Ankylosing Spondylitis

Ankylosing spondylitis (also known as Bechterew’s disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing spondylitis is most often seen in young men and is strongly associated with HLA-B27. Patients will have progressive back pain (which improves with activity), morning stiffness, and decreased range of motion of the spine. Extra-articular manifestations include fatigue, enthesitis, anterior uveitis, restrictive lung disease, and inflammatory bowel disease. The diagnosis is based on the clinical history, physical exam, and imaging demonstrating sacroiliitis and bridging syndesmophytes. Most patients are managed with physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). More severe cases may require tumor necrosis factor-alpha inhibitors or surgery.

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Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton.


To remember the seronegative arthropathies, use the mnemonic “PAIR.” 

  • Psoriatic arthritis 
  • Ankylosing spondylitis
  • Inflammatory bowel disease–associated arthritis
  • Reactive arthritis


  • Incidence: 0.4–14 per 100,000 people per year
  • Highest prevalence in northern European countries
  • Age at onset: 20–30 years
  • 3 times more common in men
  • 10–20 times more common in 1st-degree relatives of those with ankylosing spondylitits


  • Exact cause unknown
  • Strong association with HLA-B27
  • Possible triggers:
    • Klebsiella infection
    • Trauma


Process of ankylosis

Pathogenesis of ankylosing spondylitis:
Inflammation induces the formation of syndesmophytes and the fusion of the intervertebral discs and vertebral bodies.

Image by Lecturio.
Ankylosing spondylitis

Pathogenesis of ankylosing spondylitis:
Erosion of the iliac side of sacroiliac joints is the earliest radiologic sign of ankylosing spondylitis.

Image by Lecturio.

Proposed mechanism of inflammation

  • Innate immunity is triggered: 
    • Possibly from GI microbes invading the systemic circulation
    • Due to disruption of the gut mucosal barrier
  • Cytokines and interleukins (ILs) are released: 
    • IL-17 and IL-23 
    • Tumor necrosis factor alpha (TNF-alpha)
    • Transforming growth factor beta (TGF-beta)
  • Development of enthesitis (inflammation at the site of ligament or tendon insertion into bone):
    • Micro-injury from mechanical stress may make entheses susceptible to inflammation.
    • Joints are infiltrated with macrophages and with CD4 and CD8 T cells.
    • Main joints involved:
      • Sacroiliac (SI) joints
      • Paravertebral joints

Axioskeletal changes

  • Chronic inflammation of the ligaments and the annulus fibrosus of the intervertebral disc → erosion of bone and destruction of articular tissues
  • Erosion → fibrocartilage regeneration → fibrosis and ossification → syndesmophyte formation
  • Syndesmophytes bridge together → vertebral fusion

Clinical Presentation

Articular manifestations

  • Pain: 
    • Lower back and neck
    • Progressive
    • Often nocturnal
    • Varies in intensity
    • Present for > 3 months
  • Paraspinal muscle spasm
  • Morning stiffness:
    • Improves with activity or exercise 
    • Worsened by inactivity
  • Diminished range of motion of the spine
  • Oligoarthritis (50% of patients):
    • Asymmetrical involvement of ≤ 4 peripheral joints
    • Pain, warmth, swelling, and stiffness

Extra-articular manifestations

  • General:
    • Fatigue
    • Weakness
    • Low-grade fever
    • Anorexia
    • Weight loss
  • Periarticular:
    • Enthesitis
      • Plantar fasciitis
      • Costochondral junctions
    • Tendinitis
      • Achilles
      • Patellar
    • Dactylitis (sausage fingers)
  • Ocular:
    • Anterior uveitis
    • Conjunctivitis
  • Cardiac:
    • Aortitis
    • Aortic valve insufficiency
    • Conduction abnormalities 
      • Due to fibrosis of the conduction system
      • Varying degrees of atrioventricular block may result.
    • Pericarditis
  • Pulmonary
    • Restrictive lung disease
    • Nontuberculous apical fibrosis
      • Can result in cavitation
      • Secondary bacterial or fungal (Aspergillus) infections
  • Cutaneous:
    • Psoriasis
    • Painless oral ulcerations
  • GI:
    • Asymptomatic ileal and colonic inflammation
    • Inflammatory bowel disease
  • Renal:
    • Immunoglobulin A (IgA) nephropathy
    • Renal amyloidosis
  • Genitourinary: prostatitis
  • Neurologic:
    • Radiculitis
    • Cauda equina syndrome

