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Ankylosing spondylitis

Last updated: September 9, 2021

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Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy and a chronic inflammatory disease of the axial skeleton that leads to partial or complete fusion and rigidity of the spine. It is a part of a spectrum of inflammatory spondyloarthropathies known as axial spondyloarthritis and can also be referred to as radiographic axial spondyloarthritis. Males are disproportionately affected and > 90% of patients are positive for HLA-B27, which is a predisposing factor for the disease. Pain and stiffness in the lower back and neck, caused by inflammation of the vertebral column and the sacroiliac joints, are characteristic early features of AS. Pain typically improves with activity and is particularly prominent at night. Other articular findings include restricted spine mobility and tenderness of the sacroiliac joints on provocation tests, such as the FABER test. The most common extraarticular manifestation is acute, unilateral anterior uveitis. Kyphosis and fusion of the costovertebral joins can cause restrictive lung disease. Diagnosis is primarily based on typical clinical features, elevated inflammatory markers, HLA-B27 positivity, and evidence of inflammatory changes and ankylosis of the sacroiliac (sacroiliitis) and/or intervertebral joints (bamboo spine) on imaging. Typical features may be absent on imaging in early AS, but the presence of several classical clinical and laboratory features is sufficient to confirm the diagnosis and initiate treatment. There is no curative treatment for AS, but regular physiotherapy can slow disease progression. Pharmacotherapy for AS includes NSAIDs and/or TNF-α inhibitors (e.g., infliximab, adalimumab, etanercept). In severe cases, surgery (e.g., arthroplasty) may be considered to improve the patient's quality of life. Patients with AS are at an increased risk of osteoporosis and pathological fractures (chalk stick fractures). Axial spondyloarthritis also includes nonradiographic axial spondyloarthritis, a condition that causes similar symptoms to AS but without inflammatory changes on plain radiographs. Management of nonradiographic axial spondyloarthritis is the same as for AS.

Epidemiological data refers to the US, unless otherwise specified.

  • Genetic predisposition: 90–95% of patients are HLA-B27 positive.

Articular manifestations

Extraarticular manifestations

Positive SIJ pain provocation tests

Tenderness over the sacroiliac joints can be elicited on pain provocation tests, such as:

FABER test [8]

Pain in the ipsilateral SIJ on Flexion, ABduction, and External Rotation (FABER) indicates a positive test.

Mennell sign [9]

Tenderness to percussion and pain on displacement (distraction) of the SIJ indicates sacroiliitis or degeneration. The SIJ can be distracted using the following maneuvers.

  • Prone position: Lift the leg passively (i.e., extend the hip) with one hand while applying pressure on the ipsilateral SIJ with the other hand.
  • Lateral position
    • Ask the patient to flex their lower hip and knee to ∼ 90°.
    • Lift the upper leg and extend the upper hip with one hand while fixing the pelvis with the other hand.
  • Supine position: Apply posteriorly directed pressure to the anterior superior iliac spines.

Reduced spinal mobility [10]

Spinal mobility is typically significantly decreased in advanced or severe AS.

Schober test

A bedside examination to assess lumbar forward flexion

  • With the patient standing, the examiner marks two points on the patient's back: one at L5 and one 10 cm above. [11]
  • The patient is asked to touch their toes without bending their knees.
  • An increase of < 4 cm between the two points suggests impaired spine flexion.

Lateral lumbar flexion test

A bedside examination to assess lumbar lateral flexion

  • The patient is asked to stand with their back against the wall with hands by the side and flex as far as possible to one side without bending their knees.
  • The distance between the tip of the patient's middle finger and the floor is measured on the ipsilateral side.
  • A larger fingertip-to-floor distance indicates limited spinal mobility.

Chest expansion on deep breathing

A bedside examination to assess thoracic spine mobility [11]

  • Measure the chest circumference after maximal expiration and again after maximal inspiration.
  • A smaller difference in measurements (< 2.5 cm) indicates limited thoracic spine and costovertebral joint mobility. [3][11]
  • Reduced chest expansion can also be due to concomitant pulmonary disease, chest wall deformities, or poor respiratory effort.

Kyphosis [10][12][13]

Kyphosis due to loss of anterior vertebral height and wedging of the thoracic vertebrae is present in up to 50% of patients, especially those with advanced AS. The extent of the deformity may be subtle and is assessed using the occiput-to-wall distance.

