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

Etiology: 1) unknown 2) strongly associated with inflammatory bowel disease 3) some evidence suggests autoimmune etiology Epidemiology: 1) generally begins in 2nd or 3rd decade of life 2) onset after age 40 is unusual 3) male:female ratio 3:1 4) more common in white than black adults 5) affects 0.2% of white adults Pathology: 1) chronic inflammatory disorder primarily affecting the axial skeleton 2) sacroiliitis a) subchondral granulation tissue containing lymphocytes, plasma cells, mast cells, macrophages & chondrocytes b) the thinner iliac cartilage is eroded before the thicker sacral cartilage c) fibrocartilage regeneration followed by ossification d) complete obliteration of the joint may result 3) spine a) inflammatory granulation tissue at the junction of the annulus fibrosis of the disk cartilage & the vertebral bone b) erosion of the annulus fibrosis & replacement by bone (syndesmophyte) which grows by endochondral ossification eventually bridging adjacent vertebrae - calcification of longitudinal ligament of spine [3] c) diffuse osteoporosis d) inflammatory arthritis of apophyseal joints 4) arthritis begins at the sacroiliac joint & lower spine & progresses cranially, not skipping regions [3] 5) enthesitis 6) affects peripheral joints Genetics: 1) HLA-B27 is positive in 90-95% of patients [3] 2) concordance rate in identical twins is 50% 3) frequently family history Clinical manifestations: 1) generally begins in 2nd or 3rd decade of life (< 45 years) [3] 2) course of the disease is variable 3) low back pain or sacral pain (sacroiliitis) a) initial symptom b) generally dull pain c) insidious in onset d) deep in the lower lumbar or gluteal region (buttocks pain) e) pain worsens at night & may awaken patient from sleep f) low back morning stiffness (> 1 hour) [3] g) improved with activity or heat h) recurring following inactivity 5) pain tends to be persistent earlier in the disease, then becomes intermittent 6) loss of spinal mobility (Schober test) a) limitation of lumbar & cervical spine motion in all planes b) fixed forward flexion, accentuation of thoracic kypohosis c) decreased hyperextension, lateral flexion, axial rotation [3] d) obliteration of lumbar lordosis 7) pain or tenderness over the sacroiliac joints (sacroiliitis) 8) limited chest expansion (< 5 cm at nipple line or 4th intercostal space) with inspiration 9) enthesitis a) painful heel, Achilles tendonitis, tenderness over plantar insertion b) tenderness over the iliac crest c) chest wall tenderness d) tendernous over spinous processes & other bony prominences 10) arthritis of other joints in 30% a) especially in lower extremities b) asymmetric c) large joints: hip, knee, ankle, shoulder - does not involve small joints [3] d) effusion e) decreased range of motion f) periarticular inflammation 11) atrophy of buttocks 12) iritis (anterior uveitis) - ocular pain, photophobia, blurred vision - generally unilateral & recurrent 20-25% 13) cardiovascular manifestations a) aortic insufficiency (uncommon) b) cardiac conduction disturbances c) LV diastolic dysfunction d) aortitis, aortic aneurysm [3] e) coronary artery disease 14) non-specific systemic manifestations - fatigue, sleep disorder, depression, sexual dysfunction [17], - weight loss, low grade fever 15) pulmonary manifestations (< 5%) a) restrictive lung disease from costovertebral rigidity [3] b) apical pulmonary fibrosis & cavitation (rare) c) fibrobullous lesions in apices of lung - secondary infection: a] Aspergillus b] Mycobacterium species d) diaphragmatic calcification may occur e) pleural effusion is rare 16) manifestations of inflammatory bowel disease - asymptomatic intestinal ulcerations [3] - intermittent diarrhea, abdominal pain [23] 17) psoriasis may coexist [3] 18) urethritis (rare) [3] 19) cauda equina syndrome [3] Diagnostic criteria: - HLA-B27 positive* - family history - acute anterior uveitis - sacroiliitis on radiography or MRI - elevated erythrocyte sedimentation rate, serum C-reactive protein - favorable response to NSAIDs - inflammatory bowel disease* * >= 3 diagnostic criteria [25] Laboratory: 1) rheumatoid factor (RF) & antinuclear antibody (ANA) are negative - low level antinuclear antibody titers (1:80) may be observed [23] 2) elevated acute phase reactants not always elevated [3] a) erythrocyte sedimentation rate (ESR) b) serum C-reactive protein 3) elevated serum IgA 4) synovial fluid analysis from