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Therapy for

Severe Psoriasis

JASHIN J. WU, MD
Los Angeles, CA, USA

STEVEN R. FELDMAN, MD, PhD


Departments of Dermatology,
Pathology, and Public Health Sciences
Wake Forest School of Medicine
Winston-Salem, NC, USA

MARK G. LEBWOHL, MD
Department of Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY, USA
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

Therapy for Severe Psoriasis ISBN: 978-0-323-44797-3


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A catalog record for this book is available from the Library of Congress

Content Strategist: Russell Gabbedy


Content Development Specialist: Colleen Viola
Design Direction: Renee Duenow

Printed in United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1


Contributors

EDITORS HENRY W. LIM, MD


Chairman and Clarence S. Livingood Chair
JASHIN J. WU, MD Department of Dermatology
Los Angeles, CA, USA Henry Ford Hospital
Detroit, MI, USA
STEVEN R. FELDMAN, MD, PhD
Departments of Dermatology, Pathology, and
Public Health Sciences ELAINE J. LIN, MD
Wake Forest School of Medicine Department of Dermatology
Winston-Salem, NC, USA University of California—Davis
Sacramento, CA, USA
MARK G. LEBWOHL, MD
Professor and Chair
Kimberly and Eric J. Waldman Department LAUREN M. MADIGAN, MD
of Dermatology Department of Dermatology
Icahn School of Medicine at Mount Sinai Henry Ford Hospital
New York, NY, USA Detroit, MI, USA

AUTHORS CATHERINE NI, MD


David Geffen School of Medicine
JOHANN E. GUDJONSSON, MD, PhD University of California—Los Angeles
Frances and Kenneth Eisenberg Emerging Los Angeles, CA, USA
Scholar
Taubman Medical Research Institute
Assistant Professor JOHN K. NIA, MD
Department of Dermatology Clinical Dermatopharmacology Fellow
Director of Inpatient and Consultation Department of Dermatology
Dermatology Icahn School of Medicine at Mount Sinai
University of Michigan New York, NY, USA
Ann Arbor, MI, USA

PETER W. HASHIM, MD, MHS AMIT OM, BS


Clinical Dermatopharmacology Fellow Center for Dermatology Research
Department of Dermatology Department of Dermatology
Icahn School of Medicine at Mount Sinai Wake Forest School of Medicine
New York, NY, USA Winston-Salem, NC, USA

DANE HILL, MD
Center for Dermatology Research SANDRA PENA, BS
Department of Dermatology Center for Dermatology Research
Wake Forest School of Medicine Department of Dermatology
Winston-Salem, NC, USA Wake Forest School of Medicine
Winston-Salem, NC, USA

MICHAEL KELLY-SELL, MD
Department of Dermatology SHIVANI P. REDDY, BS
University of Michigan University of Illinois College of Medicine
Ann Arbor, MI, USA Chicago, IL, USA

vii
VIDHI V. SHAH, BA ANJALI S. VEKARIA, MD
University of Missouri–Kansas City School of Resident
Medicine Department of Dermatology
Kansas City, MO, USA Icahn School of Medicine at Mount Sinai
New York, NY, USA

viii
Foreword

Our knowledge of the genetics and immuno-


pathogenesis of psoriasis has exploded over the
past two decades to the extent that psoriasis
now has to be considered a systemic disease for
a significant percentage of patients having other
organ involvement, including the joints. Thus,
more than 40 genes have been shown to be asso-
ciated with psoriasis. However, a much smaller
number of genes are associated with psoriatic
arthritis, throwing into doubt the actual specific
Alan Menter, MD association between psoriasis and psoriatic
arthritis. The severity of cutaneous inflammation
Psoriasis is a common, immune-medicated, ge- is frequently “mirrored” systemically in the
netic disorder affecting up to 2% of the world bloodstream with potential negative sequelae
population with significant interracial variation, for the heart, especially the coronary vasculature,
being far less common in Africa, Asia, and North as well as the liver, including steatohepatitis. In
America Indians than in Scandinavian countries, addition, psoriasis has been shown to be statisti-
Northern Europe, and the Americas. Men and cally associated with a relatively long list of other
women, boys and girls, are equally affected, comorbidities, including obesity; with the full
with the majority of patients developing their dis- spectrum of the metabolic syndrome, including
ease before the age of 40. obesity, hypertension, diabetes mellitus, and
Psoriasis shares much of its ancient history hypercholesterolemia; and with hypertriglyceri-
with leprosy, with Biblical references to leprosy demia. Other conditions, including sleep apnea,
likely representing actual psoriasis. Hippocrates chronic obstructive pulmonary disease, and renal
in fact described a series of skin disorders under disease, are also linked to psoriasis.
the heading “Lopoi,” Greek for epidermis, which Psoriasis likewise has a major effect on patients’
possibly included both psoriasis and leprosy. The quality of life with social and personal interactions
term “psoriasis” was derived from the Greek for frequently disrupted due to the visible nature of
epidermis, which possibly included both psoriasis the disabling condition, leading to depression, fa-
and leprosy. The term “psoriasis,” derived from tigue, and indeed a higher likelihood of suicidal
the Greek “psora” meaning “itch,” was first ideation, especially in younger patients.
used by Galen (133-200 AD). Sixteen centuries It is thus incumbent on all dermatologists with
later, Robert Willan (1757-1812) published the an interest in the fascinating disorder not only to
first true description of psoriasis in 1808. assess each and every psoriatic patient’s total skin
Psoriasis is not “one disease.” It has a vast surface, head to toe, at each consultation but also
array of clinical phenotypes with the classic “pla- to evaluate for comorbidities, including psoriatic
que” form being the commonest. It can vary joint disease and psychosocial issues. Collabora-
from a few discrete areas of activity, such as tion with colleagues in other specialties, including
the scalp, elbow, and knees, to generalized cuta- cardiology, endocrinology, hepatology, general
neous involvement with various forms, shapes, internal medicine, and family practice, is
and sizes of individual lesions. In addition, frequently indicated for the betterment of the
numerous other phenotypical manifestations health of the psoriatic population as a whole. In
can include guttate, erythrodermic, inverse, patients with less severe psoriasis, who account
and palmar-plantar forms, either individually or for approximately 75% of the psoriatic popula-
in association with the classic plaque-type dis- tion, topical agents are the treatment of choice
ease. Chapters in this book address multiple in the overwhelming majority. For the remaining
classes of therapy currently available for the 25% with moderate to severe psoriasis, the
treatment of psoriasis, together with investiga- wide array of systemic therapies, both oral and
tional new drugs and the advent of biosimilar injectable, offers the opportunity to maximize
agents. the benefits of treatment to our psoriasis ix
x Foreword

population, both short term and long term, while


also reducing the impact of the multiple comor-
bidities associated with the more severe forms
of psoriasis. Thus, the future for our psoriasis
population is exciting indeed.

Alan Menter, MD
Chair, Department of Dermatology
Clinical Professor of Dermatology
University of Texas Southwestern Medical School
Dallas, TX, USA
Preface

Jashin J. Wu, MD, Editor Steven R. Feldman, MD, PhD, Editor Mark G. Lebwohl, MD, Editor

The first edition of Therapy for Severe Psoriasis fills an insight into therapies in the pipeline that may
the need for an up-to-date resource for the rapidly be approved in the near future.
changing treatment arena for severe psoriasis. High- We hope that this textbook serves as both a
lights of this book are chapters devoted to newly reference book and a practical guide in treating
approved therapies such as apremilast, secukinu- patients with severe psoriasis. We look forward
mab, ixekizumab, and biosimilars. This is the golden to further advances in therapy for severe psoriasis
era for treating patients with severe psoriasis. As in the coming years, and we plan to update this
more and more medications are approved, each textbook with a second edition in a few years’ time.
wave seems to demonstrate higher efficacy with
minimal adverse events. It is hoped that this text-
book summarizes and guides the dermatologist in ACKNOWLEDGMENTS
learning and choosing among the myriad of options. The editors thank Russell Gabbedy, Colleen Viola, Louise
The lead authors of each chapter are world Cook, and others at Elsevier for their steady support over
leaders in their fields regarding their topics, and the 6-month period of writing, revising, and editing this
we thank them and their coauthors in textbook. The editors acknowledge the patients who
developing comprehensive but readable chap- allowed their photos to be used for educational pur-
ters. The opening chapter gives an updated poses like this and also for giving the authors inspiration
overview of psoriasis, including epidemiology, in developing strategies to treat their severe psoriasis.
pathogenesis, and clinical findings in each of the
subtypes of psoriasis. Each chapter devoted to Jashin J. Wu, MD
therapy has a concluding paragraph that frames
Steven R. Feldman, MD, PhD
the therapy in their own “expert” algorithm of
when to use the treatment. The final chapter gives Mark G. Lebwohl, MD

xi
CHAPTER 1
Overview of Psoriasis
Michael Kelly-Sell, MD, Johann E. Gudjonsson, MD, PhD

KEYWORDS
 Psoriasis  Plaque psoriasis  Clinical subtypes  Pustular psoriasis  Nail psoriasis
 Comorbidities

KEY POINTS
 Today, psoriasis is a global disease causing significant impairment in quality of life, disfiguring
morbidity, and increased mortality.
 Psoriasis affects men and women equally. Two-thirds of patients are thought to have mild disease,
and one-third of patients are thought to have more severe involvement.
 Psoriasis is found in practically all racial groups and is thought to affect approximately 2% of the
world’s population.
 Psoriasis may appear at any age, but it most commonly presents between the ages of 15 and 30.
 Over the last 20 years, many of the immunologic drivers of psoriasis have been uncovered, and this
research has been translated to the clinic with the development of increasingly powerful but
selective biologic drugs targeting these immune pathways.

