical procedure
and in the informed consent, it should be made clear to
the patient that a scar will result. Location can affect
how a scar forms50 and the physician may want to
inform the patient of this. In the preoperative assess-
ment, a patient should be asked about history of hyper-
trophic scarring or keloid formation. Physical
examination is also helpful as a hypertrophic scar, or
keloid might be noted by the physician that was not
mentioned by the patient.
A variety of patient-related factors can affect scar
outcome. Sun exposure can worsen the appearance of
scars.51 Diabetes is a risk factor for infection17 and
infection can affect wound healing and result in a poor
scar.1 One study found that the most significant patient
risk factors contributing to wound complications fol-
lowing skin biopsy appeared to be corticosteroid use
and cigarette smoking.52 Nicotine acts as a vasocon-
strictor resulting in ischemia.52 Avoidance of vigorous
activities helps with split thickness skin graft survival,53
and thus it might be assumed that refraining from such
activity after other types of surgical repair will aid in
healing. It seems that poor nutrition can affect healing
M. R. Hinckley
as certain nutrients appear to be important for proper
healing.54, 55 Corticosteroid use can affect healing56, 57 ,
presumably due to the affect on the inflammatory
response.56 Chronic alcohol intake may negatively
affect wound healing by decreasing activity and prolif-
eration of T cells.58 Stress can possibly result in poorer
wound healing by affecting cytokine production.59, 60 It
could be concluded that any factor that can affect
wound healing will, as a result, have the potential to
affect the scar formation.
Several physician-influenced factors can affect scar
outcome. Perioperative handling of tissue can affect
scarring.61 High tension of a wound can result in scar
spread1 and choice of repair can influence tension.
Suture track scars are more likely to develop the longer
they are left in place.1 If wound edges are not everted,
the scar that forms may be more noticeable.62 Wound
separation can result from a hematoma1 , which could
lead to a poor scar; thus, inadequately controlling
bleeding intraoperatively could ultimately affect the
scar. Putting suture lines on the boundary of a cosmetic
subunit can help with scar formation63, and how the
excision is placed in relation to relaxed skin tension
lines can affect cosmesis.63
Management options for keloids and hypertrophic
scars include interferon or corticosteroid injections,
occlusive dressings, radiotherapy, compression ther-
apy, cryotherapy, laser, surgical excision, dermabra-
sion, surgical revision, fillers, peels, cryosurgery,
cosmetics, punch excisions and grafts, pressure ban-
dages, and massage.50, 64 Approximately 3 weeks after
surgery, a patient can massage the surgical site in an
effort to achieve improved scar appearance. Topical
preparations to help scars are available but one study
has demonstrated no advantage of an onion extract-
based gel over a petrolatum-based ointment.65 Use of a
silicone gel cushion and silicone sheeting for hypertro-
phic scars and keloids has resulted in decreased vol-
ume and symptoms of scars.64 Silicone elastomer
sheeting appears to be useful in the prevention and
treatment of keloid scars and hypertrophic scars.66 It
may be that hydration rather than silicone is what is
helping.67 Patients should be warned that scar matura-
tion can take up to 1 year and improvement can be seen
up until that time. Proper education of patients and
skillful surgeons can do much to achieve acceptable
scars for patients.
Pain, pruritus, and numbness of surgical sites are
benign but relatively common symptoms reported by
23  Prevention of Surgical Complications 273

patients. Some topical treatments might improve 23.6.1 Key Points

symptoms. Retinoic acid applied daily to hypertrophic
and keloid scars has been reported to decrease pruritus
and tenderness, and tocoretinate ointment has resulted
in decreased pruritus in mature hypertrophic scars.68
Silicone-containing products used for hypertrophic
scars and keloids have resulted in decreased tenderness
and pruritus.64 Topical lidocaine could also be tried for
symptomatic relief of scars.
Postoperative pain in dermatologic surgery will
rarely be a serious problem. After simple excisions
and repairs, acetaminophen should be adequate to
control pain. Patients should be warned that other
over-the-counter painkillers such as aspirin, ibupro-
fen, naproxen, or other NSAIDS can cause bleeding.
In larger excisions or more advanced repairs, patients
might need a prescription for stronger analgesics. If a
prescription is given for a compound containing acet-
aminophen, the patient should be warned that use of
the prescription medication in addition to acetamino-
phen could result in toxicity.
• Can result from too much tension, inadequate under-
mining, when length-to-width ratio is less than 3:1.
• Standing cones can sometimes resolve over time.
23.7 Anesthetic Toxicity
Although local anesthesia is safer than general anes-
thesia,71 toxicity can result, and the CNS and cardio-
vascular system are the two main organ systems where
adverse reactions occur72 (Table 23.4). CNS side effects
include circumoral numbness, light-headedness, dou-
ble vision, a metallic taste, tremors, slurred speech,
respiratory arrest, and seizure.72 Cardiovascular effects
include hypotension, dysrhythmias, palpitations, short-
ness of breath, diaphoresis, and chest pain.73
Epinephrine can cause several side effects (Table 23.5)
and should be used cautiously in patients on a beta-blocker

Table 23.4  Symptoms of anesthetic toxicity

23.5.1 Key Points Central nervous system Cardiovascular
Circumoral numbness Hypotension
• Tension, bleeding, infection, and vigorous activity Light-headedness Dysrhythmias
can result in an undesirable scar. Double vision Palpitations
• Placing an incision within relaxed skin tension lines
Metallic taste Shortness of breath
can help hide a scar.
• Occlusive dressings, massage, corticosteroid injec- Tremors Diaphoresis
tion can improve scar appearance. Slurred speech Chest pain
• Protect scars from the sun. Respiratory arrest
Seizure

23.6 Standing Cones
Table 23.5  Potential side effects of epinephrine
Palpitations
Standing cones (“dog ears”) are more likely to result
when length-to-width ratio of a fusiform excision is Tachycardia
less than 3–4:1, when opposing sides of a wound are of Tremor
unequal length, or if the angles at the wound apices are Headache
too big.69 Too much tension can cause depression of
Diaphoresis
the center of the wound and the skin at the ends to be
elevated, thus giving the look of dog ears.69 Inadequate Chest pain
undermining can accentuate dog ears and if during a Nervousness
fusiform excision the scalpel angle is not at 90° while
Light-headedness
approaching the apices, dog ears can result.69 Standing
cones can sometimes resolve over time.70 Increased blood pressure
274
and with heart disease.13 Conversing with the patient
during surgery may allow the physician to identify tox-
icity by noticing problems such as a change in mental
status or dysarthria.74
Epinephrine is helpful in the setting of local anes-
thetic as its use results in less absorption of the anes-
thetic, the need for a smaller amount of the anesthetic,
and decreased risk of toxicity.13 Absorption of anes-
thetic also depends on the vascularity of the area being
injected.75 Aspirating during injection can reduce the
chance of injecting a large amount of the anesthetic
intravascularly.74 Recommended maximum doses of
anesthetic are: 4–5 mg/kg alone and 7 mg/kg with epi-
nephrine for lidocaine, and 175 mg alone and 225 mg
with epinephrine for bupivacaine.73 Bupivacaine has
the advantage of a longer duration of action but also
can be particularly cardiotoxic.73 Lidocaine is metabo-
lized by the liver, and thus hepatic dysfunction can
lead to increased risk of toxicity.74 Local anesthetics
are predominantly excreted in urine,72 but renal failure
does not lead to decreased clearance because of inacti-
vation of amides in the liver and hydrolysis of esters in
the plasma.75
If toxicity does occur, supportive care and crash
cart materials should be available.
23.7.1 Key Points
• Talking to a patient during surgery can help the
physician become aware of anesthetic toxicity such
as slurred speech.
• Epinephrine can decrease absorption of the anes-
thetic, thus decreasing the risk of toxicity.
• Hepatic failure can increase toxicity due to decrease
metabolization of the anesthetic.
23.8 Nerve Damage
Nerve damage can be one of the most devastating
results of cutaneous surgery. Sensory deficits will be
suffered in many cases but sensory nerves frequently
regenerate though it may be some months.76 Injury to
sensory nerves resulting in permanent paresthesia or
injury to motor nerves resulting in functional impair-
ment can be more problematic. Unfortunately, excision
M. R. Hinckley
of large or infiltrative tumors may make damage of cer-
tain nerves unavoidable. When a tumor is not large or
infiltrative but located in the vicinity of an important
nerve, the solution to preventing nerve damage is to
have an appropriate knowledge of anatomy, particu-
larly in the facial and neck regions.
The superficial muscularoaponeurotic system (SMAS)
is a useful landmark in the face as sensory nerves ordi-
narily course through the superficial portion of the
SMAS while motor nerves course through the deeper
part of the SMAS.63 The SMAS is typically found above
the muscles but deep to the subcutaneous tissue.63 The
predominant source of sensory innervation to the face is
the fifth cranial nerve or trigeminal nerve.63 The trigem-
inal nerve branches into the ophthalmic, maxillary, and
mandibular portions.63 Cranial nerve seven or the facial
nerve supplies muscles of facial expression with motor
innervation.63 The temporal branch provides innerva-
tion to the muscles of the upper face and transection of
this branch results in lack of ability to elevate the eye-
brow and in ptosis.63 This nerve passes superficially
over the middle part of the zygoma rendering it suscep-
tible to injury.63 The marginal mandibular nerve runs
superficially near the chin and mandible, and transec-
tion leads to a droopy lip and drooling.63 The spinal
accessory nerve is susceptible to injury when surgery is
being performed on the neck and can result in arm,
shoulder and girdle weakness, shoulder sagging, and
scapula winging.77 Various methods for locating this
nerve have been described.77 One technique is to
obliquely stroke a needle over the lateral neck, marking
the hyperaesthetic points, then connect these points,
which can indicate the course of the nerve.77
Local anesthetics work rapidly on unmyelinated
sensory fibers but over time, myelinated motor fibers
can also be affected resulting in temporary paralysis of
facial muscle.63 Both the surgeon and the patient should
be aware of this possibility to avoid unnecessary
concern.
While nerve damage can result in morbidity, proper
patient education can mitigate the emotional affect if
such injury does occur. If tumor size, type or location
makes it possible that excision will result in nerve
damage, the patient should be warned what the affect
of surgery may be prior to the procedure. Through
proper education of patients and vigilant attention
to nerve identification and surgical technique, unde-
sired outcomes from nerve damage can be avoided or
minimized.
23  Prevention of Surgical Complications
23.8.1 Key Points
• Damage to nerves such as the temporal branch of
the facial nerve, the marginal mandibular nerve, and
the spinal accessory nerve can result in important
loss of function for patients.
• If a tumor is located in the vicinity of nerves that
can result in impairment, the patient needs to be
forewarned of this possibility.
• Local anesthetics can result in temporary paralysis
of nerves.
• Transected sensory nerves can regenerate but may
require months to do so.
23.9 Spitting Sutures
Spitting sutures do not pose a serious problem but can
be a nuisance for patients. Superficial placement of
suture may increase the possibility of spitting.78
Monofilament absorbable suture is less reactive than
vicryl and may be less likely to result in spitting.79
Spitting sutures can be gently removed by the physi-
cian if troublesome to the patient.
23.9.1 Key Points
• Superficial placement of sutures may increase the
likelihood of spitting sutures.
• Monofilament absorbable suture may be less likely
than vicryl to result in spitting.
23.10 Defibrillators and Pacemakers
Electrosurgery is used as a primary method of hemosta-
sis in dermatologic surgery. Although use of electrosur-
gery in most patients does not seem to result in major
complications, it has been reported to cause firing of
implantable cardioverter-defibrillators (ICDs) and pace-
maker reprogramming.80 Interference has been reported
with electrocautery use80 but because no electrical cur-
rent is generated with this method, it should be consid-
ered a safe alternative to electrosurgery in a patient with
a pacemaker or ICD. Other precautions when operating
275
on someone with a pacemaker or ICD may include the
use of short bursts, low voltage, bipolar forceps, and
avoiding electrosurgery in the area of the device.80, 81
Preoperative consultation with a cardiologist should be
considered if there are any concerns or questions.
23.10.1 Key Point
• In patients with pacemakers or defibrillators, elec-
trocautery is a safe alternative to electrosurgery for
hemostasis.
23.11 Trap Door (Pincushioning)
Deformities
Trapdoor deformity is the bulging of tissue seen in C-,
V-, or U-shaped scars and may be due to a variety of
causes, including scar contracture, hypertrophy, and
excessive tissue.82 It seems that this problem may be
related to undermining.83, 84 The bilobed flap is a repair
design that can lead to pincushioning but the rhombic
bilobed flap may decrease the incidence of pincushion-
ing.85 It has also been suggested that pincushioning
secondary to the bilobed flap repair may be minimized
if transposition of each flap is only 45° for a total of
90–100°.86 This defect may also be more likely to
occur with flaps in the medial or superior portion of the
face.84
23.11.1 Key Point
• Adequate undermining may decrease the likelihood
of trapdoor deformities.
23.12 Flap and Graft Necrosis
Skin flaps and grafts allow dermatologic surgeons to
close large surgical defects in a way that results in opti-
mal cosmesis. Unfortunately, flaps and grafts may
276 M. R. Hinckley

necrose and compromise cosmetic outcome. However, 23.13.1 Key Points

steps can be taken to decrease the risk of necrosis.
Patients smoking a pack or more a day have been found
• Vasovagal reactions can occur in surgery patients,
to have an increased risk of full-thickness graft or flap
which can result in patient harm due to falling.
necrosis compared to those who never smoked or those
• Patients who experience a vasovagal reaction should
who smoked less than a pack a day.87 While some
be placed in a recumbent position.
patients may not be willing to quit smoking prior to
surgery, the surgeon should at least encourage the
patient to try to decrease the amount smoked for a
period both before and after surgery. Skin tension can 23.14 Litigation
predispose a flap to some necrosis88 and flap design
should attempt to limit the amount of tension of the
Perhaps every physician in the United States is affected
repair. Delicate surgical technique has been employed
in some way by litigation. Whether by the indirect
to decrease the likelihood of necrosis.89 Bolsters may
effect of malpractice costs or the direct effect of utiliz-
be used but may not be needed for securing of full-
ing resources to confront a lawsuit, litigation can be an
thickness skin grafts in order to decrease the chance of
influential aspect of medical practice. While prevent-
necrosis.89 Full-thickness skin grafts are more likely to
ing complications should help prevent lawsuits, other
necrose than split thickness grafts and necrosis is more
steps can be taken that might aid in avoiding litigation.
likely in composite grafts than other graft types.53
Communication with patients and families, record
Recipient-site blood supply affects survival of a
keeping, informed consent, and availability of the
graft.53
attending doctor or an associate can potentially pre-
vent lawsuits.91 While attention to all of these details is
important, a good physician-patient relationship is
likely the best way to prevent litigation.92 Such rela-
23.12.1 Key Points tionships between dermatologic surgeons and their
patients should be an important part of every surgical
• Encourage smokers with a flap or graft to decrease practice.
smoking, at least while the defect is healing.
• Limit tension in repairs involving a flap or graft.
• Recipient site blood supply can affect the viability
of a graft. 23.14.1 Key Point

