Ankylosing Spondylitis

How to Cite This Chapter: Carmona R, Zimmermann-Górska I. Ankylosing Spondylitis. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed June 05, 2020.
Last Updated: June 17, 2019
Last Reviewed: June 17, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Ankylosing spondylitis (AS) is chronic and usually progressive arthritis that mainly affects the sacroiliac joints, intervertebral and costovertebral joints, entheses, annulus fibrosus, and ligaments of the spine and gradually leads to spinal fusion (ankylosis). Etiology is not completely understood but involves genetic and environmental factors. HLA-B27 is strongly associated with AS (75%-95% of patients) but is not necessary for diagnosis. Tumor necrosis factor (TNF) and interleukin 17 (IL-17) are major cytokines and targets of therapy.

Clinical Features and Natural HistoryTop

The onset of AS is usually in late adolescence or young adulthood and very rarely after the age of 40 years. Traditionally men were thought to be more frequently affected. However, more recent studies have shown a 1:1 ratio of males to females, especially in early disease and nonradiographic axial spondyloarthritis (nrAxSpA). The disease may follow a pattern of relapses and remissions but is generally chronic and progressive.

General symptoms: Low-grade fever, weight loss, fatigue.

Musculoskeletal manifestations: Inflammatory lower back pain is the most common initial presentation (Table 15.20-1). Pain is worst at night and early in the morning, improves with activity, does not improve with rest, and is associated with significant morning stiffness. Pain can be constant with worsening at night/morning or intermittent and occurring in flares that last days, weeks, or months. Pain is usually dull, difficult to locate (but sometimes localized to the sacroiliac joints), and unilateral or bilateral. Pain and limitation of motion progressively worsen as the inflammatory process involves other areas of the spine. Involvement of the lumbar spine can eventually lead to loss of physiologic lordosis (flattening). Inflammation of the thoracic spine can cause upper back and chest pain that increases on inspiration and is referred to the front of the thorax along the ribs (this feature differentiates it from pleuritic pain). Eventually patients can develop increased kyphosis, decreased chest expansion, and paraspinal muscle atrophy. Inflammation of the cervical spine causes limitation and subsequent loss of motion and can lead to loss of lordosis. All of these eventually result in the classic stooped posture where the spine becomes rigid and kyphotic.

Many patients can develop peripheral arthritis, which potentially may affect any joint but most commonly involves the larger joints (hips, knees, shoulders). Other features include peri-articular inflammation, such as Achilles tendonitis, plantar fasciitis, and dactylitis.

Due to spinal rigidity and frequent comorbid osteoporosis, trauma can easily lead to spinal fracture, including fractures of the cervical spine.

Anterior uveitis affects up to 25% of patients with AS. It presents with pain, redness, visual impairment, and photophobia. It usually responds to topical glucocorticoids with resolution in 4 to 6 weeks. Recurrent, chronic, or inappropriately treated anterior uveitis can lead to synechiae, cataract formation, and glaucoma.

Cardiovascular manifestations are uncommon, occurring in <10% of patients, and can include aortic regurgitation, aortitis of the ascending aorta, conduction disturbances, and pericarditis.

Gastrointestinal manifestations are common. Up to 10% of patients develop overt inflammatory bowel disease. Up to 50% of patients can have subclinical inflammation affecting the distal small intestine and colon. Gastric or duodenal ulcers can occur; the use of nonsteroidal anti-inflammatory drug (NSAIDs) in the treatment of AS is a factor contributing to their development.

Other potential manifestations:

1) Fibrosis of the upper pulmonary lobes (apical fibrosis).

2) Proteinuria due to renal amyloid deposition or IgA nephropathy.

3) Neurologic symptoms in patients with atlantoaxial subluxation, atlantooccipital subluxation, or cervical vertebral fracture.

4) Depression ­is a consequence of pain, morning stiffness, and persisting fatigue, which interfere with daily activities.

Disease progression and risk of disability is variable. Poor prognostic factors include root joint involvement (hips, shoulders), positive HLA-B27, high C-reactive protein (CRP) level, and presence of syndesmophytes at baseline.


