SPONDYLOARTHRITIS

By Aishwarya Prasad
Roll No 6
SPONDYLOARTHRITIS
 This is a group of conditions affecting the spine and peripheral
joints which cluster in families and are linked to certain type 1
HLA antigens
 The joint involvement is usually more limited than that seen in
RA and its distribution is different. There are associated extra-
articular and genetic features. These diseases occasionally
present in childhood.
 Histologically, the synovitis itself is similar to that of RA, but there
is no production of rheumatoid factors – hence ‘seronegative’.
ACPA is also usually negative. Inflammation of the enthesis
(junction of ligament or tendon and bone) and joint ankylosis
develop more commonly than in RA. All are associated with an
increased frequency of sacroiliitis and an increased frequency of
HLA-B27.
Aetiology
 The common aetiological thread of these disorders is their striking association
with HLA-B27, particularly ankylosing spondylitis (AS). HLA type B27 is present
in >90% of Caucasians with AS but only 8% of controls. HLA-B27 exhibits a
number of unusual characteristics including a high tendency to mis-fold but its
aetiological relevance remains unclear. The role of class I HLA antigens in
pathogenesis is supported by the fact that HLA-B27 transgenic mice
spontaneously develop arthritis, skin, gut and genitourinary lesions.
 There are clues that infections play a role, possibly by molecular mimicry, with
parts of the organism which are structurally similar to the HLA molecule triggering
cross-reactive antibody formation. This is unproven. AIDS is increasing the
prevalence of reactive arthritis and spondylitis in sub-Saharan Africa even in the
absence of HLA-B27. The explanation for this changing epidemiology is
unclear.The types of arthritis that follow a precipitating infection are called
reactive arthritis (p. 529). The specialized immune systems of the gut and
genitouri-nary mucous membranes may also play a causal role, perhaps reacting
to local infections or to antigens which cross the damaged mucosa.
Spondyloarthritis
 Ankylosing spondylitis (AS)
 Psoriatic arthritis
 Reactive arthritis (sexually acquired, Reiter’s
disease)
 Post-dysenteric reactive arthritis
 Enteropathic arthritis (ulcerative colitis/Crohn’s
disease
Ankylosing spondylitis
 This is an inflammatory disorder of the spine affecting mainly young
adults (late teens to early 30s). It occurs worldwide, with a male to
female ratio of 5:1. Women present later and are underdiagnosed. The
frequency of AS in different populations is roughly paralleled by the
incidence of HLA-B27; Africans and Japanese have a low incidence of
both HLA-B27 and ankylosing spondylitis, while the North American
Haida Indians have a high incidence of both. There are at least 24
subtypes of HLA-B27 (B*2701-B*2724). Some appear to increase risk;
others have a protective role. Twin studies indicate a much higher
disease concordance in HLA-B27-positive monozygotic (up to 70%)
twins than in dizygotic twins (about 20–25%). There are also other
genes lying within the major histocompatibility complex (interleukin-1
gene cluster and the gene CYP2D6) which also influence susceptibility
to AS but the disease is polygenic
Epidemiology and pathogenesis
 Environmental factors may also be involved but although Gram-negative
organisms, e.g. Yersinia, Klebsiella, Salmonella, Shigella, can cause a
reactive arthropathy, there is no conclusive evidence for their
involvement in the pathogenesis of AS.
 There is lymphocyte and plasma cell infiltration and local erosion of
bone at the attachments of the intervertebral and other ligaments
(enthesitis). This heals with new bone (syndesmophyte) formation.
Clinical features
 Episodic inflammation of the sacroiliac joints in the late teenage
years or early 20s is the first manifestation of AS. Pain in one or
both buttocks and low back pain and stiffness are typically worse
in the morning and relieved by exercise.
 Initially the diagnosis is often missed because the patient is
asymptomatic between episodes and radiological abnormalities
are absent. Retention of the lumbar lordosis during spinal flexion
is an early sign. Later, paraspinal muscle wasting develops.
 Spinal stiffness can be measured by Schober’s test: a tape
measure is placed in the midline 10
 cm above the dimples of Venus. Any movement of a marker at
15cm during flexion
 is recorded. A reading of <5cm implies spinal stiffness.
Individuals may be able to touch the floor with a stiff back if they
have good hip movements but serial measurement of the finger
tip to floor distance highlights any change.
 Non-spinal complications (uveitis or costochondritis) suggest the
diagnosis of spondyloarthritis
Clinical features
 Costochondral junction inflammation causes anterior chest pain.
Measurable reduction of chest expansion is due to
costovertebral joint involvement.
 Peripheral joint involvement is asymmetrical and affects a few,
predominantly large joints. Hip involvement leads to fixed flexion
deformities of the hips and further deterioration of the posture.
Young teenage boys occasionally present with a lower-limb
monoarthritis, which later develops into AS.
 Acute anterior uveitis is strongly associated with HLA-B27 in AS
and related diseases and is occasionally the presenting
complaint. Severe eye pain, photophobia and blurred vision are
an emergency.
 Overall clinical assessment is based on pain, tenderness,
stiffness and fatigue using, e.g. the Bath Ankylosing Spondylitis
Disease Activity Index
Back pain criteria for diagnosing
ankylosing spondylitis

