Ankylosing spondylitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Galen was the first to distinguish the difference between ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Realdo Colombo has first described ankylosing spondylitis. Bernard Connor was first to describe pathological changes occurring in ankylosing spondylitis. Axial spondyloarthritis (axSpA) may be classified according to Assessment of SpondyloArthritis International Society (ASAS) into ankylosing spondylitis (AS) and non-radiographicaxSpA (nr-axSpA). AS has been regarded as the prototype of spondyloarthritis. Ankylosing spondylitis (AS) is a chronic, multisystem inflammatory disorder involving primarily the sacroiliac (SI) joints and the axial skeleton. The outcome in patients with a spondyloarthropathy, including AS, is generally compared with that in patients with a disease such as rheumatoid arthritis. Mostly the joints where the spine joins the pelvis are also affected. Back pain is one of the most prominent symptoms of the ankylosing spondylitis (AS) which is intermittent in nature. Stiffness in the affected joints gets worse as the disease progresses. It is believed that both the combination of genetic and environmental factors play an important role in the pathogenesis of ankylosing spondylitis(AS) and the underlying etiology is believed to be autoimmune or autoinflammatory. Ankylosing spondylitis is an inflammatory disease that in overtime it causes some of the vertebrae in spine to fuse. Because of the fusion the spine less flexible and the patients present with hunched-forward posture. It can be difficult to breathe deeply when the ribs are involved. The most common cause of ankylosing spondylitis is involvement of gene HLA B27. Ankylosing spondylitis must be differentiated from other diseases causing reactive arthritis,rheumatoid arthritis and psoriatic arthritis. The prevalence of axial spondyloarthritis (axSpA) or ankylosing spondylitis in a population depends upon the following 1)Ethnic groups 2) Selection of subjects for evaluation and 3) The criteria for diagnosis.It shows a clear evidence that correlation between the prevalence of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) in a given population and the prevalence of human leukocyte antigen HLA-B27 exits. There is no known cause specific cause for ankylosing spondylitis, though genetic factors seems to play very important role in developing the disease. In particular, people who are positive for HLA-B27 are at more risk of developing ankylosing spondylitis.Ankylosing spondylitis is a form of chronic joint inflammation that mostly affects the spine. Gradually it can cause the bones of the spine to fuse together, a process which is called ankylosis. Ankylosing spondylitis symptoms can range from back pain and stiffness and in long term it can lead to disability. Ankylosing spondylitis is usually remarkable for involvement of axial joints, peripheral joints, and entheses. Physical examination of AS includes a typical diagnostic process that includes exams and tests. The physical examination of AS includes cervical spine, thoracic spine, lateral spinal flexion, Schober test, sacroiliac joint tenderness test and hip joint tests. An x-ray may be helpful in the diagnosis of ankylosing spondylitis (AS). Findings on an x-ray suggestive of ankylosing spondylitis (AS) include erosion and ankylosis of the sacroiliac joints. Findings on CT scan suggestive of ankylosing spondylitis include erosion, osteoporosis / sclerosis, and new bone formation. However,CT has poor ability to detect soft-tissue changes and best in detecting osteoporosis or osteosclerosis. Findings on MRI suggestive of ankylosing spondylitisinclude sacroiliitis, disease activity,cartilage condition and enthesitis. MRI allows assessment of all of the structures that are involved in musculoskeletal diseases. Pharmacologic medical therapies for ankylosing spondylitis(AS) include Nonsteroidal anti-inflammatory drugs(NSAIDs), tumor necrosis factor (TNF) blocker, and interleukin 17 (IL-17) inhibitors.

Galen was the first to distinguish the difference between ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Realdo Colombo has first described ankylosing spondylitis. Bernard Connor was first to describe pathological changes occurring in ankylosing spondylitis.

Axial spondyloarthritis (axSpA) may be classified according to Assessment of SpondyloArthritis International Society (ASAS) into ankylosing spondylitis (AS) and non-radiographicaxSpA (nr-axSpA). Formerly ankylosing spondylitis (AS) was termed as spondyloarthritides or spondyloarthropathies. AS has been regarded as the prototype of spondyloarthritis. Previously ankylosing spondylitis (AS), spondyloarthritis (SpA), reactive arthritis, psoriatic arthritis, arthritis and spondylitis associated with Crohn disease and ulcerative colitis which belong to inflammatory bowel disease (IBD).

