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Basics ⬇

Author(s): ScottChandler, DO and KevindeWeber, MD, FAAFP, FACSM, RMSK

Description

  • Ankylosing spondylitis (AS) is a chronic inflammatory, autoimmune arthritis characterized by inflammatory back pain (IBP).
  • It is the most common and potentially severe subtype of spondyloarthritis (SpA), which includes:
    • Reactive (Reiter) arthritis.
    • Arthritis/spondylitis with inflammatory bowel disease (IBD).
    • Arthritis/spondylitis with psoriasis.
    • Unspecified spondylitis.
    • AS without confirmed radiographic findings is classified as nonradiographic axial spondyloarthropathy (nr-axSpA) and has similar outcomes and response to treatment.
  • AS causes inflammation of the sacroiliac (SI) joints, peripheral joints, and entheses (sites where ligaments or tendons attach to bone).
  • Common sites for enthesopathy include:
    • Calcaneus (Achilles and plantar fascia insertions).
    • Patella.
    • Tibial tubercle.
    • Vertebral bodies.
  • The involvement of vertebral body entheses leads to the characteristic findings of syndesmophytes (vertical bony growths) and eventual fusion, which are responsible for the classic radiographic “bamboo” appearance of the spine in advanced disease.
  • Synonym(s): axial spondyloarthritis; inflammatory spine disease

Epidemiology

Incidence

  • Overall incidence: 0.5 to 8.2/100,000/yr
  • Incidence rate varies directly with prevalence of human leukocyte antigen (HLA)-B27 in given population.
  • Commonly presents in young adulthood
  • Predominant age:
    • 80% of patients with AS develop symptoms before age 30 yr.
    • <5% of patients with AS present after age 45 yr.
  • Predominant gender: male > female (~3:1)

Prevalence

  • Prevalence of AS is 9 to 30/10,000 depending on HLA-B27 prevalence in the population (1).
  • Higher in Alaskan Eskimos and some Native American populations owing to higher than average HLA-B27 rate
  • Lower in African Americans secondary to a lower HLA-B27 rate
  • Up to 5% of patients evaluated for chronic low back pain are ultimately diagnosed with AS.

Etiology and Pathophysiology

  • A clear etiologic pathway has not been established.
  • Speculated that an environmental/infectious trigger in a genetically susceptible individual leads to an inflammatory (T cell and macrophage) immune response that specifically targets SI, peripheral joint, and enthesis inflammation, eventually causing bony proliferation, erosions, sclerosis, and joint destruction.

Genetics

  • Expression of HLA-B27 antigen is clearly linked to the development of AS, but the exact mechanism is unknown.
  • Prevalence of HLA-B27 in African Americans is 2–4% and in Caucasians is 8%.

Risk-Factors

  • Positive family history of SpA or HLA-B27
  • 90% or more of individuals with AS are HLA-B27 positive, although an individual who is HLA-B27 positive has a 5% chance of having AS.
  • Reactive arthritis triggered by Chlamydia trachomatis and certain enteric infections (e.g., Shigella, Salmonella, Yersinia, and Campylobacter spp.) predisposes to development of AS.

General Prevention

  • Currently no preventive therapies or screening tests
  • Early recognition and initiation of treatment can prevent disease progression and complications; unfortunately, it is common for there to be 5 to 6 yr delay in diagnosis.

Commonly Associated Conditions

Diagnosis ⬆ ⬇

  • Diagnosis is primarily based on history of IBP (see “History”) and exam findings with imaging used to confirm diagnosis.
  • The modified New York criteria have historically been used for research inclusion but have never been validated for clinical use. Their limitation is requirement of radiographic evidence of disease, which may take years to develop; need at least one radiographic criteria and one clinical criteria for definitive diagnosis:
    • Radiologic criteria:
      • Bilateral sacroiliitis grades 2 to 4 or
      • Unilateral sacroiliitis grade 3 or 4
    • Clinical criteria:
      • Low back pain and stiffness of at least 3 mo duration that improves with exercise but is not relieved by rest
      • Limited lumbar spinal motion in sagittal (sideways) and frontal (forward and backward) planes
      • Chest expansion decreased relative to normal values corrected for age and sex
  • New criteria to diagnose all causes of IBP, not just AS, have been developed by the Assessment for SpondyloArthritis International Society (ASAS); intended to detect early disease without dependence on radiographic evidence of disease
  • ASAS-endorsed criteria for IBP (validated clinical rule) (3)[A]:
    • Age of onset <45 yr
    • >3 mo of back pain of insidious onset
    • Sacroiliitis on imaging + one SpA feature or positive HLA-B27 + two SpA features
      • SpA features: IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, IBD, responds to nonsteroidal anti-inflammatory drugs (NSAIDs), family history of SpA, HLA-B27 positive, elevated C-reactive protein (CRP)
    • 82.9% sensitive, 84.4% specific for SpA

