Ebook Psoriasis and psoriatic arthritis - Pathophysiology, therapeutic intervention, and complementary medicine: Part 1

Psoriasis and Psoriatic Arthritis
Pathophysiology, Therapeutic Intervention,
and Complementary Medicine





Psoriasis and Psoriatic Arthritis
Pathophysiology, Therapeutic Intervention,
and Complementary Medicine

Edited by

Siba P. Raychaudhuri
University of California Davis, School of Medicine
and Veterans Affairs Medical Center Sacramento, CA

Smriti K. Raychaudhuri
University of California Davis, School of Medicine
and Veterans Affairs Medical Center Sacramento, CA

Debasis Bagchi
University of Houston College of Pharmacy, Houston, TX, USA


CRC Press
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Library of Congress Cataloging‑in‑Publication Data
Names: Raychaudhuri, Siba P., editor. | Kundu-Raychaudhuri, Smriti K., editor. |
Bagchi, Debasis, 1954- editor.
Title: Psoriasis and psoriatic arthritis : pathophysiology, therapeutic intervention, and
complementary medicine / [edited by] Siba P. Raychaudhuri, Smriti K. Raychaudhuri & Debasis Bagchi.
Other titles: Psoriasis and psoriatic arthritis (Raychaudhuri)
Description: Boca Raton, FL : CRC Press/Taylor & Francis Group, 2018. |
Includes bibliographical references.
Identifiers: LCCN 2017036704 | ISBN 9781498756068 (hardback)
Subjects: | MESH: Psoriasis--therapy | Arthritis, Psoriatic--therapy | Psoriasis--epidemiology |
Arthritis, Psoriatic--epidemiology | Complementary Therapies
Classification: LCC RL321 | NLM WR 205 | DDC 616.5/26--dc23
LC record available at />Visit the Taylor & Francis Web site at

and the CRC Press Web site at

To my late beloved friend and colleague, Pinaki Ranjan Khan
(Bhaduri). I always see him in his smiling face, my great friend,
philosopher, and guide. May Almighty God bless him always.
Debasis Bagchi
To my parents, Durga Pada and Bilwabasani Roychowdhury,
my sister, Dr. Moitrayee Roychowdhury, and my brothers,
Dr. Debi Prasad & Vwani Prasad Roychowdhury.
Siba P. Raychaudhuri
To my parents, Mrityunjoy and Uma Kundu, and to my
daughters, Blossom, Gunjari and Genea.
Smriti K. Raychaudhuri





Contents
Preface...............................................................................................................................................xi
Editors............................................................................................................................................. xiii
Contributors...................................................................................................................................... xv

Section I  Disease Epidemiology and Genetics
Chapter 1 Epidemiology of Psoriasis and Psoriatic Arthritis........................................................3
Adarsh M. B. and Aman Sharma
Chapter 2 Genetics of Psoriasis and Psoriatic Arthritis................................................................9
Remy Pollock and Vinod Chandran

Section II  Pathogenesis
Chapter 3 Inflammation in Psoriasis and Psoriatic Arthritis....................................................... 35
Latika Gupta and Amita Aggarwal
Chapter 4 Psoriasis and Diabetes: An Unholy Alliance.............................................................. 45
Satinath Mukhopadhyay, Deep Dutta, and Dipyaman Ganguly
Chapter 5 Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease........................ 53
Asmita Hazra and Saptarshi Mandal
Chapter 6 Multifaceted Role of Th17 Cells in Psoriatic Disease............................................... 123
Soumya D. Chakravarty
Chapter 7 Nerve Growth Factor and Its Receptor System in Rheumatologic Diseases
and Pain Management: A New Dimension in Pathogenesis and Novel Drugs
in the Pipeline............................................................................................................ 133
Smriti K. Raychaudhuri and Siba P. Raychaudhuri

