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Acknowledgments
Our thanks to Dr. Christopher Sayed, Dr. Julia Lehman, Dr. Phillip Hochwalt, and Dr. Anwar Qais
Saadoon as they each contributed photos to the cover.
We would also like to thank Elsevier as well as our terric Section Editors for making this book
possible.
ix
Preface
Purpose of this book
We envision this book serving as a comprehensive review for
dermatology residents and practicing dermatologists. We
hope that the book is used not only in the United States, but
all over the world.
How the book should be used
The book can be used in many ways:
• As a resource for practicing dermatologists preparing for
recertication examinations or simply as a quick reference.
• As a resource for dermatology residents preparing for
board examinations, in-service examinations, or simply as
a quick reference (it could even be used throughout
residency as a place to compile notes and facts learned
from reading textbooks and journal articles, much the way
First Aid
©
was used during medical school).
How the book should NOT be used
There is NO substitution for reading textbooks and journal
articles during residency. This book should serve as a review or
a syllabus of dermatology, but should not take the place of
textbooks and original literature. Many great resources to truly
learn dermatology exist—our favorites are Dermatology (commonly referred to as “Bolognia”), Andrews’ Diseases of the Skin,
Comprehensive Dermatologic Drug Therapy (commonly referred
to as “Wolverton”), The Requisites in Dermatology Series (particularly dermatopathology and dermatologic surgery), Practi-
cal Dermatopathology (commonly referred to as “Rapini”), and
Hurwitz Clinical Pediatric Dermatology.
Other information
Please remember that space was limited for this book, as it is
for all books—we had to make important choices to leave
certain information out of the book.
We are extremely grateful to the authors and editors of the
textbooks listed above, as well as those of McKee’s Pathology of
the Skin and Weedon’s Skin Pathology, as nearly all of the gures
came from these resources.
Despite reading and re-reading this text many times, we
imagine that some errors may have snuck by. We encourage
you to email us at reviewofdermatology@gmail.com with any
errors or suggestions so we can correct these for our third edition. Please also email us if you have ideas to improve the
book or would like to contribute to future editions.
x
Contents
1 BASIC SCIENCE 1
Linda T. Doan and Tiffany C. Scharschmidt
1.1 Structure and Function of the Skin 1
1.2 Embryology 13
1.3 Wound Healing 13
1.4 Genetics 15
1.5 Ultraviolet Light 17
1.6 Immunology 18
1.7 Laboratory Techniques 28
2 DERMATOPHARMACOLOGY 39
Alexander Maley and Ali Alikhan
2.1 Antihistamines 39
2.2 Retinoids 40
2.3 Corticosteroids 42
2.4 Immunomodulatory Agents 46
2.5 Oncologic Agents in Dermatology 54
2.6 Antimicrobial Agents 57
2.7 Phototherapy 65
2.8 Miscellaneous Agents 67
2.9 Drug Interactions and the Cytochrome
P-450 System 70
2.10 Drug Reactions 71
3 GENERAL DERMATOLOGY 79
Christopher Sayed, Ali Alikhan, Olayemi Sokumbi,
Anand Rajpara, and Julia S. Lehman
3.1 Papulosquamous Dermatoses 79
3.2 Eczematous Dermatoses 86
3.3 Interface Dermatitis 96
3.4 Blistering Diseases 107
3.5 Connective Tissue Disease (CTD)
and Sclerosing Dermopathies 119
3.6 Granulomatous/Histiocytic Disorders 149
3.7 Monoclonal Gammopathies of
Dermatologic Interest 161
3.8 Xanthomas 164
3.9 Urticaria and Angioedema 166