 Age of onset <50 years

 Insidious onset
 Improvement of back pain with exercise
 No improvement of back pain with rest
 Pain at night with improvement on getting up
Investigations
 Blood. The ESR and CRP are usually raised.
 HLA testing is rarely of value because of the high frequency of HLA-B27
in the population, but may give supporting evidence in a difficult case.
 X-rays. The medial and lateral cortical margins of both sacroiliac joints
lose definition owing to erosions and eventually become sclerotic. The
earliest radiological appearances in the spine are blurring of the upper
or lower vertebral rims at the thoracolumbar junction (best seen on a
lateral X-ray) caused by an enthesitis at the insertion of the
intervertebral ligaments.
 These changes may eventually affect the whole spine.
 Persistent inflammatory enthesitis causes bony spurs
(syndesmophytes). Syndesmophytes are more vertically oriented than
the beak-like osteophytes of spondylosis and the disc is preserved,
unlike in spondylosis . Syndesmophytes cause bony ankylosis and
permanent stiffening. The sacroiliac joints eventually fuse, as may the
costovertebral joints, reducing chest expansion. Calcification of the
intervertebral ligaments and fusion of the spinal facet joints and
syndesmophytes leads to what is often called a ‘bamboo’ spine.
 MRI with gadolinium demonstrates sacroiliitis before it is seen on X-
rays, and persistent enthesitis
Non-articular problems in
spondyloarthritis

