Ankylosing spondylitis
Encyclopedia
Ankylosing spondylitis previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton
with variable involvement of peripheral joints and nonarticular structures. AS is a form of spondyloarthritis, is a chronic
, inflammatory arthritis
and autoimmune disease
. It mainly affects joints in the spine
and the sacroiliac joint
in the pelvis
, and can cause eventual fusion of the spine.
It is a member of the group of the spondyloarthropathies
with a strong genetic predisposition
. Complete fusion results in a complete rigidity of the spine, a condition known as "bamboo spine".
pain and stiffness in the middle part of the spine or sometimes the entire spine, often with pain referred to one or other buttock or the back of thigh from the sacroiliac joint
.
Symptoms appear gradually. Initially they are usually not specific for ankylosing spondylitis
. The average onset-to-diagnosis lag time has been estimated to be approximately 8.5 years to 11.4 years.
Men are affected more than women by a ratio
about of 3:1, with the disease usually taking a more severe course in men than women.
In 40% of cases, ankylosing spondylitis
is associated with an inflammation of the eye (iritis
and uveitis
), causing redness, eye pain, vision loss
, floater
s and photophobia
. This is thought to be due to the association these two conditions have with inheritance of HLA-B27
. Other common symptoms are generalized fatigue
and sometimes nausea. Less commonly, aortitis
, apical
lung fibrosis and ectasia
of the sacral nerve root sheaths may occur.
When the condition presents before the age of 18, it is relatively likely to cause pain and swelling of large limb joints, particularly the knee. In prepubescent cases, pain and swelling may also manifest in the ankles and feet, where calcaneal spurs may also develop.
Pain is often severe at rest, but improves with physical activity. However, many experience inflammation and pain to varying degrees regardless of rest and movement.
Ankylosing spondylitis is one of a cluster of conditions known as seronegative spondyloarthropathies, in which rheumatoid factor tests are negative and the characteristic pathological lesion is an inflammation of the enthesis
(the insertion of tensile connective tissue into bone).
Ankylosing spondylitis
(AS) is a systemic rheumatic disease, meaning it affects the entire body. Approximately 90% of AS patients express the HLA-B27
genotype, meaning there is a strong genetic association. However, only 5% of individuals with the HLA-B27 genotype contract the disease. Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Antineutrophil cytoplasmic antibodies ANCA
are associated with AS, but do not correlate with disease severity.
The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B. This interaction is not proven to involve a self antigen, and at least in the related Reiter's syndrome (reactive arthritis), which follows infections, the antigens involved are likely to be derived from intracellular microorganisms. There is, however, a possibility that CD4 T cells are involved in an aberrant way, since HLA-B27 appears to have a number of unusual properties, including possibly an ability to interact with T cell receptors in association with CD4 (usually only cytotoxic T lymphocytes with CD8 react with HLAB antigen as it is a MHC class 1 antigen).
There has been a longstanding claim that AS arises from a cross-reaction between HLA-B27 and antigens of the Klebsiella
bacterial genus (Tiwana et al. 2001). The problem with this idea is no such cross reactivity with B27 has been found (i.e. although antibody responses to Klebsiella may be increased, there is no antibody response to B27, so there seems to be no cross reactivity). Particular authorities argue elimination of the prime nutrients of Klebsiella (starches) would decrease antigenemia and improve the musculoskeletal symptoms. However, as Khan (2002) argues, evidence for a correlation between Klebsiella and AS is circumstantial so far, and the efficacy of low-starch diets has not yet been scientifically evaluated. Studies on low-starch diet and AS could be difficult to fund, while new biologics developed by the pharmaceutical industry may demonstrate efficacy, as well as financial benefit to the industry (whereas changing the diet would not). A randomized controlled trial in Turkey demonstrated that 12-week therapy with moxifloxacin
(which would kill Klebsiella) resulted in "significant and sustained improvement" in inflammatory symptoms in patients with ankylosing spondylitis.
Toivanen (1999) found no support for the role of Klebsiella in the etiology of primary AS.
There is no direct test to diagnose AS. A clinical examination, MRI and X-ray
studies of the spine, which show characteristic spinal changes and sacroiliitis
, and a simple genetic marker blood test are the major diagnostic tools. A drawback of X-ray diagnosis is the signs and symptoms of AS have usually been established as long as 8–10 years prior to X-ray-evident changes occurring on a plain film X-ray, which means a delay of as long as 10 years before adequate therapies can be introduced. Options for earlier diagnosis are tomography
and magnetic resonance imaging
of the sacroiliac joints, but the reliability of these tests is still unclear. The Schober's test
is a useful clinical measure of flexion of the lumbar spine performed during examination.