History

  • 3 mo of back pain with insidious onset
  • IBP: morning stiffness >30 min, improves with exercise but not with rest, alternating buttock pain, back pain at night

Physical Exam

Physical exam should include assessment of:

  • Entire spine: Range of motion, tenderness (although clinical spinal mobility measurements do not correlate with degree of inflammation or radiographic measure of spinal mobility):
    • Decreased cervical motion can be tested with occiput to wall test (distance between occiput to the wall when standing erect against a wall) and brow to chin angle (the degree of forward vertical angulation using a line drawn from the eyebrow to the chin compared to a vertical line perpendicular to the ground).
    • Increased thoracic kyphosis and decreased chest expansion (usually <2 cm)
    • Decreased lumbar motion can be determined by Schober test: Mark area on patient’s back at L5 and 10 cm above that point. Once patient bends forward, remeasure that distance. In normal persons, it should be >5 cm greater in flexion; <5 cm suggests loss of motion in lumbar spine.
  • Peripheral joints, especially in the lower extremity: limited range of motion, inflammatory signs such as effusion, warmth, tenderness
  • Major entheses: calcaneus for Achilles and plantar fascia attachments, patella, tibial tubercle
  • Eyes: inflammatory findings, may require slit-lamp exam
  • Skin: rash characteristic of psoriasis

Differential Diagnosis

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • No definitive serologic markers, although rheumatologic labs will be negative (antinuclear antibody [ANA], rheumatoid factor [RF], cyclic citrullinated peptide [CCP], etc.)
  • HLA-B27 with erythrocyte sedimentation rate (ESR) or CRP:
    • CRP and ESR can be elevated in 50–70% of patients with AS, but normal values do not negate presence of disease. Furthermore, normal or elevated levels in patients with established disease do not correlate with disease activity.
  • Plain radiograph of SI joints and lumbar spine:
    • Sacroiliitis is a hallmark of disease: graded 1 (suspicious), grade 2 (minimal), grade 3 (moderate), or grade 4 (ankylosis).
    • 20–30% of patients with the first 2 yr of developing IBP will have structural changes detectable by radiographs, confirming diagnosis.
    • In established AS, 95% of patients have detectable structural changes; however, structural changes may take several years or longer to become apparent radiographically.
    • Absence of radiographic findings in patients with IBP does not imply a lack of inflammation, nor does it negate the possibility of AS.

Follow-Up Tests & Special Considerations

  • Magnetic resonance imaging (MRI) (T2 and short-tau inversion recovery [STIR]):
    • Becoming more widely used due to the ability to identify early inflammatory changes before structural changes are apparent on plain radiographs
    • Not as sensitive as plain radiographs to assess degree of structural changes
  • Computed tomography (CT) scan:
    • Can detect chronic changes in SI joints, although role is limited due to high radiation exposure and the high sensitivity of the other imaging modalities

Treatment ⬆ ⬇

General Measures

  • A multidisciplinary approach of drug therapy along with exercises/physiotherapy helps decrease disease activity and progression while improving function.
  • Treatment is generally lifelong and divided into active versus stable disease.
  • Recent literature review performed by American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have provided the latest guidelines for treatment and are reviewed here.
  • Treatment same for AS and nr-axSpA

Medication

Depending on location and severity of disease, the following treatment modalities may be indicated:

  • NSAIDs
  • Tumor necrosis factor inhibitors (TNFi)
  • Disease-modifying antirheumatic drugs (DMARDs) have limited recommendations.
  • Interleukin inhibitors showing success in early trials
  • Corticosteroid injections
  • No role for systemic glucocorticoids

First Line

  • NSAIDs (4)[A]:
    • No one NSAID recommended over another diclofenac, naproxen, celecoxib, and others
    • Use full dose and regular scheduling to maximize symptom relief for active disease but can use as needed for stable disease.
    • Beneficial for both axial (spine) and peripheral (joint, enthesis) involvement
    • Data suggest that long-term therapy may have disease-controlling properties evidenced by suppression of radiographic progression.
    • Trial of two separate NSAIDs for 1 to 2 mo each prior to moving onto second-line therapy
    • Must monitor for gastrointestinal (GI), cardiovascular, renal, and hepatic side effects with ongoing NSAID use.