Section III  Psoriatic Disease: Clinical Profiles
Chapter 8 Psoriasis: Clinical Spectrum..................................................................................... 149
Chelsea Ma, Smriti K. Raychaudhuri, Emanual Maverakis,
and Siba P. Raychaudhuri

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viii

Contents

Chapter 9 Clinical Spectrum of Spondyloarthritis.................................................................... 159
Joerg Ermann
Chapter 10 Comorbidities in Psoriatic Arthritis.......................................................................... 165
Maria J. Antonelli and Marina Magrey

Section IV-A  Treatment Regimen: Pharmaceuticals and Treatment
Chapter 11 Current Recommendations for the Treatment of Psoriasis....................................... 177
Chelsea Ma and Emanual Maverakis
Chapter 12 Management of Psoriatic Arthritis............................................................................ 195
Siba P. Raychaudhuri, Reason Wilken, Debashis Sarkar,
Emanual Maverakis, and Smriti K. Raychaudhuri
Chapter 13 Targeting IL-23/IL-17 Axis for Treatment of Psoriasis and Psoriatic Arthritis....... 223
Subhashis Banerjee and Philip Mease
Chapter 14 DMARD Treatment in Patients with Psoriatic Arthritis.......................................... 235
Rafael Valle Oñate and Andrea Chaparro
Chapter 15 Topical Therapies for Psoriasis................................................................................. 243
Michael Sticherling
Chapter 16 Overview of JAK-STAT Pathways in Spondyloarthritis........................................... 261
Smriti K. Raychaudhuri, Sanchita Raychaudhuri, Debasis Bagchi,
Anand Swaroop, and Siba P. Raychaudhuri
Chapter 17 Concept of Total Care: Multidisciplinary Approach for the Management
of Psoriatic Disease................................................................................................... 271
Smriti K. Raychaudhuri, Debasis Bagchi, and Siba P. Raychaudhuri

Section IV-B  Treatment Regimen: Nutraceuticals in Psoriasis
Chapter 18 Nutraceutical Components in the Treatment of Psoriasis and Psoriatic Arthritis.... 283
Urmila Jarouliya and Raj K. Keservani
Chapter 19 Herbal Products for the Treatment of Psoriasis........................................................ 299
Anna Herman and Andrzej P. Herman


ix

Contents

Chapter 20 Impact of Nutrition and Dietary Supplementation on Psoriasis Pathology.............. 323
Odete Mendes, Mithila Shitut, and Jayson Chen
Commentary Psoriasis and Psoriatic Arthritis: Pathophysiology, Therapeutic Intervention,
and Complementary Medicine.............................................................................. 335
Smriti K. Raychaudhuri, Debasis Bagchi, and Siba P. Raychaudhuri
Index............................................................................................................................................... 337





Preface
Psoriasis is a lifelong chronic autoimmune disorder, a chronic heterogeneous skin pathophysiology characterized by thick, scaly skin lesions and accompanied by massive inflammation, extensive hyperproliferation of keratinocytes, scaly plaques, and erythema. In psoriasis lesions, skin
cells (keratinocytes) grow too quickly, resulting in thick, white, silvery, or red patches on the skin.
Generally, skin cells grow gradually and flake off about every 4 weeks. New skin cells grow to
replace the outer layers of the skin as they shed. However, in psoriasis, new skin cells move rapidly
to the surface of the skin in days rather than weeks. They build up and form thick patches known as
plaques. The patches range in size from small to large. They most often appear on the elbows, scalp,
feet, knees, hands, or lower back, or as the more embarrassing flaking of the skin and/or patches on
the face. Generally, psoriasis is most common in adults, but teenagers and children can also suffer
from it.
Psoriasis is not just a skin condition; it begins underneath the skin. It is a chronic disease of the
immune system. Psoriasis is frequently associated with a severe form of arthritis. In other words,
psoriatic arthritis is a chronic form of inflammatory arthritis accompanied by psoriasis. Psoriasis
and psoriatic arthritis together are considered psoriatic diseases. Several comorbidities are associated with psoriatic disease, such as type 2 diabetes, metabolic syndrome, cardiovascular disease,
and depression.
Several pharmaceutical therapeutics and treatment options are available for psoriasis and psoriatic arthritis. This book demonstrates a significant number of treatment modalities available for
psoriasis and psoriatic arthritis. Currently, nutraceuticals and functional food-based formulations
are becoming popular for almost every medical condition. Here we have invited several leading