During acute inflammatory periods, AS patients will sometimes show an increase in the blood concentration of C-reactive protein
(CRP) and an increase in the erythrocyte sedimentation rate
(ESR), but there are many with AS whose CRP and ESR rates do not increase, so normal CRP and ESR results do not always correspond with the amount of inflammation a person actually has. Sometimes people with AS have normal level results, yet are experiencing a significant amount of inflammation in their bodies.
Variations of the HLA-B gene increase the risk of developing ankylosing spondylitis, although it is not a diagnostic test. Those with the HLA-B27 variant are at a higher risk than the general population of developing the disorder. HLA-B27, demonstrated in a blood test
, can occasionally help with diagnosis, but in itself is not diagnostic of AS in a person with back pain. Over 95% of people that have been diagnosed with AS are HLA-B27 positive, although this ratio varies from population to population (only 50% of African American patients with AS possess HLA-B27, and it is close to 80% among AS patients from Mediterranean countries). In early onset disease HLA-B7/B*2705 heterozygotes exhibited the highest risk for disease.
In 2007, a collaborative effort by an international team of researchers in the U.K., Australia and the United States led to the discovery of two genes, ARTS1 and IL23R
, that also contribute to the cause of AS. The findings were published in the November 2007 edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. Together with HLA-B27, these two genes account for roughly 70 percent of the overall incidence of the disease.
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI
), developed in Bath (UK), is an index designed to detect the inflammatory burden of active disease. The BASDAI can help to establish a diagnosis of AS in the presence of other factors such as HLA-B27 positivity, persistent buttock pain which resolves with exercise, and X-ray or MRI evident involvement of the sacroiliac joints. (See: "Diagnostic Tools", below) It can be easily calculated and accurately assesses a patient's need for additional therapy; a patient with a score of four out of a possible 10 points while on adequate NSAID therapy is usually considered a good candidate for biologic therapy.
The Bath Ankylosing Spondylitis Functional Index (BASFI) is a functional index which can accurately assess a patient's functional impairment due to the disease, as well as improvements following therapy. (See: "Diagnostic Tools", below) The BASFI is not usually used as a diagnostic tool, but rather as a tool to establish a patient's current baseline and subsequent response to therapy.
Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are preceded by medical treatment to reduce the inflammation and pain, and are commonly followed by a physician. This way the movements will help in diminishing pain and stiffness, while exercise in an active inflammatory state would just make the pain worse. Normal occupations may be precluded by the symptoms of the disease.
Some may require the help of walking aids, such as a cane, to help assist in balance and relieve some pressure on affected joints while walking and standing. Many with AS find it very difficult to sit or stand for prolonged periods of time, which can be as little as 20 minutes; therefore, many need to alternate times of sitting and standing, as well as times of rest.
Medical professionals and experts in AS have speculated that maintaining good posture can reduce the likelihood of a fused or curved spine which occurs in a significant percentage of diagnosed persons.
TNFα blockers have been shown to be the most promising treatment, slowing the progress of AS in the majority of clinical cases, helping many patients receive a significant reduction, though not elimination, of their inflammation and pain. They have also been shown to be highly effective in treating not only the arthritis of the joints but also the spinal arthritis associated with AS. A drawback, besides the often high cost, is the fact these drugs increase the risk of infections. So, the protocol for any of the TNF-α blockers includes a test for tuberculosis
(like Mantoux
or Heaf
) before starting treatment. In case of recurrent infections, even recurrent sore throats
, the therapy may be suspended because of the involved immunosuppression. Patients taking the TNF medications are advised to limit their exposure to others who are or may be carrying a virus (such as a cold or influenza
) or who may have a bacterial or fungal infection.
Tocilizumab
, an IL-6 inhibitor currently approved for the treatment of rheumatoid arthritis, may also show promise for the treatment of ankylosing spondylitis. Rituximab
, a monoclonal antibody against CD20, has also reportedly been effective. Both of these drugs require further investigation, but may one day be viable alternatives for patients who are not responsive to TNF-alpha antagonists.
can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky.
In addition, AS can have some manifestations which make anaesthesia more complex.
Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anaesthesia may be difficult owing to calcification of ligaments, and a small number have aortic regurgitation. The stiffness of the thoracic ribs results in ventilation being mainly diaphragm-driven, so there may be a decrease in pulmonary function.
Moderate-to-high impact exercises like jogging
are generally not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some patients.
Manipulation is contraindicated. A researcher has said "Anyone with limited spinal mobility due to [spondylitis] should avoid manipulation of their back or neck by chiropractors and masseurs because it can be dangerous." Manipulation has sometimes led to spinal fractures.
Unattended cases of AS accompanied by dactylitis
or enthesitis
, especially when spine inflammation is not yet active, may result in a misdiagnosis of normal rheumatism. In a long-term undiagnosed period, osteopenia
or osteoporosis
of the AP spine may occur, causing eventual compression fractures and a back "hump". Typical signs of progressed AS are the visible formation of syndesmophyte
s on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. The fusion of the vertebrae paresthesia
is a complication due to the inflammation of the tissue surrounding nerves.
Organs commonly affected by AS, other than the axial spine
and other joints, are the heart
, lungs, eyes
, colon
, and kidneys. Other complications are aortic regurgitation, Achilles tendinitis, AV node block
and amyloidosis
. 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
.
is 0.25%. Many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder symptoms.
AS has been suggested as the first recognized disease which was different from rheumatoid arthritis
by Galen
as early as the second century A.D.; however, skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was first discovered in an archaeological dig that unearthed the skeletal remains of a 5000-year–old Egyptian mummy with evidence of bamboo spine.
The anatomist and surgeon Realdo Colombo
described what could have been the disease in 1559, and the first account of pathologic changes to the skeleton possibly associated with AS was published in 1691 by Bernard Connor. In 1818, Benjamin Brodie became the first physician to document a patient believed to have active AS who also had accompanying iritis
.
In 1858, David Tucker
published a small booklet which clearly described a patient, Leonard Trask
, who suffered from severe spinal deformity subsequent to AS. In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:
This account became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS.
It was not until the late nineteenth century, however, when the neurophysiologist Vladimir Bekhterev
of Russia in 1893, Adolph Strümpell
of Germany in 1897, and Pierre Marie of France in 1898 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 Bechterew Disease or Marie–Strümpell Disease.
antigen and high levels of immunoglobulin A
(IgA) in the blood. The HLA-B27 antigen is also expressed by Klebsiella
bacteria, which are found in high levels in the feces
of AS patients. A theory suggests the presence of the bacteria may be a trigger of the disease, and reducing the amount of starch
in the diet
(which these bacteria require to grow) may be of benefit to AS patients. A test of this diet resulted in reduced symptoms and inflammation
in patients with AS as well as IgA levels in individuals with and without AS. Further research is required to determine if diet changes may have a clinical effect on the course of the disease.
While there are anecdotal accounts from people who have reduced their symptoms of inflammation and pain by using a low starch diet, the efficacy has not been confirmed by a clinical study.
Axial skeleton
The axial skeleton consists of the 80 bones along the central axis of the human body. It is composed of six parts; the human skull, the ossicles of the middle ear, the hyoid bone of the throat, the rib cage, sternum and the vertebral column...
with variable involvement of peripheral joints and nonarticular structures. AS is a form of spondyloarthritis, is a chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
, inflammatory arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
and autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
. It mainly affects joints in the spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
and the sacroiliac joint
Sacroiliac joint
The sacroiliac joint or SI joint is the joint in the bony pelvis between the sacrum and the ilium of the pelvis, which are joined together by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side...
in the pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
, and can cause eventual fusion of the spine.
It is a member of the group of the spondyloarthropathies
Spondyloarthropathy
Spondyloarthropathy is any joint disease of the vertebral column. Spondyloarthropathy with inflammation is called spondylarthritis. In contrast, spondylopathy is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy...
with a strong genetic predisposition
Genetic predisposition
A genetic predisposition is a genetic affectation which influences the phenotype of an individual organism within a species or population but by definition that phenotype can also be modified by the environmental conditions. In the rest of the population, conditions cannot have that effect...
. Complete fusion results in a complete rigidity of the spine, a condition known as "bamboo spine".