Ankylosing spondylitis (AS), a spondyloarthropathy, is a chronic, multisystem inflammatory disorder involving primarily the sacroiliac (SI) joints and the axial skeleton. The outcome in patients with a spondyloarthropathy, including AS, is generally compared with that in patients with a disease such as rheumatoid arthritis. Mostly the joints where the spine joins the pelvis are also affected. Back pain is one of the most prominent symptoms of the ankylosing spondylitis (AS) which is intermittent in nature. Stiffness in the affected joints gets worse as the disease progresses. It is believed that both the combination of genetic and environmental factors play an important role in the pathogenesis of ankylosing spondylitis(AS) and the underlying etiology is believed to be autoimmune or autoinflammatory.

Ankylosing spondylitis is an inflammatory disease that in overtime it causes some of the vertebrae in spine to fuse. Because of the fusion the spine less flexible and the patients present with hunched-forward posture. It can be difficult to breathe deeply when the ribs are involved. The most common cause of ankylosing spondylitis is involvement of gene HLA B27.

Ankylosing spondylitis must be differentiated from other diseases causing reactive arthritis,rheumatoid arthritis and psoriatic arthritis.

The prevalence of axial spondyloarthritis (axSpA) or ankylosing spondylitis in a population depends upon the following 1)Ethnic groups 2) Selection of subjects for evaluation and 3) The criteria for diagnosis.It shows a clear evidence that correlation between the prevalence of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) in a given population and the prevalence of human leukocyte antigen HLA-B27 exits.

There is no known cause specific cause for ankylosing spondylitis, though genetic factors seems to play very important role in developing the disease. In particular, people who are positive for HLA-B27 are at more risk of developing ankylosing spondylitis.Ankylosing spondylitis is a form of chronic joint inflammation that mostly affects the spine. Gradually it can cause the bones of the spine to fuse together, a process which is called ankylosis.

The natural history of ankylosing spondylitis(AS) remains poorly documented. Documentation of the early course of ankylosing spondylitis (AS) has been limited by the lack of appropriate criteria to diagnose early. New York criteria plays an important role in the study of ankylosing spondylitis (AS).

Ankylosing spondylitis is a form of arthritis which is progressive and painful. In ankylosing spondylitis some or all of the joints and bones of the spine fuse together and causes pain and restriction of the movement of the spine.The spinal involvement is more extensive in ankylosing spondylitis (AS). Ankylosing spondylitis symptoms can range from back pain and stiffness and in long term it can lead to disability.Although cause of ankylosing spondylitis is unknown but mostly it is associated with genetic marker called HLA-B27.

Ankylosing spondylitis is usually remarkable for involvement of axial joints, peripheral joints, and entheses. Physical examination of AS includes a typical diagnostic process that includes exams and tests. The physical examination of AS includes cervical spine, thoracic spine, lateral spinal flexion, Schober test, sacroiliac joint tenderness test and hip joint tests.

There are no specific diagnostic laboratory findings associated with ankylosing spondylitis (AS). There are certain blood tests that can check for markers of inflammation.Most of the time patients with AS their blood is tested for the HLA-B27 gene, but again most people who are positive for that gene don’t have ankylosing spondylitis. Other laboratory findings consistent with ankylosing spondylitis (AS) include ESR and CRP levels.

An x-ray may be helpful in the diagnosis of ankylosing spondylitis (AS). Findings on an x-ray suggestive of ankylosing spondylitis (AS) include erosion and ankylosis of the sacroiliac joints.

CT allows direct visualization of the abnormalities in peripheral and axial joints. CT has resulted in a major improvement in the evaluation and management of patients with AS. Findings on CT scan suggestive of ankylosing spondylitis include erosion, osteoporosis / sclerosis, and new bone formation. However,CT has poor ability to detect soft-tissue changes and best in detecting osteoporosis or osteosclerosis.

MRI may be helpful in the diagnosis of ankylosing spondylitis. Findings on MRI suggestive of ankylosing spondylitisinclude sacroiliitis, disease activity,cartilage condition and enthesitis. MRI allows assessment of all of the structures that are involved in musculoskeletal diseases. MRI is more sensitive in inflammatory and degenerative rheumatological disorders. However, not all patients with nr-axSpA have abnormal MRI findings.

