Ankylosing spondylitis

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Ankylosing spondylitis
Classification and external resources
0510 Spondylitis ankylosans (morbus bechterew) anagoria.JPG
An ankylosing spine in which the vertebrae become fused together.
ICD-10 M08.1, M45
ICD-9 720.0
OMIM 106300
DiseasesDB 728
MedlinePlus 000420
eMedicine radio/41
MeSH D013167

Ankylosing spondylitis (AS, from Greek ankylos, fused; spondylos, vertebra; -itis, inflammation), previously known as Bechterew's disease (or syndrome) and Marie-Strümpell disease, is a chronic inflammatory disease of the axial skeleton, with variable involvement of peripheral joints and nonarticular structures. AS is a member of the group of the spondyloarthropathies,[1] with a strong genetic predisposition.[1] It mainly affects joints in the spine and the sacroiliac joint in the pelvis. In severe cases, it can eventually cause complete fusion and rigidity of the spine. [2]

"Bamboo spine" develops when the outer fibers of the fibrous ring of the intervertebral disks ossify, which results in the formation of marginal syndesmophytes between adjoining vertebrae.

It usually begins in the second or third decade of life and tends to occur more often in males.

Signs and symptoms[edit]

Illustration depicting Ankylosing Spondylitis.
  • Symptoms appear gradually, most commonly between 15 and 25 years of age.[1]
  • Sacroiliitis is usually one of the earliest manifestation of AS. The initial symptom is usually a typical chronic dull pain, insidious in onset, felt deep in the lower lumbar or gluteal region, accompanied by low-back morning stiffness. It can occur in in the middle part of the spine or the entire spine, often with pain referred to one or the other buttock or the back of the thigh from the sacroiliac joint.
  • Pain is often severe at rest, but improves with physical activity. However, many experience inflammation and pain to varying degrees regardless of rest and movement.
  • Enthesopathy: Ankylosing spondylitis is one of a cluster of conditions known as seronegative spondyloarthropathies, in which rheumatoid factor tests are negative and the characteristic pathological lesion is an inflammation of the enthesis (the insertion of tensile connective tissue into bone).
  • Since the initial signs and symptoms are not specific for ankylosing spondylitis, there is a lag-time between onset of disease and diagnosis, which averages between 8.5 years and 11.4 years.[3]
  • Arthritis in the hips and shoulders may occur.
  • The most common extraarticular manifestation is acute anterior uveitis which can antedate the spondylitis. About 40 percent of AS patients experience inflammation in the anterior chamber of the eye (uveitis), causing redness, eye pain, floaters and photophobia. Visual acuity is usually maintained and the fundus is normal. This is thought to be due to the association that both AS and uveitis have with the inheritance of the HLA-B27 antigen.
  • Loss of spinal mobility, with limitation of anterior flexion, lateral flexion, and extension of the lumbar spine, is seen.
  • The Schober test: It is a useful measure of forward flexion of the lumbar spine. It is reduced in AS.
  • Pulmonary involvement, is characterized by slowly progressive apical lung fibrosis. There is limitation of chest expansion. Recurrent chest infection is the most common cause of death.
  • Aortitis, aortic valve insufficiency or cardiac conduction disturbances.
  • Prostatitis occurs with increased frequency in men.
  • The most serious complication of the spinal disease is spinal fracture, which can occur with even minor trauma to the rigid, osteoporotic spine.
  • Mortality attributable to AS is largely the result of spinal trauma, aortic insufficiency, respiratory failure, amyloid nephropathy, or complications of therapy such as upper gastrointestinal hemorrhage.
  • Other common symptoms of AS include: chest pain and generalized fatigue. Less commonly ectasia of the sacral nerve root sheaths may occur.
  • When the condition presents before the age of 18, it is relatively likely to cause pain and swelling of large limb joints, particularly the knee. In prepubescent cases, pain and swelling may also manifest in the ankles and feet, where calcaneal spurs may also develop.