authorities to contribute their opinion on nutraceuticals and functional food-based therapy for psoriasis and psoriatic arthritis.
A total of 21 chapters have been compiled in this book involving global leaders in the field. The
first two sections present an extensive discussion of the epidemiology, genetics, pathogenesis, and
­inflammatory sequences of psoriasis; the association of the metabolic syndrome; angiogenesis and the
roles of adhesion molecules; the regulatory role of Th17 cells; and the nerve growth factor and its receptor system.
Section III emphasizes the clinical profiles, including the clinical spectrum of psoriasis and
spondyloarthritis, comorbidities in psoriatic arthritis.
Section IV, Part A, highlights the treatment regimen in seven discrete chapters, including the
current treatment recommendations for psoriasis, the management of psoriatic arthritis, intricate
aspects and the role of IL-23/IL-17 inhibitors, the roles of disease-modifying antirheumatic drugs,
topical therapies, JAK-STAT pathophysiology, and finally, the concept of total care, which is a multidisciplinary approach for the management of psoriatic disease.
Section IV, Part B, includes three classic chapters highlighting the beneficial roles of nutraceutical components, herbal products, and the impact of nutrition and dietary supplements on psoriasis
pathology. Bioactive whey extract has demonstrated the presence of growth factors, active peptides, and immunoglobulins that block skin inflammation by inhibiting the actions of tumor necrosis factor-alpha and inflammatory cascade at the molecular level. Several antioxidants, including
alpha lipoic acid, N-acetyl cysteine, glutathione, curcumin and turmeric, astaxanthin, and several
structurally diverse antioxidants, demonstrate a potential natural therapeutic strategy for psoriasis.
Nutraceutical therapeutic options are far less expensive and not associated with adverse side effects.

xi


xii

Preface

Section V provides a commentary from the editors’ desk, discussing the final take-home message for the readers.
The editors sincerely thank all the eminent authors and contributors in this book, and more
importantly, the editors thank Randy Brehm and Sylvester O’Gilvie for their cooperation and assistance. We sincerely hope that our readers enjoy reading this book.
Siba P. Raychaudhuri
Smriti K. Raychaudhuri
Debasis Bagchi

