ankylosing spondylitis, axial spondyloarthritis; Marie Strumpell disease; Bechterew's disease (AS)

Etiology

• unknown
• strongly associated with inflammatory bowel disease
• some evidence suggests autoimmune etiology

Epidemiology

• generally begins in 2nd or 3rd decade of life
• onset after age 40 is unusual
• male:female ratio 3:1
• more common in white than black adults
• affects 0.2% of white adults

Pathology

• chronic inflammatory disorder primarily affecting the axial skeleton
• sacroiliitis
  • subchondral granulation tissue containing lymphocytes, plasma cells, mast cells, macrophages & chondrocytes
  • the thinner iliac cartilage is eroded before the thicker sacral cartilage
  • fibrocartilage regeneration followed by ossification
  • complete obliteration of the joint may result
• spine
  • inflammatory granulation tissue at the junction of the annulus fibrosis of the disk cartilage & the vertebral bone
  • erosion of the annulus fibrosis & replacement by bone (syndesmophyte) which grows by endochondral ossification eventually bridging adjacent vertebrae
    • calcification of longitudinal ligament of spine
  • diffuse osteoporosis
  • inflammatory arthritis of apophyseal joints
• arthritis begins at the sacroiliac joint & lower spine & progresses cranially, not skipping regions
• enthesitis
• affects peripheral joints

Genetics

• HLA-B27 is positive in 90-95% of patients
• concordance rate in identical twins is 50%
• frequently family history

Clinical manifestations

• generally begins in 2nd or 3rd decade of life (< 45 years)
• course of the disease is variable
• low back pain or sacral pain (sacroiliitis)
  • initial symptom
  • generally dull pain
  • insidious in onset
  • deep in the lower lumbar or gluteal region (buttocks pain)
  • pain worsens at night & may awaken patient from sleep
  • low back morning stiffness (> 1 hour)
  • improved with activity or heat
  • recurring following inactivity
• pain tends to be persistent earlier in the disease, then becomes intermittent
• loss of spinal mobility (Schober test)
  • limitation of lumbar & cervical spine motion in all planes
  • fixed forward flexion, accentuation of thoracic kypohosis
  • decreased hyperextension, lateral flexion, axial rotation
  • obliteration of lumbar lordosis
• pain or tenderness over the sacroiliac joints (sacroiliitis)
• limited chest expansion (< 5 cm at nipple line or 4th intercostal space) with inspiration
• enthesitis
  • painful heel, Achilles tendonitis, tenderness over plantar insertion
  • tenderness over the iliac crest
  • chest wall tenderness
  • tendernous over spinous processes & other bony prominences
• arthritis of other joints in 30%
  • especially in lower extremities
  • asymmetric
  • large joints: hip, knee, ankle, shoulder
    • does not involve small joints
  • effusion
  • decreased range of motion
  • periarticular inflammation
• atrophy of buttocks
• iritis (anterior uveitis)
  • ocular pain, photophobia, blurred vision
  • generally unilateral & recurrent 20-25%
• cardiovascular manifestations
  • aortic insufficiency (uncommon)
  • cardiac conduction disturbances
  • LV diastolic dysfunction
  • aortitis, aortic aneurysm
  • coronary artery disease
• non-specific systemic manifestations
  • fatigue, sleep disorder, depression, sexual dysfunction,
  • weight loss, low grade fever
• pulmonary manifestations (< 5%)
  • restrictive lung disease from costovertebral rigidity
  • apical pulmonary fibrosis & cavitation (rare)
  • fibrobullous lesions in apices of lung
    • secondary infection:
      • Aspergillus
      • Mycobacterium species
  • diaphragmatic calcification may occur
  • pleural effusion is rare
• manifestations of inflammatory bowel disease
  • asymptomatic intestinal ulcerations
  • intermittent diarrhea, abdominal pain
• psoriasis may coexist
• urethritis (rare)
• cauda equina syndrome

Laboratory

• rheumatoid factor (RF) & antinuclear antibody (ANA) are negative
  • low level antinuclear antibody titers (1:80) may be observed
• elevated acute phase reactants not always elevated
  • erythrocyte sedimentation rate (ESR)
  • serum C-reactive protein
• elevated serum IgA
• synovial fluid analysis from inflamed joint shows typical inflammatory pattern
• HLA-B27 in blood generally positive (not diagnostic)
  • helpful prior to sacroiliac MRI
• complete blood count (CBC)
  • monocytosis seen with inflammatory bowel disease

Diagnostic procedures

• pulmonary function tests
  • increased vital capacity
  • decreased functional residual capacity
  • airflow measurements are normal