Pharmacologic medical therapies for ankylosing spondylitis(AS) include Nonsteroidal anti-inflammatory drugs(NSAIDs), tumor necrosis factor (TNF) blocker, and interleukin 17 (IL-17) inhibitors. Ankylosing spondylitis (AS) is a chronic inflammatory disease which is manifested by back pain and gradually to spinal stiffness.While treating the AS patients the primary goal is to maximize long-term health-related quality of life.

Surgery is not the first-line treatment option for patients with ankylosing spondylitis. Surgical options, such as knee and hip replacements, can be an option for patients with ankylosing spondylitis. Surgical correction is also possible for those with severe flexion deformities, such as a severe downward curvature of the spine.

There are no established measures for the primary prevention of ankylosing spondylitis.

There are no established measures for the secondary prevention of ankylosing spondylitis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Galen was the first to distinguish the difference between ankylosing spondylitis and rheumatoid arthritis.Realdo Colombo has first described ankylosing spondylitis.Bernard Connor was first to describe ankylosing spondylitis pathologic changes.

• In 2nd century, Galen was the first to distinguish the difference between ankylosing spondylitis and rheumatoid arthritis.^[1]
• A 5000-year-old Egyptian mummy skeletal remains shows skeletal evidence of the disease ankylosing spondylitis.^[2]
• Ankylosing spondylitis was first described by Realdo Colombo,a anatomist and surgeon, in in 1559.^[3]
• Ankylosing spondylitis pathologic changes was first described by Bernard Connor,in 1691.

• Monoclonal antibodies was developed to treat ankylosing spondylitis was an important landmark events in the treatment strategies.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Axial spondyloarthritis (axSpA) may be classified according to Assessment of SpondyloArthritis International Society (ASAS) into ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Formerly ankylosing spondylitis (AS) termed as spondyloarthritides or spondyloarthropathies. AS has been regarded as the prototype of spondyloarthritis. Previously ankylosing spondylitis (AS), spondyloarthritis (SpA), reactive arthritis, psoriatic arthritis, arthritis and spondylitis associated with Crohn disease and ulcerative colitis which belong to inflammatory bowel disease (IBD).

• Spondyloarthritis (axSpA) may be classified according to Assessment of SpondyloArthritis International Society (ASAS) into following^{[1][2][3][4][5]}
  • Axial SpA: Which includes ankylosing spondylitis (AS)
    • Predominantly axial disease, is a potentially disabling inflammatory arthritis of the spine.
    • Patients with ankylosing spondylitis present with abnormal radiographic findings consistent with sacroiliitis.
    • Patients with ankylosing spondylitis mostly carry the gene for human leukocyte antigen (HLA)-B27.
    • Patients who are suffering with inflammatory bowel disease(IBD) often an elevated acute phase response.
  • Peripheral SpA: In peripheral SpA Symptoms and findings are predominantly peripheral rather than axial which include arthritis mostly seen in the lower limbs,enthesitis, and dactylitis.
  • Patients included in this category are with psoriatic arthritis (PsA), reactive arthritis.
  • Patients with AS and non-radiographic axial SpA are not included within the peripheral SpA category.
  • Non-radiographic axial spondyloarthritis 
    •  The clinical course and disease process still remains unclear.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Ankylosing spondylitis (AS), a spondyloarthropathy, is a chronic, multisystem inflammatory disorder involving primarily the sacroiliac (SI) joints and the axial skeleton. The outcome in patients with a spondyloarthropathy, including AS, is generally compared with that in patients with a disease such as rheumatoid arthritis.Mostly the joints where the spine joins the pelvis are also affected.Back pain is one of the most prominent symptoms of the ankylosing spondylitis (AS) which is intermittent in nature.Stiffness in the affected joints gets worse.It is believed that both the combination of genetic and environmental factors play an important role in the pathogenesis of ankylosing spondylitis (AS) and the underlying etiology is believed to be autoimmune or autoinflammatory.

Pathogenesis^[1]

• It is understood that ankylosing spondylitis (AS) is the result of genetic and environmental factors.
• Ankylosing spondylitis (AS) is a chronic inflammatory disease that can affect sacroiliac joints and axial skeleton and cause significant functional and structural implications of the affected joints.
• Ankylosing spondylitis (AS) has a familial associations particularly among the patients who are positive for human leukocyte antigen (HLA)–B27 .