Editors
Siba P. Raychaudhuri, MD, FACP, FACR, is the chief of the Rheumatology Division at the VA
Medical Center in Sacramento, California, and a senior faculty in the Division of Rheumatology,
Allergy and Clinical Immunology at the University of California, Davis. Dr. Raychaudhuri is a
dermatologist, rheumatologist, and immunologist. He has an extensive background in translational research that extends back to his fellowship period at Stanford University, California.
Dr. Raychaudhuri’s research group works in arthritis, human autoimmune diseases, cell biology, the
nerve growth factor, and animal models of human diseases. His research group has dissected the
regulatory role of the nerve growth factor and its receptor system in cell trafficking, angiogenesis,
the growth and survival of keratinocytes, T cells, and fibroblast-like synovium. These observations have provided new insights into the pathogenesis of psoriasis, psoriatic arthritis, rheumatoid
arthritis, and osteoarthritis. Dr. Raychaudhuri’s research over the last three decades has promoted
significant insight into and understanding of the cytokine network in autoimmune arthritis, which
includes the regulatory roles of RANTES, fractalkine, IL-9, IL-17, and IL-22 in psoriasis, psoriatic
arthritis, and rheumatoid arthritis.
Smriti K. Raychaudhuri, MD, is a professor of medicine and medical microbiology at California
Northstate University College of Medicine. She is also the director of the Cellular and
Clinical Immunology Research Laboratory at the Sacramento VA Medical Center, California.
Dr. Raychaudhuri earned her MD in 1987 from the All India Institute of Medical Sciences, Delhi
and received her postdoctoral training in immunology at Stanford University, California. She
conducted clinical trials on immune-based therapy for HIV at Stanford University. Currently, her
research group works on the pathogenesis of autoimmune diseases, with a focus on elucidating the
cytokine network and cell trafficking in psoriasis and psoriatic arthritis.
Debasis Bagchi, PhD, MACN, CNS, MAIChE, received his PhD in medicinal chemistry in 1982.
He is the chief scientific officer at Cepham Research Center, Piscataway, New Jersey; a professor
in the Department of Pharmacological and Pharmaceutical Sciences at the University of Houston
College of Pharmacy, Texas; and an adjunct faculty at Texas Southern University, Houston. He
served as the senior vice president of research and development of InterHealth Nutraceuticals Inc.,
Benicia, California, from 1998 until February 2011, and then as director of innovation and clinical
affairs at Iovate Health Sciences, Oakville, Ontario, until June 2013. Dr. Bagchi received the Master

of American College of Nutrition Award in October 2010. He is a past chairman of the International
Society of Nutraceuticals and Functional Foods, a past president of the American College of
Nutrition, Clearwater, Florida, and a past chair of the Nutraceuticals and Functional Foods Division
of the Institute of Food Technologists, Chicago. He is serving as a distinguished advisor on the
Japanese Institute for Health Food Standards, Tokyo. Dr. Bagchi is a member of the Study Section
and Peer Review Committee of the National Institutes of Health, Bethesda, Maryland. He has 324
papers in peer-reviewed journals, 30 books, and 19 patents. Dr. Bagchi is also a member of the
Society of Toxicology, a member of the New York Academy of Sciences, a fellow of the Nutrition
Research Academy, and a member of the TCE stakeholder Committee of the Wright-Patterson Air
Force Base, Ohio. Dr. Bagchi is the associate editor of the Journal of Functional Foods, the Journal
of the American College of Nutrition, and Archives of Medical and Biomedical Research, and he
also serves on the editorial boards of numerous peer-reviewed journals, including Antioxidants &
Redox Signaling, Cancer Letters, Toxicology Mechanisms and Methods, and The Original Internist
among other journals.

xiii





Contributors
Amita Aggarwal
Department of Clinical Immunology
Sanjay Gandhi Postgraduate Institute
of Medical Sciences
Lucknow, India
Maria J. Antonelli
MetroHealth Medical Center/Case Western
Reserve University

Cleveland, Ohio
Debasis Bagchi
Department of Pharmacological
and Pharmaceutical Sciences
University of Houston College of Pharmacy
Houston, Texas
and
Cepham Inc.
Piscataway, New Jersey
Subhashis Banerjee
Bristol-Myers Squibb
Princeton, New Jersey
Soumya D. Chakravarty
Division of Rheumatology
Drexel University College of Medicine
Philadelphia, Pennsylvania
and
Janssen Scientific Affairs, LLC
Horsham, Pennsylvania
Vinod Chandran
Department of Medicine
Division of Rheumatology
University of Toronto
Toronto, Ontario, Canada
Andrea Chaparro
Rheumatology and Clinical Immunology
Military Hospital/EMNG
Bogota, Colombia