Radiology

• plain radiographs:
  • radiography of sacroiliac joint
    • sacroiliitis is generally present
      • erosions, pseudowidening of joints, sclerosis, ankylosis
    • patients with sacroiliitis are more likely to progress to ankylosing spondylitis
  • radiography of spine
    • spinal radiography should not be repeated more frequently than every 2 years unless clinically indicated
    • earliest changes are blurring of cortical margins of subchondral bone
    • erosions & subchrondral bony sclerosis
    • fibrous & bony ankylosis 'bamboo spine'
    • calcification of longitudinal ligament of spine
    • bridging vertical enthesophytes
    • pseudowidening of joint space
    • obliteration of joints
    • squaring of the vertebral bodies
    • syndesmophytes
    • changes generally symmetric
• computed tomography
  • can detect abnormalies earlier than plain radiographs
  • diagnostic test of choice for suspected fracture of cervical spine
• magnetic resonance imaging of the sacroiliac joints
  • indicated if diagnosis suspected by radiographs negative
  • may reveal bone marrow edema, synovitis & erosions
  • bone marrow edema earliest change not visible on CT
  • sacroiliac joint MRI more sensitive than lumbar spine MRI
  • obtain HLA-B27 in blood first
• bone density scan to detect osteopenia, osteoporosis
  • bone mineral density may be falsely elevated due to syndesmophytes
• do not use CT or MRI to monitor disease activity, patients are monitored clinically

Complications

• spinal fracture
  • may occur with even minor trauma
  • cervical spine most commonly involved
    • may lead to quadriplegia
  • immobilize neck, obtain CT scan
• cauda equina syndrome
• cardiovascular complications
  • proximal aortitis
  • aortic insufficiency
  • conduction system defects
    • 3rd degree heart block
  • left ventricular diastolic dysfunction
  • coronary artery disease
  • increased risk of cardiovascular mortality (RR=1.36)
• fibrotic changes in upper lung fields
• renal
  • IgA nephropathy (hematuria +/- proteinuria)
  • renal amyloidosis (proteinuria)
• increased overall mortality (RR=1.6)

Differential diagnosis

• diffuse hypertrophic skeletal hyperostosis (DISH)
• osteitis condensans ilii
• fusion of the sacroiliac joint in paraplegia
• osteitis pubis
• degenerative joint disease

Management

• physical therapy & exercise program
  • maintain functional posture
  • preserve range of motion
    • spinal mobility
    • chest expansion
  • NSAIDs generally required to carry out exercise program
• pharmaceutical agents
  • non-steroidal anti-inflammatory drugs (NSAIDs) are 1st line
    • continuous NSAIDs but not aspirin are disease-modifying
    • diclofenac, naproxen, ibuprofen ...
      • scheduled diclofenac no better than PRN
    • indomethacin 75 mg (sustained release) PO QD or BID
    • sulfasalazine 2-3 g/day for peripheral joint disease
      • not FDA approved for AS
      • not useful for treatment of axial disease
      • coexistant psoriasis or inflammatory bowel disease
    • phenylbutazone 200-400 mg PO QD for patients who do not respond to NSAIDs
    • aspirin not recommended
    • response to NSAIDs does not distinguish chronic axial spondyloarthritis from chronic low back pain
  • methotrexate has not been proven to be effective
    • not effective for axial disease
  • hydroxychloroquine not effective for axial disease
  • no therapeutic role for gold, penicillamine, or systemic glucocorticoids
  • intra-articular glucocorticoids
    • may be of benefit for patients with persistent synovitis, enthesitis
    • CT-guided glucocorticoids into sacroiliac joints
  • iritis
    • ophthalmic agents containing glucocorticoid
    • mydriatic agents
  • TNF-alpha inhibitor for severe active disease refractory to conventional (NSAID) therapy
    • etanercept
    • inflimixab
    • adalimumab
    • certolizumab
    • golimumab
    • screening for tuberculosis prior to initiating therapy
  • other biologic agents
    • secukinumab (Cosentyx) an IL-17A inhibitor FDA-approved
    • ixekizumab (Taltz) FDA-approved
• screen for & treat osteoporosis
  • calcium & vitamin D for all patients
  • bisphosphonate for osteopenia, osteoporosis
• surgery
  • severe hip joint arthritis - total hip arthroplasty
  • extreme flexion deformities of the spine
  • atlantoaxial subluxation
• prognosis
  • most patients remain gainfully employed
  • in the absence of complications, life span is normal

More general terms

• autoimmune disease
• spondyloarthropathy
• spondylitis

Additional terms

• 1996 New York criteria for ankylosing spondylitis
• sacroiliitis

Patient information

ankylosing spondylitis patient information

Database

• OMIM: https://mirror.omim.org/entry/106300