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250 Kwok Fu Jacobus NG
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Epidemiology and Impact of
Arthritis and Rheumatic Diseases
e increased life expectancy recorded in recent decades,
together with changes in lifestyle and diet, has led to a rise
in the incidence of non-communicable diseases globally.
Of the various non-communicable diseases, rheumatic or
musculoskeletal disorders are the major cause of morbidity
throughout the world, having a substantial influence on
health and quality of life, and inflicting an enormous burden
of cost on health systems. In 1998, an estimated 355 million
people suffered from arthritis [91]. is number is expected
to rise dramatically over the next two decades so that by 2025
degenerative bone and joint disorders will be the commonest
cause of physical disabilities accounting for one-quarter of all
incapacitating conditions [82].
As a result of the epidemic of musculoskeletal disease that is
occurring worldwide, the Bone and Joint Decade (BJD) was
launched in Geneva by the World Health Organization (WHO)
in 2000 [12]. e Decade has four major aims: 1. to raise
awareness of the growing burden of musculoskeletal disorders
on society; 2. to promote prevention of musculoskeletal
disorders and empower patients through education campaigns;
3. to advance research on prevention, diagnosis and treatment
of musculoskeletal disorders; and 4. to improve diagnosis and
treatment of musculoskeletal disorders.
In a major report on the burden of musculoskeletal diseases
published by the WHO in collaboration with the BJD
(WHO 2003), rheumatoid arthritis (RA) and osteoarthritis
(OA), osteoporosis, spinal disorders, low back pain, and
severe trauma have been identified as frequent causes of
disability severely affecting individuals’ ability to carry out
EPIDEMIOLOGY AND IMPACT
OF ARTHRITIS AND RHEUMATIC
DISEASES
CLASSIFICATION OF ARTHRITIS
AND RHEUMATIC DISEASES
AN OVERVIEW OF THE
TREA
TMENT
OF ARTHRITIS AND
RHEUMATIC DISEASES
NON-STEROIDAL ANTI-
INFLAMAMTORY DRUGS AND
SELECTIVE CYCLO-OXYGENASE-2
INHIBITORS
COMMON ARTHRITIS
CONDITIONS
Osteoarthritis
Rheumatoid arthritis
Ankylosing spondylitis and
related conditions
Gouty arthritis
Periarticular and regional
rheumatic pain syndromes
CONCLUSION
REFERENCES
Painful Arthritis and Rheumatic
Conditions
16
Chak Sing LAU
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254 Chak Sing LAU
their activities of daily living and that this burden
is seen in both the developed and developing
countries (Table 16.01).
Within a decade of onset, RA leads to work
disability, defined as a total cessation of
employment, in 51–59% of patients. In cases
with OA, 80% of patients have some degree of
limitation of movement and 25% cannot perform
their major daily activities of life. Osteoporosis
is another major cause of morbidity and
mortality as osteoporotic fractures always require
hospitalisation, are fatal in 20% of cases and
permanently disable a further 50% of patients.
In 1990, a worldwide estimate of 1.7 million hip
fractures occurred as a result of osteoporosis, of
which only 30% recovered fully. e number of
hip osteoporotic fractures is expected to rise to
6 million by 2050. Low back pain has reached
epidemic proportions, being reported by about
80% of people at some time in their life. e
cost of arthritis and rheumatism conditions also
appears to be growing with the ageing of the
population, increased utilisation of new medical
technologies and loss of work. In the United
States, for example, this is now approaching 3%
of the gross domestic product (GDP), which
is equivalent to a permanent severe economic
recession. e economic impact of RA is in the
range of US$4,000–6,000 per case for direct cost
and US$12,000–24,000 for indirect cost [92].
While the impact of arthritis and rheumatic
diseases on the economy is high, the prevalence
of these conditions does not accurately reflect the
proportion of the population who may be suffering
physically and/or psychologically. One of the areas
that is often not emphasised in musculoskeletal
epidemiology studies is that of musculoskeletal
pain. In a study based on two population-based
cross-sectional surveys conducted over 40 years
apart, a high prevalence of musculoskeletal pain,
particularly in the shoulder and back, was observed
in a community in the United Kingdom and also
that there was a two- to four-fold increase over
the 40-year period [29]. e observation of a high
prevalence of musculoskeletal pain is mirrored in
other populations around the world, including
both industrialised and developing countries [14,
18, 30, 51, 63]. In many of these studies, not only
is musculoskeletal pain found to be associated with
significant physical and psychological suffering, but
it is a major cause of work day and productivity
loss. In the management of arthritis and rheumatic
diseases, therefore, treatment should target
correction of the underlying pathology, as well as
pain control.
