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{{Short description|Type of arthritis in which there is long-term inflammation of the joints of the spine}}
{{Short description|Type of arthritis of the spine}}
{{Use dmy dates|date=December 2017}}
{{Use dmy dates|date=December 2017}}
{{Use American English|date=December 2017}}
{{Use American English|date=December 2017}}
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| complications = Eye inflammation (uveitis), Compression fractures, Heart problems.<ref>{{cite web |title=Ankylosing spondylitis |url=https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptoms-causes/syc-20354808 |website=mayoclinic.org |publisher=Mayo Clinic |access-date=June 5, 2022}}</ref>
| complications = Eye inflammation (uveitis), Compression fractures, Heart problems.<ref>{{cite web |title=Ankylosing spondylitis |url=https://www.mayoclinic.org/diseases-conditions/ankylosing-spondylitis/symptoms-causes/syc-20354808 |website=mayoclinic.org |publisher=Mayo Clinic |access-date=June 5, 2022}}</ref>
| onset = Young adulthood<ref name=NIH2016/>
| onset = Young adulthood<ref name=NIH2016/>
| duration = Long term<ref name=NIH2016/>
| duration = Lifetime<ref name=NIH2016/>
| causes = Unknown<ref name=NIH2016/>
| causes = Unknown<ref name=NIH2016/>
| risks =
| risks =
| diagnosis = Symptom based, [[medical imaging]], blood tests<ref name=NIH2016/>
| diagnosis = Symptoms, [[medical imaging]] and blood tests<ref name=NIH2016/>
| differential =
| differential =
| prevention =
| prevention =
| treatment = Medication, exercise, physical therapy
| treatment = Medication, physical therapy
| medication = [[NSAIDs]], [[corticosteroids|steroids]], [[Disease-modifying antirheumatic drug|DMARDs]],<ref name=NIH2016/> TNF Inhibitor
| medication = [[NSAIDs]], [[corticosteroids|steroids]], [[Disease-modifying antirheumatic drug|DMARDs]],<ref name=NIH2016/> TNF Inhibitor
| prognosis =
| prognosis =
| frequency = 0.1 to 0.8%<ref name=Kh2009/>
| frequency = 0.1 to 0.8%<ref name=Kh2009/>
| deaths =
| deaths =
}}
}}
'''Ankylosing spondylitis''' ('''AS''') is a type of [[arthritis]] from the disease spectrum of [[axial spondyloarthritis]].<ref>{{Cite journal |last=Ivanova |first=Mariana |last2=Zimba |first2=Olena |last3=Dimitrov |first3=Ivan |last4=Angelov |first4=Alexander K. |last5=Georgiev |first5=Tsvetoslav |date=2024-09-01 |title=Axial Spondyloarthritis: an overview of the disease |url=https://link.springer.com/article/10.1007/s00296-024-05601-9 |journal=Rheumatology International |language=en |volume=44 |issue=9 |pages=1607–1619 |doi=10.1007/s00296-024-05601-9 |issn=1437-160X}}</ref> It is characterized by long-term [[inflammation]] of the [[joints]] of the [[Vertebral column|spine]], typically where the spine joins the pelvis.<ref name="NIH2016">{{cite web|title=Questions and Answers about Ankylosing Spondylitis|url=http://www.niams.nih.gov/health_info/ankylosing_spondylitis/|website=NIAMS|access-date=28 September 2016|date=June 2016|url-status=dead|archive-url=https://web.archive.org/web/20160928175058/http://www.niams.nih.gov/health_info/ankylosing_spondylitis/|archive-date=28 September 2016|df=dmy-all}}</ref> With AS, eye and [[Gastrointestinal tract|bowel]] problems—as well as back pain—may occur.<ref name="NIH2016" /> Joint mobility in the affected areas sometimes worsens over time.<ref name="NIH2016" /><ref>{{cite web|title=Ankylosing spondylitis|url=https://rarediseases.info.nih.gov/diseases/9518/ankylosing-spondylitis|website=GARD|access-date=28 September 2016|date=9 February 2015|url-status=live|archive-url=https://web.archive.org/web/20161002084025/https://rarediseases.info.nih.gov/diseases/9518/ankylosing-spondylitis|archive-date=2 October 2016|df=dmy-all}}</ref>
<!-- Definition and symptoms -->
Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors.<ref name="NIH2016" /> More than 90% of people affected in the [[United Kingdom|UK]] have a specific [[human leukocyte antigen]] known as the [[HLA-B27]] antigen.<ref name="The ramifications of HLA-B27">{{cite journal | vauthors = Sheehan NJ | title = The ramifications of HLA-B27 | journal = Journal of the Royal Society of Medicine | volume = 97 | issue = 1 | pages = 10–4 | date = January 2004 | pmid = 14702356 | pmc = 1079257 | doi = 10.1177/014107680409700102 }}</ref> The underlying mechanism is believed to be [[autoimmune disease|autoimmune]] or [[autoinflammatory disease|autoinflammatory]].<ref>{{cite journal | vauthors = Smith JA | s2cid = 24623808 | title = Update on ankylosing spondylitis: current concepts in pathogenesis | journal = Current Allergy and Asthma Reports | volume = 15 | issue = 1 | pages = 489 | date = January 2015 | pmid = 25447326 | doi = 10.1007/s11882-014-0489-6 }}</ref> Diagnosis is based on symptoms with support from [[medical imaging]] and [[blood tests]].<ref name="NIH2016" /> AS is a type of [[Spondyloarthropathy#Seronegative spondyloarthropathy|seronegative spondyloarthropathy]], meaning that tests show no presence of [[rheumatoid factor]] (RF) [[antibody|antibodies]].<ref name="NIH2016" />
'''Ankylosing spondylitis''' ('''AS''') is a type of [[arthritis]] characterized by long-term [[inflammation]] of the [[joints]] of the [[Vertebral column|spine]] typically where the spine joins the pelvis.<ref name=NIH2016>{{cite web|title=Questions and Answers about Ankylosing Spondylitis|url=http://www.niams.nih.gov/health_info/ankylosing_spondylitis/|website=NIAMS|access-date=28 September 2016|date=June 2016|url-status=dead|archive-url=https://web.archive.org/web/20160928175058/http://www.niams.nih.gov/health_info/ankylosing_spondylitis/|archive-date=28 September 2016|df=dmy-all}}</ref> Occasionally areas affected may include other joints such as the shoulders or hips. Eye and [[Gastrointestinal tract|bowel]] problems may occur as well as back pain.<ref name=NIH2016/> Joint mobility in the affected areas generally worsens over time.<ref name=NIH2016/><ref>{{cite web|title=Ankylosing spondylitis|url=https://rarediseases.info.nih.gov/diseases/9518/ankylosing-spondylitis|website=GARD|access-date=28 September 2016|date=9 February 2015|url-status=live|archive-url=https://web.archive.org/web/20161002084025/https://rarediseases.info.nih.gov/diseases/9518/ankylosing-spondylitis|archive-date=2 October 2016|df=dmy-all}}</ref>


There is no cure for AS. Treatments may include medication, physical therapy, and surgery. Medication therapy focuses on relieving the pain and other symptoms of AS, as well as stopping disease progression by counteracting long-term inflammatory processes. Commonly used medications include [[NSAIDs]], [[TNF inhibitor]]s, [[Interleukin-17A|IL-17]] antagonists, and [[Disease-modifying antirheumatic drug|DMARDs]]. [[Glucocorticoid]] injections are often used for acute and localized flare-ups.<ref name=":0" />
<!-- Cause and diagnosis -->
Although the cause of ankylosing spondylitis is unknown, it is believed to involve a combination of genetic and environmental factors.<ref name=NIH2016/> More than 85% of those affected in the [[United Kingdom|UK]] have a specific [[human leukocyte antigen]] known as the [[HLA-B27]] antigen.<ref name="The ramifications of HLA-B27">{{cite journal | vauthors = Sheehan NJ | title = The ramifications of HLA-B27 | journal = Journal of the Royal Society of Medicine | volume = 97 | issue = 1 | pages = 10–4 | date = January 2004 | pmid = 14702356 | pmc = 1079257 | doi = 10.1177/014107680409700102 }}</ref> The underlying mechanism is believed to be [[autoimmune disease|autoimmune]] or [[autoinflammatory disease|autoinflammatory]].<ref>{{cite journal | vauthors = Smith JA | s2cid = 24623808 | title = Update on ankylosing spondylitis: current concepts in pathogenesis | journal = Current Allergy and Asthma Reports | volume = 15 | issue = 1 | pages = 489 | date = January 2015 | pmid = 25447326 | doi = 10.1007/s11882-014-0489-6 }}</ref> Diagnosis is typically based on the symptoms with support from [[medical imaging]] and [[blood tests]].<ref name=NIH2016/> AS is a type of [[Spondyloarthropathy#Seronegative spondyloarthropathy|seronegative spondyloarthropathy]], meaning that tests show no presence of [[rheumatoid factor]] (RF) [[antibody|antibodies]].<ref name=NIH2016/>


About 0.1% to 0.8% of the population are affected, with onset typically occurring in young adults.<ref name="NIH2016" /><ref name="Kh2009">{{cite book| vauthors = Khan MA |title=Ankylosing Spondylitis|date=2009|publisher=Oxford University Press |isbn=9780195368079 |page=15 |url=https://books.google.com/books?id=ZFZnDAAAQBAJ&pg=PT27|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908183556/https://books.google.com/books?id=ZFZnDAAAQBAJ&pg=PT27|archive-date=8 September 2017|df=dmy-all}}</ref> While men and women are equally affected with AS, women are more likely to experience inflammation rather than fusion.<ref>{{Cite web |date=|title=Facts and Figures|url=http://nass.co.uk/about-as/as-facts-and-figures/|access-date=2021-01-27|website=National Axial Spondyloarthritis Society|language=en}}</ref>
<!-- Treatment -->
There is no known cure for AS.<ref name=NIH2016/> Treatments may include medication, exercise, physical therapy, and in rare cases surgery.<ref name=NIH2016/> Medications used include [[NSAIDs]], [[corticosteroids|steroids]], [[Disease-modifying antirheumatic drug|DMARDs]] such as [[sulfasalazine]], and biologic agents such as [[TNF inhibitor]]s.<ref name=NIH2016/>

<!-- Epidemiology, history, and culture -->
Approximately 0.1% to 0.8% of all humans are affected with onset typically occurring in young adults.<ref name=Kh2009>{{cite book| vauthors = Khan MA |title=Ankylosing Spondylitis|date=2009|publisher=Oxford University Press |isbn=9780195368079 |page=15 |url=https://books.google.com/books?id=ZFZnDAAAQBAJ&pg=PT27|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908183556/https://books.google.com/books?id=ZFZnDAAAQBAJ&pg=PT27|archive-date=8 September 2017|df=dmy-all}}</ref><ref name=NIH2016/> Males and females are equally affected; however, women are more likely than men to experience inflammation rather than fusion.<ref>{{Cite web |date=|title=Facts and Figures|url=http://nass.co.uk/about-as/as-facts-and-figures/|access-date=2021-01-27|website=National Axial Spondyloarthritis Society|language=en}}</ref>