Diagnostic Tests

1. Laboratory tests: Elevated erythrocyte sedimentation rate (ESR) and CRP levels during active disease (~40% of patients with spinal involvement and ~60% of patients with peripheral arthritis), leukocytosis, mild normochromic anemia (in <15% of patients), hypergammaglobulinemia (frequently IgA); negative rheumatoid factor (RF), positive HLA-B27 (in 75%-95% of white patients versus 8% of the general population).

2. Imaging studies: Standard anteroposterior (AP) pelvis radiographs are adequate for radiographic assessment of sacroiliitis without the need for dedicated oblique sacroiliac (SI) joint views. Radiographs can be normal in early disease. Changes are graded as follows:

– Grade 0: Normal.

– Grade 1: Suspicious changes.

– Grade 2: Minimal abnormality (small localized areas with erosion or sclerosis without alteration in the joint width).

– Grade 3: Unequivocal abnormality (moderate or advanced sacroiliitis with ≥1 of erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis).

– Grade 4: Total ankylosis of sacroiliac joints.

Conventional radiography of the sacroiliac joints is the first-choice imaging modality for the assessment of sacroiliitis as part of axial SpA. Imaging of the spine may reveal squaring of the vertebral bodies, syndesmophytes (bony bridging across vertebrae through calcification of annulus fibrosus), and complete fusion of the spine (bamboo spine). Ossification of ligament attachments (enthesophytes) may also be seen. Patients with long-standing disease may develop osteoporosis. In the peripheral joints narrowing of articular spaces with subsequent fusion of the joints may be found.

In patients with suspected axial spondyloarthritis (SpA) but normal radiographs magnetic resonance imaging (MRI) of the SI joints with or without the spine should be considered. MRI may reveal active inflammatory lesions (osteitis/bone marrow edema, enthesitis, capsulitis, synovitis) and structural lesions (bone erosion, new bone formation, sclerosis and fat infiltration). Active inflammatory lesions may predict response to biologic therapy but are not required for initiating such treatment.

Computed tomography (CT), ultrasonography, and scintigraphy are not recommended for diagnosing axial SpA. In patients with suspected peripheral SpA ultrasonography and MRI may be used to detect enthesitis, peripheral arthritis, tenosynovitis, and bursitis.

3. Synovial fluid analysis in patients with peripheral arthritis reveals features of inflammation.

4. Other studies, depending on indications (eg, high-resolution computed tomography [HRCT] of the chest in patients with pulmonary involvement).

Diagnostic Criteria

There are no diagnostic criteria. However, classification criteria are often adapted in clinical practice to establish diagnosis. According to the modified New York criteria (Table 15.20-2), radiologic features are crucial for diagnosis. The new Assessment of SpondyloArthritis International Society (ASAS) criteria (Table 15.20-3) facilitate earlier diagnosis of SpA through the inclusion of MRI before development of structural damage on radiographs. These criteria also include a “clinical arm” that does not require any imaging modality but has lower specificity.

Differential Diagnosis

Scheuermann disease (juvenile kyphosis), other SpAs (Table 15.20-4), rheumatoid arthritis, degenerative disc disease, malignancy, infections (eg, tuberculosis, brucellosis), metabolic bone diseases, diffuse idiopathic skeletal hyperostosis (DISH).


Nonpharmacologic Management

1. Patient education: Advise the patient about the nature of the disease and importance of their active role in disease management and prevention of disability. Proper posture, deep breathing exercises, spinal extension and range-of-movement exercises, and maintenance of spinal alignment during sleep are all important. Avoidance of smoking is also significant, as smoking is associated with greater disease progression.

2. Physiotherapy is helpful for core strengthening, maintenance of spine and joint range of movement, and pain management.


1. NSAIDs are the first-line agents in patients with spinal pain and stiffness.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Sieper J, Lenaerts J, Wollenhaupt J, et al; All INFAST Investigators. Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1. Ann Rheum Dis. 2014 Jan;73(1):101-7. doi: 10.1136/annrheumdis-2012-203201. Epub 2013 May 21. PubMed PMID: 23696633; PubMed Central PMCID: PMC3888606. Agents and dosage: see Table 15.11-2.