Classication of Arthritis
and Rheumatic Diseases
Arthritis and rheumatic diseases include more
than 150 different conditions and syndromes
with the common denomination of pain and
inflammation. ere have been many attempts to
classify these conditions. However, most have been
hampered by the lack of a firm pathoaetiological
basis for many of these syndromes. us,
working classifications used in individual
practices, disease discussions and investigations
are often dynamic as our understanding of these
conditions evolves.
Table 16.01 Estimated burden of musculoskeletal diseases by gender and developed or developing regions,
2001 [12]
Percentage of
total DALYS
Total Male Female Developing regions
(both genders)
Developed regions
(both genders)
RA
OA
Other MS
diseases
All MS diseases
0.32
1.12
0.59
2.03
0.18
0.86
0.65
1.69
0.49
1.39
0.52
2.40
0.27
0.91
0.56
1.74
0.59
2.05
0.73
3.37
DALYS = disability-adjusted-life-years; MS = musculoskeletal; OA = osteoarthritis; RA = rheumatoid arthritis. (Table adopted
with the permission of Dr. Peter M. Brooks.)
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Painful Arthritis and Rheumatic Conditions 255
In 1983, the American College of Rheumatology
(ACR, formerly American Rheumatism Association)
classified arthritis and rheumatic conditions based
on their pathoaetiology and clinical presentation
[20]. While it is considered to be the most
comprehensive outline of known arthritis and
rheumatic diseases, many find this classification
overwhelming and cumbersome. In general, most
of the rheumatic diseases can be grouped under 10
major categories (Table 16.02).
Systemic connective tissue diseases include RA,
juvenile idiopathic arthritis, systemic lupus
erythematosus, Sjögren’s syndrome, systemic
sclerosis, polymyositis, dermatomyositis,
polymyalgia rheumatica, etc. ese conditions
are characterised by various immune aberrations
and patients present with a wide variety of clinical
manifestations including constitutional symptoms,
arthritis and other major organ disease. Many patients
with systemic connective tissue diseases develop
vasculitic complications (secondary vasculitis)
involving mainly the small blood vessels. However,
a distinct group of patients present with features
characterised by a primary vascular inflammatory
and necrotising pathology. ese patients are said
to have a primary vasculitide. Examples of primary
vasculitides include polyarteritis nodosa, Wegener’s
granulomatosis, Churg Strauss syndrome, giant
cell arteritis, Takayasu’s arteritis and Henoch
Schonlein purpura. Almost all of these conditions
are associated with significant morbidity and
mortality. Treatment usually involves the use of
high dose glucocorticoids and immunosuppressive
drugs.
Arthritis associated with spondylitis is also often
referred as sero-negative spondyloarthritis (SpA).
is form of arthritis includes ankylosing spondylitis
(AS), psoriatic arthritis, arthritis associated with
inflammatory bowel diseases and Reiter’s syndrome.
ese conditions share several common features,
including familial aggregation, asymmetric joint
involvement and mucocutaneous lesions. Some of
these conditions may follow gastrointestinal (GI) or
sexually acquired infections and may be associated
with human immunodeficiency virus (HIV).
Reiter’s syndrome is one such classical condition
and patients present with urethritis, conjunctivitis
and arthritis (which is sterile) following infectious
dysentery. e major causes of septic arthritis can
be viral, bacterial, fungal, or helminthic. Each can
present as either a polyarticular presentation or a
monoarthritis. Many of the helminthic infections
present with more generalised aches and pains and
involvement of muscle tissues as well as joints. All
the conditions have specific diagnostic features
and treatments. Bacterial infection of the joint is
a potential serious cause of morbidity, mortality,
joint damage and functional disability and warrants
immediate antibiotic treatment.