Pathophysiology[edit]

The ankylosis process

Ankylosing spondylitis (AS) is a systemic rheumatic disease, meaning it affects the entire body. Approximately 90% of AS patients express the HLA-B27 genotype, meaning there is a strong genetic association. 1-2% of individuals with the HLA-B27 genotype contract the disease.[1] Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with AS, but do not correlate with disease severity.[citation needed] In a study of 40 patients with AS, ANCA was an infrequent finding, being present in six patients.[4]

The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B.[citation needed] This interaction is not proven to involve a self antigen, and at least in the related Reiter's syndrome (reactive arthritis), which follows infections, the antigens involved are likely to be derived from intracellular microorganisms.[citation needed] There is, however, a possibility that CD4 T cells are involved in an aberrant way, since HLA-B27 appears to have a number of unusual properties, including possibly an ability to interact with T cell receptors in association with CD4 (usually cytotoxic T lymphocytes with CD8 react with HLAB antigen as it is a MHC class 1 antigen).

In 2001, it was suggested that AS arises from a cross-reaction between HLA-B27 and antigens of the Klebsiella bacterial genus.[5] There is evidence such cross reactivity with B27 as well as collagen fibers I,III, and IV in those patients suffering from AS.[6] Some authorities argue that the elimination of the prime nutrients of Klebsiella (i.e. starches) would decrease antigenemia and improve the musculoskeletal symptoms. However, as Khan (2002) argues, evidence for a correlation between Klebsiella and AS is circumstantial so far, and the efficacy of low-starch diets has not yet been scientifically evaluated.[7] Studies on low-starch diet and AS could be difficult to fund; new biologics developed by the pharmaceutical industry may demonstrate efficacy, as well as financial benefit to the industry, whereas changing the diet would not. A randomized controlled trial in Turkey demonstrated that 12-week therapy with moxifloxacin (which would kill Klebsiella) resulted in "significant and sustained improvement" in inflammatory symptoms in patients with ankylosing spondylitis.[8]

Toivanen (1999) found no support for the role of Klebsiella in the etiology of primary AS.[9]

Diagnosis[edit]

T1-weighted MRI with fat suppression after administration of gadolinium contrast showing sacroiliitis in a patient with ankylosing spondylitis
X-ray showing bamboo spine in a patient with ankylosing spondylitis.
CT scan showing Bamboo spine in ankylosing spondylitis

There is no direct test to diagnose AS. A clinical examination, magnetic resonance imaging (MRI), and X-ray studies of the spine, which show characteristic spinal changes and sacroiliitis, combined with a genetic marker blood test are the major diagnostic tools.

Radiographic features[edit]

  • The earliest changes in the sacroiliac joints demonstrable by plain x–ray shows erosions and sclerosis.
  • Progression of the erosions leads to pseudo widening of the joint space and bony ankylosis.
  • X-ray spine can reveal bamboo spine appearance.
  • A drawback of X-ray diagnosis is the signs and symptoms of AS have usually been established as long as 8–10 years prior to X-ray-evident changes occurring on a plain film X-ray, which means a delay of as long as 10 years before adequate therapies can be introduced. Options for earlier diagnosis are tomography and MRI of the sacroiliac joints, but the reliability of these tests is still unclear.
  • The Schober's test is a useful clinical measure of flexion of the lumbar spine performed during examination.[10]

Blood parameters[edit]

During acute inflammatory periods, AS patients will sometimes show an increase in the blood concentration of C-reactive protein (CRP) and an increase in the erythrocyte sedimentation rate (ESR), but there are many with AS whose CRP and ESR rates do not increase, so normal CRP and ESR results do not always correspond with the amount of inflammation that is actually present. In other words, some people with AS have normal levels of CRP and ESR, despite experiencing a significant amount of inflammation in their bodies.

