Ankylosing spondylitis

Ankylosing spondylitis (axial spondyloarthritis), a type of seronegative spondyloarthropathy, is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell's sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease. The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumor necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life.

• Sex: ♂ > ♀ (3:1)
• Age: 15–40 years
• Lifetime prevalence in the US: ∼0.5%

Epidemiological data refers to the US, unless otherwise specified.

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

Articular symptoms

• Most common presenting symptoms: back and neck pain
  • Gradual onset of dull pain that progresses slowly
  • Morning stiffness that improves with activity
  • Pain is independent of positioning; , also appears at night
  • Tenderness over the sacroiliac joints
• Limited mobility of the spine (especially reduced forward lumbar flexion)
• Inflammatory enthesitis (e.g., of the Achilles tendon, iliac crests, tibial tuberosities): painful on palpation
• Dactylitis
• Arthritis outside the spine (hip, shoulder, knee joint)

Extra-articular manifestations

• Most common: acute, unilateral anterior uveitis (∼ 25% of cases)
• Fatigue , weakness, fever, weight loss
• Restrictive pulmonary disease due to decreased mobility of the spine and thorax
• Gastrointestinal symptoms: associated with chronic inflammatory bowel disease (∼ 5–10% of cases, see also: ulcerative colitis or Crohn disease)
• Prostatitis
• Rare
  • Cardiac: aortic root inflammation and subsequent aortic valve insufficiency, atrioventricular blocks
  • Kidney: IgA-nephropathy

Diagnostic approach

1. Physical examination, patient history, and pelvic x-ray: If results are conclusive, no additional testing is required!
2. If inconclusive → HLA-B27 testing
3. If still inconclusive → pelvic MRI

Clinical tests

• Chest expansion measurement: to monitor disease severity
  • Method: measure chest circumference in full expiration and inspiration
    • Pathological difference: < 2 cm
    • Physiological difference: > 5 cm
• Spine mobility tests
  • Schober test : Mark two points, S1 and another point 10 cm above → patient touches toes (without bending the knees) → distance between the two points increases by ≥ 4 cm → physiological test result; a smaller increase in distance between these two points is pathological
• Examination of the hip ^[1]
  • Mennell sign: tenderness to percussion and pain on displacement of the sacroiliac joints
  • FABER test: FABER (Flexion, ABduction, and External Rotation) provokes pain in the ipsilateral hip

The degree of decrease in chest expansion is an important determinant of disease severity.

Laboratory findings

• ↑ CRP and ESR
• Auto-antibodies (e.g., rheumatoid factor, antinuclear antibodies) are negative
• HLA-B27 positive in 90–95% of cases
  • However, < 5% of HLA-B27 positive individuals have ankylosing spondylitis.

Imaging

X-ray

• Helps confirm a diagnosis and evaluate the severity of disease
• Changes are generally more evident in later disease.
• The changes usually occur symmetrically.
• Pelvis (best initial test): to examine the sacroiliac joints
  • Signs of sacroiliitis, including ankylosis (fusion of the articular surfaces)
• Spine
  • Loss of lordosis with increasing abnormal straightening of the spine
  • Sclerosis of the vertebral ligamentous apparatus
  • Syndesmophytes resulting in a so-called 'bamboo spine' in anteroposterior radiograph in the later stages (see the table in “Differential diagnosis” below)
  • Signs of spondyloarthritis, including ankylosis of intervertebral joints ^[2]
• Thorax: ankylosis of costosternal and costovertebral joints

Mild courses may only exhibit inflammatory changes in the sacroiliac joints on x-ray after a number of years.

MRI

• More sensitive than CT scan for detecting sacroiliitis ^[3]
• Best method for early detection

References:^[4][5][6]

• Mechanical low back pain
• Fibromyalgia
• Disc prolapse
• Vertebral osteomyelitis
• Other spondyloarthritides (e.g., reactive arthritis, psoriasis arthritis, arthritis associated with inflammatory bowel disease)
• Diffuse idiopathic skeletal hyperostosis (DISH; also called Forestier's disease or hyperostotic spondylosis)
  • Definition: degenerative disease of the vertebral column (especially the thoracic and lumbar spine), which is characterized by calcification and ossification of spinal ligaments and entheses
  • Epidemiology
    • Not related to HLA-B27 ^[7]
    • Mostly affects men
    • Common in patients with diabetes
  • Clinical presentation
    • Limited mobility
    • Mild or even no pain at all
  • Diagnosis
    • X-ray of the spine
      • Formation of osteophytes (see table below)
      • No sacroiliitis
  • Treatment: symptomatic
• Osteophytes of the spine ^[8][9]

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

The differential diagnoses listed here are not exhaustive.

• Physical therapy
  • Consistent and rigorous physical therapy
  • Independent exercises
• Medical therapy
  • First choice: NSAIDs (e.g., indomethacin)
  • Additional options
    • Tumor necrosis factor-α inhibitors (e.g., etanercept, adalimumab) ^[10]
    • In case of peripheral arthritis: DMARDs (especially sulfasalazine)
    • In severe cases: temporary, intra-articular glucocorticoids
• Surgery: in severe cases to improve quality of life
  • Indications
    • Severe deformity of the spinal column
    • Instability of the spine
    • Neurologic deficits
  • Procedures
    • Osteotomy
    • Joint replacement
    • Spinal fusion

Physical therapy is the most important treatment modality!References:^[4][11]

• Complete fusion of the spine → severely limited mobility
• Increased risk of osteoporosis → pathological fractures and possibly spinal cord injury
• Restricted chest expansion and spine mobility → breathing difficulties
• Lungs: fibrosis of upper lobes (apical fibrosis) ^[12]

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

1. Stone JH. A Clinician's Pearls & Myths in Rheumatology. Springer ; 2009
2. Ankylosing spondylitis. https://radiopaedia.org/articles/ankylosing-spondylitis. Updated: April 12, 2017. Accessed: April 12, 2017.
3. Blum U, Buitrago-tellez C, Mundinger A, et al. Magnetic resonance imaging (MRI) for detection of active sacroiliitis: a prospective study comparing conventional radiography, scintigraphy, and contrast enhanced MRI. J Rheumatol. 1996; 23 (12): p.2107-2115.
4. Brent LH. Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy. Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy. New York, NY: WebMD. http://emedicine.medscape.com/article/332945. Updated: January 20, 2016. Accessed: April 11, 2017.
5. Yu DT, van Tubergen A. Diagnosis and differential diagnosis of ankylosing spondylitis and non-radiographic axial spondyloarthritis in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-ankylosing-spondylitis-and-non-radiographic-axial-spondyloarthritis-in-adults.Last updated: October 19, 2016. Accessed: April 12, 2017.
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7. 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.
8. Hutcheson CJ, Howe JW. The Low Back and Pelvis: Clinical Applications. Aspen Publications ; 1996
9. 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
10. Maxwell LJ, Zochling J, Boonen A, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015 . doi: 10.1002/14651858.CD005468.pub2 . | Open in Read by QxMD
11. Yu DT. Assessment and treatment of ankylosing spondylitis in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/assessment-and-treatment-of-ankylosing-spondylitis-in-adults.Last updated: April 21, 2016. Accessed: April 11, 2017.
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13. 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
14. 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
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16. 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
17. 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
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