inflamed joint shows typical inflammatory pattern 5) HLA-B27 in blood generally positive (not diagnostic) - helpful prior to sacroiliac MRI [3] 6) complete blood count (CBC) - monocytosis seen with inflammatory bowel disease Special laboratory: - pulmonary function tests a) increased vital capacity b) decreased functional residual capacity c) airflow measurements are normal Radiology: 1) plain radiographs: a) 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 [14] b) radiography of spine - spinal radiography should not be repeated more frequently than every 2 years unless clinically indicated [3,8] - 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 [3] - bridging vertical enthesophytes - pseudowidening of joint space - obliteration of joints - squaring of the vertebral bodies - syndesmophytes - changes generally symmetric 2) computed tomography a) can detect abnormalies earlier than plain radiographs b) diagnostic test of choice for suspected fracture of cervical spine 3) magnetic resonance imaging of the sacroiliac joints [7] a) indicated if diagnosis suspected by radiographs negative b) may reveal bone marrow edema, synovitis & erosions [3] c) bone marrow edema earliest change not visible on CT d) sacroiliac joint MRI more sensitive than lumbar spine MRI e) obtain HLA-B27 in blood first [3] 4) bone density scan to detect osteopenia, osteoporosis - bone mineral density may be falsely elevated due to syndesmophytes 5) do not use CT or MRI to monitor disease activity, patients are monitored clinically [3] Complications: 1) spinal fracture a) may occur with even minor trauma b) cervical spine most commonly involved - may lead to quadriplegia c) immobilize neck, obtain CT scan 2) cauda equina syndrome 3) cardiovascular complications a) proximal aortitis b) aortic insufficiency c) conduction system defects - 3rd degree heart block d) left ventricular diastolic dysfunction e) coronary artery disease [3] f) increased risk of cardiovascular mortality (RR=1.36) [13,22] 4) fibrotic changes in upper lung fields 5) renal a) IgA nephropathy (hematuria +/- proteinuria) [2] b) renal amyloidosis (proteinuria) 6) increased overall mortality (RR=1.6) [22] Differential diagnosis: 1) diffuse hypertrophic skeletal hyperostosis (DISH) 2) osteitis condensans ilii 3) fusion of the sacroiliac joint in paraplegia 4) osteitis pubis 5) degenerative joint disease Management: 1) physical therapy & exercise program a) maintain functional posture b) preserve range of motion - spinal mobility - chest expansion c) NSAIDs generally required to carry out exercise program 2) pharmaceutical agents a) non-steroidal anti-inflammatory drugs (NSAIDs) are 1st line - continuous NSAIDs but not aspirin are disease-modifying [3] - diclofenac, naproxen, ibuprofen ... [3,4] - scheduled diclofenac no better than PRN [16] - indomethacin 75 mg (sustained release) PO QD or BID - sulfasalazine 2-3 g/day for peripheral joint disease [3] - not FDA approved for AS - not useful for treatment of axial disease [3] - coexistant psoriasis or inflammatory bowel disease - phenylbutazone 200-400 mg PO QD for patients who do not respond to NSAIDs - aspirin not recommended [3] - response to NSAIDs does not distinguish chronic axial spondyloarthritis from chronic low back pain [24] b) methotrexate has not been proven to be effective [3] - not effective for axial disease [3] c) hydroxychloroquine not effective for axial disease [3] d) no therapeutic role for gold, penicillamine, or systemic glucocorticoids e) intra-articular glucocorticoids - may be of benefit for patients with persistent synovitis, enthesitis - CT-guided glucocorticoids into sacroiliac joints f) iritis - ophthalmic agents containing glucocorticoid - mydriatic agents g) TNF-alpha inhibitor for severe active disease refractory to conventional (NSAID) therapy [3,5] - etanercept - inflimixab [3,15] - adalimumab [3] - certolizumab [3] - golimumab [3] - screening for tuberculosis prior to initiating therapy h) other biologic agents - secukinumab (Cosentyx) an IL-17A inhibitor FDA-approved [18,21] - ixekizumab (Taltz) FDA-approved 3) screen for & treat osteoporosis a) calcium & vitamin D for all patients [3] b) bisphosphonate for osteopenia, osteoporosis 4) surgery a) severe hip joint arthritis - total hip arthroplasty b) extreme flexion deformities of the spine c) atlantoaxial subluxation 5) prognosis a) most patients remain gainfully employed b) in the absence of complications, life span is normal

