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Ankylosing Spondylitis

By Apostolos Kontzias, MD, Assistant Professor of Medicine and Director, Autoinflammatory Clinic, Cleveland Clinic Foundation

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Ankylosing spondylitis is the prototypical spondyloarthropathy and a systemic disorder characterized by inflammation of the axial skeleton, large peripheral joints, and digits; nocturnal back pain; back stiffness; accentuated kyphosis; constitutional symptoms; aortitis; cardiac conduction abnormalities; and anterior uveitis. Diagnosis requires showing sacroiliitis on x-ray. Treatment is with NSAIDs and/or tumor necrosis factor antagonists or IL-17 antagonists and physical measures that maintain joint flexibility.

Ankylosing spondylitis (AS) is 3 times more frequent in men than in women and begins most often between ages 20 and 40. It is 10 to 20 times more common among 1st-degree relatives of AS patients than in the general population. The HLA-B27 allele is present in 90% of AS patients, but it is also present in up to 10% of the general population depending on ethnicity. The risk of AS in 1st-degree relatives with the HLA-B27 allele is about 20%. Increased prevalence of HLA-B27 in whites or HLA-B7 in blacks supports a genetic predisposition. However, the concordance rate in identical twins is only about 50%, suggesting that environmental factors contribute. The pathophysiology probably involves immune-mediated inflammation.


Most patients with AS have predominantly axial involvement (called axial AS). Some have predominately peripheral involvement. Among those with axial involvement, some have no evidence of sacroiliitis on plain x-rays. Thus, some experts have classified AS as follows:

  • Axial AS: Has predominantly axial involvement and x-ray findings typical of sacroiliitis

  • Nonradiographic AS: Clinically similar to axial AS but without x-ray findings typical of sacroiliitis

  • Peripheral AS: AS with predominantly peripheral involvement

Symptoms and Signs

The most frequent manifestation of ankylosing spondylitis is back pain, but disease can begin in peripheral joints, especially in children and women, and rarely with acute iridocyclitis (iritis or anterior uveitis). Other early symptoms and signs are diminished chest expansion from diffuse costovertebral involvement, low-grade fever, fatigue, anorexia, weight loss, and anemia.

Back pain—often nocturnal and of varying intensity—eventually becomes recurrent. Morning stiffness, typically relieved by activity, and paraspinal muscle spasm develop. A flexed or bent-over posture eases back pain and paraspinal muscle spasm; thus, kyphosis is common in untreated patients. Severe hip arthritis can eventually develop. In late stages, the patient has accentuated kyphosis, loss of lumbar lordosis, and fixed bent-forward posturing, with compromised pulmonary function and inability to lie flat. There may be peripheral potentially deforming joint involvement, sometimes involving the digits (dactylitis). Achilles and patellar tendinitis can occur.

Systemic manifestations of AS occur in one third of patients. Recurrent, acute anterior uveitis is common and usually responds to local therapy; less commonly it becomes protracted and severe enough to impair vision. Neurologic signs occasionally result from compression radiculitis or sciatica, vertebral fracture or subluxation, or cauda equina syndrome. Cardiovascular manifestations can include aortic insufficiency, aortitis, angina, pericarditis, and cardiac conduction abnormalities (which may be asymptomatic). Dyspnea, cough, or hemoptysis can rarely result from nontuberculous fibrosis or cavitation of an upper lobe of the lung; cavitary lesions can become secondarily infected with Aspergillus. Rarely, AS results in secondary amyloidosis. Subcutaneous nodules do not develop.


  • Lumbosacral spine and sacroiliac joint radiography

  • Blood tests (ESR, C-reactive protein, HLA-B27, and CBC) or explicit clinical criteria (modified New York criteria or Assessment of SpondyloArthritis international Society criteria)

  • Pelvic MRI in select patients

AS should be suspected in patients, particularly young men, with nocturnal back pain and kyphosis, diminished chest expansion, Achilles or patellar tendinitis, or unexplained anterior uveitis. A 1st-degree relative with AS should heighten suspicion.