As has been highlighted above, osteoporosis and
OA are the most important bone and cartilage
diseases respectively. Osteoporosis is characterised
by low bone mass and deterioration in the micro-
architecture of the bone, which leads to fracture
after minor or moderate trauma. It is defined by
diagnostic criteria based on bone mineral density
as follows: a bone mineral density of more than
-2.5 standard deviations below the average bone
mineral density of young adult women. Clinical
features of osteoporosis are primarily due to
its major outcome: fracture which commonly
occurs in the distal radius, vertebrae, or hip often
following minor trauma. Vertebral fractures lead
to loss of height, kyphosis and back pain. e
incidence of fracture varies with country and with
type of fracture. Hip fractures are low in African
countries but high and increasingly reported in
Australasia, Europe and North America. Fracture
risk increases with age and is beginning to have a
significant impact on quality of life, mortality and
health care costs in many countries [69]. Other
important causes of bone disease include rickets,
Table 16.02 Classification of arthritis and
rheumatic diseases
1. Systemic connective tissue diseases
2. Vasculitides
3. Arthritis associated with spondylitis
4. Rheumatic diseases associated with infectious
agents
5. Bone and cartilage diseases
6. Rheumatic diseases associated with metabolic,
endocrine and haematological disorders
7. Periarticular and regional rheumatic pain
syndromes
8. Rheumatic syndromes associated with
systemic medical disorders including
neoplasms and tumour-like lesions
9. Rheumatic syndromes associated with
hereditary, congenital and inborn errors of
metabolism
10. Miscellaneous rheumatic disorders
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256 Chak Sing LAU
osteomalacia, hypertrophic osteoarthropathy,
avascular osteonecrosis and Paget’s disease.
Crystal arthritis, particularly gouty arthritis,
is probably the commonest rheumatic disease
associated with a metabolic disorder. Gout is
characterised by tissue deposition of crystals of
monosodium urate from supersaturated extracellular
fluids and may result in acute or chronic arthritis
and periarthritis, tophaceous deposition and gouty
nephropathy. Its prevalence has increased over the
last few decades in countries with a high standard
of living. Regional rheumatic pain syndromes or
soft tissue rheumatism (STR) are among the most
commonly encountered rheumatic complaints
and yet they are often overlooked. e diagnosis
of most of these lesions relies on the physician’s
clinical acumen, and a thorough understanding
of the anatomy and function of the soft tissue
involved is essential. Other rheumatic diseases are
less commonly encountered but should not be
overlooked. For example, it is not uncommon for
patients with an underlying malignant condition
to present with arthritis.
It is beyond the scope of this chapter to describe all
of the rheumatic diseases listed above. However, a
brief account of the epidemiology, pathoaetiology,
clinical presentation and management of common
conditions including RA, AS and related conditions,
OA, gouty arthritis and STR will be given below.
An Overview of the
Treatment of Arthritis and
Rheumatic Diseases
e principles in the management of all forms
of arthritis and rheumatic diseases are similar.
A multidisciplinary approach involving the
rheumatologist, orthopaedic surgeon, pain specialist,
family physician, specialty nurse, physiotherapist,
occupational therapist, social worker, podiatrist
and clinical psychologist is commonly employed.
e main objective is to reduce pain and enable the
patient to maintain as near normal a life as possible.
Effective communication between physician
and patient is important. Educating the patient
and his or her family about the cause, treatment
and prognosis of the underlying condition,
particularly chronic arthritis, is useful in allaying
anxiety and improving treatment compliance.
Misunderstandings about the disease may lead to
frustration, depression and withdrawal. In recent
years, self-management education, with emphasis
on theory-based self-management support, has
also been shown to have significant positive effects
on patient knowledge, behaviours and health
outcomes. Furthermore, the importance of patient
support groups must not be overlooked.
People with arthritis often have limited range of
motion, decreased muscle strength and endurance.
Together with possible changes in gait and posture,
chronic arthritis often leads to functional limitations
and general deconditioning. Physiotherapists can
recommend appropriate regular physical activity and
exercises which can lead to improvements in these
areas and can reduce pain, fatigue and depression.