Second Line

  • TNFi (4)[A]:
    • Infliximab, adalimumab, and etanercept
    • No clear recommendation for one TNFi versus another; infliximab and adalimumab considered for recurrent iritis or concomitant IBD
    • Try two separate TNFi before moving onto DMARD if no clinical response.
    • With extended therapy, up to 1/3 of patients may develop remission.
    • TNFi increases risk for infection; should screen for tuberculosis, HIV, and hepatitis before initiating. Ensure vaccinations are up to date; do not give live vaccines while on therapy.
  • DMARDs (4)[A]:
    • Considered if failure to NSAID and TNFi contraindicated; use over non-TNFi biologics.
    • Limited role for sulfasalazine; some benefit with peripheral disease only.
    • High-dose pamidronate may be beneficial but needs further studies.
    • No role for methotrexate
  • Interleukin-17A inhibitor (5)[B]:
    • Secukinumab has shown significant reduction in signs/symptoms of disease.
    • Considered if contraindications or failure of NSAIDs and/or TNFi

Issues for Referral

  • Early rheumatology referral for patients with IBP may help prevent a delay in diagnosis and can help with initiating biologics.
  • Refer to ophthalmology if signs/symptoms of iritis, which may consider prescription of topical steroids to use PRN for flares.

Additional Therapies

  • Physiotherapy/physical therapy helps improve spinal mobility and overall function (6)[A].
  • Supervised training and home exercises improve long-term functional outcomes when compared to no intervention or educational/behavioral intervention.

Surgery/Other Procedures

  • Local corticosteroid injections: for isolated sacroiliitis or peripheral joint disease if more than three joints involved
  • Hip arthroplasty as indicated for progressive arthropathy
  • Thoracolumbar osteotomy can be considered for severe kyphotic disease, or cervicothoracic osteotomy for chin to chest deformity to restore horizontal gaze, but should be performed at specialized spine centers.

Ongoing Care ⬆ ⬇

Follow-up Recommendations

Patient Monitoring

  • Can continue to monitor response to treatment using validated AS disease activity measures (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI], or Ankylosing Spondylitis Disease Activity Score [ASDAS]) and regular interval CRP (5)[A]
  • The BASDAI is a valid and appropriate composite to defining disease activity during treatment:
    • Five major symptoms (fatigue, spinal pain, joint pain/swelling, areas of tenderness, and duration/severity of morning stiffness) are individually rated on 0 to 10 scale and the sum of each score is divided by 5 to obtain final score.
    • A score >4 suggest suboptimal disease control and is a candidate for change in therapy.
  • The BASFI is a set of 10 questions used to assess and follow functional limitations.

Prognosis

  • The key to good outcomes and prevention of disease progression and severe complications is early recognition and initiation of treatment.
  • AS has an unpredictable clinical course independent of age of onset or sex.
  • Most patients have a fluctuating course with flares and periods of relative remission.

Complications

  • Fusion of vertebrae leading to loss of function or restrictive lung disease
  • Aortitis or aortic insufficiency, rare
  • Hip arthritis with refractory pain or disability requiring arthroplasty

Additional Reading ⬆ ⬇

  • Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369(9570):1379–1390.
  • Sieper J, Rudwaleit M, Khan MA, et al. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol. 2006;20(3):401–417.

References ⬆ ⬇

  1. Wang R, Ward M. Epidemiology of axial spondyloarthritis: an update. Curr Opin Rheumatol. 2018;30(2):137–143.
  2. De Winter JJ, van Mens LJ, van der Heijde D, et al. Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis. Arthritis Res Ther. 2016;18(1):196.
  3. Sieper J, van der Heijde DM, Landewé RB, et al. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise of the Assessment in SpondyloArthritis International Society (ASAS). Ann Rheum Dis. 2009;68(6):784–788.
  4. 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. 2016;68(2):282–298.
  5. Braun J, Baraliakos X, Deodhar A, et al. Effect of secukinumab on clinical radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheumatic Dis. 2017;76(6):1070–1077.
  6. Dagfinrud H, Kvien TK, Hagen KB. Physiotherapy interventions for ankylosing spondylitis. Cochrane Database Syst Rev. 2008;(1):CD002822.

Clinical Pearls ⬆

  • Diagnosing AS can be difficult because there is no clear diagnostic criteria, yet a delay in diagnosis can lead to unnecessary disease progression and irreversible changes.
  • Identifying the features of IBP is key to the diagnosis of AS.
  • Plain radiographs are typically diagnostic, but MRI can show early evidence of disease/inflammation when radiographs are normal.
  • Treatment is multimodal and typically includes both drug therapy with NSAIDs ± TNFi along with physical therapy/physiotherapy.