ankylosing spondylitis ankylosing spondylitis ankylosing spondylitis (as) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. occasionally areas affected may include other joints such as the shoulders or hips. eye and bowel problems may occur as well as back pain. joint mobility in the affected areas generally worsens over time. ankylosing spondylitisother namesbekhterev's disease, bechterew's disease, morbus bechterew, bekhterev–strümpell–marie disease, marie's disease, marie–strümpell arthritis, pierre–marie's diseasea 6th-century skeleton showing fused vertebrae, a sign of severe ankylosing spondylitisspecialtyrheumatologysymptomsback pain, joint stiffnesscomplicationseye inflammation (uveitis), compression fractures, heart problems.usual onsetyoung adulthooddurationlong termcausesunknowndiagnostic methodsymptom based, medical imaging, blood teststreatmentmedication, exercise, physical therapymedicationnsaids, steroids, dmards, tnf inhibitorfrequency0.1 to 0.8% although the cause of ankylosing spondylitis is unknown, it is believed to involve a combination of genetic and environmental factors. more than 85% of those affected in the uk have a specific human leukocyte antigen known as the hla-b27 antigen. the underlying mechanism is believed to be autoimmune or autoinflammatory. diagnosis is typically based on the symptoms with support from medical imaging and blood tests. as is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (rf) antibodies. there is no known cure for as. treatments may include medication, exercise, physical therapy, and in rare cases surgery. medications used include nsaids, steroids, dmards such as sulfasalazine, and biologic agents such as tnf inhibitors. approximately 0.1% to 0.8% of all humans are affected with onset typically occurring in young adults. males and females are equally affected; however, women are more likely than men to experience inflammation rather than fusion. signs and symptoms illustration depicting ankylosing spondylitis the signs and symptoms of ankylosing spondylitis often appear gradually, with peak onset between 20 and 30 years of age. initial symptoms are usually a chronic dull pain in the lower back or gluteal region combined with stiffness of the lower back. individuals often experience pain and stiffness that awakens them in the early morning hours. 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. 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. in prepubescent cases, pain and swelling may also manifest in the ankles and feet where heel pain and enthesopathy commonly develop. less common occurrences include ectasia of the sacral nerve root sheaths. 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. 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. pathophysiology 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. 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. single nucleotide polymorphism (snp) a/g variant rs10440635 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 (ep4), one of four receptors for prostaglandin e2. activation of ep4 promotes bone remodeling and deposition (see 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. 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 reactive arthritis, which follows infections, the antigens involved are likely to be derived from intracellular microorganisms. 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 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. 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). 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. 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) 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. mri can show inflammation of the sacroiliac joint. x-rays 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. options for earlier diagnosis are tomography and mri of the sacroiliac joints, but the reliability of these tests is still unclear. lateral x-ray of the mid back in ankylosing spondylitis lateral x-ray of the neck in ankylosing spondylitis x-ray showing bamboo spine in a person with ankylosing spondylitis ct scan showing bamboo spine in ankylosing spondylitis t1-weighted mri with fat suppression after administration of gadolinium contrast showing sacroiliitis in a person with ankylosing spondylitis blood parameters 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. genetic testing 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). basdai 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. 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. 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 juvenile ankylosing spondylitis (jas) is a rare form of the disease which differs from the more common adult form. enthesophathy and arthritis of large joints of the lower extremities is more common than the characteristic early-morning back pain seen in adult as. 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. 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. schober's test the schober's test is a useful clinical measure of flexion of the lumbar spine performed during the physical examination. treatment there is no cure for as, although treatments and medications can reduce symptoms and pain. medication 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 nsaids such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and cox-2 inhibitors, which reduce inflammation and pain. 2012 research showed that those with as and elevated levels of acute phase reactants seem to benefit most from continuous treatment with nsaids. medications used to treat the progression of the disease include the following: disease-modifying antirheumatic drugs (dmards) such as sulfasalazine can be used in people with peripheral arthritis. for axial involvement, evidence does not support sulfasalazine. 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. tumor necrosis factor-alpha (tnfα) blockers (antagonists), such as the 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. trials are ongoing to determine their long-term effectiveness and safety. 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