Genetic testing[edit]

Variations of the HLA-B gene increase the risk of developing ankylosing spondylitis, although it is not a diagnostic test. Those with the HLA-B27 variant are at a higher risk than the general population of developing the disorder. HLA-B27, demonstrated in a blood test, can occasionally help with diagnosis, but in itself is not diagnostic of AS in a person with back pain. Over 95% of people that have been diagnosed with AS are HLA-B27 positive, although this ratio varies from population to population (about 50% of African American patients with AS possess HLA-B27, and it is close to 80% among AS patients from Mediterranean countries). In early onset disease HLA-B7/B*2705 heterozygotes exhibited the highest risk for disease.[11]

BASDAI[edit]

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), developed in Bath (UK), is an index designed to detect the inflammatory burden of active disease. The BASDAI can help to establish a diagnosis of AS in the presence of other factors such as HLA-B27 positivity, persistent buttock pain which resolves with exercise, and X-ray or MRI evident involvement of the sacroiliac joints. (See: "Diagnostic Tools", below)[12] It can be easily calculated and accurately assesses a patient's need for additional therapy; a patient with a score of four out of a possible 10 points while on adequate NSAID therapy is usually considered a good candidate for biologic therapy.

The Bath Ankylosing Spondylitis Functional Index (BASFI) is a functional index which can accurately assess a patient's functional impairment due to the disease, as well as improvements following therapy. (See: "Diagnostic Tools", below)[13] The BASFI is not usually used as a diagnostic tool, but rather as a tool to establish a patient's current baseline and subsequent response to therapy.

Treatment[edit]

There is no cure for AS, although treatments and medications can reduce symptoms and pain.[14][15]

Medication[edit]

The major types of medications used to treat ankylosing spondylitis are pain-relievers and drugs aimed at stopping or slowing the progression of the disease. Pain-relieving drugs come in two major classes:

Drugs used to treat the progression of the disease include:

  • Disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine can be used in patients with peripheral arthritis. For axial involvement, sulfasalazine is less effective. Other DMARDS, such as methotrexate did not have enough evidence to prove their effect. Generally, systemic corticosteroids were not used due to lack of evidence. Local injection with corticosteroid can be used for selected patients with peripheral arthritis.[17][18][19]

Surgery[edit]

In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky.

In addition, AS can have some manifestations which make anaesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anaesthesia may be difficult owing to calcification of ligaments, and a small number of patients have aortic insufficiency. The stiffness of the thoracic ribs results in ventilation being mainly diaphragm-driven, so there may also be a decrease in pulmonary function.

Physical therapy[edit]

Though physical therapy remedies have been scarcely documented, some therapeutic exercises are used to help manage lower back, neck, knee, and shoulder pain. Some therapeutic exercises include:[23][24]

Low intensity aerobic exercises have shown to have profound positive effects regarding pulmonary function, quality of life, and functional capacity.[25]

Spa treatments utilizing thermal baths coupled with tumor necrosis factor inhibitors (TNF) have shown a long-term improvement in AS patients.[26] Spa treatments coupled with TNF inhibitors have no disease relapse among AS patients.[26]

Moderate-to-high impact exercises like jogging are generally not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some patients.

Prognosis[edit]

Prognosis is related to disease severity.[1] AS can range from mild to progressively debilitating and from medically controlled to refractory. Some cases may have times of active inflammation followed by times of remission resulting in minimal disability, while others never have times of remission and have acute inflammation and pain, leading to significant disability.[1] Complete fusion of the spine can lead to a reduced range of motion and increased pain, as well as total joint destruction which could lead to a joint replacement.[27]

Over a long-term period, osteopenia or osteoporosis of the AP spine may occur, causing eventual compression fractures and a back "hump". Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. The fusion of the vertebrae paresthesia is a complication due to the inflammation of the tissue surrounding nerves.