==Signs and symptoms==
==Signs and symptoms==
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==Pathophysiology==
==Pathophysiology==
[[File:Ankylosing process.jpg|thumb|256px|The [[ankylosis]] process]]
[[File:Ankylosing process.jpg|thumb|256px|The [[ankylosis]] process]]
Ankylosing [[spondylitis]] (AS) is a systemic [[Rheumatology|rheumatic]] disease, meaning it affects the entire body. 1–2% of individuals with the [[HLA-B27|HLA-B27 genotype]] develop the disease.<ref name="Patient UK_5">{{cite web|title=Ankylosing Spondylitis – Professional reference for Doctors – Patient UK|url=http://www.patient.co.uk/doctor/ankylosing-spondylitis|work=Patient UK|access-date=22 December 2013|url-status=live|archive-url=https://web.archive.org/web/20131224103215/http://www.patient.co.uk/doctor/ankylosing-spondylitis|archive-date=24 December 2013|df=dmy-all}}</ref> [[Tumor necrosis factor-alpha]] (TNF α) and [[Interleukin-1 family|Interleukin 1]] (IL-1) are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. [[Anti-neutrophil cytoplasmic antibody|Anti-neutrophil cytoplasmic antibodies]] (ANCAs) are associated with AS, but do not correlate with disease severity.<ref>{{cite journal | vauthors = Rautenstrauch J, Gause A, Csernok E, Holle J, Gross WL | title = [Presentation of the Lubeck/Bad Bramstedt Competence Center] | journal = Zeitschrift für Rheumatologie | volume = 60 | issue = 4 | pages = 255–62 | date = August 2001 | pmid = 11584722 | doi = 10.1007/s003930170050 | s2cid = 43006040 }}</ref>
Ankylosing [[spondylitis]] (AS) is a systemic [[Rheumatology|rheumatic]] disease, meaning it affects the entire body. 1–2% of individuals with the [[HLA-B27|HLA-B27 genotype]] develop the disease.<ref name="Patient UK_5">{{cite web|title=Ankylosing Spondylitis – Professional reference for Doctors – Patient UK|url=http://www.patient.co.uk/doctor/ankylosing-spondylitis|work=Patient UK|access-date=22 December 2013|url-status=live|archive-url=https://web.archive.org/web/20131224103215/http://www.patient.co.uk/doctor/ankylosing-spondylitis|archive-date=24 December 2013|df=dmy-all}}</ref> [[Tumor necrosis factor-alpha]] (TNF α) and [[Interleukin-1 family|interleukin 1]] (IL-1) are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. [[Anti-neutrophil cytoplasmic antibody|Anti-neutrophil cytoplasmic antibodies]] (ANCAs) are associated with AS, but do not correlate with disease severity.<ref>{{cite journal | vauthors = Rautenstrauch J, Gause A, Csernok E, Holle J, Gross WL | title = [Presentation of the Lubeck/Bad Bramstedt Competence Center] | journal = Zeitschrift für Rheumatologie | volume = 60 | issue = 4 | pages = 255–62 | date = August 2001 | pmid = 11584722 | doi = 10.1007/s003930170050 | s2cid = 43006040 }}</ref>


[[Single nucleotide polymorphism]] (SNP) A/G variant rs10440635<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=10440635&pt=1ZE8FQPqPAQkPZT20n43IXH8IWKSLTH11tw4GNzhASRTSOTsS0 |title=Reference SNP (refSNP) Cluster Report: Rs10440635 |access-date=2017-02-14 |url-status=live |archive-url=https://web.archive.org/web/20170218235145/https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=10440635&pt=1ZE8FQPqPAQkPZT20n43IXH8IWKSLTH11tw4GNzhASRTSOTsS0 |archive-date=18 February 2017 |df=dmy-all }}</ref> is close to the ''[[Prostaglandin EP4 receptor|PTGER4]]'' gene on human chromosome 5 has been associated with an increased number of cases of AS in a population recruited from the United Kingdom, Australia, and Canada. The ''PTGER4'' gene codes for the [[prostaglandin EP4 receptor|prostaglandin EP4 receptor (EP4)]], one of four receptors for [[prostaglandin E2]]. Activation of EP4 promotes bone remodeling and deposition (see [[Prostaglandin EP4 receptor#Bone|EP4, bone]]) and EP4 is highly expressed at vertebral column sites involved in AS. These findings suggest that excessive EP4 activation contributes to pathological bone remodeling and deposition in AS and that the A/G variant rs10440635a of ''PTGER4'' predisposes individuals to this disease, possibly by influencing EP4's production or expression pattern.<ref name="pmid21743469">{{cite journal | vauthors = Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Oppermann U, Opperman U, Dilthey A, Pirinen M, Stone MA, Appleton L, Moutsianas L, Moutsianis L, Leslie S, Wordsworth T, Kenna TJ, Karaderi T, Thomas GP, Ward MM, Weisman MH, Farrar C, Bradbury LA, Danoy P, Inman RD, Maksymowych W, Gladman D, Rahman P, Morgan A, Marzo-Ortega H, Bowness P, Gaffney K, Gaston JS, Smith M, Bruges-Armas J, Couto AR, Sorrentino R, Paladini F, Ferreira MA, Xu H, Liu Y, Jiang L, Lopez-Larrea C, Díaz-Peña R, López-Vázquez A, Zayats T, Band G, Bellenguez C, Blackburn H, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Corvin A, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Freeman C, Gillman M, Gray E, Gwilliam R, Hammond N, Hunt SE, Jankowski J, Jayakumar A, Langford C, Liddle J, Markus HS, Mathew CG, McCann OT, McCarthy MI, Palmer CN, Peltonen L, Plomin R, Potter SC, Rautanen A, Ravindrarajah R, Ricketts M, Samani N, Sawcer SJ, Strange A, Trembath RC, Viswanathan AC, Waller M, Weston P, Whittaker P, Widaa S, Wood NW, McVean G, Reveille JD, Wordsworth BP, Brown MA, Donnelly P | display-authors = 6 | title = Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility | journal = Nature Genetics | volume = 43 | issue = 8 | pages = 761–7 | date = July 2011 | pmid = 21743469 | pmc = 3640413 | doi = 10.1038/ng.873 }}</ref><ref name="pmid25935456">{{cite journal | vauthors = Haroon N | s2cid = 25930196 | title = Ankylosis in ankylosing spondylitis: current concepts | journal = Clinical Rheumatology | volume = 34 | issue = 6 | pages = 1003–7 | date = June 2015 | pmid = 25935456 | doi = 10.1007/s10067-015-2956-4 }}</ref>
[[Single nucleotide polymorphism]] (SNP) A/G variant rs10440635<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=10440635&pt=1ZE8FQPqPAQkPZT20n43IXH8IWKSLTH11tw4GNzhASRTSOTsS0 |title=Reference SNP (refSNP) Cluster Report: Rs10440635 |access-date=2017-02-14 |url-status=live |archive-url=https://web.archive.org/web/20170218235145/https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=10440635&pt=1ZE8FQPqPAQkPZT20n43IXH8IWKSLTH11tw4GNzhASRTSOTsS0 |archive-date=18 February 2017 |df=dmy-all }}</ref> is close to the ''[[Prostaglandin EP4 receptor|PTGER4]]'' gene on human chromosome 5 has been associated with an increased number of cases of AS in a population recruited from the United Kingdom, Australia, and Canada. The ''PTGER4'' gene codes for the [[prostaglandin EP4 receptor|prostaglandin EP<sub>4</sub> receptor]], one of four receptors for [[prostaglandin E2|prostaglandin E<sub>2</sub>]]. Activation of EP<sub>4</sub> promotes bone remodeling and deposition (see {{slink|prostaglandin EP4 receptor#Bone}}) and EP<sub>4</sub> is highly expressed at vertebral column sites involved in AS. These findings suggest that excessive EP<sub>4</sub> activation contributes to pathological bone remodeling and deposition in AS and that the A/G variant rs10440635a of ''PTGER4'' predisposes individuals to this disease, possibly by influencing EP4's production or expression pattern.<ref name="pmid21743469">{{cite journal | vauthors = Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, Oppermann U, Opperman U, Dilthey A, Pirinen M, Stone MA, Appleton L, Moutsianas L, Moutsianis L, Leslie S, Wordsworth T, Kenna TJ, Karaderi T, Thomas GP, Ward MM, Weisman MH, Farrar C, Bradbury LA, Danoy P, Inman RD, Maksymowych W, Gladman D, Rahman P, Morgan A, Marzo-Ortega H, Bowness P, Gaffney K, Gaston JS, Smith M, Bruges-Armas J, Couto AR, Sorrentino R, Paladini F, Ferreira MA, Xu H, Liu Y, Jiang L, Lopez-Larrea C, Díaz-Peña R, López-Vázquez A, Zayats T, Band G, Bellenguez C, Blackburn H, Blackwell JM, Bramon E, Bumpstead SJ, Casas JP, Corvin A, Craddock N, Deloukas P, Dronov S, Duncanson A, Edkins S, Freeman C, Gillman M, Gray E, Gwilliam R, Hammond N, Hunt SE, Jankowski J, Jayakumar A, Langford C, Liddle J, Markus HS, Mathew CG, McCann OT, McCarthy MI, Palmer CN, Peltonen L, Plomin R, Potter SC, Rautanen A, Ravindrarajah R, Ricketts M, Samani N, Sawcer SJ, Strange A, Trembath RC, Viswanathan AC, Waller M, Weston P, Whittaker P, Widaa S, Wood NW, McVean G, Reveille JD, Wordsworth BP, Brown MA, Donnelly P | display-authors = 6 | title = Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility | journal = Nature Genetics | volume = 43 | issue = 8 | pages = 761–7 | date = July 2011 | pmid = 21743469 | pmc = 3640413 | doi = 10.1038/ng.873 }}</ref><ref name="pmid25935456">{{cite journal | vauthors = Haroon N | s2cid = 25930196 | title = Ankylosis in ankylosing spondylitis: current concepts | journal = Clinical Rheumatology | volume = 34 | issue = 6 | pages = 1003–7 | date = June 2015 | pmid = 25935456 | doi = 10.1007/s10067-015-2956-4 }}</ref>


The association of AS with HLA-B27 suggests the condition involves [[Cytotoxic T cell|CD8 T cells]], which interact with [[HLA-B]].<ref>{{cite journal | vauthors = Boyle LH, Goodall JC, Opat SS, Gaston JS | title = The recognition of HLA-B27 by human CD4(+) T lymphocytes | journal = Journal of Immunology | volume = 167 | issue = 5 | pages = 2619–24 | date = September 2001 | pmid = 11509603 | doi = 10.4049/jimmunol.167.5.2619 | url = https://www.jimmunol.org/content/167/5/2619 | doi-access = free }}</ref> This interaction is not proven to involve a self-antigen, and at least in the related [[reactive arthritis]], which follows infections, the antigens involved are likely to be derived from intracellular microorganisms.<ref name="The ramifications of HLA-B27"/> There is, however, a possibility that [[CD4+ T lymphocytes]] 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 [[CD8+ cytotoxic T cell]] with HLAB antigen as it is a [[MHC class I|MHC class 1 antigen]]).
The association of AS with HLA-B27 suggests the condition involves [[Cytotoxic T cell|CD8 T cells]], which interact with [[HLA-B]].<ref>{{cite journal | vauthors = Boyle LH, Goodall JC, Opat SS, Gaston JS | title = The recognition of HLA-B27 by human CD4(+) T lymphocytes | journal = Journal of Immunology | volume = 167 | issue = 5 | pages = 2619–24 | date = September 2001 | pmid = 11509603 | doi = 10.4049/jimmunol.167.5.2619 |url=https://www.jimmunol.org/content/167/5/2619 | doi-access = free }}</ref> This interaction is not proven to involve a self-antigen, and at least in the related [[reactive arthritis]], which follows infections, the antigens involved are likely to be derived from intracellular microorganisms.<ref name="The ramifications of HLA-B27"/> There is, however, a possibility that [[CD4+ T lymphocytes]] 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 [[CD8+ cytotoxic T cell]] with HLAB antigen as it is a [[MHC class I|MHC class 1 antigen]]).