Physical examination

  • Spine:
    • Cervical and upper thoracic vertebrae:
      • Accentuated thoracic kyphosis
      • Stooped, forward-flexed position (when fused)
      • Distance between chin and sternum with flexed head > 2 cm
    • Lumbar vertebrae:
      • Reduced range of motion (Schober’s test)
      • Loss of lumbar lordosis 
  • Sacroiliac joint:
    • Localized tenderness
    • Mennell’s sign
    • FABER (Flexion, Abduction, and External Rotation) test
  • Tenderness at the following points:
    • Achilles tendon insertion
    • Insertion of the plantar fascia on the calcaneus or the metatarsal heads
    • Base of the 5th metatarsal head
    • Tibial tuberosity
    • Superior and inferior poles of the patella
    • Iliac crest
  • Reduced chest expansion (< 4 cm) on deep inspiration
Preoperative imaging findings of a 47-year-old female patient with ankylosing spondylitis

Stooped, forward-flexed position in a patient with ankylosing spondylitis

Image: “Preoperative imaging” by Hongqi Zhang et al. License: CC BY 4.0, cropped by Lecturio.


Physical examination tests

  • Schober’s test:
    • Tests limitation of lumbar movement 
    • Procedure:
      • Place a mark 5 cm below and 10 cm above the L5 spinous process. 
      • Have the patient touch the toes.
      • If distance does not increase by > 5 cm, the patient has reduced lumbar flexion.
  • FABER test:
    • Also known as Patrick’s test
    • Nonspecific test that detects joint dysfunction in the sacroiliac joint 
    • Procedure:
      • The patient’s leg is flexed at the hip, abducted, and placed in a figure-4 position.
      • Force is applied to the ipsilateral knee.
      • Test is deemed positive if it reproduces pain in the ipsilateral sacroiliac joint.
  • Mennell’s sign: 
    • Helps determine whether pain is coming from the hip, lumbar spine, or sacroiliac joint
    • Procedure:
      • Performed with the patient facedown
      • Passive hyperextension of the upper leg 
      • This procedure provokes pain in the sacroiliac joint, hip, or lumbar spine depending on where the physician fixates (places the hand) on the spine or hip.
  • Chin–brow vertical angle (CBVA)
    • An assessment for kyphotic deformity 
    • Procedure:
      • Measures the angle between a vertical line and a line connecting the brow to the chin while the patient is standing
      • Any degree greater than zero is abnormal.


  • Radiography:
    • Diagnostic and assesses severity of the disease
    • Should be performed in all patients in whom AS is suspected
    • Bilateral sacroiliitis:
      • Subchondral erosions (“pseudo-widening” of the SI joint)
      • Subchondral sclerosis
      • SI joint narrowing
      • Fusion of the SI joint (end-stage)
    • Spine findings: 
      • Small erosions with reactive sclerosis
      • Squaring of vertebrae
      • Ligament calcifications
      • Evolving syndesmophytes
      • Bridging syndesmophytes (“bamboo spine”)
  • MRI: 
    • Aids in early detection
    • May reveal inflammatory changes not seen on radiographs

Laboratory Tests

  • Nonspecific
  • ↑ CRP 
  • ↑ Erythrocyte sedimentation rate (ESR)
  • Mildly ↑ alkaline phosphatase
  • Negative rheumatoid factor (RF)
  • Negative ANA test
  • Genetic testing for HLA-B27: 
    • May be considered if clinical evaluation and radiography are inconclusive
    • Positive in approximately 90% of Caucasian patients with AS
    • Not required for diagnosis

Management and Complications

Management requires a multidisciplinary approach to reduce pain, increase range of motion, decrease inflammation, and improve quality of life.

