Ankylosing Spondylitis and Axial Spondyloarthritis, 2nd
Edition
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Dedication
I dedicate this book to my father, Umar Khan, my mother, Hameeda Khanam,
and to her father, Sadr-ud-Din Khan (a high school principal who retired as
inspector of schools) for having inculcated in me the passion to pursue know-
ledge and impart it to others. They all worked tirelessly to re-establish when
we became refugees, uprooted from our ancestral lands when I was a little
over three years old. Therefore, I also dedicate this book to all the refugees like
me in this world who may still be longing for a home, and most of them also
happen to share my faith.
vi
Advance praise
‘Written for patients by a patient who is also a leading authority on spondyloarthritis, this
book is an essential reference and reading for people living with axial spondyloarthritis—
with ankylosing spondylitis as its prototype—and their caregivers who want to learn
about the disease and how to manage it well.’
Michael Mallinson,
Patient Advocate and Volunteer,
Axial Spondyloarthritis International Federation (ASIF)
Preface
There have been tremendous advances in clinical understanding, early disease
recognition, and more effective management of ankylosing spondylitis (AS)
and related diseases. The advent of newer imaging methods, such as magnetic
resonance imaging (MRI) and very low-dose computerized tomography (CT),
have also facilitated early diagnosis and initiation of increasingly more effective
(but costly) drugs called “biologics” (administered by injection under the skin
or by intravenous infusion), and most recently JAK-inhibitors that are taken
orally as tablets. These drugs target inflammatory proteins (cytokines), such as
tumor necrosis factor (TNF) and interleukin-17 (IL-17).
All these new development and progress in diagnosis and management of AS
and related diseases has necessitated this second edition of the book. I have
updated its title by adding the term “Axial Spondyloarthritis” that requires
some explanation.
The term “spondyloarthritis” (or SpA) refers to a family of chronic inflam-
matory non-contagious (non-infectious) forms of arthritis involving the spine
and the limbs that share many of their clinical features and genetic predis-
posing factors. Those patients with SpA who primarily have inflammation of
the joints and ligaments of the back and neck (i.e., the axial skeleton) are now
sub-classified as having “axial spondyloarthritis” (axSpA); whereas those with
involvement predominantly of the peripheral (distal) limb joints (other than
hip and shoulder joints that are part of the axial skeleton), are labeled as having
“peripheral SpA.” The typical example of axSpA is AS, while that of peripheral
SpA is psoriatic arthritis (PsA).
X-ray evidence of damage to the sacroiliac joints (sacroiliitis) is required for
the diagnosis of AS. We first reported in 1985 that one can clinically recog-
nize the disease even when there is no X-ray evidence of sacroiliitis. We called
it “spondylitic disease without radiological evidence of sacroiliitis.” It is now
called “non-radiographic axSpA” (nr-axSpA). The name axSpA encompasses
both nr-axSpA and AS.
Most of the current knowledge about axSpA was gained when the disease was
called AS, and this is my reason for the use of both AS and axSpA in the title of
vi
Preface
this second edition. It is my hope that the third edition of this book will simply
be titled Axial Spondyloarthritis: The Facts. The term “radiographic axSpA” (r-
axSpA) has sometimes been equated with AS but I have preferred to use the
term AS in this book as it is the most widely accepted name.
This book is written in a clear and accessible style with American English
spellings for patients and their families and friends. But it is also ideal for
students and healthcare professionals of all levels who are looking for concise
and practical information on all aspects of AS/axSpA. Discussions about the
associated forms of SpA, including PsA, reactive arthritis, inflammatory bowel
disease associated SpA, juvenile SpA, and some other diseases that may be
confused with SpA (the so-called disease mimickers or look-alikes) are also
discussed. A glossary of medical terms, a list of abbreviations, links to patient
support groups and other helpful organizations, a list of medical references for
further reading, and an index are also included.