Organs commonly affected by AS, other than the axial spine and other joints, are the heart, lungs, eyes, colon, and kidneys. Other complications are aortic regurgitation, Achilles tendinitis, AV node block and amyloidosis.[28] Owing to lung fibrosis, chest X-rays may show apical fibrosis, while pulmonary function testing may reveal a restrictive lung defect. Very rare complications involve neurologic conditions such as the cauda equina syndrome.[28][29]

Mortality[edit]

Mortality is increased in patients with AS and circulatory disease is the most frequent cause of death;[30] and because increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting patient outcome include:[30][31]

  • Male gender
  • Plus 3 of the following in the first 2 years of disease:

Effect on Gait[edit]

The hunched position that often results from complete spinal fusion can have an effect on a person’s gait. Increased spinal kyphosis will lead to a forward and downward shift in center of mass (COM). This shift in COM has been shown to be compensated by increased knee flexion and ankle plantarflexion. The gait of someone with ankylosing spondylitis often has a cautious pattern because they have decreased ability to absorb shock, and they cannot see the horizon.[32]

Research[edit]

In 2007, a collaborative effort by an international team of researchers in the United Kingdom, Australia and the United States led to the discovery of two genes that also contribute to the cause of AS: ARTS-1 and IL23R. The findings were published in the November 2007 edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases.[33] Together with HLA-B27, these two genes account for roughly 70 percent of the overall incidence of the disease.

Epidemiology[edit]

The overall prevalence of AS is between 0.1 and 0.2 percent of the general population.[1] The disease is most prevalent in Northern European countries, and seen least in people of Afro-Caribbean descent.[1] It is more commonly diagnosed in men, with two males being diagnosed for every one female[34] though the sex differences may be higher in some populations.[35] Many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease.[36] The majority of AS patients, including 95 percent of white patients, express the HLA-B27 antigen[37] and high levels of immunoglobulin A (IgA) in the blood. The onset of the disease is typically between 15 and 25 years of age.[37]

Risk factors for ankylosing spondylitis are a family history of spondyloarthritis, the presence of the antigen HLA-B2.[38] in the body, as well as various environmental factors. One's risk of developing the disease increases by 16% when they have one or more of these factors.[38] As the disease progresses, it can cause the vertebrae and the lumbosacral joint to ossify, resulting in the fusion of the spine.[39] This places the spine in a vulnerable state because it becomes one bone, which causes it to lose its range of motion as well as putting it at risk for spinal fractures. This not only limits mobility but reduces the affected person's quality of life.

History[edit]

AS has a long history, having been distinguished from rheumatoid arthritis by Galen as early as the second century AD.[40] Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was found in an archaeological dig that unearthed the skeletal remains of a 5000-year–old Egyptian mummy with evidence of bamboo spine.[41]

The anatomist and surgeon Realdo Colombo described what could have been the disease in 1559,[42] and the first account of pathologic changes to the skeleton possibly associated with AS was published in 1691 by Bernard Connor.[43] In 1818, Benjamin Brodie became the first physician to document a patient believed to have active AS who also had accompanying iritis.[44]

In 1858, David Tucker published a small booklet which clearly described a patient, Leonard Trask, who suffered from severe spinal deformity subsequent to AS.[45] In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:

It was not until he [Trask] had exercised for some time that he could perform any labor ... [H]is neck and back have continued to curve drawing his head downward on his breast.

This account became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS.

It was not until the late nineteenth century, however, when the neurophysiologist Vladimir Bekhterev of Russia in 1893,[46] Adolph Strümpell of Germany in 1897,[47] and Pierre Marie of France in 1898[48] were the first to give adequate descriptions which permitted an accurate diagnosis of AS prior to severe spinal deformity. For this reason, AS is also known as Bekhterev Disease, Bechterew's Disease or Marie–Strümpell Disease.

