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Fifth stage
Medicine
Lec. 1
.د
علي عبد الرحم
ن
26/2/2017
SERONEGATIVE
SPONDYLOARTHROPATHIES
SERONEGATIVE SPONDYLOARTHROPATHIES
These comprise a group of related inflammatory joint diseases, which show
considerable overlap in their clinical features and a shared immunogenetic
association with the HLAB27 antigen . They include:
• ankylosing spondylitis
• axial spondyloarthritis
• reactive arthritis, including Reiter’s syndrome
• psoriatic arthritis
• arthropathy associated with inflammatory bowel disease.
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Ankylosing spondylitis
Ankylosing spondylitis (AS) is characterised by a chronic inflammatory arthritis
predominantly affecting the sacroiliac joints and spine, which can progress to bony
fusion of the spine.
The onset is typically between the ages of 20 and 30, with a male preponderance of
about 3 : 1.
In Europe, more than 90% of those affected are HLAB27 positive.
Even if severe ankylosis develops, functional limitation may not be marked as long as
the spine is fused in an erect posture.
Pathophysiology
Ankylosing spondylitis is thought to arise from an as yet illdefined interaction
between environmental pathogens and the host immune system in genetically
susceptible individuals.
Increased faecal carriage of Klebsiella Aerogenes occurs in patients with established
AS and may relate to exacerbation of both joint and eye disease.
Wider alterations in the human gut microbial environment are increasingly
implicated, which could lead to increased levels of circulating cytokines such as IL23
that can activate enthesial or synovial T cells.
The HLAB27 molecule itself is implicated through its antigenpresenting function (it is
a class I MHC molecule) or because of its propensity to form homodimers that
activate leucocytes.
Clinical features
The cardinal feature is low back pain and early morning stiffness with radiation to the
buttocks or posterior thighs.
Symptoms are exacerbated by inactivity and relieved by movement.
The disease tends to ascend slowly, ultimately involving the whole spine, although
some patients present with symptoms of the thoracic or cervical spine.
As the disease progresses, the spine becomes increasingly rigid as ankylosis occurs.
Secondary osteoporosis of the vertebral bodies frequently occurs, leading to an
increased risk of vertebral fracture.
Early physical signs include a reduced range of lumbar spine movements in all
directions and pain on sacroiliac stressing.
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As the disease progresses, stiffness increases throughout the spine and chest
expansion becomes restricted.
Spinal fusion varies in its extent and in most cases does not cause a gross flexion
deformity, but a few patients develop marked kyphosis of the dorsal and cervical
spine that may interfere with forward vision.
Pleuritic chest pain aggravated by breathing is common and results from
costovertebral joint involvement.
Plantar fasciitis, Achilles tendinitis and tenderness over bony prominences such as
the iliac crest and greater trochanter may all occur, reflecting inflammation at the
sites of tendon insertions (enthesitis).
Describe six physical examination tests used to assess sacroiliac joint
tenderness or progression of spinal disease in AS.
Occiput-to-wall test. Assesses loss of cervical range of motion. Normally with the
heels and scapulae touching the wall, the occiput should also touch the wall. Any
distance from the occiput to the wall represents a forward stoop of the neck
secondary to cervical spine involvement with AS. The tragus-to-wall test could also be
used.
Chest expansion. Detects limited chest mobility. Measured at the fourth intercostal
space in men and just below the breasts in women, normal chest expansion is
approximately 5 cm. Chest expansion less than 2.5 cm is abnormal.
Schober test (modified).Detects limitation of forward flexion of the lumbar spine.
Place a mark at the level of the posterior superior iliac spine (dimples of Venus) and
another 10 cm above in the midline. With maximal forward spinal flexion with locked
knees, the measured distance should increase from 10 cm to at least 15 cm .
Other spinal mobility tests will show that lateral flexion and spinal rotation are also
diminished, establishing that the patient has a global loss of spinal mobility.
Pelvic compression. With the patient lying on one side, compression of the pelvis
should elicit sacroiliac joint pain.
Gaenslen’s test. With the patient supine, a leg is allowed to drop over the side of the
examination table while the patient draws the other leg toward the chest. This test
should elicit sacroiliac joint pain on the side of the dropped leg .