People who are knowledgeable about their disease show more self-responsibility,
comply better with recommended treatment, and are more likely to make posi-
tive behavioral changes that will help them achieve an improved health status
in the long run. I hope this book will serve people living with AS/axSpA and
their families and friends in their need for self-education.
Lastly, I would add that this book provides a general information that cannot
replace the care and knowledge provided by your professional healthcare pro-
viders. You need to consult them if you have questions as you read this book.
Muhammad Asim Khan
Professor Emeritus of Medicine
Case Western Reserve University, Cleveland, Ohio, USA
viii
Acknowledgments
I am most grateful to my wife Mastoora and my sons Ali and Raza for their
help; and also very thankful to the many patients, colleagues, and students who
have, over the years, enhanced my knowledge of ankylosing spondylitis, an
illness I have myself lived with for more than sixty-six years.
x
Contents
Abbreviations xiii
1 What is ankylosing spondylitis? 1
2 Axial spondyloarthritis 16
3 What is the underlying cause? HLA-B27 and other
disease-predisposing genes 22
4 Disease prevalence 31
5 Early symptoms and pointers to early diagnosis 36
6 Eye inflammation (acute anterior uveitis) 41
7 Other manifestations 45
8 Physical examination and laboratory tests 49
9 Radiology, MRI, and CT 57
10 Diagnosis and management of other forms of SpA
and “look-alikes” 60
11 Other causes of chronic back pain 73
12 Assessment of disease activity and functional impairment 79
13 Patient education 85
14 Exercise and physical therapy 88
15 Management: An overview 101
16 Management: Patient’s role 105
17 Management: Rheumatologist’s role 108
18 NSAIDs and conventional DMARDs 111
19 Tumor Necrosis Factor inhibitors 117
xi
Contents
20 IL-17 and IL-23 inhibitors and targeted synthetic DMARDs 124
21 Living with the disease and its socio-economic impact 128
22 Fused (ankylosed) spine and risk of fractures 137
23 Surgical treatment 141
24 Non-traditional (complementary or alternative) therapy 145
25 Disease course and effect on life span 154
26 Brief illustrative case histories 157
Appendix 1. Patient support groups and other helpful
organizations 161
Appendix 2. Glossary 165
Appendix 3. Further reading 189
Index 199
xii
Abbreviations
3D three-dimensional
AAU acute anterior uveitis
ACE angiotensin-converting-enzyme
ACR American College of Rheumatology
ADL activities of daily living
AI artificial intelligence
AS ankylosing spondylitis
ASAS Assessment of SpondyloArthritis international
Society
ASAS H I ASAS Health Index
ASDA S Ankylosing Spondylitis Disease Activity Score
ASDA S _C R P Ankylosing Spondylitis Disease Activity Score
based on CRP
ASIF Axial Spondyloarthritis International Federation
ASQoL ankylosing spondylitis quality of life measure
AP anteroposterior
axSpA axial spondyloarthritis
BASDA I Bath Ankylosing Spondylitis Disease Activity Index
BASF I Bath Ankylosing Spondylitis Functional Index
BAS- G Bath Ankylosing Spondylitis Patient Global score
BASM I Bath Ankylosing Spondylitis Metrology Index
BASRI Bath Ankylosing Spondylitis Radiology Index
b- D M A R D biologic DMARD
BiPAP bilevel positive airways pressure
BMC bone mineral content
BMD bone mineral density
BMI body mass index
CASPA R Classification Criteria for Psoriatic Arthritis
CBD cannabidiol
CD Crohn’s disease
vxi
Abbreviations
CDC Centers for Disease Control and Prevention in the
United States.