"Bamboo spine" develops when the outer fibers of the [[Anulus fibrosus disci intervertebralis|fibrous ring]] (''anulus fibrosus disci intervertebralis'') of the [[intervertebral disc]]s ossify, which results in the formation of marginal [[syndesmophyte]]s between adjoining vertebrae.
"Bamboo spine" develops when the outer fibers of the [[Anulus fibrosus disci intervertebralis|fibrous ring]] (''anulus fibrosus disci intervertebralis'') of the [[intervertebral disc]]s ossify, which results in the formation of marginal [[syndesmophyte]]s between adjoining vertebrae.
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==Diagnosis==
==Diagnosis==
[[File:12891 2006 Article 297 Fig5 HTML.jpg|thumb|34-year-old male with AS. Inflammatory lesions of the anterior chest wall are shown (curved arrows). Inflammatory changes are seen in the lower thoracic spine and L1 (arrows).]]
[[File:12891 2006 Article 297 Fig5 HTML.jpg|thumb|34-year-old male with AS. Inflammatory lesions of the anterior chest wall are shown (curved arrows). Inflammatory changes are seen in the lower thoracic spine and L1 (arrows).]]
Ankylosing spondylitis is a member of the more broadly defined disease [[axial spondyloarthritis]].<ref name="Classification2009">{{cite journal | vauthors = Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sørensen IJ, Ozgocmen S, Roussou E, Valle-Oñate R, Weber U, Wei J, Sieper J | display-authors = 6 | title = The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection | language = en | journal = Annals of the Rheumatic Diseases | volume = 68 | issue = 6 | pages = 777–83 | date = June 2009 | pmid = 19297344 | doi = 10.1136/ard.2009.108233 | doi-access = free }}</ref><ref>{{cite journal |display-authors=6 |vauthors=Deodhar A, Reveille JD, van den Bosch F, Braun J, Burgos-Vargas R, Caplan L, Clegg DO, Colbert RA, Gensler LS, van der Heijde D, van der Horst-Bruinsma IE, Inman RD, Maksymowych WP, Mease PJ, Raychaudhuri S, Reimold A, Rudwaleit M, Sieper J, Weisman MH, Landewé RB |date=October 2014 |title=The concept of axial spondyloarthritis: joint statement of the spondyloarthritis research and treatment network and the Assessment of SpondyloArthritis international Society in response to the US Food and Drug Administration's comments and concerns |journal=Arthritis & Rheumatology |volume=66 |issue=10 |pages=2649–56 |doi=10.1002/art.38776 |pmid=25154344 |doi-access=free |s2cid=38228595}}</ref> Axial spondyloarthritis can be divided into two categories: radiographic axial spondyloarthritis (which is a synonym for ankylosing spondylitis) and non-radiographic axial spondyloarthritis (which include less severe forms and early stages of ankylosing spondylitis).<ref name="Classification2009" />
Ankylosing spondylitis is a member of the more broadly defined disease [[axial spondyloarthritis]].<ref name="Classification2009">{{cite journal | vauthors = Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sørensen IJ, Ozgocmen S, Roussou E, Valle-Oñate R, Weber U, Wei J, Sieper J | display-authors = 6 | title = The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection | language = en | journal = Annals of the Rheumatic Diseases | volume = 68 | issue = 6 | pages = 777–83 | date = June 2009 | pmid = 19297344 | doi = 10.1136/ard.2009.108233 | doi-access = free }}</ref><ref>{{cite journal |display-authors=6 |vauthors=Deodhar A, Reveille JD, van den Bosch F, Braun J, Burgos-Vargas R, Caplan L, Clegg DO, Colbert RA, Gensler LS, van der Heijde D, van der Horst-Bruinsma IE, Inman RD, Maksymowych WP, Mease PJ, Raychaudhuri S, Reimold A, Rudwaleit M, Sieper J, Weisman MH, Landewé RB |date=October 2014 |title=The concept of axial spondyloarthritis: joint statement of the spondyloarthritis research and treatment network and the Assessment of SpondyloArthritis international Society in response to the US Food and Drug Administration's comments and concerns |journal=Arthritis & Rheumatology |volume=66 |issue=10 |pages=2649–56 |doi=10.1002/art.38776 |pmid=25154344 |doi-access= |s2cid=38228595}}</ref> Axial spondyloarthritis can be divided into two categories: radiographic axial spondyloarthritis (which is a synonym for ankylosing spondylitis) and non-radiographic axial spondyloarthritis (which include less severe forms and early stages of ankylosing spondylitis).<ref name="Classification2009" />


While AS can be diagnosed through the description of radiological changes in the [[sacroiliac joint]]s and [[Vertebral column|spine]], there are currently no direct tests (blood or imaging) to unambiguously diagnose early forms of ankylosing spondylitis ([[non-radiographic axial spondyloarthritis]]). Diagnosis of non-radiologic axial spondyloarthritis is therefore more difficult and is based on the presence of several typical disease features.<ref name="Classification2009" /><ref name="Poddubnyyvan Tubergen2015">{{cite journal | vauthors = Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D | title = Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis | journal = Annals of the Rheumatic Diseases | volume = 74 | issue = 8 | pages = 1483–7 | date = August 2015 | pmid = 25990288 | doi = 10.1136/annrheumdis-2014-207151 | s2cid = 42585224 }}</ref>
While AS can be diagnosed through the description of radiological changes in the [[sacroiliac joint]]s and [[Vertebral column|spine]], there are currently no direct tests (blood or imaging) to unambiguously diagnose early forms of ankylosing spondylitis ([[non-radiographic axial spondyloarthritis]]). Diagnosis of non-radiologic axial spondyloarthritis is therefore more difficult and is based on the presence of several typical disease features.<ref name="Classification2009" /><ref name="Poddubnyyvan Tubergen2015">{{cite journal | vauthors = Poddubnyy D, van Tubergen A, Landewé R, Sieper J, van der Heijde D | title = Development of an ASAS-endorsed recommendation for the early referral of patients with a suspicion of axial spondyloarthritis | journal = Annals of the Rheumatic Diseases | volume = 74 | issue = 8 | pages = 1483–7 | date = August 2015 | pmid = 25990288 | doi = 10.1136/annrheumdis-2014-207151 | s2cid = 42585224 }}</ref>


These diagnostic criteria include:
These diagnostic criteria include:
* Inflammatory back pain:<br>Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up)
* Inflammatory back pain:<br>Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up). Pain often subsides as the day progresses with movement being of importance to alleviate the joint stiffness.
* Past history of inflammation in the joints, heels, or tendon-bone attachments
* Past history of inflammation in the joints, heels, or tendon-bone attachments
* Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions
* Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions
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==Treatment==
==Treatment==
There is no cure for AS,<ref>{{cite web |title=Ankylosing Spondylitis |url=https://www.niams.nih.gov/health-topics/ankylosing-spondylitis |website=NIAMS |date=5 April 2017 |publisher=NIH |access-date=25 March 2023}}</ref> although treatments and medications can reduce symptoms and pain.
There is no cure for AS,<ref>{{cite web |title=Ankylosing Spondylitis |url=https://www.niams.nih.gov/health-topics/ankylosing-spondylitis |website=NIAMS |date=5 April 2017 |publisher=NIH |access-date=25 March 2023}}</ref> but treatments and medications can reduce symptoms and pain.


===Medication===
===Medication===
Medications for AS may be broadly considered either "disease-modifying" or "non-disease-modifying". Disease-modifying medications for ankylosing spondylitis aim to slow disease progression and include drugs like tumor necrosis factor (TNF) inhibitors. Non-disease-modifying medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), primarily address symptoms like pain and inflammation but do not alter the course of the disease.<ref>{{Cite journal |last1=Akkoc |first1=Nurullah |last2=van der Linden |first2=Sjef |last3=Khan |first3=Muhammad Asim |date=June 2006 |title=Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy |url=https://pubmed.ncbi.nlm.nih.gov/16777581 |journal=Best Practice & Research. Clinical Rheumatology |volume=20 |issue=3 |pages=539–557 |doi=10.1016/j.berh.2006.03.003 |issn=1521-6942 |pmid=16777581}}</ref>
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. All of these have potentially serious side effects. Pain-relieving drugs come in two major classes:
* The mainstay of therapy in all seronegative spondyloarthropathies are [[anti-inflammatory drugs]], which include [[Non-steroidal anti-inflammatory drug|NSAID]]s such as [[ibuprofen]], [[phenylbutazone]], [[diclofenac]], [[indomethacin]], [[naproxen]] and [[COX-2 inhibitor]]s, which reduce inflammation and pain. 2012 research showed that those with AS and elevated levels of [[Acute-phase proteins|acute phase reactant]]s seem to benefit most from continuous treatment with NSAIDs.<ref name="pmid22532639">{{cite journal | vauthors = Kroon F, Landewé R, Dougados M, van der Heijde D | title = Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 71 | issue = 10 | pages = 1623–9 | date = October 2012 | pmid = 22532639 | doi = 10.1136/annrheumdis-2012-201370 | doi-access = free }}</ref>