Besides, physical agents of heat, cold and electricity
may be used to alleviate the symptoms of rheumatic
diseases. Wax baths, ice packs, ultrasound and
weak electrical current stimulation (interferential
therapy) are useful treatment modalities for patients
with chronic arthritis. Occupational therapists can
advise on joint protection and can provide aids and
appliances which allow chronic arthritis sufferers
to be independent. Splints are extensively used
to protect, immobilise, or mobilise various parts
of the body. ey are also used to prevent and
correct deformities and are particularly useful in
the management of hand arthritis in patients with
RA.
Surgery also has an important role in the
management of many arthritis and rheumatic
diseases. Useful operations range from the
removal of local areas of diseased synovial tissue,
to the removal of subluxed joints and total joint
replacement in patients with chronic diseases such
as RA and AS. It is beyond the scope of this chapter
to discuss the many forms of surgical interventions
available in the management of chronic arthritis.
e use of drugs has a central role in the treatment
of chronic arthritis. e ideal drug should provide
symptomatic relief and eradicate the underlying
condition without causing side effects. While
such a drug(s) is not yet available and there is
still no cure, progress made in recent years in our
understanding of arthritis means that it is now
possible to keep arthritis symptoms under good
control with judicious use of therapeutic agents that
are well tolerated and specific in their mechanisms
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Painful Arthritis and Rheumatic Conditions 257
of action. Broadly, these agents may be divided into
those that provide symptomatic relief, and others
which are capable of delaying disease progression
— the so called disease modifying anti-rheumatic
drugs (DMARDs).
Non-Steroidal Anti-
Inammatory Drugs and
Cyclo-Oxygenase-2 Selective
Inhibitors
Non-steroidal anti-inflammatory drugs (NSAIDs)
are among the most commonly prescribed symptom
relieving drugs for arthritis and rheumatic diseases.
e primary mechanism of action of NSAIDs is
due to their inhibitory effects on the production
of pro-inflammatory prostaglandins via the enzyme
cyclo-oxygenase (COX) [87]. Unfortunately, the
use of NSAIDs is limited by their high incidence
of adverse reactions, particularly upper GI tract
erosion and ulceration, bleeding tendency and
renal toxicity due to their inhibitory actions on
GI mucosal, endothelial and renal prostaglandin
synthesis, particularly PGE2 and PGI2. Non-
steroidal anti-inflammatory drug-induced upper
GI complications are major iatrogenic disorders.
e point prevalence of upper GI ulceration
ranges from 10–20% [47]. Of clinical importance
are ulcers that cause symptoms or develop into
potentially life-threatening complications such as
upper GI bleeding, perforation and gastric outlet
obstruction. ese complications are reported to
occur in 2–4% of patients taking NSAIDs for 1
year [61]. Table 16.03 shows the risk factors for
serious upper GI complications associated with
NSAID use [74, 75]. Unfortunately, most chronic
arthritis patients who require long-term NSAID
therapy belong to one or more of these categories.
It is now known that COX exists in 2 isoforms:
COX-1 and COX-2 (Simmons et al., 1989). COX-
1 is the constitutive form of the enzyme which
is present in many tissues including the gastric
mucosa, endothelium, kidney and platelets. COX-
1 has clear physiological functions; it produces
prostaglandins involved in cytoprotective and
regulatory functions of these organs. Gastric
prostaglandins are derived almost exclusively
from COX-1. In contrast, the activity of COX-
2 is normally very low in cells except in those of
the brain, reproductive organs and kidney. COX-
2 is tightly controlled by a number of factors
including cytokines and intracellular messengers,
and by the availability of substrate. Its expression
is rapidly induced in the context of inflammation
(and other pathological conditions) [58]. COX-2 is
unregulated in inflammatory cells such as activated
macrophages and synoviocytes in patients with
chronic arthritis such as RA. All currently available
NSAIDs inhibit COX-1 and COX-2, each to
varying degrees. us, the anti-inflammatory
effects of NSAIDs are mediated through COX-2
inhibition while their typical adverse effects in the
GI tract and antiplatelet effects result mainly from
the inhibition of COX-1.
Selective COX-2 inhibitors have been approved
for use in common arthritis conditions. ese
drugs were considered a revolution in pain
management because of their ability to relieve pain
and inflammation while being less toxic to the GI
tract [9, 73]. However, this wave of enthusiasm has
recently been blunted with studies which showed
that selective COX-2 inhibition is associated with
an increased risk of vascular thrombosis [9, 77].
