Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy Workup

  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Apr 16, 2012
 

Approach Considerations

The diagnosis of ankylosing spondylitis (AS) is not dependent on laboratory data; no laboratory tests are specific for AS.

Radiographic studies are most helpful in establishing a diagnosis.[73] Computed tomography (CT) and magnetic resonance imaging (MRI) may be useful in selected patients but, for reasons of expense, are not typically part of routine evaluation.

Power Doppler ultrasonography can be used to document active enthesitis. In addition, this technology may be useful to assess changes in inflammatory activity at entheses during institution of new therapies.[74]

Biopsy and histologic analysis are not indicated for individuals with AS.

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Laboratory Studies

Approximately 15% of patients present with a normochromic normocytic anemia of chronic disease. The erythrocyte sedimentation rate (ESR) or the C-reactive protein (CRP) level is elevated in approximately 75% of patients and may correlate with disease activity in some, but not all, patients; these values may also be used as markers of response to treatment.[75, 76]

Alkaline phosphatase (ALP) is elevated in 50% of patients; this indicates active ossification but does not correlate with disease activity. Creatine kinase (CK) is occasionally elevated but is not associated with muscle weakness. The serum immunoglobulin A (IgA) level may be elevated, correlating with elevated acute-phase reactants.

Ninety-two percent of white patients with AS are HLA-B27 –positive; the percentage is lower in patients of other ethnic backgrounds. Determining HLA-B27 status is not a necessary part of the clinical evaluation and is not required to establish the diagnosis. However, in patients suspected of having a spondyloarthropathy, determining HLA-B27 status may help support the diagnosis, especially in populations with a low prevalence of HLA-B27.

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Radiography

Radiographic evidence of inflammatory changes both in the sacroiliac (SI) joints and in the spine are useful in the diagnosis and ongoing evaluation of the disease process.[77] This disease generally begins in the distal portions of the spine and progresses more proximally with time in a continuous fashion.

Involvement of the SI joint is a requirement for the diagnosis of AS. Sacroiliitis is a bilateral inflammatory condition leading to bony erosions and sclerosis of the joints (see the images below).

Anteroposterior radiograph of sacroiliac joint of Anteroposterior radiograph of sacroiliac joint of patient with ankylosing spondylitis. Bilateral sacroiliitis with sclerosis can be observed. This radiograph of the pelvis of a patient with anThis radiograph of the pelvis of a patient with ankylosing spondylitis shows bilateral sacroiliitis with sclerosis and narrowing of the sacroiliac joints.

The sacroiliitis seen in AS is usually bilateral, symmetric, and gradually progressive over years. The lesions progress from blurring of the subchondral bone plate to irregular erosions of the margins of the SI joints (pseudowidening) to sclerosis, narrowing, and finally fusion. Erosions of the subchondral bone of the SI joint are generally seen earlier in the lower portion of the joint (because this portion is lined by synovium) and on the iliac side (because of the thinner cartilage covering this side of the joint).

The radiographic signs of AS are due to enthesitis, particularly of the anulus fibrosus. Early radiographic signs include squaring of the vertebral bodies caused by erosions of the superior and inferior margins of these bodies, resulting in loss of the normal concave contour of the anterior surface of the vertebral bodies (see the images below). The inflammatory lesions at vertebral entheses may result in sclerosis of the superior and inferior margins of the vertebral bodies, called shiny corners (Romanus lesion).

Anteroposterior radiograph of spine of patient witAnteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus at multiple levels and squaring of vertebral bodies can be observed. Anteroposterior radiograph of spine of patient witAnteroposterior radiograph of spine of patient with ankylosing spondylitis. Anteroposterior (left) and lateral (right) radiogrAnteroposterior (left) and lateral (right) radiographs of patient with ankylosing spondylitis. This radiograph of the lumbar spine of a patient wThis radiograph of the lumbar spine of a patient with ankylosing spondylitis shows sclerosis of vertebral margins, which are referred to as shining corners.