See also[edit]

References[edit]

  1. ^ a b c d e f g h "Ankylosing Spondylitis -Professional reference for Doctors - Patient UK". Patient UK. Retrieved 26 May 2014. 
  2. ^ Jiménez-Balderas FJ, Mintz G (1993). "Ankylosing spondylitis: clinical course in women and men". J Rheumatol 20 (12): 2069–72. PMID 7516975. 
  3. ^ Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J (2003). "Age at disease onset and diagnosis delay in HLA-B27 negative vs. Positive patients with ankylosing spondylitis". Rheumatology international 23 (2): 61–66. doi:10.1007/s00296-002-0237-4 (inactive 2014-05-05). PMID 12634937. 
  4. ^ Locht H, Skogh T, Kihlström E (1999). "Anti-lactoferrin antibodies and other types of anti-neutrophil cytoplasmic antibodies (ANCA) in reactive arthritis and ankylosing spondylitis". The Journal of Clinical & Experimental Immunology 117 (3): 568–569. doi:10.1046/j.1365-2249.1999.01008.x. PMC 1905360. PMID 10469064. 
  5. ^ Tiwana H, Natt RS, Benitez-Brito R, Shah S, Wilson C, Bridger S, Harbord M, Sarner M, Ebringer A (2001). "Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis". Rheumatology (Oxford) 40 (1): 15–23. doi:10.1093/rheumatology/40.1.15. PMID 11157137. 
  6. ^ Rashid, Taha. "The Link between Ankylosing Spondylitis, Crohn’s Disease, Klebsiella, and Starch Consumption". Journal of Immunology Research. 
  7. ^ Khan MA. (2002). Ankylosing spondylitis: The facts. Oxford University Press. ISBN 0-19-263282-5. 
  8. ^ Ogrendik M (2007). "Treatment of ankylosing spondylitis with moxifloxacin.". Southern Medical Journal 100 (4): 366–70. doi:10.1097/smj.0b013e31802fa2a8. PMID 17458395. 
  9. ^ Toivanen P, Hansen DS, Mestre F, Lehtonen L, Vaahtovuo J, Vehma M, Möttönen T, Saario R, Luukkainen R, Nissilä M (1 September 1999). "Somatic serogroups, capsular types, and species of fecal Klebsiella in patients with ankylosing spondylitis". J Clin Microbiol 37 (9): 2808–12. PMC 85385. PMID 10449457. 
  10. ^ Thomas E, Silman AJ, Papageorgiou AC, Macfarlane GJ, Croft PR (1998). "Association between measures of spinal mobility and low back pain. An analysis of new attenders in primary care". Spine 23 (2): 343–7. doi:10.1097/00007632-199802010-00011. PMID 9507623. 
  11. ^ Harjacek M, Margetić T, Kerhin-Brkljacić V, Martinez N, Grubić Z (2008). "HLA-B*27/HLA-B*07 in combination with D6S273-134 allele is associated with increased susceptibility to juvenile spondyloarthropathies". Clin. Exp. Rheumatol. 26 (3): 498–504. PMID 18578977. 
  12. ^ Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994). "A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index". J Rheumatol 21 (12): 2286–91. PMID 7699630. 
  13. ^ Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T (1994). "A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index". J Rheumatol 21 (12): 2281–5. PMID 7699629. 
  14. ^ Toivanen A, Möttönen T (1998). "Ankylosing spondylitis: current approaches to treatment". BioDrugs 10 (3): 193–200. doi:10.2165/00063030-199810030-00003. PMID 18020595. 
  15. ^ Williams RO, Paleolog E, Feldmann M (2007). "Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases". Curr Opin Pharmacol 7 (4): 412–7. doi:10.1016/j.coph.2007.06.001. PMID 17627887. 