Confusion followed when recent large population
studies showed similar vascular risk increase with
long-term NSAID use [27, 36, 76]. While the COX-
2 inhibitors/NSAID stories may have caused panic
in patients and medical practitioners alike, they
have been positive when viewed from a different
angle. First, most of the findings, desirable or not,
Table 16.03 Risk factors for serious upper
gastrointestinal complications associated with
NSAID use
• Previous history of peptic ulcer disease, upper
GI bleeding and GI hospitalisation
• Prior NSAID-associated GI side effects
• Old age
• Arthritis-related disability
• High dose or multiple NSAIDs being used
• Concurrent high dose steroid use
• History of cardiovascular disease
• Concurrent use of H2 antagonists or antacids
• The requirement of symptomatic treatment
indicates an increased risk
• Antacids and H2 antagonists (at ordinary
doses) do not prevent NSAID-induced
gastric ulcers but may mask relevant
symptoms and delay medical attention
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258 Chak Sing LAU
were made in unprecedented large scale outcome
studies. is not only emphasises that modern
medicine is evidence based but sets a new standard
for evaluating future therapies, which ultimately
means enhanced safety for our patients. Second,
the swift actions taken by the pharmaceutical firms
and regulatory authorities involved should reassure
patients and prescribers that patient safety is in
the forefront of their considerations. ird, carers
of patients with rheumatic disorders should learn
from these lessons that treatment of pain syndromes
involves not only the use of anti-inflammatory
drugs but a multidisciplinary approach involving
a number of other drug and non-drug modalities.
e pros and cons of all pharmaceutical agents
must be carefully weighed before they are used.
Please also refer to Chapter 22 for more details on
NSAIDs and COX-2 inhibitors.
Common Arthritis
Conditions
Osteoarthritis
Scope of the problem
OA is the most common form of arthritis,
encompassing 60–70% of all joint diseases. It is
commonly referred to as a degenerative arthritis and
is a major health problem throughout the world,
second among causes of permanent incapacity in
people over age 50 years. Radiographic evidence
of OA can be found at some site in the majority
of people older than 65 years of age, while more
than 80% of those over the age of 75 are affected.
However, estimates of the incidence of OA are
imprecise because of the difficulties in defining
the condition and how to determine its onset. It
is also important to note that less than one-half
of all those with radiographically identifiable OA
have symptoms. Worldwide estimates are that
9.6% of men and 18.0% of women aged 60 years
or above have symptomatic OA [57]. However,
racial differences exist for both the prevalence
of OA and the pattern of joint involvement. In
general, OA is more prevalent in Europe and the
USA than in other parts of the world. For example,
African-American women are more prone than
white women to OA of the knee but not the hip
— similarly in South African blacks, South Asian
Indians and Chinese [81].
While the prevalence of OA increases with
age, in any given joint, OA may result from a
combination of risk factors including genetic
predisposition, local aetiological factors, such as
trauma, and comorbidities. For example, there is
a strong genetic component in primary nodal OA
which is often found in women of menopausal
age and most commonly affects the proximal
interphalangeal (Bouchard’s nodes) and distal
interphalangeal (Heberden’s nodes) joints of the
hand. Further, patients with primary nodal OA are
more likely to develop secondary OA of the knee
after menisectomy [21]. Local trauma may speed
up the joint degeneration process. For example,
people who are obese are more prone to develop
OA as their joints are constantly under more stress.
Severe and recurrent trauma to the joint may also
predispose to the development of OA. Many athletes
suffer from OA due to excessive use and recurrent
trauma to their joints. Co-morbidities include
other chronic arthritis such as RA and sero-negative
SpA. is is because a diseased joint is more likely
to be subject to an abnormal distribution of load
and hence more liable to accelerated degeneration.
Table 16.04 shows the risk factors for the incidence
and progression of OA.
Data are available from developed countries on
the economic consequences of work loss from OA,
health resource utilisation and joint replacements
(most of which are carried out for OA). In Australia,
the total health system cost for OA in 1993–1994
Table 16.04 Risk factors for the incidence and
progression of osteoarthritis
• Hereditary
• Age
• Female sex
• Congenital deformities, e.g. slipped capital
epiphyses in the hip
• Local trauma, previous injuries and physically
demanding activities
• High bone mass index
• Co-morbidities
• coexisting inflammatory arthritis, e.g. RA,
AS
• coexisting metabolic disorders, e.g.
diabetes, gout, acromegaly, ochronosis
• coexistent neurological disorders, e.g.
