Ankylosing Spondylitis

Bernard Zimmermann, M.D.

Basic Information

Definition

Ankylosing spondylitis is a type of inflammatory arthritis involving the sacroiliac joints and axial skeleton characterized by ankylosis and enthesitis (inflammation at tendon insertions). It is one of a family of overlapping syndromes called seronegative spondyloarthropathies (SpA) that includes reactive arthritis (formerly Reiter syndrome), psoriatic spondylitis, and enteropathic arthritis.

Synonyms

Marie-Strümpell disease

ICD-10CM CODES
M45.9	Ankylosing spondylitis of unspecified sites in spine
M08.1	Juvenile ankylosing spondylitis
M45.0	Ankylosing spondylitis of multiple sites in spine
M45.1	Ankylosing spondylitis of occipito-atlanto-axial region
M45.2	Ankylosing spondylitis of cervical region
M45.3	Ankylosing spondylitis of cervicothoracic region
M45.4	Ankylosing spondylitis of thoracic region
M45.5	Ankylosing spondylitis of thoracolumbar region
M45.6	Ankylosing spondylitis lumbar region
M45.7	Ankylosing spondylitis of lumbosacral region
M45.8	Ankylosing spondylitis sacral and sacrococcygeal region

Epidemiology & Demographics

Prevalence

Between 0.1% and 1% of the population. Varies with prevalence of HLA-B27. Much higher in those with positive family history of spondyloarthropathy.

Predominant Age at Onset

15 to 35 years

Predominant Sex

Male/female ratio 2 to 3:1

Physical Findings & Clinical Presentation

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Prolonged morning back stiffness of insidious onset lasting more than 3 months
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Bilateral sacroiliac tenderness (sacroiliitis)
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Back pain often improves with exercise and is worse with rest
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Limited lumbar spine motion (Fig. 1)

FIG.1

Loss of lumbodorsal spine mobility in a boy with ankylosing spondylitis. The lower spine remains straight when the patient bends forward.

From Behrman RE: Nelson textbook of pediatrics, ed 17, Philadelphia, 2005, Saunders.
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Tenderness at tendon insertion sites, especially the Achilles tendons and plantar fascia
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Loss of chest expansion reflecting rib cage involvement
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Peripheral joint arthritis, usually involving the large joints of the lower extremities, may be present
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In advanced cases the typical posture consists of compensatory hyperextension of neck, fixed flexion of hips, and compensatory flexion of knees (Fig. 2)

FIG.2

Ankylosing spondylitis.

Typical posture in advanced cases compared with normal posture.

From Ballinger A: Kumar & Clark’s essentials of clinical medicine, ed 6, Edinburgh, 2012, Saunders.
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There is an increased incidence of iritis and uveitis (30%-40% lifetime prevalence)
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Other extraskeletal manifestations include effects on the cardiovascular system (aortic insufficiency and cardiovascular disease) and lungs (pulmonary fibrosis). There is also an increased risk for osteoporosis.

Etiology

Genetic factors, particularly HLA-B27, play an important role in susceptibility to the spondyloarthropathies. Infectious triggers have been implicated in some cases. Tumor necrosis factor is important in the inflammatory response.

Diagnosis

Differential Diagnosis

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Diffuse idiopathic skeletal hyperostosis (Forestier disease)
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Noninflammatory back pain (A clinical algorithm for the evaluation of back pain is described in Section III.)

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Table 1 compares ankylosing spondylitis and related disorders.

TABLE1 Comparison of Ankylosing Spondylitis and Related DisordersFrom Hochberg MC et al: Rheumatology, ed 5, St Louis, 2011, Mosby.