2. Analgesics: Acetaminophen (INN paracetamol) and weak opioids (eg, tramadol) are used when NSAIDs are contraindicated, ineffective, or not tolerated.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the lack of experimental evidence; formal evidence for the efficacy of analgesics in spondyloarthritis is lacking (not tested).

3. Glucocorticoids: Intra-articular injections are helpful for short-term management of active peripheral arthritis. SI joint injections (under imaging guidance) can be considered for sacroiliitis, especially when biologic therapy is contraindicated. Injections around the Achilles tendon should be avoided due to the risk of tendon rupture.

4. Disease-modifying antirheumatic drugs (DMARDs):

1) Conventional synthetic DMARDs (sulfasalazine, methotrexate, leflunomide) are not effective for the treatment of axial SpA.Evidence 3Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Chen J, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004800. Review. Update in: Cochrane Database Syst Rev. 2014;11:CD004800. PubMed PMID: 15846731. Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004524. Review. Update in: Cochrane Database Syst Rev. 2013;2:CD004524. PubMed PMID: 17054209. However, they may be effective in peripheral arthritis, either as monotherapy or combination therapy, and can be tried for 3 to 6 months.

2) Biologic DMARDs are indicated in patients with active axial SpA with inadequate response to NSAIDs (or where NSAIDs are contraindicated). Tumor necrosis factor (TNF) inhibitors (etanercept, infliximab, adalimumab, golimumab, certolizumab) were the first class of biologics approved in SpA.Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015 Apr 18;(4):CD005468. doi: 10.1002/14651858.CD005468.pub2. Review. PubMed PMID: 25887212. IL-17 inhibitors (secukinumab, ixekizumab) were approved subsequently.Evidence 5Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Marzo-Ortega H, Sieper J, Kivitz A, et al; Measure 2 Study Group. Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1020-1029. doi: 10.1002/acr.23233. Epub 2017 Jun 7. PubMed PMID: 28235249; PubMed Central PMCID: PMC5518281. Treatment with synthetic DMARDs is not required before or during biologic therapy for axial SpA.

In peripheral SpA biologic DMARDs are indicated in patients with inadequate response to synthetic DMARDs. Biologics are effective for peripheral arthritis, enthesitis, dactylitis, and psoriatic skin and nail disease.

The choice of biologic agents is affected by concurrent extra-articular manifestations. All anti-TNF and anti-IL-17 agents are effective for psoriasis. With the exception of etanercept, anti-TNF agents are effective for inflammatory bowel disease and uveitis. Anti-IL-17 agents are not effective for the treatment of inflammatory bowel disease

Dosage, contraindications, and adverse effects of DMARDs: see Table 15.18-3.

Surgical Treatment

Consider hip arthroplasty in patients with severe pain or disability and radiographic features of joint destruction, regardless of the patient’s age.Evidence 6Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to retrospective observational studies with small numbers of patients. Putnis SE, Wartemberg GK, Khan WS, Agarwal S. A Literature Review of Total Hip Arthroplasty in Patients with Ankylosing Spondylitis: Perioperative Considerations and Outcome. Open Orthop J. 2015 Sep 30;9:483-8. doi: 10.2174/1874325001509010483. eCollection 2015. PubMed PMID: 26587066; PubMed Central PMCID: PMC4645831. Surgical correction of kyphosis (kyphoplasty) is rarely performed but can be considered in patients with severe kyphosis.Evidence 7Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to observational (cohort) data. Kim KT, Park DH, Lee SH, Lee JH. Results of Corrective Osteotomy and Treatment Strategy for Ankylosing Spondylitis with Kyphotic Deformity. Clin Orthop Surg. 2015 Sep;7(3):330-6. doi: 10.4055/cios.2015.7.3.330. Epub 2015 Aug 13. PubMed PMID: 26330955; PubMed Central PMCID: PMC4553281.


Follow-up assessment of disease activity includes history, physical examination, CRP levels, and clinical tools such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (available at Repeat radiographs of the SI joints and/or spine may be considered for long-term monitoring of structural damage but often do not impact clinical decision-making. If uncertainty about disease activity exists (eg, other conditions confounding back pain or response to therapy), MRI of the sacroiliac joints and/or spine can be performed. MRI short tau inversion recovery (STIR) sequences are sufficient; contrast enhancement is not necessary. In peripheral SpA power Doppler ultrasonography or MRI can be considered if uncertainty exists after clinical assessment.