  • Ask the patient to stand against a wall with their heels, buttocks, and shoulders pressed against the wall.
  • Measure the distance between the occiput and the wall.
  • In a healthy individual, the occiput should be touching the wall; the inability to do so is considered abnormal.

Approach [4][14]

  • Suspect AS in patients < 45 years of age who present with features of inflammatory back pain lasting > 3 months.
  • Initial test in all individuals with suspected AS: x-ray of the sacroiliac joints
    • X-ray findings consistent with AS in a patient with typical features of AS: diagnosis confirmed
    • X-ray findings equivocal: Obtain CRP (or ESR) and HLA-B27.
  • HLA-B27 positive
    • High likelihood of AS (compelling clinical picture): diagnosis confirmed; no further imaging required
    • Only a few classical clinical features of AS: MRI of the sacroiliac joints
  • HLA-B27 negative
  • Consider imaging of the spine in patients with pain in the cervical, thoracic, or lumbar spine.
  • Further workup for associated conditions may be appropriate depending on extraarticular manifestations.

Diagnostic criteria [3]

There are several diagnostic criteria for AS (e.g., New York criteria, Rome criteria). The Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis, which is based on a combination of clinical features and imaging or laboratory findings, is detailed here.

Laboratory findings

Interpret a positive HLA-B27 test in conjunction with clinical features as only ∼ 1% of individuals who are positive for HLA-B27 have AS.

Imaging [14]

X-ray

Sacroiliac joints (PA view) [3]

  • Indication: best initial test to confirm the diagnosis of AS and evaluate disease severity
  • Characteristic findings (usually symmetrical)

Spine (AP and lateral views)

Early stages of AS may be unidentifiable on x-ray (low sensitivity for early-stage). Hence, a patient with several classical clinical and laboratory findings fulfills the diagnostic criteria for AS even if x-ray findings are inconclusive. [4][14]

MRI

MRI is the most sensitive method for early detection of inflammatory changes of AS. However, MRI is not routinely required to confirm a diagnosis of AS as specialized MRI techniques and radiology expertise is required to accurately identify AS findings. [18]

Sacroiliac joints with gadolinium contrast

  • Indication: negative or equivocal radiographs of sacroiliac joints in a patient with some classical features of AS [4]
  • Characteristic findings

Spine without contrast

  • Indications: suspected AS in a patient with any of the following
  • Characteristic findings [19]
    • Romanus lesions: inflammatory lesions (high signal intensity) seen anterior or posterior vertebral corners
    • Reparative changes: secondary bone formation, e.g., on the periphery of or within intervertebral disks

CT sacroiliac joints and/or spine

Further evaluation for extraarticular disease

Symptom-based workup for extraarticular manifestations
Extraarticular complication Characteristic clinical features Recommended diagnostic studies and characteristic findings
Restrictive lung disease
Anterior uveitis
Inflammatory bowel disease
Aortic root and valve disease [5]
Atrioventricular blocks [5]
IgA nephropathy

Syndesmophytes vs. osteophytes

Syndesmophytes

Osteophytes
Definition

Radiographic features

  • Horizontal growth
Etiology
  • Inflammatory spine disease (e.g., AS)

Syndesmophytes grow vertically, as opposed to osteophytes, which grow horizontally!

The differential diagnoses listed here are not exhaustive.

Approach [2][4]

  • Early referral to rheumatology is recommended in all patients with suspected or confirmed AS.
  • Ensure all patients receive supportive therapy.
  • Assess symptom severity.
    • Severe ongoing symptoms: Manage as active disease.
    • Asymptomatic patient or manageable symptoms for > 6 months: Manage as stable disease.
    • New, acute pain (could indicate a pathological fracture): See “Management of acute pain.”
  • Manage extraarticular complications and associated diseases accordingly.
  • The management of Nr-axSpA is similar to AS.

Supportive therapy

All patients with AS, regardless of the disease stage, should receive appropriate supportive therapy to improve their mobility and prevent complications.

Physical therapy is vital in the management of patients with AS.