• Communication and a good physician–patient rela-

23.13 Vasovagal Reaction tionship can help avoid litigation.

A vasovagal reaction can result in patient harm if the

patient falls and strikes a body part. In one study, 1%
of surgical patients experienced vasovagal syncope,
which occurred before, during, and after surgery.90
Fear, emotional stress, or acute pain may be triggers
but the cause is often not identified.47 Skin may
become cool and pale, bradycardia may follow tachy-
cardia, blood pressure may drop initially, and acute
brief loss of consciousness may occur.47 If a vasovagal
reaction occurs, patient should be placed in a recum-
bent position.47
23.15 Conclusion
Dermatologic surgery has proven to be a safe and
effective method for treating skin disease. With a
proper understanding of this field of medicine and by
taking appropriate precautions, the majority of signifi-
cant surgical complications can be kept to a minimum.
Such practices will result in satisfying outcomes for
physicians and healthier, happier patients.
23  Prevention of Surgical Complications
References
  1. Stasko T, Henghold WB. Complications in cutaneous proce-
dures. In: Roenigk RK, Ratz JL, Roenigk HH Jr, eds.
Roenigk’s Dermatologic Surgery: Current Techniques in
Procedural Dermatology. 3rd ed. New York: Informa
Healthcare; 2007
  2. Mukamal KJ, Massaro JM, Ault KA, et al Alcohol consump-
tion and platelet activation and aggregation among women
and men: the Framingham offspring study alcoholism.
Alcohol Clin Exp Res. 2005;29(10):1906–1912
  3. Baldassarre D, Amato M, Eligini S, et al Effect of n-3 fatty
acids on carotid atherosclerosis and haemostasis in patients
with combined hyperlipoproteinemia: a double-blind pilot
study in primary prevention. Ann Med. 2006;38(5):367–375
  4. Furst DE, Ulrich RW. Nonsteroidal antiinflammatory drugs, dis-
ease-modifying antirheumatic drugs, nonopioid analgesics, and
drugs used in gout. In: Katzung BG, ed. Basic and Clinical
Pharmacology. 10th ed. New York: McGraw Hill Medical; 2007
  5. Wickersham RM, Novak KK, eds. Drug Facts and Comparisons
2008. St. Louis, MO: Wolters Kluwer Health; 2007
  6. Alcalay J, Alkalay R. Controversies in perioperative man-
agement of blood thinners in dermatologic surgery: continue
or discontinue? Dermatol Surg. 2004;30(8):1091–1094
  7. Otley CC. Continuation of medically necessary aspirin and
warfarin during cutaneous surgery. Mayo Clin Proc. 2003;
78(11):1392–1396
  8. Shimizu I, Jellinek NJ, Dufresne RG, et  al Multiple anti-
thrombotic agents increase the risk of postoperative hemor-
rhage in dermatologic surgery. J Am Acad Dermatol. 2008;
58(5):810–816
  9. Kirkorian AY, Moore BL, Siskind J, Marmur ES.
Perioperative management of anticoagulant therapy during
cutaneous surgery: 2005 survey of Mohs surgeons. Dermatol
Surg. 2007;33(10):1189–1197
10. Ah-Weng A, Natarajan S, Velangi S, Langtry JA. Preoperative
monitoring of warfarin in cutaneous surgery. Br J Dermatol.
2003;149(2):386–389
11. Leonard AL, Hanke CW, Greist A. Perioperative manage-
ment of von Willebrand disease in dermatologic surgery.
Dermatol Surg. 2007;33(4):403–409
12. Peterson SR, Joseph AK. Inherited bleeding disorders in der-
matologic surgery. Dermatol Surg. 2001;27(10):885–889
13. Koay J, Orengo I. Application of local anesthetics in derma-
tologic surgery. Dermatol Surg. 2002;28(2):143–148
14. Ho J, Hruza G. Hydrophilic polymers with potassium salt
and microporous polysaccharides for use as hemostatic
agents. Dermatol Surg. 2007;33(12):1430–1433
15. Cohen SN, Sidebottom AJ, Varma S. Intraoral hematoma: a
novel complication of dermatologic surgery. Dermatol Surg.
2007;33(9):1139–1141
16. Maragh SL, Brown MD. Prospective evaluation of surgical
site infection rate among patients with Mohs micrographic
surgery without the use of prophylactic antibiotics. J Am
Acad Dermatol. 2008;59(2):275–278
17. Maragh SL, Otley CC, Roenigk RK, Phillips PK. Antibiotic
prophylaxis in dermatologic surgery: updated guidelines.
Dermatol Surg. 2005;31(1):91-93
277
18. Rogues AM, Lasheras A, Amici JM, et al. Infection control
practices and infectious complications in dermatological
surgery. J Hosp Infect. 2007;65(3):258–263
19. Rhinehart MB, Murphy MM, Farley MF, et al. Sterile versus
nonsterile gloves during Mohs micrographic surgery: infec-
tion rate is not affected. Dermatol Surg. 2006;32(6):819–826
20. Wright TI, Baddour LM, Berbari EF, et al. Antibiotic pro-
phylaxis in dermatologic surgery: advisory statement 2008.
J Am Acad Dermatol. 2008;59(3):464–473
21. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infec-
tive endocarditis: guidelines from the American Heart
Association: a guideline from the American Heart
Association Rheumatic Fever, Endocarditis, and Kawasaki
Disease Committee, Council on Cardiovascular Disease in
the Young, and the Council on Clinical Cardiology, Council
on Cardiovascular Surgery and Anesthesia, and the Quality
of Care and Outcomes Research Interdisciplinary Working
Group. Circulation. 2007;116(15):1736–1754
22. American Academy of Orthopaedic Surgeons. Dental Work
After a Joint Replacement. At: http://orthoinfo.aaos.org/
topic.cfm?topic=A00226; 2007 Accessed 12.12.07
23. American Academy of Orthopaedic Surgeons. Your Joint
Replacement: Urological Procedures and Antibiotics. At:
http://orthoinfo.aaos.org/topic.cfm?topic=A00383; 2007
Accessed 12.12.07
24. Messingham MJ, Arpey CJ. Update on the use of antibiotics
in cutaneous surgery. Dermatol Surg. 2005;31(8 Pt
2):1068–1078
25. Ritter MA, French ML, Eitzen HE, Gioe TJ. The antimicro-
bial effectiveness of operative-site preparative agents: a
microbiological and clinical study. J Bone Joint Surg Am.
1980;62:826–828
26. Balin AK, Pratt L. Dilute povidone-iodine solutions inhibit
human skin fibroblast growth. Dermatol Surg. 2002;28(3):
210–214
27. Jacob SE, Amado A, Cohen DE. Dermatologic surgical
implications of allergic contact dermatitis. Dermatol Surg.
2005;31(9 Pt 1):1116–1123
28. Garibaldi RA, Skolnick D, Lerer T, et al. The impact of pre-
operative skin disinfection on preventing intraoperative
wound contamination. Infect Control Hosp Epidemiol.
1988;9(3):109–113
29. Spann CT, Taylor S, Weinberg J. Topical antimicrobial
agents in dermatology. Dis Mon. 2004;50(7):407–421
30. Varley GA, Meisler DM, Benes SC, et al. Hibiclens keratop-
athy. A clinicopathologic case report. Cornea. 1990;9(4):
341–346
31. Perez R, Freeman S, Sohmer H, Sichel JY. Vestibular and
cochlear ototoxicity of topical antiseptics assessed by evoked
potentials. Laryngoscope. 2000;110(9):1522–1527
32. Igarashi Y, Oka Y. Vestibular ototoxicity following intratym-
panic applications of chlorhexidine gluconate in the cat.
Arch Otorhinolaryngol. 1988;245(4):210–217
33. Spann CT, Tutrone WD, Weinberg JM, et al. Topical anti-
bacterial agents for wound care: a primer. Dermatol Surg.
2003;29(6):620–626
34. Mayo Clinic. Top Ten Contact Dermatitis Allergens
Identified in Mayo Clinic Study. At: http://www.mayoclinic.
org/news2006-rst/3268.html; 2007 Accessed 12.12.07
278
35. Bernstein SC, Roenigk RK. Surgical pearl: erythromycin
ointment for topical antibiotic wound care. J Am Acad
Dermatol. 1995;32:659–660
36. Orange A, van der Wouden J, Konig S, et al. Retapamulin
ointment for the treatment of impetigo in adults and chil-
dren: results of a phase III, placebo-controlled, double-blind
trial. J Am Acad Dermatol. 2007;56(suppl 2):AB4
37. Smack DP, Harrington AC, Dunn C, et  al. Infection and
allergy incidence in ambulatory surgery patients using a
white petrolatum vs bacitracin ointment: a randomized con-
trolled trial. JAMA. 1996;276(12):972–977
38. James WD. Use of antibiotic-containing ointment versus
plain petrolatum during and after clean cutaneous surgery.
J Am Acad Dermatol. 2006;55(5):915–916
39. Campbell RM, Perlis CS, Fisher E, Gloster HM Jr.
Gentamicin ointment versus petrolatum for management of
auricular wounds. Dermatol Surg. 2005;31(6):664–669
40. Budnitz DS, Pollock DA, Weidenbach KN, et  al. National
surveillance of emergency department visits for outpatient
adverse drug events. JAMA. 2006;296:1858–1866
41. Billingsley E. The Role of Antibiotics in Cutaneous Surgery.
Emedicine Oct 14, 2006. At: http://www.emedicine.com/
derm/topic821.htm; 2007 Accessed 18.12.07
42. Dodek P, Phillips P. Questionable history of immediate-type
hypersensitivity to penicillin in staphylococcal endocarditis:
treatment based on skin-test results versus empirical alterna-
tive treatment – a decision analysis. Clin Infect Dis.
1999;29(5):1251–1256
43. Pichichero ME. Cephalosporins can be prescribed safely for
penicillin-allergic patients. J Fam Pract. 2006;55(2):
106–112
44. Adachi A, Fukunaga A, Hayashi K, et  al. Anaphylaxis to
polyvinylpyrrolidone after vaginal application of povidone-
iodine. Contact Derm. 2003;48(3):133–136
45. Berkun Y, Ben-Zvi A, Levy Y, et al. Evaluation of adverse
reactions to local anesthetics: experience with 236 patients.
Ann Allergy Asthma Immunol. 2003;91(4):342–345
46. Amsler E, Flahault A, Mathelier-Fusade P, Aractingi S.
Evaluation of rechallenge in patients with suspected lido-
caine allergy. Dermatology. 2004;208:109–111
47. Fader DJ, Johnson TM. Medical issues and emergencies in
the dermatology office. J Am Acad Dermatol. 1997;36(1):
1–16
48. The American Academy of Dermatology Joint AAD/ASDS
Liaison Committee. Current issues in dermatologic office-
based surgery. The American Academy of Dermatology
Joint AAD/ASDS Liaison Committee. Dermatol Surg. 1999;
25(10):806–815
49. Warshaw EM, Ahmed RL, Belsito DV, et al. North American
Contact Dermatitis Group. Contact dermatitis of the hands:
cross-sectional analyses of North American Contact
Dermatitis Group data, 1994–2004. J Am Acad Dermatol.
2007;57(2):301–314
50. American Academy of Dermatology. What is a Scar. At:
http://www.aad.org/public/Publications/pamphlets/
WhatisaScar.htm; 2007 Accessed 12.12.07
51. Due E, Rossen K, Sorensen LT, et al. Effect of UV irradia-
tion on cutaneous cicatrices: a randomized, controlled trial
with clinical, skin reflectance, histological, immunohis-
tochemical and biochemical evaluations. Acta Derm
Venereol. 2007;87(1):27–32
M. R. Hinckley
52. Wahie S, Lawrence CM. Wound complications following
diagnostic skin biopsies in dermatology inpatients. Arch
Dermatol. 2007;143(10):1267–1271
53. Adams DC, Ramsey ML. Grafts in dermatologic surgery:
review and update on full- and split-thickness skin grafts,
free cartilage grafts, and composite grafts. Dermatol Surg.
2005;31(8 Pt 2):1055–1067
54. Lazareth I, Hubert S, Michon-Pasturel U, Priollet P. Vitamin
C deficiency and leg ulcers. A case control study. J Mal
Vasc. 2007;32(2):96–99
55. Rojas AI, Phillips TJ. Patients with chronic leg ulcers show
diminished levels of vitamins A and E, carotenes, and zinc.
Dermatol Surg. 1999;25(8):601–604
56. Wicke C, Halliday B, Allen D, et al. Effects of steroids and
retinoids on wound healing. Arch Surg. 2000;135:1265–1270
57. Dostal GH, Gamelli RL. The differential effect of corticos-
teroids on wound disruption strength in mice. Arch Surg.
1990;125(5):636–640
58. Gordon AJ, Olstein J, Conigliaro J. Identification and treat-
ment of alcohol use disorders in the perioperative period.
Postgrad Med. 2006;119(2):46–55
59. Kiecolt-Glaser JK, Loving TJ, Stowell JR, et al. Hostile mari-
tal interactions, proinflammatory cytokine production, and
wound healing. Arch Gen Psychiatry. 2005;2(12):1377–1384
60. Glaser R, Kiecolt-Glaser JK, Marucha PT, et  al. Stress-
related changes in proinflammatory cytokine production in
wounds. Arch Gen Psychiatry. 1999;56(5):450–456
61. Chen MA, Davidson TM. Scar management: prevention and
treatment strategies. Curr Opin Otolaryngol Head Neck
Surg. 2005;13(4):242–247
62. Zitelli JA. Wound healing by second intention. In: Roenigk
RK, Ratz JL, Roenigk HH Jr, eds. Roenigk’s Dermatologic
Surgery: Current Techniques in Procedural Dermatology.
3rd ed. New York: Informa Healthcare; 2007
63. Orengo I, Iyengar V. Anatomy in cutaneous surgery.
Emedicine. December 15, 2006. At: http://www.emedicine.
com/derm/topic820.htm; 2007 Accessed 12.12.07
64. Berman B, Flores F. Comparison of a silicone gel-filled
cushion and silicon gel sheeting for the treatment of hyper-
trophic or keloid scars. Dermatol Surg. 1999;25(6):484–486
65. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel ver-
sus petrolatum emollient on new surgical scars: a prospective
double-blinded study. Dermatol Surg. 2006;32(2):193–197
66. Berman B, Perez OA, Konda S, et al. A review of the bio-
logic effects, clinical efficacy, and safety of silicone elasto-
mer sheeting for hypertrophic and keloid scar treatment and
management. Dermatol Surg. 2007;33(11):1291–1302
67. Chang CC, Kuo YF, Chiu HC, et al. Hydration, not silicone,
modulates the effects of keratinocytes on fibroblasts. J Surg
Res. 1995;59:705–711
68. Zurada JM, Kriegel D, Davis IC. Topical treatments for hyper-
trophic scars. J Am Acad Dermatol. 2006;55(6):1024–1031
69. Weisberg NK, Nehal KS, Zide BM. Dog-ears: a review.
Dermatol Surg. 2000;26(4):363–370
70. Lee KS, Kim NG, Jang PY, et al. Statistical analysis of surgi-
cal dog-ear regression. Dermatol Surg. 2008;34(8):
1070–1076
71. Robinson JK. The eye and eyelid. In: Roenigk RK, Ratz JL,
Roenigk HH Jr, eds. Roenigk’s Dermatologic Surgery:
Current Techniques in Procedural Dermatology. 3rd ed.
New York: Informa Healthcare; 2007
23  Prevention of Surgical Complications
72. Revis DR, Seagle MB. Local anesthetics. Emedicine.
October 26, 2005. At: http://www.emedicine.com/ent/
topic20.htm; 2007 Accessed 12.12.07
73. Zamanian RT, Olsson JK, Ginther B. Toxicity, local anes-
thetics. Emedicine. June 20, 2005. At: http://www.emedi-
cine.com/emerg/topic761.htm; 2007 Accessed 12.12.07
74. Peralta R, Bastings E, Guzofski S. Toxicity, Lidocaine. April
25, 2007. Emedicine. At: http://www.emedicine.com/med/
topic1297.htm; 2007 Accessed 12.12.07
75. Cox B, Durieux ME, Marcus MA. Toxicity of local anaes-
thetics. Best Pract Res Clin Anaesthesiol. 2003;17(1):
111–136
76. Stasko S, Clayton AS. Surgical complications and optimiz-
ing outcomes. In: Bolognia JL, Jorizzo JL, Rapini RP, eds.
Dermatology. New York: Mosby; 2003
77. Fisher DA. A simple method of identifying the spinal acces-
sory nerve. Dermatol Surg. 2000;26(4):384–386
78. Alam M, Goldberg LH. Two-lobed advancement flap for
cutaneous helical rim defects. Dermatol Surg. 2003;29(10):
1044–1049
79. See A, Smith HR. Partially buried horizontal mattress suture:
modification of the Haneke-Marini suture. Dermatol Surg.
2004;30(12 Pt 1):1491–1492
80. El-Gamal HM, Dufresne RG, Saddler K. Electrosurgery,
pacemakers and ICDs: a survey of precautions and compli-
cations experienced by cutaneous surgeons. Dermatol Surg.
2001;27(4):385–390
81. Matzke TJ, Christenson LJ, Christenson SD, et  al.
Pacemakers and implantable cardiac defibrillators in derma-
tologic surgery. Dermatol Surg. 2006;32(9):1155–1162
82. Koranda FC, Webster RC. Trapdoor effect in nasolabial
flaps. Causes and corrections. Arch Otolaryngol. 1985;111(7):
421–424
279
83. Fader DJ, Johnson TM. Ear reconstruction utilizing the sub-
cutaneous island pedicle graft (flip-flop) flap. Dermatol
Surg. 1999;25(2):94–96
84. Albertini JG. Regarding the modified Burow’s wedge flap
for upper lateral lip defects. Dermatol Surg. 2000;26(10):
981–982
85. Dinehart SM. The rhombic bilobed flap for nasal reconstruc-
tion. Dermatol Surg. 2001;27(5):501–504
86. Zitelli JA. The bilobed flap for nasal reconstruction. Arch
Dermatol. 1989;125:957–959
87. Goldminz D, Bennett RG. Cigarette smoking and flap and
full-thickness graft necrosis. Arch Dermatol. 1991;127:
1012–1015
88. Dixon AJ, Dixon MP. Reducing opposed multilobed flap
repair, a new technique for managing medium-sized low-leg
defects following skin cancer surgery. Dermatol Surg.
2004;30(11):1406–1411
89. Cook JL, Perone JB. A prospective evaluation of the inci-
dence of complications associated with Mohs micrographic
surgery. Arch Dermatol. 2003;139(2):143–152
90. Amici JM, Rogues AM, Lasheras A, et  al. A prospective
study of the incidence of complications associated with der-
matological surgery. Br J Dermatol. 2005;153(5):967–971
91. Colon VF. 10 ways to reduce medical malpractice exposure
– doctors, lawyers and lawsuits. Physician Executive March,
2002. At: http://findarticles.com/p/articles/mi_m0843/
is_2_28/ai_84236558/pg_1; 2007 Accessed 12.12.07
92. Rice B. 10 ways to guarantee a lawsuit: medical mishaps are
only part of the malpractice story. Here’s how to prevent the
nonclinical errors that get doctors in legal trouble. Medical
Economics Jul 8, 2005. At: http://www.memag.com/memag/
article/articleDetail.jsp?id=168737&sk=&date=&%0A%
09%09%09&pageID=3; 2007 Accessed 12.12.07
 Prevention of Keloids
Hillary E. Baldwin
24.1 Introduction
Unlike many skin disorders discussed in textbooks,
keloids have been described in detail dating back to
3,000 bc.1 The Yoruba tribe of Western Africa recorded
their knowledge of keloids in painting and sculpture
ten centuries prior to modern times.2 Despite this con-
siderable head start, we have made remarkably little
progress since the Yorubas toward understanding kel-
oid etiology. This fundamental ignorance is partially
responsible for our current lack of consistently reli-
able, safe treatment, and prevention measures.
Since treatment methods are inadequate in many
and challenging in all, prevention becomes vitally
important. Here, too, our efforts may be thwarted.
There are aspects of keloids that are preventable; one
can avoid trauma resulting from voluntary and elective
procedures to adorn, augment, or improve. Aggressive
prevention of keloids after accidental trauma and nec-
essary surgery is also within our abilities. However,
some putative causative factors of keloid formation are
out of our control: ethnicity, skin pigmentation, age,
gender, and genetic makeup.
This chapter will focus on two aspects of preven-
tion: avoidance techniques for the keloid prone and
prevention of recurrence after surgical intervention.
First, it will briefly review what is known about keloid
epidemiology and pathogenesis to gain insight into the
development of a rational prevention plan for these
unsightly lesions.
H. E. Baldwin  more common in women than men as are the resulting
Department of Dermatology,
SUNY – Brooklyn, Brooklyn, New York, USA
e-mail: hbaldwin@downstate.edu
R. A. Norman (ed.), Preventive Dermatology,
DOI: 10.1007/978-1-84996-021-2_24, © Springer-Verlag London Limited 2010
24
24.2 Epidemiology
The reported incidence of keloid formation has ranged
from a low of 0.09% in England to a high of 16% in
Zaire.3 Such variation is explained by numerous vari-
ables, including race and degree of skin pigmentation. In
predominately black and Hispanic populations, inci-
dences between 4.5 and 16% have been reported.4 Darkly
pigmented individuals form keloids 2–19 times more fre-
quently than Caucasians.5, 6 But ethnicity, regardless of
pigment intensity, is also a factor. In Aruba, more chil-
dren of the lighter-skinned Polynesian population form
keloids than those of African descent.7 In Malaysia, those
of Chinese decent are more prone to keloid formation
than are the darker-skinned Indians and Malays.8
Although Caucasians form keloids less frequently, those
who do can have a very light complexion. These patients
are often among the most difficult to treat.
Keloids can occur at any age. New keloid formation
is relatively less common in the very young and the
elderly. In young children, this may be a function of
low trauma frequency and severity. Aging fibroblasts
may be less capable of collagen over production.9, 10
Keloid regression after menopause has been reported.11
In an unpublished study of 212 Caribbean-American
and African-American keloid-formers at Kings County
Hospital, we found that age as an isolated factor did
not correlate with keloid frequency. Rather, the timing
of the pierce relative to puberty was predictive of kel-
oid incidence.
Small gender differences that have been reported in
the literature are likely to have resulted from cultural
trends and reporting bias. Multiple ear pierces are far
keloids. Additionally, women may more readily seek
medical attention for cosmetic improvement.
281
282
24.3 Etiology
The plethora of existing theories regarding the etiol-
ogy of keloids is indicative of our lack of understand-
ing of the condition. The factors that are most consistent
are some form of skin trauma occurring in individuals
with a genetic predisposition for keloids.
24.3.1 Trauma
“Spontaneous” keloids arising in nontraumatized skin
have been suggested. It is more likely however that the
severity of the trauma was so minor as to go unnoticed
by the patient. Minor abrasions and burns, insect bites,
varicella and zoster, vaccinations and tattoos can result
in significant keloiding. Acne lesions of the anterior
chest and deltoid areas often morph imperceptibly into
keloids. Isotretinoin treatment in these patients can
prevent additional keloids even when the acne lesions
are not readily identifiable. Deep and significant surgi-
cal wounds are often less likely to keloid than are the
minor wounds described above.
However, trauma is merely the precipitating etio-
logic factor. Most patients experiencing the same
trauma do not keloid. Intrapatient variation is also
