Does this patient have ankylosing spondylitis?

Ankylosing spondylitis (AS) is prototype axial spondyloarthropathy (SpA); historically the diagnosis requires the presence of radiographic spinal damage which evolves over years. Patients present with inflammatory low back pain long before they demonstrate characteristic radiographic changes of sacroiliitis, and findings of syndesmophyte formation may take more than 10 years to develop. A typical patient is under the age of 40 and presents with inflammatory low back pain: back pain which is insidious in onset:

  • present for greater than 3 months.

  • worse in the morning with at least one half hour of morning stiffness.

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  • improves with exercise.

  • Night pain may awaken the patient.

  • alternating buttock pain.

  • pain is typically relieved by nonsteroidal anti-inflammatory drugs (NSAIDS).

The physical exam of the spine in the patient with early AS may reveal tenderness over the sacroiliac joints, but patients may have loss of the normal lumbar lordosis as well as an exaggerated and fixed cervical kyphosis that may impair horizontal gaze.

The Schober’s test measures the loss of spinal flexion (for any reason) in a 10 cm segment of the patient’s lower spine, which should increase by at least 3.5 cm when someone with a normal spine flexes forward with their knees locked. Occiput to wall distance can also be measured with knee straight and heels and buttocks touching the wall.

Musculoskeletal manifestations outside the spine include hip and shoulder involvement, which are considered axial joints, and are involved in 40% of patients with AS. There is a predilection for enthesitis, or inflammation of the sites of tendon, fashion, or ligament insertion into bone. This produces characteristic pain which is most common in the lower extremities, particularly affecting the Achilles tendon and plantar fascia, which produces heel pain. Dactylitis may produce characteristic sausage digits.

Chest pain may occur when chest wall enthesopathy affects the costovertebral or costosternal junctions, and may produce restriction of chest wall expansion as well as mechanical restrictive pulmonary disease. A normal adult can expand their chest by 5 cm, but significant loss of motion can occur early in the course of AS.

SpA may be indistinguishable from early AS in the pre-radiographic form, but not all patients with undifferentiated SpA will develop the structural damage necessary to confirm the diagnosis of AS. Markers such as CRP are being sought to differentiate SpA from AS, and the presence of clinical features such as inflammatory bowel disease, uveitis, and psoriasis, are the same in both groups.

The genetic marker HLA-B27 has also failed to differentiate early AS from SPA; all of the similarities support the concept that they represent the same fundamental disease.

Recent emphasis on early diagnosis to encourage early therapy has prompted this reassessment of the long-standing radiographic criteria, a concept influenced by the dramatic improvements in rheumatoid arthritis outcomes based on early diagnosis and therapy. New classification criteria proposed by the Assessment of Spondyloarthritis International Society (ASAS) emphasized differentiation of SpA by axial dominant involvement, which includes AS, versus peripheral arthritis dominated SpA, and is controversial given the overlap and fluidity between the groups.

The new criteria permit diagnosis of SpA prior to the development of radiographic sacroiliitis, if the HLA-B27 marker is present plus inflammatory low back pain or other typical features of SpA such as psoriasis, dactylitis, or uveitis. The justification of earlier diagnosis and classification for study and inclusion in clinical trials has supported the use of more sensitive modalities such as magnetic resonance imaging (MRI) as well.

Spondyloarthropathy features that comprise the ASAS criteria are listed below, and are meant to be applied in patients under the age of 45 who have had back pain for greater than 3 months. When sacroiliitis is present on an imaging study, one feature is required; if not, the HLA-B27 marker plus two features are required.

SpA features:

  • inflammatory back pain.

  • iritis or uveitis.

  • enthesitis.

  • dactylitis.

  • psoriasis.

  • Crohn’s/colitis.

  • good response to NSAIDs.

  • family history of SpA.

  • HLA-B27.

  • elevated CRP.

What tests to perform?


There is no single laboratory test which is diagnostic of AS, although the presence of the genetic marker HLA-B27 is supportive in a patient who has inflammatory low back pain. Although 85-90% of patients with AS are HLA-B27 positive, approximately 10% of the unaffected population of European and North American descent bear this genetic marker. This marker is not helpful in patients of African descent.

