History

Fact Explanation
Back pain [1,11] Inflammatory back pain is characteristic of ankylosing spondylitis. This is due to sacroiliitis and inflammation in the axial skeleton and subsequent damage to the spine. [2,6] Later spinal stiffness develops in both sagittal and frontal planes. Stiffness lasts more than 30 minutes in the mornings. The patient may wake up in the middle of the night due to the pain and stiffness. The pain and stiffness is markedly reduced after exercise but nor after rest. Presence of this typical pain for more than three months or the stiffness with radiological evidence of ankylosing spondylitis are diagnostic. [7]
Peripheral arthritis [2] Asymmetrical peripheral monoarticular or oligoarticular arthritis [8] with predominant involvement of the lower limbs. However involvement of the hip joint is a sign of adverse prognosis. [9]
Enthesitis [2,4] This is the inflammation at the insertion of bone and ligaments, tendons, or joint capsules. [12] Patients present with pain at the above sites. This is associated with the expression of HLA-B27. [12]
Anterior uveitis [5,10] Uveitis is usually unilateral but may migrate from one eye to the other. [10] Patients present with soreness and redness of the eye and photophobia.
Psoriasis Psoriasis is a known association with ankylosing spondylitis. [13] Patients have erythematic, plaque like silver color skin lesions, mainly over the extensor surfaces.
Inflammatory bowel disease IBD is also associated with ankylosing spondylitis. Patients present with chronic diarrhea and or abdominal pain. [14]
Tarsitis [2] This is relatively common in young patients. [3]
Chest pain This is due to the involvement of costovertebral joints. [15]
References
  1. WILLKENS RF, ARNETT FC, BITTER T, CALIN A, FISHER L, FORD DK: Reiter's syndrome: evaluation of preliminary criteria for definite disease. Arthritis Rheum [online] 1981, 24:844-849. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7247978?dopt=Abstract&holding=f1000,f1000m,isrctn
  2. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  3. BURGOS-VARGAS R, VAZQUEZ-MELLADO J. The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis. Arthritis Rheum [online] 1995; 38: 835-844. [viewed 31 March 2014] Available from: DOI: 10.1002/art.1780380618
  4. MCGONAGLE D, GIBBON W, EMERY P. Classification of inflammatory arthritis by enthesitis. Lancet [online] 1998; 352: 1137-1140. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(97)12004-9
  5. MARTIN TM, SMITH JR, ROSENBAUM JT. Anterior uveitis: current concepts of pathogenesis and interactions with the spondyloarthropathies. Curr Opin Rheumatol [online] 2002; 14: 337-341. [viewed 31 March 2014] Available from: http://journals.lww.com/co-rheumatology/pages/articleviewer.aspx?year=2002&issue=07000&article=00001&type=abstract
  6. WANDERS A, LANDEWE R, DOUGADOS M, MIELANTS H, VAN DER LINDEN S, VAN DER HEIJDE D. Association between radiographic damage of the spine and spinal mobility for individual patients with ankylosing spondylitis: can assessment of spinal mobility be a proxy for radiographic evaluation?. Ann Rheum Dis [online] 2005; 64: 988-994. [viewed 31 March 2014] Available from: doi:10.1136/ard.2004.029728
  7. VAN DER LINDEN S, VALKENBURG HA, CATS A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum [online] 1984; 27: 361-368. [viewed 31 March 2014] Available from: DOI: 10.1002/art.1780270401
  8. DOUGADOS M, VAN DER LINDEN S, JUHLIN R, ET al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum [online] 1991; 34: 1218-1227. [viewed 31 March 2014] Available from: DOI: 10.1002/art.1780341003
  9. AMOR B, SANTOS RS, NAHAL R, LISTRAT V, DOUGADOS M. Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol [online] 1994; 21: 1883-1887. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7837155
  10. MARTIN TM, SMITH JR, ROSENBAUM JT. Anterior uveitis: current concepts of pathogenesis and interactions with the spondyloarthropathies. Curr Opin Rheumatol [online] 2002; 14: 337-341. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12118164
  11. CALIN A, PORTA J, FRIES JF, SCHURMAN DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA 1977; 237: 2613-2614. http://www.ncbi.nlm.nih.gov/pubmed/140252
  12. DENNIS MCGONAGLE , WAYNE GIBBON, PAUL EMERY, Classification of inflammatory arthritis by enthesitis. The Lancet, [online] 3 October 1998: 352(9134): 1137 – 1140. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(97)12004-9
  13. PEDRO MACHADO, ROBERT LANDEWÉ, JÜRGEN BRAUN, XENOFON BARALIAKOS, KAY-GEERT A HERMANN, BENJAMIN HSU, DANIEL BAKER, DÉSIRÉE VAN DER HEIJDE. Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype. Ann Rheum Dis [online] 19 February 2013 [viewed 31 March 2014] Available from: doi:10.1136/annrheumdis-2012-202922
  14. RUDWALEIT M, BAETEN D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol. [online] 2006 Jun;20(3):451-71. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16777576
  15. SHARP J. The differential diagnosis of ankylosing spondylitis. Proc R Soc Med. [online] May 1966; 59(5): 453–455. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1900856/?page=2