Signs and symptoms
The typical patient is a young male, aged 20–40, however the condition also presents in females. The condition is known to be hereditary. Symptoms of the disease first appear, on average, at age 23 years. These first symptoms are typically chronicChronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
pain and stiffness in the middle part of the spine or sometimes the entire spine, often with pain referred to one or other buttock or the back of thigh from the sacroiliac joint
Sacroiliac joint
The sacroiliac joint or SI joint is the joint in the bony pelvis between the sacrum and the ilium of the pelvis, which are joined together by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side...
.
Symptoms appear gradually. Initially they are usually not specific for ankylosing spondylitis
Spondylitis
Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joint as well, which itself is called spondylarthritis.-Examples:...
. The average onset-to-diagnosis lag time has been estimated to be approximately 8.5 years to 11.4 years.
Men are affected more than women by a ratio
Ratio
In mathematics, a ratio is a relationship between two numbers of the same kind , usually expressed as "a to b" or a:b, sometimes expressed arithmetically as a dimensionless quotient of the two which explicitly indicates how many times the first number contains the second In mathematics, a ratio is...
about of 3:1, with the disease usually taking a more severe course in men than women.
In 40% of cases, ankylosing spondylitis
Spondylitis
Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joint as well, which itself is called spondylarthritis.-Examples:...
is associated with an inflammation of the eye (iritis
Iritis
Iritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....
and uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
), causing redness, eye pain, vision loss
Vision loss
Vision loss or visual loss is the absence of vision where it existed before, which can happen either acutely or chronically .-Ranges of vision loss:...
, floater
Floater
Floaters are deposits of various size, shape, consistency, refractive index, and motility within the eye's vitreous humour, which is normally transparent. At young age the vitreous is perfectly transparent, but during life imperfections gradually develop. The common type of floater, which is...
s and photophobia
Photophobia
Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
. This is thought to be due to the association these two conditions have with inheritance of HLA-B27
HLA-B27
Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells...
. Other common symptoms are generalized fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
and sometimes nausea. Less commonly, aortitis
Aortitis
-Causes:This inflammation has a number of possible causes, to include: trauma, viral infection, certain immune disorders, and bacterial infection .-Treatment:...
, apical
Apex of lung
The apex of the lung is the rounded upper part of the human lung. It extends into the root of the neck, reaching from 2.5 cm to 4 cm above the level of the sternal end of the first rib....
lung fibrosis and ectasia
Ectasia
Dilation or distention of a tubular structure. It occurs as part of a pathophysiological process.-Specific conditions:* Duct ectasia of breast, a dilated milk duct...
of the sacral nerve root sheaths may occur.
When the condition presents before the age of 18, it is relatively likely to cause pain and swelling of large limb joints, particularly the knee. In prepubescent cases, pain and swelling may also manifest in the ankles and feet, where calcaneal spurs may also develop.
Pain is often severe at rest, but improves with physical activity. However, many experience inflammation and pain to varying degrees regardless of rest and movement.
Ankylosing spondylitis is one of a cluster of conditions known as seronegative spondyloarthropathies, in which rheumatoid factor tests are negative and the characteristic pathological lesion is an inflammation of the enthesis
Enthesis
Enthesis is the point at which a tendon or ligament or muscle inserts into bone, where the collagen fibers are mineralized and integrated into bone tissue...
(the insertion of tensile connective tissue into bone).
Pathophysiology
Spondylitis
Spondylitis is an inflammation of the vertebra. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joint as well, which itself is called spondylarthritis.-Examples:...
(AS) is a systemic rheumatic disease, meaning it affects the entire body. Approximately 90% of AS patients express the HLA-B27
HLA-B27
Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells...
genotype, meaning there is a strong genetic association. However, only 5% of individuals with the HLA-B27 genotype contract the disease. Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis. Autoantibodies specific for AS have not been identified. Antineutrophil cytoplasmic antibodies ANCA
ANCA
ANCA Pty Ltd is an Australia company which designs and manufactures CNC grinding machines. The company was founded in 1974 by Pat Boland and Pat McCluskey in Melbourne, Australia....
are associated with AS, but do not correlate with disease severity.
The association of AS with HLA-B27 suggests the condition involves CD8 T cells, which interact with HLA-B. This interaction is not proven to involve a self antigen, and at least in the related Reiter's syndrome (reactive arthritis), which follows infections, the antigens involved are likely to be derived from intracellular microorganisms. There is, however, a possibility that CD4 T cells are involved in an aberrant way, since HLA-B27 appears to have a number of unusual properties, including possibly an ability to interact with T cell receptors in association with CD4 (usually only cytotoxic T lymphocytes with CD8 react with HLAB antigen as it is a MHC class 1 antigen).