Charcot arthropathy
• Smoking (protective)
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Painful Arthritis and Rheumatic Conditions 259
was AUS$624 million, which accounted for
21% of the total expenditure on musculoskeletal
diseases. ere were approximately 41,000 hospital
admissions, 13.9% of all hospitalisations for
musculoskeletal conditions (n = 295,000). e
average length of hospital stay for OA was 9.4 days,
whereas that for all musculoskeletal conditions
combined was 5.0 days. In the same year period
(1993–1994), patients with OA also received the
greatest number of prescriptions (3,058,400),
accounting for 22.9% of all prescriptions written
for musculoskeletal disease [55]. In other developed
countries such as the USA, Canada, the UK and
France, the total cost of OA has been estimated to
vary from 1–2.5% of GNP [53].
Clinical presentation of osteoarthritis
Almost all joints may be affected by OA. However,
joints that bear the most weight are more liable
to develop wear and tear. Osteoarthritis therefore
commonly affects the hip, knee and lumbar spine.
Joints that are mobile, e.g. the first carpometacarpal
joint (base of the thumb), distal interphalangeal
joints (end joints of the fingers) and the neck, may
also develop OA. e wrists, shoulders and ankles
are less often involved.
Not all patients with joint symptoms have
radiographic changes; and not all radiographic
changes are associated with joint symptoms.
Pain is the predominant complaint of all patients
symptomatic of OA. is tends to be worse after
exercise and towards the end of the day, and is
relieved by rest. Patients usually feel at their best
first thing in the morning. In addition to pain,
there may be stiffness (gelling), which is worse
after prolonged inactivity. e joint may feel
swollen and bony. Although OA is essentially a
degenerative disease of the joint, there may be a
minor component of inflammation and some
patients complain of an increase in temperature
and redness of the joint. In some cases, OA may
be complicated by deposition of calcium crystals
within the joint and patients present with an acute
onset of intense pain, swelling and redness of the
affected joint. ese symptoms mimic those of
gout and the complication is called pseudo-gout.
Blood tests are usually unhelpful, but they may
sometimes reveal underlying metabolic disorders.
Radiographs may show loss of joint space resulting
from cartilage damage, osteophytosis (formation of
new bone), altered bone contour and subchondral
sclerosis (increased bone density), and cystic
formation resulting from bony remodelling. ere
may also be soft tissue swelling and periarticular
calcification.
Management of osteoarthritis
Guidelines for OA management have been
developed by the ACR [3] and the European
League Against Rheumatism (EULAR) [35, 93].
e treatments recommended in these guidelines
should be tailored to each individual patient,
carefully weighing adverse event risks relative
to potential benefits. Patient education must be
emphasised as misconceptions exist about this
disease at both extremes. Many patients require
only reassurance that they have no generalised
crippling form of rheumatic diseases.
e primary treatment objectives include pain
relief and restoration of function. e general
principles in the management of various forms of
arthritis conditions have been highlighted above.
A multidisciplinary approach is essential. Physical
therapy includes protection of joints from overuse,
particularly if weight-bearing joints are involved.
Weight reduction should be advised, especially in
patients with marked obesity. Appropriate exercises
should be taught to strengthen the various muscle
groups acting on the affected joint.
Pharmacological therapies are primarily used to
alleviate painful symptoms. Analgesic agents such
as paracetamol (acetaminophen), administered on a
regular basis, are frequently effective. Other analgesic
agents such as propoxyphene hydrochloride may be
used temporarily as needed. Opioid preparation,
required only occasionally for acute flares, should
be very limited in use. e use of NSAIDs has been
described in more detail above.
It should be noted that oral or parenteral use of
glucocorticoids is generally not indicated in the
treatment of OA, although intra-articular injection
of these agents may be beneficial when used
judiciously in the management of acute disease
flares. However, injections should be infrequent,
especially if given in weight-bearing joints. Joint
deterioration may be accelerated due to masking
of pain and subsequent joint overuse or to a direct
deleterious effect of these drugs on cartilage.
Pericapsular and ligamentous injections in areas of
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