Ossification of the anulus fibrosus leads to the radiographic appearance of syndesmophytes, which, in AS, are typically marginal. Over time, development of continuous (bridging) syndesmophytes may result in a bamboo spine, which is essentially fused (see the images below).

Anteroposterior radiograph of spine of patient witAnteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus can be observed at multiple levels, which has led to fusion of spine with abnormal curvature. This radiograph of the lumbar spine of a patient wThis radiograph of the lumbar spine of a patient with end-stage ankylosing spondylitis shows bridging syndesmophytes, resulting in bamboo spine. This radiograph of the cervical spine of a patientThis radiograph of the cervical spine of a patient with ankylosing spondylitis shows fusion of vertebral bodies due to bridging syndesmophytes.

Spinal disease associated with inflammatory bowel disease (IBD) is similar to AS with bilateral symmetric sacroiliitis and gradually ascending spondylitis and marginal syndesmophytes. On the other hand, reactive arthritis (ReA) and psoriatic arthritis (PsA) typically exhibit asymmetric sacroiliitis and discontinuous spondylitis with nonmarginal syndesmophytes.

Radiographs of other areas may show evidence of enthesitis with osteitis or arthropathy. Radiographs of the pelvis may show ossification of various entheses, such as the iliac crest, ischial tuberosity, and femoral trochanter, which is termed whiskering. Occasionally, the symphysis pubis develops erosive changes (osteitis pubis).

Peripheral entheses may develop radiographic changes, including erosion, periosteal new bone formation, and finally, ossification, especially in the feet at the insertion of the Achilles tendon and the plantar fascia on the calcaneus (see the image below).

This radiograph of the heel of a patient with undiThis radiograph of the heel of a patient with undifferentiated spondyloarthropathy shows bony changes secondary to enthesitis, with an erosion at the insertion of the Achilles tendon and periosteal new-bone formation at the insertion of the plantar fascia on the calcaneus.

Peripheral joint involvement is most common in the hips and shoulders and may result in uniform joint space narrowing, cystic or erosive changes, deformation, and subchondral sclerosis without osteopenia (see the image below). Heterotopic bone formation may occur after total joint replacement, especially in the hip. Ultimately, peripheral joints may undergo ankylosis. See the radiographs below for an example.

Radiographs of hand (top) and arm (bottom) of patiRadiographs of hand (top) and arm (bottom) of patient with peripheral involvement of ankylosing spondylitis. Fusion of joint spaces and deformity can be observed.

Patients with AS are vulnerable to cervical spine fractures. Long-standing pain may mask the symptoms of fracture. Radiologic imaging may fail to identify the fracture as a consequence of the distorted anatomy, ossified ligaments, and artifacts.

A retrospective case series of 32 patients with AS and cervical spine fractures revealed that in 19 patients (59.4%), a fracture was not identified on plain radiographs.[78] Only 5 patients (15.6%) presented immediately after the injury. Of the 15 patients (46.9%) who were initially neurologically intact, 3 patients had neurologic deterioration before admission. Early diagnosis with appropriate radiologic investigations may prevent possible long-term neurologic cord damage.

Patients with a history of AS who report any recent trauma or an increased level of back or neck pain should be fully evaluated for the possibility of a vertebral fracture and subsequent spinal instability (see the image below).

Radiograph shows vertebral fracture in patient witRadiograph shows vertebral fracture in patient with ankylosing spondylitis.
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MRI and CT

MRI or CT scanning of the SI joints, spine, and peripheral joints may reveal evidence of early sacroiliitis, erosions, and enthesitis that are not apparent on standard radiographs.[79, 80] MRI using fat-saturating techniques such as short tau inversion recovery (STIR) or MRI with gadolinium is sensitive for inflammatory lesions of enthesitis.[81, 82] The so-called MR corner sign, characterized by inflammatory lesions at the corners of vertebral bodies, was common in the thoracolumbar region of the spine in patients with AS.[83]

Investigations of patients with AS using serial MRI over time has shown a link between inflammatory lesions and the later development of syndesmophytes.[84] MRI can be used as an adjunct to evaluate the inflammatory changes and to assess neural compromise (see the image below). However, MRI and CT are not part of the routine evaluation of AS patients, because of their relatively high cost.