Deep Dutta

Department of Endocrinology
Venkateshwar Hospitals
Dwarka, New Delhi, India
Joerg Ermann
Division of Rheumatology, Immunology
and Allergy
Department of Medicine
Brigham and Women’s Hospital
and
Harvard Medical School
Boston, Massachusetts
Dipyaman Ganguly
IICB-Translational Research Unit of Excellence
(TRUE) and Division of Cancer Biology
and Inflammatory Disorders
CSIR-Indian Institute of Chemical Biology
Kolkata, India
Latika Gupta
Department of Clinical Immunology
Sanjay Gandhi Postgraduate Institute
of Medical Sciences
Lucknow, India
Asmita Hazra
Department of Biochemistry
Christian Medical College Vellore
Vellore, Tamil Nadu, India
Andrzej P. Herman
Laboratory of Molecular Biology
Kielanowski Institute of Animal Physiology
and Nutrition

Polish Academy of Sciences
Warsaw, Poland
Anna Herman
Faculty of Cosmetology
Academy of Cosmetics and Health Care
Warsaw, Poland

Jayson Chen
Product Safety Laboratories
Dayton, New Jersey
xv


xvi

Urmila Jarouliya
School of Studies in Biotechnology
Jiwaji University
Gwalior, Madhya Pradesh, India
Raj K. Keservani
School of Pharmaceutical Sciences
Rajiv Gandhi Proudyogiki Vishwavidyalaya
Bhopal, Madhya Pradesh, India
Adarsh M. B.
Post-Graduate Institute of Medical Education
and Research (PGIMER)
Chandigarh, Panjab, India
Chelsea Ma
Department of Dermatology
School of Medicine

University of California
Davis, California

Contributors

Satinath Mukhopadhyay
Department of Endocrinology
Institute of Postgraduate Medical Education
and Research (IPGMER) and Seth Sukhlal
Karnani Memorial (SSKM) Hospital
Kolkata, India
Remy Pollock
Psoriatic Arthritis Program
Center for Prognosis Studies in the Rheumatic
Diseases
Toronto Western Hospital
Toronto, Ontario, Canada
Sanchita Raychaudhuri
Harvard College
Molecular and Cellular Biology
Cambridge, Massachusetts

Saptarshi Mandal
Department of Transfusion Medicine
and Blood Bank
All India Institute of Medical Sciences Jodhpur
Jodhpur, Rajasthan, India

Siba P. Raychaudhuri
VA Sacramento Medical Center

Department of Veterans Affairs
Northern California Health Care System
Mather, California
and
Department of Medicine
Division of Rheumatology, Allergy
and Clinical Immunology
School of Medicine
University of California
Davis, California

Emanual Maverakis
Department of Dermatology
School of Medicine
University of California
Davis, California

Smriti K. Raychaudhuri
VA Sacramento Medical Center
Department of Veterans Affairs
Northern California Health Care System
Mather, California

Philip Mease
Swedish Medical Center and University
of Washington
Seattle, Washington

Debashis Sarkar
Department of Dermatology and Venereology

MGM Medical College and LSK Hospital
Kishanganj, India

Odete Mendes
Product Safety Laboratories
Dayton, New Jersey

Aman Sharma
Clinical Immunology and Rheumatology
Services
Department of Internal Medicine
Postgraduate Institute of Medical Education
and Research
Chandigarh, India

Marina Magrey
MetroHealth Medical Center/Case Western
Reserve University
Cleveland, Ohio


xvii

Contributors

Mithila Shitut
Product Safety Laboratories
Dayton, New Jersey
Michael Sticherling
Hautklinik Universitätsklinikum Erlangen

Erlangen, Germany
Anand Swaroop
Cepham Inc.
Piscataway, New Jersey

Rafael Valle Oñate
Colombian Clinic of Rheumatology
Military Hospital/EMNG
Bogota, Colombia
and
Brigham and Women’s Hospital
Harvard University
Boston, Massachusetts
Reason Wilken
Department of Dermatology
School of Medicine
University of California
Davis, California