Feature	Ankylosing Spondylitis	Psoriatic Arthritis	Reactive Arthritis	Enteropathic Arthropathy
Gender (M:F)	2-3:1	1:1	8:1 (GU) [1:1 (GI)]	1:1
Age at onset	<40	35-55	20-40	Young adult
Sacroiliitis or spondylitis	100%	∼20%	∼40%	<20%
Symmetry of sacroiliitis	Symmetric	Asymmetric	Asymmetric	Symmetric
Peripheral arthritis	∼25%	95%	90%	15%-20%
Distribution	Axial and lower limbs	Any joint	Lower limbs	Variable
HLA-B27	85%-95%	25%	30%-80%	7%
Uveitis	25%-40%	25%	25%	10%-36%

Laboratory Tests

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Elevated sedimentation rate, C-reactive protein
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Mild hyperchromic anemia
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Demonstration of inflammatory sacroiliitis by radiography or MRI is diagnostic for most patients, although some patients may meet criteria for “preradiographic spondyloarthropathy” based on compelling clinical evaluation.
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HLA-B27 antigen is not useful in the evaluation of noninflammatory back pain because it is present in up to 8% to 10% of the normal population.

Imaging Studies

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Classic features are those of bilateral sacroiliitis on radiographs of the pelvis
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Vertebral bodies lose anterior concave shape and become square
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With progression, calcification of the annulus fibrosus and paravertebral ligaments develops, giving rise to the so-called bamboo spine and a “trolley track” appearance (Fig. 3).

FIG.3

Ankylosing spondylitis.

A, Fusion of the facet joints and ossification of the adjacent soft tissue have produced a “trolley track” appearance (arrows). The sacroiliac joints are fused, and syndesmophytes are present. B, In another patient, there is a prominent fusion of the interspinous ligaments producing a “saber sheath” appearance.

From Harris ED: Kelley’s textbook of rheumatology, ed 7, Philadelphia, 2005, Saunders.
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MRI (Fig. 4) may be useful in detecting early inflammatory lesions and is especially helpful when the history is suggestive but radiographs are equivocal.

FIG.4

Spine inflammation in ankylosing spondylitis (magnetic resonance imaging [MRI]).

A 43-year-old

Treatment

Nonpharmacologic Therapy

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Exercises primarily to maintain flexibility and aerobic activity are important
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Postural training
1. 1.
  
  Patients must be instructed on spinal extension exercises to avoid fusion in a flexed position.
2. 2.
  
  Sleeping should be in the supine position on a firm mattress; pillows should not be placed under the head or knees.

Pharmacologic Therapy

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NSAIDs: Patients with ankylosing spondylitis should be prescribed full-dose continuous NSAID therapy. There is anecdotal evidence suggesting that indomethacin may be more effective than other NSAIDs, but other NSAIDs are efficacious and may be better tolerated. One study suggested that continuous NSAID therapy may retard the radiographic progression of ankylosing spondylitis, but conflicting data have been published.
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Sulfasalazine may be efficacious in some patients, especially for peripheral arthritis.
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Tumor necrosis factor (TNF) antagonists such as etanercept, infliximab, and adalimumab have been shown to be very effective for relieving symptoms of spinal inflammatory arthritis in numerous controlled studies. Anti-TNF therapy should be recommended for patients whose symptoms are not completely controlled with NSAIDs, and it sometimes results in dramatic improvement in symptoms, range of motion of the spine, and quality of life for these patients. There is evidence suggesting that anti-TNF therapy slows the radiographic progression of the disease.
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Secukinumab, an anti-interleukin-17A monoclonal antibody, has been approved for treatment of ankylosing spondylitis, but its role has yet to be defined.

Disposition

Most patients have a normal life span but many suffer significant disability from loss of spinal mobility.

Referral

All patients with seronegative spondyloarthropathy should be referred to a rheumatologist for consideration of anti-TNF therapy.

Pearls & Considerations

A family history of seronegative spondyloarthropathy increases the specificity of testing for HLA-B27. Surgical osteotomy may benefit selected patients with severe spinal deformity. Recent data suggest that men with AS have increased risk of vascular mortality.

Ferri – Ankylosing Spondylitis