==== NSAIDs ====
Medications used to treat the progression of the disease include the following:
Unless otherwise contraindicated, all people with AS are recommended to take [[Nonsteroidal anti-inflammatory drug|non-steroidal anti-inflammatory drugs]] (NSAIDs). The dose, frequency, and specific drug may depend on the individual and the symptoms they experience. NSAIDs, such as ibuprofen and naproxen, are used to alleviate pain, reduce inflammation, and improve joint stiffness associated with AS. These medications work by inhibiting the activity of [[cyclooxygenase]] (COX) enzymes, which are involved in the production of inflammatory [[prostaglandin]]s. By reducing the levels of prostaglandins, NSAIDs help mitigate the [[Inflammation|inflammatory response]] and relieve symptoms in individuals with ankylosing spondylitis.<ref name=":0">{{Cite journal |last1=Ward |first1=Michael M. |last2=Deodhar |first2=Atul |last3=Gensler |first3=Lianne S. |last4=Dubreuil |first4=Maureen |last5=Yu |first5=David |last6=Khan |first6=Muhammad Asim |last7=Haroon |first7=Nigil |last8=Borenstein |first8=David |last9=Wang |first9=Runsheng |last10=Biehl |first10=Ann |last11=Fang |first11=Meika A. |last12=Louie |first12=Grant |last13=Majithia |first13=Vikas |last14=Ng |first14=Bernard |last15=Bigham |first15=Rosemary |date=October 2019 |title=2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis |journal=Arthritis & Rheumatology |volume=71 |issue=10 |pages=1599–1613 |doi=10.1002/art.41042 |issn=2326-5191 |pmc=6764882 |pmid=31436036}}</ref><ref>{{Cite journal |last1=Vane |first1=J. R. |last2=Botting |first2=R. M. |date=October 1998 |title=Anti-inflammatory drugs and their mechanism of action |url=https://pubmed.ncbi.nlm.nih.gov/9831328 |journal=Inflammation Research|volume=47 |issue=Suppl 2 |pages=S78–87 |doi=10.1007/s000110050284 |issn=1023-3830 |pmid=9831328|s2cid=1866687 }}</ref>
* [[Disease-modifying antirheumatic drug]]s (DMARDs) such as [[sulfasalazine]] can be used in people with peripheral arthritis. For axial involvement, evidence does not support sulfasalazine.<ref>{{cite journal | vauthors = Chen J, Lin S, Liu C | title = Sulfasalazine for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD004800 | date = November 2014 | pmid = 25427435 | doi = 10.1002/14651858.CD004800.pub3 }}</ref> 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 certain people with peripheral arthritis.<ref>{{cite journal | vauthors = Chen J, Veras MM, Liu C, Lin J | title = Methotrexate for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 2 | issue = 2 | pages = CD004524 | date = February 2013 | pmid = 23450553 | doi = 10.1002/14651858.CD004524.pub4 }}</ref><ref name="pmid21540199">{{cite journal | vauthors = 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 | display-authors = 6 | title = 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 70 | issue = 6 | pages = 896–904 | date = June 2011 | pmid = 21540199 | pmc = 3086052 | doi = 10.1136/ard.2011.151027 }}</ref>

* [[Tumor necrosis factor-alpha]] (TNFα) blockers ([[Receptor antagonist|antagonists]]), such as the [[biologic medical product|biologics]] [[etanercept]], [[infliximab]], [[golimumab]] and [[adalimumab]], have shown good short-term effectiveness in the form of profound and sustained reduction in all clinical and laboratory measures of disease activity.<ref>{{cite journal | vauthors = Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, Benkhalti Jandu M, Tugwell P, Wells GA | display-authors = 6 | title = TNF-alpha inhibitors for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD005468 | date = April 2015 | pmid = 25887212 | doi = 10.1002/14651858.CD005468.pub2 | url = http://ecite.utas.edu.au/120128 }}</ref> Trials are ongoing to determine their long-term effectiveness and safety.<ref name="pmid17448825">{{cite journal | vauthors = Braun J, Sieper J | title = Ankylosing spondylitis | journal = Lancet | volume = 369 | issue = 9570 | pages = 1379–1390 | date = April 2007 | pmid = 17448825 | doi = 10.1016/S0140-6736(07)60635-7 }}</ref> The major drawback is the cost. An alternative may be the newer, orally-administered non-biologic [[apremilast]], which inhibits TNF-α secretion, but a recent study did not find the drug useful for ankylosing spondylitis.<ref>{{cite web| vauthors = Cush J |title=POSTURE Study: Apremilast Fails in Ankylosing Spondylitis|url=http://rheumnow.com/content/posture-study-apremilast-fails-ankylosing-spondylitis|website=Rheum Now|access-date=10 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170410220647/http://rheumnow.com/content/posture-study-apremilast-fails-ankylosing-spondylitis|archive-date=10 April 2017|df=dmy-all}}</ref>
==== TNF inhibitors ====
* [[Anti-IL-6|Anti-interleukin-6]] inhibitors such as [[tocilizumab]], currently approved for the treatment of rheumatoid arthritis,<ref>{{cite journal | vauthors = Henes JC, Horger M, Guenaydin I, Kanz L, Koetter I | s2cid = 31849478 | title = Mixed response to tocilizumab for ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 69 | issue = 12 | pages = 2217–8 | date = December 2010 | pmid = 20525837 | doi = 10.1136/ard.2009.126706 }}</ref> and [[rituximab]], a monoclonal antibody against CD20, are also undergoing trials.<ref>{{cite journal | vauthors = Rodríguez-Escalera C, Fernández-Nebro A | title = The use of rituximab to treat a patient with ankylosing spondylitis and hepatitis B | journal = Rheumatology | volume = 47 | issue = 11 | pages = 1732–3 | date = November 2008 | pmid = 18786966 | doi = 10.1093/rheumatology/ken362 | doi-access = free }}</ref>
Tumor necrosis factor inhibitors (TNFi) are a class of biologic drugs used in the treatment of ankylosing spondylitis. TNFi drugs, such as [[etanercept]], [[infliximab]], [[adalimumab]], [[Certolizumab pegol|certolizumab]], and [[golimumab]], target the inflammatory cytokine [[tumor necrosis factor-alpha]] (TNF-alpha). TNF-alpha plays a key role in the inflammatory process in ankylosing spondylitis. By blocking TNF-alpha, TNFi drugs help reduce inflammation, pain, and stiffness associated with AS, and may also slow down the progression of spinal damage.<ref name=":0" /><ref>{{Cite journal |last1=Tracey |first1=Daniel |last2=Klareskog |first2=Lars |last3=Sasso |first3=Eric H. |last4=Salfeld |first4=Jochen G. |last5=Tak |first5=Paul P. |date=February 2008 |title=Tumor necrosis factor antagonist mechanisms of action: a comprehensive review |url=https://pubmed.ncbi.nlm.nih.gov/18155297 |journal=Pharmacology & Therapeutics |volume=117 |issue=2 |pages=244–279 |doi=10.1016/j.pharmthera.2007.10.001 |issn=0163-7258 |pmid=18155297}}</ref>
* [[Interleukin 17A|Interleukin-17A]] inhibitors [[secukinumab]] and [[ixekizumab]] are options for the treatment of active ankylosing spondylitis in patients that have responded inadequately to (TNFα) blockers.<ref name="National Institute for Health and Care Excellence">{{cite web|title=Secukinumab for active Ankylosing Spondylitis|url=https://www.nice.org.uk/guidance/ta407/chapter/1-Recommendations|work=NICE|date=28 September 2016 |access-date=26 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170202035240/https://www.nice.org.uk/guidance/ta407/chapter/1-Recommendations|archive-date=2 February 2017|df=dmy-all}}</ref>

* [[Janus kinase inhibitor|Janus kinase]] inhibitor [[tofacitinib]] is approved for the treatment of active ankylosing spondylitis in adult patients that show an inadequate response to prior DMARD therapy.
==== Non-TNFi biologics ====
Non-TNFi "biologic" drugs used in the treatment of ankylosing spondylitis include drugs that target different pathways involved in the inflammatory process. Two of the most important drugs in this class target [[Interleukin-17A|IL-17]], an important part of the inflammatory system: [[secukinumab]] and [[ixekizumab]]. They are often considered in cases where TNFi drugs are not effective or cause too many side effects. Additionally, they may sometimes be used as an [[Adjuvant therapy|adjunct]] to a TNFi when symptoms persist, but improve, while the patient is on the TNFi. The choice of a specific non-TNFi biologic depends on various factors, including the patient's medical history, preferences, and the recommendations of the healthcare provider.<ref name=":0" />

[[Ustekinumab]] has frequently been used as a [[Second-line medication|second-line therapy]] for AS, but it has recently been scrutinized for a lack of efficacy, and is no longer recommended.<ref>{{Cite journal |last1=Cantini |first1=Fabrizio |last2=Niccoli |first2=Laura |last3=Nannini |first3=Carlotta |last4=Cassarà |first4=Emanuele |last5=Kaloudi |first5=Olga |last6=Giulio Favalli |first6=Ennio |last7=Becciolini |first7=Andrea |last8=Benucci |first8=Maurizio |last9=Gobbi |first9=Francesca Li |last10=Guiducci |first10=Serena |last11=Foti |first11=Rosario |last12=Mosca |first12=Marta |last13=Goletti |first13=Delia |date=October 2017 |title=Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis |url=https://pubmed.ncbi.nlm.nih.gov/28413099 |journal=Seminars in Arthritis and Rheumatism |volume=47 |issue=2 |pages=183–192 |doi=10.1016/j.semarthrit.2017.03.008 |issn=1532-866X |pmid=28413099}}</ref><ref name=":0" />

==== Biosimilar drugs ====
[[Biosimilar]] drugs are biological products that are highly similar to an already approved biologic drug, with few or no clinically meaningful differences in terms of safety, purity, and potency. These drugs are developed to be equivalent to the reference biologic, often at a lower cost, providing alternative treatment options. In the context of ankylosing spondylitis, biosimilars are typically used as alternatives to the original biologic drugs. Biosimilars for ankylosing spondylitis may include versions of tumor necrosis factor inhibitors or other biologics commonly used in the treatment of the condition. When possible, physicians are recommended to use the original drugs over the biosimilar versions. Even biosimilars with perfect replication of the quality, composition, and other properties of the original drug are susceptible to [[nocebo]] effects.<ref name=":0" /><ref>{{Cite journal |last1=Leone |first1=Gian Marco |last2=Mangano |first2=Katia |last3=Petralia |first3=Maria Cristina |last4=Nicoletti |first4=Ferdinando |last5=Fagone |first5=Paolo |date=2023-02-17 |title=Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy |journal=Journal of Clinical Medicine |volume=12 |issue=4 |pages=1630 |doi=10.3390/jcm12041630 |doi-access=free |issn=2077-0383 |pmc=9963154 |pmid=36836166}}</ref>

==== csARDs ====
[[Conventional synthetic antirheumatic drugs]] (csARDs) are a class of disease-modifying medications. Unlike biologics or targeted synthetic drugs, which act on specific pathways in the immune system, csARDs have a broader effect on the immune system and are often considered traditional or conventional treatments. The most common drugs in this class are [[methotrexate]] and [[sulfasalazine]]. These medications are only used when others fail, or when certain specific conditions are met, and are often discontinued if a patient's symptoms become manageable with just a TNFi or other medication. Conventional [[Disease-modifying antirheumatic drug|DMARDs]] such as [[leflunomide]] are also considered to be part of this class.<ref name=":0" />

Concerns exist about a possible lack of [[efficacy]] of some drugs in this class.<ref>{{Cite journal |last1=Chen |first1=Junmin |last2=Veras |first2=Mirella M. S. |last3=Liu |first3=Chao |last4=Lin |first4=Junfang |date=2013-02-28 |title=Methotrexate for ankylosing spondylitis |url=https://pubmed.ncbi.nlm.nih.gov/23450553 |journal=The Cochrane Database of Systematic Reviews |issue=2 |pages=CD004524 |doi=10.1002/14651858.CD004524.pub4 |issn=1469-493X |pmid=23450553}}</ref>