• Genes involved in the pathogenesis of ankylosing spondylitis (AS) include Human Leukocyte Antigen–B27(HLA-B27).^[2]
• The expression of HLA-B27 is more in the antigen presenting cells.
• HLA-B27 binds to b2 microglobulin after translation and tertiary folding and then loaded with an oligopeptide.
• The complex now passes via Golgi apparatus to the cell surface where the antigenic peptide is presented to either CD8+ lymphocytes or NK cells.^[3]
• 90% of the time HLA B27 shows strong genetic association with AS, But only 5% of the patients who are positive for HLA B27 are going to develop ankylosing spondylitis (AS).
• HLA-B27 was found to have at least 25 allele subtypes which encode for 25 different gene products. Among all the 25 different alleles B*2705 is most common subtype which is thought to be a parent molecule and associated with higher risk of ankylosing spondylitis (AS).
• B*2701, B*2702, B*2704, and B*2707 are the other subtypes which confer disease susceptibility.^[4]
• In peripheral blood mononuclear cells HLA–B27 has been found to be more highly expressed, than in healthy HLA-B27+ individuals. Furthermore, B*2705 expression levels were found to be higher in AS patients.^[5]
• Many theories have been postulated with regard to the molecular pathogenesis role of HLA-B27 in AS which include arthritogenic peptides, aberrant folding, HLA-B27 misfolding, and increased intracellular microbial survival.^[6]

• Single amino acid changes from aspartate in the B*2705 allele to histidine in the B*2709 allele results in loss of the association with AS.^[7][8]
• A common feature shared by the two caucasoid AS-associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C-terminal anchor.^[9][10]
• A 9 amino acid fragment of VIPIR (residues 400–408) which is peptide, a sequence highly homologous to an Epstein–Barr virus derived epitope of latent membrane protein 2.^[11][12]
• Aggrecan is the another antigen of interest it is proteoglycan of chondroitin sulfate. In some patients a strong cellular immune response is noted with people who are suffering with AS and these patients also show presence of circulating and synovial CD4+ T cells.
• Aggrecan is found in anterior uveal tract, aorta, and aortic valve and it is similar proteins such as versican that helps in cyclic compression and relaxation.Immunity to aggrecan in BALB/c mice results in spondylitis and peripheral arthritis.^[13][14]

Evidence of Other Genetic Associations in Ankylosing spondylitis (AS):

• There is very significant evidence to prove that other genetic conditions also act to determine which the patients have a increased susceptibility in developing the ankylosing spondylitis (AS), and studies show that HLA-B27+ patients who have a first-degree relative with ankylosing spondylitis(AS) have increased rates of disease development 6–16 times more than those without such a family history with ankylosing spondylitis.^{[15][16][17][18][19]}
• Evenmore, the radiographic severity tested with the Bath AS radiographic index has a heritability rate index of 0.62.^[20][21]

HLA-B27 in the pathogenesis of ankylosing spondylitis

• The immunopathogenesis of ankylosing spondylitis(AS) is suspected to involve upregulation of proinflammatory cytokines like especially tumor necrosis factor–a(TNF-a) which is more increased than others in patients with ankylosing spondylitis(AS).^[22]
• Increased serum levels of IL-6 and IL-17 shows associate with the development and progression of ankylosing spondylitis.^[23][24][25]

On gross pathology, The following are the characteristic findings of ankylosing spondylitis(AS).

• Involvement of sacroiliac joints.
• Synovitis which destroys articular cartilage and results in bony ankylosis.
• Posterior longitudinal ligament calcification.
• Fixed kyphosis (Bamboo spine).

Spine with spondylitis ankylosans

Anterior flexion in ankylosing spondylitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Ankylosing spondylitis is an inflammatory disease that in overtime it causes some of the vertebrae in your spine to fuse.Because of the fusion the spine less flexible and the patients present with hunched-forward posture. It can be difficult to breathe deeply when the ribs are involved.The most common cause of ankylosing spondylitis is involvement of gene HLA B27.

Common Causes

• Heredity
  • People who are positive for HLA-B27 gene are more prone to develop ankylosing spondylitis.^[1][2]
• Sex
  • When compared to women, men are more likely to develop ankylosing spondylitis.
• Age
  • Most commonly seen in adolescence.^[3]
• Race
  • Ankylosing spondylitis is more common in Native American tribes.^[4]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Ankylosing spondylitis needs to be differentiated from certain conditions such as a strain of the lumbosacral joint, osteoarthritis, and Forestier’s disease.