Psoriasis was first described by the ancient Greeks, EPIDEMIOLOGY


Hippocrates and Galen, and grouped together Psoriasis affects male and female patients equally.
with leprosy. The term psoriasis was derived from Two-thirds of patients are thought to have mild
the Greek “psora” which means an, “itch, mange, disease, and one-third of patients are thought to
scab.” In the early nineteenth century, Robert have more severe involvement. Psoriasis is found
Wilan and Hebra refined the description of psoria- in practically all racial groups and is thought to
sis and distinguished it from leprosy. In 1879, affect approximately 2% of the world’s popula-
Koebner described the appearance of psoriatic le- tion. Although psoriasis is a global disease, there
sions at sites of injury, called the “Koebner phe- are some regional variations in prevalence, with
nomenon.” Today, psoriasis a global disease rates varying from 0.4% in Asians to 2.6% in the
affecting 125 million people across the world and United States and 2.9% in Denmark. In Africa,
causing significant impairment in quality of life, dis- there is a higher prevalence in East Africans as
figuring morbidity, and even mortality. In the late opposed to West Africans, which may help
twentieth century, basic science research demon- explain racial differences within the United States.
strated that psoriasis is an immune-mediated poly- Interestingly, a study of 26,000 South American
genic disorder that can be triggered by various Native Americans did not document a single
environmental triggers. Over the last 20 years, case of psoriasis.
many of the immunologic drivers of psoriasis
have been uncovered, and this research has been
translated to the clinic with the development of AGE OF ONSET
increasingly powerful but selective biologic drugs Psoriasis may appear at any age, but it most
targeting these immune pathways. This increased commonly presents between the ages of 15 and
understanding of the immunology of psoriasis 30. An earlier age of onset and family history
has led to remarkable improvements in the treat- have been associated with particular HLA class I
ment of psoriasis and makes it an exciting time to antigens, most notably HLA-Cw6. Based on this
care for patients with psoriasis. finding, Henseler and Christophers1 proposed

1
2 Therapy for Severe Psoriasis

that 2 different forms of psoriasis exist: type I pso- center with increasing parakeratosis, capillary
riasis, with onset before the age of 40; and type II elongation, and perivascular infiltration of various
psoriasis, with age of onset after the age of 40. types of immune cells. Mature psoriatic lesions
Both types of psoriasis respond similarly to contain elongated and uniform rete ridges with
treatment. thinning of the epidermis overlying the dermal
papillae. The tips of the rete ridges may become
Cause and Pathogenesis clubbed with dilated, tortuous capillaries in the
The root cause of psoriasis remains unknown. How- dermal papillae. There is typically confluent para-
ever, research is beginning to link the complex ge- keratosis and hyperkeratosis.5 More inflammatory
netic, biochemical, and immunologic abnormalities cells are present with CD41 T cells and dendritic
that underlie the disease. These changes can be cells in the upper dermis and CD81 T cells in the
seen in both psoriatic lesions and normal- epidermis. Neutrophils are commonly seen in pso-
appearing skin of psoriatic patients. riatic lesions and form characteristic collections in
There is strong evidence suggesting at least a the spinous layer (spongiform pustules of Kogoj)
partial genetic basis in psoriasis. Genome linkage and in the stratum corneum (Munro microab-
studies in the 1990s identified a locus termed pso- scesses). Eosinophils are not seen in psoriasis, un-
riasis susceptibility 1 (PSORS1) in the major histo- less the disease is drug induced.
compatibility complex (chromosome 6p21.3),
home of the HLA genes.2 Many HLA markers
have been associated with psoriasis, but HLA- T CELLS
Cw6 has constantly demonstrated the highest The role of T cells in psoriasis was first documented
relative risk for psoriasis in Caucasian popula- in the 1980s, and the last 30 years of scientific and
tions.3 HLA-Cw6 is also strongly associated with clinical research on psoriasis have further high-
early onset, guttate psoriasis, and psoriatic lighted their role in the pathophysiology of the dis-
arthritis. However, only about 10% of HLA-Cw6 ease. The latest biologic medications for psoriasis
carriers develop psoriasis and the PSORS1 may ac- target T-cell immune pathways, and their ability to
count for only one-third of the genetic liability to clear plaques underlines the importance of the
psoriasis.4 In recent years, additional genetic risk T-cell pathways these medications target.
variants have been identified for psoriasis, with In 1984, Dr Baker and colleagues6 were the
more than 60 genetic loci identified to date. These first to show a correlation between the eruption
findings confirm the polygenic nature of psoriasis of psoriatic skin lesions and the epidermal influx
and also its heterogeneity because most patients and activation of T cells. Subsequently, deletion
carry different combinations of these risk variants, of epidermal T cells was shown to predate resolu-
and this may influence clinical course of the dis- tion of psoriatic plaques in patients on photother-
ease as well as therapeutic responses. apy.7 In 1986, cyclosporine was shown to be
highly efficacious in treating psoriasis due to its
blockade of T-cell function.8 Ten years later in
DEVELOPMENT OF A LESION 1996, activated autologous T cells initiated psori-
Psoriasis is characterized clinically by red and scaly atic lesions when injected into uninvolved psori-
plaques sharply demarcated from normal skin. atic skin transplanted onto severe combined
Histologically, it is characterized by marked prolif- immunodeficient mice.9 This showed that T cells
eration of keratinocytes, altered epidermal differ- were sufficient to induce a psoriatic process.
entiation, and proliferation of endothelial cells More recently, using xenograft models where hu-
accompanied by an influx of a variety of inflamma- man skin is grafted onto immunodeficient mice,
tory cells. The development of a psoriatic lesion trafficking of T cells to the epidermis, particularly
is a complex and multicellular process that CD81 T cells, was shown to be critical for devel-
involves keratinocytes, T cells, dendritic cells, mac- opment of psoriatic plaques, highlighting the
rophages, mast cells, endothelial cells, and neutro- importance of these cells in psoriasis.
phils. Cytokines and growth factors initiate and Psoriatic lesions are typified by T helper 1 (Th1)
sustain inflammation in this process through path- polarized CD41 cells and T cytotoxic 1 (Tc1)
ways that involve cells of both the innate and the polarized CD81 T cells producing interferon
acquired immune systems. Initial pinhead-sized (IFN)-g, which is the dominant cytokine profile of
macular lesions show edema and mononuclear psoriatic lesions.10 IFN-g drives the production
cell infiltrates within the upper dermis. The over- of interleukin-12 (IL-12) and IL-23 by dendritic
lying epidermis becomes spongiotic, and there is cells. IL-23 supports and expands CD41 T cells,
a focal loss of the granular layer. As the plaque ma- and likely CD81 T cells, that produce IL-17 and/or
tures, the epidermis becomes thickened in the IL-22, whereas IL-12 promotes development of
Chapter 1 Overview of Psoriasis 3

Th1 and Tc1 cells. The secretion of IL-17 and IL-22 enzymes. These changes lead to histopathologic
by these cell types likely maintains the chronic findings that can be identified on microscopic ex-
inflammation in psoriasis,11,12 but the exact role amination and have been termed “histochemical
of IFN-g in this process is still unclear. T cells parakeratosis.”
also contribute to the production of tumor necro-
sis factor-a (TNF-a), but TNF-a is a potent proin-
flammatory cytokine, the main role of which may CLINICAL FINDINGS
be to amplify the effect of other cytokines, History
including IFN-g and TNF-a. Biologic medications In approaching a patient with psoriasis, it is impor-
targeted at inhibiting these inflammatory media- tant for the clinician to obtain a thorough personal,
tors, including TNF-a, IL-12/IL-23, and IL-17, family, and social history because it often will influ-
have shown great efficacy in treating psoriasis, ence the choice of therapeutic agent. Relevant in-
underlining the important role this molecule plays formation includes the age of onset of psoriasis
in driving the disease. and whether psoriasis is present in any close rela-
tives, because both a younger age of onset and
a positive family history have been associated
MACROPHAGES AND DENDRITIC CELLS with more widespread and recurrent disease.18
Macrophages are important phagocytic cells that In addition, the prior course of disease and fre-
reside under the basement membrane, adjacent quency of relapses should be recorded, because
to proliferating keratinocytes, and are important there is significant variability in the clinical presen-
in the early development of psoriatic lesions. tation of disease and the disease may change from
They express Factor XIIIa and secrete the chemo- one clinical phenotype to another (Box 1.1). In
kine MCP-1 (CCL2).13 They are an important source some patients, the disease frequently relapses,
of TNF-a, inducible nitric oxide synthase, and and this has been associated with more severe dis-
IL-23.13,14 It has been shown in mouse models ease with rapidly enlarging lesions covering signif-
that the selective elimination of macrophages leads icant portions of the body surface.19 Other
to prompt improvement of psoriatic lesions.15 patients have more chronic, slowly developing le-
Dendritic cells have an important role in both sions with only occasional recurrences.
priming the adaptive immune response and The presence or absence of joint symptoms
inducing self-tolerance. Subtypes of dendritic should be recorded—such as painful, warm, or
cells, such as Langerhans cells, dermal dendritic swollen joints. Any of these complaints are con-
cells, and myeloid dendritic cells, help drive the cerning for psoriatic arthritis and prompt a more
Th1, Th17/Th22 polarization of psoriatic plaques. thorough evaluation. It is important to remember
In particular, myeloid dendritic cells help make that osteoarthritis is common and frequently co-
IL-12 and IL-23 cytokines that promote Th1 and exists with psoriasis.
Th17 differentiation and responses, respec-
tively.16 In a psoriatic plaque, myeloid dendritic
cells can be increased up to 30-fold as compared BOX 1.1
Clinical subtypes of psoriasis
with uninvolved skin and make up about 80% to
90% of the dendritic cells.17  Chronic plaque psoriasis (psoriasis vulgaris)
 Psoriasis geographica
NEUTROPHILS  Psoriasis gyrata
Although neutrophils are a common histopatho-  Annular
logic finding in the upper epidermis of psoriatic  Rupioid
lesions, they do not seem to a have a significant
role in lesional development in chronic plaque  Ostraceous
psoriasis, although they have a key role in pustular  Elephantine
variants of psoriasis.  Guttate psoriasis (eruptive psoriasis)
 Small plaque psoriasis
UNINVOLVED PSORIATIC SKIN  Flexural (Inverse) psoriasis
Normal-appearing skin of patients with psoriasis  Erythrodermic psoriasis
has been shown to have subclinical biochemical
changes that lead to subtle histologic findings.  Sebopsoriasis
Lipid biosynthesis is predominantly affected with  Napkin psoriasis
measurable changes in the levels, constitution of  Linear psoriasis
phospholipids, free a-amino acids, and hydrolytic
4 Therapy for Severe Psoriasis