There has been a longstanding claim that AS arises from a cross-reaction between HLA-B27 and antigens of the Klebsiella
Klebsiella
Klebsiella is a genus of non-motile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. It is named after the German microbiologist Edwin Klebs...
bacterial genus (Tiwana et al. 2001). The problem with this idea is no such cross reactivity with B27 has been found (i.e. although antibody responses to Klebsiella may be increased, there is no antibody response to B27, so there seems to be no cross reactivity). Particular authorities argue elimination of the prime nutrients of Klebsiella (starches) would decrease antigenemia and improve the musculoskeletal symptoms. However, as Khan (2002) argues, evidence for a correlation between Klebsiella and AS is circumstantial so far, and the efficacy of low-starch diets has not yet been scientifically evaluated. Studies on low-starch diet and AS could be difficult to fund, while new biologics developed by the pharmaceutical industry may demonstrate efficacy, as well as financial benefit to the industry (whereas changing the diet would not). A randomized controlled trial in Turkey demonstrated that 12-week therapy with moxifloxacin
Moxifloxacin
Moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent developed by Bayer AG . It is marketed worldwide under the brand names Avelox, Avalox, and Avelon for oral treatment. In most countries, the drug is also available in parenteral form for intravenous infusion...
(which would kill Klebsiella) resulted in "significant and sustained improvement" in inflammatory symptoms in patients with ankylosing spondylitis.
Toivanen (1999) found no support for the role of Klebsiella in the etiology of primary AS.
Diagnosis
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
studies of the spine, which show characteristic spinal changes and sacroiliitis
Sacroiliac joint
The sacroiliac joint or SI joint is the joint in the bony pelvis between the sacrum and the ilium of the pelvis, which are joined together by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side...
, and a simple genetic marker blood test are the major diagnostic tools. A drawback of X-ray diagnosis is the signs and symptoms of AS have usually been established as long as 8–10 years prior to X-ray-evident changes occurring on a plain film X-ray, which means a delay of as long as 10 years before adequate therapies can be introduced. Options for earlier diagnosis are tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
and magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
of the sacroiliac joints, but the reliability of these tests is still unclear. The Schober's test
Schober's test
Schober's test is a test used in rheumatology to measure the ability of a patient to flex his/her lower back.-Procedure:The examiner makes a mark approximately at the level of L5 . The examiner then places one finger ~5 cm below this mark, and another, second, finger, ~10 cm above this mark. The...
is a useful clinical measure of flexion of the lumbar spine performed during examination.
During acute inflammatory periods, AS patients will sometimes show an increase in the blood concentration of C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
(CRP) and an increase in the erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
(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 a person actually has. Sometimes people with AS have normal level results, yet are experiencing a significant amount of inflammation in their bodies.
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
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
, can occasionally help with diagnosis, but in itself is not diagnostic of AS in a person with back pain. Over 95% of people that have been diagnosed with AS are HLA-B27 positive, although this ratio varies from population to population (only 50% of African American patients with AS possess HLA-B27, and it is close to 80% among AS patients from Mediterranean countries). In early onset disease HLA-B7/B*2705 heterozygotes exhibited the highest risk for disease.
In 2007, a collaborative effort by an international team of researchers in the U.K., Australia and the United States led to the discovery of two genes, ARTS1 and IL23R
Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages...
, that also contribute to the cause of AS. The findings were published in the November 2007 edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. Together with HLA-B27, these two genes account for roughly 70 percent of the overall incidence of the disease.
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI
BASDAI
The BASDAI is important because it is a validated diagnostic test which allows a physician to determine the effectiveness of a current drug therapy, or the need to institute a new drug therapy for the treatment of ankylosing spondylitis...
), developed in Bath (UK), is an index designed to detect the inflammatory burden of active disease. The BASDAI can help to establish a diagnosis of AS in the presence of other factors such as HLA-B27 positivity, persistent buttock pain which resolves with exercise, and X-ray or MRI evident involvement of the sacroiliac joints. (See: "Diagnostic Tools", below) It can be easily calculated and accurately assesses a patient's need for additional therapy; a patient with a score of four out of a possible 10 points while on adequate NSAID therapy is usually considered a good candidate for biologic therapy.