common. Acne lesions immediately adjacent to each
other, bilateral pierces, or adjacent pierces often have
different outcomes. Lastly, areas prone to trauma such
as the hands and feet rarely keloid.
24.3.2 Skin Tension
Keloids appear most commonly on areas in which skin
tension is the highest, namely the anterior chest, upper
back, and deltoid areas. The fleshy earlobes are obvi-
ous exceptions to this rule. As keloids progress in these
areas, they tend to stretch along skin tension lines
forming linear or bow-tie shaped lesions.
Closing a wound against the relaxed skin tension
lines results in a wound with twice the tension of one
closed along Langer’s lines.12 Postsurgical wound ten-
sion has been implicated in the literature as a contrib-
uting factor in keloid formation.13, 14 The loss of tissue
that results from surgical excisions also increases
H. E. Baldwin
wound tension. Skin grafts may be preferable to
­primary closure of a tight wound, however, the donor
wound may also be subject to keloid formation. The
use of tissue expanders to stretch the skin preopera-
tively offers an alternative that both reduces wound
closure tension and applies pressure preoperatively
that might help reduce fibroblast function.
Wound tension as a primary etiologic factor in kel-
oid formation loses credibility when one considers the
high incidence of earlobe keloids following piercing.
The only tension on this wound is that of the minor
edema that results from the trauma of the pierce.
Chronic edema has been reported to increase gly-
cosaminoglycans (GAGs) in the dermis.15 It is possible
that the chronic edema caused by the pierce (and sub-
sequent reaction to the presence of a metal foreign
body) could result in increased incidence of keloid
formation.
24.3.3 Infection
There is no evidence to support the supposition that the
infectious agents themselves cause keloids. However,
the trauma, edema, and increased tension that occur as
a result of wound infection might incite keloid forma-
tion. This possibility highlights the importance of assid-
uous avoidance and aggressive treatment of wound
infections, especially in the keloid-prone individual.
24.3.4 Endocrine Factors
Multiple and diverse endocrine factors have been asso-
ciated with keloid incidence although causality is
unproven. Keloids have been reported to grow more
readily or to appear de  novo during pregnancy.11, 13
Keloids have been shown to be more common after
puberty than before. This was well known by the
Yorubas in the 1600s who knew to pierce ears early in
life to prevent keloiding. They also used this knowl-
edge to perfect ritual keloiding in intricate designs
after the age of puberty. In our King’s County Hospital
study, ear pierces that resulted in keloids occurred at a
median age of 6.4 years postmenarche, whereas those
that did not keloid were pierced at a median age of
4.25 years premenarche.16
24  Prevention of Keloids
Melanocyte-stimulating hormone (MSH) has been
postulated to play a role in keloid formation. This
hypothesis is based on the observation that keloids are
more common in patients with hyperpigmentation
associated with pregnancy, puberty, and hyperthyroid-
ism. Melanocytes in patients with skin of color may be
more reactive to MSH than Caucasians, explaining the
higher incidence of keloids in darker-skinned patients.
Additionally, keloids are rare on the melanocyte-poor
regions of the palms and soles. However, the highly
pigmented area of the genitalia is also an infrequent
site of keloid formation. Finally, there has never been a
reported case of keloid development in an albino
patient, even one of African descent.
24.3.5 Genetic Predisposition
Keloids are believed to have a familial predisposition,
although the pattern of inheritance is unclear.3, 17 In our
study at King’s County Hospital, we found a familial
pattern in 32% of keloid formers. However, it is pos-
sible that the familial tendency to keloid is more a fac-
tor of similarity of skin coloration between family
members than it is genetically inherited.
24.4 Pathogenesis
Our understanding of keloid pathogenesis is com-
posed of numerous isolated facts that as yet fail to
form a cohesive picture. The simple answer to the
pathogenesis puzzle is that keloid formation is caused
by an increase in anabolic activity in the absence
of increased catabolism. Why this happens is not
known.
After normal wounding takes place, various signals
are sent to the neighboring fibroblasts to increase col-
lagen and GAG production. Upon completion of the
rebuilding task, signals are again sent to the fibroblasts
to return to their prewound status. Abnormalities in
these signals, particularly those that indicate reduction
in collagen production, are believed to be responsible
for keloid growth. Interferons may be one of those
“stop” signals. In normal wounds, there is regression
of connective tissue elements after the third week. In
keloid tissue, however, fibroblasts proliferate around
283
the plentiful new and dilated capillaries. Collagen
­synthesis and GAG synthesis are markedly increased;
collagen synthesis is 20 times greater in keloids than in
normal skin.18, 19 The absolute number of fibroblasts
within the entire keloid is not increased, and they
appear histologically normal, but the activity of pro-
line hydroxylase is markedly elevated, suggesting that
the rate of collagen biosynthesis is increased in a nor-
mally-sized fibroblast population.18, 20 Keloidal fibro-
blasts also appear to resist programmed cell death.21, 22
Defective apoptosis within keloids may be due to a
dysfunctional form of p53. As we will see, injectable
interferon may be effective in treating keloids by its
enhancement of native p53.
Although collagenase is also increased, collagen
degradation is not, possibly due to an increased depo-
sition of alpha-globulins within the keloid.23, 24 Serum
alpha-globulins are known inhibitors of collagenase.23
Estrogens increase the level of serum alpha-globulins,
which may help to explain the increased incidence of
keloids in pregnant women.23 Corticosteroids, in con-
trast, have been shown to reduce the alpha-globulin
deposits within keloids.23 They too may act by increas-
ing activation of collagenase with subsequent break-
down and resorption of the excessive collagen and
clinical flattening.
24.5 Preventative Therapy
In any medical inquiry, a literature review of available
therapy requires attention to study design and validity
of conclusions. This is nowhere more evident than in
the field of keloidal scarring in which one must sift
through large numbers of anecdotal reports and pure
conjecture. The problem begins with the delineation of
hypertrophic scars (HTSs) from keloids. Many studies
include both entities in the admittance criteria yet fail
to reveal, which lesions ultimately responded to ther-
apy. Other patient and lesion characteristics routinely
omitted from these studies include such important fac-
tors as patient race and age, lesion age and symptoma-
tology, lesion size and location, recurrence vs. virgin
lesion and lesion morphology (sessile vs. pedunculated
or dome-shaped). Most reports also suffer from inad-
equate follow-up time of less than 6 months. It is an
undisputable truth that keloid removal is easy; the trick
is preventing recurrence or occurrence.
284
In a recent review article, Shaffer et al. conclude that
despite a plethora of papers on the topic of keloids,
“there are no definitive treatment protocols.”25 This is a
result of poorly designed and uncontrolled studies in
which the endpoint of therapy (cosmesis, function, or
symptoms) is rarely identified. Only radiation therapy
(RT) in combination with surgery met their standards
for proven therapy. Mustoe et  al also lamented the
absence of well-controlled studies and concluded that
corticosteroid injection and silicone gel sheeting (SGS)
are the “… only treatments for which sufficient evi-
dence exists to make evidence-based recommenda-
tions.”26 Durani and Bayat found SGS and laser therapy
to have the highest level of support, albeit sub par.27
Leventhal et al noted that “most treatments for keloidal
and hypertrophic scarring offer minimal likelihood of
improvement.”28 Other treatments at this time are still
lacking the proof of efficacy that arises only from a
well-designed, randomized, placebo-controlled trial
with adequate patient numbers. The nature of keloid
therapy is such that a comparison of various techniques
is often not amenable to double-blinding. We look for-
ward to more studies in which single techniques are
compared to controls, vehicles, or dummy therapy.
At the present time, we must recognize that keloid
prevention techniques are not necessarily evidence-
based. We are using techniques for which definitive
data does not exist. Presented below are the techniques
that have become the standard of care in the field.
24.5.1 Corticosteroids
Because of their ease of administration, low cost, and
low risk, intralesional corticosteroids alone and in
combination are the work horses of keloid occurrence
and recurrence prevention. Although no solid evi-
dence-based literature supports their use in this role,
they have become the first-line approach of most phy-
sicians dealing with this condition worldwide.
24.5.1.1 Corticosteroids as Monotherapy
for Keloid Prevention
Triamcinolone acetonide (TAC) is the most commonly
utilized corticosteroid. Concentrations from 10 to
40  mg/kg are used. Injections can be repeated every
H. E. Baldwin
2–4 weeks, depending on the total dose of steroid used
and the size of the injected space. The most common
cause of steroid “failure” is the use of inadequate con-
centrations. Concentrations less than 10 mg/mL are
rarely effective in prevention. To avoid the risk of
hypothalamic-pituitary axis suppression, this author
does not inject more than 40 mg/session. This means
that the total area treated in one session will be limited
by total safe dose constraints. Better to inject an effica-
cious dose in a smaller area than to spread it so thin
that it is ineffective. This concept must be kept in mind
when planning the surgical excision of an existing kel-
oid. It is imprudent to remove more keloid volume
than can be subsequently injected for recurrence pre-
vention; staged excisions may therefore be preferable.
Although additional areas may be injected on the fol-
lowing weeks, it is best not to inject the same area with
high doses at less than 2-week intervals. The depot effect
of the injected steroids is such that repeat injections done
too frequently can result in atrophy. Hypopigmentation
is also more likely in this setting. With subsequent treat-
ments, the strength of the steroid is often reduced in
order to fine-tune the ultimate outcome.
24.5.1.2 Corticosteroids as Part of Polytherapy
for Keloid Prevention
Corticosteroids can be combined with any other treat-
ment modality to improve outcome. Following surgi-
cal excision, many authors have shown a reduction in
recurrence rates with the addition of postoperative cor-
ticosteroids.29, 30 Combinations with cryotherapy and
silicone gel sheets have been shown to be superior to
either modality alone.31 Corticosteroids plus alpha
interferon have been shown to be more effective than
corticosteroids alone.32, 33 Combinations with lasers
and alpha interferon also have shown promise (see
Sect. 24.5.10).34
Corticosteroids are an integral part of keloid
prevention – both de novo occurrence in a new surgi-
cal wound and recurrence following keloid excision.
This author follows the following injection schedule.
On the day of surgery, and then at 2, 4, and 6 weeks,
the wound margins are injected with TAC 40 mg/mL
regardless of the appearance of the wound. At 2
months, and every month thereafter, injections are
given as clinically necessary. At that point, dosage of
the corticosteroids given at each session is determined
24  Prevention of Keloids
clinically by the site, size, degree of firmness, and
symptoms the patient is experiencing. Preventative
therapy is best carried out for 1 full year; early discon-
tinuation is associated with a higher incidence of
unnecessary recurrences.
Common side effects of steroid injections include
hypopigmentation and skin atrophy. The hypopigmen-
tation can be pronounced and may last 6–12 months
before resolving. However, hypopigmentation can also
be used as a marker of clinical success. Both hypopig-
mentation and atrophy can be reduced by avoiding
injecting into the surrounding normal tissue. Skin atro-
phy is often a necessary consequence of adequate ther-
apy. After treatment, the atrophic surface may appear
wrinkled or shiny, and telangiectasias are common. This
appearance improves with time. Alternatively, vascular
lasers can be utilized to lessen the telangiectasias.
24.5.2 Surgical Methods to Prevent
Keloid Recurrence
Surgical removal of large, bulky keloids is often neces-
sary. However, monotherapy results in a high incidence
of recurrence, often 50–100%.30, 35 Surgery must be
combined with adjunctive techniques such as RT, ste-
roids, or interferon.
24.5.2.1 Use the Smallest Incision as Possible
The smallest incision possible is made, extending less
than the entire length of the keloid. Dissect off any
usable epidermis from the keloid for ease of closure.
24.5.2.2 Remove all Keloidal Tissue
Unless it would result in gross deformity or loss of
function, all of the keloid material should be removed.
Care should be taken to remove any trapped hairs.
24.5.2.3 Minimize Wound Tension
Closure should be done with the least amount of ten-
sion. Surgery followed by grafting alone results in a
285
superior nonrecurrence rate over primary closure
(59%).17 However, donor-site keloids are likely. As a
result, tissue expanders may be preferable.
24.5.2.4 Suture Considerations
Whenever possible monofilament suture should be
used to reduce the incidence of wound infection,
abscess formation and inflammation along the suture
line. Sutures often need to be left in longer than usual
to prevent dehiscence. This is especially true when ste-
roids are injected postoperatively. If the resulting
wound is fairly superficial or very broad, and the
patient is amenable, allowing the wound to heal by
secondary intention often results in better cosmetic
outcome and a lower incidence of recurrence.
24.5.3 Earlobe Keloids
Earlobes keloids need to be considered separately.
Many authors have noted a lower rate of keloid recur-
rence in the earlobe.36, 37 Studies have shown a recur-
rence rate of only 41% respectively after surgery
alone.38 Studies utilizing both surgery and steroids
have shown recurrence rates of 1–20%.39 – 41 Surgery
with adjunctive RT has resulted in recurrence rates of
0–8.6%.39, 42 – 44 With careful, aggressive therapy and
using multiple modalities, earlobe keloids rarely
recur.
Better surgical results on earlobes are probably the
result of several factors. First-time earlobe lesions tend
to be very discrete, and easily separated from the sur-
rounding dermis and epidermis. Complete removal of
all keloidal tissue is thus easier to accomplish. Most
earlobe keloids occur in women who are profoundly
motivated to wear earrings again, and are far more
compliant than the average keloid patient. The fleshy
tissue of the ear makes closure without tension easier
to accomplish. Postoperative pressure is easily applied
with the use of pressure earrings. These earrings are
not particularly cosmetically appealing, but the patients
find them easy to wear and comfortable. They also
make an ideal postoperative dressing, obviating the
need for bulky, and often, inadequate pressure dress­
ings.
286
24.5.4 Laser Surgery
After initial excitement over the demonstrated ability
of the CO2 laser to decrease fibroblast activity in vitro,
its use in keloid therapy was a disappointment.44 – 47
Used in the defocused mode, recurrence rate is
extremely high.48 In the focused mode, recurrence rate
is similar to surgery alone (50–70%).46, 49 The Nd-YAG
laser has been demonstrated to cause an in vitro selec-
tive bioinhibition of collagen production, but recur-
rence rates of 53–100% in vivo.50 The pulsed dye laser
(PDL) has been reported to improve hypertrophic scar
(HTS) symptoms, decrease scar height, and improve
skin texture. Alster and Williams showed a 57–83%
improvement with the 585 nm flashpump PDL in the
prevention of keloids in sternotomy scars.51 They noted
the importance of starting therapy early for the best
results. It has been proposed that the PDL decreases
the microvasculature in early keloids and HTSs result-
ing in anoxia. Several combination studies have shown
that PDL works better in combination with other
modalities, including corticosteroids, interferon, and
carbon dioxide laser.24, 52 – 55
24.5.5 Radiation Therapy
The mechanism of action of RT in prevention of kelo-
ids is unknown. It may decrease fibroblast collagen
synthesis.56 Alternatively, it may act by decreasing vas-
cular hyperplasia.57
For prophylaxis in keloid-prone individuals,
X-radiation, electron beam, and interstitial radiation
have all been reported to result in similar cure rates
(recurrence rates near 20%, which are far superior to
other modalities).58 – 60 Dosing schedule and fractionation
have varied greatly from one study to another, but out-
comes are similar. A minimum of 1,000 rads or equiva-
lent appears to be the common consensus for successful
outcome.61 Kal and Veen concluded that RT should be
done within 2 days of surgical removal, and that short
treatment durations and “relatively high doses” are nec-
essary.62 In a study of earlobe keloids, surgery plus RT
was compared to surgery plus corticosteroids.39
Recurrence rates were 12.5 and of 33%, respectively.
Recurrence rates of 4.7% with high-dose-rate brachyther-
apy,63 21% with interstitial iridium-192,64 16, 19, and
H. E. Baldwin
32% with electron beam65 – 67 have been demonstrated.
Recurrence rates have been shown to be higher in areas
of high tension such as the chest, scapula, and suprapu-
bic areas in three studies.66 – 68 The short treatment plan
required with RT may aid in patient compliance.
Despite its high incidence of success in preventing
keloid recurrence, RT is avoided by many clinicians
due to largely unfounded concerns regarding the long-
term risks of malignancy of the skin or underlying
structures. Numerous large studies report a 0%
­carcinogenesis rate.61 Only one reported case of
squamous cell carcinoma arising in postkeloid radia-
tion site is evident in the literature, and the causality is
unclear.69 Botwood et  al attempted to put these con-
cerns into perspective.61 In more than 100 years in
clinical use, there are only three case reports of
malignancies occurring postkeloid RT. Breast cancer
in a 57-year-old woman occurring 29 years after RT to
a chest keloid was reported in 1999.61 Breast cancer in
a 36-year-old woman 23 years after chest wall keloid
radiation was reported in 198270 In both cases, con-
founding variables were also evident (7-year history of
hormone replacement therapy and evidence of unusu-
ally high radiation doses, respectively). A single case
report of thyroid cancer occurring in a 27-year-old
man 8 years after RT to a keloid of the chin has also
been reported.71 Histopathology revealed a medullary
carcinoma; radiation-induced carcinomas of the thy-
roid are exclusively papillary carcinomas.72 Based on
dosimetry studies, RT in standard dosages to the ear
with proper shielding would expose the ipsilateral thy-
roid lobe to only 2 rads.61 Studies therefore do not war-
rant a high level of concern. Common side effects to
consider are skin atrophy, radiation dermatitis, abnor-
mal skin pigmentation, and local alopecia. RT is not
recommended in children with keloids; if used, meta-
physes must be shielded to prevent retardation of bone
growth, which may occur at doses of 400 R and
less.73
24.5.6 Compression Therapy
Compression therapy – applying pressure greater than
that of capillary pressure [24 mmHg) – causes a reduc-
tion in soft tissue cellularity. Histopathology shows
increased interstitial space and collagen bundles that are
more widely dispersed.74 It is theorized that pressure
24  Prevention of Keloids
creates hypoxia resulting in fibroblast degeneration and
subsequent collagen degradation.
Dressings, which apply 15–45 mmHg, worn 24 h a
day for 4–6 months are often successful in reducing
keloid recurrence rates postoperatively. Not all areas
are amenable to pressure dressings, which in any event
are uncomfortable, hot, and unsightly. Ears are the
exception to this rule. Newer pressure earrings have
large compression plates that are more comfortable to
wear. “Sleeper” styles are less bulky and less con­
spicuous.
24.5.7 Silicone Products
SGS has been touted in many studies to be efficacious
in preventing the development of HTSs and kelo-
ids.75 – 77 These studies are marred by the absence of
blinding and control, small patient numbers and inad-
equate follow-up time. SGS has been shown in small
studies to reduce HTS formation by as much as 70%
when used consistently.77 It must be worn over a scar
for 2–3 months, 12–24  h a day to prevent develop-
ment.78 Sheets are available in varying thicknesses and
consistency. Adhesive tape is necessary for consistent