Management of active disease

Pharmacological therapy

Pharmacological therapy in ankylosing spondylitis [2]
Medication class Indications Dosage and administration Cautions
NSAIDs
  • First-line treatment for patients without concurrent IBD or renal impairment [26]
  • Should be taken continuously (i.e., not on-demand)
  • See “Oral analgesics” for agents and dosages.
TNF-α inhibitors
  • First-line treatment in patients with concurrent IBD or recurrent anterior uveitis
  • Second-line in patients with insufficient response to two different NSAIDs
Antiinterleukin-17 antibodies
Local parenteral glucocorticoids
  • Persistent symptoms despite NSAID treatment and any of the following:
  • Risk of infection (localized or joint)
  • Can cause elevated blood glucose and blood pressure
Sulfonamides
  • Risk of hepatic and renal toxicity, bone marrow suppression, and development of fibrosing alveolitis; monitor regularly.
Antimetabolites

Advanced therapeutic options [2]

Spinal osteotomy is a high-risk procedure with unclear benefits; for most patients, the risks outweigh the potential benefits!

Management of stable disease [2]

Patients with AS may have stable disease at diagnosis or following management of active disease.

Monitoring treatment response [2]

  • Treatment efficacy should be assessed by a physician.
  • Treatment response can be assessed based on the impact of symptoms on quality of life and the trend of inflammatory markers and imaging findings.
  • In patients with stable AS, regular follow-up imaging is not recommended.

Management of acute pain [24][28]

Spinal fractures can occur following minor trauma, e.g., a fall from standing, or even spontaneously.

Immobilizing the patient using standard techniques can cause iatrogenic spinal cord injury!

We list the most important complications. The selection is not exhaustive.