Examination

Fact Explanation
Reduced chest expansion Reduction of the chest expansion lower than the expected range is one of the diagnostic criterion for ankylosing spondylitis. This occurs in the latter stages of the disease and it is due to the chronic inflammation of the costochondral and manubrio-sternal joints. [1]
Tenderness at the sites of enthesitis Enthesitis causes tenderness at the sites of inflammation of tendon insertion. [2,7]
Positive Schober test The midpoint of the two posterior superior iliac spines is marked. Then the point 10cm vertically above is also marked when the patient is standing. The patient is asked to bend forward when the patient is in maximal forward flexion, the distance between the above marked points is measured. In patients with ankylosing spondylitis the distance is less than 15cm. [5] The limitation of the flexion is due to the syndesmophyte formation and the development of ankylosis of the lumbar vertebrae. [5]
Stooped posture The chronic inflammation of the vertebral joints causes ankylosis. Ankylosis fixes the vertebrae in the flexed position. This markedly reduces the range of movement of the spine. Stooped posture results due to long standing disease so commonly seen in elderly patients.
Positive straight leg raising test This is due to the ankylosis of the lumbar vertebrae.
Signs of uveitis Erythema, soreness, photophobia and constricted pupil are examination findings. [4]
Psoriatic skin lesions Psoriasis causes erythematous, silver color skin plaques. [3]
Signs of aortic regurgitation These include bounding pulse, increased pulse pressure, diastolic murmur over the aortic area of the precordium and other peripheral signs of aortic regurgitation. (Eg: de Musset’s sign, Quincke’s sign, Muller’s sign) [6]
Features of cauda equina syndrome Patients present with bladder, bowel, or sexual dysfunction with saddle back anesthesia. [9]
References
  1. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  2. DENNIS MCGONAGLE , WAYNE GIBBON, PAUL EMERY, Classification of inflammatory arthritis by enthesitis. The Lancet, [online] 3 October 1998: 352(9134): 1137 – 1140. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(97)12004-9
  3. PEDRO MACHADO, ROBERT LANDEWÉ, JÜRGEN BRAUN, XENOFON BARALIAKOS, KAY-GEERT A HERMANN, BENJAMIN HSU, DANIEL BAKER, DÉSIRÉE VAN DER HEIJDE. Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype. Ann Rheum Dis [online] 19 February 2013 [viewed 31 March 2014] Available from: doi:10.1136/annrheumdis-2012-202922
  4. American Optometric association. Anterior Uveitis. [viewed 31 March 2014] Available from: https://www.aoa.org/patients-and-public/eye-and-vision-problems/glossary-of-eye-and-vision-conditions/anterior-uveitis
  5. ZOCHLING J., BRAUN J. Assessment of ankylosing spondylitis. Clin Exp Rheumatol [online] 2005; 23 (39): S133-S14. [viewed 31 March 2014] Available from: http://www.clinexprheumatol.org/article.asp?a=2698..
  6. RAFFI B., PAUL A., GRAYBURN, Aortic Regurgitation. Circulation. [online] 2005; 112: 125-134. [viewed 31 March 2014] Available from: doi: 10.1161/​CIRCULATIONAHA.104.488825
  7. VAN D. L. S., VAN D. H. D. Ankylosing spondylitis. Clinical features. Rheum Dis Clin North Am. [online] Nov 1998;24(4):663-76, vii. [viewed 31 March 2014]
  8. JESSE N. B., The Lasègue Test. JAMA. [online] 1967;201(8):641. [viewed 31 March 2014] Available from: doi:10.1001/jama.1967.03130080083032.
  9. CHRIS L., ANDREW J., JAMES W.M., JEREMY F. BMJ [online] 2009; 338 [viewed 31 March 2014] Available from: doi: http://dx.doi.org/10.1136/bmj.b936