Sagittal MRI of thoracolumbar spine of a patient wSagittal MRI of thoracolumbar spine of a patient with ankylosing spondylitis. Degenerative disc disease and bridging osteophytes can be observed at multiple levels.

Patients with a fused spine are prone to fractures, which may be hard to diagnose with standard radiography. CT scanning or MRI may be required to document the presence of a fracture in patients with late-stage spinal disease (see the images below).

This 15-year-old female patient presented with recThis 15-year-old female patient presented with recent onset of right-sided low back pain. Plain radiography findings were normal. MRI of the same patient whose radiography findingsMRI of the same patient whose radiography findings were normal (Picture 7). She underwent further evaluation, including MRI. The MRI (short tau inversion recovery [STIR]) showed increased sinal intensity in the right sacroiliac joint, revealing sacroiliitis. Other laboratory study findings were essentially normal. The patient was started on indomethacin and rapidly improved.

Patients who develop bowel or bladder dysfunction should be evaluated immediately with MRI to assess for possible cauda equina syndrome secondary to spinal stenosis. The presence of cauda equina syndrome is a surgical emergency necessitating decompression within 48 hours to prevent permanent loss of function.

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Histologic Findings

Histopathologic evaluation is not generally part of the diagnostic workup in patients with ankylosing spondylitis.

The basic pathologic lesion is inflammation at the enthesis (enthesitis), which occurs at the site of insertion of ligaments and tendons into bone. The histologic picture is that of chronic inflammation with CD4+ and CD8+ T lymphocytes and macrophages. Early AS lesions include subchondral granulation tissue that erodes the joint. Over time, fibrosis and ossification occur, which can be seen radiographically as periostitis and ossification at sites of enthesitis, particularly the SI joints, spine, and heels.

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Contributor Information and Disclosures
Author

Lawrence H Brent, MD  Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Coauthor(s)

Rajni Kalagate, MD  Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center

Rajni Kalagate, MD is a member of the following medical societies: American Academy of Pediatrics and Indian Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

Jason C Eck, DO, MS Assistant Professor, Department of Orthopedics and Physical Rehabilitation, UMass Memorial Medical Center

Jason C Eck, DO, MS is a member of the following medical societies: American Osteopathic Academy of Orthopedics, American Osteopathic Association, International Society for the Study of the Lumbar Spine, and North American Spine Society

Disclosure: Medtronic Honoraria Speaking and teaching

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Scott D Hodges, DO Consulting Surgeon, Department of Orthopedic Surgery, Center for Sports Medicine and Orthopedics

Scott D Hodges, DO is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Medical Association, American Osteopathic Association, American Spinal Injury Association, North American Spine Society, Southern Medical Association, Southern Orthopaedic Association, and Tennessee Medical Association

Disclosure: Medtronic Royalty Consulting; Biomet Spine Royalty Consulting

S Craig Humphreys, MD Orthopedic Spine Surgeon, Department of Orthopedic Surgery, Center for Sports Medicine and Orthopedics

S Craig Humphreys, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Orthopaedic Surgeons, American Medical Association, American Spinal Injury Association, North American Spine Society, Southern Medical Association, Southern Orthopaedic Association, and Tennessee Medical Association

Disclosure: Nothing to disclose.

James F Kellam, MD Vice-Chair, Department of Orthopedic Surgery, Director of Orthopedic Trauma and Education, Carolinas Medical Center

James F Kellam, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Orthopaedic Trauma Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

William O Shaffer, MD Professor, Vice-Chairman and Residency Program Director, Department of Orthopedic Surgery, University of Kentucky at Lexington

William O Shaffer, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, International Society for the Study of the Lumbar Spine, Kentucky Medical Association, Kentucky Orthopaedic Society, North American Spine Society, Southern Medical Association, and Southern Orthopaedic Association

Disclosure: DePuySpine 1997-2007 (not presently) Royalty Consulting; DePuySpine 2002-2007 (closed) Grant/research funds SacroPelvic Instrumentation Biomechanical Study; DePuyBiologics 2005-2008 (closed) Grant/research funds Healos study just closed; DePuySpine 2009 Consulting fee Design of Offset Modification of Expedium

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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  75. Ruof J, Stucki G. Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review. J Rheumatol. Apr 1999;26(4):966-70. [Medline].