Interactions

disease interactions

Related

1996 New York criteria for ankylosing spondylitis sacroiliitis

General

autoimmune disease spondylitis spondyloarthropathy (HLA B27-associated arthritis, seronegative spondyloarthropathy)

Properties

THERAPY: indomethacin sulfasalazine

Database Correlations

OMIM 106300

References

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  4. Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum. 2008 Apr;58(4):929-38 PMID: 18383378
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  9. van der Heijde D, Sieper J, Maksymowych WP et al 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis. 2011 Jun;70(6):905-8 PMID: 21540200
  10. de Vries MK, van Eijk IC, van der Horst-Bruinsma IE et al Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis. Arthritis Rheum. 2009 Nov 15;61(11):1484-90 PMID: 19877087
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  12. Rudwaleit M, Taylor WJ. Classification criteria for psoriatic arthritis and ankylosing spondylitis/axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2010 Oct;24(5):589-604. PMID: 21035082
  13. Haroon NN et al. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: A population- based study. Ann Intern Med 2015 Aug 11 PMID: 26258401
  14. Wang R et al. Progression of nonradiographic axial spondyloarthritis to ankylosing spondylitis: A population-based cohort study. Arthritis Rheumatol 2016 Jun; 68:1415 PMID: 26663907
  15. Baraliakos X, Heldmann F, van den Bosch F et al Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction. RMD Open. 2016 Jul 19;2(2):e000272. eCollection 2016. PMID: 27493791 Free PMC Article
  16. Sieper J, Listing J, Poddubnyy D et al. Effect of continuous versus on-demand treatment of ankylosing spondylitis with diclofenac over 2 years on radiographic progression of the spine: results from a randomised multicentre trial (ENRADAS). Ann Rheum Dis 2016 Aug 75:1438 PMID: 26242443
  17. Strand V, Singh JA. Patient Burden of Axial Spondyloarthritis. J Clin Rheumatol. 2017 Oct;23(7):383-391. PMID: 28937474 Free PMC Article
  18. Pavelka K, Kivitz A, Dokoupilova E et al Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther. 2017 Dec 22;19(1):285. PMID: 29273067 Free PMC Article
  19. Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016 Jun 30;374(26):2563-74. PMID: 27355535
  20. Kirkner M Working Group Proposes MRI Definitions of Structural Lesions Indicative of Axial Spondyloarthritis. Medscape - Jun 08, 2020. https://www.medscape.com/viewarticle/931907
  21. Yin Y, Wang M, Liu M et al Efficacy and Safety of IL-17 Inhibitors for the Treatment of Ankylosing Spondylitis. Arthritis Res Ther. 2020;22(111) via Medscape PMID: 32398096 PMCID: PMC7216398 Free PMC article https://www.medscape.com/viewarticle/932033 - Franki L FDA Approves Cosentyx for Treatment ofActive nr-axSpA Medscape - Jun 18, 2020. https://www.medscape.com/viewarticle/932574
  22. Harris S Mortality in Ankylosing Spondylitis and Psoriatic Arthritis. AS alone linked with greater all-cause mortality; CV deaths elevated with both diseases. MedPage Today April 15, 2022 https://www.medpagetoday.com/reading-room/acrr/psoriaticarthritis/98224 - Chaudhary H, Bohra N, Syed K et al All-Cause and Cause-Specific Mortality in Psoriatic Arthritis and Ankylosing Spondylitis: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken). 2021 Nov 17 PMID: 34788902 https://onlinelibrary.wiley.com/doi/10.1002/acr.24820
  23. NEJM Knowledge+ Hematology
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  26. National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Ankylosing Spondylitis https://www.niams.nih.gov/health-topics/ankylosing-spondylitis