The Bath Ankylosing Spondylitis Functional Index (BASFI) is a functional index which can accurately assess a patient's functional impairment due to the disease, as well as improvements following therapy. (See: "Diagnostic Tools", below) The BASFI is not usually used as a diagnostic tool, but rather as a tool to establish a patient's current baseline and subsequent response to therapy.
Treatment
No cure is known for AS, although treatments and medications are available to reduce symptoms and pain.Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are preceded by medical treatment to reduce the inflammation and pain, and are commonly followed by a physician. This way the movements will help in diminishing pain and stiffness, while exercise in an active inflammatory state would just make the pain worse. Normal occupations may be precluded by the symptoms of the disease.
Some may require the help of walking aids, such as a cane, to help assist in balance and relieve some pressure on affected joints while walking and standing. Many with AS find it very difficult to sit or stand for prolonged periods of time, which can be as little as 20 minutes; therefore, many need to alternate times of sitting and standing, as well as times of rest.
Medical professionals and experts in AS have speculated that maintaining good posture can reduce the likelihood of a fused or curved spine which occurs in a significant percentage of diagnosed persons.
Medication
There are three major types of medications used to treat ankylosing spondylitis.- Pain-relieving drugs come in two major classes. First, anti-inflammatory drugs, which include NSAIDNon-steroidal anti-inflammatory drugNonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s such as ibuprofenIbuprofenIbuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, phenylbutazonePhenylbutazonePhenylbutazone, often referred to as bute, is a non-steroidal anti-inflammatory drug for the short-term treatment of pain and fever in animals. In the United States, it is no longer approved for human use.-In humans:...
, diclofenacDiclofenacDiclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
, indomethacin, naproxenNaproxenNaproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
and COX-2 inhibitorCOX-2 inhibitorCOX-2 selective inhibitor is a form of non-steroidal anti-inflammatory drug that directly targets COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration, and is the main feature of celecoxib, rofecoxib and other members of this...
s, which reduce inflammation and pain. Second, some patients require opioid analgesicsOpioidAn opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
, which are very effective in alleviating the type of chronic pain commonly experienced by those suffering from AS, especially in extended-release formulations. - DMARDDisease-modifying antirheumatic drugDisease-modifying antirheumatic drugs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression...
s such as cyclosporin, methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, sulfasalazine, and corticosteroids, used to reduce the immune system response through immunosuppressionImmunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
; - TNFα blockers (antagonistsReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
) such as etanerceptEtanerceptEtanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...
, infliximabInfliximabInfliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
, golimumabGolimumabGolimumab is a human monoclonal antibody which is used as an immunosuppressive drug and marketed under the brand name Simponi. Golimumab targets tumor necrosis factor alpha , a pro-inflammatory molecule and hence is a TNF inhibitor....
and adalimumabAdalimumabAdalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...
(also known as biologics), are indicated for the treatment of and are effective immunosuppressantImmunosuppressionImmunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
s in AS as in other autoimmune diseases.
TNFα blockers have been shown to be the most promising treatment, slowing the progress of AS in the majority of clinical cases, helping many patients receive a significant reduction, though not elimination, of their inflammation and pain. They have also been shown to be highly effective in treating not only the arthritis of the joints but also the spinal arthritis associated with AS. A drawback, besides the often high cost, is the fact these drugs increase the risk of infections. So, the protocol for any of the TNF-α blockers includes a test for tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
(like Mantoux
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...
or Heaf
Heaf test
The Heaf test is a diagnostic skin test performed in order to determine whether or not a child has been exposed to tuberculosis. Also known as the Sterneedle test, it is administered by a Heaf gun which is a spring-loaded instrument with six needles arranged in a circular formation.Patients who...
) before starting treatment. In case of recurrent infections, even recurrent sore throats
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
, the therapy may be suspended because of the involved immunosuppression. Patients taking the TNF medications are advised to limit their exposure to others who are or may be carrying a virus (such as a cold or influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
) or who may have a bacterial or fungal infection.
Tocilizumab
Tocilizumab
Tocilizumab is an immunosuppressive drug, mainly for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of RA in children. It is a humanized monoclonal antibody against the interleukin-6 receptor...
, an IL-6 inhibitor currently approved for the treatment of rheumatoid arthritis, may also show promise for the treatment of ankylosing spondylitis. Rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, a monoclonal antibody against CD20, has also reportedly been effective. Both of these drugs require further investigation, but may one day be viable alternatives for patients who are not responsive to TNF-alpha antagonists.
Surgery
In severe cases of AS, surgerySurgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky.