Patients should generally be tested with ESR, HLA-B27, C-reactive protein, and CBC. Rheumatoid factor (RF) and antinuclear antibodies are needed only if peripheral arthritis suggests other diagnoses. The HLA-B27 allele is present in 90% of AS patients, but it is also present in up to 10% of the general population depending on ethnicity. No laboratory test is diagnostic, but results can increase suspicion for the disorder or rule out other disorders that can simulate AS. If, after these tests, AS is still suspected, patients should undergo x-ray of the lumbosacral spine and sacroiliac joint; demonstration of sacroiliitis on x-ray strongly supports the diagnosis.

Some patients should undergo pelvic MRI to look for sacroiliitis that is not seen on x-rays. In these patients, MRI shows osteitis or early erosions.

AS has traditionally been diagnosed by the modified New York criteria. Using these criteria, the patient must have imaging study evidence of sacroiliitis and one of the following:

  • Restriction of lumbar spinal motion in both the sagittal (looking from the side) and frontal (looking from the back) planes

  • Restriction of chest expansion, adjusted for age

  • A history of inflammatory back pain

To diagnose patients earlier in the disease process, particularly those without spondyloarthritis on imaging, the novel Assessment of SpondyloArthritis international Society (ASAS) criteria (1) have been established. The ASAS criteria for axial spondyloarthritis are applied to patients who have had back pain for > 3 mo and who are < 45 yr of age at onset.

Diagnosis can be done using ASAS imaging or clinical criteria. To fulfill the imaging criteria, patients must have radiographic or MRI evidence of sacroiliitis plus at least 1 spondyloarthritis feature. To fulfill the clinical criteria, patients must have HLA-B27 plus at least 2 separate spondyloarthritis features. ASAS spondyloarthritis features include the following:

  • Dactylitis

  • Enthesitis of the heel

  • Family history of spondyloarthritis

  • History of inflammatory back pain

  • IBD

  • Presence of HLA-B27

  • Elevated C-reactive protein

  • Good response to NSAIDs

Historical features that distinguish inflammatory back pain from noninflammatory back pain include onset at 40 yr, gradual onset, morning stiffness, improvement with activity, and duration 3 mo before seeking medical attention.

ESR and other acute-phase reactants (eg, C-reactive protein) are inconsistently elevated in patients with active AS. Tests for RF and antinuclear antibodies are negative. The HLA-B27 genetic marker is not usually helpful because positive and negative predictive values are low.

The earliest x-ray abnormalities are pseudowidening caused by subchondral erosions, followed by sclerosis or later narrowing and eventually fusion in the sacroiliac joints. Changes are symmetric. Early changes in the spine are upper lumbar vertebral squaring with sclerosis at the corners; spotty ligamentous calcification; and one or two evolving syndesmophytes. Late changes result in a “bamboo spine” appearance, resulting from prominent syndesmophytes, diffuse paraspinal ligamentous calcification, and osteoporosis; these changes develop in some patients on average over 10 yr.

Changes typical of AS may not become visible on plain x-rays for years. MRI shows changes earlier, but there is no consensus regarding its role in routine diagnosis given the lack of prospective, validated data in regard to its diagnostic utility. Pelvic MRI should be done if the index of suspicion of spondyloarthritis is high or if there is a need to rule out other causes of the patient's symptoms.

A herniated intervertebral disk can cause back pain and radiculopathy similar to AS, but the pain is limited to the spine and nerve roots, usually causes more sudden symptoms, and causes no systemic manifestations or laboratory test abnormalities. If necessary, CT or MRI can differentiate it from AS. Involvement of a single sacroiliac joint suggests a different spondyloarthropathy, possibly infection. Tuberculous spondylitis can simulate AS (see TB of bones and joints).

Diffuse idiopathic skeletal hyperostosis (DISH) occurs primarily in men > 50 yr and may resemble AS clinically and on x-ray. Patients uncommonly have spinal pain, stiffness, and insidious loss of motion. X-ray findings in DISH include large ossifications anterior to spinal ligaments (the calcification appears as if someone poured candle wax in front and on the sides of the vertebrae), bridging several vertebrae and usually starting at the lower thoracic spine, eventually affecting the cervical and lumbar spine. There is often subperiosteal bone growth along the pelvic brim and at insertion of tendons (such as the Achilles tendon insertion). However, the anterior spinal ligament is intact and frequently bulging, and sacroiliac and spinal apophyseal joints are not eroded. Additional differentiating features are stiffness that is usually not markedly accentuated in the morning and a normal ESR.