application. A new formulation of silicone gel has
recently been reported.79, 80 The gel is self-drying and
forms a flexible and transparent sheet after application,
obviating the need for tape.
The mechanism of action of SGS is unknown. SGS
is known to retard epidermal water loss. The drier
agents have been shown to create static electricity,
which some believe to play a role in its effectiveness.
In a controlled, prospective nonblinded study, SGS
was compared to an occlusive dressing without sili-
cone.81 SGS was not found to be superior, leading the
authors to conclude that it was wound hydration, not
the presence of silicone that was responsible for the
clinical effect.
24.5.8 Interferon
As discussed previously, fibroblast activity increases
dramatically after wounding. Once the wound is ade-
quately stabilized, signals are sent to the fibroblasts to
shut off this excessive production of ground substance
287
and collagen. Interferons are one of these signals.
Berman and Duncan reported that short-term intrale-
sional interferon alpha-2b treatment of a keloid resulted
in a selective and persistent normalization of keloidal
fibroblast collagen, GAG and collagenase production
in vitro, and a rapid reduction in the area of the kel-
oid.82 Interferon has also been shown to upregulate
native p53 that is dysfunctional in keloidal fibroblasts.83
This might promote the natural cell death of the over-
active fibroblasts.
Both alpha and gamma interferon are available for
use. Initial clinical trials with gamma interferon were
disappointing and it is no longer in use.84 Granstein has
reported on an unpublished study where 18 of 19 kel-
oid reexcisions were accomplished without recurrence
at 1 year by two postoperative injections of interferon
alpha (Granstein, Personal communication, 1996).
Berman reported response in 11/12 recurrent keloids
of the head and neck after surgical excision and inter-
feron alpha 2b.85 Berman and Flores reported a recur-
rence rate of 51.5% following surgery alone, 58.4%
after surgery and corticosteroids, and 18.7% when sur-
gery was combined with both interferon and corticos-
teroid injections.32 At Kings County Hospital, we have
found that interferon alpha injections can be used to
decrease keloid recurrence after earlobe keloid exci-
sions in which keloidal tissue was left behind.
Injections of interferon alpha-2b are done on the
day of surgery and then 1 week postoperatively directly
into the wound. One million units per linear centimeter
are injected into the wound base and margins. In the
case of a wound allowed to heal by secondary inten-
tion, injections are given approximately every square
centimeter. Side effects are reduced by limiting total
dose to less than five million units per treatment.
Side effects of interferon alpha-2b include a flu-like
syndrome, which can be reduced or eliminated by the
prophylactic use of acetaminophen, and timing of the
injection late in the afternoon so that mild febrile reac-
tions pass unnoticed during sleep.
24.5.9 Imiquimod Application
Imiquimod 5% cream is a potent and rapid inducer of
interferon after topical application. Topical application
of imiquimod to keloids has been shown to signifi-
cantly alter gene expression of markers of apoptosis.83
288
As such, its use in keloid therapy was a logical
­continuance from injectable interferon. Berman and
Kaufman reported its use postoperatively in an uncon-
trolled pilot study of 13 keloids removed from 12
patients.86 Applications were done twice daily, begin-
ning on the day of surgery and continuing for 8 weeks.
At 24 weeks, none of 11 keloids (ten earlobe, one
trunk) evaluated had recurred. The authors have subse-
quently reported one recurrence in the lesion removed
from the back.
Since then, several other small, uncontrolled trials
have suggested that imiquimod is most effective on
the  earlobes. Stashower showed no recurrence at 12
months in four patients with eight earlobe keloids.87
Martin-Garcia and Busquets reported a 25% recur-
rence rate in eight earlobe keloids.88 Chaungsuwanich
and Gunjittisomram showed an overall 6-month recur-
rence rate of 28.6% in 35 patients.89 Recurrences on
the pinna were rare (2.9%) and those of the chest com-
mon (83.3%). Malhotra et al showed an improvement
after surgical excision of three presternal keloids in
two patients over the 8-week treatment phase, but
recurrence 4 weeks later in all patients.90 In an ongoing
study, we have found a modest reduction in keloid
recurrence in nonearlobe keloids treated with imiqui-
mod. In a placebo-controlled, double-blind study of
six patients with 12 nonadjacent keloids, we found a
50% reduction in keloid reformation. The recurrences
in the imiquimod-treated areas occurred later and were
easier to treat than placebo-treated recurrences. More
controlled studies need to be performed to assess the
effectiveness of this treatment modality.
In all of the studies mentioned, there were few topi-
cal and no systemic side effects noted. Application of
imiquimod to open wounds was mostly nonirritating.
Discontinuation for several days was adequate to con-
trol this unlikely side effect.
24.5.10 Combination Therapy
There is no medical reason to limit preventative treat-
ment to a single agent or modality. Prevention of recur-
rence or occurrence can be greatly improved when all
available modalities are utilized simultaneously.
Interferon injections at day 1 and day 8 combined with
RT can deliver two adjunctive therapies in the first 2
weeks post-op when patient compliance is at its peak.
H. E. Baldwin
Pressure dressings if possible, imiquimod application
and continue corticosteroid injections as previously
delineated can be used in conjunction to maximize
outcome.
24.6 Keloid Avoidance Behaviors
The first goal of therapy is, of course, prevention of
unnecessary trauma. Cosmetic procedures should be
discouraged. Ears from which keloids have been
removed should not be repierced.
Early and aggressive treatment of accidental wounds
or nonelective surgeries is crucial in keloid-prone indi-
viduals. Necessary surgical procedures should be
closed parallel to relaxed skin tension lines with mini-
mal stress. Skin grafts, tissue expanders, and healing
by secondary intention should be considered to mini-
mize wound tension. Wounds should be covered with
SGS and/or pressure garments whenever possible.
Preventative intralesional corticosteroids should be
injected at the time of the procedure and regularly
thereafter. Intralesional interferon and RT should also
be considered. Often this must be coordinated in
advance with the patient’s general surgeon. Such inter-
ference is not always appreciated and it is prudent to
elicit the help of the patient in convincing the surgeon
of the importance of early intervention.
Patients in whom acne lesions tend to form keloids
must be carefully monitored and treated. They should
be educated to present at the first sign of an inflamma-
tory acne lesion for intralesional steroids. Multiple
lesions are an indication for oral antibiotics or a course
of isotretinoin. Similarly, in dark-skinned individuals
with a family history of keloid formation, varicella or
zoster should be aggressively treated with antiviral
agents.
24.7 Summary
Keloids are a challenging problem for which there is no
quick fix, or indeed the promise of a fix at all. Beyond
the futility of telling a patient not to get injured, many
aspects of keloids cannot be changed. Age, ethnicity,
skin coloration, genetic makeup, and hormonal influ-
ences are not alterable. Preventative care therefore, is
24  Prevention of Keloids
more focused on prevention of occurrence of new
lesions in a keloid-prone individual and the prevention
of recurrence after surgical removal.
References
  1. Breasted JH. The Edwin Smith Surgical Papyrus, Vol I:
Hieroglyphic Translation and Commentary. Chicago: University
of Chicago; 1930:403–406
  2. Omo-Dare P. Yoruban contribution to literature on keloids.
J Nat Med Assoc. 1973;65:367–406
  3. Bloom D. Heredity of keloids: review of the literature and
report of a family with multiple keloids for five generations.
N Y State J Med. 1956;56:511
  4. Abrahms B, Benedetto A, Humeniuk H. Exuberant keloidal
formation. JAOAC Int. 1993;93:863–865
  5. Brenizer A. Keloid formation in the Negro. Ann Surg. 1915;
61:87
  6. Fox H. Observations on skin diseases in the American
Negro. J Cutan Dis. 1908;26:67
  7. Alhady SM, Sivanantharajah K. Keloids in various races; a
review of 175 cases. Plast Reconstr Surg. 1969;44:564
  8. Arnold H, Graver F. Keloids: etiology and management.
Arch Dermatol. 1959;80:772
  9. Rockwell W, Cohen I, Erlich H. Keloids and hypertrophic
scars. A comprehensive review. Plast Reconstr Surg. 1989;
84:827–837
10. Davies D. Scars, hypertrophic scars and keloids. Plast
Reconstr Surg. 1985;290:1056–1058
11. Kelly P. Keloids. Dermatol Clin. 1988;6:413–424
12. Flint M. The biological basis of Langer’s lines. In: Longacre JJ,
ed. The Ultrastructure of Collagen. Springfield IL: Charles C
Thomas; 1976:132–140
13. Stucker F, Shaw G. An approach to management of keloids.
Arch Otolaryngol Head Neck Surg. 1992;118:63–67
14. Asboe-Hansen G. Hypertrophic scars and keloids; etiology,
pathogenesis and dermatologic therapy. Dermatologia.
1960;120:178
15. Kormoczy B. Enormous keloid (?) on a penis. Br J Plast
Surg. 1978;31:268
16. Lane J, Waller J, Davis L. Relationship between age of ear
piercing and keloid formation. Pediatrics. 2005;115:
1312–1314
17. Cosman B, Crikelair G, Ju M, Gaulin J, Lattes R. The surgical
treatment of keloids. Plast Reconstr Surg. 1961;27:335–345
18. Abergel R, Pizzurro D, Meeker C, et al Biochemical compo-
sition of the connective tissue in keloids and analysis of col-
lagen metabolism in keloid fibroblast cultures. J Invest
Dermatol. 1985;84:384–390
19. Cohen I, Keiser H, Sjoerdsma A. Collagen synthesis in
human keloid patients. Plast Reconstr Surg. 1979;63:689
20. Tan E, Rouda S, Greenbaum S, et al Acidic and basic fibro-
blast growth factors downregulate collagen gene expression
in keloid fibroblasts. Am J Pathol. 1993;142:463–470
21. Sayah DN, Soo C, Shaw WW, et al Downregulation of apop-
tosis-related genes in keloid tissues. J Surg Res. 1999;87:
209–216
289
22. Akasaka Y, Fujita K, Ishikawa Y, et al Detection of apoptosis
in keloids and a comparative study on apoptosis between
keloids, hypertrophic scars, normal healed fibrotic scars, and
dermatofibroma. Wound Repair Regen. 2001;9:501–506
23. Diegelmann R, Bryant C, Cohen I. Tissue alpha globulins in
keloid formation. Plast Reconstr Surg. 1977;59:481
24. Bauer E, Eisen A, Jeffrey J. Regulation of vertebrate colla-
genase activity in  vivo and in  vitro. J Invest Dermatol.
1972;59:50–55
25. Shaffer J, Taylor S, Cook-Bolden F. Keloidal scars: a review
with a critical look at therapeutic options. J Am Acad
Dermatol. 2002;46:S63–S97
26. Mustoe T, Cooter R, Gold M, et al International clinical rec-
ommendations on scar management. Plast Reconstr Surg.
2002;110:560–571
27. Durani P, Bayat A. Levels of evidence for the treatment of
keloid disease. J Plast Reconstr Aesthet Surg. 2008;61:4–17
28. Lenventhal D, Furr M, Reiter D. Treatment of keloids and
hypertrophic scars: a meta-analysis and review of the litera-
ture. Arch Facial Plast Surg. 2006;8:362–368
29. Lahiri A, Tsiliboti D, Gaze N. Experience with difficult
keloids. Br J Plast Surg. 2001;54:633–635
30. Lawrence W. In search of the optimal treatment of keloids:
report of a series and a review of the literature. Ann Plast
Surg. 1991;27:164–178
31. Yosipovitch G, Widijanti Sugene M, Goon A, et  al A
Comparison of the combined effect of cryotherapy and corti-
costeroid injections versus corticosteroids and cryotherapy on
keloids: a controlled study. J Dermatol Treat. 2001;12:87–90
32. Berman B, Flores F. Recurrence rates of excised keloids
treated with postoperative triamcinolone injections of inter-
feron alpha 2b. J Am Acad Dermatol. 1997;37:755–757
33. Lee J, Kim S, Lee A. Effects of interferon-alpha2b on keloid
treatment with triamcinolone acetonide intralesional injec-
tion. Int J Dermatol. 2008;47:183–186
34. Akoz T, Gideroglu K, Akan M. Combination of different
techniques for the treatment of earlobe keloids. Aesthetic
Plast Surg. 2002;26:184–188
35. Darzi M, Chowdi N, Kaul S, et  al Evaluation of various
methods of treating keloids and hypertrophic scars: a 10-year
follow-up study. Br J Plast Surg. 1992;45:374–379
36. Ogawa R, Miyashita T, Hyakusoku H, et  al Postoperative
radiation protocol for keloids and hypertrophic scars: statis-
tical analysis of 370 sites followed for over 18 months. Ann
Plast Surg. 2007;59:688–691
37. Narkwong L, Thirakhupt P. Postoperative radiotherapy with
high-dose-rate iridium 192 mould for prevention of earlobe
keloids. J Med Assoc Thai. 2006;89:428–433
38. Rauscher G, Kolmer W. Treatment of recurrent earlobe kelo-
ids. Cutis. 1996;38:67–68
39. Sclafani A, Gordon L, Chadha M, Romo T. Prevention of
earlobe keloid recurrence with postoperative corticosteroid
injections versus radiation therapy. Dermatol Surg. 1996;22:
569–574
40. Shons A, Press B. The treatment of earlobe keloids by surgi-
cal excision and postoperative triamcinolone injection. Ann
Plast Surg. 1983;10:480–482
41. Rosen D, Patel M, Freeman K, Weiss P. A primary protocol
for the management of ear keloids: results of excision com-
bined with intraoperative and postoperative steroid injec-
tions. Plast Reconstr Surg. 2007;120:1395–1400
290
42. Akita S, Akino K, Yakabe A, et al Combined surgical exci-
sion and radiation therapy for keloid treatment. J Craniofac
Surg. 2007;18:1164–1169
43. Ragoowansi R, Cornes P, Glees J, et al Earlobe keloids: treat-
ment by a protocol of surgical excision and immediate post-
operative adjuvant radiotherapy. Br J Plast Surg. 2001;54:
504–508
44. Chaudhry M, Akhtar S, Duvalsaint F, et al Earlobe keloids,
surgical excision followed by radiation therapy: a 10-year
experience. Ear Nose Throat J. 1994;73:779–781
45. Stern J, Lucente F. Carbon dioxide laser excision of earlobe
keloids. Arch Otolaryngol Head Neck Surg. 1988;113:
1107–1111
46. Kantor G, Wheeland R, Bailin P, et al Treatment of earlobe
keloids with carbon dioxide laser excision: a report of 16
cases. J Dermatol Surg Oncol. 1985;11:1063–1067
47. Driscoll B. Treating keloids with carbon dioxide lasers. Arch
Otolaryngol Head Neck Surg. 2001;127:1145
48. Alster T. Laser treatment of hypertrophic scars, keloids, and
striae. Dermatol Clin. 1997;15:419–429
49. Apfelberg D, Maser M, White D, Lash H. Failure of carbon
dioxide laser excision of keloids. Lasers Surg Med. 1989;9:
382–388
50. Sherman R, Rosenfeld H. Experience with the NDYAG laser
in the treatment of keloid scars. Ann Plast Surg. 1988;24:
231–233
51. Alster T, Williams C. Treatment of keloid sternotomy scars
with 585 nm flashlamp-pumped pulsed-dye laser. Lancet.
1995;345:118–200
52. Connell P, Harland C. Treatment of keloid scars with pulsed
dye laser and intralesional steroids. J Cutan Laser Ther.
2000;2:147–159
53. Maniskiatti W, Fitzpatrick R. Treatment response of keloidal
and hypertrophic, sternotomy scars: comparison among
intralesional corticosteroid, 5-fluorouracil, and 585-nm flash-
lamp-pumped pulsed-dye laser treatments. Arch Dermatol.
2002;138:1149–1155
54. Asilian A, Darougheh A, Shariati F. New combination of
triamcinolone, 5-fluorouracil, and pulsed-dye laser for treat-
ment of keloid and hypertrophic scars. Dermatol Surg.
2006;32:907–915
55. Alster T, Handrick C. Laser treatment of hypertrophic scars,
keloids, and striae. Semin Cutan Med Surg. 2000;19:287–292
56. Order S, Donaldsen S. Radiation Therapy for Benign
Disease. Springer; 1990:147–153
57. Borok T, Brav M, Sinclair I, et al Role of ionizing irradiation for
393 keloids. Int J Radiat Oncol Biol Phys. 1988;15:865–870
58. Ollstein R, Siegel H, Gillooley J, et al Treatment of keloids
by combined surgical excision and immediate postoperative
X-ray therapy. Ann Plast Surg. 1981;7:281–285
59. Khumpar D, Murray J, Anscher M. Keloids treated with
excision followed by radiation therapy. J Am Acad Dermatol.
1994;31:225–231
60. Darzi M, Chowdi N, Kaul S, Kahn M. Evaluation of various
methods of treating keloids and hypertrophic scars: a 10-year
experience. Int J Radiat Oncol Biol Phys. 1989;17:77–80
61. Botwood N, Lewanski C, Lowdell C. The risks of treating
keloids with radiotherapy. Br J Radiol. 1999;72:1222–1224
62. Kal H, Veen R. Biologically effective doses of postoperative
radiotherapy in the prevention of keloids. Dose-effect rela-
tionship. Strahlenther Onkol. 2005;181:717–723
H. E. Baldwin
63. Guix B, Henriquez I, Andres A, et al Treatment of keloids by
high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys.
2001;50:167–172
64. Escarmant P, Zimmerman S, Amar A, et al The treatment of
783 keloid scars by iridium 192 interstitial radiation after surgi-
cal excision. Int J Radiat Oncol Biol Phys. 1993;26:245–251
65. Maarouf M, Schleicher U, Schmachtenberg A, Ammon J.
Radiotherapy in the management of keloids. Clinical experi-
ence with electron beam irradiation and comparison with
X-ray therapy. Strahlenther Onkol. 2002;178:330–335
66. Bischof M, Krempien R, Debus J, Treiber M. Postoperative
electron beam radiotherapy for keloids: objective findings
and patient satisfaction in self-assessment. Int J Dermatol.
2007;46:971–975
67. Ogawa R, Mitsuhashi K, Hyakusoku H, Miyashita T.
Postoperative electron-beam irradiation therapy for keloids
and hypertrophic scars: retrospective study of 147 cases fol-
lowed for more than 18 months. Plast Reconstr Surg.
2003;111:547–553
68. Wagner W, Alfrink M, Micke O, et al Results of prophylac-
tic irradiation in patients with resected keloids: a retrospec-
tive analysis. Acta Oncol. 2000;39:217–220
69. Mizuno H, Cagri Uysal A, Koike S, Hyakusoku H. Squamous
cell carcinoma of the auricle arising from keloid after radium
needle therapy. J Craniofac Surg. 2006;17:360–362
70. Bilbey J, Muller N, Miller R, Nelemus B. Localized fibrous
mesothelioma of pleura following external ionizing radia-
tion therapy. Chest. 1988;94:1291–1292
71. Hoffman S. Radiotherapy for keloids? Ann Plast Surg. 1982;
9:265
72. Sampson R, Kev C, Buschler C, Iijima S. Thyroid carcinoma
and radiation. JAMA. 1969;209:65
73. Doornbos J, Stoffel T, Hass A, et al The role of kilovoltage
irradiation in the treatment of keloids. Int J Radiat Oncol
Biol Phys. 1990;18:833–838
74. Kosaka M, Kamiishi H. New concept of balloon-compression
wear for the treatment of keloids and hypertrophic scars.
Plast Reconstr Surg. 2001;108:1454–1455
75. Gold M. A controlled clinical trial of topical silicone gel
sheeting in the treatment of hypertrophic scars and keloids.
J Am Acad Dermatol. 1994;30:506–507
76. Fulton J. Silicone gel sheeting for the prevention and man-
agement of evolving hypertrophic and keloid scars. Dermatol
Surg. 1995;21:947–951
77. Ahn S, Monafo W, Mustoe T. Topical silicone gel: a new
treatment for hypertrophic scars. Surgery. 1989;106:781–786
78. Berman B, Perez O, Konda S, et al A review of the biologic
effects, clinical efficacy, and safety of silicone elastomer
sheeting for hypertrophic and keloid scar treatment and
management. Dermatol Surg. 2007;33:1291–1302
79. Mustoe T. Evolution of silicone therapy and mechanism of
action in scar management. Aesthetic Plast Surg. 2008;32:
82–92
80. Signorini M, Clementoni M. Clinical evaluation of a new
self-drying silicone gel in the treatment of scars: a prelimi-
nary report. Aesthetic Plast Surg. 2007;31(2):183–187
81. Viana de Oliveira G, Nunes T, Magna L, et al Silicone versus
nonsilicone gel dressings: a controlled trial. Dermatol Surg.
2001;27:721–726
82. Berman N, Duncan M. Short-term keloid treatment in vivo
with human interferon alfa-2b results in a selective and
24  Prevention of Keloids
persistent normalization of keloidal fibroblast collagen,
glycosaminoglycans and collagenase production in  vitro.
J Am Acad Dermatol. 1989;21(4 Pt 1):694–702
83. Jacob S, Berman B, Vincek V. Topical application of imiqui-
mod 5% cream to keloids alters expression genes associated
with apoptosis. Br J Dermatol. 2008;149:62–65
84. Granstein R, Rook A, Flotte T, et al Intralesional interferon
gamma treatment for keloids and hypertrophic scars. Arch
Otolaryngol Head Neck Surg. 1990;118:1159–1162
85. Berman B, Bieley H. Adjunct therapies of surgical manage-
ment of keloids. Dermatol Surg. 1996;22:126–130
86. Berman B, Kaufman J. Pilot study of the effect of postopera-
tive imiquimod 5% cream recurrence rate of excised keloids.
J Am Acad Dermatol. 2002;47:S209–S211
291
87. Stashower M. Successful treatment of earlobe keloids with
imiquimod after tangential shave excision. Dermatol Surg.
2006;32:380–386
88. Martin-Garcia R, Busquets A. Postsurgical use of imiqui-
mod 5% cream in the prevention of earlobe keloid recur-
rences: results of an open-label, pilot study. Dermatol Surg.
2005;31:1394–1398
89. Chuangsuwanich A, Gunjittisomram S. The efficacy of 5%
imiquimod cream in the prevention of recurrence of excised
keloids. J Med Assoc Thai. 2007;90:1363–1367
90. Malhotra A, Gupta S, Khaitan B, Sharma V. Imiquimod 5%
cream for the prevention of recurrence after excision of
presternal keloids. Dermatology. 2007;215:63–65
 Appendix
Patient Handouts: Preventive Dermatology Topics
1
Robert A. Norman and Lana H. McKinley