Conservative measures

  • Lifestyle changes:
    • Urge smoking cessation.
    • Encourage regular physical activity.
  • Physical therapy:
    • Crucial for maintaining mobility
    • Exercises for: 
      • Mobilization of the vertebral joints and muscle stability 
      • Maintenance of adequate posture and range of motion
  • Depression and anxiety screening
  • Psychosocial support

Medical management

  • Initial therapy: 
    • Nonsteroidal anti-inflammatory drugs (NSAIDs)
    • 70% of patients achieve clinical improvement.
  • 2nd line: 
    • TNF inihibitors 
      • Etanercept, adalimumab, golimumab, infliximab
      • Used in patients in whom NSAID therapy fails
    • IL-17 inhibitors
      • Secukinumab or ixekizumab
      • Alternative to TNF inhibitors
    • Disease-modifying antirheumatic drugs (DMARDs)
      • Sulfasalazine or methotrexate
      • Used for persistent peripheral arthritis

Surgical interventions

  • Indications:
    • Severe deformities resulting in functional impairment
    • Severe pain causing diminished quality of life
    • Acute fracture
    • Neurologic deficits
  • Options:
    • Spinal fusion
    • Osteotomy
    • Total hip arthroplasty


  • In addition to the manifestations of this disease, patients may develop:
    • Osteoporosis
      • Most frequent complication
      • Predisposes patients to fractures
    • Vertebral fracture
      • Most serious complication
      • Cervical spine fractures can lead to paralysis or death.
    • Respiratory compromise
  • Adverse effects on the patient’s quality of life:
    • Sleep disturbances
    • Disability
    • Diminished psychologic health (depression)


  • Ankylosing spondylitis is a chronic disease.
  • Most patients retain complete functionality.
  • Indicators of a poor prognosis:
    • Younger age at onset
    • Peripheral arthritis
    • ↑ Inflammatory markers
    • Poor response to NSAIDs
  • Severe and long-standing AS is associated with ↑ risk of mortality.

Differential Diagnosis

  • Lumbar spinal stenosis: narrowing of the lumbar spinal canal resulting in compression of nerve rootlets. This condition is more common in older patients. Patients may experience chronic back, buttock, and thigh pain that is relieved by flexing the back. Neurologic signs and symptoms, including paresthesias, weakness, and diminished reflexes, are also prominent. The diagnosis is based on clinical evaluation and MRI. Management includes physical therapy, analgesics, and surgery for severe cases.
  • Psoriatic arthritis: a seronegative spondyloarthropathy that occurs in patients with psoriasis. This asymmetric, inflammatory arthritis involves small and large joints, including the distal interphalangeal joints and the sacroiliac spine. Enthesopathy and dactylitis are also seen. The diagnosis is clinical, and the condition should be suspected in patients with psoriasis. Management includes DMARDs and biologic agents.
  • Reactive arthritis: a seronegative spondyloarthropathy that is often precipitated by a GI or genitourinary infection. Patients may present with asymmetric arthritis, typically of the lower extremities. This arthritis can be associated with fever, tendinitis, enthesitis, mucocutaneous ulcers, and conjunctivitis. The diagnosis is clinical. Treatment includes NSAIDs, DMARDs, and treatment of the underlying infection.
  • Rheumatoid arthritis (RA): a seropositive autoimmune disease resulting in joint inflammation and destruction. This arthritis is typically symmetric, and patients will frequently have tender inflammation in the joints of the hands and feet (although any peripheral joints can be involved). The axial skeleton is less commonly included. The diagnosis is made with the presence of positive RF and anti–cyclic citrullinated peptide (anti-CCP) laboratory studies. Management includes NSAIDs, DMARDs, corticosteroids, immunosuppressive medications, biologics, and TNF inhibitors. 
  • Fibromyalgia: a nonarticular disorder of unknown etiology that causes generalized pain, including the muscles, points of tendon insertion (which can mimic enthesitis), and soft tissues. Associated symptoms include fatigue, muscle stiffness, cognitive disturbances, depression, and anxiety. The diagnosis is based on clinical criteria. Imaging and laboratory testing will be unrevealing. Management includes exercise, nonopioid analgesics, and efforts to improve sleep and stress.
  • Diffuse idiopathic skeletal hyperostosis: a noninflammatory disease causing ossification of spinal ligaments and entheses. Patients may be asymptomatic or may have progressive back and neck pain with reduced range of motion (particularly of the thoracic spine). The diagnosis is made with imaging, which may show the changes of AS. However, the SI joints are usually spared, and there may be extra-axial joint involvement. Management involves analgesics and physical therapy for pain relief.


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