  16. ^ Kroon F, Landewé R, Dougados M, van der Heijde D (October 2012). "Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis". Ann. Rheum. Dis. 71 (10): 1623–9. doi:10.1136/annrheumdis-2012-201370. PMID 22532639. 
  17. ^ Chen J, Veras MM, Liu C, Lin J (Feb 28, 2013). "Methotrexate for ankylosing spondylitis.". The Cochrane database of systematic reviews 2: CD004524. doi:10.1002/14651858.CD004524.pub4. PMID 23450553. 
  18. ^ Chen J, Liu C (Apr 18, 2005). "Sulfasalazine for ankylosing spondylitis.". The Cochrane database of systematic reviews (2): CD004800. doi:10.1002/14651858.CD004800.pub2. PMID 15846731. 
  19. ^ Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, Dagfinrud H, Dijkmans B, Dougados M, Emery P, Geher P, Hammoudeh M, Inman RD, Jongkees M, Khan MA, Kiltz U, Kvien T, Leirisalo-Repo M, Maksymowych WP, Olivieri I, Pavelka K, Sieper J, Stanislawska-Biernat E, Wendling D, Ozgocmen S, van Drogen C, van Royen B, van der Heijde D (June 2011). "2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis". Ann. Rheum. Dis. 70 (6): 896–904. doi:10.1136/ard.2011.151027. PMC 3086052. PMID 21540199. 
  20. ^ Braun J, Sieper J (2007). "Ankylosing spondylitis". Lancet 369 (9570): 1379–90. doi:10.1016/S0140-6736(07)60635-7. PMID 17448825. 
  21. ^ Brulhart L, Nissen MJ, Chevallier P, Gabay C (February 2010). "Mixed response to tocilizumab for ankylosing spondylitis". Annals of the Rheumatic Diseases 69 (12): 2217–2218. doi:10.1136/ard.2009.126706. PMID 20851032. 
  22. ^ Rodríguez-Escalera C, Fernández-Nebro A (2008). "The use of rituximab to treat a patient with ankylosing spondylitis and hepatitis B". Rheumatology 47 (11): 1732–1733. doi:10.1093/rheumatology/ken362. PMID 18786966. 
  23. ^ "Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions: overview and methodology". Phys Ther 81 (10): 1629–40. 2001. PMID 11589641. 
  24. ^ Dagfinrud H, Kvien TK, Hagen KB (Jan 23, 2008). "Physiotherapy interventions for ankylosing spondylitis.". The Cochrane database of systematic reviews (1): CD002822. doi:10.1002/14651858.CD002822.pub3. PMID 18254008. 
  25. ^ Ortancil O, Sarikaya S, Sapmaz P, Basaran A, Ozdolap S (2009). "The effect(s) of a six-week home-based exercise program on the respiratory muscle and functional status in ankylosing spondylitis". J Clin Rheumatol 15 (2): 68–70. doi:10.1097/RHU.0b013e31819b5ed0. PMID 19265348. 
  26. ^ a b Ciprian L, Lo Nigro A, Rizzo M, Gava A, Ramonda R, Punzi L, Cozzi F (2013). "The effects of combined spa therapy and rehabilitation on patients with ankylosing spondylitis being treated with TNF inhibitors". Rheumatol. Int. 33 (1): 241–5. doi:10.1007/s00296-011-2147-9. PMID 21947374. 
  27. ^ Bond D (2013). "Ankylosing spondylitis: diagnosis and management". Nurs Stand 28 (16-18): 52–9; quiz 60. doi:10.7748/ns2013.12.28.16.52.e7807. PMID 24345154. 
  28. ^ a b Alpert, Joseph S. (2006). The AHA Clinical Cardiac Consult. Lippincott Williams & Wilkins. ISBN 0-7817-6490-4. 
  29. ^ Ahn NU, Ahn UM, Nallamshetty L, Springer BD, Buchowski JM, Funches L, Garrett ES, Kostuik JP, Kebaish KM, Sponseller PD (2001). "Cauda Equina Syndrome in AS (The CES-AS Syndrome): Meta-analysis of outcomes after medical and surgical treatments". J of Spinal Disorders 14 (5): 427–433. doi:10.1097/00002517-200110000-00009. PMID 11586143. 