Psoriasis is associated with several comorbid- response is still unclear. There is a broad differen-
ities, including increased incidence of myocardial tial diagnosis for psoriasis that physicians should
infarction, stroke, and death, particularly in pa- consider (Table 1.1), and treatment failures may
tients with moderate-to-severe psoriasis.20–23 prompt a reconsideration of the diagnosis.
Psoriasis has been shown to be an independent
risk factor for cardiovascular disease,24,25 and it
is important to screen patients for other cardio- CUTANEOUS LESIONS
vascular risk factors in their social and medical his- Psoriasis Vulgaris
tories, because modification of these can help Psoriasis vulgaris, or chronic plaque psoriasis, is the
offset their increased risk. Cardiovascular risk fac- most common clinical manifestation of psoriasis,
tors include smoking status, diet, and any previ- affecting approximately 90% of psoriasis patients.
ous diagnoses of hypertension, diabetes, Psoriasis vulgaris is characterized by well-
dyslipidemia, or obesity. demarcated, erythematous, raised plaques with
Treatment history should also be recorded. white micaceous scale. Lesions vary in size from
Although the ability to predict treatment re- pinpoint papules to large plaques and tend to be
sponses to a given agent are still very limited, pa- symmetrically distributed on the scalp, postauricu-
tients that have been on previous biologics and lar skin, elbows, gluteal cleft, and knees. These le-
failed generally respond less well to other biologic sions produce significant amounts of scale and
agents, even when these are in a different removing the scale produces pinpoint bleeding
class. The nature of this decreased therapeutic (the Auspitz sign), which is a sign of the dilated

TABLE 1.1
Differential diagnosis of psoriasis
Psoriasis Vulgaris Guttate Erythrodermic Pustular
Common
 Discoid/nummular eczema  Pityriasis rosea  Drug-  Impetigo
 Cutaneous T-cell lymphoma  Pityriasis lichenoides induced  Superficial candidiasis
(CTCL) chronica erythroderma  Reactive arthritis
 Tinea corporis  Lichen planus  Eczema syndrome
 CTCL/Sézary  Superficial folliculitis
syndrome
 Pityriasis
rubra
pilaris
Consider
 Pityriasis rubra pilaris  Small plaque  Pemphigus foliaceus
 Seborrheic dermatitis parapsoriasis  Immunoglobulin A
 Subacute cutaneous lupus  Pityriasis lichenoides pemphigus
erythematosus et varioliformis acuta  Sneddon-Wilkinson
 Erythrkeratoderma (either (PLEVA) disease (subcorneal
erythrokeratoderma variabi-  Lichen planus pustular dermatosis)
lis and/or progressive sym-  Drug eruption  Migratory necrolytic
metric erythrokeratoderma)  Secondary syphilis erythema
 Hypertrophic lichen planus  Transient neonatal pus-
 Lichen simplex chronicus tular
 Contact dermatitis melanosis
 Chronic cutaneous lupus er-  Acropustulosis of infancy
ythematosus/discoid lupus  Acute generalized
erythematosus exanthematous
 Hailey-Hailey disease (more pustulosis
flexural)
 Intertrigo (flexures)
 Candida infection (flexures)
 Bowen disease/squamous
cell carcinoma in situ
 Extramammary Paget
disease
Chapter 1 Overview of Psoriasis 5

capillaries below the epidermis and thinned supra- psoriatic papules across the upper trunk and
papillary plate. Disease presentation is impres- proximal extremities (Fig. 1.2). Guttate psoriasis
sively variable among patients, and the clinical typically presents in children, adolescents, and
findings can change quickly even within the same young adults. It is often preceded by a strepto-
patient. coccal throat infection, and less commonly, peri-
Psoriatic lesions can be induced by trauma, and anal strep infections, and more than half of
this is known as Koebnerization or the isomorphic patients will have molecular evidence of a recent
response. This phenomenon is more likely to occur streptococcal infection, such as an elevated anti-
when the disease is flaring and is an all-or-nothing streptolysin O, anti-DNase B, or streptozyme titer.
response (meaning if psoriasis appears at one site Despite this association, antibiotics are not helpful
of injury then it will appear at all sites of injury). The in the treatment of guttate psoriasis and do not
isomorphic response typically appears 7 to 14 days alter the course of the disease.28 One-third to
after injury, and the lifetime prevalence of the phe- one-half of patients who develop guttate psoriasis
nomenon is estimated to be 25% to 75%.26 The will later develop chronic plaque psoriasis. As
isomorphic response is not specific to psoriasis. mentioned above, guttate psoriasis shows the
Historically, psoriasis vulgaris has been subclas- strongest association with HLA-Cw6.29
sified by the shape and scale of the plaques.
Today, the terms have little significance clinically, Inverse Psoriasis (Flexural Psoriasis)
but they connect the modern disease to its long Inverse, or flexural, psoriasis is distinguished by
history. Psoriasis geographica describes plaques psoriatic lesions appearing in the major skin folds,
that resemble a land map. Psoriasis gyrata consists such as in the axillae, inguinal creases, intergluteal
of confluent, connected plaques with a circinate cleft, umbilicus, and inframammary folds. Lesions
appearance. Rupioid lesions present in the shape are erythematous and sharply demarcated, with a
of a cone or limpet. Ostraceous plaques have a cir- glossy appearance and little to no scale. The
cular, hyperkeratotic concave lesion resembling an lesion may contain a central fissure. The sharp
oyster shell. Elephantine psoriasis refers to large, demarcation and glossy appearance help distin-
thick, scaly plaques on the lower extremities. guish the lesions from other diseases of the skin
Annular lesions have partial central clearing, giving folds. Sweating is decreased in affected areas
a ring-shaped appearance, and are associated and localized fungal or bacterial infections may
with a good prognosis because the annular shape be a trigger.
suggests clearing (Fig. 1.1). Finally, a hypopig-
mented ring on the periphery of an individual pla- Erythrodermic Psoriasis
que, or Woronoff ring, may be seen after Erythrodermic psoriasis is the generalized form of
treatment with UV radiation or topical steroids. disease and affects all body sites: face, trunk, ex-
Woronoff rings are thought to be caused by inhibi- tremities, hands, and feet. Erythema is more
tion of prostaglandin synthesis and are associated prominent and the scaling is finer, more superfi-
with lesional clearing and a good prognosis.27 cial and diffuse, as compared with psoriasis vulga-
ris. Patients lose their autonomic control of body
Guttate Psoriasis temperature and may present with systemic
Derived from the Latin gutta, “a drop,” guttate symptoms. They lose excessive heat from gener-
psoriasis is distinguished by the eruption of small alized vasodilation and so may shiver to try to
compensate. In warm climates, there is a risk for
hyperthermia because patients do not sweat
from their psoriatic lesions.30 The generalized
vasodilatation also puts patients at risk for high-
output cardiac failure, impaired hepatic and renal
function, and lower extremity edema. Erythroder-
mic psoriasis is thought to have 2 general presen-
tations: first, as a chronic form that is thought to
be a slow progression of psoriasis vulgaris
(Fig. 1.3). A second form is distinguished by its
sudden onset and may be a generalized Koebner
reaction to treatments such as phototherapy or
anthralin. Finally, other generalized forms of pso-
Fig. 1.1 Annular plaque psoriasis. There are well- riasis may give an appearance of erythrodermic
defined erythematous plaques with thick micaceous psoriasis as they heal, such as generalized pustular
scale on the periphery. psoriasis.
6 Therapy for Severe Psoriasis

Fig. 1.2 Erythrodermic psoriasis associated with HIV. (A) Cutaneous disease often worsens as a patient’s CD4 count
drops. (B) Thick micaceous scale. (C) There was confluent erythema and scale on the hands. Note the prominent oil
spots below the fingernails and swelling of the left fifth PIP joint. (D) There is confluent scale on the feet with subtle
erythema. Note the left third toe dactylitis, also known as a “sausage digit,” a manifestation of psoriatic arthritis.

Pustular Psoriasis neutrophils on histopathologic examination


Clinically, pustular psoriasis is distinguished (Fig. 1.4). There are 4 main clinical categories
by the appearance of 2- to 3-mm sterile of pustular psoriasis: generalized pustular psori-
pustules that show infiltrated subcorneal asis (von Zumbusch type), annular pustular pso-
riasis, impetigo herpetiformis, and localized
forms (including pustulosis palmaris et plantaris
[PPP] and acrodermatitis continua of Hallopeau)
(Box 1.2). Finally, SAPHO syndrome (synovitis,
acne, pustulosis, hyperostosis, osteitis) is a ge-
netic syndrome that typically presents in chil-
dren and young adults, and palmoplantar
pustulosis is a main feature.