3.10 Neutrophilic Dermatoses 169
3.11 Eosinophilic Disorders 172
3.12 Figurate Erythemas 173
3.13 Follicular and Eccrine/Apocrine Disorders 176
3.14 Drug Reactions 184
3.15 Photodermatoses and Other Physical
Dermatoses 184
3.16 Amyloidoses 188
3.17 Neurodermatology and Psychodermatology 189
3.18 Palmoplantar Keratodermas 192
3.19 Nutritional Disorders in Dermatology 192
3.20 Depositional and Calcication
Disorders Not Discussed Elsewhere 194
3.21 Ulcers 194
3.22 Vasculitides, Vasculopathies,
and Other Vascular Disorders 194
3.23 Panniculitides and Lipodystrophies 210
3.24 Dermatoses of Pregnancy 212
3.25 Hair, Nail, and Mucosal Disorders 212
3.26 Pigmentary Disorders 220
4 PEDIATRIC DERMATOLOGY 229
Brea Prindaville and Jennifer J. Schoch
4.1 Neonatal Dermatology 229
4.2 Viral Exanthems and Select Infectious
Disorders of Childhood 229
xi
Contents
4.3 Inherited Pigmentary Disorders 240
4.4 Epidermolysis Bullosa 244
4.5 Tumor Syndromes 248
4.6 Vascular Tumors, Malformations,
and Related Vascular Disorders 250
4.7 Disorders of Hair and Nails 255
4.8 Inherited Metabolic and Nutritional
Disorders 258
4.9 Inherited Connective Tissue Disorders 263
4.10 Autoinammatory Disorders (Periodic
Fever Syndromes) 269
4.11 Neurocutaneous Syndromes 271
4.12 Premature Aging Syndromes and DNA
Repair Disorders 275
4.13 Primary Immunodeciency Disorders
With Cutaneous Manifestations 278
4.14 Disorders of Cornication 278
4.15 Miscellaneous Pediatric Dermatologic
Disorders 281
5 INFECTIOUS DISEASES 293
Ali Alikhan and Thomas L.H. Hocker
5.1 Viral Diseases 293
5.2 HIV/AIDS Dermatology 301
5.3 Bacterial Infections 304
5.4 Fungal Diseases 322
5.5 Parasites and Other Creatures 329
6 NEOPLASTIC DERMATOLOGY 337
Monisha N. Dandekar, Roberto A. Novoa, and
Phillip C. Hochwalt
7 DERMATOPATHOLOGY 391
Julia S. Lehman and Roberto A. Novoa
7.1 Essential Concepts in Dermatopathology 391
7.2 High-Yield Dermatopathology Diagnoses
at a Glance 415
7.3 High-Yield Dermatopathology Differential
Diagnoses 415
8 DERMATOLOGIC SURGERY 443
Phillip C. Hochwalt and Thomas L.H. Hocker
8.1 Surgical Anatomy 443
8.2 Local Anesthetics and Perioperative
Pain Control 450
8.3 Surgical Instruments
and Needles 454
8.4 Suture Techniques 455
8.5 Wound Closure Materials 455
8.6 Antisepsis and Sterilization 458
8.7 Electrosurgery 458
8.8 Cryosurgery 461
8.9 Excisions 461
8.10 Mohs Surgery 463
8.11 Flaps 463
8.12 Grafts 472
8.13 Surgical Complications
and Measures to Avoid Them 473
8.14 Scar Improvement 476
8.15 Nail Surgery 477
8.16 Wound Dressings 479
Neoplastic Dermatology 337
6.1 Keratinocytic Neoplasms 337
6.2 Cysts 343
6.3 Melanocytic Neoplasms 344
6.4 Adnexal Neoplasms
and Hamartomas 351
6.5 Hair Follicle Neoplasms/Hamartomas 359
6.6 Sebaceous Proliferations 363
6.7 Neural Neoplasms 364
6.8 Smooth Muscle Neoplasms 367
6.9 Hematolymphoid Neoplasms 368
6.10 Fibrohistiocytic Neoplasms 373
6.11 Vascular Proliferations 378
6.12 Neoplasms of Adipocytic Lineage 382
6.13 Dermoscopy 382
xii
9 COSMETIC DERMATOLOGY 481
Ronda S. Farah
9.1 Lasers 481
9.2 Botulinum Toxin 488
9.3 Dermal Fillers 491
9.4 Liposuction and Fat Reduction 494
9.5 Sclerotherapy and Vein Management 494
9.6 Cosmeceuticals, Nutraceuticals,
and Other Supplements 497
9.7 Hair Transplantation 498
9.8 Chemical Peels 498
9.9 Other Esthetic Procedures and Scales 500
Contents
10 CUTANEOUS MANIFESTATIONS OF
INTERNAL DISEASE AND
METASTASES 505
Nada Elbuluk
10.1 Cardiovascular/Cardiopulmonary 505
10.2 Endocrine 512
10.3 Gastroenterology 514