Section I
Disease Epidemiology and Genetics

1

Epidemiology of Psoriasis
and Psoriatic Arthritis
Adarsh M. B. and Aman Sharma

CONTENTS
1.1Introduction...............................................................................................................................3
1.2 Prevalence of Psoriasis..............................................................................................................3
1.3 Incidence and Prevalence of Psoriatic Arthritis........................................................................3
1.4 Classification Criteria of Psoriatic Arthritis..............................................................................4
1.5 Clinical Characteristics and Prevalence of Psoriatic Arthritis in Psoriasis..............................4
1.6 Risk Factors for the Development of Psoriatic Arthritis in Psoriasis........................................5
1.7 Genetic Epidemiology of Psoriasis and Psoriatic Arthritis.......................................................5
1.8 Role of Screening Tools.............................................................................................................5
1.9 Epidemiology of Metabolic Syndrome and Cardiovascular Disease Risk Factors
in Psoriatic Arthritis and Psoriasis............................................................................................6
References...........................................................................................................................................6

1.1 INTRODUCTION
Psoriasis (PsO), the great dermatologic mystery, has been known since the days of Hippocrates
and is one of the oldest maladies. From that dark era when it was a social stigma, with people
being kept in isolation, the modern-day treatment instills confidence of good treatment outcomes.
From the historical use of arsenic and boiled viper, we have reached a stage where the therapeutic
armamentarium has expanded to include an increasing array of biological agents. Still, a lot needs
to be done, and thus the quest to know continues. Epidemiological aspects play a crucial role in
describing any disease. These help in analyzing the distribution as well as determinants of a disease.
Epidemiological studies have often helped in policy making on disease prevention and treatment.

1.2 PREVALENCE OF PSORIASIS

The prevalence of PsO in most of the population is around 0.5%–5%.1,2 It has been reported to
be 4.2% in Norway,1 2.8% in Italy,3 0.47% in China,4 and 0.34% in Japan2 in various populationbased studies. The prevalence is higher in clinic-based studies, with PsO accounting for up to 8%
of patients. The prevalence of PsO was found to be higher among young women in a Norwegian
population survey. The onset of PsO was also early among females in this population,1 while in most
other studies, the prevalence of PsO was higher among males.4,5

1.3 INCIDENCE AND PREVALENCE OF PSORIATIC ARTHRITIS
Since the time Alibert described an arthritis associated with PsO, psoriatic arthritis (PsA) has evoked
curiosity in numerous minds. It is a chronic inflammatory arthritis characterized by enthesitis, spinal
involvement, and nail changes. Against the initial belief of a relatively benign nature, it is now accepted
that it can be as crippling and chronic as rheumatoid arthritis (RA), with up to one-third of patients
developing erosions within the first year of the disease. Based on the population surveyed and the methods
3


4

Psoriasis and Psoriatic Arthritis

used (registry based or population based), the prevalence rates vary. The prevalence of PsA in registrybased studies varies from 0.19% in the United Kingdom6 to 0.74% in a Latin American population.7
The prevalence in population-based studies was reported to be 0.47% in the Czech Republic,8 0.25% in
the United States,9 and 0.13% in Norway.10 The incidence rate was 6.9/100,000 in the Norwegian study.
Studies in the Asian population are lacking, except for a single Chinese study that reported a low prevalence of 0.02%.11 As in the case of PsO, there is a male predominance in PsA, with a male-to-female
ratio of 1.2–2:1 in various studies,7,10,12 with the onset of arthritis in the third or fourth decade.7

1.4 CLASSIFICATION CRITERIA OF PSORIATIC ARTHRITIS
The evolution of criteria used in the classification of PsA over the years hints at the ongoing efforts
to develop the most suitable criteria. One reason for the difference in incidence of PsA in various
epidemiological studies is the use of different classification criteria. Since the first criteria proposed
by Moll and Wright, which was simple and based on clinical variables alone, the criteria evolved