Generalized Pustular Psoriasis (von


Zumbusch)
Generalized pustular psoriasis (von Zumbusch) is
an acute variant of pustular psoriasis typified by
several days of fever preceding the sudden gener-
alized eruption of sterile pustules across the
body—face, trunk, extremities, nail beds, palms,
and soles. The attacks may occur in waves, and
the skin is painful. On examination, there is a
background of erythematous skin that initially
Fig. 1.3 Guttate psoriasis, involving the upper extrem- starts as patches but spreads to become
ities and torso. Clinically, the micaceous scale helps confluent, leading to erythroderma. With chronic
differentiate this disorder. disease, there may be atrophy of the fingertips.
Chapter 1 Overview of Psoriasis 7

Fig. 1.4 Pustular psoriasis. The patient shown in (A) and (B) demonstrates flaccid subcorneal pustules on an
erythematous base. Note the pus accumulating in the dependent half of the pustules. The patient shown in (C)
and (D) had pustules form an annular or circinate pattern with an erythematous center. This may resemble erythema
annulare centrifugum or impetigo herpetiformis.

The cause of attacks is unknown but possible trig- successfully include methotrexate, cyclosporine,
gering factors include infections, irritating topical infliximab,33 and systemic corticosteroids.34
treatments (provoking a Koebner phenomenon), Loss-of-function mutations in the IL36RN gene,
and withdrawal of systemic corticosteroids. encoding IL-36 receptor antagonist (IL-36ra), have
Generalized pustular psoriasis may have been found in patients with generalized pustular
life-threatening complications, including hypocal- psoriasis. IL-36ra is an anti-inflammatory cytokine
cemia, acute respiratory distress syndrome, that inhibits signaling of proinflammatory IL-36
bacterial superinfection leading to sepsis, and proteins (a, b, and g).35
dehydration.31,32 The severity of the disease
makes rapid control important, and therefore, Annular Pustular Psoriasis and Impetigo
medications with a rapid onset of action should Herpetiformis
be chosen. Drugs that have been used Annular pustular psoriasis is a rare form of pustu-
lar psoriasis that presents with pustules on an
erythematous ring. It may initially resemble gyrate
BOX 1.2 erythemas, such as erythema annulare centrifu-
Clinical subtypes of pustular psoriasis gum. It can present during pregnancy, typically
in the early third trimester, and is called impetigo
 Generalized pustular psoriasis (von herpetiformis. There is significant risk for hypocal-
Zumbusch) cemia, and while the disease typically improves af-
 Annular pustular psoriasis ter delivery, it may recur during subsequent
 Impetigo herpetiformis pregnancies.31,36 There is often no personal or
family history of psoriasis.
 Localized pustular psoriasis
 Pustulosis palmaris et plantaris Localized Pustular Psoriasis Variants
 Acrodermatitis continua (of Hallopeau) There are 2 main forms of localized pustular pso-
 SAPHO (synovitis, acne, pustulosis, riasis: PPP and acrodermatitis continua (of Hallo-
hyperostosis, osteitis) peau). PPP is characterized by sterile pustules on
the palmoplantar surfaces with yellow-brown
8 Therapy for Severe Psoriasis

macules. There may be scaly, erythematous pla- BOX 1.3


ques. A minority of patients has psoriatic plaques Nail findings in psoriasis
elsewhere, and the pustules primarily remain on
the palmoplantar surfaces throughout the dis-  Nail matrix
ease. PPP is thought to affect femalemore than  Nail plate pits
male patients, with a ratio of approximately 3:1,  Onychorrhexis
and typically presents between the ages of 20 to
 Beau lines
60. In contrast to plaque psoriasis, PPP is not
associated with any HLA type. In epidemiologic  Nail plate thinning
surveys, PPP has been highly associated with  Erythema of the lunula
smoking, and cessation of smoking is the most  Nail bed
important measure to treat the disease.37 If a pa-
tient continues to smoke, PPP is highly resistant to  Oil drops or “salmon patch”
treatment.  Subungual hyperkeratosis
Acrodermatitis continua is a rare eruption of  Onycholysis
sterile pustules on the fingers or toes that slowly
 Splinter hemorrhages
extends proximally. Chronic disease leads to atro-
phy of the digit and destruction of the nail matrix.  Proximal and lateral nail folds
It is difficult to treat.  Cutaneous psoriasis

Napkin Psoriasis
Napkin psoriasis typically presents in the diaper arranged on the dorsal nail plate. Nail pitting is
(napkin) areas between the ages of 3 and 6 months caused by foci of parakeratosis at the proximal
with a red, confluent patch. Scattered small, red, nail matrix, which forms the dorsal nail plate,
papules with psoriatic white scale may appear a causing poor keratinization. Nail pitting is not
few days later on the rest of the body. It typically unique to psoriasis and can also be seen in alope-
responds readily to topical steroids and usually re- cia areata and other disorders. The nail pitting of
solves by 1 year of age. alopecia areata is typically thought to be more
linear than in psoriasis, although this is not always
Linear Psoriasis the case. Other findings of nail matrix disease
Linear psoriasis is a rare form of the disease that include leukonychia, a result of disease in the mid-
typically presents as a linear plaque on an extrem- portion of the nail matrix, and widespread disease
ity or dermatome of the trunk. There may be an leads to crumbling of the nail plate.
underlying nevus, such as an inflammatory linear Oil drops are translucent red-yellow discolor-
verrucous epidermal nevus (ILVEN). Separating ations on the nail bed, below the nail plate. They
linear psoriasis and ILVEN into distinct diseases are a result of psoriasiform hyperplasia, parakera-
is controversial.38 tosis, and microvascular changes of the nail bed
and trapping of neutrophils under the nail plate.39
Unlike nail pits, oil drops on the nail bed are a
RELATED PHYSICAL FINDINGS unique finding of psoriasis. Other nail bed findings
Nail Findings with psoriasis include splinter hemorrhages, from
Nail involvement is common in psoriasis and is capillary bleeding at thinned suprapapillary plates,
seen in up to 40% of psoriasis patients.18 It in- onycholysis, and subungual hyperkeratosis. These
creases with age, extent of disease, duration of findings are not as specific to psoriasis. Anonychia,
disease, and presence of psoriatic arthritis. Find- complete loss of nails, is common in acrodermati-
ings are classified as either evidence of nail matrix tis continua, but nail findings are not typically seen
or nail bed disease (Box 1.3). Nail matrix disease in other localized variants of pustular psoriasis.
leads to pitting, onychorrhexis, Beau lines, leuko- Nail changes are important to note clinically
nychia, and thinning of the nail plate. Nail bed dis- because they have been associated with increased
ease leads to findings of oil drops (or “salmon risk for psoriatic arthritis.
patches”), subungual hyperkeratosis, and splinter
hemorrhages. Fingernails are more often affected
than toenails, and nail involvement may cause PSORIATIC ARTHRITIS
pain and restrictions on activities of daily life. Psoriatic arthritis occurs in 5% to 30% of pa-
Nail pitting is one of the most common nail tients with cutaneous psoriasis, and its preva-
findings with psoriasis. Typically, there are single lence may be underestimated.40 Cutaneous
or multiple 0.5- to 2.0-mm pits irregularly disease typically precedes the joint disease by
Chapter 1 Overview of Psoriasis 9