  76. Dougados M, Gueguen A, Nakache JP, et al. Clinical relevance of C-reactive protein in axial involvement of ankylosing spondylitis. J Rheumatol. Apr 1999;26(4):971-4. [Medline].

  77. van der Heijde D, Spoorenberg A. Plain radiographs as an outcome measure in ankylosing spondylitis. J Rheumatol. Apr 1999;26(4):985-7. [Medline].

  78. Anwar F, Al-Khayer A, Joseph G, Fraser MH, Jigajinni MV, Allan DB. Delayed presentation and diagnosis of cervical spine injuries in long-standing ankylosing spondylitis. Eur Spine J. Mar 2011;20(3):403-7. [Medline]. [Full Text].

  79. Vinson EN, Major NM. MR imaging of ankylosing spondylitis. Semin Musculoskelet Radiol. Jun 2003;7(2):103-13. [Medline].

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  82. Hermann KG, Landewé RB, Braun J, van der Heijde DM. Magnetic resonance imaging of inflammatory lesions in the spine in ankylosing spondylitis clinical trials: is paramagnetic contrast medium necessary?. J Rheumatol. Oct 2005;32(10):2056-60. [Medline].

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  84. Maksymowych WP, Chiowchanwisawakit P, Clare T, Pedersen SJ, Østergaard M, Lambert RG. Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthritis Rheum. Jan 2009;60(1):93-102. [Medline].

  85. [Best Evidence] Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. Apr 2006;65(4):442-52. [Medline].

  86. Halm H, Metz-Stavenhagen P, Zielke K. Results of surgical correction of kyphotic deformities of the spine in ankylosing spondylitis on the basis of the modified arthritis impact measurement scales. Spine (Phila Pa 1976). Jul 15 1995;20(14):1612-9. [Medline].

  87. Hunter T, Dubo HI. Spinal fractures complicating ankylosing spondylitis. A long-term followup study. Arthritis Rheum. Jun 1983;26(6):751-9. [Medline].

  88. Escalas C, Trijau S, Dougados M. Evaluation of the treatment effect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: results of a meta-analysis. Rheumatology (Oxford). Jul 2010;49(7):1317-25. [Medline].

  89. Wanders A, Heijde D, Landewe R, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. Jun 2005;52(6):1756-65. [Medline].

  90. Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. Mar 2008;67(3):323-9. [Medline]. [Full Text].

  91. [Best Evidence] Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol. Apr 2006;33(4):722-31. [Medline].

  92. Clegg DO, Reda DJ, Weisman MH, Blackburn WD, Cush JJ, Cannon GW, et al. Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. Dec 1996;39(12):2004-12. [Medline].

  93. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondylarthropathies: a Department of Veterans Affairs cooperative study. Arthritis Rheum. Nov 1999;42(11):2325-9. [Medline].

  94. Braun J, Pavelka K, Ramos-Remus C, Dimic A, Vlahos B, Freundlich B, et al. Clinical efficacy of etanercept versus sulfasalazine in ankylosing spondylitis subjects with peripheral joint involvement. J Rheumatol. Apr 2012;39(4):836-40. [Medline].

  95. Inman RD, Maksymowych WP. A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol. Jun 2010;37(6):1203-10. [Medline].

  96. Braun J, Davis J, Dougados M, et al. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis. Mar 2006;65(3):316-20. [Medline].

  97. Braun J, Baraliakos X, Golder W, et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum. Apr 2003;48(4):1126-36. [Medline].

  98. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. May 2 2002;346(18):1349-56. [Medline].