10.4 Neurology 519
10.5 Renal 519
10.6 Paraneoplastic Syndromes 520
11 EPIDEMIOLOGY, STATISTICS,
STUDY DESIGN, PUBLIC HEALTH
PRINCIPLES, AND BILLING 527
Jonathan I. Silverberg and Alexander Maley
11.1 Epidemiologic Denitions 527
11.2 Epidemiologic Principles 527
11.3 Types of Studies and Their Limitations 528
11.4 Types of Bias 530
11.5 Maintenance of Certication for
the American Board of Dermatology 530
11.6 Billing 530
Index 535
xiii
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1
Basic Science
Linda T. Doan and Tiffany C. Scharschmidt
CONTENTS LIST
1.1 STRUCTURE AND FUNCTION OF THE SKIN
1.2 EMBRYOLOGY
1.3 WOUND HEALING
1.4 GENETICS
1.5 ULTRAVIOLET LIGHT
1.6 IMMUNOLOGY
1.7 LABORATORY TECHNIQUES
1.1 STRUCTURE AND FUNCTION OF THE SKIN
• Functions: interfaces with environment, collects sensory
data, protects against infection and chemical penetration,
temperature regulation, water retention, and excretion of
drugs/waste
• Composed of three layers: epidermis, dermis, and
subcutis
Epidermis
Cellular biology of the epidermis
• Squamous epithelium composed of keratinocytes
connected by desmosomes, adherens junctions, tight
junctions, and gap junctions (Table 1.1)
■
Intercellular junctions
Desmosomes: primary keratinocyte intercellular
junction
◆ Provide structure and integrity to the epidermis
by anchoring/attaching to keratins
◆ Components (see Table 1.1)
◆ Desmocollins, desmogleins, and other cadherins
are calcium-dependent
Adherens junctions: also mediate tight intercellular
binding (Fig. 1.1)
◆ Anchor/attach to actin laments
◆ Consist of a-catenin (cytoplasmic), b-catenin
(cytoplasmic), plakoglobin (cytoplasmic), and
classic cadherins (E and P; transmembrane)
Tight junctions: composed of claudins and
occludin; form tight seal against water loss in
granular layer
Gap junctions: facilitate intercellular communication;
composed of connexons (tubular channels composed
of six connexins)
• Cells originate in the cuboidal basal layer and atten out
as they ascend to the surface—four to ve layers/strata
(deep to supercial): s. basale, s. spinosum, s.
granulosum, s. lucidum (only on palmoplantar surfaces),
and s. corneum (Table 1.2)
• An increasing total (intra- and extracellular) calcium
gradient is present in the epidermis, with low levels of
calcium in the stratum basale and increasingly higher
levels of calcium toward the stratum granulosum
■
Multiple calcium-dependent processes in the epidermis
are driven by the calcium gradient including
keratinocyte maturation, desmosome formation,
transglutaminase function, cleavage of prolaggrin, and
extrusion and degradation of keratohyalin granules
• Stratum basale: mitotically active cuboidal cells from
which the upper layers of the epidermis are derived
■
Attached to dermis by hemidesmosomes
■
Cellular proliferation stimulated by various factors,
including trauma and UV (↑ ornithine decarboxylase
expression is associated with (a/w) proliferative
states)
Ornithine decarboxylase is inhibited by
corticosteroids, retinoids, and vitamin D3
■
10% of cells in the basal layer are stem cells, which give
rise to other stem cells, and to transient amplifying
cells that will replicate for a few cycles until they
1
CHAPTER 1 • Basic Science
Table 1.1 Intercellular Junction Proteins
Junction Type Protein Family Protein Disease State
Desmosome
Anchor/attach to keratin filaments
Desmosome and adherens junction Armadillo (catenin)
Adherens junction
Attach to actin laments
Gap junction
Facilitate intercellular communication.