through Bennette, Vasey, Gladman, the European Spondyloarthropathy Study Group (ESSG),
McGonagle, and the latest Classification Criteria for Psoriatic Arthritis (CASPAR). Except for the
Bennette criteria, none of the others used synovial fluid assessment or synovial biopsy as a variable.
It was ESSG criteria that introduced the family history of PsO into the criteria for the first time.
The CASPAR, which were formed as the result of an international collaboration, have a sensitivity
and specificity above 90% in most of the validation studies.13,14 Although the recent Assessment of
Spondyloarthritis Society (ASAS) criteria for peripheral spondyloarthropathy can be used to classify PsA, when compared with CASPAR, it has a low sensitivity (48% vs. 89%).15 Some authors
suggest giving a differential weight to the variables in CASPAR, especially those of present PsO
and a past history of PsO, as well as defining the musculoskeletal symptoms to improve it. Most of
the current epidemiological studies and clinical trials on PsA use CASPAR.

1.5 CLINICAL CHARACTERISTICS AND PREVALENCE
OF PSORIATIC ARTHRITIS IN PSORIASIS
The prevalence of PsA among PsO patients varies widely. The variation is due to the different criteria used, the geographic area, and the investigator (rheumatologist or dermatologist). It varies from
1% to 48%.16–19 The prevalence is lower among the Asian population, with most studies reporting a
prevalence of less than 10%.16,20,21 In an Indian study, the prevalence was 8.7%.20 The annual incidence rate of developing arthritis in a PsO cohort, which was followed for a duration of 4 years,
was 1.87 per 100 person-years.22 In a multicentric clinic-based cross-sectional study in Europe, the
incidence rate was found to be 74 per 1000 persons, and it remained constant after PsO diagnosis.23
The prevalence of arthritis was 20% at 30 years in the same study. The cumulative incidence of PsA
was 1.7%, 3.1%, and 5.1% at 5, 10, and 20 years of PsO diagnosis, respectively.24 Subclinical arthritis
with capsular distension and periarticular edema has been shown on MRI in 68% of PsO patients.25
Arthritis is most common among patients with plaque-type PsO compared with the guttate or pustular type.16,26,27 In most series, including that by Moll and Wright,28 the most common presentation
of PsA is assymetrical oligoarthritis.10,27,29,30 However, many studies in the Asian population have
reported polyarthritis, either symmetrical or asymmetrical, as the most common pattern of involvement.20,26 The presence of polyarthritis itself has been shown to be a predictor for erosive disease.12
The incidence of spinal involvement varies among various populations and is reported to be higher
in the Asian population than in the Western population.20,21,26,31 Arthritis mutilans is seen in less than
5% of patients.10,27 It has also been observed that PsA patients with early-onset PsO have fewer skin
lesions and less joint involvement at presentation and a higher frequency of spondyloarthropathy.

Epidemiology of Psoriasis and Psoriatic Arthritis

5

1.6 RISK FACTORS FOR THE DEVELOPMENT
OF PSORIATIC ARTHRITIS IN PSORIASIS
Patients with PsA have severe scalp involvement, skin disease, and nail changes.30,32 Nail dystrophy, intergluteal/perianal PsO, and scalp lesions have also been shown to be associated with PsA.24
Among the Asian population, Indian ethnicity has been suggested as a risk factor for the development of PsA.31 Patients with PsA have a higher mortality than the general population. High disease
burden, as suggested by an elevated erythrocyte sedimentation rate (ESR) and erosive disease, is a
predictor of mortality in PsA.33