1.1 Your General Health • Do not smoke.

Achieving healthy skin involves establishing and
maintaining your general health. This includes obtain-
ing optimal nutrition, exercising regularly, and caring
for your overall mental and physical health.
• Consume a variety of foods and beverages within
the basic food groups that are nutrient-dense. Limit
the intake of saturated and trans fats, cholesterol,
added sugars, salt, and alcohol.
• For those who do drink alcoholic beverages, mod-
eration is key. One drink per day for women, and up
to two drinks per day for men.
• Reduce a sedentary lifestyle by engaging in regular
physical activity. This will help promote your psy-
chological well-being and help you maintain a
healthy body weight.
–– Engage in at least 30 min of moderate-intensity
physical activity, above usual activity, at work or
home on most days of the week. This will help
reduce the occurrence of chronic disease in
adulthood.
–– Greater health benefits can be obtained by engag-
ing in physical activity of more vigorous inten-
sity or longer duration. It is important to check
with your physician regarding the intensity, fre-
quency, and duration of your exercise routine.
–– Concentrate on cardiovascular conditioning,
stretching exercises, and resistance exercises for
muscle strength and endurance.
R. A. Norman (*)
Nova Southeastern University, Ft. Lauderdale,
Florida and Private Practice, Tampa, FL, USA
e-mail: skindrrob@aol.com
• Schedule regular visits with your physician.
1.1.1 Helpful Websites
http://www.americanheart.org/
http://www.mayoclinic.com/health/
1.2 Sun Damage and Skin Cancer
Prevention
General skin health can be maintained by avoiding
damage to the skin by acute irritations, such as sun-
burn, or chronic damage resulting in precancerous and
cancerous lesions. Photodamage from natural or artifi-
cial sunlight can affect people differently depending on
their skin type. However, no skin type is totally immune
from the long-term exposure to ultraviolet radiation.
1.2.1 Tips on Prevention
• Avoid peak sunlight hours (10:00 am to 3:00 pm).
• Avoid artificial sources of ultraviolet radiation,
especially tanning beds and sunlamps.
• Make sun exposure gradual by limiting the first day
to 15 min, 30 min the second, and 45 min the third
even if you use sunscreen each time.
• Be aware of any photosensitizing medications such
as certain antibiotics; avoid ultraviolet radiation
during the course of the medication.