Diagnosis reference

  • 1. Sepriano A, Landewé R, van der Heijde D, et al: Predictive validity of the ASAS classification criteria for axial and peripheral spondyloarthritis after follow-up in the ASAS cohort: A final analysis. Ann Rheum Dis 75(6):1034–1042, 2016. doi: 10.1136/annrheumdis-2015-208730.


AS is characterized by mild or moderate flares of active inflammation alternating with periods of little or no inflammation. Proper treatment in most patients results in minimal or no disability and in a full, productive life despite back stiffness. Occasionally, the course is severe and progressive, resulting in pronounced incapacitating deformities.


  • NSAIDs

  • Sulfasalazine, methotrexate, TNF-alpha antagonists, or IL-17 antagonists (eg, secukinumab)

  • Exercises and supportive measures

The goals of treatment of AS are relieving pain, maintaining joint range of motion, and preventing end-organ damage. Because the condition may cause lung fibrosis, cigarette smoking is discouraged. See the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network's 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

NSAIDs reduce pain and suppress joint inflammation and muscle spasm, thereby increasing range of motion, which facilitates exercise and prevents contractures. Most NSAIDs work in AS, and tolerance and toxicity dictate drug choice. The daily dose of NSAIDs should be as low as possible, but maximum doses may be needed with active disease. Drug withdrawal should be attempted only slowly, after systemic and joint signs of active disease have been suppressed for several months.

Sulfasalazine may help reduce peripheral joint symptoms and laboratory markers of inflammation in some patients. Dosage should be started at 500 mg/day and increased by 500 mg/day at 1-wk intervals to 1 to 1.5 g bid maintenance; because acute neutropenia can occur, cell counts must be monitored when initiating therapy or increasing drug dose. Peripheral joint symptoms may also abate with methotrexate, but spinal symptoms are usually not reduced.

TNF-alpha antagonists (eg, etanercept, infliximab, adalimumab, certolizumab, golimumab) are often strikingly effective treatments for inflammatory back pain.

Secukinumab, an IL-17 antagonist, has also been effective in reducing inflammation and joint symptoms. Secukinumab can be given at a dose of 150 mg sc at wk 0, 1, 2, 3, and 4 and every 4 wk thereafter. Without the loading (weekly) doses, secukinumab is 150 mg sc q 4 wk. Adverse effects include urticaria, URIs, fungal infections due to Candida, diarrhea, herpes zoster, and inflammatory bowel disease.

Systemic corticosteroids, immunosuppressants, and most disease-modifying antirheumatic drugs (DMARDs) have no proven benefit and should generally not be used.

For proper posture and joint motion, daily exercise and other supportive measures (eg, postural training, therapeutic exercise) are vital to strengthen muscle groups that oppose the direction of potential deformities (ie, the extensor rather than flexor muscles). Reading while lying prone and pushing up on the elbows or pillows and thus extending the back may help keep the back flexible. Because chest wall motion can be restricted, which impairs lung function, cigarette smoking, which also impairs lung function, is strongly discouraged.

Intra-articular depot corticosteroids may be beneficial, particularly when one or two peripheral joints are more severely inflamed than others, thereby compromising exercise and rehabilitation. They may also help if systemic drugs are ineffective. Imaging-guided corticosteroid injections into the sacroiliac joints may occasionally help severe sacroiliitis.

For acute uveitis, topical corticosteroids and mydriatics are usually adequate.

If severe hip arthritis develops, total hip arthroplasty may lessen pain and improve flexibility dramatically.

Key Points

  • Ankylosing spondylitis is a systemic disorder that affects the joints and can cause constitutional symptoms, cardiac symptoms, and anterior uveitis.

  • Initial manifestation is usually back pain and stiffness sometimes along with peripheral joint symptoms and/or anterior uveitis.

  • Diagnose based on the results of lumbosacral spine imaging, sacroiliac joint imaging, pelvic MRI, blood tests (ESR, C-reactive protein, HLA-B27, and CBC), and/or explicit clinical criteria.

  • Use NSAIDs to help reduce symptom severity and improve function.

  • Use sulfasalazine, methotrexate, TNF-alpha antagonists, or IL-17 antagonists to relieve joint symptoms.

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