Introduction:
This term is applied to a group of inflammatory joint diseases distinct
from RA that share a number of clinical features:
● Ankylosing spondylitis.
● Reactive arthritis, including Reiter’sdisease.
● Psoriatic arthropathy.
● Arthritis associated with inflammatory bowel disease
(Crohn’s disease, ulcerative colitis).
An association with HLA-B27 occurs in all seronegative
spondarthritides but is particularly strong for ankylosing spondylitis and Reiter’s
disease (> 90%). The suggested pathogenesis
is an aberrant response to infection in genetically predisposed individuals. In
some situations a triggering organism can be identified, as in Reiter’s disease
following bacterial dysentery or chlamydial urethritis, but in others the environmental
trigger remains obscure.
Ankylosing
spondylitis
Ankylosing spondylitis is a chronic inflammatory arthritis
predominantly affecting the sacroiliac joints and spine. The onset is typicallybetween
the ages of 20 and 30, with a male : female ratio of 3 : 1.
Clinical features
The cardinal feature is low back pain radiating to the buttocks or
posterior thighs and early morning stiffness. Symptoms are exacerbated by
inactivity and relieved by movement. The disease tends to ascend slowly,
ultimately involving the whole spine. Examination reveals a reduced range of
lumbar spine movements and pain on sacroiliac stressing. As the disease
progresses, the spine and chest become rigid as ankylosis occurs. Secondary
vertebral osteoporosis frequently occurs, causing an increased fracture risk.
Clinical
features common to seronegative spondarthritis
• Asymmetrical
inflammatory oligoarthritis (lower > upper limb)
• Sacroiliitis and
inflammatory spondylitis
• Inflammatory
enthesitis (e.g. tendons, ligaments)
• Tendency for
familial aggregation
• RF and ACPA
negative
• Absence of nodules
and other extra-articular features of RA
• Extra-articular
features:
Mucosal: conjunctivitis,
buccal ulceration, urethritis, prostatitis, bowel ulceration
Pustular skin
lesions, nail dystrophy Anterior uveitis
Aortic root fibrosis
(aortic incompetence, conduction defects)
Erythema nodosum
Spinal fusion is usually mild, but a few patients develop
incapacitating kyphosis of the thoracic and cervical spine with fixed flexion contractures
of hips or knees. Pleuritic chest pain 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 occur, reflecting inflammation at tendon
insertions (enthesitis).
Up to 40% of patients also have asymmetrical peripheral arthritis,
affecting large joints such as the hips, knees, ankles and shoulders.
In ~10%, involvement of a peripheral joint antedates spinal
symptoms, and in a further 10%, symptoms begin in childhood.
Fatigue is common and reflects both chronic sleep disturbance by pain,
and systemic inflammation with direct effects of inflammatory cytokines on the
brain. Anterior uveitis is the most common extraarticular feature, which
occasionally precedes joint disease.
Investigations
In established ankylosing spondylitis, X-rays of the sacroiliac
joint show irregularity and loss of cortical margins, sclerosis, joint space narrowing
and fusion. Lateral thoracolumbar spine X-rays may show anterior ‘squaring’ of
vertebrae, bridging syndesmophytes, ossification of the anterior longitudinal
ligament and facet joint fusion (‘bamboo’ spine). Erosive changes may be seen
in the symphysis pubis, ischial tuberosities and peripheral joints.
Osteoporosis
and atlanto-axial dislocation can occur. MRI is valuable for
detecting spinal or sacroiliac inflammation in early disease.
The ESR and CRP are usually raised in active disease but may be normal.
HLA-B27 is usually present. Autoantibodies such as RF, ACPA and ANA are
negative.
Management and
prognosis
Education and regular back exercises are essential to maintain mobility
and avoid deformity. NSAIDs are effective in relieving symptoms and may alter
the course of the disease. Long-acting NSAIDs at night are particularly helpful
for morning stiffness.
Sulfasalazine, methotrexate or azathioprine may control peripheral
arthritis but these drugs have no effect on axial disease. Anti-TNF therapy may
improve symptoms in active disease resistant to standard therapy but does not
alter disease course.
Local corticosteroid injections may help persistent plantar
fasciitis, other enthesitis and peripheral arthritis. Severe hip, knee, ankle or
shoulder symptoms may require surgery.
Reactive
arthritis
Reactive arthritis classically affects young men. It follows an episode of bacterial dysentery (due to Salmonella, Shigella, Campylobacter or Yersinia) or non-specific urethritis (due to Chlamydia). The triad of urethritis, conjunctivitis and reactive arthritis constitutes classical Reiter’s disease but incomplete forms are common.