Important for calcium regulation
PNP, paraneoplastic pemphigus; PV, pemphigus vulgaris; PPK, palmoplantar keratosis; SSSS, staph scalded skin syndrome; SPD, subcorneal pustular derma-
tosis; KID, keratosis ichthyosis deafness syndrome
Cadherin (transmembrane)
Cadherins are calcium-
dependent transmembrane
proteins.
Plakin (cytoplasmic) Desmoplakin Carvajal syndrome
Armadillo (cytoplasmic) Plakophilin Ectodermal dysplasia with skin fragility
(cytoplasmic)
Cadherin (transmembrane) E-Cadherin Somatic mutations in many neoplasms
Armadillo (cytoplasmic)
Connexin (transmembrane) Connexin 26 (GJB2) Vohwinkel syndrome, KID syndrome, Bart-Pumphrey
Desmoglein 1 Autoimmune: pemphigus foliaceus, PNP, PV (mucocutane-
Desmoglein 3 Pemphigus vulgaris (mucosal-predominant and
Desmoglein 4 Monilethrix (autosomal recessive form), autosomal
Desmocollin 1 IgA pemphigus (SPD type)
Desmocollin 2 Carvajal-like phenotype in one family
Desmocollin 3 Hypotrichosis
Plakoglobin Naxos syndrome
b-Catenin
Connexin 30 (GJB6) Hidrotic ectodermal dysplasia
Connexin 30.3 (GJB 4) Erythrokeratoderma variabilis
Connexin 31 (GJB 3) Erythrokeratoderma variabilis
ous form), IgA pemphigus (intraepidermal neutrophilic type)
Inherited: striate PPK
Infectious: bullous impetigo and SSSS
mucocutaneous forms), PNP, IgA pemphigus
(intraepidermal neutrophilic type)
recessive hypotrichosis
Somatic mutations in many neoplasms, including
pilomatricomas; also may be seen in myotonic
dystrophy and Rubinstein-Taybi
syndrome, PPK with deafness; also common in non-
syndromic deafness!
differentiate and move upward, eventually
desquamating
■
Transit time from basal layer to stratum corneum 5 14
days; transit through the stratum corneum/
desquamation 5 14 days (total 5 28 days from basal
layer to desquamation)
• Stratum spinosum: named for the “spiny” appearance
of intercellular desmosomal connections on
microscopy
■
Contains multiple types of intercellular junctions
■
Terminal keratinocyte differentiation 2° to ↑ calcium
in suprabasal epidermis
■
Odland bodies (lamellar granules) are produced by
Golgi bodies in spinous layer
Primarily contain ceramide (most important
lipid involved in epidermal barrier function),
along with glycoproteins, glycolipids, and
phospholipids
Are specialized lysosomes that exert most of their
action in the stratum corneum, by discharging
ceramides and other lipids into the extracellular
space of the junction between the stratum
granulosum and stratum corneum → ceramides
help form the cornied cell envelope (see below),
and eventually replace the cell membrane
• Stratum granulosum: attened cells with prominent
basophilic keratohyalin granules, which contain
prolaggrin (converted to laggrin at the junction of
stratum granulosum and stratum corneum), loricrin,
keratin intermediate laments, and involucrin
■
Cells begin to lose nuclei, but keep overall structure
■
Cornied cell envelope production primarily takes
place in the granular layer (Fig. 1.2)
Cross-linked protein and lipid structure encased in
extracellular lipids forming a strong polymer that