about 10 to 12 years, but about 10% to 15% of Many patients with psoriasis manifest altered
patients with psoriatic arthritis present without lipid profiles with elevated levels of high-density li-
skin findings. Diagnosis is difficult to establish poproteins, altered cholesterol-triglyceride ratios
because there is no serologic marker, and the in very low-density lipoprotein particles, and
radiographic hallmark, erosive changes, may elevated plasma apolipoprotein-A1 concentra-
occur years after the initial periarticular inflam- tions.43 These alterations in lipids may contribute
mation. Classic findings include asymmetric to the increased cardiovascular risk for psoriasis
involvement of both the distal (DIP) and prox- patients. Other risk factors of cardiovascular dis-
imal (PIP) interphalangeal joints, seen in about ease should be considered and appropriate labo-
40% of patients.41 In contrast to rheumatoid ratory tests ordered, because patients with
arthritis, involvement of the metacarpophalan- psoriasis are predisposed to cardiovascular dis-
geal joints is rare. Prolonged disease in the PIP ease (see later discussion). General markers of sys-
and DIP of a single digit can lead to swelling temic inflammation, such as C-reactive protein and
(dactylitis) and the appearance of a “sausage” erythrocyte sedimentation rate, are elevated in a
digit. Enthesitis, or inflammation at the insertion minority of patients with chronic plaque psoriasis
site of tendons into bones, is also a common and may suggest the presence of psoriatic arthritis.
finding in psoriatic arthritis and is seen in
approximately 20% of patients with psoriatic
arthritis.42 Arthritis mutilans is the most severe COMPLICATIONS
form of psoriatic arthritis with extensive joint Psoriatic patients have increased morbidity and
damage and bone resorption and is seen in mortality from cardiovascular disease, which cor-
5% of patients.41 Early diagnosis of psoriatic relates with the severity and length of disease.44
arthritis alters the treatment approach for a Younger patients with psoriasis are at particular
patient, as the physician should consider sys- risk, because a large population-based cohort
temic or biologic medications to prevent life- study using the UK General Practice Research
changing morbidity from arthritic changes, Database found that 30-year-olds with severe
even when cutaneous disease is limited. psoriasis had a relative risk of myocardial infarc-
tion of 3.10 as compared with healthy controls.21
Other large epidemiology studies have shown
LABORATORY TESTS that patients with psoriasis are 2.9-fold more likely
Most patients can be diagnosed based on their to have a diagnosis of metabolic syndrome—
clinical history and features alone. However, histo- which is defined by having 3 of 5 risk factors for
pathologic examination can be helpful to estab- cardiovascular disease, including obesity, hyper-
lish the diagnosis in difficult cases. The typical triglyceridemia, low high-density lipoprotein, hy-
histopathologic features of chronic plaque psoria- pertension, or diabetes. Psoriasis patients had
sis and guttate psoriasis have been discussed pre- increased rates of hypertension (35.6% in psoriatic
viously (see “Development of Lesions”). patients vs 20.6% in controls), and hyperlipidemia
Pustular psoriasis is distinguished on histopa- (29% vs 17.1%).45 Psoriasis is thought to be an in-
thology by the presence of neutrophils migrating dependent risk factor for the development of
from dilated vessels and pooling in the upper metabolic syndrome because psoriasis patients
epidermis, within the upper Malpighian layer have increased odds of having hypertension
below the stratum corneum. In newer lesions, even after controlling for age, sex, smoking sta-
there may be mild acanthosis, whereas older le- tus, and other variables.46 There is an increased
sions have more typical psoriasiform hyperplasia. prevalence of rheumatoid arthritis (prevalence ra-
There are no serum markers that are specific tio [PR] 3.8), Crohn disease (PR 2.1), and ulcerative
for psoriasis and regularly used to establish a colitis (PR 2.0) in patients with psoriasis.45 There is
diagnosis. Laboratory workup is typically aimed an increased risk of both Hodgkin lymphoma and
at ruling out other disease processes in the differ- cutaneous T-cell lymphoma in psoriasis, particu-
ential diagnosis, such as checking an antinuclear larly in patients with severe disease.47
antibody to test for connective tissue disease. The psychological impact of psoriasis on
Nonetheless, it can be important to check serum patients is profound. Cutaneous disease leads
markers in patients with severe disease to assess to concerns about appearance, lowered self-
for systemic complications. Patients may have a esteem, social rejection, guilt, embarrassment,
decreased serum albumin, secondary to the nega- emptiness, sexual problems, and impairment of
tive nitrogen balance from the turnover of their professional ability (Fig. 1.5). These stressors
skin, or elevated uric acid, increasing their risk lead to higher rates of anxiety, depression, and sui-
for developing gouty arthritis. cidal ideation in psoriasis patients than in the
10 Therapy for Severe Psoriasis

Smoking also seems to play a role in the onset


of psoriasis. Neither characteristic affects treat-
ment strategies, although all patients should be
encouraged to quit and follow a healthy diet.
Quitting tobacco is particularly important for pa-
tients with palmoplantar pustulosis because to-
bacco use may drive the process and is
associated with recalcitrant disease.
Bacterial and viral infections have also been
associated with psoriasis flares or the onset of dis-
ease. There is a clear association between strepto-
coccal throat infection and guttate psoriasis, but
streptococcal infections may exacerbate chronic
plaque psoriasis, too.51,52 HIV infection can pre-
sent as a severe psoriasis exacerbation and, para-
doxically, a patient’s psoriasis may become more
severe as the immunodeficiency progresses.53
This helps to explain why treatment of a patient’s
underlying HIV with highly active antiretroviral
therapy improves the patient’s psoriasis.54
Finally, medications may help either induce dis-
ease or aggravate a patient’s psoriasis. Medica-
tions that have been reported to aggravate
psoriasis include lithium, b-blockers, TNF-a inhibi-
tors, antimalarials, nonsteroidal anti-inflammatory
drugs, type I and type II IFNs, imiquimod,
angiotensin-converting enzyme inhibitors, and
gemfibrozil. The mechanism and clinical presenta-
tion of drug-exacerbated psoriasis vary. For
example, lithium is thought to decrease levels of
inositol, an important component of the intracel-
lular second messenger system, altering calcium
homeostasis and keratinocyte differentiation.
b-Blockers decrease cellular AMP, an important
intracellular signaling protein, altering calcium ho-
meostasis, driving keratinocyte proliferation and
inhibiting keratinocyte differentiation.55 Counter-
intuitively, TNF-a inhibitors may cause a psoriasi-
form dermatitis in patients with rheumatoid
Fig. 1.5 Psoriatic alopecia and plaque psoriasis. (A) arthritis or inflammatory bowel disease.56 Most
Chronic inflammation and scale from psoriasis have patients reported developed palmoplantar pustu-
led to alopecia. This is typically a nonscarring alopecia losis, but about one-third developed chronic pla-
but the inflammation may be so severe that there is per-
que psoriasis.57 Psoriasis patients traveling to
manent destruction of hair follicles. (B) The same patient
countries where antimalarial prophylaxis is needed
demonstrated widespread erythematous plaques with
micaceous scale in a symmetric distribution. should be warned that their disease may flare and
plan accordingly.
general population.48 Pruritus and pain may exac-
erbate these psychosocial stressors. These issues
impact a large number of psoriatic patients with TREATMENT
one survey finding 79% of respondents reporting Psoriasis is an exciting field because the number of
their psoriasis caused a negative impact on their medications available for treating patients is broad
life.49 and growing quickly. Most, but not all, of these
agents are immunomodulatory medications.
Despite the high efficacy of these medications,
MODIFYING FACTORS older and more traditional therapies still have an
Obesity and smoking have both been associated important role as adjunctive treatment. This chap-
with more severe presentations of psoriasis.50 ter provides a general introduction to the major
Chapter 1 Overview of Psoriasis 11

categories of treatment: topical therapies, photo- treatment available (Box 1.4). Topical treatments
therapy, oral medications, and biologic medica- are often inexpensive and efficacious and have an
tions (Table 1.2). This chapter covers topical excellent safety profile. Despite these benefits,
treatments at depth but leaves the other modal- 40% of patients report being noncompliant with
ities for the remainder of this book. their topical treatments because they feel these
In formulating a treatment regimen, the clini- treatments are time-consuming and cosmetically
cian must balance the patient’s goals with the unacceptable.58 Cosmetic considerations are
measurable severity of the disease, patient- particularly important, and physicians should pre-
specific factors (such as psoriatic arthritis, preg- scribe a medication as both a cream, to be used
nancy, or a history of malignancy), and limits set during the day, and a more potent ointment, to
by payors. There is no cure for psoriasis, and treat- be used at night. It is important to give a sufficient
ment can be frustrating, with many patients volume of medication for the patient to treat their
reporting their treatment regimens being ineffec- skin lesions appropriately, and 400 g of a topical
tive. With the advent of highly effective biologics agent is required to entirely cover an average
and the high level of treatment responses sized adult twice daily for 1 week.
achieved with these drugs, patient’s expectations
have grown. Therefore, these feelings are only
likely to grow. CORTICOSTEROIDS
As patients will use these medications for Topical corticosteroids are commonly first-line
years, safety is also a major concern and deserves therapy in mild-to-moderate psoriasis and on sen-
a frank discussion with patients. New treatments, sitive skin, such as the flexures and genitalia.
which can be highly efficacious, often have the These medications work by causing nuclear trans-
shortest safety record. Furthermore, although location of glucocorticoid receptors, leading to a
some treatments are safe for continuous use, wide variety of effects. Patients typically see
others have cumulative toxicity that limits their improvement with 2 to 4 weeks of daily treatment
use. Treatments may lose efficacy over time either and then can taper to a maintenance phase of
through a process called tachyphylaxis, which is applying the creams only 2 to 3 days per week.
mostly limited to topical treatments, through the Long-term daily use of topical corticosteroids
development of neutralizing antibodies to a may cause skin atrophy, telangiectasias, stretch
particular biologic agent, or possibly through marks, and adrenal suppression (from systemic
the changing nature of inflammatory responses absorption). With long-term use, these agents
in psoriatic skin, requiring the change or the addi- lose their efficacy, and patients should be
tion of other modalities. Physicians must individu- switched to an alternative formulation. Upon
alize a treatment regimen to the patient and, if discontinuation of a topical steroid, a patient’s
there is disease progression, progression of dis- disease may rebound.59 Topical corticosteroids
ease will likely have to use treatments in combina- are inexpensive, effective, and safe, when used
tion to achieve long-term control. appropriately; therefore, they should be a part
of every patient’s treatment plan.