Differential Diagnoses

Fact Explanation
Reactive Arthritis (Reiter's syndrome) Characteristic triad of peripheral arthritis, urethritis and/or cervicitis and conjunctivitis. [1]
Tuberculous artheritis [3] Raised inflammatory markers and involvement of the large joints are in favor of tuberculous arthritis.
Rheumatic fever [3] Migrating oligoarthritis with a history of sorethroat are in favor of rheumatic fever. Ankylosing spondylitis involves sacroiliac joints and it helps in differentiating the two. [3]
Rheumatoid arthritis [3] Extra-articular manifestations like rheumatoid nodules and main involvement of large pheripheral joints and small joints in the hand are features of rheumatoid arthritis. [4]
Osteoarthritis [3] Osteoarthritis mainly involves weight bearing joints.
Psoriatic Arthritis [3] Skin lesions will also be seen.
References
  1. WILLKENS RF, ARNETT FC, BITTER T, CALIN A, FISHER L, FORD DK: Reiter's syndrome: evaluation of preliminary criteria for definite disease. Arthritis Rheum [online] 1981, 24:844-849. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7247978?dopt=Abstract&holding=f1000,f1000m,isrctn
  2. MARTIN TM, SMITH JR, ROSENBAUM JT. Anterior uveitis: current concepts of pathogenesis and interactions with the spondyloarthropathies. Curr Opin Rheumatol [online] 2002; 14: 337-341. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12118164
  3. SHARP J. The differential diagnosis of ankylosing spondylitis. Proc R Soc Med. [online] May 1966; 59(5): 453–455. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1900856/?page=2

Investigations - for Diagnosis

Fact Explanation
X-ray Osteo-proliferation [3] presence of syndesmophytes and ankylosis decreased bone density are radiological features. In the latter part of the illness pathological fractures can be seen. [4] Presence of bilateral sacroiliitis of grade two or more or unilateral sacroiliitis of grade 3—4 are radiological diagnostic criteria. [1] Presence of radiological evidence and one clinical condition is diagnostic. [5]
MRI This enables the early detection of the disease, well before the sacroilitis is evident in the X-ray film. [7]
Computer tomography (CT) CT is able to detect the chronic sacroilitis. [10]
C-reactive protein (CRP)[8] Raised due to the inflammatory process. However only about half of the patients will have raises CRP. [9]
MHC class I molecule [1,8] The presence of this molecule is more predictive of the disease than the HLA-B27. [5,6]
HLA B27 [1] Presence of HLA-B27 is associated with increased risk of cardiac complications. [2]
Erythrocyte Sedimentation Rate (ESR) Raised due to inflammation. This has limited use in the diagnosis. [1]
References
  1. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  2. LAUTERMANN D, BRAUN J. Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol [online] 2002; 20 (suppl 28): S11-S15. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12463440
  3. KARBERG K, ZOCHLING J, SIEPER J, FELSENBERG D, BRAUN J. Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol [online] 2005; 32: 1290-1298. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15996067
  4. COOPER C, CARBONE L, MICHET CJ, ATKINSON EJ, O'FALLON WM, MELTON LJ. Fracture risk in patients with ankylosing spondylitis: a population based study. J Rheumatol [online] 1994; 21: 1877-1882. [viewed 31 March 2014] Available from: : http://www.ncbi.nlm.nih.gov/pubmed/7837154
  5. VAN DER LINDEN S, VALKENBURG HA, CATS A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum [online] 1984; 27: 361-368. [viewed 31 March 2014] Available from: DOI: 10.1002/art.1780270401
  6. BROWN MA, KENNEDY LG, MACGREGOR AJ, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum [online] 1997; 40: 1823-1828. [viewed 31 March 2014] Available from: doi:10.1002/1529-0131(199710)40:10<1823::AID-ART15>3.0.CO;2-1
  7. BRAUN J, BOLLOW M, NEURE L, ET AL. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum [online] 1995; 38: 499-505. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7718003
  8. RUDWALEIT M, VAN DER HEIJDE D, KHAN MA, BRAUN J, SIEPER J. How to diagnose axial spondyloarthritis early. Ann Rheum Dis [online] 2004; 63: 535-543. [viewed 31 March 2014] Available from: doi:10.1136/ard.2003.011247
  9. SPOORENBERG A, VAN DER HEIJDE D, DE KLERK E, et al. Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol [online] 1999; 26: 980-984. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10229432
  10. VAN TUBERGEN A, HEUFT-DORENBOSCH L, SCHULPEN G, et al. Radiographic assessment of sacroiliitis by radiologists and rheumatologists: does training improve quality?. Ann Rheum Dis [online] 2003; 62: 519-525. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12759287