c- D MA R D conventional DMARD
CD- S p A CD-associated spondyloarthritis
CES- D Center for Epidemiological Studies Depression
CLBP chronic low back pain
CNO chronic non-infectious osteitis
COA Certificate of Analysis
COX cyclooxygenase
CPAP continuous positive airway pressure
CRP C-reactive protein
cs- D M A R D conventional synthetic DMARD
CT computed tomography
DAS disease activity score
DEXA (o r D X A ) dual energy x-ray absorptiometry
DISH diffuse idiopathic skeletal hyperostosis
DKK abbreviation for protein named Dickkopf
DMAR D disease modifying anti-rheumatic drug
DXA dual-energy X-ray absorptiometry
EAM extra articular manifestation
EMA Europeans Medicines Agency
EMAS European Mapping of Axial Spondyloarthritis
EMR electronic medical record
ERAP endoplasmic reticulum aminopeptidase
ESR erythrocyte sedimentation rate
ESSG European Spondyloarthropathy Study Group criteria
EULAR European Alliance of Associations for Rheumatology
FACIT Functional Assessment of Chronic Illness Therapy
FDA Food and Drug Administration of USA
GI gastrointestinal
GP general practitioner
GWAS gnome-wide association study
HAQ Health Assessments Questionnaire
HAQ- D I HAQ Disability Index
HAQ- S HAQ spondylitis
HCP healthcare providers
HLA human leucocyte antigen
HR- Q o L health-related quality of life
IASP International Association for the Study of Pain
xiv
Abbreviations
IBD inflammatory bowel disease
IBP inflammatory back pain
Ig immunoglobulin
IL Interleukin, such as IL-17 and IL-23
IBS irritable bowel syndrome
JAK Janus kinase
JAKi Janus kinase inhibitor
JAKin JAK inhibitors
JAS juvenile AS
JIA juvenile idiopathic arthritis
MCS Mental Component Score
MFI Multidimensional Fatigue Inventory
MHC major histocompatibility complex
mNY modified New York (criteria for ankylosing
spondylitis)
MRI magnetic resonance imaging
mSAS S S modified Stoke Ankylosing Spondylitis Spine Score
NASS National Axial Spondyloarthritis Society
NHAN ES National Health and Nutritional Examination Survey
NHS National Health Service of UK
NIH National Institute of Health of USA
nr-a xS p A non-radiographic axial spondyloarthritis
NSAID nonsteroidal anti-inflammatory drugs
OA osteoarthritis
OCT optical coherence tomography
OTC over-the-counter
PAMP pathogen-associated molecular pattern
PASS Patient-Acceptable Symptom State
PCP primary healthcare provider
PCS Physical Component Score
PD phosphodiesterase
PET positron emission tomography
PGA Patient Global Assessment
PGE2 prostaglandin E2
PhD Doctor of Philosophy
PPD purified protein derivative
PPR pattern recognition receptor
PRO Patient Reported Outcome
PROM Patient Reported Outcome Measure
xv
xvi
Abbreviations
PsA psoriatic arthritis
QoL quality of life
RA rheumatoid arthritis
RAPID 3 Routine Assessment of Patient Index Data 3
r-a xSpA radiographic axSpA
RCT randomized controlled trial
SAARD slow-acting anti-rheumatic drug
SAPHO synovitis, acne, palmoplantar pustulosis, hyperostosis,
and aseptic osteomyelitis
SASSS Stoke Ankylosing Spondylitis Spine Score
SEA seronegative enthesitis and arthritis
SF- 3 6 Short-Study Form-36
SI sacroiliac (or sacroiliitis)
SI join t o r S I J sacroiliac joint
SpA spondyloarthritis or spondyloarthropathy
THA total hip arthroplasty
THC tetrahydrocannabinol
THR total hip joint replacement
TMJ temporo-mandibular joint
TNF tumor necrosis factor
TNFi tumor necrosis factor inhibitor
ts-DMA R Ds targeted synthetic-DMARDs
UC ulcerative colitis
VAS visual analog scale
WBC white blood-cell count
WHO World Health Organization
WLQ- 2 5 Work Limitations Questionnaire-25
WPAI Work Productivity and Activity Impairment
xvi
1
What is ankylosing
spondylitis?
