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Ankylosing Spondylitis
Damon F. Lee, MD
image BASICS
DESCRIPTION
  • Ankylosing spondylitis (AS) is an axial inflammatory spondyloarthropathy (axSpA) characterized by radiologic evidence of sacroiliitis.
  • System(s) affected: musculoskeletal; eyes; cardiac; neurologic; pulmonary
  • Synonym(s): Marie-Strümpell disease; “bamboo spine”
EPIDEMIOLOGY
  • Onset usually in early 20s; rarely occurs after age 40
  • Male > female (approximately 2 to 3:1)
Incidence
Age- and gender-adjusted rate of 6.3 to 7.3/100,000 person-years
Prevalence
˜0.55% for AS and ˜1.4% for all axSpA in the United States (1)
ETIOLOGY AND PATHOPHYSIOLOGY
  • Autoinflammation at sites of bacterial exposure (e.g., intestines) or mechanical stress in genetically susceptible individuals (2)
  • Inflammation at the insertion of tendons, ligaments, and fasciae to bone (enthesopathy) causes erosion, remodeling, and new bone formation
  • Inflammation-independent pathways of bony changes have also been hypothesized (2).
Genetics
  • 80-90% of patients with AS are HLA-B27-positive.
  • Other genetic associations include endoplasmic reticulum aminopeptidase 1 (ERAP1), interleukin 23 receptor (IL23R), and gene deserts on chromosome 2p15 and 21q22 (2).
RISK FACTORS
  • HLA-B27
    • 1-8% of HLA-B27-positive adults have AS.
  • Positive family history
    • HLA-B27-positive child of a parent with AS has a 10-30% risk of developing the disease.
COMMONLY ASSOCIATED CONDITIONS
  • Uveitis/iritis (up to 40%)
  • Enthesopathy: Achilles tendonitis, plantar fasciitis
  • Dactylitis (sausage digit) from oligoarthritis
  • Peripheral spondyloarthritis (SpA): psoriatic arthritis, reactive arthritis, inflammatory bowel disease (IBD)-related arthritis, juvenile idiopathic arthritis
  • Aortitis and cardiac conduction defects
image DIAGNOSIS
PHYSICAL EXAM
  • Sacroiliac joint tenderness, loss of lumbar lordosis, and cervical spine rotation
  • Diminished range of motion in the lumbar spine in all three planes of motion
  • Modified Wright-Schober test for lumbar spine flexion:
    • Mark patient's back over the L5 spinous process (or at dimples of Venus) and measure 10 cm above and 5 cm below this point. Normal is at least 5 cm of expansion between these two marks on maximal forward flexion.
  • Thoracocervical kyphosis (usually after at least 10 years of symptoms)
  • Occiput-wall distance increased (distance between occiput and wall when standing with back flat against a vertical surface; zero is normal)
  • Respiratory excursion of chest wall
    • Normal is >5 cm of maximal respiratory excursion of chest wall measured at 4th intercostal space; <2.5 cm is consistent with AS.
  • Tenderness of insertional sites—Achilles, plantar fascia
  • Peripheral oligoarthritis/dactylitis seen mostly with peripheral SpA
  • Cauda equina syndrome rarely occurs in late disease.
  • Extra-articular manifestations: uveitis, psoriasis, IBD
  • Aortic regurgitation murmur (1%)
DIFFERENTIAL DIAGNOSIS
  • Nonradiographic axSpA (features AS without x-ray evidence of sacroiliitis; MRI detects changes earlier than plain films); other SpA
  • Osteoarthritis of the axial spine
  • Diffuse idiopathic skeletal hyperostosis (DISH)
  • Osteitis condensans ilii: benign sclerotic changes in the iliac portion of the SI joint after pregnancy
  • Infectious arthritis or discitis, unilateral sacroiliitis: tuberculosis, brucellosis, bacterial infection (particularly in IV drug users)
DIAGNOSTIC TESTS & INTERPRETATION
  • Up to 10% of Caucasian population and 4% of African American population are HLA-B27-positive. Genetic testing is not necessary as part of initial evaluation, particularly with a consistent history and exam.
  • ESR and C-reactive protein (CRP) may be mildly elevated or normal; if high, correlates with disease activity and prognosis.
  • Absence of rheumatoid factor
  • Mild normochromic anemia (15%)
  • Synovial fluid: mild leukocytosis
  • SI joints: Oblique projection is preferred.
    • X-ray changes may not be apparent for up to 10 years after disease onset. MRI is more sensitive; increased signal from the bone and bone marrow suggests osteitis and edema.