eventually replaces the plasma membrane
◆ Process starts with envoplakin, periplakin, and
involucrin scaffolding along the inner cell
membrane (which is eventually replaced by
ceramides from lamellar granules)
◆ Further reinforcement by cross-linking loricrin
(a major component of cornied envelope, rst
appears in granular layer; mutated in Vohwinkel
syndrome variant lacking deafness), small
proline-rich proteins, keratin, and laggrin
◆ Cross-linking occurs via transglutaminase 1 →
g-glutamyl lysine isopeptide bonds (Boards
factoids: TG-1 is mutated in lamellar ichthyosis;
TG-3 is antigenic target in dermatitis herpetiformis)
◆ Other components include envoplakin (helps
connect desmosomes to cornied envelope),
periplakin, elan, and others
◆ Outer surface of the cornied envelope is
ultimately surrounded by lipids (primarily
ceramide) 5 cornied lipid envelope
◆ Ultimately provides strong water-impermeable
outer barrier
• Stratum corneum: outermost layer, which serves as a
mechanical barrier between the epidermis and the
environment
2
THE ADHERENS JUNCTION AND DESMOSOME
A B
Actin
Intercellular space
Actin
PG
α
α
β
NC
Cad
Cad
Cad
Cad
PG
Cad
Cad
Cad
Cad
α
CN
α
β
Keratin
PG
DP
PP
DP
PG
Intercellular space
NC
Dsc
Dsg
Dsc
Dsg
Dsg
Dsc
Dsg
Dsc
Cytoplasm
Plasma membrane
Classic cadherin (Cad)
Plakoglobin (PG)
β-catenin (β)
α-catenin (α)
Fig. 1.1 The adherens junction and desmosome. (A) The adherens junction complex contains classic cadherins as transmembrane constituents, and a-catenins, bcatenins, and plakoglobin as cytoplasmic constituents. A classic cadherin is directly coupled through its cytoplasmic tail to b-catenin or plakoglobin, which in turn is
linked to b-catenin, which binds to actin. (B) The desmosome complex includes desmogleins and desmocollins as transmembrane constituents, and plakoglobin,
plakophilin, and desmoplakin as cytoplasmic constituents. Desmogleins and desmocollins associate with plakoglobin, which in turn binds to desmoplakin and links
keratin to the membrane. C, Carboxy-terminus. N, amino-terminus. (From Amagai M. Pemphigus. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed.
Philadelphia: Elsevier; 2018:494–509.)
Desmoglein (Dsg)
Desmocollin (Dsc)
Plakoglobin (PG)
Plakophilin (PP)
Desmoplakin (DP)
Keratin
PG
DP
PP
DP
CN
PG
1.1 Structure and Function of the Skin
3
CHAPTER 1 • Basic Science
Table 1.2 Layers of the Epidermis
Epidermal Layer Stage of Maturation Products of Significance Associated Diseases
S. basale 10% of cells in basal layer are stem cells Keratin 5/14 Epidermolysis bullosa simplex
S. spinosum Terminal keratinocyte differentiation secondary to
↑ intracellular calcium
S. granulosum Cells lose nuclei, flatten, produce keratohyalin
granules (KHG) which contributes to the cornified
cell envelope which forms beginning in this layer
S. corneum Anucleate, protein-rich corneocytes
Keratin 1/10 Epidermolytic ichthyosis
Odland bodies (lamellar granules)
Contains ceramides
KHG which contain profilaggrin,
loricrin, keratin IF, and involucrin
Flegel’s and Harlequin’s ichthyosis are
2° to ↓ lamellar granules.