Patrick’s test.With the patient’s heel placed on the opposite knee, downward
pressure on the flexed knee with the hip now in flexion, abduction, and external
rotation (FABER) should elicit sacroiliac joint tenderness.
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Up to 40% of patients also have peripheral arthritis. This is usually asymmetrical,
affecting large joints such as the hips, knees, ankles and shoulders.
In about 10% of cases, involvement of a peripheral joint may antedate spinal
symptoms.
In a further 10%, symptoms begin in childhood, as in the syndrome of oligoarticular
juvenile idiopathic arthritis.
Fatigue is a major complaint and may result from both chronic interruption of sleep
due to pain, and chronic systemic inflammation with direct effects of inflammatory
cytokines on the brain.
Assessment of disease activity
Disease activity in AS can be assessed by the Bath Ankylosing Spondylitis Disease
Activity Index (BASDAI), a questionnaire in which patients and their physician rate
severity of various symptoms
This is important in assessing eligibility for biological treatment.
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Investigations
In established AS, radiographs of the sacroiliac joint show irregularity and loss of
cortical margins, widening of the joint space and subsequently sclerosis, joint space
narrowing and fusion.
Lateral thoracolumbar spine Xrays may show anterior ‘squaring’ of vertebrae due to
erosion and sclerosis of the anterior corners and periostitis of the waist.
Bridging syndesmophytes may also be seen. These are areas of calcification that
follow the outermost fibres of the annulus.
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In advanced disease, ossification of the anterior longitudinal ligament and facet joint
fusion may also be visible. The combination of these features may result in the typical
‘bamboo’ spine.
Erosive changes may be seen in the symphysis pubis, the ischial tuberosities and
peripheral joints.
Osteoporosis and atlantoaxial dislocation can occur as late features.
Patients with early disease can have normal Xrays, and if clinical suspicion is high,
MRI should be performed. This is much more sensitive for detection of early
sacroiliitis than Xray and can also detect inflammatory changes in the lumbar spine.
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The ESR and CRP are usually raised in active disease but may be normal.
Testing for HLAB27 can be helpful, especially in patients with back pain suggestive of
an inflammatory cause, when other investigations have yielded equivocal results.
Autoantibodies such as RF, ACPA and ANA are negative.
Management
The aims of management are to relieve pain and stiffness, maintain a maximal range
of skeletal mobility and avoid the development of deformities.
Education and appropriate physical activity are the cornerstones of management.
Early in the disease, patients should be taught to perform daily back extension
exercises, including a morning ‘warmup’ routine, and to punctuate prolonged periods
of inactivity with regular breaks. Swimming is ideal exercise. Poor posture must be
avoided.
NSAIDs and analgesics are often effective in relieving symptoms and may alter the
underlying course of the disease. A longacting NSAID at night is helpful for alleviation
of morning stiffness.
Peripheral arthritis can be treated with methotrexate or sulfasalazine, but these
drugs have no effect on axial disease.
AntiTNF therapy should be considered in patients who are inadequately controlled
on standard therapy with a BASDAI score of ≥4.0 and a spinal pain score of ≥4.0.
AntiTNF therapy frequently improves symptoms but has not been shown to prevent
ankylosis or alter natural history of the disease.
Other biological interventions using agents developed for RA have been
disappointing, suggesting fundamental differences in disease pathogenesis.
Local corticosteroid injections can be useful for persistent plantar fasciitis, other
enthesopathies and peripheral arthritis.
Oral corticosteroids may be required for acute uveitis but do not help spinal disease.
Severe hip, knee or shoulder restriction may require surgery. Total hip arthroplasty
has largely removed the need for difficult spinal surgery in those with advanced
deformity.
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Reactive arthritis
Reactive arthritis (previously known as Reiter’s disease) is predominantly a disease of
young men, with a male preponderance of 15 : 1.
It is the most common cause of inflammatory arthritis in men aged 16–35 but may
occur at any age.
Reactive arthritis may present with triad of non-specific urethritis, reactive
arthritis,and conjunctivitis, but many patients present with arthritis only.