Acute phase reactants

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) measurements are not useful as activity measures as they are frequently normal in AS, but may reflect activity when peripheral arthritis dominates the clinical picture, or there is associated inflammatory bowel disease. When elevated, these inflammatory markers may help differentiate inflammatory from non-inflammatory back pain. When inflammatory markers are elevated, they may be repeated as an indicator of the response to therapy.


Patients may have a mild normochromic normocytic anemia, another nonspecific finding.

Synovial fluid analysis

Reveals a typical leukocytosis seen in the joint fluid in any inflammatory arthritis patient, often more neutrophils than with rheumatoid effusions.


Plain radiographs demonstrating sacroiliitis provide the classic basis for the diagnosis of AS. Symmetric erosions are seen in the synovial component of the SI joint, which is the anterior inferior two thirds, with eventual ankylosis. These characteristic changes on plain radiographs may not appear until symptoms of low back pain have been present for 10 years, however, and SpA cannot be distinguished from AS on the basis of sacroiliac radiographs.

Early changes of the discovertebral joint result from erosions at the corners of the vertebrae, producing a square appearance of the vertebrae, with shiny corners resulting from attempt at repair. Syndesmophytes form later as the annulus fibrosis and longitudinal ligament ossify, forming a “bamboo spine”. These late changes are highly characteristic of AS, but present late. See Figure 1.

Figure 1.

Spine radiograph in ankylosing spondylitis.

MRI is a sensitive imaging technique and is an important component of the ASAS criteria.

Active inflammation can be visualized on fat-suppressed T2 images, where high intensity subchondral bone marrow lesions, corresponding to erosions on CT scan, have been recognized. Chronic damage is well visualized by standard T1 images, where fatty replacement is seen as high-intensity lesions, and low intensity areas correspond with erosions and sclerotic lesions.

MRI is more sensitive and specific than any other imaging modality, with the additional potential for use in monitoring response to therapy when potent disease modifying drugs are used. Plain x-ray should be obtained when the patient is initially evaluated. When symptoms are severe, and the diagnosis is unclear, MRI can be employed.

There is no commonly accepted radiographic scoring system to follow AS. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) is currently the best accepted, but consistent quantification of change on serial radiographs is difficult. This is a 1-72 point scale which grades each vertebral unit for erosion, sclerosis, squaring, or syndesmophytes formation. Although this is an accurate assessment of radiographic change, it is very time consuming and cumbersome to employ in an office practice. MRI based scores are being developed to assess inflammation and response to therapy, but expense makes widespread adoption of this difficult.


Biopsies are not employed to make a diagnosis of AS.

Overall interpretation of test results (diagnosis, prognosis)

Radiographic AS may take years before characteristic plain radiograph findings are present, yet over dependence on MRI cannot be generally recommended due to its significant expense. The findings, if present, however, are specific. The presence of the HLA-B27 genetic marker is most useful in Northern Europeans and Americans of European descent.

How should patients with ankylosing spondylitis be managed?

The ASAS and European League Against Rheumatism (EULAR) recently reviewed their recommendations for the treatment of AS and formulated overarching principles which stressed the importance of involving the patient in designing the treatment plan. Additional principals include recognition that undertaking the treatment of patients with AS requires an understanding of the potentially severe manifestations of the disease, and the need for multidisciplinary collaboration. They stressed the importance of long-term goals, which are felt to be necessary as this is a lifelong condition.

Controlling symptoms and inflammation and preventing structural damage to permit normal activity should therefore be the primary goal of therapy. Optimal care should require both medication as well as nonpharmacologic therapy. Lastly, specific interventions need to consider the specific disease manifestations and its severity.


NSAIDs are first-line pharmacologic therapy in AS and provide significant benefit in treating pain and stiffness in many patients. Continuous therapy with NSAIDs provides symptom relief and also decreases the rate of radiographic progression. Although significant gastrointestinal, cardiac, and renal toxicities are recognized as due to NSAIDs, they remain valuable in these patients.

There is no evidence of benefit from systemic corticosteroid use for axial disease symptoms in AS, although guided sacroiliac injections with corticosteroids can decrease inflammation and decrease pain. Conventional DMARDs such as sulfasalazine and methotrexate show little benefit and AS patients with axial disease, but may be helpful in patients with peripheral arthritis.

Anti-TNF therapy

Biologic agents in the anti-TNF class are beneficial for patient who have active disease in spite of therapy with NSAIDs, and provide relief of pain and improve function. Patients with persistent pain and inflammation after treatment with at least two NSAIDs over 3 months should be considered for anti-TNF therapy.