R. A. Norman (ed.), Preventive Dermatology, 293

DOI: 10.1007/978-1-84996-021-2_A1, © Springer-Verlag London Limited 2010
294
• Use a sunscreen rated SPF-15 or higher that is PABA-
free on all areas of exposed skin 30–45  min before
going out into sun. Do not forget to include your lips.
• Remember that the sun can still be harmful on
cloudy days. Reapply sunscreen every 2–3 h when
in the sun.
• Wear sunglasses, hats, and protective clothing when
in the sun.
• Educate your children about the harmful effects of
sunlight.
• Inspect your skin monthly for changes and visit
your dermatologist routinely to be examined for
precancerous or cancerous skin growths. Skin
changes to be aware of include: scaly red patches
that itch or bleed and do not heal, elevated growths,
and open sores.
• Other skin changes to watch out for are moles that
appeared after the age of 21, which have increased
in thickness or size, or have changed in color, shape,
or texture.
• Discuss treatment options for precancerous lesions
such as actinic keratoses with your dermatologist.
Treating these lesions early can prevent the poten-
tial for cancerous transformation.
1.2.2 Helpful Websites
http://www.skincancer.org/squamous/
http://www.cancer.org
1.3 Acne
Acne is the term for pimples, clogged pores, or even cysts
that can be found on the face, back, neck, shoulders, and
upper arms. It is very common in teenagers, but may per-
sist into adulthood. There are many different variants of
acne. Acne scarring varies from patient to patient.
1.3.1 Treatments
Treatment of acne often involves a variety of different
combinations of medications. These include both oral
and topical antibiotic therapy, agents that promote
R. A. Norman and L. H. McKinley
drying and peeling, and medications that help free
blocked pores. One or all may be necessary to help
control acne. Severe nodular and cystic acne may
require more aggressive therapy and often is treated
with isotretinoin.
1.3.2 Tips on Prevention
• Keep face clean with gentle washings once or twice
daily.
• Avoid picking or “pimple popping” as this may pro-
mote scarring.
• Wash pillow cases and towels often.
• Shower and wash face shortly after workouts.
• Throw out old makeup and be sure to clean cos-
metic brushes.
• Use nonclog-forming, oil-free cosmetics, and sun-
tan lotions.
• Keep hair off face, neck, and shoulders by pulling it
back if it is long.
• Hair conditioner or oil-based hair products should
be avoided.
• Avoid tight fitting clothing on acne prone areas.
• Regular exercise works to promote increased circu-
lation and oxygenation to the skin.
• Avoid aggressive scrubbing of face; this tends to
only irritate and cause existent acne.
1.3.3 Helpful Websites
http://www.acne.org/
http://www.acne.com/
http://www.acneguide.ca/
1.4 Rosacea
Rosacea is a disorder of the skin characterized by red-
dening and flushing of the face that is sometimes mis-
taken for acne. Often the skin will consist of red
pimples and visible small blood vessels on the cheeks,
nose, forehead, and chin. This condition typically
lasts for years, sometimes with periods of
improvement.
Appendix 1 Patient Handouts: Preventive Dermatology Topics
1.4.1 Treatments
Topical as well as systemic antibiotics are usually
needed to control rosacea.
1.4.2 Tips on Prevention
• Sun exposures can often exacerbate rosacea.
• Avoid excessive washing of the face.
• Avoid facial lotions and cosmetics that may irritate
rosacea.
• Avoid alcohol, especially red wines which may
worsen rosacea.
• Emotional stress may play a part.
• Stay away from spice foods, excessive caffeine, and
smoking.
• Avoid extremes of hot and cold.
• Certain prescription drugs may cause rosacea-like
symptoms; be sure to discuss these symptoms with
your doctor.
1.4.3 Helpful Websites
http://www.rosacea.org/
http://www.rosaceaguide.com/
1.5 Atopic Dermatitis
Sometimes referred to as hereditary eczema, atopic
dermatitis is the most common childhood skin disorder
that usually appears on the hands, face, limbs, and is
accompanied by an intense itch. The skin tends to be
sensitive and may flare up during times of stress,
changes in weather, or for no apparent reason. In about
half of cases, this condition goes away on its own in
early adulthood but could be lifelong in some people.
1.5.1 Treatments
Topical steroids or immune modulators, antibiotics,
and oral antihistamines are often used alone or in com-
bination to help with flare-ups. Alternating applications
295
of topical steroids with effective moisturizers may
allow less overall topical steroid use.
1.5.2 Tips on Prevention
• Children should take daily baths or showers using a
gentle cleanser.
• Immediately after bathing, dry excess water and
apply thick moisturizer.
• Keep skin hydrated using fragrance-free moisturiz-
ers at least twice daily and especially when skin
becomes increasingly dry and itchy.
• Excessive sweating should be avoided.
• Stress reduction can be helpful.
• Choose soft, light cotton clothing as wool and syn-
thetic fibers can be irritating.
• Always wash new clothing with a mild detergent
before wearing.
• It is sometimes helpful to add an extra rinse cycle
when doing laundry to remove residual irritants.
• Keep fingernails short and clean to reduce scratch-
ing and infections.
• Control aggravating external factors by remaining
in a consistent, comfortable environment.
• Protect the skin from the sun with moisturizing SPF
15 or higher sunscreen.
1.5.3 Helpful Websites
http://www.kidshealth.org/parent/infections/skin/
eczema_atopic_dermatitis.html
http://dermnetnz.org/dermatitis/atopic.html
1.6 Contact Dermatitis
Skin inflammation (especially on the hands, feet, and
groin) caused by contact with an irritating substance.
Contact with irritants such as sprays, acids, or solvents
remove the fatty layer of the skin causing shrinking of
the surface cells. Common irritants include metals in
jewelry, poison ivy, chemicals in cosmetics, and cer-
tain topical medications. Contact dermatitis is not con-
tagious. Skin is often itchy, red, and often cracks.
296
1.6.1 Treatment
Effective treatments involve eliminating allergens,
avoiding irritants and other precipitating factors, and
relieving itching and inflammation. Topical creams,
ointments, or lotions can be used. These may include
steroid preparations to reduce inflammation or lubri-
cants to preserve moisture.
1.6.2 Tips on Prevention
• Avoid constant exposure to hot water, detergents, or
any irritant that changes the moisture content of skin.
• Avoid occupations or hobbies that bring you in con-
tact with irritants.
• Avoid contact with irritants that have caused der-
matitis in the past.
• Wearing protective gloves may be helpful.
• Protect skin from sunburn and other burns.
• Use bath oil or glycerin-based soap instead of soap
for bathing. Pat skin dry rather than rubbing it.
• Remove rings before doing housework.
• Do not use fabric softeners in the wash or antistatic
sheets in the dryer.
1.6.3 Helpful Websites
http://www.eczemaguide.ca/
1.7 Hand Eczema
Hand eczema can sometimes be caused by substances
that come in contact with the skin and cause an irrita-
tion. Atopic hand eczema or dishidrotic eczema can
occur without any outside causes. Hands often become
itchy, dry, red, and scaly. In some cases, blisters can
develop.
1.7.1 Treatment
Treatment usually consists of a topical steroid cream.
Other nonsteroid creams may be helpful as well.
R. A. Norman and L. H. McKinley
1.7.2 Tips on Prevention
• If irritants can be identified, avoid if possible.
• Avoid frequent hand washing.
• When washing hands, use moisturizing soaps or
nonsoap cleansers and use lukewarm water.
• Moisturizing lotions can be very helpful, especially
during the winter months when the air tends to be dry.
• Wear nonlatex gloves when doing household clean-
ing and washing dishes as frequent wet work may
exacerbate the condition.
1.7.3 Helpful Websites
http://www.eczemaguide.ca/
http://www.skincarephysicians.com
1.8 Herpes Simplex
Herpes simplex is a virus that can cause a blistering-
type rash on almost any part of the body. Sometimes the
initial or primary infection can occur without symptoms.
This is when most transmission of the virus occurs.
However, the virus can remain “dormant” for long peri-
ods of time, and can be reactivated under times of stress
on the body. Type I herpes simplex is usually associated
with oral infections (usually presents like a “cold sore”),
while type II is associated with genital infections.
1.8.1 Treatments
Antiviral therapy may be indicated for the treatment of
herpes simplex depending on the extent of disease.
Cold compresses to the area can help alleviate some
discomfort. Docosanol is an over-the-counter medica-
tion that can be applied topically to cold sores. This
generally shortens healing time.
1.8.2 Tips on Prevention
• Patients should take measures to prevent spread of
herpes simplex virus (HSV) by avoiding contact
with open lesions.
Appendix 1 Patient Handouts: Preventive Dermatology Topics
• Avoid sharing drinking glasses or razors with
others.
• Condoms should be used to prevent transmission of
HSV-2 during intercourse.
• Athletes, especially in contact sports such as wres-
tling, should be aware of the potential to transmit
the virus by direct skin-to-skin contact.
1.8.3 Helpful Websites
http://cdc.gov/std/Herpes/
http://www.herpesguide.ca/
1.9 Dry Skin (Xerosis)
Dry skin is a common problem, especially during the
winter months. The skin becomes scaly and rough.
The incidence of dry skin increases with age.
1.9.1 Treatment
Daily moisturizers can help skin retain water and pre-
vent dryness. Creams containing urea can also be
helpful.
1.9.2 Tips on Prevention
• Apply moisturizers immediately after shower or
bath to lock-in water within the skin.
• Decrease frequency of showers or baths and use
moderately warm water to avoid scalding or further
irritation.
• Use mild soaps for sensitive skin.
• Decision on over-the-counter moisturizer is based
on effectiveness, cost, and ease of application.
• Scaly skin can be treated by ammonium lactate
which must be prescribed by your dermatologist.
• Use gloves when washing dishes or cleaning around
the house.
• Wear gloves, socks, hats, when the weather is cold
for added protection.
• Humidifiers may or may not be helpful.
297
1.9.3 Helpful Websites
http://www.aocd.org/skin/dermatologic_diseases/dry_
skin.html
1.10 Psoriasis
Psoriasis is a common, chronic, inflammatory disease
of the skin most commonly found on the elbows,
knees, and scalp. Psoriasis is considered to be an
immunologic disease and about 30% of people with
psoriasis have a family history of the condition.
Severity of disease varies widely and is characterized
by red and silvery scaly areas of skin. Some forms of
psoriasis can also affect the nails and joints.
1.10.1 Treatments
Treatment of psoriasis involves one or a combination
of topical, systemic, and phototherapy (ultraviolet
light) depending on the extent of disease. For severe
disease immunomodulatory therapy may be indicated.
1.10.2 Tips on Prevention
• Psoriasis is often worsened by emotional anxiety
and stress.
• Excess alcohol may aggravate the condition.
• Eliminate smoking and excess weight.
• A warm and humid climate, combined with natural
sunlight is helpful. Plan moderate exposure to sun-
light without burning.
• Keep skin moist with gentle skin moisturizers.
• Certain medications may trigger or worsen psoria-
sis, be sure to discuss this with your physician if
you suspect a medication may be responsible.
1.10.3 Helpful Websites
http://www.psoriasis.org
http://www.psoriasisguide.com/
298
1.11 Molluscum Contagiosum
Molluscum contagiosum is a skin condition character-
ized by rounded discrete lesions that are flesh-toned or
yellow-white which are caused by a virus. They can
occur anywhere on the body. Most commonly affects
young healthy children, adults who are sexually active,
and HIV positive patients.
1.11.1 Treatment
Most lesions disappear without treatment within 6–12
months. However, available treatments include removing
the lesion with a skin curette, topical treatments, ucryo-
therapy, laser vaporization, or light electrodesiccation.
1.11.2 Tips on Prevention
• Avoid contact with others if they have suspicious
lesions.
• Avoid contact with objects which may come into
contact with lesions.
• Avoid picking or scratching the lesions.
• When lesions are present on the penis, condoms
may provide protection.
• Those who come into close physical contact with the
person with lesions should be examined and treated.
1.11.3 Helpful Websites
http://www.mayoclinic.com/health/molluscum-
contagiosum
1.12 Warts
Warts are very common skin growths caused by a type
of virus called human papilloma virus (HPV). There
are several different types of warts including common,
plantar, and flat warts. Warts are transmitted by simple
contact, usually in areas of skin trauma. Warts appear
R. A. Norman and L. H. McKinley
as flesh-colored, dome-shaped pimples. Common sites
include hands, knees, elbows, and feet.
1.12.1 Treatment
Warts can be treated with over-the-counter salicyclic
acid preparations, cryotherapy, light electrocautery, or
blunt dissection.
1.12.2 Tips on Prevention
• Do not bite or pick at the warts. Doing so can pro-
mote spreading to other areas on the body.
• Shaving should be avoided as flat warts easily
spread within these areas.
1.13 Genital Warts
Genital warts are caused by a specific type of HPV but
not the same viruses that cause the common wart. Most
often, these are spread by sexual contact and are seen in
the regions of the penis, vulva, cervix, vagina, and anus.
1.13.1 Treatment
Genital warts are treated differently than common
warts because of the very sensitive skin. There are no
treatments that actually destroy the virus.
1.13.2 Tips on Prevention
• Some spread of warts can be lessened by use of
condoms.
1.13.3 Helpful Websites
http://www.kidshealth.org/kid/ill_injure/aches/warts.html
http://www.cdc.gov/STD/HPV/STDFact-HPV.htm
Appendix 1 Patient Handouts: Preventive Dermatology Topics 299

1.14 Fungal Infections 1.15 Onychomycosis (Nail Fungus

Infection)
Fungal infections are caused by microscopic plants that
become parasites on your skin. Eventually they grow Onychomycosis is caused by many different species of
enough to cause infectious colonies. Ringworm of the fungus that infect the nail plate of the finger or toe.
skin or scalp, athlete’s foot, and jock itch are caused by
mold-fungi. Ringworm can appear as red scaly expand-
ing rings that sometimes itch. Yeast or candida infec-
tions can cause diaper rash, infections in folds of skin of 1.15.1 Treatment
overweight people, and oral infections (thrush). Another
yeast called tinea versicolor is a thin coating of fungus Topical antifungal are less effective than oral therapy.
on the skin that appears as patches of discolored skin. Removing the infected nail plate first provides higher
cure rates.

1.14.1 Treatment
1.15.2 Tips on Prevention
Topical or oral antifungal therapy is used to treat fun-
gal infections. A combination may be necessary
depending on the extent of disease. Shampoos are also • Keep nails short.
available which can be lathered all over the affected • File down irregular nails.
area and rinsed in the shower. • Avoid trauma or irritants to nails such cotton and
vinyl gloves for wet work or heavy cotton gloves
for dry work.
• Do not use same instruments on both infected and
1.14.2 Tips on Prevention
uninfected nails.
• Wear properly fitting shoes with good support and a
• Maintaining good hygiene is helpful in preventing wide toe box, and avoid high heels and narrow toed
fungal infections. shoes.
• Address care of minor skin or nail injuries as these • Take your own instruments when receiving pedi-
may be sites of entry for infection. cures or manicures at nails salons.
• Moist skin may also increase susceptibility espe- • Use antifungal foot powder daily.
cially to yeast infections. It is helpful to keep folded • Keep feet cool and dry.
skin areas as dry as possible.
• Losing weight may help decrease susceptibility to
yeast infections.
• To help prevent another infection with tinea versi- 1.15.3 Helpful Websites
color, it is best to be treated with antifungal therapy
before the warm season.
http://www.emedicinehealth.com/onychomycosis/
• Certain medications including antibiotics may
article_em.htm
increase your susceptibility to infection.
• You are more likely to get a fungal infection if you
have a weakened immune system. Discuss your
concerns with your physician. 1.16 Keratosis Pilaris

Keratosis pilaris is a skin condition most commonly

1.14.3 Helpful Websites seen on the upper arms, buttocks, and thighs. It is
caused by the accumulation of dead skin (keratin)
www.dermnetnz.org/fungal/tinea.html around hair follicles. The condition is generally worse
300
in the winter months. Keratosis pilaris often improves
by adulthood.
1.16.1 Treatment
Lac-hydrin cream or lotion prescribed by your dermatol-
ogist can reduce roughness and help appearance. Tretinoin
is occasionally prescribed for severe cases. Prescription
antibiotics or low potency topical corticosteroids may be
needed if the spots are very red and inflamed.
1.16.2 Tips on Prevention
• Daily intensive moisturizing is essential.
• Avoid scratching the skin or using gritty body
scrubs to prevent aggravating the condition.
• Using glycolic acid moisturizing lotions and washes
may help.
• Plugged pores can be removed by taking long, hot
soaking tub baths and then gently rubbing with a
coarse wash cloth.
• Avoid wearing tight-fitting clothing.
1.16.3 Helpful Websites
www.helpforkp.com/
1.17 Impetigo
Impetigo is a fairly common superficial skin infection
caused by bacteria staphylococci or streptococci. It
may occur on normal skin, but the bacteria usually
invade at the site of a skin scratch or abrasion. It
appears as a sore with yellow or gray crusts on face,
legs, or arms.
1.17.1 Treatment
Topical antibiotic medications are effective in limited
and minor infections. For extensive infections, your
R. A. Norman and L. H. McKinley
physician may prescribe antibiotics (such as penicillin
or erythromycin) to be taken orally.
1.17.2 Tips on Prevention
• Keeping children’s skin clean is the best way to
keep it healthy.
• Several washings daily with antibacterial soap or cleanser
soften crusts so that they can be gently removed.
• Wash clothing, bedding, and towels frequently and
do not share them with anyone else in the family.
• Physical contact including scratching can spread the
infection to other parts of the body or even other peo-
ple; it is therefore necessary to wash hands frequently.
• Wear gloves when applying antibiotic ointments to
your children.
• Cut nails to avoid scratching.
1.17.3 Helpful Websites
www.kidshealth.org/parent/infections/bacterial_viral/
impetigo.html
www.dermnetnz.org/bacterial/impetigo.html
1.18 Folliculitis
Folliculitis is the name given to a group of skin condi-
tions with inflamed hair follicles. The causes of folli-
culitis include bacterial infection, contact reactions,
and inflammatory skin diseases.
1.18.1 Treatment
If the causative agent is infectious, topical or oral anti-
biotics may be needed depending on the extent of the
skin condition.
1.18.2 Tips on Prevention
• Shaving, waxing, plucking, and use of any epilday
may cause persistent folliculitis. Stop removing
hairs with this method.
Appendix 1 Patient Handouts: Preventive Dermatology Topics
• Use a ladies’ electric razor which is the gentlest
method of hair removal.
• Overuse of topical steroids may produce folliculitis.
• Friction, tight-fitting clothing, and heat should be
minimized.
• Antibacterial soaps are helpful.
• Change razors frequently to avoid reinfection.
• Avoidance of close shaving is helpful.
• Certain chemicals such as coal tar or cutting oils
may cause irritant folliculitis. Avoiding contact
with these products will prevent folliculitis.
1.18.3 Helpful Websites
www.aocd.org/skin/dermatologic_diseases/folliculi-
tis.html
1.19 Scabies
Scabies are tiny mites that can cause skin to be
extremely infection most often at night. Usually, sca-
bies affects more than just one member of a family.
Scabies appears as a rash most often found between
the fingers, the sides of the hands and feet, the belly
button, and wrists.
1.19.1 Treatment
Permethrin cream by prescription is used to treat the
skin condition. Typically this cream is kept on over-
night and washed off in the morning. It is normal to
itch for days to weeks after treatment, but it is usually
less intense. Oral medications (ivermectin) are also
used.
1.20 Lice
Lice are wingless insects that infest the hair of the
body, especially on the scalp and pubic region. Usually
this causes mild itching at the neck or no symptoms at
all. Infestation is highly contagious. Nits are small
white eggs that can be seen in the hair.
301
1.20.1 Treatment
Permethrin rinse is an over-the-counter preparation
usually used to treat lice infections. Other various
shampoos and lotions can be prescribed by your physi-
cian. Nit removal with special combs is also essential
for treatment.
1.20.2 Tips on Prevention
• All bed linens, towels, and undergarments should
be washed with hot water.
• Once a family member is suspected to have scabies
or lice, it is best to treat everyone in the household.
• Do not share hair brushes with anyone suspected of
having lice.
1.20.3 Helpful Websites
www.headlice.org
www.mayoclinic.com/health/scabies
www.kidshealth.org/parent/infections/skin/scabies.
html
1.21 Neurodermatitis
Neurodermatitis is itching aggravated by nervous ten-
sion or anxiety. Although the conditions are not pre-
cisely the same, the names neurodermatitis and lichen
simplex chronicus are used interchangeably. In simple
terms, these common skin disorders consist of small
flat growths of various sizes with definite margins that
have become thickened and leather-like. Long-
standing neurodermatitis may lead to brownish
pigmentation.
1.21.1 Treatment
The primary treatment of these skin problems is to
stop scratching. Perhaps by understanding the disor-
der, you may be able to stop or minimize the tendency
302 R. A. Norman and L. H. McKinley

to continue irritating the skin by scratching. Steroid • To minimize nighttime itching, covering affected
creams may be recommended by your physician to skin may be helpful.
decrease itching and inflammation. Sedatives may also • Use gentle body cleansers and moisturizers.
be helpful.

1.21.3 Helpful Websites
1.21.2 Tips on Prevention
http://www.skincarephysicians.com/eczemanet/neuro-
• Seek avenues for stress reduction. dermatitis.html
• Resist the urge to scratch with fingernails and gen- http://www.mayoclinic.com/health/neurodermati-
tly rub with a soft cloth instead. tis/DS00712
 Appendix 
Skin Performance Assessment Questionnaire
2
Robert A. Norman

Complete my questionnaire to assess your level of skin

health!
Give yourself zero points for each “Never” response,
one point for each “Sometimes” response, and two points
for each “Always” response. Add up your responses.