==== Corticosteroids ====
[[Glucocorticoid]]s, such as [[prednisone]] or [[methylprednisolone]], are sometimes used in the treatment of ankylosing spondylitis to manage acute flares and provide short-term relief from inflammation and symptoms. They are powerful anti-inflammatory medications that can help reduce pain, swelling, and stiffness associated with AS. However, glucocorticoids are generally not recommended for long-term use. They are more commonly used as localized [[Intramuscular injection|injections]] when someone with AS has a temporary pain flare in a particular joint or area.<ref name=":0" />


===Surgery===
===Surgery===
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 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 that make anesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anesthesia may be difficult owing to calcification of ligaments, and a small number of people 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.
In addition, AS can have some manifestations which make anesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anesthesia may be difficult owing to calcification of ligaments, and a small number of people 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===
===Physical therapy===
Though physical therapy remedies have been scarcely documented, some therapeutic exercises are used to help manage lower back, neck, knee, and shoulder pain. There is moderate quality evidence that therapeutic exercise programmes help reduce pain and improve function.<ref>{{cite journal | vauthors = Regnaux JP, Davergne T, Palazzo C, Roren A, Rannou F, Boutron I, Lefevre-Colau MM | title = Exercise programmes for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 10 | pages = CD011321 | date = October 2019 | issue = 10 | pmid = 31578051 | pmc = 6774752 | doi = 10.1002/14651858.cd011321.pub2 }}</ref> Some therapeutic exercises include:<ref name="Philadelphia Panel 2001">{{cite journal | vauthors = | title = Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions: overview and methodology | journal = Physical Therapy | volume = 81 | issue = 10 | pages = 1629–40 | date = October 2001 | pmid = 11589641 }}</ref><ref>{{cite journal | vauthors = Dagfinrud H, Kvien TK, Hagen KB | title = Physiotherapy interventions for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD002822 | date = January 2008 | volume = 2009 | pmid = 18254008 | doi = 10.1002/14651858.CD002822.pub3 | pmc = 8453259 }}</ref>
Though physical therapy remedies have been scarcely documented, some therapeutic exercises are used to help manage lower back, neck, knee, and shoulder pain. There is moderate quality evidence that therapeutic exercise programs help reduce pain and improve function.<ref>{{cite journal | vauthors = Regnaux JP, Davergne T, Palazzo C, Roren A, Rannou F, Boutron I, Lefevre-Colau MM | title = Exercise programmes for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 10 | pages = CD011321 | date = October 2019 | issue = 10 | pmid = 31578051 | pmc = 6774752 | doi = 10.1002/14651858.cd011321.pub2 }}</ref> Therapeutic exercises include:<ref name="Philadelphia Panel 2001">{{cite journal | vauthors = | title = Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions: overview and methodology | journal = Physical Therapy | volume = 81 | issue = 10 | pages = 1629–40 | date = October 2001 | pmid = 11589641 }}</ref><ref>{{cite journal | vauthors = Dagfinrud H, Kvien TK, Hagen KB | title = Physiotherapy interventions for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD002822 | date = January 2008 | volume = 2009 | pmid = 18254008 | doi = 10.1002/14651858.CD002822.pub3 | pmc = 8453259 }}</ref>
* Exercise programs, either at home or supervised
* Exercise programs, either at home or supervised
* Low intensity aerobic exercise, e.g. [[Pilates]]
* Low intensity aerobic exercise, e.g. [[Pilates]]
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* [[Heat therapy]]
* [[Heat therapy]]
* Cryotherapy in conjunction with exercise<ref>{{cite journal | vauthors = Romanowski MW, Straburzyńska-Lupa A | title = Is the whole-body cryotherapy a beneficial supplement to exercise therapy for patients with ankylosing spondylitis? | journal = Journal of Back and Musculoskeletal Rehabilitation | volume = 33 | issue = 2 | pages = 185–192 | date = 2020-03-19 | pmid = 31594196 | doi = 10.3233/BMR-170978 | s2cid = 203984335 }}</ref>
* Cryotherapy in conjunction with exercise<ref>{{cite journal | vauthors = Romanowski MW, Straburzyńska-Lupa A | title = Is the whole-body cryotherapy a beneficial supplement to exercise therapy for patients with ankylosing spondylitis? | journal = Journal of Back and Musculoskeletal Rehabilitation | volume = 33 | issue = 2 | pages = 185–192 | date = 2020-03-19 | pmid = 31594196 | doi = 10.3233/BMR-170978 | s2cid = 203984335 }}</ref>

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 with AS.{{medical citation needed|date=August 2021}}


===Diet===
===Diet===
Research by Alan Ebringer at King's College in London, beginning in the 1980s, has implicated overgrowth of the bacterium ''Klebsiella pneumoniae'' in the symptoms of ankylosing spondylitis. The body produces antibodies that attack ''Klebsiella pneumoniae''. Enzymes made by the bacterium resemble human proteins, including three types of collagen (I, III, IV) and the HLA-B27 complex of glycoproteins. The antibodies therefore attack these human proteins, producing the symptoms of ankylosing spondylitis. Ebringer and others recommend low-starch or no-starch diets. <ref>{{cite journal | vauthors = Rashid T, Wilson C, Ebringer A | title = The link between ankylosing spondylitis, Crohn's disease, Klebsiella, and starch consumption | journal = Clinical & Developmental Immunology | volume = 2013 | pages = 872632 | date = 2013-05-27 | pmid = 23781254 | pmc = 3678459 | doi = 10.1155/2013/872632 | doi-access = free }}</ref>
Research by Alan Ebringer at King's College in London, beginning in the 1980s, implicates overgrowth of the bacterium ''Klebsiella pneumoniae'' in the symptoms of ankylosing spondylitis. The body produces antibodies that attack ''Klebsiella pneumoniae''. Enzymes made by the bacterium resemble human proteins, including three types of collagen (I, III, IV) and the HLA-B27 complex of glycoproteins. The antibodies therefore attack these human proteins, producing the symptoms of ankylosing spondylitis. Ebringer and others recommend low-starch or no-starch diets.<ref>{{cite journal | vauthors = Rashid T, Wilson C, Ebringer A | title = The link between ankylosing spondylitis, Crohn's disease, Klebsiella, and starch consumption | journal = Clinical & Developmental Immunology | volume = 2013 | pages = 872632 | date = 2013-05-27 | pmid = 23781254 | pmc = 3678459 | doi = 10.1155/2013/872632 | doi-access = free }}</ref>

The site kickAS.org, referencing the work of Ebringer and others, created a "No Starch Diet" guide.<ref>[https://kickas.org/asfood.shtml Asfood guide]</ref>


==Prognosis==
==Prognosis==
Line 147: Line 151:


===Mortality===
===Mortality===
Mortality is increased in people with AS and circulatory disease is the most frequent cause of death.<ref name="pmid21784726">{{cite journal | vauthors = Bakland G, Gran JT, Nossent JC | title = Increased mortality in ankylosing spondylitis is related to disease activity | journal = Annals of the Rheumatic Diseases | volume = 70 | issue = 11 | pages = 1921–5 | date = November 2011 | pmid = 21784726 | doi = 10.1136/ard.2011.151191 | s2cid = 39397817 }}</ref> People with AS have an increased risk of 60% for cerebrovascular mortality, and an overall increased risk of 50% for vascular mortality.<ref name="Medscape">{{cite web|title=Ankylosing Spondylitis Linked to Cardiovascular Mortality|url=http://www.medscape.com/viewarticle/849332|work=Medscape|access-date=7 October 2015|url-status=live|archive-url=https://web.archive.org/web/20150914044950/http://www.medscape.com/viewarticle/849332|archive-date=14 September 2015|df=dmy-all}}</ref> About one third of those with ankylosing spondylitis have severe disease, which reduces life expectancy.<ref>{{cite journal | vauthors = Braun J, Pincus T | title = Mortality, course of disease and prognosis of patients with ankylosing spondylitis | journal = Clinical and Experimental Rheumatology | volume = 20 | issue = 6 Suppl 28 | pages = S16-22 | date = 2002 | pmid = 12463441 | url = https://www.researchgate.net/publication/11008397 | url-status = live | archive-url = https://web.archive.org/web/20161101102544/https://www.researchgate.net/publication/11008397_Mortality_course_of_disease_and_prognosis_of_patients_with_ankylosing_spondylitis | df = dmy-all | archive-date = 1 November 2016 }}</ref>
Mortality is increased in people with AS and circulatory disease is the most frequent cause of death.<ref name="pmid21784726">{{cite journal | vauthors = Bakland G, Gran JT, Nossent JC | title = Increased mortality in ankylosing spondylitis is related to disease activity | journal = Annals of the Rheumatic Diseases | volume = 70 | issue = 11 | pages = 1921–5 | date = November 2011 | pmid = 21784726 | doi = 10.1136/ard.2011.151191 | s2cid = 39397817 }}</ref> People with AS have an increased risk of 60% for cerebrovascular mortality, and an overall increased risk of 50% for vascular mortality.<ref name="Medscape">{{cite web|title=Ankylosing Spondylitis Linked to Cardiovascular Mortality|url=http://www.medscape.com/viewarticle/849332|work=Medscape|access-date=7 October 2015|url-status=live|archive-url=https://web.archive.org/web/20150914044950/http://www.medscape.com/viewarticle/849332|archive-date=14 September 2015|df=dmy-all}}</ref> About one third of those with ankylosing spondylitis have severe disease, which reduces life expectancy.<ref>{{cite journal | vauthors = Braun J, Pincus T | title = Mortality, course of disease and prognosis of patients with ankylosing spondylitis | journal = Clinical and Experimental Rheumatology | volume = 20 | issue = 6 Suppl 28 | pages = S16-22 | date = 2002 | pmid = 12463441 |url=https://www.researchgate.net/publication/11008397 | url-status = live | archive-url=https://web.archive.org/web/20161101102544/https://www.researchgate.net/publication/11008397_Mortality_course_of_disease_and_prognosis_of_patients_with_ankylosing_spondylitis | df = dmy-all | archive-date = 1 November 2016 }}</ref>


As increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting outcomes include:<ref name="pmid21784726" /><ref name="pmid887115">{{cite journal | vauthors = Radford EP, Doll R, Smith PG | title = Mortality among patients with ankylosing spondylitis not given X-ray therapy | journal = The New England Journal of Medicine | volume = 297 | issue = 11 | pages = 572–6 | date = September 1977 | pmid = 887115 | doi = 10.1056/NEJM197709152971103 }}</ref>
As increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting outcomes include:<ref name="pmid21784726" /><ref name="pmid887115">{{cite journal | vauthors = Radford EP, Doll R, Smith PG | title = Mortality among patients with ankylosing spondylitis not given X-ray therapy | journal = The New England Journal of Medicine | volume = 297 | issue = 11 | pages = 572–6 | date = September 1977 | pmid = 887115 | doi = 10.1056/NEJM197709152971103 }}</ref>
* Male sex <ref>{{cite journal | vauthors = Lehtinen K | title = Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 52 | issue = 3 | pages = 174–6 | date = March 1993 | pmid = 8484668 | pmc = 1005012 | doi = 10.1136/ard.52.3.174 }}</ref>
* Male sex<ref>{{cite journal | vauthors = Lehtinen K | title = Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 52 | issue = 3 | pages = 174–6 | date = March 1993 | pmid = 8484668 | pmc = 1005012 | doi = 10.1136/ard.52.3.174 }}</ref>
* Plus three of the following in the first two years of disease:
* Plus three of the following in the first two years of disease:
** [[Erythrocyte sedimentation rate]] (ESR) >30 mm/h
** [[Erythrocyte sedimentation rate]] (ESR) >30 mm/h
Line 163: Line 167:


==Epidemiology==
==Epidemiology==
Between 0.1% and 0.8% of people are affected.<ref name=Kh2009/> The disease is most common in Northern European countries, and seen least in people of Afro-Caribbean descent.<ref name="Patient UK_7">{{cite web|title=Ankylosing Spondylitis -Professional reference for Doctors - Patient UK|url=http://www.patient.co.uk/doctor/ankylosing-spondylitis|work=Patient UK|access-date=26 May 2014|url-status=live|archive-url=https://web.archive.org/web/20140407162116/http://www.patient.co.uk/doctor/ankylosing-spondylitis|archive-date=7 April 2014|df=dmy-all}}</ref> Although the ratio of male to female disease is reportedly 3:1,<ref name="Patient UK_7"/> many [[rheumatologist]]s believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease. The majority of people with AS, including 95 percent of people of European descent with the disease, express the [[HLA-B27]] antigen<ref name=Cecil>{{cite book| vauthors = Goldman L |title=Goldman's Cecil Medicine|publisher=Elsevier Saunders|location=Philadelphia|isbn=978-1-4377-2788-3|year=2011|page=607|edition=24th}}</ref> and high levels of [[immunoglobulin A]] (IgA) in the blood.<ref>{{cite journal | vauthors = Veys EM, van Leare M | title = Serum IgG, IgM, and IgA levels in ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 32 | issue = 6 | pages = 493–6 | date = November 1973 | pmid = 4202498 | pmc = 1006157 | doi = 10.1136/ard.32.6.493 }}</ref> In 2007, a team of researchers discovered two genes that may contribute to the cause of AS: [[ARTS-1]] and [[Interleukin 23|IL23R]].<ref>{{cite journal | vauthors = Brionez TF, Reveille JD | title = The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis | journal = Current Opinion in Rheumatology | volume = 20 | issue = 4 | pages = 384–91 | date = July 2008 | pmid = 18525349 | doi = 10.1097/BOR.0b013e32830460fe | s2cid = 205485848 }}</ref> Together with HLA-B27, these two genes account for roughly 70 percent of the overall number of cases of the disease.
Between 0.1% and 0.8% of people are affected.<ref name=Kh2009/> The disease is most common in Northern European countries, and seen least in people of Afro-Caribbean descent.<ref name="Patient UK_7">{{cite web|title=Ankylosing Spondylitis -Professional reference for Doctors Patient UK|url=http://www.patient.co.uk/doctor/ankylosing-spondylitis|work=Patient UK|access-date=26 May 2014|url-status=live|archive-url=https://web.archive.org/web/20140407162116/http://www.patient.co.uk/doctor/ankylosing-spondylitis|archive-date=7 April 2014|df=dmy-all}}</ref> Although the ratio of male to female disease is reportedly 3:1,<ref name="Patient UK_7"/> many [[rheumatologist]]s believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease. The majority of people with AS, including 95 per cent of people of European descent with the disease, express the [[HLA-B27]] antigen<ref name=Cecil>{{cite book| vauthors = Goldman L |title=Goldman's Cecil Medicine|publisher=Elsevier Saunders|location=Philadelphia|isbn=978-1-4377-2788-3|year=2011|page=607|edition=24th}}</ref> and high levels of [[immunoglobulin A]] (IgA) in the blood.<ref>{{cite journal | vauthors = Veys EM, van Leare M | title = Serum IgG, IgM, and IgA levels in ankylosing spondylitis | journal = Annals of the Rheumatic Diseases | volume = 32 | issue = 6 | pages = 493–6 | date = November 1973 | pmid = 4202498 | pmc = 1006157 | doi = 10.1136/ard.32.6.493 }}</ref> In 2007, a team of researchers discovered two genes that may contribute to the cause of AS: [[ARTS-1]] and [[Interleukin 23|IL23R]].<ref>{{cite journal | vauthors = Brionez TF, Reveille JD | title = The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis | journal = Current Opinion in Rheumatology | volume = 20 | issue = 4 | pages = 384–91 | date = July 2008 | pmid = 18525349 | doi = 10.1097/BOR.0b013e32830460fe | s2cid = 205485848 }}</ref> Together with HLA-B27, these two genes account for roughly 70 percent of the overall number of cases of the disease.


==History==
==History==
Line 169: Line 173:
[[File:AS trask closeup.png|thumb|Drawing from 1857 of [[Leonard Trask]] who had a severe case of AS]]
[[File:AS trask closeup.png|thumb|Drawing from 1857 of [[Leonard Trask]] who had a severe case of AS]]


Ankylosing spondylitis has a long history, having been distinguished from [[rheumatoid arthritis]] by [[Galen]] as early as the 2nd century AD.<ref>{{cite journal | vauthors = Dieppe P | title = Did Galen describe rheumatoid arthritis? | journal = Annals of the Rheumatic Diseases | volume = 47 | issue = 1 | pages = 84–5 | date = January 1988 | pmid = 3278697 | pmc = 1003452 | doi = 10.1136/ard.47.1.84-b }}</ref> Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was thought to be found in the skeletal remains of a 5000-year-old Egyptian mummy with evidence of bamboo spine.<ref>{{cite journal | vauthors = Calin A | title = Ankylosing spondylitis | journal = Clinics in Rheumatic Diseases | volume = 11 | issue = 1 | pages = 41–60 | date = April 1985 | doi = 10.1016/S0307-742X(21)00588-9 | pmid = 3158467 }}</ref><ref>{{cite book |url=https://books.google.com/books?id=kFhZGjFwjVYC&pg=PA25 |title=Spinal Disorders: Fundamentals of Diagnosis and Treatment |vauthors=Boos N, Aebi M |date=2008 |publisher=Springer Science & Business Media |isbn=9783540690917 |page=25 |language=en |archive-url=https://web.archive.org/web/20170908183556/https://books.google.com/books?id=kFhZGjFwjVYC&pg=PA25 |archive-date=8 September 2017 |url-status=live |df=dmy-all}}</ref> However, a subsequent report found that this was not the case.<ref>{{cite journal | vauthors = Saleem SN, Hawass Z | title = Ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis in royal Egyptian mummies of 18th -20th Dynasties? CT and archaeology studies | journal = Arthritis & Rheumatology | volume = 66 | issue = 12 | pages = 3311–6 | date = December 2014 | pmid = 25329920 | doi = 10.1002/art.38864 | s2cid = 42296180 }}</ref>
Ankylosing spondylitis was distinguished from [[rheumatoid arthritis]] by [[Galen]] as early as the 2nd century AD.<ref>{{cite journal | vauthors = Dieppe P | title = Did Galen describe rheumatoid arthritis? | journal = Annals of the Rheumatic Diseases | volume = 47 | issue = 1 | pages = 84–5 | date = January 1988 | pmid = 3278697 | pmc = 1003452 | doi = 10.1136/ard.47.1.84-b }}</ref> Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was thought to be found in the skeletal remains of a 5000-year-old Egyptian mummy with evidence of bamboo spine.<ref>{{cite journal | vauthors = Calin A | title = Ankylosing spondylitis | journal = Clinics in Rheumatic Diseases | volume = 11 | issue = 1 | pages = 41–60 | date = April 1985 | doi = 10.1016/S0307-742X(21)00588-9 | pmid = 3158467 }}</ref><ref>{{cite book |url=https://books.google.com/books?id=kFhZGjFwjVYC&pg=PA25 |title=Spinal Disorders: Fundamentals of Diagnosis and Treatment |vauthors=Boos N, Aebi M |date=2008 |publisher=Springer Science & Business Media |isbn=9783540690917 |page=25 |language=en |archive-url=https://web.archive.org/web/20170908183556/https://books.google.com/books?id=kFhZGjFwjVYC&pg=PA25 |archive-date=8 September 2017 |url-status=live |df=dmy-all}}</ref> However, a subsequent report found that this was not the case.<ref>{{cite journal | vauthors = Saleem SN, Hawass Z | title = Ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis in royal Egyptian mummies of 18th −20th Dynasties? CT and archaeology studies | journal = Arthritis & Rheumatology | volume = 66 | issue = 12 | pages = 3311–6 | date = December 2014 | pmid = 25329920 | doi = 10.1002/art.38864 | s2cid = 42296180 }}</ref>


The anatomist and surgeon [[Realdo Colombo]] described what could have been the disease in 1559,<ref>{{cite journal | vauthors = Benoist M | title = Pierre Marie. Pioneer investigator in ankylosing spondylitis | journal = Spine | volume = 20 | issue = 7 | pages = 849–52 | date = April 1995 | pmid = 7701402 | doi = 10.1097/00007632-199504000-00022 }}</ref> and the first account of pathologic changes to a skeleton possibly associated with AS was published in 1691 by [[Bernard Connor]].<ref>{{cite journal | vauthors = Blumberg BS | title = Bernard Connor's description of the pathology of ankylosing spondylitis | journal = Arthritis and Rheumatism | volume = 1 | issue = 6 | pages = 553–63 | date = December 1958 | pmid = 13607268 | doi = 10.1002/art.1780010609 | doi-access = free }}</ref> In 1818, [[Sir Benjamin Collins Brodie, 1st Baronet|Benjamin Brodie]] became the first physician to document a person believed to have active AS who also had accompanying [[iritis]].<ref>{{cite journal | vauthors = Leden I | title = Did Bechterew describe the disease which is named after him? A question raised due to the centennial of his primary report | journal = Scandinavian Journal of Rheumatology | volume = 23 | issue = 1 | pages = 42–5 | year = 1994 | pmid = 8108667 | doi = 10.3109/03009749409102134 }}</ref>
The anatomist and surgeon [[Realdo Colombo]] described what could have been the disease in 1559,<ref>{{cite journal | vauthors = Benoist M | title = Pierre Marie. Pioneer investigator in ankylosing spondylitis | journal = Spine | volume = 20 | issue = 7 | pages = 849–52 | date = April 1995 | pmid = 7701402 | doi = 10.1097/00007632-199504000-00022 }}</ref> and the first account of pathologic changes to a skeleton possibly associated with AS was published in 1691 by [[Bernard Connor]].<ref>{{cite journal | vauthors = Blumberg BS | title = Bernard Connor's description of the pathology of ankylosing spondylitis | journal = Arthritis and Rheumatism | volume = 1 | issue = 6 | pages = 553–63 | date = December 1958 | pmid = 13607268 | doi = 10.1002/art.1780010609 | doi-access = free }}</ref> In 1818, [[Sir Benjamin Collins Brodie, 1st Baronet|Benjamin Brodie]] became the first physician to document a person believed to have active AS who also had accompanying [[iritis]].<ref>{{cite journal | vauthors = Leden I | title = Did Bechterew describe the disease which is named after him? A question raised due to the centennial of his primary report | journal = Scandinavian Journal of Rheumatology | volume = 23 | issue = 1 | pages = 42–5 | year = 1994 | pmid = 8108667 | doi = 10.3109/03009749409102134 }}</ref>


In 1858, David Tucker published a small booklet which clearly described the case of [[Leonard Trask]], who had severe spinal deformity subsequent to AS.<ref>{{cite web | title=Life and sufferings of Leonard Trask | url=http://www.HLAB27.com.com/members/life%20and%20sufferings%20of%20leonard%20trask.pdf | publisher=Ankylosing Spondylitis Information Matrix. | url-status=live | archive-url=https://web.archive.org/web/20110708180013/http://www.hlab27.com.com/members/life%20and%20sufferings%20of%20leonard%20trask.pdf | archive-date=8 July 2011 | df=dmy-all }}</ref> In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:
In 1858, David Tucker published a small booklet which clearly described the case of [[Leonard Trask]], who had severe spinal deformity subsequent to AS.<ref>{{cite web | title=Life and sufferings of Leonard Trask |url=http://www.HLAB27.com.com/members/life%20and%20sufferings%20of%20leonard%20trask.pdf | publisher=Ankylosing Spondylitis Information Matrix. | url-status=live | archive-url=https://web.archive.org/web/20110708180013/http://www.hlab27.com.com/members/life%20and%20sufferings%20of%20leonard%20trask.pdf | archive-date=8 July 2011 | df=dmy-all }}</ref> In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:
{{blockquote|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.}}
{{blockquote|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.}}
The account of Trask 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.
The account of Trask 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.