Active disease can be measured with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which combines pain level with duration of morning stiffness and fatigue. Decreased radiographic progression of syndesmophytes and ankylosis has not been demonstrated with therapy, although decreased inflammation of the spine has been reported on follow-up MRI.

Pulmonary function impairment does improve with anti-TNF therapy. There is no recognized benefit of one anti-TNF agent over others and treatment of AS, although coexistent GI disease such as Crohn’s / colitis may require use of Infliximab or adalimumab.

Other classes of biologic have not demonstrated efficacy in AS patients, and should not be used. The usual precautions apply regarding risk of infection (prescreening for TB and vigilance for fungal infections).

Physical therapy

Physical therapy and exercise are a crucial component of AS care, and have proven benefit in improving function and decreasing pain. The goal of physical therapy is to decrease the flexion deformity of the spine and decrease disability. Extension and rotation exercises are fundamental to an AS patient’s regimen, and should be performed daily. Patient education plays an important role in reinforcing the importance of regular exercise.


Can be considered in those patients who have advanced cartilage erosion with pain and restricted mobility. Total hip arthroplasty (THA) is very successful for AS patients with advanced erosive hip involvement, with excellent pain relief and durability of the implant. Younger age of onset predicts more severe disease and increases the likelihood of undergoing THA.

Perioperative concerns include the prevention of heterotopic ossification (HO) with NSAIDs or low-dose irradiation, HO may complicate surgery in young male patients such as the typical AS patient, and may contribute to functional limitations in range of motion.

Anesthesia should be consulted preoperatively so that airway management can be planned when cervical spine kyphosis and fusion are present. Nasotracheal intubation and intubation with direct visualization may be necessary to protect the cervical spine.

Spine surgery

May be considered to correct severe flexion deformity, and can be indicated to improve posture and restore horizontal gaze. Fractures may complicate AS, given the frequency of associated osteoporosis as well as the altered biomechanics of the ankylosed spine. These occur most commonly in the cervical spine, and usually occur after low intensity trauma.

Diagnosis is frequently delayed, and neurologic compromise is common, with neurologic deficits reported in 67% of AS patients who sustained a spinal fracture. Prompt consultation with a spine surgeon is mandatory, although complications including neurologic deterioration remain high.

What happens to patients with ankylosing spondylitis?

AS is a systemic disease in patients may have extra-articular manifestations. Anterior uveitis, usually unilateral but recurrent, is common, occurring in 30% of AS patients. These patients should be referred for ophthalmologic care. Treatment with local corticosteroid and mydriatics is frequently successful. More severe cases may require systemic therapy. Although anti-TNF therapy has been shown to decrease the frequency of uveitis flares by 50%, episodes while on anti-TNF therapy remain common.

Cardiac involvement in AS is multifactorial. Ischemic cardiac disease (CAD) is increasingly recognized as a complication of sustained inflammation with CRP elevation. AS patients are also more likely to have other CAD risk factors such as dyslipidemia, hypertension, and diabetes mellitus. Aortic regurgitation and aortic root dilatation are uncommon but characteristic cardiac findings associated with the HLA B27 gene. Heart block is also associated with the B27 gene.

Pulmonary parenchymal involvement is rare by routine evaluation, although high-resolution CT scans reveal a higher prevalence of abnormalities such as linear opacities and reticulonodular infiltrates. The chest wall is frequently effected by AS, where costovertebral, sternomanubrial, and thoracic involvement can restrict chest wall expansion producing significant restrictive pulmonary pathology. Patients become obligate diaphragmatic breathers if chest wall involvement is advanced.

It is difficult to reconcile the disconnect of inflammatory spine lesions from syndesmophyte formation. Although recent studies have demonstrated a decrease in inflammatory spine lesions seen on MRI, the rate of syndesmophyte formation and the development of new syndesmophytes continue, in spite of anti-TNF therapy.

Although the TNF cytokine has had dramatic success in the treatment of RA, where the pathologic process is characterized by boney erosion, blocking TNF has little effect on new bone formation, which is mediated by other cytokine pathways and proceeds in spite of anti-TNF therapy.


How to utilize team care?