TOPICAL THERAPIES
Most patients with psoriasis are treated initially VITAMIN D3 AND ANALOGUES
with topical treatments, and these medications The topical vitamin D preparations that are
can be used safely with nearly every other commercially available for the treatment of skin

TABLE 1.2
Treatments for psoriasis
Topical Phototherapy Systemic Biologics
 Corticosteroids  Narrowband UVB  Cyclosporine TNF-a inhibitors
 Vitamin D analogues (310–331 NM)  Methotrexate  Etanercept
 Tazarotene  Broadband UVB  Acitretin  Humira
 Salicylic acid  PUVA  Fumaric acid esters  Infliximab
 Calcineurin inhibitors (for  Excimer laser (308 NM) (available in Germany IL-12/IL-23
inverse psoriasis) but not the US or UK) inhibitor
 Apremilast  Ustekinumab
IL-17 inhibitor
 Secukinumab
 Ixekizumab
12 Therapy for Severe Psoriasis

BOX 1.4 TOPICAL CALCINEURIN INHIBITORS


Topical therapies Tacrolimus and pimecrolimus are topical calci-
neurin inhibitors, blocking both T-lymphocyte
 Topical steroids function and IL-2 production. In clinical trials,
 Vitamin D analogues neither agent proved efficacious for chronic pla-
 Tazarotene que psoriasis. However, there is evidence that
tacrolimus is effective for the treatment of inverse
 Calcineurin inhibitors
psoriasis.62,63 Clinically, these agents are limited
 Tacrolimus by their main side effect, which is a burning sensa-
 Pimecrolimus tion at the application site. The US Food and Drug
 Dithranol Administration has placed a “black-box warning”
on these medications after anecdotal reports of
 Coal tar
malignancy were published. The American Acad-
 Salicylic acid emy of Dermatology and the American Academy
of Allergy, Asthma, and Immunology have pro-
tested these warnings. Furthermore, large after-
marketing surveillance databases of the topical
disease include calcipotriene (or calcipotriol), cal- formulations have not detected any increased
citriol, tacalcitol, and maxacalcitol (tacalcitol and risk of lymphoma or cutaneous malignancies.64
maxacalcitol are not currently available in the
United States). Topical calcipotriene is commonly
thought of as being about as potent as a mild SALICYLIC ACID
topical steroid. These medications are more effec- Salicylic acid is a topical keratolytic that lowers the
tive if applied twice daily rather than once daily pH of the stratum corneum and reduces keratino-
and do not lose their efficacy with long-term cyte adhesion. This helps to soften plaques and
use.60 Irritation to the skin is a common side ef- reduce their scale, which enhances the penetra-
fect, so patients should be instructed not to apply tion of other therapies. Like tazarotene, it is often
vitamin D preparations to sensitive skin. There are best used in combination with a topical cortico-
almost no systemic side effects when these med- steroid. Unlike tazarotene, salicylic acid decreases
ications are used appropriately. However, hyper- the efficacy of UVB phototherapy.59 Systemic ab-
calcemia can occur if a patient applies more sorption can occur if applied to more than 20% of
than 100 g per week of calcipotriene or 200 g the body surface area, particularly in patients with
per week of calcitriol. Treatment with calcipo- renal or hepatic dysfunction. There are no
triene can complement the use of potent topical placebo-controlled studies using salicylic acid as
corticosteroids, with patients applying topical cal- monotherapy.
cipotriene 5 times per week when they taper their
topical steroid to 2 times per week, minimizing
the risk for steroid-induced atrophy. BLAND EMOLLIENTS
Patients should be encouraged to apply bland
emollients regularly between medical treatments.
TAZAROTENE Emollients can limit dryness, scale, and pruritus.
Tazarotene is a third-generation retinoid available They should be applied immediately after bathing
in 0.05% and 0.1% gels and a cream formulation. or showering for maximum effect. They can also be
It is used primarily to reduce plaque thickness and applied over a thin layer of a topical medication to
scaling. It is not as effective for plaque erythema. improve hydration of the skin. By smoothing the
The drug’s specific molecular targets are un- skin and preventing epidermal scatter, emollients
known, but it is thought to act by binding to reti- may increase the efficacy of phototherapy.
noic acid receptors. Local irritation is a significant
side effect and is dose related. Therefore, this
medication is best used in combination with PHOTOTHERAPY
topical corticosteroids or phototherapy. By Goeckerman first started using artificial light sour-
decreasing thickness and causing irritation, tazar- ces to treat psoriasis in the 1920s—using a combi-
otene lowers the minimal erythema dose for both nation of topical crude coal tar and subsequent
UVB and UVA. Therefore, if tazarotene is started UV irradiation. In the 1970s, photochemotherapy
in the middle of a phototherapy course, it is rec- with psoralen and UVA light (PUVA) was devel-
ommended that the UV dose be reduced by at oped, but has now been mostly discontinued
least one-third.61 given increased incidence of skin cancer,
Chapter 1 Overview of Psoriasis 13

BOX 1.6
Biologic therapies
 TNF-a inhibitors
 Etanercept
 Adalimumab
 Infliximab
 IL-12/IL-23 p40 subunit inhibitor
 Ustekinumab
 IL-17 inhibitor
 Secukinumab
Fig. 1.6 Lentigines from ultraviolet treatment of psori-
asis. Chronic damage from the ultraviolet treatment of  Ixekizumab
these psoriatic patches has led to the formation of len-
tigines bilaterally. There is also epidermal atrophy,
likely from chronic use of topical steroids. A closer that they have an excellent safety profile. This is
view of the lentigines and epidermal atrophy (inset). an exciting time for the treatment of psoriasis
with multiple classes of biologics available:
particularly squamous cell carcinoma (Fig. 1.6).65 TNF-a inhibitors, anti-p40 (IL-12/IL-23 antago-
In the 1980s, narrow band UVB (311–313 nm) nists), IL-17 inhibitors, and the promise of new
was developed and shown to be efficacious. Since anti-p19 inhibitors (selective for IL-23) on the hori-
that time, phototherapy has proven to be a safe, zon. These medications are changing the treat-
effective treatment for psoriasis that does not ment of patients with psoriasis and improving
cause immunosuppression. clinical outcomes.

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model of keratinocyte-induced psoriasis-like acute respiratory distress syndrome. Br J Dermatol
skin inflammation. J Clin Invest 2006;116(8): 2004;150(2):353–6.
2094–104. 33. Varma R, Cantrell W, Elmets C, et al. Infliximab for
16. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, the treatment of severe pustular psoriasis: 6 years
et al. Psoriasis is characterized by accumulation of later. J Eur Acad Dermatol Venereol 2008;22(10):
immunostimulatory and Th1/Th17 cell-polarizing 1253–4.
myeloid dendritic cells. J Invest Dermatol 2009; 34. Umezawa Y, Ozawa A, Kawasima T, et al. Therapeu-
129(1):79–88. tic guidelines for the treatment of generalized pus-
17. Zaba LC, Krueger JG, Lowes MA. Resident and “in- tular psoriasis (GPP) based on a proposed
flammatory” dendritic cells in human skin. J Invest classification of disease severity. Arch Dermatol
Dermatol 2009;129(2):302–8. Res 2003;295(Suppl 1):S43–54.
18. Gudjonsson JE, Karason A, Runarsdottir EH, et al. 35. Marrakchi S, Guigue P, Renshaw BR, et al. Inter-
Distinct clinical differences between HLA-Cw*0602 leukin-36-receptor antagonist deficiency and
positive and negative psoriasis patients–an analysis generalized pustular psoriasis. N Engl J Med 2011;
of 1019 HLA-C- and HLA-B-typed patients. J Invest 365(7):620–8.
Dermatol 2006;126(4):740–5. 36. Oumeish OY, Parish JL. Impetigo herpetiformis.
19. Christophers E. Psoriasis–epidemiology and clinical Clin Dermatol 2006;24(2):101–4.
spectrum. Clin Exp Dermatol 2001;26(4):314–20. 37. Michaelsson G, Gustafsson K, Hagforsen E. The
20. Wu JJ, Choi YM, Bebchuk JD. Risk of myocardial psoriasis variant palmoplantar pustulosis can be
infarction in psoriasis patients: a retrospective improved after cessation of smoking. J Am Acad
cohort study. J Dermatolog Treat 2015;26(3):230–4. Dermatol 2006;54(4):737–8.
21. Gelfand JM, Neimann AL, Shin DB, et al. Risk of 38. Happle R. Linear psoriasis and ILVEN: is lumping or
myocardial infarction in patients with psoriasis. splitting appropriate? Dermatology 2006;212(2):
JAMA 2006;296(14):1735–41. 101–2.
22. Gelfand JM, Troxel AB, Lewis JD, et al. The risk of 39. Kvedar JC, Baden HP. Nail changes in cutaneous
mortality in patients with psoriasis: results from a disease. Semin Dermatol 1991;10(1):65–70.
population-based study. Arch Dermatol 2007; 40. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J
143(12):1493–9. Med 2009;361(5):496–509.
23. Gelfand JM, Dommasch ED, Shin DB, et al. The risk 41. Reich K, Kruger K, Mossner R, et al. Epidemiology
of stroke in patients with psoriasis. J Invest Derma- and clinical pattern of psoriatic arthritis in Germany:
tol 2009;129(10):2411–8. a prospective interdisciplinary epidemiological
24. Hjuler KF, Bottcher M, Vestergaard C, et al. study of 1511 patients with plaque-type psoriasis.
Increased prevalence of coronary artery disease in Br J Dermatol 2009;160(5):1040–7.
Chapter 1 Overview of Psoriasis 15