Always (2 points) Sometimes (1 point) Never (0 points)

Lifestyle
1. I use sun block and avoid the sun as much
as possible, especially during the hours
of 10 am to 4 pm
2. I use a sunscreen with a skin-protection
factor of 15 or greater and always wear
a hat and sunglasses outdoors
3. If I have a fair complexion, blue eyes, and
blond hair I know I am the most
susceptible to melanomas
4. I make sure my children avoid sunburns
5. I have no addictions or any self-destructive
behavior
6. I laugh a lot and enjoy a good sense of
humor
7. If I choose to tattoo or pierce, I am aware
of the possible transmission of
dangerous blood-borne diseases,
infections, and keloid formation among
other problems

R. A. Norman
Nova Southeastern University, Ft. Lauderdale, Florida and
Private Practice, Tampa, FL, USA
e-mail: skindrrob@aol.com

R. A. Norman (ed.), Preventive Dermatology, 303

DOI: 10.1007/978-1-84996-021-2_A2, © Springer-Verlag London Limited 2010
304 R. A. Norman

Always (2 points) Sometimes (1 point) Never (0 points)

8. If I want to get a tan, I avoid sun-tanning
parlors and only use spray-on products.
I exercise at least 3 times a week for
better health and great skin
9. I take precautions to not develop cold
sores
10. If I have had a history of blistering
sunburns during childhood, I make
sure I am especially diligent about
doing self-examinations to detect skin
cancers
11. I rarely get less than 8 h sleep a night and I
go to sleep and wake at consistent
times
12. I get regular, age-appropriate health
check-ups and tests
13. I have many healthy ways to relax
14. I practice deep breathing, meditation, and
other ways to relieve stress
15. I use mental imagery to prepare myself for
my best health and skin care
Diet questions
16. I eat healthy foods and drink plenty of
healthy liquids such as water and green
tea
17. My alcohol and sugar intake is low
18. I avoid eating a diet high in fat
19. I take proper vitamin supplementation to
enhance my energy levels and my skin
20. I plan my day and I am prepared by
including healthy snacks
21. I do not go through big ups and downs in
my eating habits and intake
Skin therapies
22. I know there are many products for under
$25 that are safe and effective for my
skin
23. I do not use products that make my skin
feel and look greasy
24. I do not use products that make my skin
turn dry and flaky
25. My skin cleansers, moisturizers, toners,
and night creams all do not have
irritating fragrances and work quite
well
26. I use a moisturizer with a sun block of at
least SPF 15
Appendix 2 Skin Performance Assessment Questionnaire 305

Always (2 points) Sometimes (1 point) Never (0 points)

27. I take the time to learn my skin type so I
can match it with the correct products
28. My skin seldom gets red and blotchy
29. My skin shows few fine lines and wrinkles
from sun damage (photo-aging), solar
hyperpigmentation (brown spots from
sun)
30. I use just the minimal amount of products
to be safe and effective and no more
31. My skin most often looks refreshed
32. I keep up with tips on health and my skin
and avoid products that can’t be backed
up by good studies
Motivation
33. I use a common-sense philosophy of life
and keep it simple
34. I am up and ready to go in the morning
35. I am an optimist and live life fully
36. While I am on the Internet, I use sites such
as “http://www.aolhealth.com” to help
improve my life and attitude
37. I keep myself on task when it comes to
problem-solving and know what I want
to accomplish
38. I have people that I can trust to discuss and
help with my skin and health
problemsI never give up because I
know that things may change for the
better as time goes on

Add them up Total score: _______________

2.1 Preventive Dermatology
Questionnaire
By using this questionnaire, you have an excellent
teaching tool for your patients. Go over the results and
find ways your patients can practice prevention and
improve their health. There are no grades given, except
that 76 is an A+!
Here are the tips:
Lifestyle Habits – Explain in simple terms how to evalu-
ate any problems, prevent diseases, and intervene when
it is needed. To solve skin problems and improve the
patient’s skin, always address the patient’s diet, nutrient
intake, medications, natural dietary supplements, sleep
quality and quantity, exercise, sun exposure, cigarette
smoking, alcohol, recreational drugs, and more. By hav-
ing this information, you can quickly identify the areas
that need to be changed and give the patient some sim-
ple steps to make these changes—quickly.
Diet Tips – Often a patient’s skin condition (or appear-
ance) is linked to his or her diet. Tips to include in any
patient program include key information on dietary
fats (saturated, polyunsaturated and trans fats) and
their link to skin inflammation and skin cancer, aging
306
skin, the Glycemic Index and acne, phytochemicals
and antioxidants that can improve wrinkled or sun
damaged skin, and more.
Skin Therapies – Our patients have many questions
that give us a chance to talk about prevention. They
may ask about self-tanners, the best skincare regi-
men for the adult that still gets acne, their skin type
and what particular skin concerns they have related
to the type, how to choose “anti-aging” products and
practical tips on avoiding the marks and growths of
aging skin, the best soaps, shampoos, diapers, pow-
ders, and lotions for their baby, and many other
questions.
Motivation – anticipate questions and answers that
your patients can use to improve their skin. If you have
a patient with acne, rosacea, or any other skin problem
that has tried most conventional therapies without suc-
cess, what do you do now? What if you are treating a
45-year-old man who smokes a pack a day and has
extensive skin rhytides? What can you advise? What if
R. A. Norman
a patient asks about supplements to improve his or her
skin health? Can you advise a patient about getting
into the best skin-saving exercise program?
References
Norman R. 100 Questions and Answers about Aging Skin Jones
and Bartlett 2009
Norman R. 100 Questions and Answers about Atopic Dermatitis
Jones and Bartlett 2010
Norman R, Reusher L. 100 Questions and Answers about
Chronic Illness Jones and Bartlett 2009
Norman R, Reusher L. 100 Questions and Answers about Lupus
Jones and Bartlett 2010
Langley R. Psoriasis—Everything You Need to Know Firefly
Books 2005
Day D. 100 Questions and Answers about Acne Jones and
Bartlett 2005
Bergstrom K. 100 Questions and Answers about Psoriasis Jones
and Bartlett 2004
McClay E. et al 100 Questions and Answers about Melanoma
and Other Skin Cancers Jones and Bartlett 2003
Day D. 100 Questions and Answers about Acne Jones and
Barlett 2005
 Index

A licorice, 196
Acne nonenzymatic endogenous antioxidants, 194
acne cosmetica, 183 procyanidins, 195
acnegenicity vs. comedogenicity, 184 pycnogenol, 196
acneiform eruptions and cosmetics, 184–185 resveratrol, 196
comedogenic ingredients, 184 silymarin, 196
comedogenicity testing, 184 soybean, 196
occupational acne, 105 Apocrine perspiration, 182
prevention tips, 294 Arbutin, 180
treatment, 294 Arterial and ischemic ulcers
websites, 294 LEAD, 252–253
Acrodermatitis enterohepatica, 200 PVD, 253
Advisory Committee on Immunization Practices vasoconstriction, 253
(ACIP) recommendations Arthropod-borne infections, 244–245
catch-up vaccination, 238 Artificial dermis, 58
HPV vaccine, 238 Ascorbic acid, 179, 192–193
routine vaccination, 238 Athletes. See Sports dermatology
VZV vaccine, 236 Atopic dermatitis (AD), 53, 295
Aleosin, 179–180 Atopic eczema (AE)
Alpha lipoic acid, 179, 194 allergologic workup, 141–142
American Academy of Pediatrics (AAP), 220, 221, 224 allergy, 139
Amiodarone, 69 antimicrobial therapy, 146
Anapsos, 195 antipruritic treatment, 146–147
Anesthetic toxicity azathioprine, 147
bupivacaine, 274 clinical presentation, 140
epinephrine, 273–274 cyclosporine, 147
lidocaine, 274 diagnostic criteria, 140–141
symptoms, 273 dietary restrictions, 146
Ankle brachial index (ABI), 250 differential diagnoses, 142
Ankle brachial pressure index (ABPI), 77, 78 genetics, 138–139
Antimicrobial therapy, atopic eczema, 146 immunology, 139
Antioxidants, 193 mycophenolate mofetil, 147
alpha-lipoic acid, 194 nonpharmacological intervention strategies, 147–148
anapsos, 195 pathophysiology, 138–140
botanical antioxidant, 195–196 prevalence, 137
chamomile, 195–196 prevention, 142–148
coenzyme Q10 (CoQ10), 194 primary prevention, 142–143
curcumin, 196 secondary prevention, 143–144
echinacea, 196 skin physiology, 138
endogenous antioxidant, 194–195 Staphylococci and Herpes virus infection, 140
exogenous antioxidant, 195 stress and itch, 139–140
garlic, 196 systemic immunosuppression, 147
gingko biloba, 196 topical therapy, 144–146
glutathione, 195 UV light therapy, 146
green tea, 196 Atopy patch test (APT), 142. See also Patch testing
isoflavone genistein, 195 Autoimmune bullous diseases. See Bullous diseases

307
308 Index

Avobenzone, 85 epidermolysis bullosa acquisita, 125–126

Azelaic acid, hyperpigmentation, 179 infective causes
erythema multiforme (EM), 128
B herpes simplex virus (HSV), 128
Bacterial infections herpes zoster (HZ), 129
antibacterial agents, 241 oral acyclovir, 129
methicillin-resistant Staphylococcus aureus, 241–242 Orf virus, 129
Pseudomonas folliculitis, 242, 243 linear IgA dermatosis, 127–128
Biologics mucous membrane pemphigoid, 125
combination therapy/concomitant medications, 100 neonatal pemphigus
definition, 93 acantholysis, 122
dosage and administration, 94 in-vivo immunoadsorbent, placenta, 123
elderly, 100–101 nonthiol nonphenol drugs, 122
indications, 93–94 oral corticosteroids and plasmapheresis, 122
side effects pemphigus vulgaris (PV), 122
anaphylaxis/allergic reactions, 96–97 phenol drugs, 122
autoantibodies and autoimmunity, 96 thiol drugs, 122
blood disorders, 96 vaginal delivery, 122
cardiovascular disease, 95 pemphigoid gestationis, 124–125
hepatitis/hepatic dysfunction, 95–96 pemphigus
infections, 95 acantholysis, 119
malignancy, 96 desmoglein 3 and 1, 119
neurological disease, 95 endpoints, 121
pregnancy/breast-feeding, 97 enzyme-linked immunosorbent assay (ELISA), 119
skin irritation, 94 paraneoplastic pemphigus (PNP), 119, 120
treatment risk reduction strategies pemphigus foliaceus (PF), 120
baseline screening tests, 97–98 pemphigus vulgaris (PV), 119–121
periodic monitoring, 98 relapse/flare, 121
therapy, withdrawal of, 99–100 treatment failure, 121
treatment exclusion criteria, 97 Tzanck phenomenon, 119
tuberculosis risk, 99 variants, 119
vaccinations, 99 toxic epidermal necrolysis (TEN), 128
Biotin, 192 Bullous pemphigoid, 123–124
Bleeding Burns
antiplatelet effect, blood thinners, 267–268 airbag injuries, 112
hematomas, 268 anhydrous ammonia, 111
vasoconstrictor epinephrine, 268 betadine, 112
Body mass index (BMI), 188 burn severity, 111
Brass chills, 200 cement burns, 111–112
Bullous diseases chemical agents and medical management, 112
bullous pemphigoid chemical burns, workplace, 110–112
clinical variants, 123 chromic acid, 111
ELISA index, 124 degrees, 111
indirect immunoflourescence (IIF), 123, 124 fluid resuscitation, 112
prevention, 124 hydrofluoric (HF) acids, 110–111
dermatitis herpetiformis, 126–127 necrosis, 110
epidermolysis bullosa oral burns, 111
COL7A1 gene, 117 patient care, 112
collagen IV, immunohistochemical staining, 118 phenol, 111
DDEB and RDEB, 117 physical examination, 111
Dowling-Meara type of EB simplex (EBS-DM), 115 scars and pruritus, 110
fetal skin biopsy, 118 sulfur mustard, 112
gastrostomy, RDEB-HS, 117 systemic effect, 112
generalized severe type, 117 white phosphorus, 112
Herlitz JEB, 115, 116
laminin 5, 116 C
main inherited subtypes, 115, 116 Calcitriol, 86
muscular dystrophy, 115 Care delivery method, 59
preimplantation genetic diagnosis (PGD), 118 Casal’s necklace, 192
prenatal genetic diagnosis (PND), 118 Center for disease control and prevention
pyloric atresia, 116 (CDCP) report, 214–216, 219–221, 224
Index 309

Cervical cancer general prevention principles, 66

CIN II/III vaccination, 214, 215 nondermatologic symptoms, 66
HPV 16 and 18, 214–215 preventability, 64
pap testing, 215 serious and life-threatening, 64
sexually transmitted diseases, 215–216 specific medications
vaccine, 238 amiodarone, 69
Chamomile, 195–196 anticonvulsants, 68
Cheilitis corticosteroids, 67
allergic contact, 177 topical calcineurin inhibitors, 67–68
occurrence, 176 tumor necrosis factor alpha inhibitors, 68–69
xerotic, 176–177 Cyanocobalamin, 192
Chemically bonding collagen, 58
Child abuse prevention and treatment act (CAPTA), 36 D
Child sexual abuse. See Sexual abuse Defibrillators, 275
Cholecalciferol, 193 Dermatitis herpetiformis, 126–127
Chronic stasis dermatitis, 71 Diabetic ulcers
Chronic venous leg insufficiency (CVI), 52 footwear specifics, 252
Coenzyme Q10 (CoQ10), 194 incidence reduction, 251–252
Combination therapy, keloids, 288 multidisciplinary prevention approach, 252
Compression therapy, keloids, 286–287 Diaper dermatitis. See Perineal dermatitis
Condoms N, N-Diethyl-3-methylbenzamide (DEET), 244–245
air-burst test, 216 Dimethicone, skin protectants, 258
clinical trials, 218 Diphenhydramine, 147
effectiveness, 218 Dog ears. See Standing cones
laboratory tests, 216–217 Domestic violence, abuse, and neglect
mechanism of action, 216 abusers, common characteristics of, 37
“method” failure, 217 assessment and diagnoses, 41
prophylactic devices, 216 clinical assessments and diagnosis, dermatologist, 45
public education, 217–218 definition
sexual behavior change, 218–219 sexual abuse, 35, 36
“user” failure, 217 United States Centers for Disease Control and
water leak test, 216 Prevention, 35
Contact dermatitis, 295–296 healthcare provider, role of, 37, 39
eyelid dermatitis, 175 identification and assessment, patient
inflammation, 167–169 admissibility, records, 44–45
occupational (see Occupational contact dermatitis) physical examination, 43–44
perineal dermatitis, 253–255 record/chart, 44
Corneotherapy, 259 mandatory reporting, 37
Corticosteroids, 67 multidisciplinary approach, 45
monotherapy, 284 prevalence
polytherapy, 284–285 Bureau of Justice statistics, 41
Cosmetic problems violence-related injury, 42–43
acne, 183–185 statistics
cheilitis, 176–177 coin rubbing, 41
eyelid dermatitis, 175–176 cupping, 40–41
facial eczema, 173–175 dermatitis, 41
hyperhidrosis, 182–183 female genital mutilation (FGM), 40
over-the-counter (OTC) drug, 173 male victims, 39
postinflammatory hyperpigmentation, 177–181 moxibustion, 40
Cowpox, 208 women and children victims, 39, 40
Curcumin, 196 victims, common characteristics of
Cutaneous drug reactions children, 36
clinical classification elder abuse, 36
drug-induced erythema multiforme, 66 warning signs, 37, 38
exanthematous reactions, 65 Doxepin, 147
fixed drug eruptions, 65–66 Dystrophic epidermolysis bullosa (DEB), 115, 117, 118
Stevens–Johnson syndrome, 66
toxic epidermal necrolysis, 66 E
urticaria and angioedema, 65 Earlobe keloids, 285
frequency, 63–64 Eccrine perspiration, 182
Gell-Coombs classification, hypersensitivity reactions, 65 Echinacea, 196
310 Index

Eczema Craquelé, 71, 72 medications, 55

Efalizumab, 97 patient care, 54
EFUDEX®, 54, 55 patient history, 53–54
Elder sexual abuse. See Sexual abuse physical examination, 54
Emotional immaturity, 37 scope, 48
Epidemiology Senior Health Clinic note, 54–55
health literacy social work staff, 47
document literacy, 23 team creation, 49
prose literacy, 22 training, 50
quantitative literacy, 23 various patient groups
stasis dermatitis, 77 gerontological patients, 50–51
stress, 7 language difficulties, 52
xerosis, 73 pediatric patients, 50
Epidermolysis bullosa, 115–119 psychiatric patients, 51
Epidermolysis bullosa acquisita, 125–126 Health literacy
Epidermolysis bullosa simplex (EBS), 115, 118 age, 25–26
Ergocalciferol, 193 American Medical Association
Eyelid dermatitis (AMA), 22, 29
cleansers, 176 assessment tools
eczema, 176 newest vital sign (NVS), 23–24
eyelid, 175 rapid estimate of adult literacy in medicine
eyelid cosmetics, 175–176 (REALM), 23
irritant and allergic contact dermatitis, 175 test of functional health literacy in adults
moisturizers, 176 (TOFHLA), 23, 24
childhood and adolescent, 27
F cultural preferences, 30
Face transplants, 59 culture, race and ethnicity, 27
Facial eczema definition, 22
cleansers, 174–175 diabetic retinopathy rate, increase, 25
face, 173 education, 25
moisturizers, 173–174 effective patient–physician communication, 22, 29
Female genital mutilation (FGM), 40 epidemiology
Fish oil, 88 document literacy, 23
Flap and graft necrosis, 275–276 prose literacy, 22
Folliculitis, 300–301 quantitative literacy, 23
Foot ulceration, 251–252 hospitalization rates, 24
Fungal infections, 243, 299 Institute of Medicine (IOM), 22, 29, 32
joint commission on accreditation of healthcare
G organizations (JCAHO), 29
Garlic, 196 mortality, 27–29
General health, 293 national assessment of adult literacy (NAAL), 22
Genistein, 195 oral communication, 30
Genital warts, 298 parents and pediatric health, 26–27
Gingko biloba, 196 plain language, 30
Glutathione, 195 poor glycemic control, 25
Green tea, 86, 196 REALM-Teen, 31
teach back strategy, 30
H Tuskegee syphilis study, 31
Hair growth and transplantation, 59 Heel pressure ulcers, 260
Hand eczema, 296 Hemosiderosis, 200
Healthcare, multidisciplinary work Herpes gestationis factor, 125
assessment and plan, 54 Herpes simplex virus (HSV)
challenges, 48–49 dermatologic perspective, STD, 212–213
clinic follow-up, 55 genital herpes, 212–213
collaborative experience, 47 herpes gladiatorum, 213
communication, 50 HSV II seroprevalence, 213
dermatological care, 48 skin infection, 242–243
dermatological clinical staff call, 54 treatment, 296–297
disorders types, 296
atopic dermatitis (AD), 53 websites, 297
melanoma, 52–53 Herpes zoster (shingles), 234, 236
wound healing, 52 HIV reduction, Uganda
Index 311

abstinence and faithfulness, 226–227 Staphylococcus transmission, fomites, 161, 162