Clinical features
Patients present with acute-onset, inflammatory oligoarthritis
affecting the large and small joints of the lower limbs 1–3 wks following sexual
exposure or an attack of dysentery. Symptoms of urethritis and conjunctivitis
may be present. It occasionally presents with
insidious onset of single joint involvement, minimal features of
urethritis and conjunctivitis, and no clear history of ‘trigger’ illness.
Achilles tendinitis or plantar fasciitis may occur. Additional
extra-articular features include:
● Circinate balanitis: causes vesicles (often painless)
on the prepuce and glans.
● Buccal erosions.
● Keratoderma blennorrhagica: waxy yellow–brown skin
lesions, particularly affecting the palms and soles.
● Nail dystrophy identical to psoriatic nail dystrophy. The
first attack of reactive arthritis is usually self-limiting, with spontaneous
remission within 2–4 mths. Recurrent arthritis develops in > 60% of patients. Uveitis is rare with the first attack
but occurs in 30% of patients with recurring arthritis.
Investigations
● Raised ESR and CRP.
● Aspirated synovial fluid: leucocyte-rich with
multinucleated macrophages. ● High vaginal swab: may reveal Chlamydia.
● Stool cultures: usually negative by the time the
arthritis presents.
● Serum RF, ACPA and ANA: negative.
● X-ray changes: usually absent during the acute attack,
other than soft tissue swelling. Joint space narrowing and marginal erosions
may develop with recurrent disease.
Management
Rest and NSAIDs provide symptomatic relief during the acute phase.
Intra-articular corticosteroid injections may help severe synovitis.
Non-specific chlamydial urethritis is treated with a short course of
doxycycline. DMARDs are occasionally used for severe progressive arthritis and
keratoderma blennorrhagica. Anterior uveitis is a medical emergency requiring
topical or systemic corticosteroids.
Psoriatic
arthropathy
Psoriatic arthritis affects 7–20% of patients with psoriasis. It
typically presents between the ages of 25 and 40 yrs. The seronegative
arthritis usually occurs in individuals with pre-existing cutaneous psoriasis but
can predate the skin disease.
Clinical features
Five major presentations of joint disease are recognised:
Asymmetrical
inflammatory oligoarthritis (40%):
May affect lower and upper limb joints. Involvement of a finger or toe by
synovitis, together with enthesitis and inflammation of intervening tissue, can
give rise to a ‘sausage digit’ or dactylitis. Usually only one or two large
joints are involved, mainly knees.
Symmetrical
polyarthritis (25%): May strongly resemble RA,
with symmetrical involvement of small and large joints in both upper and lower
limbs. However, nodules and other extra-articular features of RA are absent.
Distal interphalangeal
joint (DIPJ) arthritis (15%):
Predominantly affects men, almost invariably with accompanying nail dystrophy.
Psoriatic spondylitis (15%): Presents a similar clinical picture to ankylosing
spondylitis but tends to be less severe.
Arthritis mutilans (5%): This deforming erosive arthritis targets fingers
and toes. Marked cartilage and bone attrition results in loss of the joint and
instability.
The general pattern of psoriatic arthritis is one of intermittent exacerbation
followed by periods of remission. Residual damage and disability are relatively
mild, except in arthritis mutilans.
Extra-articular features include:
● Skin lesions.
● Nail changes: pitting, onycholysis (separation of the nail
from the nail bed) and subungual hyperkeratosis.
● Uveitis (in HLA-B27–positive cases with spondylitis).
Investigations
● ESR and CRP: may be raised but are often normal.
● Serum RF and ANA: negative.
● X-rays: may be normal or show erosive change with
joint space narrowing.
Management and
prognosis
Simple analgesics and NSAIDs provide symptomatic relief.
Intraarticular corticosteroids may help control florid synovitis. Regular exercise
is important in preventing ankylosis. DMARDs may be required for persistent
unresponsive synovitis. Methotrexate is the treatment of choice, as it may also
help severe skin psoriasis. Anti- TNF therapy should be considered in those
unresponsive to DMARDs. The retinoid acitretin is effective in treating both
the
arthritis and the skin lesions but is teratogenic.
Enteropathic
arthritis
This inflammatory arthritis is associated with ulcerative colitis
and Crohn’s disease, predominantly affecting large lower limb joints. The
arthritis coincides with exacerbations of the underlying bowel disease and improves
with effective treatment of the bowel disease. Sacroiliitis and ankylosing
spondylitis indistinguishable from classic ankylosing spondylitis also occur
with bowel disease but are not correlated with the activity of the bowel
disease.
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