In addition, AS can have some manifestations which make anaesthesia more complex.
Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anaesthesia may be difficult owing to calcification of ligaments, and a small number have aortic regurgitation. The stiffness of the thoracic ribs results in ventilation being mainly diaphragm-driven, so there may be a decrease in pulmonary function.
Physical therapy
Some of the therapies that have been shown to benefit AS patients include:- Physical therapyPhysical therapyPhysical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
/osteopathyOsteopathyOsteopathy and osteopathic medicine are often used interchangeably for the philosophy and system of alternative medical practice first proposed by A. T. Still MD, DO in 1874....
/physiotherapy, shown to be of great benefit to AS patients; - Swimming, one of the preferred exercises since it involves all muscles and joints in a low-impact, buoyant environment;
- Slow movement muscle extending exercises like stretchingStretchingStretching is a form of physical exercise in which a specific skeletal muscle is deliberately elongated, often by abduction from the torso, in order to improve the muscle's felt elasticity and reaffirm comfortable muscle tone. The result is a feeling of increased muscle control, flexibility and...
, yogaYogaYoga is a physical, mental, and spiritual discipline, originating in ancient India. The goal of yoga, or of the person practicing yoga, is the attainment of a state of perfect spiritual insight and tranquility while meditating on Supersoul...
, climbing, t'ai chi, Pilates methodPilatesPilates is a physical fitness system developed in the early 20th century by Joseph Pilates in Germany, the UK and the USA. As of 2005, there were 11 million people practicing the discipline regularly and 14,000 instructors in the United States....
, etc.
Moderate-to-high impact exercises like jogging
Jogging
Jogging is a form of trotting or running at a slow or leisurely pace. The main intention is to increase fitness with less stress on the body than from faster running.-Definition:...
are generally not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some patients.
Manipulation is contraindicated. A researcher has said "Anyone with limited spinal mobility due to [spondylitis] should avoid manipulation of their back or neck by chiropractors and masseurs because it can be dangerous." Manipulation has sometimes led to spinal fractures.
Prognosis
AS can range from mild to progressively debilitating and from medically controlled to refractive. Some have times of active inflammation followed by times of remission, while others never have times of remission and have acute inflammation and pain.Unattended cases of AS accompanied by dactylitis
Dactylitis
Dactylitis or sausage digit is inflammation of an entire digit , and can be painful.The word dactyl comes from the Greek word "daktylos" meaning "finger"...
or enthesitis
Enthesitis
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or...
, especially when spine inflammation is not yet active, may result in a misdiagnosis of normal rheumatism. In a long-term undiagnosed period, osteopenia
Osteopenia
Osteopenia is a condition where bone mineral density is lower than normal. It is considered by many doctors to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis...
or osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
of the AP spine may occur, causing eventual compression fractures and a back "hump". Typical signs of progressed AS are the visible formation of syndesmophyte
Syndesmophyte
A syndesmophyte is a bony growth originating inside a ligament, commonly seen in the ligaments of the spine, specifically the ligaments in the intervertebral joints leading to fusion of vertebrae. Syndesmophytes are pathologically similar to osteophytes. Ankylosing spondylitis patients are...
s on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. The fusion of the vertebrae paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
is a complication due to the inflammation of the tissue surrounding nerves.
Organs commonly affected by AS, other than the axial spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
and other joints, are the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, lungs, eyes
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
, colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, and kidneys. Other complications are aortic regurgitation, Achilles tendinitis, AV node block
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
and amyloidosis
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
. Owing to lung fibrosis, chest X-rays may show apical fibrosis, while pulmonary function testing
Pulmonary function testing
Pulmonary Function Testing is a complete evaluation of the respiratory system including patient history, physical examinations, chest x-ray examinations, arterial blood gas analysis, and tests of pulmonary function. The primary purpose of pulmonary function testing is to identify the severity of...
may reveal a restrictive lung defect. Very rare complications involve neurologic
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
conditions such as the cauda equina syndrome
Cauda equina syndrome
Cauda equina syndrome ' is a serious neurologic condition in which there is acute loss of function of the lumbar plexus, neurologic elements of the spinal canal below the termination of the spinal cord.-Causes:...
.