% K ey points
◆ Ankylosing spondylitis (AS) is a chronic (long-term), slowly progres-
sive, and painful inflammatory arthritis of the sacroiliac (SI) joints and
the spine that can lead to gradually progressive impairment of spinal
mobility.
◆ It affects both males and females, and the symptoms typically start
during adolescence and early adulthood, and it is very uncommon for
the symptoms to begin after age 45.
◆ The inflammation can also involve the hip and shoulder joints, and less
often other limb joints, such as knees, ankles, and heels.
◆ One or more episodes of acute eye inflammation (acute anterior uveitis)
can occur in >30% of patients, and 6 to 10% suffer from psoriasis and/or
inflammatory bowel disease.
◆ The disease is observed worldwide with very variable prevalence, e.g., it
affects one in 200 (0.5% prevalence) adults of European ancestry, but is
very uncommon in most of the sub-Saharan African populations.
◆ Its cause is not fully understood but is largely genetically determined,
and there is a strong association with a gene called HLA-B27.
◆ There is no cure as yet but most patients can be very well managed if
diagnosed and treated early with increasingly effective, though costly,
drugs that markedly reduce the risk of irreversible structural damage
and help patients pursue a very active and productive lifestyle.
Ankylosing Spondylitis and Axial Spondyloarthritis, Second Edition. Muhammad Asim Khan, Oxford University Press.
© Oxford University Press 2023. DOI: 10.1093/oso/9780198864158.003.0001
2
What is ankylosing spondylitis? · the
thefacts
Introduction
Ankylosing spondylitis (AS) is a chronic (progressive) painful inflammatory
rheumatic non-contagious (non-infectious) disease that involves the back, i.e.
the sacroiliac (SI) joints and the spine, that often results in some degree of
stiffness (decreased flexibility) of the spine (Figure 1.1). The word ankylosing
comes from the Greek root ankylos, meaning bent, although it has now come to
imply something that restricts motion (stiffening) and may ultimately result in
fusion. When the joint loses its mobility and becomes stiff it is said to be anky-
losed. The word spondylitis means inflammation in the joints of the spine, and
is derived from spondylos, which is the Greek word for vertebra, and -itis, which
implies presence of inflammation. The name therefore suggests that AS is an
inflammatory disease of the spine that can lead to stiffening of the back. It is
important to point out that the words spondylitis and spondyloarthritis should
not be confused with spondylosis, which relates to wear and tear in the spinal
column (degenerative disc disease) as we get older.
Ankylosing spondylitis in history
Skeletal specimens in several museum collections testify to the existence of
AS from the earliest times. But its first definite anatomical description can be
credited to Bernard Conner (1666–1698). He was an Irish physician studying
medicine in France when some farmers brought him a skeleton they had found
in a cemetery. He wrote in his report, accompanied by the drawing of the
skeleton (see Figure 1.2), that the bones were “so straightly and intimately
joined, their ligaments perfectly bony, and their articulations so effaced, that
they really made but one uniform continuous bone.”
The clinical descriptions of the disease date from the late nineteenth cen-
tury, with a series of publications in the 1890s by Vladimir von Bechterew
(1857–1927) in St Petersburg, Russia, Pierre Marie (1853–1940) in France,
and Adolf Strümpell (1853–1926) in Germany. Report of the earliest X-ray
examination of a patient with AS was published in 1899, and the characteristic
X-ray finding of obliteration of the SI joints was described in 1934.
The name ankylosing spondylitis is widely in use in English speaking countries,
with its translation spondylarthrite ankylosante in French, spondylitis ankylopoëtica
in Dutch, and espondilartritis ankylosante in Spanish. Older names include
Morbus Bechterew (Bekhterew’s or Bekhterev’s disease), Bekhterev-Strümpell-
Marie disease and Marie-Strümpell spondylitis. Although the use of eponyms
is now discouraged for naming a disease, the term: “Morbus Bechterew” is
still being widely used in German-speaking countries. Other names that have
been used include spondyloarthritis ankylopoëtica, pelvospondylitis ossificans, and