condom use, 226, 227 sterile surgical gloves, 269
global paradigm, 227–228 wrestlers, 162–163
pregnant women, 226 Inflammation
President Museveni, 225 allergic contact dermatitis, 167
Hot tub folliculitis, 243 exercise-induced anaphylaxis, 168, 169
Human herpes 3 (HHV3). See Varicella zoster virus (VZV) irritant contact dermatitis, 167–169
Human papilloma virus (HPV), 207–208 urticaria, 168
ACIP recommendations, 238 Inherited bullous diseases. See Bullous diseases
anogenital cancer, 214 Insect bites
CDCP report, 214 DEET, 244–245
CIN II/III, 214 fipronil, 245
dermatologic perspective, 213 lufenuron, 245
epidemiology, 237 mosquitoes, 244
genital warts, 213, 214 neem oil, 245
gynecologic perspective, 213–214 permethrin, 245
infection, 237 ticks, 245
intervention, 237–238 vector-borne disease, 244
life cycle, 237 Interferon, keloids, 287
papillomaviridae family, 236 Intranasal FluMist vaccine, 99
pap testing, 215 Isoflavone genistein, 195
pathogenicity, 237 Itchscratch cycle, 53
structure, 236
types 16 and 18 vaccination, 214–215 J
vaccine, 214–215, 238 Junctional epidermolysis bullosa
viral shedding, 214 (JEB), 115, 116, 118
Hydroquinone, 178
Hydroxycine, 147 K
5-Hydroxymethyl-4H-pyrane-4-one. See Kojic acid KEFLEX®, 55
Hygiene hypothesis, 137, 143 Keloids
Hyperhidrosis combination therapy, 288
antiperspirant efficacy optimization, 182–183 compression therapy, 286–287
antiperspirant mechanism of action, 182 corticosteroids, 284–285
perspiration, 182 earlobe keloids, 285
Hypertrophic scars (HTSs), 283 endocrine factors, 282–283
Hypothalamic-pituitary-adrenal (HPA) axis, 3, 4, 6 epidemiology, 281
etiology, 282–283
I genetic predisposition, 283
Imiquimod, 287–288 imiquimod, 287–288
Immunotherapy, atopic eczema, 143–144 infection, 282
Impetiginized wound, 241, 242 interferon, 287
Impetigo, 300 keloid avoidance behaviors, 288
Implantable cardioverter-defibrillators (ICDs), 275 laser surgery, 286
Infections pathogenesis, 283
antibiotic ointment, 270 preventative therapy, 283–288
chlorhexidine gluconate, 270 radiation therapy, 286
cleansing, 162 silicone products, 287
general infection techniques, 161–163 skin tension, 282
Herpes gladiatorum, 163 surgical method, 285
itraconazole, tinea corporis gladiatorum, 164 trauma, 282
MRSA, 163 Keratosis pilaris, 299–300
petrolatum, 270 Koebner phenomenon, 157
pitted keratolysis, 163–164 Kojic acid, 179
postoperative wound infection, 270
preventative measures, tinea pedis and L
tinea ungium, 161, 162 Laser surgery, keloids, 286
prevention techniques, skin infection, 161, 162 Leg ulcers, 51
prophylactic antibiotics, 269–270 Lice, 301
Pseudomonas folliculitis, 163 Licorice, 179, 196
risk factors, 268–269 Lifestyle abstinence, 219, 220
skin-to-skin contact, 161–162 Linear IgA dermatosis, 127–128
specific infection techniques, 163–164 Lower extremity arterial disease (LEAD), 252–253
312 Index

M Occupational contact dermatitis

Malnutrition allergic contact dermatitis, 106
obesity, 189 antimicrobial allergy, 107
protein–energy malnutrition, 188 barrier creams and moisturizers, 110
Measles (Rubeola), 205–206 causes, 106–108
Melanoma, 52–53 gloves, 110
Menkes kinky hair syndrome, 199 hairdressers and dog groomers, 107
Mequinol, 178 irritant contact dermatitis, 106
Methicillin resistant Staphylococcus aureus latex allergies, 107–108
(MRSA), 163, 241, 242 patch test, 108–110
Microfine zinc oxide, 85 prevention and treatment, 110
Minerals seafood processing, 107
acrodermatitis enterohepatica, 200 women, 107
adults, 198 Occupational dermatology
balanced intake, 199 burns, 110–112
calcium, 199 chrome holes, 106
children, 197 diagnosis, 103–104
copper, 199–200 occupational acne, 105
hemosiderosis, 200 occupational dermatitis, 106–110
hypercalciuria, 199 occupational skin cancers, 105
iron, 200 occupational skin infections, 105, 106
Menkes kinky hair syndrome, 199 phototoxic and photoallergic reactions, 105
metal-fume fever, 200 pigment changes, 105
osteoporosis, 199 segmental vibration, 106
RDA, 197–199 skin notations, 105
selenium, 200 worker’s compensation system, 104–105
Wilson’s disease, 199–200 Occupational skin cancers. See Skin cancer
zinc, 200 occupational skin cancers, 105
Molluscum contagiosum, 298 Octinoxate, 84
Mucous membrane pemphigoid, 125 Onychomycosis, 299
Mumps, 206 Oxybenzone, 84

N P
N-acetylcysteine (NAC), 88 Pacemakers, 275
Nail fungus infection, 299 Pantothenic acid, 192
Narcissism, 37 Pap testing, 215
National Elder Abuse Incidence Study, 37 Paramyxoviruses, 205–206
National Health and Nutrition Examinations Survey Paraneoplastic pemphigus (PNP), 119, 120
(NHANES), 213 Parental health literacy. See Health literacy
Neonatal pemphigus, 121–123 Patch testing
Nerve damage, surgery, 274–275 Finn chamber test, 109–110
Neurodermatitis, 301–302 TRUE test, 108–109
Nitrogen balance, 263 Pathogenesis
Nutrition. See also Malnutrition; Supplements; Vitamins stasis dermatitis, 77
biochemical data, 263 xerosis, 72–73
definition, 187 Patient interviews, 39
malnutrition, 262 Pemphigoid gestationis, 124–125
nitrogen balance, 263 Pemphigus, 119–121
nutritional assessment, 262 Perineal dermatitis
risk factors, 262 absorptive and/or occlusive devices, 254
vitamins and minerals, 263 assessment tools, 253–254
WHO report, 187 Braden risk assessment score, 255
causes, 253
O denudation, 255
Obesity and nutrition grading scale, 253–254
obesity prevention and nutritional education, 19 interventions, 254
prevention programs, 19 perineal skin injury, 253
risk synergy and integrating prevention, 19–20 underpads, 254–255
skin complications, 18–19 Peripheral vascular disease
skin disorders, 19 (PVD), 252–253
Index 313

Perirectal skin assessment tool (PSAT), 253–254 psoralen, 159

Photoprotection remicade, 156, 159
recommendations and rationales risk factors/triggers, 153–154, 157
automobile glass, 90 severity/types/distribution, 152
clothing, 88–89 soriatane, 156, 158
hats, 89 systemic therapy, 155–156
inorganic filters, 85 taclonex, 155, 157
makeup, 89 tazorac, 155, 157–158
organic ultraviolet A (UVA) filters, 84–85 topicals, 154–155
organic ultraviolet B (UVB) filters, 84 topical steroids, 155, 158
shade, 88 treatment, 154–157, 297
shadow rule, 82 websites, 297
sunglasses, 89–90 Psychodermatologic disorders, 51
sunless tanning agents, 89 Pycnogenol, 196
sunscreen, 82, 83, 85–86 Pyridoxine, 192
topical, oral, and dietary photoprotection agents, 86–88
vitamin D oral supplementation, 83 R
window glass, 90 Radiation therapy (RT), keloids, 286
ultraviolet (UV) radiation, cutaneous effects, 81–82 Raynaud’s phenomenon, 106
Polidocanol, 146 Recommended daily allowances (RDA)
Polypodium leucotomos, 88 fat-soluble vitamins, 191
Postinflammatory hyperpigmentation minerals, 197–199
nonprescription topical agents, 179–180 water-soluble vitamins, 190
prescription topical agents, 178–179 Resveratrol, 196
skin-lightening ingredients, 177 Riboflavin, 192
sunscreens, 180–181 Rocky mountain spotted fever, 244
Postoperative scars, pain, and pruritus, 272–273 Rosacea, 294–295
Poxviruses, 208 Rubella (German measles), 206
Pressure ulcers
causes, 259 S
geriatric patient, 259 Safe sex, 219
guidelines, 260 Scabies, 301
heel pressure ulcers, 260 Serum albumin, 263
prevalence, 259 Sexual abuse, 35–37, 40, 44, 45
prevention, 260–261 Sexually transmitted diseases (STD)
skin and tissue breakdown, 259 abstinence, 219, 220
support surfaces, 261–262 adverse consequences, 212
Procyanidins, 195 age and gender matched abstinence analysis, 221
Psoriasis center for disease control and prevention (CDCP) report,
amevive, 156, 159 214
anthralin cream, 157 cervical cancer, 215–216
biologics, 156, 158–159 clinical manifestation, 211–212
Crohn’s disease, 153 condom strategy, 216–219
cyclosporine, 155–156, 158 dermatologic perspective, 212–213
depression, 154 ethnicity, 220
diet, 157 global paradigm, 227–228
dovonex, 154, 157 herpes simplex virus, 212–213
genetics, 152–153 human papilloma virus, 213–215
health education, 159 lifestyle abstinence counseling, 221, 223
inflammatory bowel disorders, 153 management, 211
methotrexate, 156, 158 oral sex, 219
myocardial infarction (MI), 154 patient response, counseling, 221, 223
obesity, 153 physician counseling style, 221
onset, 151 prevention in office, 219–224
oral medications, 158 prophylactic device, 211
pathogenesis, 151 recommended guidelines, 219–220
phototherapy, 156–157, 159 return for care, 221, 223
prevalence/incidence, 151 risk elimination counsel, 221
prevention, 157–159 safe sex, 219
prevention tips, 297 sexual abstinence counsel, 221, 222
314 Index
sexual behavior change, 225–227
skin and STD relationship, 223–224
trends and expectations, STD
prevention, 224
Uganda, 225–227
Silicone gel sheeting (SGS), 284, 287
Silymarin, 196
Skin cancer, 105, 293–294
Skin care
cleanser, 256
dry skin, 257–258
moisturizers, 256–257
products, 257
skin hydration, 256–258
skin nutrition, 258–259
skin protectants, 258
soaps and surfactants, 256
xerosis, 257–258
Skin infections
arthropod-borne infections, 244–245
bacterial infections, 241–243
fungal infections, 243
surgical wound infections, 243–244
viral infections, 242–243
Skin performance assessment, 303–305
Skin tears, 262
Smallpox (Variola), 208
Smoking
collagen and elastin, damage, 18
health education programs, 18
hydrophobic agents, 17
poor wound healing, 17, 18
premature aging, 17, 18
premature wrinkling, 18
risk synergy and integrating
prevention, 19–20
Soybean, 196
Spitting sutures, 275
Sports dermatology
athletic clothing, 170
environmental encounters, 168–170
green hair, 170
infections, 161–164
inflammation, 167–168
insect attacks, 170
sun safety, 169–170
trauma, 164–167
ultraviolet damage, 168–169
Standing cones, 273
Staphylococcal folliculitis, 241, 242
Stasis dermatitis
compression, 78
deep venous thrombosis (DVT), 77
emollient therapy, 78
epidemiology, 77
exercise, 78
gaiter, 76
leg elevation, 78
pathogenesis, 77
pharmaceutical interventions, 78
predisposing factors, 77
Stress
acute and chronic, 3
allostasis, 3–4
epidemiology, 7
fight-or-flight response, 3
General Adaptation Syndrome, 3
immune function and skin
atopic dermatitis, 6
catecholamine (CA), 4
central neuroendocrine stress mediators, 5
flares and psoriasis, 6
glucocorticoids (GC), 4, 5
hypothalamic-pituitary-adrenal (HPA) axis, 4, 6
lipopolysaccharides, 4–5
malignancy, 6, 7
matrix metalloproteinases (MMPs), 6
nerve growth factor (NGF), 6
squamous cell carcinomas (SCCs), 7
Th1 and Th2-derived cytokines, 4
tissue inhibitors of metalloproteinases (TIMPs), 6
Stress-reducing modalities
aromatherapy, 9–10
autogenic training, 11–12
biofeedback, 11
deep breathing, 8
hypnosis, 12
massage therapy, 10
mindfulness meditation, 10–11
prayer, 12–13
progressive muscle relaxation, 9
QI Gong/Reiki/healing touch, 12
Tai Chi, 8–9
yoga, 7–8
Sun damage, 293–294
general risk, 19
risk synergy and integrating prevention, 19–20
Sun protection factor (SPF), 81–86, 89, 91
Sunscreen, 82, 83
compensation hypothesis, 85
contact, photocontact, and phototoxic reactions, 85
hormonal effects, 85–86
Sunscreens
cosmeceutical, 180
efficacy, 181
longevity, 181
sun protection factor, 181
tanning response, 180–181
UVA filters, 180–181
water-resistant, 181
Supplements. See also Nutrition; Vitamins
antioxidants, 193–196
minerals, 197–200
Surgical complications
allergic reactions, 271–272
anesthetic toxicity, 273–274
bleeding, 267–268
defibrillators and pacemakers, 275
flap and graft necrosis, 275–276
infection, 268–270
litigation, 276
nerve damage, 274–275
Index 315

postoperative scars, pain, and pruritus, 272–273 pressure, 259–262

spitting sutures, 275 venous insufficiency, 249–252
standing cones, 273
trap door (pincushioning) deformities, 275 V
vasovagal reaction, 276 Vaccines, viral diseases. See also Viral vaccines
Surgical wound infections, 243–244 Edward Jenner’s vaccine, 233
human papilloma virus, 236–238
T varicella zoster virus, 233–236
Teledermatology, 59 vexing diseases, 233
T4 endonuclease V (T4N5), 57 Varicella (chickenpox), 234
Thiamine, 192 Varicella zoster virus (VZV), 206–207
Tinea infection, 243 ACIP provisional recommendations, 236
Titanium dioxide, 85 epidemiology, 233–234
Toad skin, 190, 200 herpesviridae family, 233
Toe brachial index (TBI), 250 herpes zoster (shingles), 234, 236
Topical calcineurin inhibitors, 67–68 immunization practices, 235–236
Topical therapy life cycle, 234
aleosin, 179–180 structure, 233
alpha lipoic acid, 179 varicella (chickenpox), 234
antiperspirants, 165 Vasovagal reaction, 276
arbutin, 180 Vector-borne disease, 244
ascorbic acid, 179 Venous insufficiency ulcers
azelaic acid, 179 ankle brachial index (ABI), 250
calcineurin inhibitors, 145–146 causes, 249, 250
clothing, 144 circulatory status determination, 250
corticosteroids, 145 compression hosiery, 251
dovonex, 154–155 diabetic ulcer, 251–252
emollients, 144 peripheral vascular disease (PVD), 250
hydroquinone, 178 prevention tactics, 249–250
imiquimod, 287–288 Vexing diseases, 233
Kojic acid, 179 Viral infections, 242–243
licorice extract, 179 Viral vaccines
lidocaine, 273 cowpox, 208
mequinol, 178 efficacy, 205
skin care, 144 human herpes viruses, 206–207
synthetic detergents, skin, 144 human papillomavirus, 207–208
taclonex, 155 measles, 205–206
tazorac, 155 measles, mumps, and rubella (MMR) vaccine, 205
tretinoin, 178 mumps, 206
Transepidermal water loss (TEWL), 173–174 paramyxoviruses, 205–206
facial moisturizers, 173–174 poxviruses, 208
lip balms, 177 rubella, 206
perineal dermatitis, 254 smallpox (variola), 208
skin hydration, 256 types, 205
skin nutrition, 258 varicella zoster virus, 206–207
Trapdoor deformity, 275 Vitamin C. See Ascorbic acid
Trauma Vitamins. See also Nutrition; Supplements
acne mechanica, 167, 168 acute vitamin A intoxication, 191–192
callosities, 165–166 adults, 190, 191
friction bullae, 164–165 anemia, 192
nodules, 166–167 balanced diet, 191
shoe lacing techniques, 164, 165 B vitamins, 192
toenail abnormalities, 167 children, 190, 191
Tretinoin, 178 definition, 189
Triamcinolone acetonide (TAC), 284 fat-soluble vitamins, 191
Tumor necrosing factor-alpha (TNF-a), 68–69, 95 hemorrhage, 193
hypervitaminosis/hypovitaminosis, 189–193
U pellagra, 192
Ulcers phrynoderma, 190
arterial and ischemic, 252–253 recommended daily allowances (RDA), 189, 190
diabetic, 251–252 scurvy, 193
316 Index

vitamin A, 189–192 full-circle-prevention, 263–264

vitamin C, 192–193 nutrition, 262–263
vitamin D, 193 perineal dermatitis and denudation, 253–255
vitamin E, 193 pressure ulcers, 259–262
vitamin K, 193 prevention and reimbursement, 263
water-soluble vitamins, 190 skin care, 256–259
skin functional changes, 249, 250
W skin tears, 262
Warts, 298. See also Genital warts venous insufficiency ulcers, 249–252
Wounds
infections X
bacitracin vs. petrolatum, 244 Xerosis, 257–258, 297
clindamycin, 243 epidemiology, 73
incidence, 243 moisturizer and soap-substitute, 75
retapamulin, 244 moisturizing, adverse effects, 76
risk, Mohs surgery, 243 occupational factors, 76
prevention pathogenesis, 72–73
aging, chronic wounds, 249 prevention, 73–74
arterial and ischemic ulcers, 252–253 specific body areas, 76