 Uveitis, in all types

 Cutaneous lesions in reactive arthritis
(keratoderma blennorrhagica), histologically
identical to pustular psoriasis
 Nail dystrophy, in psoriasis and reactive arthritis
 Aortitis, occasionally in AS and reactive arthriti
Treatment
 The key to effective management of AS is early diagnosis so that a
regimen of preventative exercises is started before syndesmophytes
have formed. Morning exercises aim to maintain spinal mobility, posture
and chest expansion.
 Failure to control pain and to encourage regular spinal and chest
exercises leads to an irreversible dorsal kyphosis and wasted
paraspinal muscles. This, along with stiffening of the cervical spine,
makes forward vision difficult.
 When the inflammation is active and the morning pain and stiffness are
too severe to permit effective exercise, an evening dose of a long-acting
or slow-release NSAID or an NSAID suppository improves sleep, pain
control and exercise compliance. Peripheral arthritis and enthesitis are
managed with NSAIDs or local steroid injections.
 Methotrexate is effective for peripheral arthritis but not for spinal
disease.
 The TNF-α blocking drugs adalimumab and etanercept have
revolutionized the lives of people
 with AS. They produce a rapid, dramatic and sustained reduction of
symptoms and of spinal and peripheral joint inflammation. Around half
the patients are able to stop NSAIDs. Relapse occurs on stopping
 In advanced disease there is calcification of
the interspinous ligaments and fusion of the facet joints
as well as syndesmophytes at all levels. The sacroiliac
Psoriatic arthritis
 The prevalence of psoriasis is 2–3% worldwide, and in this
population around 10% have arthritis. A family history of
psoriasis may be a clue to the diagnosis.
 Clinical features
 Patterns of psoriatic arthritis include:Mono- or oligoarthritis,
Polyarthritis virtually indistinguishable from RA . Ankylosing
spondylitis: uni- or bilateral sacroiliitis and early cervical spine
involvement; only 50% are HLA-B27 positive. Distal
interphalangeal arthritis, which is the most typical pattern of joint
involvement in psoriasis, often with adjacent nail dystrophy
reflecting enthesitis extending into the nail root
Arthritis mutilans, which affects about 5% of patients who have
psoriatic arthritis and causes marked periarticular osteolysis and
bone shortening
 Radiologically, psoriatic arthritisis erosive but the erosions are
central in the joint, not juxta-articular, and produce a ‘pencil in
Treatment and prognosis
 NSAIDs and/or analgesics help the pain but they can
occasionally worsen the skin lesions. Local synovitis responds to
intra-articular corticosteroid injections.
 In milder, polyarticular cases, sulfasalazine or methotrexate
slows the development of joint damage.
 When the disease is severe, methotrexate or ciclosporin is given
because they control both the skin lesions and the arthritis. Anti-
TNF-α agents, e.g. etanercept and golimumab and ustekinumab,
are highly effective and safe for severe skin and joint disease.
They should be given when methotrexate has failed.
Corticosteroids orally may destabilize the skin disease and are
best avoided but are valuable when injected into a single
inflamed joint. Rituximab has no role in treating psoriatic arthritis.
 The prognosis for the joint involvement is generally better than in
RA
Reactive arthritis
 Reactive arthritis is a sterile synovitis, which
occurs following an infection .
 Spondyloarthritis develops in 1–2% of patients
after an
acute attack of dysentery, or a sexually acquired
infection –nonspecific urethritis (NSU) in the
male, nonspecific cervicitis in the female. In male
patients who are HLA-B27 positive, the relative
risk is 30–50. Not all patients are HLA-B27
positive.
 Women are less commonly affected.
Aetiology
 A variety of organisms can be the trigger, including some strains of
Salmonella or Shigella spp. in bacillary dysentery.
 Yersinia enterocolitica causes diarrhoea and a reactive arthritis. In NSU,
the organisms are Chlamydia trachomatis
or Ureaplasma urealyticum. People with reactive arthritis are not more
susceptible to infection but appear to respond differently. Bacterial
antigens or bacterial DNA have been found in the inflamed synovium of
affected joints, suggesting that this persistent antigenic material is
driving the inflammatory process. The methods by which HLA-B27
increases susceptibility to reactive arthritis may include: T cell receptor
repertoire selection
 Molecular mimicry causing autoimmunity against HLA-B27 and/or other
self antigens
 Mode of presentation of bacteria-derived peptides to T lymphocytes.
 These are not mutually exclusive. There are other organisms that also
trigger reactive arthritis but have a different genetic basis. In these, the
borderline between reactive arthritis and septic arthritis is more indistinct
and they can cause both
 Clinical features
 The arthritis is typically an acute, asymmetrical, lower-limb
arthritis, occurring a few days to a couple of weeks after the
infection. The arthritis may be the presenting complaint if the
infection is mild or asymptomatic. Enthesitis is common, causing
plantar fasciitis or Achilles tendon enthesitis . Seventy per cent
recover fully within 6 months but many have a relapse.
 In susceptible individuals with reactive arthritis, sacroiliitis and
spondylitis may also develop. Sterile conjunctivitis occurs in
30%. Acute anterior uveitis complicates more severe or relapsing
disease but is not synchronous with the arthritis.
 The skin lesions resemble psoriasis:
 Circinate balanitis in the uncircumcised male causes painless
superficial ulceration of the glans penis. In the circumcised male
the lesion is raised, red and scaly. Both heal without scarring.
 Keratoderma blennorrhagica – the skin of the feet and hands
develops painless, red and often confluent raised plaques and
pustules histologically similar to pustular psoriasis.
 Nail dystrophy occurs
Treatment
 Treating persisting infection with antibiotics alters
the course of the arthritis, once it has developed.
Cultures should be taken and any infection
treated. Sexual partners must be screened.
 Pain responds well to NSAIDs and locally injected
or oral corticosteroids. The majority of individuals
with reactive arthritis have a single attack which
settles, but a few develop a disabling relapsing
and remitting arthritis. Relapsing cases are
sometimes treated with sulfasalazine or
methotrexate .
 TNF-αblocking agents remain the drugs of next
choice in severe and persistent disease but are
rarely necessary.
Enteropathic arthritis associated with
inflammatory bowel disease
 Enteropathic synovitis occurs in up to 10–15% of
patients who have ulcerative colitis and Crohn’s
disease
 The link between the bowel disease and the
inflammatory arthritis is not clear. Selective mucosal
leakiness may expose the individual to antigens that
trigger synovitis.
 The arthritis is asymmetrical and predominantly
affects lower-limb joints. An HLA-B27-associated
sacroiliitis or spondylitis also occurs. The joint
symptoms may predate the development of bowel
disease and lead to its diagnosis.
 Remission of ulcerative colitis or total colectomy
usually leads to remission of the joint disease, but
arthritis can persist even in well-controlled Crohn’s
Treatment
 The inflammatory bowel disease should be
treated. In all cases of enteropathic arthritis, the
symptoms are helped by NSAIDs, although they
may make diarrhoea worse.
 A monoarthritis is best treated by intra-articular
corticosteroids. Sulfasalazine is more frequently
prescribed than mesalazine as it may help both
bowel and joint disease. The TNF-α blocking drug
infliximab is used in inflammatory bowel disease
and can help the arthritis.
World AS Day is celebrated on the
first Saturday of May each year.
In an effort to shine the light of
awareness on Ankylosing
Spondylitis.
THANK YOU.