Investigations - Followup

Fact Explanation
X-ray This is useful and more sensitive in detecting the structural progression of the chronic disease than the MRI. [5]
Magnetic resonance imaging (MRI) This detects even mild improvement in inflammation and is the investigation of choice in follow up of the patients who are taking antiTNF (Tumor Necrosis Factor) therapy. [3,4]
Ultrasonography This detects the associated joint complications like enthesitis and synovitis better than the MRI. [6]
Computer tomography (CT) CT is able to detect the chronic sacroilitis. However since the risk of radiation is high this is not practiced routinely.[7]
Echocardiogram Detects aortic root involvement. [1] Aortitis and aortic regurgitation are possible complications. [2]
ECG Detects conduction abnormalities [1,2]
References
  1. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  2. LAUTERMANN D, BRAUN J. Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol [online] 2002; 20 (suppl 28): S11-S15. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12463440
  3. 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 [online] 2003; 48: 1126-1136. [viewed 31 March 2014] Available from: doi:10.1002/art.10883
  4. BRAUN J, LANDEWE 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 [online] 2006; 54: 1646-1652. [viewed 31 March 2014] Available from: doi:10.1002/art.21790
  5. HEUFT-DORENBOSCH L, LANDEWE R, WEIJERS R, et al. Combining information obtained from magnetic resonance imaging and conventional radiographs to detect sacroiliitis in patients with recent onset inflammatory back pain. Ann Rheum Dis [online] 2006; 65: 804-808. [viewed 31 March 2014] Available from: doi:10.1136/ard.2005.044206
  6. BALINT PV, KANE D, WILSON H, MCINNES IB, STURROCK RD. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis [online] 2002; 61: 905-910. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12228161
  7. VAN TUBERGEN A, HEUFT-DORENBOSCH L, SCHULPEN G, et al. Radiographic assessment of sacroiliitis by radiologists and rheumatologists: does training improve quality?. Ann Rheum Dis [online] 2003; 62: 519-525. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12759287

Investigations - Screening/Staging

Fact Explanation
MRI Able to detect the early disease. Also used on screening of asymptomatic patients. [1]
References
  1. HERMANN KG, LANDEWE 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 [online] 2005; 32: 2056-2060. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16206370