42. Radtke MA, Reich K, Blome C, et al. Prevalence and 54. Vittorio Luigi De Socio G, Simonetti S, Stagni G.
clinical features of psoriatic arthritis and joint com- Clinical improvement of psoriasis in an AIDS patient
plaints in 2009 patients with psoriasis: results of a effectively treated with combination antiretroviral
German national survey. J Eur Acad Dermatol Vene- therapy. Scand J Infect Dis 2006;38(1):74–5.
reol 2009;23(6):683–91. 55. O’Brien M, Koo J. The mechanism of lithium and
43. Mallbris L, Granath F, Hamsten A, et al. Psoriasis is beta-blocking agents in inducing and exacerbating
associated with lipid abnormalities at the onset psoriasis. J Drugs Dermatol 2006;5(5):426–32.
of skin disease. J Am Acad Dermatol 2006;54(4): 56. Famenini S, Wu JJ. Infliximab-induced psoriasis in
614–21. treatment of Crohn’s disease-associated ankylosing
44. Mallbris L, Akre O, Granath F, et al. Increased risk spondylitis: case report and review of 142 cases.
for cardiovascular mortality in psoriasis inpatients J Drugs Dermatol 2013;12(8):939–43.
but not in outpatients. Eur J Epidemiol 2004;19(3): 57. Ko JM, Gottlieb AB, Kerbleski JF. Induction and
225–30. exacerbation of psoriasis with TNF-blockade ther-
45. Augustin M, Reich K, Glaeske G, et al. Co-morbidity apy: a review and analysis of 127 cases.
and age-related prevalence of psoriasis: analysis of J Dermatolog Treat 2009;20(2):100–8.
health insurance data in Germany. Acta Derm Vene- 58. Richards HL, Fortune DG, O’Sullivan TM, et al. Pa-
reol 2010;90(2):147–51. tients with psoriasis and their compliance with
46. Cohen AD, Weitzman D, Dreiher J. Psoriasis and hy- medication. J Am Acad Dermatol 1999;41(4):581–3.
pertension: a case-control study. Acta Derm Vene- 59. Menter A, Korman NJ, Elmets CA, et al. Guidelines
reol 2010;90(1):23–6. of care for the management of psoriasis and psori-
47. Gelfand JM, Shin DB, Neimann AL, et al. The risk of atic arthritis. Section 3. Guidelines of care for the
lymphoma in patients with psoriasis. J Invest Der- management and treatment of psoriasis with
matol 2006;126(10):2194–201. topical therapies. J Am Acad Dermatol 2009;60(4):
48. Gupta MA, Gupta AK, Watteel GN. Early onset (< 643–59.
40 years age) psoriasis is comorbid with greater psy- 60. Ramsay CA. Management of psoriasis with calcipo-
chopathology than late onset psoriasis: a study of triol used as monotherapy. J Am Acad Dermatol
137 patients. Acta Derm Venereol 1996;76(6):464–6. 1997;37(3 Pt 2):S53–4.
49. Krueger G, Koo J, Lebwohl M, et al. The impact of 61. Hecker D, Worsley J, Yueh G, et al. Interactions be-
psoriasis on quality of life: results of a 1998 National tween tazarotene and ultraviolet light. J Am Acad
Psoriasis Foundation patient-membership survey. Dermatol 1999;41(6):927–30.
Arch Dermatol 2001;137(3):280–4. 62. Zonneveld IM, Rubins A, Jablonska S, et al. Topical
50. Herron MD, Hinckley M, Hoffman MS, et al. Impact tacrolimus is not effective in chronic plaque psori-
of obesity and smoking on psoriasis presentation asis. A pilot study. Arch Dermatol 1998;134(9):
and management. Arch Dermatol 2005;141(12): 1101–2.
1527–34. 63. Gribetz C, Ling M, Lebwohl M, et al. Pimecrolimus
51. Telfer NR, Chalmers RJ, Whale K, et al. The role of cream 1% in the treatment of intertriginous psoria-
streptococcal infection in the initiation of guttate sis: a double-blind, randomized study. J Am Acad
psoriasis. Arch Dermatol 1992;128(1):39–42. Dermatol 2004;51(5):731–8.
52. Gudjonsson JE, Thorarinsson AM, Sigurgeirsson B, 64. Margolis DJ, Abuabara K, Hoffstad OJ, et al.
et al. Streptococcal throat infections and exacerba- Association between malignancy and topical use
tion of chronic plaque psoriasis: a prospective of pimecrolimus. JAMA Dermatol 2015;151(6):
study. Br J Dermatol 2003;149(3):530–4. 594–9.
53. Obuch ML, Maurer TA, Becker B, et al. Psoriasis and 65. Chuang TY, Heinrich LA, Schultz MD, et al. PUVA
human immunodeficiency virus infection. J Am and skin cancer. A historical cohort study on 492 pa-
Acad Dermatol 1992;27(5 Pt 1):667–73. tients. J Am Acad Dermatol 1992;26(2 Pt 1):173–7.
CHAPTER 2
Ultraviolet B Phototherapy
Sandra Pena, BS, Dane Hill, MD, Steven R. Feldman, MD, PhD

KEYWORDS
 Phototherapy  Narrowband UV-B  UV therapy  Psoriasis  Excimer laser

KEY POINTS
 Phototherapy with UV light can be used in the treatment of several cutaneous disorders.
 Phototherapy is an efficacious treatment option in the management of psoriasis and should be a
first therapy considered in patients with moderate-to-severe plaque psoriasis.
 Narrowband UV-B is used as the first-line phototherapy treatment option for moderate-to-severe
psoriasis due to its clinical efficacy and mild side-effect profile.
 Targeted UV-B therapy phototherapy and employment of excimer lasers are excellent options for
patients with more limited disease, although there are now reports of use for extensive disease.

INTRODUCTION lamps. However, in 1978, Wiskemann introduced


Definition broadband UV-B radiation in a closed chamber
Phototherapy refers to the use of nonionizing ra- to treat psoriasis, which mitigated this drawback.8
diation, from the UV range, in the treatment of Despite these advances, broadband UV-B radia-
skin disorders (Table 2.1).1 It represents an effica- tion was less efficacious than psoralens followed
cious, cost-effective, and generally nonimmuno- by UV-A radiation, also known as PUVA therapy,
suppressive staple in the management of and as a result, did not gain widespread popu-
psoriasis.2 larity.5 It was not until the late 1970s when Parrish
and Jaenicke determined the action spectrum of
History psoriasis with a peak response at 313 nm that
The use of sunlight in the treatment of cutaneous gave impetus to narrowband (NB) UV-B as a new
diseases can be traced back to ancient times. Ev- phototherapeutic modality.9 In 1988, both Van
idence dating thousands of years demonstrates Weelden and colleagues10 and Green and col-
the use of plant extracts, including those from leagues11 demonstrated the superior clinical effi-
the Ammi majus plant (psoralens), followed by cacy of NB UV-B and subsequently marked the
sun exposure to treat vitiligo in Egypt and India.3 decline of broadband-UV-B (BB-UV-B) use for
However, it was not until the late nineteenth cen- psoriasis.
tury that heralded major advances in the develop-
ment and use of phototherapy.4 In 1901, Niels Types
Ryberg Finsen published the results of the treat- This chapter provides an overview of UVB photo-
ment of lupus vulgaris with a carbon arc lamp, therapy in the management of psoriasis.
which marked a breakthrough in the treatment
of skin diseases. For this, Finsen received a Nobel Broadband ultraviolet B (290–320 nm)
Prize in medicine, the first and only one ever Broadband (BB) UV-B phototherapy was initially
awarded in the field of dermatology.5 described in the Goeckerman regimen in 1925.
Shortly after in 1925, William Goeckerman For many decades, BB-UV-B remained an option
combined the use of UV radiation with coal tar in in the psoriasis treatment arsenal despite being
the treatment of psoriasis.6 The Goeckerman less efficacious than other treatment modalities.
regimen as it came to be known would remain a Presently, however, BB-UV-B has largely been
mainstay in phototherapy treatment of psoriasis replaced by NB-UV-B radiation, which has
for several decades.7 A major shortcoming of the demonstrated superior efficacy in clearing psori-
Goeckerman regimen was the low output of the atic lesions.12
17
18 Therapy for Severe Psoriasis

TABLE 2.1 it can also be used for severe psoriasis of the


Ultraviolet radiation spectrum palms/soles or even for extensive disease.
UV Spectrum (10–400 nm)
Abbreviation Wavelength (nm) TANNING BEDS
The use of commercial tanning beds may be a
UV-A 320–400
viable alternative for patients in which in-office
UV-B 290–320 and home phototherapy are either unaccessible
UV-C 200–290 or impractical. Although evidence to support the
routine use of tanning beds may be sparse,
approximately 36% to 52% of patients have
Narrowband ultraviolet B (311–313 nm) used tanning beds in the treatment of their psori-
First defined in 1976, NB-UV-B has taken the asis.20,21 However, given the increased risk of skin
place of BB-UV-B in the treatment and manage- cancer and full-body UV exposure, tanning bed
ment of psoriasis.9 NB-UV-B has gained popu- use remains controversial, and not all dermatolo-
larity over PUVA in the treatment of psoriasis for gists agree that they should be used.
several reasons. First, NB-UV-B had similar effi-
cacy rates compared with PUVA.12 Therefore,
NB-UV-B is generally favored over PUVA due to INDICATIONS
greater ease of use for the patient. Another factor Indications for UV-B radiation include psoriasis,
is the increased risk of squamous cell cancer (SCC) atopic dermatitis, vitiligo, and mycosis fungoides,
associated with PUVA treatments. The risk of SCC among several others (Table 2.2).22
increases as the number of PUVA treatments in-
creases.13 NB-UV-B phototherapy has not been
shown to incur any increased risk of skin cancer.14 MECHANISM OF ACTION
Last, NB-UV-B is safe to use in children and preg- The epidermal layer of human skin, composed pri-
nant patients and lacks psoralen-related side ef- marily of keratinocytes, absorbs most UV radia-
fects, which ultimately makes it more favorable tion, with only the longer wavelengths having
as an initial phototherapy modality.15 the ability to penetrate the dermis. It was thought
that UV-B’s antiproliferative properties were a