In the late nineteenth century, the [[neurophysiologist]] [[Vladimir Bekhterev]] of Russia in 1893,<ref>{{cite journal | vauthors = Bechterew W | title=Steifigkeit der Wirbelsaule und ihre Verkrummung als besondere Erkrankungsform | journal = Neurol Centralbl | year = 1893 | volume = 12 | pages = 426–434}}</ref> [[Adolph Strümpell]] of Germany in 1897,<ref>{{cite journal | vauthors = Strumpell A | s2cid=34700673 | title=Bemerkung uber die chronische ankylosirende Entzundung der Wirbelsaule und der Huftgelenke | journal=Dtsch Z Nervenheilkd | year=1897 | volume=11 | pages = 338–342 | doi = 10.1007/BF01674127 | issue = 3–4 | url=https://zenodo.org/record/1615818 }}</ref> and [[Pierre Marie]] of France in 1898<ref>{{cite journal | vauthors = Marie P | title=Sur la spondylose rhizomelique | journal = Rev Med | year=1898 | volume=18 | pages = 285–315 }}</ref> 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.
In the late nineteenth century, the [[neurophysiologist]] [[Vladimir Bekhterev]] of Russia in 1893,<ref>{{cite journal | vauthors = Bechterew W | title=Steifigkeit der Wirbelsaule und ihre Verkrummung als besondere Erkrankungsform | journal = Neurol Centralbl | year = 1893 | volume = 12 | pages = 426–434}}</ref> [[Adolf Strümpell]] of Germany in 1897,<ref>{{cite journal | vauthors = Strumpell A | s2cid=34700673 | title=Bemerkung uber die chronische ankylosirende Entzundung der Wirbelsaule und der Huftgelenke | journal=Dtsch Z Nervenheilkd | year=1897 | volume=11 | pages = 338–342 | doi = 10.1007/BF01674127 | issue = 3–4 |url=https://zenodo.org/record/1615818 }}</ref> and [[Pierre Marie]] of France in 1898<ref>{{cite journal | vauthors = Marie P | title=Sur la spondylose rhizomelique | journal = Rev Med | year=1898 | volume=18 | pages = 285–315 }}</ref> 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.


The word is from [[Greek language|Greek]] ''ankylos'' meaning crooked, curved or rounded, ''spondylos'' meaning vertebra, and ''-itis'' meaning inflammation.<ref name="NIH2016" />
The word is from [[Greek language|Greek]] ''ankylos'' meaning crooked, curved or rounded, ''spondylos'' meaning vertebra, and ''-itis'' meaning inflammation.<ref name="NIH2016" />

== See also ==

* [[Fibrodysplasia ossificans progressiva]]


== References ==
== References ==
Line 188: Line 196:
* [https://www.niams.nih.gov/health-topics/ankylosing-spondylitis Questions and Answers about Ankylosing Spondylitis] - US National Institute of Arthritis and Musculoskeletal and Skin Diseases
* [https://www.niams.nih.gov/health-topics/ankylosing-spondylitis Questions and Answers about Ankylosing Spondylitis] - US National Institute of Arthritis and Musculoskeletal and Skin Diseases


{{Medical condition classification and resources
{{Medical resources
| ICD11 = {{ICD11|FA92.0Z}}
| ICD10 = {{ICD10|M|08|1|m|05}}, {{ICD10|M|45||m|45}}
| ICD10 = {{ICD10|M|08|1|m|05}}, {{ICD10|M|45||m|45}}
| ICD9 = {{ICD9|720.0}}
| ICD10CM = <!-- {{ICD10CM|Xxx.xxxx}} -->
| ICDO =
| ICD9 = {{ICD9|720}}
| OMIM = 106300
| ICDO =
| MedlinePlus = 000420
| OMIM = 106300
| eMedicineSubj = radio
| MeshID = D013167
| eMedicineTopic = 41
| DiseasesDB = 728
| DiseasesDB = 728
| SNOMED CT = 9631008
| MeshID = D013167
| Curlie =
| MedlinePlus = 000420
| eMedicineSubj = radio
| eMedicineTopic = 41
| PatientUK =
| NCI =
| GeneReviewsNBK =
| GeneReviewsName =
| NORD =
| GARDNum =
| GARDName =
| RP = 904
| AO =
| WO =
| OrthoInfo =
| Orphanet =
| Scholia = Q52849
| OB =
}}
}}

{{Arthropathies and related conditions}}
{{Arthropathies and related conditions}}
{{Dorsopathies}}
{{Dorsopathies}}

Latest revision as of 13:08, 3 September 2024

Ankylosing spondylitis
Other namesBekhterev's disease, Bechterew's disease, morbus Bechterew, Bekhterev–Strümpell–Marie disease, Marie's disease, Marie–Strümpell arthritis, Pierre–Marie's disease[1]
A 6th-century skeleton showing fused vertebrae, a sign of severe ankylosing spondylitis
SpecialtyRheumatology
SymptomsBack pain, joint stiffness[2]
ComplicationsEye inflammation (uveitis), Compression fractures, Heart problems.[3]
Usual onsetYoung adulthood[2]
DurationLifetime[2]
CausesUnknown[2]
Diagnostic methodSymptoms, medical imaging and blood tests[2]
TreatmentMedication, physical therapy
MedicationNSAIDs, steroids, DMARDs,[2] TNF Inhibitor
Frequency0.1 to 0.8%[4]

Ankylosing spondylitis (AS) is a type of arthritis from the disease spectrum of axial spondyloarthritis.[5] It is characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis.[2] With AS, eye and bowel problems—as well as back pain—may occur.[2] Joint mobility in the affected areas sometimes worsens over time.[2][6] Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors.[2] More than 90% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen.[7] The underlying mechanism is believed to be autoimmune or autoinflammatory.[8] Diagnosis is based on symptoms with support from medical imaging and blood tests.[2] AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.[2]

There is no cure for AS. Treatments may include medication, physical therapy, and surgery. Medication therapy focuses on relieving the pain and other symptoms of AS, as well as stopping disease progression by counteracting long-term inflammatory processes. Commonly used medications include NSAIDs, TNF inhibitors, IL-17 antagonists, and DMARDs. Glucocorticoid injections are often used for acute and localized flare-ups.[9]

About 0.1% to 0.8% of the population are affected, with onset typically occurring in young adults.[2][4] While men and women are equally affected with AS, women are more likely to experience inflammation rather than fusion.[10]

Signs and symptoms

[edit]
Illustration depicting ankylosing spondylitis

The signs and symptoms of ankylosing spondylitis often appear gradually, with peak onset between 20 and 30 years of age.[11] Initial symptoms are usually a chronic dull pain in the lower back or gluteal region combined with stiffness of the lower back.[12] Individuals often experience pain and stiffness that awakens them in the early morning hours.[11]

As the disease progresses, loss of spinal mobility and chest expansion, with a limitation of anterior flexion, lateral flexion, and extension of the lumbar spine are seen. Systemic features are common with weight loss, fever, or fatigue often present.[11] Pain is often severe at rest but may improve with physical activity. Inflammation and pain may recur to varying degrees regardless of rest and movement.

AS can occur in any part of the spine or the entire spine, often with pain localized to either buttock or the back of the thigh from the sacroiliac joint. Arthritis in the hips and shoulders may also occur. When the condition presents before the age of 18, AS is more likely to cause pain and swelling of large lower limb joints, such as the knees.[13] In prepubescent cases, pain and swelling may also manifest in the ankles and feet where heel pain and enthesopathy commonly develop.[13] Less common occurrences include ectasia of the sacral nerve root sheaths.[14]

About 30% of people with AS will also experience anterior uveitis causing eye pain, redness, and blurred vision. This is thought to be due to the association that both AS and uveitis have with the presence of the HLA-B27 antigen.[15] Cardiovascular involvement may include inflammation of the aorta, aortic valve insufficiency or disturbances of the heart's electrical conduction system. Lung involvement is characterized by progressive fibrosis of the upper portion of the lung.[16]

Pathophysiology

[edit]
The ankylosis process

Ankylosing spondylitis (AS) is a systemic rheumatic disease, meaning it affects the entire body. 1–2% of individuals with the HLA-B27 genotype develop the disease.[17] Tumor necrosis factor-alpha (TNF α) and interleukin 1 (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.[18]

Single nucleotide polymorphism (SNP) A/G variant rs10440635[19] is close to the PTGER4 gene on human chromosome 5 has been associated with an increased number of cases of AS in a population recruited from the United Kingdom, Australia, and Canada. The PTGER4 gene codes for the prostaglandin EP4 receptor, one of four receptors for prostaglandin E2. Activation of EP4 promotes bone remodeling and deposition (see prostaglandin EP4 receptor § Bone) and EP4 is highly expressed at vertebral column sites involved in AS. These findings suggest that excessive EP4 activation contributes to pathological bone remodeling and deposition in AS and that the A/G variant rs10440635a of PTGER4 predisposes individuals to this disease, possibly by influencing EP4's production or expression pattern.[20][21]

The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B.[22] This interaction is not proven to involve a self-antigen, and at least in the related reactive arthritis, which follows infections, the antigens involved are likely to be derived from intracellular microorganisms.[7] There is, however, a possibility that CD4+ T lymphocytes 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 CD8+ cytotoxic T cell with HLAB antigen as it is a MHC class 1 antigen).

"Bamboo spine" develops when the outer fibers of the fibrous ring (anulus fibrosus disci intervertebralis) of the intervertebral discs ossify, which results in the formation of marginal syndesmophytes between adjoining vertebrae.

Diagnosis

[edit]
34-year-old male with AS. Inflammatory lesions of the anterior chest wall are shown (curved arrows). Inflammatory changes are seen in the lower thoracic spine and L1 (arrows).