X-Linked ichthyosis 2° to absent ste-
roid sulfatase in lamellar granules
Ichthyosis vulgaris (laggrin)
Atopic dermatitis (laggrin)
Vohwinkel without deafness (loricrin)
■
Composed primarily of protein-rich corneocytes
(“bricks”; normally contain NO nuclei; keratin
laments attached to cornied envelope) embedded in
a lipid matrix (“mortar,” cornied lipid envelope)
■
Serves as a barrier to water loss (conditions that perturb
the skin barrier → ↑ transepidermal water loss) and
toxins/infectious agents
Epidermal cells of importance
• Keratinocytes: the primary cells of the epidermis;
responsible for producing proteins (e.g., keratin laments)
and lipids important for barrier function
■
Keratins: intermediate laments that comprise the
primary cytoskeleton of the epidermis (Table 1.3)
Type I keratins: low molecular weight; acidic; K9-
28, K31-40 (hair keratins); chromosome 17
Type II keratins: high molecular weight; basic; K1-
8, K81-86 (hair keratins); chromosome 12
Basic structure is an a-helical rod domain
(consisting of heptad amino acid repeats) divided
into four segments (1A, 1B, 2A, and 2B) that are
interrupted by three non-helical segments
(“linkers”)
Functional unit consists of heterodimers of type I
and type II laments that form tetramers and
ultimately laments
Anchored to plasma membrane by desmosomes
40 to 70 kD
■
Keratinocytes produce IL-1, IL-6, IL-8, IL-10, IL-12, and
TNF-a, among others
■
Keratinocytes respond to IL-2, IL-4, IL-13, IL-22, and
TNF-a, among others
• Melanocytes: Neural crest-derived, melanin-producing
cells; dendritic morphology; found in the stratum basale
in1:10 ratio with keratinocytes (when viewed in twodimensional plane)
■
c-kit activation is needed for melanocyte
development/migration; piebaldism occurs as a result
of c-kit loss → impaired melanocyte migration and
proliferation; c-kit mutations are a/w mucosal and
acral melanoma
■
Each melanocyte interfaces with 36 keratinocytes
when analyzed three-dimensionally (epidermal
melanin unit)
■
Melanin is produced in melanosomes (lysosome-type
organelles) from its precursor, tyrosine, through a
multistep enzymatic process involving tyrosinase
(copper-dependent enzyme)
Tyrosine
(tyr osinase -depend ent ste p)
→ DOPAquinone →
(tyr osinase -depend ent ste p)
→ DOPA
pheomelanin (yellow/red; made by round
melanosomes) or eumelanin (black/brown; made
by elliptical melanosomes)
Melanosomes are transported along the dendritic
processes and transferred to keratinocytes through
phagocytosis of dendrite tips
Racial variation in pigmentation: identical
melanocyte density in dark- and light-skinned
individuals; melanosomes in darker-skinned
individuals are larger, darker (↑ melanin), more
stable, and are transferred individually (vs.
smaller, lighter, less stable, and clustered
melanosomes in lighter-skinned individuals)
Melanin production is stimulated by melanocytestimulating hormone (MSH) and ACTH activity on
MC1-R on melanocytes; also stimulated through
various pathways induced by UV radiation
SOX10 is a transcription factor that controls
melanocyte differentiation
MC1-R loss of function mutations → ↑
pheomelanin:eumelanin ratio (phenotype 5 red
hair/fair skin, ↑ risk of melanoma)
Melanin absorbs UV → protects against UV-induced
mutations
UV exposure → biphasic tanning response:
immediate tanning (from oxidation and
redistribution of existing melanin) and delayed
tanning (occurs with new melanin synthesis,
melanocytic proliferation, increased transfer of
melanin from melanocyte to keratinocyte). (See
Section 1.5 for discussion on roles of UVA and UVB
in tanning).
■
Other high-yield examination facts:
Defects in enzymes required to convert tyrosine to
melanin → oculocutaneous albinism; OCA1
(Tyrosinase), OCA2 (P gene), OCA3 (TRP-1)
Defects in packaging of melanosome-specic
proteins → Hermansky-Pudlak syndrome (HPS1 .
HPS3 . other gene mutations)
Defects in lysosome and melanosome trafcking to
dendrites → Griscelli (MYO5A, RAB27A, and MLPH
mutations) and Chédiak-Higashi syndrome (LYST
mutations)
4