Table 15.20-1. Assessment of SpondyloArthritis International Society (ASAS) criteria for inflammatory back pain

– Age at onset < 40 years

– Insidious onset

– Improvement with exercise

– No improvement with rest

– Pain at night (with improvement upon getting up)

Inflammatory back pain present if ≥4 criteria are present. Sensitivity, 79.6%; specificity 72.4%.

Adapted from Ann Rheum Dis. 2009;68(6):784-8.

Table 15.20-2. Modified New York diagnostic criteria for ankylosing spondylitis

Clinical criteria

1) Low back pain persisting for ≥3 months, reduced by exercise and not relieved by rest

2) Limited motion in the lumbar spine in coronal and sagittal planes

3) Limited chest expansion compared with normal values for age and sex

Radiologic criterion

Grade 3-4 unilateral or grade 2-4 bilateral sacroiliitis

Definite ankylosing spondylitis: The radiologic criterion and ≥1 of clinical criteria are fulfilled.

Probable ankylosing spondylitis: Three clinical criteria are fulfilled or the radiologic criterion alone is fulfilled.

Adapted from Arthritis Rheum. 1984;27(4):361-8.

Table 15.20-3. 2010 Assessment of SpondyloArthritis International Society (ASAS) criteria for classification of spondyloarthritis

Axial SpA (to be applied in patients with back pain present for ≥3 months and age of onset <45 years)

Sacroiliitis on imaging (MRI or radiography) and ≥1 other feature of SpA


Presence of HLA-B27 antigen and ≥2 other features of SpA

Features of SpA:

– Inflammatory back paina

– Peripheral arthritis

– Enthesitis (heel)

– Uveitis

– Dactylitis

– Psoriasis

– Crohn disease or ulcerative colitis

– Good response to NSAIDs (resolution or significant improvement of back pain within 24-48 h of administration of a full dose)

– Family history of SpA

– HLA-B27

– Elevated serum CRP level (when other causes have been excluded)

Peripheral SpA

Arthritis, enthesitis, or dactylitis


≥1 of the following features of SpA:

– Anterior uveitis

– Psoriasis

– Crohn disease or ulcerative colitis

– Prior infection

– HLA-B27

– Sacroiliitis on imaging


≥2 of the following features of SpA:

– Arthritis

– Enthesitis

– Dactylitis

– Inflammatory back paina (at any time in history)

– Family history of SpA

a Characterized by ≥4 of the following: (1) age of onset <40 years; (2) insidious onset; (3) reduced by exercise; (4) not relieved by rest; (5) present at night (decreases after getting up).

CRP, C-reactive protein; MRI, magnetic resonance imaging; NSAID, nonsteroidal anti-inflammatory drug; SpA, spondyloarthritis.

Table 15.20-4. Differential diagnosis of arthritis








M:F 1:1

M:F 1:3

OA of hands and feet more common in women

M:F 3:1

(but 1:1 in nrAxSpA)

Peripheral arthritis




Involvement of distal interphalangeal joints


Heberden nodes





Morning stiffness of peripheral joints, cervical and lumbar spine

Morning stiffness

Stiffness associated with prolonged physical inactivity

Severe spinal stiffness




Rheumatoid factor



B27, DR4



Radiographic features

Erosions without osteopenia, “pencil-in-cup” deformity, juxta-articular new bone formation, large asymmetric syndesmophytes

Erosions, periarticular osteopenia


Thin and symmetric syndesmophytes, vertebral osteopenia

AS, ankylosing spondylitis; F, female; M, male; nrAxSpA, nonradiographic axial spondyloarthritis; OA, osteoarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis.

We would love to hear from you

  • Do you have any comments?
  • Have you found a mistake?
  • Would you like to suggest a feature?

We use cookies to ensure you get the best browsing experience on our website. Refer to our Cookies Information and Privacy Policy for more details.