Diseases that can have similar symptoms are

• Strain of lumbosacral joint
• Osteoarthritis
• Forestier’s disease
• Tuberculous spondylitis
• Rheumatoid arthritis
• Bone cancer

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

The prevalence of axial spondyloarthritis (axSpA) or ankylosing spondylitis in a population depends upon the following 1)Ethnic groups 2) Selection of subjects for evaluation and 3) The criteria for diagnosis.It shows a clear evidence that correlation between the prevalence of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) in a given population and the prevalence of human leukocyte antigen HLA-B27 exits.

• The prevalence of ankylosing spondylitis is approximately 7-490 per 100,000 individuals worldwide.^[1][2]
• In the year 2009, according to National Health and Nutrition Examination Survey (NHANES) the incidence of ankylosing spondylitis was estimated to be 6.1% cases per 100,000 individuals worldwide.

• The incidence of ankylosing spondylitis is approximately 7.26 per 100,000 persons in the adult population.

• The incidence of fractures in ankylosing spondylitis is approximately  4 to 18 percent .
• The incidence of ankylosing spondylitis is approximately 6–7 per 100,000 persons in caucasian populations.

• The mortality rate of ankylosing spondylitis is approximately was 1.60 (95% CI 1.44-1.77).
• The mortality rate of ankylosing spondylitis increased mostly because of circulatory disease that associated with ankylosing spondylitis.

• The incidence of ankylosing spondylitis increases with age; the median age at diagnosis is second and third decades of life years.
• Mostly 80% of the patients with ankylosing spondylitis(AS) experience symptoms at ≤ 30 years of age, But only 5% will present with symptoms at ≥ 45 years of age.

• Ankylosing spondylitis(AS) usually affects individuals of the North America race. Japan individuals are less likely to develop ankylosing spondylitis(AS).

• Men are more commonly affected by Ankylosing spondylitis(AS) than women. The men to women ratio is approximately 2:1.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

There is no known cause specific cause for ankylosing spondylitis, though genetic factors seems to play very important role in developing the disease. In particular, people who are positive for HLA-B27 are at more risk of developing ankylosing spondylitis.Ankylosing spondylitis is a form of chronic joint inflammation that mostly affects the spine. Gradually it can cause the bones of the spine to fuse together, a process which is called ankylosis.

• There is no known cause specific cause for ankylosing spondylitis, though genetic factors seem to play a very important role in developing the disease. In particular, people who are positive for HLA-B27 are at more risk of developing ankylosing spondylitis.Ankylosing spondylitis is a form of chronic joint inflammation that mostly affects the spine. Gradually it can cause the bones of the spine to fuse together, a process which is called ankylosis.^[1]
• The most potent risk factor in the development of ankylosing spondylitis is positive for HLA-B27. Other risk factors include environmental, gender, and age.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

The natural history of ankylosing spondylitis(AS) remains poorly documented.Documentation of the early course of ankylosing spondylitis(AS) has been limited by the lack of appropriate criteria to diagnose early.New York criteria had played important role in the study of ankylosing spondylitis(AS).

• The natural history of ankylosing spondylitis(AS) remains poorly documented.
• The heterogeneity of the ankylosing spondylitis(AS) has made studies technically difficult.
• Documentation of the early course of ankylosing spondylitis(AS) has been limited by the lack of appropriate criteria to diagnose early.
• Modified New York criteria had played important role in the study of ankylosing spondylitis(AS).
• Rudwaleit pointed that ankylosing spondylitis(AS) passes through three stages ^[4][5]
  • Pre-radiographic
  • Radiographic  sacroiliitis 
  • Radiographic spinal changes

• Common complications of ankylosing spondylitis(AS) include:^{[6][7][8][9][10]}
  • Acute anterior uveitis
  • Inflammatory bowel disease
  • Psoriasis 
  • Psychosocial  issues
  • Cardiovascular problems
  • Pulmonary problems
  • Osteopenia
  • Fractures
  • Neurologic manifestations
  • Renal manifestations

• It’s hard to predict the long-term effects for the people who are suffering with ankylosing spondylitis because it varies from person to person.
• The presence of hip involvement is associated with a particularly poor prognosis among patients with ankylosing spondylitis patients.^[11]
• In many patients onset of the disease and symptoms varies.
• In a very small percentage of the patients with AS they develop life-threatening complications like abnormal heart rhythm or the aortic heart valve.

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