  1. Boel A, Molto A, van der Heijde D, et al. Do patients with axial spondyloarthritis with radiographic sacroiliitis fulfil both the modified New York criteria and the ASAS axial spondyloarthritis criteria? Results from eight cohorts. Ann Rheum Dis. 2019; 78 (11): p.1545-1549. doi: 10.1136/annrheumdis-2019-215707 . | Open in Read by QxMD
  2. Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019; 71 (10): p.1599-1613. doi: 10.1002/art.41042 . | Open in Read by QxMD
  3. Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009; 68 (Suppl 2): p.ii1-ii44. doi: 10.1136/ard.2008.104018 . | Open in Read by QxMD
  4. Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016; 374 (26): p.2563-2574. doi: 10.1056/nejmra1406182 . | Open in Read by QxMD
  5. Momeni M, Taylor N, Tehrani M. Cardiopulmonary Manifestations of Ankylosing Spondylitis. International Journal of Rheumatology. 2011; 2011 : p.1-6. doi: 10.1155/2011/728471 . | Open in Read by QxMD
  6. Ozkan Y. Cardiac Involvement in Ankylosing Spondylitis.. Journal of clinical medicine research. 2016; 8 (6): p.427-30. doi: 10.14740/jocmr2488w . | Open in Read by QxMD
  7. Eder L, Sadek M, McDonald-Blumer H, Gladman DD. Aortitis and spondyloarthritis--an unusual presentation: case report and review of the literature.. Semin Arthritis Rheum. 2010; 39 (6): p.510-4. doi: 10.1016/j.semarthrit.2008.11.004 . | Open in Read by QxMD
  8. Stone JH. A Clinician's Pearls & Myths in Rheumatology. Springer ; 2009
  9. Rickenbacher J, Landolt AM, Theiler K. Applied Anatomy of the Back. Springer Science & Business Media ; 2013
  10. Haywood KL, Garratt AM, Jordan K, Dziedzic K, Dawes PT. Spinal mobility in ankylosing spondylitis: reliability, validity and responsiveness. Rheumatology. 2004; 43 (6): p.750-757. doi: 10.1093/rheumatology/keh169 . | Open in Read by QxMD
  11. 2010 National Health and Nutrition Examination Survey: Arthritis Body Measures.
  12. Mundwiler ML, Siddique K, Dym JM, Perri B, Johnson JP, Weisman MH. Complications of the spine in ankylosing spondylitis with a focus on deformity correction. Neurosurg Focus. 2008; 24 (1): p.E6. doi: 10.3171/foc/2008/24/1/e6 . | Open in Read by QxMD
  13. D Vosse et al.. What causes hyperkyphosis in patients with ankylosing spondylitis?. Nature Clinical Practice Rheumatology. 2006; 2 (9): p.463-463. doi: 10.1038/ncprheum0261 . | Open in Read by QxMD
  14. Bernard SA et al. ACR Appropriateness Criteria ® Chronic Back Pain Suspected Sacroiliitis-Spondyloarthropathy. J Am Coll Radiol. 2017; 14 (5): p.S62-S70. doi: 10.1016/j.jacr.2017.01.048 . | Open in Read by QxMD
  15. Sheehan NJ. The ramifications of HLA-B27.. J R Soc Med. 2004; 97 (1): p.10-4. doi: 10.1258/jrsm.97.1.10 . | Open in Read by QxMD
  16. Bakland G, Nossent HC. Epidemiology of Spondyloarthritis: A Review. Curr Rheumatol Rep. 2013; 15 (9). doi: 10.1007/s11926-013-0351-1 . | Open in Read by QxMD
  17. Shevchuk S, Zviahina O. Frequency and spectrum of anemic syndrome in patients with ankylosing spondylitis, peculiarities of cytometric characteristics and hemopoiesis. Ann Rheum Dis. 2019 . doi: 10.1136/annrheumdis-2019-eular.4365 . | Open in Read by QxMD
  18. Bennett AN, Marzo-Ortega H, Emery P, McGonagle D. Diagnosing axial spondyloarthropathy. The new Assessment in SpondyloArthritis international Society criteria: MRI entering centre stage. Ann Rheum Dis. 2009; 68 (6): p.765-767. doi: 10.1136/ard.2009.111435 . | Open in Read by QxMD
  19. Canella C, Schau B, Ribeiro E, Sbaffi B, Marchiori E. MRI in Seronegative Spondyloarthritis: Imaging Features and Differential Diagnosis in the Spine and Sacroiliac Joints. Am J Roentgenol. 2013; 200 (1): p.149-157. doi: 10.2214/ajr.12.8858 . | Open in Read by QxMD
  20. Hutcheson CJ, Howe JW. The Low Back and Pelvis: Clinical Applications. Aspen Publications ; 1996
  21. Nascimento FA, Gatto LA, Lages RO, Neto HM, Demartini Z, Koppe GL. Diffuse idiopathic skeletal hyperostosis: A review. Surg Neurol Int. 2014; 5 (Suppl 3): p.S122-125. doi: 10.4103/2152-7806.130675 . | Open in Read by QxMD
  22. Mata S, Fortin PR, Fitzcharles MA, et al. A controlled study of diffuse idiopathic skeletal hyperostosis: Clinical features and functional status. Medicine. 1997; 76 (2): p.104-117.
  23. Dülger S, Aykurt Karlibel İ, Kasapoğlu Aksoy M, Altan L, Şengören Dikiş Ö, Yildiz T. How Does Smoking Cessation Affect Disease Activity, Function Loss, and Quality of Life in Smokers With Ankylosing Spondylitis?. J Clin Rheumatol. 2019; 25 (7): p.288-296. doi: 10.1097/RHU.0000000000000851 . | Open in Read by QxMD
  24. Van der Heijde D, Ramiro S, Landewé R, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017; 76 (6): p.978-991. doi: 10.1136/annrheumdis-2016-210770 . | Open in Read by QxMD
  25. Hinze AM, Louie GH. Osteoporosis Management in Ankylosing Spondylitis.. Curr Treatm Opt Rheumatol. 2016; 2 (4): p.271-282. doi: 10.1007/s40674-016-0055-6 . | Open in Read by QxMD
  26. Fragoulis GE, Liava C, Daoussis D, Akriviadis E, Garyfallos A, Dimitroulas T. Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment.. World journal of gastroenterology. 2019; 25 (18): p.2162-2176. doi: 10.3748/wjg.v25.i18.2162 . | Open in Read by QxMD
  27. Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2015; 68 (2): p.282-298. doi: 10.1002/art.39298 . | Open in Read by QxMD
  28. Chaudhary SB, Hullinger H, Vives MJ. Management of acute spinal fractures in ankylosing spondylitis.. ISRN rheumatol. 2011; 2011 : p.150484. doi: 10.5402/2011/150484 . | Open in Read by QxMD
  29. Lukasiewicz AM et al. Spinal Fracture in Patients With Ankylosing Spondylitis. Spine. 2016; 41 (3): p.191-196. doi: 10.1097/brs.0000000000001190 . | Open in Read by QxMD
  30. Kim K-T et al. Results of Corrective Osteotomy and Treatment Strategy for Ankylosing Spondylitis with Kyphotic Deformity. Clin Orthop Surg. 2015; 7 (3): p.330. doi: 10.4055/cios.2015.7.3.330 . | Open in Read by QxMD