Clinical features
The onset is typically acute, with an inflammatory oligoarthritis that is asymmetrical
and targets lower limb joints, such as the knees, ankles, midtarsal and MTP joints.
It occasionally presents with single joint involvement and no clear history of an
infectious trigger.
There may be considerable systemic disturbance, with fever and weight loss.
Achilles tendinitis or plantar fasciitis may also be present.
The first attack of arthritis is usually selflimiting, but recurrent or chronic arthritis
develops in more than 60% of patients, and about 10% still have active disease 20
years after the initial presentation.
Low back pain and stiffness are common and 15–20% of patients develop sacroiliitis.
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Investigations
The diagnosis is usually made clinically but joint aspiration may be required to
exclude crystal arthritis and articular infection.
Synovial fluid is leucocyterich and may contain multinucleated macrophages (Reiter’s
cells).
ESR and CRP are raised during an acute attack.
Urethritis may be confirmed in the ‘twoglass test’ by demonstration of mucoid
threads in the firstvoid specimen that clear in the second.
High vaginal swabs may reveal Chlamydia on culture.
Except for postSalmonella arthritis, stool cultures are usually negative by the time
the arthritis presents, but serum agglutinin tests may help confirm previous
dysentery.
RF, ACPA and ANA are negative.
In chronic or recurrent disease, Xrays show periarticular osteoporosis, joint space
narrowing and proliferative erosions.
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Another characteristic feature is periostitis, especially of metatarsals, phalanges and
pelvis, and large, ‘fluffy’ calcaneal spurs.
In contrast to AS, radiographic sacroiliitis is often asymmetrical and sometimes
unilateral, and syndesmophytes are predominantly coarse and asymmetrical, often
extending beyond the contours of the annulus (‘nonmarginal’)
Xray changes in the peripheral joints and spine are identical to those in psoriasis.
Management
The acute attack should be treated with rest, oral NSAIDs and analgesics.
Intraarticular steroids may be required in patients with severe synovitis.
Nonspecific chlamydial urethritis is usually treated with a short course of doxycycline
or a single dose of azithromycin, and this may reduce the frequency of arthritis in
sexually acquired cases.
Treatment with DMARDs should be considered for patients with persistent marked
symptoms, recurrent arthritis or severe keratoderma blennorrhagica.
Anterior uveitis is a medical emergency requiring topical, subconjunctival or systemic
corticosteroids.
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Psoriatic arthritis
Psoriatic arthritis (PsA) occurs in 7–20% of patients with psoriasis and in up to 0.6% of
the general population.
The onset is usually between 25 and 40 years of age.
Most patients (70%) have preexisting psoriasis but in 20% the arthritis predates the
occurrence of skin disease. Occasionally, the arthritis and psoriasis develop
synchronously.
Clinical features
The presentation is with pain and swelling affecting the joints and entheses.
Several patterns of joint involvement are recognised but the course is generally one
of intermittent exacerbation followed by varying periods of complete or near-
complete remission.
Destructive arthritis and disability are uncommon, except in the case of arthritis
mutilans.
PATTERNS OF PsA
Asymmetrical inflammatory oligoarthritis affects about 40% of patients and often
presents abruptly with a combination of synovitis and adjacent periarticular
inflammation.
This occurs most characteristically in the hands and feet, when synovitis of a finger or
toe is coupled with tenosynovitis, enthesitis and inflammation of intervening tissue
to give a ‘sausage digit’ or dactylitis.
Large joints, such as the knee and ankle, may also be involved, sometimes with very
large effusions.
Symmetrical polyarthritis occurs in about 25% of cases.
It predominates in women and may strongly resemble RA, with symmetrical
involvement of small and large joints in both upper and lower limbs.
Nodules and other extraarticular features of RA are absent and arthritis is generally
less extensive and more benign.
Much of the hand deformity often results from tenosynovitis and soft tissue
contractures.
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Distal IPJ arthritisis an uncommon but characteristic pattern affecting men more
often than women. It targets finger DIP joints and surrounding periarticular tissues,
almost invariably with accompanying nail dystrophy.