    • Sequential radiographic changes over time: widening of SI joint, erosions, sclerosis on both sides of joint not extending >1 cm from articular surface, and (lastly) ankyloses.
  • Spine
    • Early plain radiograph changes: “shiny corners” due to osteitis and sclerosis at site of annulus fibrosus attachments to the corners of vertebral bodies with “squaring” due to erosion and remodeling of vertebral body; contrast-enhanced MRI is more sensitive for detecting early changes.
    • Late changes: ossification of annulus fibrosis resulting in bony bridging between vertebral bodies (syndesmophytes) giving classic “bamboo spine” appearance; ankylosis of apophyseal joints, ossification of spinal ligaments, and/or spondylo-discitis also occurs.
  • Peripheral joints
    • Asymmetric pericapsular ossification, sclerosis, loss of joint space, and erosions may occur.
Diagnostic Procedures/Other
  • ECG: conduction defects
  • Echocardiogram: aortic valvular abnormalities
  • Dual energy x-ray absorptiometry scan may reveal osteopenia/osteoporosis.
Test Interpretation
  • Erosive changes and new bone formation at bony attachment of the tendons and ligaments result in ossification of periarticular soft tissues.
  • Synovial hypertrophy and pannus formation, mononuclear cell infiltrate into subsynovium and subchondral bone marrow inflammation in the SI joint with erosions, followed by granulation tissue formation, and finally obliteration of joint space by fusion of joint and sclerosis of para-articular bone
image TREATMENT
GENERAL MEASURES
  • Aggressive physical therapy is the most important nonpharmacologic management.
  • Posture training and spinal range-of-motion exercises are essential.
  • Firm bed; sleep in supine position without a pillow
  • Breathing exercises 2 to 3 times per day
  • Smoking cessation
MEDICATION
First Line
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are first line for pain and stiffness in AS (3)[C].
  • NSAIDs provide rapid and dramatic symptomatic relief, which may be diagnostic. No single NSAID preferred. Higher doses tend to be more efficacious.
  • Continuous NSAID therapy may slow radiographic disease progression but may not be superior to intermittent therapy for symptom control (4)[A].
  • Precautions
    • Consider CVD, GI, and renal risks of NSAIDs.
    • Consider GI prophylaxis (PPIs or misoprostol) while on NSAIDs in patients with hx of PUD, gastritis, or age >60 years
    • Use NSAIDS with caution in patients with a bleeding diathesis or patients receiving anticoagulants.
  • Injection of intra-articular corticosteroids into SI joints and prostheses can provide transient relief, but systemic corticosteroids are usually ineffective.
P.59

Pregnancy Considerations
Infants exposed to NSAIDs in 1st trimester may have a higher incidence of cardiac malformations (5)[A].
Second Line
  • Biologic agents: tumor necrosis factor (TNF)-α antagonists
    • Recommended for high disease activity or when a trial of two NSAIDs over 4 weeks have failed (3)[C]
    • FDA-approved agents for AS include etanercept (recombinant TNF receptor fusion protein), infliximab (chimeric monoclonal IgG1 antibody to TNF-α), adalimumab (fully humanized IgG1 monoclonal antibody to TNF-α), and golimumab (human IgG1 kappa monoclonal antibody to TNF-α).
    • Approved agents improve pain, function, and symptoms of AS as compared to placebo (6)[A].
    • No definitive evidence for TNF-α blockers with regards to disease remission, prevention of radiologic progression, or prevention of extra-articular manifestations (7).
    • Monoclonal TNF-α blockers are preferred when IBD is involved (3)[C].
    • Further investigation as to the effectiveness of TNF blocker therapy with NSAIDs is needed (8).
  • Precautions with TNF-α blockers
    • Anti-TNFs increase the risk of serious bacterial, mycobacterial, fungal, opportunistic, and viral infections. Screen for tuberculosis and hepatitis B.
    • Monitor for reactivation of tuberculosis and invasive fungal infections, such as histoplasmosis, in all patients, especially those who travel to (or residents in) endemic areas.
    • Lymphomas, nonmelanoma skin cancers, and other malignancies have been reported in patients receiving anti-TNFs.
    • Immunizations (especially live vaccines) should be updated before initiating anti-TNFs; live vaccines are contraindicated once patients receive anti-TNFs.
  • Disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and sulfasalazine, are ineffective for axial disease; sulfasalazine may be effective for peripheral arthritis (3)[C].
ISSUES FOR REFERRAL
  • Physical therapy can assist with treatment plan (including home regimens).