  30. ^ a b Bakland G, Gran JT, Nossent JC (November 2011). "Increased mortality in ankylosing spondylitis is related to disease activity". Ann. Rheum. Dis. 70 (11): 1921–5. doi:10.1136/ard.2011.151191. PMID 21784726. 
  31. ^ Radford EP, Doll R, Smith PG (September 1977). "Mortality among patients with ankylosing spondylitis not given X-ray therapy". N. Engl. J. Med. 297 (11): 572–6. doi:10.1056/NEJM197709152971103. PMID 887115. 
  32. ^ Del Din S, Carraro E, Sawacha Z, Guiotto A, Bonaldo L, Masiero S, Cobelli C (2011). "Impaired gait in ankylosing spondylitis". Med Biol Eng Comput 49 (7): 801–9. doi:10.1007/s11517-010-0731-x. PMID 21229328. 
  33. ^ Brionez TF, Reveille JD (July 2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Curr Opin Rheumatol 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID 18525349. 
  34. ^ Chen, Hsin-Hua; Chen, Tzeng-Ji; Chen, Yi-Ming; Ying-Ming, Chiu; Chen, Der-Yuan. "Gender differences in ankylosing spondylitis-associated cumulative healthcare utilization: a population-based cohort study". Clinics 66 (2): 251–254. doi:10.1590/S1807-59322011000200012. PMC 3059876. 
  35. ^ Gran, JT; Husby, G; Hordvik, M (Jun 1985). "Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromsø, northern Norway.". Annals of the rheumatic diseases 44 (6): 359–67. doi:10.1136/ard.44.6.359. PMC 1001653. PMID 3160312. 
  36. ^ "Arthritis Research Campaign – Ankylosing Spondylitis Case History". Arthritis Research Campaign. 2009. Retrieved 25 August 2009. 
  37. ^ a b Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 607. ISBN 1-4377-2788-3. 
  38. ^ a b van der Linden SM, Valkenburg HA, de Jongh BM, Cats A (1984). "The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population". Arthritis Rheum. 27 (3): 241–9. PMID 6608352. 
  39. ^ Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A (2002). "Ankylosing spondylitis: an overview". Ann. Rheum. Dis. 61 Suppl 3: iii8–18. PMC 1766729. PMID 12381506. 
  40. ^ Dieppe P (1988). "Did Galen describe rheumatoid arthritis?". Annals of the Rheumatic Diseases 47 (1): 84–87. doi:10.1136/ard.47.1.84-b. PMC 1003452. PMID 3278697. 
  41. ^ Calin A (April 1985). "Ankylosing spondylitis". Clin Rheum Dis 11 (1): 41–60. PMID 3158467. 
  42. ^ Benoist M (April 1995). "Pierre Marie. Pioneer investigator in ankylosing spondylitis". Spine 20 (7): 849–52. doi:10.1097/00007632-199504000-00022. PMID 7701402. 
  43. ^ Blumberg BS (December 1958). "Bernard Connor's description of the pathology of ankylosing spondylitis". Arthritis Rheum. 1 (6): 553–63. doi:10.1002/art.1780010609. PMID 13607268. 
  44. ^ Leden I (1994). "Did Bechterew describe the disease which is named after him? A question raised due to the centennial of his primary report". Scand J Rheumatol 23 (1): 42–5. doi:10.3109/03009749409102134. PMID 8108667. 
  45. ^ "Life and sufferings of Leonard Trask" (PDF). Ankylosing Spondylitis Information Matrix. 
  46. ^ Bechterew W. (1893). "Steifigkeit der Wirbelsaule und ihre Verkrummung als besondere Erkrankungsform". Neurol Centralbl 12: 426–434. 
  47. ^ Strumpell A. (1897). "Bemerkung uber die chronische ankylosirende Entzundung der Wirbelsaule und der Huftgelenke". Dtsch Z Nervenheilkd 11 (3–4): 338–342. doi:10.1007/BF01674127. 
  48. ^ Marie P. (1898). "Sur la spondylose rhizomelique". Rev Med 18: 285–315. 

External links[edit]

Diagnostic tools[edit]