TARGETED PHOTOTHERAPY
Targeted phototherapy is a method of photother-
apy in which only affected areas of skin are treated. TABLE 2.2
Various devices can be used to deliver focused Ultraviolet B phototherapy indications
UV-B radiation on skin lesions while sparing unin-
Common Less Common
volved skin. These devices include high fluence
devices, like the excimer laser and flash lamp, Psoriasis Acquired perforating
and lower output devices, like UV-B light-emitting Vitiligo dermatosis
Atopic dermatitis Chronic urticaria
diodes.16 Introduced in 1997, the 308-nm excimer
Mycosis fungoides Cutaneous graft-
laser contains an unstable mixture of xenon and Pruritus (associated versus-host disease
chloride, which form “excited dimmers.” It is the with renal disease, Polymorphous light
dissociation of these dimers that produces the polycythemia vera) eruption
monochromatic wavelength, which is transmitted Cutaneous
via a fiber-optic cable to the lesion.17 The excimer mastocytosis
laser allows for targeted therapy that spares unin- Granuloma annulare
volved skin, especially in areas that are otherwise Lichen planus
difficult to treat, like the scalp, hands, and feet.17 Lichen simplex
In addition, it can generate high fluencies of chronicus
Lymphomatoid
UV-B, resulting in faster clearing and fewer expo-
papulosis
sures.18 Although the excimer laser is not suitable Parapsoriasis
for large body surface areas because the treat- Pityriasis lichenoides
ment may be considerably resource intensive Pityriasis rosea
and lengthy, the availability of more powerful UV Pityriasis rubra pilaris
emitting devices (and aggressive treatment proto- Seborrheic dermatitis
col) is extending the range of area that can be From Walker D, Jacobe H. Phototherapy in the age of bi-
treated.7,19 Although targeted treatment has ologics. Semin Cutan Med Surg 2011;30(4):196; with
generally been used for mild, localized psoriasis, permission.
Chapter 2 UV-B Phototherapy 19

result of direct DNA damage; however, recent ev- Broadband Ultraviolet B


idence suggests that phototherapy also exerts UV-B radiation is efficacious in the treatment and
immunomodulatory effects.23 Specifically, UV-B management of psoriasis. By virtue of being
radiation diminishes type-1 T-cell predominance discovered first, BB-UV-B has a longer safety re-
by altering cytokine profiles, induces apoptosis cord than NB-UV-B but is less efficacious in the
of keratinocytes and T cells, and depletes Langer- treatment of psoriasis. Only selective BB-UV-B
han cell numbers.24–26 (305–325 nm) has shown evidence of being as
Human T helper (Th) lymphocytes can be effective as NB-UV-B in clearing chronic plaque
separated into T effector cells, which protect the psoriasis.12
body from pathogens, and regulatory T cells, which
dampen immune responses when they become Narrowband Ultraviolet B
dangerous to the host. Different subsets of effector NB-UV-B phototherapy is an effective therapeutic
T helper cells are distinguished based on their cyto- option in the treatment of plaque psoriasis. In a
kine production profiles in addition to transcription systematic review of 41 randomized control trials,
factors and homing receptor expression.27 The 68% of patients receiving NB-UV-B monotherapy
main T helper subsets include Th1, Th2, and achieved plaque clearance, whereas 62%
Th17. In psoriasis, it is the Th1/Th17 T cells that achieved PASI-75.34 When compared with oral
overexpress Th1 and Th17 cytokines, which, in PUVA, NB-UV-B may be less efficacious in clearing
turn, influence the hyperproliferation of keratino- lesions but favored overall because of less risk of
cytes and the resultant inflammation.28 adverse events and increased ease of use.12,35
UV-B radiation shifts the dysregulated predom- If NB-UV-B phototherapy alone is insufficient
inance of Th1/Th17-mediated immune response in to manage a patient’s disease, then a combina-
psoriasis to more of a Th2 response. Specifically, tion of NB-UV-B plus topical or systemic adjuncts
UV-B phototherapy induces interleukin-10 (IL-10) may be considered.4 Emollients, including petro-
production in human keratinocytes, which is a ma- leum jelly, mineral oil, and coal tar, may result in
jor regulatory cytokine in the Th2 pathway.29 In improved plaque clearance.35 In addition, calcipo-
addition, phototherapy downregulates Th1/Th17 triol and maxacalcitol (vitamin D analogues) and
proinflammatory pathways by decreasing patho- psoralens at higher concentrations may also facil-
genic cytokine (IL-23, IL-20, interferon-g, IL-17, IL- itate lesion resolution.35 Regarding systemic ad-
22) production.30 juncts to NB-UV-B phototherapy, the addition of
Furthermore, UV-B exerts its therapeutic ef- methotrexate to NB-UV-B renders the treatment
fects by inducing apoptosis. Apoptosis is a pro- more efficacious than NB-UV-B alone.35
cess of programmed cell death in response to Combining phototherapy with retinoids or cyclo-
noxious stimuli. Evidence indicates that one sporine decreases the cumulative NB-UV-B dose
mechanism in which UV-B clears psoriatic lesions needed to clear psoriasis. Combination therapy
is through the induction of apoptosis in keratino- using biologics may potentiate their efficacy, but
cytes, epidermal T cells, and to a lesser extent, sufficient data are lacking.35
Langerhans cells.26,31,32 Data in children and pregnant women have
Last, UV-B is involved in promoting localized also been promising, because 51% of pediatric
immunosuppression. In addition to apoptosis, patients achieved complete clearance and an
UV-B radiation influences the migration of Langer- additional 41% had a 75% reduction in their
hans cells from the epidermis as well as decreases PASI score.36
dendritic cell expression of B7 costimulatory sig-
nals, which is necessary for the stimulation and TARGETED PHOTOTHERAPY
activation of T cells.32,33 Recent meta-analyses using a PASI clearance of
75% evaluated the efficacy of targeted NB-UV-B
in the treatment of plaque psoriasis and demon-
EFFICACY strated efficacy rates for the excimer (308-nm)
Efficacy can be evaluated with regards to fluency, laser to be 70%, 59% for excimer (308-nm) light,
clearance, remission times, and number of treat- and 49% for localized NB-UV-B (311–313-nm)
ments.16 The Psoriasis Area and Severity Index light.37
(PASI) score was developed as a tool to measure In addition, the excimer laser can clear psoria-
the severity of psoriasis. A variant of that score, sis, with about 70% of patients having a 75% or
the PASI-75, determines the percentage of pa- greater reduction in their psoriatic lesions.37,38
tients that achieved 75% reduction in the baseline Although partial clearance is possible in as few
PASI score and is a common measure of treat- as one session, usually higher frequency treat-
ment efficacy. ments (2 to 3 per week) are considered to be
194 Index

REVEAL (continued ) retinoids in prevention of, 55


efficacy in, 112–114 Suicide, ixekizumab and, 159
in open trial extension of, 112–113, 115
safety in, 117, 120
Rheumatoid arthritis T
biosimilars in, 165 TALTZ. See Ixekizumab (Taltz)
methotrexate and adalimumab combination Tanning beds
for, 173 in delivery of phototherapy, 18
methotrexate in, 37 efficacy of, 20
in psoriasis, 9 Tazarotene, 12
Risankizumab, anti-IL-23 agent, 183, 185 TEMPO trial of methotrexate-etanercept
combination, 175
Teratogenicity
S of acretin, 55–56
SABER, safety assessment of adalimumab, 117 of methotrexate, 44–45
Salicylic acid, 12 Third space fluids, excessive, methotrexate
Sandimmune. See Cyclosporine (CsA) and, 44
(Sandimmune; Neoral) Tildrakizumab, investigational anti-IL-23 agent,
Secukinumab (Cosentyx), 139–151 183, 185
adverse events Topical therapies, 11–13
Candida, 145 Tuberculosis
in ERASURE and FIXTURE trials, 145–147 with adalimumab, 121
immunogenicity risk, 147 with etanercept, 90
in JUNCTURE and FEATURE trials, 145–147 with infliximab, 104
neutropenia, 145 ixekizumab and, 159
described, 139 with secukinumab, 147–148
dosage and administration of, 139–140 Tumor necrosis factor (TNF) inhibitor therapy, and
efficacy of cardiovascular risk reduction, 93–94, 123–124
in CLEAR trial, 142, 144–145
in ERASURE trial, 141–144
in FEATURE trial, 142, 144–145 U
in FIXTURE trial, 140–144 UNCOVER trials of ixekizumab (Taltz)
in JUNCTURE trial, 142 efficacy of, 153–155, 157
mechanism of action of safety of, 157–159
IL-17A binding and neutralizing, 139–140 U.S. psoriasis pivotal trial of etanercept
monitoring of efficacy of, 84–86
American Academy of Dermatology safety of, 88
recommendations, 148 Ustekinumab, 127–137
baseline, 148–149 defined, 127
Centers for Disease Control and Prevention dosing of, 127–128
recommendations, 148 efficacy of
for TB, 148 in ACCEPT trial, 129–130
pharmacokinetics of, 139 assessments in, 128
precautions in CADMUS trial in pediatric patients, 131
Crohn disease, 148 decreased, factors affecting, 130–131
hypersensitivity reactions, 148 in palmoplantar psoriasis, 131
infections, 147 in PHOENIX 1 trial, 128–129
pregnancy, 148 in PHOENIX 2 trial, 129–130
tuberculosis, 147–148 PSOLAR trial, 130–131
safety of, in comparison to placebo, 145 in psoriatic psoriasis, 131
vaccination recommendations, National mechanism of action of
Psoriasis Foundation, 149–150 cytokines IL-12 and IL-23 blockade in,
Skin cancer, from PUVA therapy, 31–32 127–128
Smoking, psoriasis and, 10 JAK-STAT signaling pathway in, 127
SPIRIT trial, induction of infliximab, 98–99 monitoring of
Squamous cell carcinoma American Academy of Dermatology
acretin in prevention of, 55 recommendations, 132
Index 195

baseline TB test, 132 National Psoriasis Foundation


Centers for Disease Control and Prevention recommendations, 133–134
recommendations, 132–133
initial baseline, 133
pharmacokinetics of, 128 V
safety of Vitamin D3 and analogues, 11–12
infections, 132 von Zumbusch psoriasis, 6–7
major adverise cardiovascular events
risk, 132
malignancies, 132 W
vaccinations Woronoff rings, 5

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