Physical therapy consultation should be part of AS care for all patients, given the importance of exercise in preventing and slowing functional loss. Education regarding the importance of a physical therapy regimen is useful to reinforce an exercise routine. Decreasing the flexion deformity of the spine can be addressed by physical therapy, where in addition to an active exercise program, can also stress the importance of simple maneuvers such as eliminating the pillow at night so that the neck is not held in flexion.

Specialty consultations are routine part of AS management. Spondyloarthropathy features such as inflammatory bowel disease, uveitis, and psoriasis are best managed in consultation with ophthalmology, gastroenterology, and dermatology. Surgical consultation for consideration of arthroplasty or corrective spine surgery is also appropriate. Total hip arthroplasty is an effective treatment for patients with advanced symptomatic hip arthritis.

Are there clinical practice guidelines to inform decision making?

The ASAS/EULAR recommendations for management of AS are based on results of a systematic literature review that informed discussion among the group of international experts, AS patients and physical therapists.

Disease activity can be measured with the ankylosing spondylitis disease activity scale (AS DAS), for the Bath AS Disease Activity Index (BASDAI). These include function, pain as measured by a visual analog scale (VAS), spinal mobility as measured in a modified Schober’s test and occiput to wall distance, Patient Global Assessment by VAS, duration of morning stiffness, number swollen peripheral joints, fatigue, inflammatory markers such as ESR and CRP, and radiographs of the lumbar spine, cervical spine and pelvis.

Radiographic scales to document progression have also been developed, but are not as useful and outcome measures given the disappointing lack of benefit in affecting radiographic progression seen with current therapy and a slow timeframe of radiographic change. The scales are important in clinical trials, but have not been adopted into practice as widely as the activity measures for rheumatoid arthritis, and may seem cumbersome to use them in routine office practice.

Other considerations

Axial spondyloarthropathy; Psoriatic arthritis; Arthritis associated with inflammatory bowel disease; enthesitis; tendonitis; uveitis.

Patients are not usually hospitalized for AS.

What is the evidence?

Braun, J, van den Berg, R, Baraliakos, X. “2010 Update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis”. Ann Rheum Dis. vol. 70. 2011 Jun. pp. 896-904.

Dougados, M, Braun, J, Szanto, S. “Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double blind placebo controlled study”. Ann Rheum Dis.. vol. 70. 2011 May. pp. 799-804.

Szabo, S, Levy, A, Rao, S. “Increased risk of cardiovascular and cerebrovascular disease in individuals with ankylosing spondylitis: a population based study”. Arthritis and Rheum. 2011.

Song, I-H, Hermann, KG, Haibel, H. “Relationship between active inflammatory lesions in the spine and sacroiliac joints and new development of chronic lesions on whole body MRI in early axial spondyloarthritis: results of the ESTHER trial at week 48”. Ann Rheum Dis. vol. 70. 2011. pp. 1257-1263.

Rudalweit, M, van der Heijde, D, Landewe, R. “The assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general”. Ann Rheum Dis. vol. 70. 2011. pp. 25-31.

van der Heijde, D, Sieper, J, Maksymowych, W. “2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis”. Ann Rheum Dis. vol. 70. 2011. pp. 905-908.

van der Heijde, D, Landewe, R, Einstein, S. “Radiographic progression of ankylosing spondylitis after up to two years of treatment with Etanercept”. Arthritis Rheum. vol. 58. 2008. pp. 1324-1331.

Braun, J, Baraliakos, X. “Imaging of axial spondyloarthritis including ankylosing spondylitis”. Ann Rheum Dis. vol. 70. 2011. pp. 97-103.

Bremander, A, Petersson, I, Bergman, S, Englund, M. “Population based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis”. Arth Care and Res. vol. 63. 2011. pp. 550-556.

Revielle John, D. “The genetic basis of spondyloarthritis”. Ann Rheum Dis. vol. 70. 2011. pp. 44-50.

Colbert, Robert. “Early axial spondyloarthritis”. Curr Opinion Rheumatol. vol. 22. 2010. pp. 603-607.

Kanathur, N, Lee-Chong, T. “Pulmonary manifestations of ankylosing spondylitis”. Clinics in Chest Med.. 2010. pp. 31

Song, IH, Poddibnyy, DA, Rudalweit, M, Sieper, J. “Benefits and risks of ankylosing spondylitis treatment With nonsteroidal anti-inflammatory drugs”. Arthritis & Rheum. vol. 58. 2008. pp. 929-938.