  99. Davis JC, Van Der Heijde D, Braun J, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. Nov 2003;48(11):3230-6. [Medline].

  100. [Best Evidence] van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. Feb 2005;52(2):582-91. [Medline].

  101. Braun J, Landewé R, Hermann KG, et al. Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Arthritis Rheum. May 2006;54(5):1646-52. [Medline].

  102. Gengenbacher M, Sebald HJ, Villiger PM, Hofstetter W, Seitz M. Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis. May 2008;67(5):620-4. [Medline].

  103. van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. Jul 2006;54(7):2136-46. [Medline].

  104. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. Nov 2008;58(11):3402-12. [Medline].

  105. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Emery P, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis. Nov 2006;65 Suppl 3:iii2-15. [Medline].

  106. [Best Evidence] Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev. Oct 18 2006;CD004524. [Medline].

  107. [Best Evidence] van Denderen JC, van der Paardt M, Nurmohamed MT, de Ryck YM, Dijkmans BA, van der Horst-Bruinsma IE. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis. Dec 2005;64(12):1761-4. [Medline].

  108. van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. ASsessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis Rheum. Feb 2005;52(2):386-94. [Medline].

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  111. Van Royen BJ, De Gast A. Lumbar osteotomy for correction of thoracolumbar kyphotic deformity in ankylosing spondylitis. A structured review of three methods of treatment. Ann Rheum Dis. Jul 1999;58(7):399-406. [Medline]. [Full Text].

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The family of spondyloarthropathies
This radiograph of the pelvis of a patient with ankylosing spondylitis shows bilateral sacroiliitis with sclerosis and narrowing of the sacroiliac joints.
This radiograph of the lumbar spine of a patient with ankylosing spondylitis shows sclerosis of vertebral margins, which are referred to as shining corners.
This radiograph of the lumbar spine of a patient with end-stage ankylosing spondylitis shows bridging syndesmophytes, resulting in bamboo spine.
This radiograph of the cervical spine of a patient with ankylosing spondylitis shows fusion of vertebral bodies due to bridging syndesmophytes.
This radiograph of the heel of a patient with undifferentiated spondyloarthropathy shows bony changes secondary to enthesitis, with an erosion at the insertion of the Achilles tendon and periosteal new-bone formation at the insertion of the plantar fascia on the calcaneus.
This 15-year-old female patient presented with recent onset of right-sided low back pain. Plain radiography findings were normal.
MRI of the same patient whose radiography findings were normal (Picture 7). She underwent further evaluation, including MRI. The MRI (short tau inversion recovery [STIR]) showed increased sinal intensity in the right sacroiliac joint, revealing sacroiliitis. Other laboratory study findings were essentially normal. The patient was started on indomethacin and rapidly improved.
Patient with ankylosing spondylitis affecting cervical and upper thoracic spine. Patient's spine has been fused in flexed position.
Posterior view of patient with ankylosing spondylitis affecting cervical and upper thoracic spine. Patient's spine has been fused in flexed position.
Anteroposterior radiograph of sacroiliac joint of patient with ankylosing spondylitis. Bilateral sacroiliitis with sclerosis can be observed.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus can be observed at multiple levels, which has led to fusion of spine with abnormal curvature.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus at multiple levels and squaring of vertebral bodies can be observed.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis.
Anteroposterior (left) and lateral (right) radiographs of patient with ankylosing spondylitis.
Radiographs of hand (top) and arm (bottom) of patient with peripheral involvement of ankylosing spondylitis. Fusion of joint spaces and deformity can be observed.
Sagittal MRI of thoracolumbar spine of a patient with ankylosing spondylitis. Degenerative disc disease and bridging osteophytes can be observed at multiple levels.
Radiograph shows vertebral fracture in patient with ankylosing spondylitis.
Table 1. Association of Spondyloarthropathies With HLA-B27
Population or Disease EntityHLA-B27 –Positive
Healthy whites8%
Healthy African Americans4%
Ankylosing spondylitis (whites)92%
Ankylosing spondylitis (African Americans)50%
Reactive arthritis60-80%
Psoriasis associated with spondylitis60%
IBD associated with spondylitis60%
Isolated acute anterior uveitis50%
Undifferentiated spondyloarthropathy20-25%
Table 2. Genetics of Ankylosing Spondylitis
GenesChromosome LocationGene Product/Function
Definitely associated