  • Coordinate care with a rheumatologist for diagnosis, monitoring, and management (anti-TNF therapy).
  • Management of aortic regurgitation, uveitis, spinal fractures, pulmonary fibrosis, hip joint involvement, renal amyloidosis, and cauda equina syndrome may require referral to appropriate specialty.
ADDITIONAL THERAPIES
  • Bisphosphonate medications if osteopenia or osteoporosis is present
  • Monitoring and management of CVD risk factors and comorbidities
SURGERY/OTHER PROCEDURES
  • Evaluate for C-spine ankylosis/instability before intubation in patients with AS undergoing surgery.
  • Total hip replacement if necessary to restore mobility and to control pain.
  • Vertebral osteotomy can improve posture for patients with severe cervical or thoracolumbar flexion.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Symptom control and maintenance of mobility and function are primary treatment goals.
  • Monitor posture and range of motion with 6- to 12-month visits; increase frequency if higher disease activity.
  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or Ankylosing Spondylitis Disease Activity Score (ASDAS) can be used to measure disease activity.
PATIENT EDUCATION
  • Maintain physical activity and posture.
  • Swimming, tai chi, and walking are excellent activities.
  • Avoid trauma/contact sports.
  • Appropriate ergonomic modification of workplace
  • Counsel about risk of spinal fracture.
  • MedicAlert bracelet (helpful if intubation required)
  • Arthritis Foundation: http://www.arthritis.org
  • Spondylitis Association of America: http://www.spondylitis.org
PROGNOSIS
  • Extent and rapidity of progression of ankylosis are highly variable.
  • Progressive limitation of spinal mobility necessitates lifestyle modification.
REFERENCES
1. Reveille JD, Weisman MH. The epidemiology of back pain, axial spondyloarthritis and HLA-B27 in the United States. Am J Med Sci. 2013;345(6):431-436.
2. Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011;377(9783):2127-2137.
3. Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896-904.
4. Guellec D, Nocturne G, Tatar Z, et al. Should non-steroidal anti-inflammatory drugs be used continuously in ankylosing spondylitis? Joint Bone Spine. 2014;81(4):308-312.
5. Adams K, Bombardier C, van der Heijde DM. Safety of pain therapy during pregnancy and lactation in patients with inflammatory arthritis: a systematic literature review. J Rheumatol Suppl. 2012;90:59-61.
6. Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database of Syst Rev. 2015;(4):CD005468. doi:10.1002/14651858.CD005468.pub2.
7. Gensler L, Inman R, Deodhar A. The “knowns” and “unknowns” of biologic therapy in ankylosing spondylitis. Am J Med Sci. 2012;343(5):360-363.
8. Sieper J. Treatment challenges in axial spondyloarthritis and future directions. Curr Rheumatol Rep. 2013;15(9):356. doi:10.1007/s11926-013-0356-9.
Additional Reading
  • Baraliakos X, van den Berg R, Braun J, et al. Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis. Rheumatology (Oxford). 2012;51(8):1378-1387.
  • Garg N, van den Bosch F, Deodhar A. The concept of spondyloarthritis: where are we now? Best Pract Res Clin Rheumatol. 2014;28(5):663-672.
  • Sieper J. Developments in therapies for spondyloarthritis. Nat Rev Rheumatol. 2012;8(5):280-287.
  • 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): ii1-ii44.
  • van den Berg R, Baraliakos X, Braun J, et al. First update of the current evidence for the management of ankylosing spondylitis with non-pharmacological treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Rheumatology (Oxford). 2012;51(8):1388-1396.
See Also
Arthritis, Psoriatic; Arthritis, Rheumatoid (RA); Crohn Disease; Reactive Arthritis (Reiter Syndrome); Ulcerative Colitis
Codes
ICD10
  • M45.9 Ankylosing spondylitis of unspecified sites in spine
  • M08.1 Juvenile ankylosing spondylitis
  • M45.8 Ankylosing spondylitis sacral and sacrococcygeal region
Clinical Pearls
  • Diagnosis of AS is suggested by a history of inflammatory back pain, evidence of limited chest wall expansion, restricted spinal movements in all planes, radiographic evidence of sacroiliitis, and a therapeutic response to NSAIDs.
  • HLA-B27 testing supports the diagnosis if clinical features are not definitive.
  • MRI is more sensitive at detecting SI joint inflammation than plain radiography.
  • Physical therapy is important in helping to maintain posture and mobility.
  • NSAIDs and TNF-α blockers are the mainstays of pharmacologic treatment of AS.