Management - General Measures

Fact Explanation
Education Education about the disease and the treatment options is essential. [1]
Psychological support This is a chronic and debilitating disease. [1] Younger the age at the time of diagnosis severe the disease course and results in worse functional status. [2]
Exercise [5] Limits the stiffness and improves the functional outcome.
Spa treatment This is considered a better option than the self-monitored exercise programs. [6]
Corrective surgery of aortic regurgitation [3] Aortic valve replacement is the preferred treatment method of aortic regurgitation. [4]
Treatment of cardiac complications Management of conduction disturbances may need pacemaker implantation. [3]
References
  1. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  2. STONE M, WARREN RW, BRUCKEL J, COOPER D, CORTINOVIS D, INMAN RD. Juvenile-onset ankylosing spondylitis is associated with worse functional outcomes than adult-onset ankylosing spondylitis. Arthritis Rheum [online] 2005; 53: 445-451. [viewed 31 March 2014] Available from: DOI: 10.1002/art.21174
  3. LAUTERMANN D, BRAUN J. Ankylosing spondylitis—cardiac manifestations. Clin Exp Rheumatol [online] 2002; 20 (suppl 28): S11-S15. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12463440
  4. Guidelines for the Management of Patients With Valvular Heart Disease. Circulation. [online] 1998; 98: 1949-1984. [viewed 31 March 2014] Available from: http://circ.ahajournals.org/content/98/18/1949.long
  5. KRAAG G, STOKES B, GROH J, HELEWA A, GOLDSMITH C. The effects of comprehensive home physiotherapy and supervision on patients with ankylosing spondylitis—a randomized controlled trial. J Rheumatol [online] 1990; 17: 228-233. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2181127
  6. VAN TUBERGEN A, LANDEWE R, VAN DER HEIJDE D, et al. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial. Arthritis Rheum [online] 2001; 45: 430-438. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11642642

Management - Specific Treatments

Fact Explanation
Non-steroidal anti-inflammatory agents [1] These drugs inhibit the synthesis of prostaglandin E2 and reduce the inflammatory process. [2] Both non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors are used in the treatment. NSAIDs have shown to arrest the radiological progression of the disease,[3] and the osteophyte formation. [4] Poor response to NSAIDs is recognized an indicator of poor prognosis of the disease. [5]
Disease-modifying antirheumatic drugs (DMARDs) Generally DMARDs are not much effective in the treatment of the ankylosing spondylitis. [1] However sulfasalazine is proven to improve peripheral arthritis, but there is no significant improvement in back pain. [6] Leflunomide is proven to improve peripheral arthritis. [7]
Physiotherapy [1] Improves the functional status of the patient.
Tumor necrosis factor blockers [1] Infliximab is the commonly used drug in this group. [8]
Joint replacement surgery When the hip joint damage adversely affects the mobility of the patient joint replacement surgery is an option. [1]
References
  1. JURGEN B., JOACHIM S. Ankylosing spondylitis. The Lancet [online] 21 April 2007: 369 (9570) 1379 – 1390. [viewed 31 March 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  2. RADI ZA, KHAN NK. Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing. Inflamm Res [online] 2005; 54: 358-366. [viewed 31 March 2014] Available from: doi:10.1007/s00011-005-1367-4
  3. 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 [online] 2005; 52: 1756-1765. [viewed 31 March 2014] Available from: doi:10.1002/art.21054
  4. BARTHEL T, BAUMANN B, NOTH U, EULERT J. Prophylaxis of heterotopic ossification after total hip arthroplasty: a prospective randomized study comparing indomethacin and meloxicam. Acta Orthop Scand [online] 2002; 73: 611-614. [viewed 31 March 2014] Available from: doi:10.1080/000164702321039543
  5. AMOR B, SANTOS RS, NAHAL R, LISTRAT V, DOUGADOS M. Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol [online] 1994; 21: 1883-1887. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7837155
  6. DOUGADOS M, VAM DER LINDEN S, LEIRISALO-REPO M, et al. Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study. Arthritis Rheum [online] 1995; 38: 618-627. [viewed 31 March 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7748217
  7. HAIBEL H, RUDWALEIT M, BRAUN J, SIEPER J. Six months open label trial of leflunomide in active ankylosing spondylitis. Ann Rheum Dis [online] 2005; 64: 124-126. [viewed 31 March 2014] Available from: doi:10.1136/ard.2003.019174
  8. HEIBERG MS, NORDVAG BY, MIKKELSEN K, et al. The comparative effectiveness of tumor necrosis factor-blocking agents in patients with rheumatoid arthritis and patients with ankylosing spondylitis: a six-month, longitudinal, observational, multicenter study. Arthritis Rheum [online] 2005; 52: 2506-2512. [viewed 31 March 2014] Available from: doi:10.1002/art.21209