HLA-B27



IL-1 gene cluster



CYP 2D6



ARTS1 (ERAP1)



IL23R



6p21.3



2q12.1



22q13.2



5q15



1p31.1



Antigen presentation



Modulator of inflammation



Metabolism of xenobiotics



ER aminopeptidase 1



IL-23 receptor



Possibly associated



ANKH



HLA-DRB1



5p15



6p21.3



Ectopic mineralization



Antigen presentation



Not associated



TGF-ß, MMP3, IL-10, IL-6, Ig allotypes, TCR, TLR4, NOD2/CARD15, CD14, NFßBIL1, PTPN22, etc



MultipleMultiple
Table 3. Diagnostic Criteria for Undifferentiated Spondyloarthropathy Using Modified Amor Criteria
Inclusion CriteriaExclusion Criteria
Inflammatory back pain1 pointDiagnosis of specific spondyloarthropathy
Unilateral buttock pain1 pointSacroiliitis on radiograph = grade 2
Alternating buttock pain2 pointsPrecipitating genitourinary/gastrointestinal infection
Enthesitis2 pointsPsoriasis
Peripheral arthritis2 pointsKeratoderma blennorrhagicum
Dactylitis (sausage digit)2 pointsInflammatory bowel disease (Crohn disease or ulcerative colitis)
Acute anterior uveitis2 pointsPositive rheumatoid factor
HLA-B27 –positive or family history of spondyloarthropathy2 pointsPositive antinuclear antibody, titer > 1:80
Good response to nonsteroidal anti-inflammatory drugs2 points
Diagnosis of spondyloarthropathy with 6 or more points
Table 4. Clinical and Laboratory Features of Undifferentiated Spondyloarthropathy
Clinical or Laboratory FeatureFrequency
Inflammatory back pain90%
Buttock pain80%
Enthesitis75%
Peripheral arthritis40%
Dactylitis (sausage digits)20%
Acute anterior uveitis1-2%
Fatigue55%
Elevated ESR32%
HLA-B27 –positive25%
ESR = erythrocyte sedimentation rate.
Table 5. ESSG and Amor Criteria for Diagnosis of Spondyloarthropathy
ESSG CriteriaAmor Criteria*
Inflammatory spinal pain or synovitis and one of the following:Inflammatory back pain1 point
Alternating buttock painUnilateral buttock pain1 point
EnthesitisAlternating buttock pain2 points
SacroiliitisEnthesitis2 points
IBDPeripheral arthritis2 points
Positive family history of spondyloarthropathyDactylitis (sausage digit)2 points
Acute anterior uveitis2 points
HLA-B27 –positive or family history of spondyloarthropathy2 points
Good response to NSAIDs2 points
*Diagnosis of spondyloarthropathy with 6 or more points.



European Spondyloarthropathy Study Group (ESSG); IBD = inflammatory bowel disease; NSAID = nonsteroidal anti-inflammatory drug.



Table 6. New York and Rome Criteria for Diagnosis of Ankylosing Spondylitis
New York CriteriaRome Criteria
  • Low back pain with inflammatory characteristics
  • Limitation of lumbar spine motion in sagittal and frontal planes
  • Decreased chest expansion
  • Bilateral sacroiliitis grade 2 or higher
  • Unilateral sacroiliitis grade 3 or higher
  • Low back pain and stiffness for >3 months that is not relieved by rest
  • Pain and stiffness in the thoracic region
  • Limited motion in the lumbar spine
  • Limited chest expansion
  • History of uveitis
Definite ankylosing spondylitis when the fourth or fifth criterion mentioned presents with any clinical criteriaDiagnosis of ankylosing spondylitis when any clinical criteria present with bilateral sacroiliitis grade 2 or higher
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