Factors that may affect recovery
Prognosis may not be favorable if the following symptoms continue:- Hip involvement
- Plus 3 of the following in the first 2 years of disease:
- ESRErythrocyte sedimentation rateThe erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
>30 mm/h - Unresponsive to NSAIDs
- Limitation of lumbar spine
- Sausage-like fingerFingerA finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....
s or toes - OligoarthritisOligoarthritisOligoarthritis is defined as arthritis affecting one to four joints during the first six months of disease.- Types :Two subcategories are recognized:* Persistent oligoarthritis: Affecting not more than 4 joints throughout the disease course...
- Onset <16 years old
- ESR
Epidemiology
Three men are diagnosed with AS for every one woman; the overall prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
is 0.25%. Many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder symptoms.
History
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
by Galen
Galen
Aelius Galenus or Claudius Galenus , better known as Galen of Pergamon , was a prominent Roman physician, surgeon and philosopher...
as early as the second century A.D.; however, skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was first discovered in an archaeological dig that unearthed the skeletal remains of a 5000-year–old Egyptian mummy with evidence of bamboo spine.
The anatomist and surgeon Realdo Colombo
Realdo Colombo
Realdo Colombo was an Italian professor of anatomy and a surgeon at the University of Padua between 1544 and 1559.- Early life and education :Matteo Realdo Colombo or Renaldus Columbus, was born in Cremona, Lombardy to an apothecary named Antonio Colombo...
described what could have been the disease in 1559, and the first account of pathologic changes to the skeleton possibly associated with AS was published in 1691 by Bernard Connor. In 1818, Benjamin Brodie became the first physician to document a patient believed to have active AS who also had accompanying iritis
Iritis
Iritis is a form of anterior uveitis and refers to the inflammation of the iris of the eye.-Types:There are two main types of iritis: acute and chronic. They differ in numerous ways....
.
In 1858, David Tucker
David Tucker
-Life:He graduated from the University of Michigan, where he studied with Donald Hall.He is an assistant managing editor of the Metro section of The Star-Ledger of Newark.He married and had a daughter, Calisa...
published a small booklet which clearly described a patient, Leonard Trask
Leonard Trask
Leonard Trask was an American who suffered from a "contortion of neck and spine" during his late 20s after an accident while horse riding, which led to Trask becoming a medical curiosity...
, who suffered from severe spinal deformity subsequent to AS. In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:
This account became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS.
It was not until the late nineteenth century, however, when the neurophysiologist Vladimir Bekhterev
Vladimir Bekhterev
Vladimir Mikhailovich Bekhterev was a Russian Neurologist and the Father of Objective Psychology. He is best known for noting the role of the hippocampus in memory, his study of reflexes, and Bekhterev’s Disease...
of Russia in 1893, Adolph Strümpell
Adolph Strümpell
Ernst Adolf Gustav Gottfried von Strümpell was a German neurologist who was born at Neu-Autz Estate, Courland Governorate...
of Germany in 1897, and Pierre Marie of France in 1898 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 Bechterew Disease or Marie–Strümpell Disease.
Research
The majority of patients with AS exhibit the HLA-B27HLA-B27
Human Leukocyte Antigen B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex on chromosome 6 and presents antigenic peptides to T cells...
antigen and high levels of immunoglobulin A
Immunoglobulin A
Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....
(IgA) in the blood. The HLA-B27 antigen is also expressed by Klebsiella
Klebsiella
Klebsiella is a genus of non-motile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. It is named after the German microbiologist Edwin Klebs...
bacteria, which are found in high levels in the feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
of AS patients. A theory suggests the presence of the bacteria may be a trigger of the disease, and reducing the amount of starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
in the diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
(which these bacteria require to grow) may be of benefit to AS patients. A test of this diet resulted in reduced symptoms and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
in patients with AS as well as IgA levels in individuals with and without AS. Further research is required to determine if diet changes may have a clinical effect on the course of the disease.
While there are anecdotal accounts from people who have reduced their symptoms of inflammation and pain by using a low starch diet, the efficacy has not been confirmed by a clinical study.
See also
- NIAMS, the National Institute of Arthritis and Musculoskeletal and Skin Diseases
- SAASpondylitis Association of AmericaThe Spondylitis Association of America started in 1983 as a charity by people affected by ankylosing spondylitis, a crippling, debilitating form of spinal arthritis that often strikes young people...
, Spondylitis Association of America - AFArthritis FoundationThe Arthritis Foundation is the largest national nonprofit organization solely dedicated to the prevention, control and cure of arthritis, the leading cause of disability in the United States....
, Arthritis Foundation