Ankylosing spondylitis is a member of the more broadly defined disease axial spondyloarthritis.[23][24] Axial spondyloarthritis can be divided into two categories: radiographic axial spondyloarthritis (which is a synonym for ankylosing spondylitis) and non-radiographic axial spondyloarthritis (which include less severe forms and early stages of ankylosing spondylitis).[23]

While AS can be diagnosed through the description of radiological changes in the sacroiliac joints and spine, there are currently no direct tests (blood or imaging) to unambiguously diagnose early forms of ankylosing spondylitis (non-radiographic axial spondyloarthritis). Diagnosis of non-radiologic axial spondyloarthritis is therefore more difficult and is based on the presence of several typical disease features.[23][25]

These diagnostic criteria include:

  • Inflammatory back pain:
    Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up). Pain often subsides as the day progresses with movement being of importance to alleviate the joint stiffness.
  • Past history of inflammation in the joints, heels, or tendon-bone attachments
  • Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions
  • Positive for the biomarker HLA-B27
  • Good response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate)
  • Manifestation of psoriasis, inflammatory bowel disease, or inflammation of the eye (uveitis)

If these criteria still do not give a compelling diagnosis magnetic resonance imaging (MRI) may be useful.[23][25] MRI can show inflammation of the sacroiliac joint.

Imaging

[edit]

X-rays

[edit]

The earliest changes demonstrable by plain X-ray shows erosions and sclerosis in sacroiliac joints. Progression of the erosions leads to widening of the joint space and bony sclerosis. X-ray spine can reveal squaring of vertebrae with bony spur formation called syndesmophyte. This causes the bamboo spine appearance. A drawback of X-ray diagnosis is the signs and symptoms of AS have usually been established as long as 7–10 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.[26]

Options for earlier diagnosis are tomography and MRI of the sacroiliac joints, but the reliability of these tests is still unclear.

Blood parameters

[edit]

During acute inflammatory periods, people with AS may show an increase in the blood concentration of CRP and an increase in the 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.[27]

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 85% of people that have been diagnosed with AS are HLA-B27 positive, although this ratio varies from population to population (about 50% of African Americans with AS possess HLA-B27 in contrast to the figure of 80% among those with AS who are of Mediterranean descent).[28]

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.[29] It can be easily calculated and accurately assesses the need for additional therapy; a person with AS 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 functional impairment due to the disease, as well as improvements following therapy.[30] The BASFI is not usually used as a diagnostic tool, but rather as a tool to establish a current baseline and subsequent response to therapy.

Children

[edit]

Juvenile ankylosing spondylitis (JAS) is a rare form of the disease which differs from the more common adult form.[13] Enthesophathy and arthritis of large joints of the lower extremities is more common than the characteristic early-morning back pain seen in adult AS.[13] Ankylosing tarsitis of the ankle is a common feature, as is the more classical findings of seronegative ANA and RF as well as presence of the HLA-B27 allele.[13] Primary engagement of the appendicular joints may explain delayed diagnosis; however, other common symptoms of AS such as uveitis, diarrhea, pulmonary disease and heart valve disease may lead suspicion away from other juvenile spondyloarthropathies.[13]

Schober's test

[edit]

The Schober's test is a useful clinical measure of flexion of the lumbar spine performed during the physical examination.[31]

Treatment

[edit]

There is no cure for AS,[32] but treatments and medications can reduce symptoms and pain.

Medication

[edit]

Medications for AS may be broadly considered either "disease-modifying" or "non-disease-modifying". Disease-modifying medications for ankylosing spondylitis aim to slow disease progression and include drugs like tumor necrosis factor (TNF) inhibitors. Non-disease-modifying medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), primarily address symptoms like pain and inflammation but do not alter the course of the disease.[33]

NSAIDs

[edit]

Unless otherwise contraindicated, all people with AS are recommended to take non-steroidal anti-inflammatory drugs (NSAIDs). The dose, frequency, and specific drug may depend on the individual and the symptoms they experience. NSAIDs, such as ibuprofen and naproxen, are used to alleviate pain, reduce inflammation, and improve joint stiffness associated with AS. These medications work by inhibiting the activity of cyclooxygenase (COX) enzymes, which are involved in the production of inflammatory prostaglandins. By reducing the levels of prostaglandins, NSAIDs help mitigate the inflammatory response and relieve symptoms in individuals with ankylosing spondylitis.[9][34]

TNF inhibitors

[edit]

Tumor necrosis factor inhibitors (TNFi) are a class of biologic drugs used in the treatment of ankylosing spondylitis. TNFi drugs, such as etanercept, infliximab, adalimumab, certolizumab, and golimumab, target the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). TNF-alpha plays a key role in the inflammatory process in ankylosing spondylitis. By blocking TNF-alpha, TNFi drugs help reduce inflammation, pain, and stiffness associated with AS, and may also slow down the progression of spinal damage.[9][35]

Non-TNFi biologics

[edit]

Non-TNFi "biologic" drugs used in the treatment of ankylosing spondylitis include drugs that target different pathways involved in the inflammatory process. Two of the most important drugs in this class target IL-17, an important part of the inflammatory system: secukinumab and ixekizumab. They are often considered in cases where TNFi drugs are not effective or cause too many side effects. Additionally, they may sometimes be used as an adjunct to a TNFi when symptoms persist, but improve, while the patient is on the TNFi. The choice of a specific non-TNFi biologic depends on various factors, including the patient's medical history, preferences, and the recommendations of the healthcare provider.[9]

Ustekinumab has frequently been used as a second-line therapy for AS, but it has recently been scrutinized for a lack of efficacy, and is no longer recommended.[36][9]

Biosimilar drugs

[edit]

Biosimilar drugs are biological products that are highly similar to an already approved biologic drug, with few or no clinically meaningful differences in terms of safety, purity, and potency. These drugs are developed to be equivalent to the reference biologic, often at a lower cost, providing alternative treatment options. In the context of ankylosing spondylitis, biosimilars are typically used as alternatives to the original biologic drugs. Biosimilars for ankylosing spondylitis may include versions of tumor necrosis factor inhibitors or other biologics commonly used in the treatment of the condition. When possible, physicians are recommended to use the original drugs over the biosimilar versions. Even biosimilars with perfect replication of the quality, composition, and other properties of the original drug are susceptible to nocebo effects.[9][37]

csARDs

[edit]

Conventional synthetic antirheumatic drugs (csARDs) are a class of disease-modifying medications. Unlike biologics or targeted synthetic drugs, which act on specific pathways in the immune system, csARDs have a broader effect on the immune system and are often considered traditional or conventional treatments. The most common drugs in this class are methotrexate and sulfasalazine. These medications are only used when others fail, or when certain specific conditions are met, and are often discontinued if a patient's symptoms become manageable with just a TNFi or other medication. Conventional DMARDs such as leflunomide are also considered to be part of this class.[9]

Concerns exist about a possible lack of efficacy of some drugs in this class.[38]

Corticosteroids

[edit]

Glucocorticoids, such as prednisone or methylprednisolone, are sometimes used in the treatment of ankylosing spondylitis to manage acute flares and provide short-term relief from inflammation and symptoms. They are powerful anti-inflammatory medications that can help reduce pain, swelling, and stiffness associated with AS. However, glucocorticoids are generally not recommended for long-term use. They are more commonly used as localized injections when someone with AS has a temporary pain flare in a particular joint or area.[9]

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 that make anesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anesthesia may be difficult owing to calcification of ligaments, and a small number of people 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. There is moderate quality evidence that therapeutic exercise programs help reduce pain and improve function.[39] Therapeutic exercises include:[40][41]

Diet

[edit]

Research by Alan Ebringer at King's College in London, beginning in the 1980s, implicates overgrowth of the bacterium Klebsiella pneumoniae in the symptoms of ankylosing spondylitis. The body produces antibodies that attack Klebsiella pneumoniae. Enzymes made by the bacterium resemble human proteins, including three types of collagen (I, III, IV) and the HLA-B27 complex of glycoproteins. The antibodies therefore attack these human proteins, producing the symptoms of ankylosing spondylitis. Ebringer and others recommend low-starch or no-starch diets.[44]

Prognosis

[edit]
Fracture of the T5 and C7 vertebra due to trauma in a person with ankylosing spondylitis as seen on a CT scan

Prognosis is related to disease severity.[11] 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.[11] As the disease progresses, it can cause the vertebrae and the lumbosacral joint to ossify, resulting in the fusion of the spine.[45] 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. 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.[46]

Osteoporosis is common in ankylosing spondylitis, both from chronic systemic inflammation and decreased mobility resulting from AS. Over a long-term period, osteopenia or osteoporosis of the AP spine may occur, causing eventual compression fractures and a back "hump".[47] Hyperkyphosis from ankylosing spondylitis can also lead to impairment in mobility and balance, as well as impaired peripheral vision, which increases the risk of falls which can cause fracture of already-fragile vertebrae.[47] Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. In compression fractures 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.[48] 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.[48][49]

Mortality

[edit]

Mortality is increased in people with AS and circulatory disease is the most frequent cause of death.[50] People with AS have an increased risk of 60% for cerebrovascular mortality, and an overall increased risk of 50% for vascular mortality.[51] About one third of those with ankylosing spondylitis have severe disease, which reduces life expectancy.[52]

As increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting outcomes include:[50][53]

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 dorsiflexion. 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.[55]

Epidemiology

[edit]

Between 0.1% and 0.8% of people are affected.[4] The disease is most common in Northern European countries, and seen least in people of Afro-Caribbean descent.[11] Although the ratio of male to female disease is reportedly 3:1,[11] many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder cases of the disease. The majority of people with AS, including 95 per cent of people of European descent with the disease, express the HLA-B27 antigen[56] and high levels of immunoglobulin A (IgA) in the blood.[57] In 2007, a team of researchers discovered two genes that may contribute to the cause of AS: ARTS-1 and IL23R.[58] Together with HLA-B27, these two genes account for roughly 70 percent of the overall number of cases of the disease.

History

[edit]
Drawing from 1857 of Leonard Trask who had a severe case of AS

Ankylosing spondylitis was distinguished from rheumatoid arthritis by Galen as early as the 2nd century AD.[59] Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was thought to be found in the skeletal remains of a 5000-year-old Egyptian mummy with evidence of bamboo spine.[60][61] However, a subsequent report found that this was not the case.[62]

The anatomist and surgeon Realdo Colombo described what could have been the disease in 1559,[63] and the first account of pathologic changes to a skeleton possibly associated with AS was published in 1691 by Bernard Connor.[64] In 1818, Benjamin Brodie became the first physician to document a person believed to have active AS who also had accompanying iritis.[65]

In 1858, David Tucker published a small booklet which clearly described the case of Leonard Trask, who had severe spinal deformity subsequent to AS.[66] 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.

The account of Trask 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.

In the late nineteenth century, the neurophysiologist Vladimir Bekhterev of Russia in 1893,[67] Adolf Strümpell of Germany in 1897,[68] and Pierre Marie of France in 1898[69] 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.

The word is from Greek ankylos meaning crooked, curved or rounded, spondylos meaning vertebra, and -itis meaning inflammation.[2]

See also

[edit]

References

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