Psoriatic spondylitis presents a similar clinical picture to AS but with less severe
involvement. It may occur alone or with any of the other clinical patterns described
above and is typically unilateral or asymmetric in severity.
Arthritis mutilansis a deforming erosive arthritis targeting the fingers and toes that
occurs in 5% of cases of PsA. Prominent cartilage and bone destruction results in
marked instability. The encasing skin appears invaginated and ‘telescoped’ and the
finger can be pulled back to its original length.
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Extra-articular features
Nail changes include pitting, onycholysis, subungual hyperkeratosis and horizontal
ridging. They are found in 85% of those with PsA and only 30% of those with
uncomplicated psoriasis, and can occur in the absence of skin disease.
The characteristic rash of psoriasis may be widespread, or confined to the scalp,
natal cleft and umbilicus, where it is easily overlooked.
Conjunctivitis can occur, whereas uveitis is mainly confined to HLAB27positive
individuals with sacroiliitis and spondylitis.
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Investigations
The diagnosis is made on clinical grounds.
Autoantibodies are generally negative and acute phase reactants, such as ESR and
CRP, are raised in only a proportion of patients with active disease.
Xrays may be normal or show erosive change with joint space narrowing. Features
that favour PsA over RA include the characteristic distribution of proliferative
erosions with marked new bone formation, absence of periarticular osteoporosis and
osteosclerosis.
Imaging of the axial skeleton often reveals features similar to those in chronic
reactive arthritis, with coarse, asymmetrical, nonmarginal syndesmophytes and
asymmetrical sacroiliitis.
MRI and ultrasound with power Doppler are increasingly employed to detect synovial
inflammation and inflammation at the entheses.
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Management
Therapy with NSAID and analgesics may be sufficient to control symptoms in mild
disease.
Intraarticular steroid injections can control synovitis in problem joints.
Splints and prolonged rest should be avoided because of the tendency to fibrous and
bony ankylosis.
Patients with spondylitis should be prescribed the same exercise and posture regime
as in AS.
Therapy with DMARDs should be considered for persistent synovitis unresponsive to
conservative treatment. Methotrexate is the drug of first choice since it may also
help skin psoriasis, but other DMARDs may also be effective, including sulfasalazine,
ciclosporin and leflunomide.
DMARD monitoring should take place with particular attention to liver function since
abnormalities are common in PsA.
Hydroxychloroquine is generally avoided, as it can cause exfoliative skin reactions.
AntiTNF treatment should be considered for patients with active synovitis who
respond inadequately to standard DMARDs. This is effective for both PsA and
psoriasis.
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Other biological treatments, such as ustekinumab, are emerging, which target the IL-
12/23 receptor. Ustekinumab is highly effective in the treatment of psoriatic skin
disease and is often effective in PsA.
The retinoid acitretin is effective for skin lesions and, anecdotally, may also help
arthritis, but it is teratogenic so must be avoided in young women. It also causes
mucocutaneous sideeffects, hyperlipidaemia, myalgias and extraspinal calcification.
Photochemotherapy with methoxypsoralen and longwave ultraviolet light (psoralen
+UVA, PUVA) is primarily used for skin disease, but can also help those with
synchronous exacerbations of inflammatory arthritis.
Enteropathic arthritis
An acute inflammatory oligoarthritis occurs in around 10% of patients with ulcerative
colitis and 20% of those with Crohn’s disease. It predominantly affects the large
lower limb joints (knees, ankles, hips) but wrists and small joints of the hands and
feet can also be involved. The arthritis usually coincides with exacerbations of the
underlying bowel disease, and sometimes is accompanied by aphthous mouth ulcers,
iritis and erythema nodosum.
It improves with effective treatment of the bowel disease, and can be cured by total
colectomy in patients with ulcerative colitis.
Patients with inflammatory bowel disease may also develop sacroiliitis (16%) and AS
(6%), which are clinically and radiologically identical to classic AS. These can predate
or follow the onset of bowel disease and there is no correlation between activity of
the spondylitis and bowel disease.
The arthritis often remits with treatment of the bowel disease but DMARD and
biological treatment is occasionally required.