1.7 GENETIC EPIDEMIOLOGY OF PSORIASIS AND PSORIATIC ARTHRITIS
Both PsO and PsA have a multifactorial pattern of inheritance. Most of the initial evidence for the
genetic predisposition of a disease comes from twin studies. In PsO, the risk is three times more
in monozygotes than in heterozygotes.34 There have not been many studies done in twins. Moll
and Wright described PsA among monozygotic twins in a set of triplets. Among the populationbased studies, the sibling recurrence risk for PsO varies between 4 and 10.35 The lifetime risk for
PsO, as calculated by Swanbeck et al., was 0.04 if no parent was affected and 0.65 if both were
affected.36 For PsA, the sibling recurrence rate is substantially higher than that for PsO. In the
United Kingdom, the sibling recurrence risk was calculated to be 55 based on the prevalence rates
for PsA.35 The estimated heritability for PsO is 60%–90%. Although most of the time inheritance
is multifactorial, an autosomal pattern has also been shown. It has also been seen that affected
children with PsO are more likely to have an affected father than an affected mother, and this is
attributed to genetic imprinting.37 Considering human leukocyte antigen (HLA) studies, type I PsO
(onset less than 40 years) had a stronger HLA association with HLA-Cw6 and HLA-DR7 than type
II PsO. Early-onset and more severe PsO has been associated with HLA-Cw*0602.38 A candidate
region was identified in chromosome 16 in a genome-wide scan for PsA.39 PsA patients with earlyonset PsO have a stronger HLA association. HLA-Cw*0602 has been shown to be associated with
PsA. HLA-B27 is more common with back involvement, while HLA-B37 and HLA-B38 are more
common with peripheral arthritis.40

1.8 ROLE OF SCREENING TOOLS

Undiagnosed PsA among patients with PsO varies from 4.9% to 85% in various studies highlighting the unmet need for having a sensitive screening tool for diagnosing PsA in patients with
PsO. Many such screening tools have been developed, but their utility rests on the sensitivity, as
well as the ease of administration. This includes the Psoriatic Arthritis Screening and Evaluation
(PASE) tool, the Psoriasis Epidemiology Screening Tool (PEST), the Toronto Psoriatic Arthritis
Screen (ToPAS), and Early Arthritis for Psoriasis Patients (EARP) questionnaires. The PASE
questionnaire had a sensitivity and specificity of 82% and 73% at a cutoff score of 47,41 while
they were 76% and 76% at a score of 44.42 Although the PASE score correlated with the disease
severity and treatment response, the complexity of its administration made it less attractive.
The sensitivity and specificity of the PEST questionnaire were 92% and 78%,43 while those of
ToPAS were 87% and 93%44 and those of EARP were 85% and 92%.45 In the COMPAQ study,
EARP was found to have the greatest sensitivity, while ToPAS II had the highest specificity
among the four questionnaires.46 The ease of doing EARP makes it more attractive. The use of
these screening questionnaires may help in early identification, and thereby in early initiation
of treatment.


6

Psoriasis and Psoriatic Arthritis

1.9 EPIDEMIOLOGY OF METABOLIC SYNDROME AND CARDIOVASCULAR
DISEASE RISK FACTORS IN PSORIATIC ARTHRITIS AND PSORIASIS
Being chronic inflammatory conditions, PsO and PsA predispose to metabolic syndrome and coronary events. This is brought about by endothelial dysfunction,47 accelerated atherogenesis, increased
insulin resistance, and hyperleptinemia.48 The prevalence of diabetes mellitus, systemic hypertension, obesity, and dyslipidemia was found to be higher in PsO, with an odds ratio of around 2 for each
of these factors.2,5,49,50 The incidence of metabolic syndrome was reported to be 59% in an Indian
PsA cohort.51 The adjusted relative risk for myocardial infarction was 3.1 in a study,50 although
higher rates of obesity and smoking might have had confounding effects in these PsO patients.49 The
chronic inflammatory state in PsO appears to play a part in the development of metabolic syndrome.
Early identification of these comorbidities will help to decrease morbidity in these patients.
To conclude, there are varying prevalence rates of PsO and PsA among various populations.

The incidence and prevalence of PsA among PsO also vary significantly. Part of this difference is
due to the different classification criteria used. The increasing use of CASPAR has brought some
uniformity in recent times. There is a need to have better screening strategies for the early diagnosis
of PsA. There is also an unmet need to have a uniform screening strategy for metabolic syndrome
in these patients.

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