Also Known As: Ankylosing spondylitis, Bechterew's disease, Marie-Strumpell disease
Ankylosing spondylitis (AS, from Greek ankylos, crooked; spondylos, vertebrae; -itis, inflammation), previously known as Bechterew's disease, (or syndrome) and Marie-Strümpell disease, is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures. AS is a form of spondyloarthritis, a chronic, inflammatory arthritis where immune mechanisms are thought to have a key role. It mainly affects joints in the spine and the sacroiliac joint in the pelvis, and can cause eventual fusion of the spine.
Ankylosing spondylitis 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". There is no cure for AS, although treatments and medications can reduce symptoms and pain.
Three males are diagnosed with AS for every one female; the overall prevalence is 0.25%. Many rheumatologists believe the number of women with AS is underdiagnosed, as most women tend to experience milder symptoms. The majority of patients with AS exhibit the HLA-B27 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.
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. In a study of 40 patients with AS, ANCA was an infrequent finding, being present in only six patients.
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 toKlebsiella 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 andsacroiliitis, 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 United Kingdom, Australia and the United States led to the discovery of two genes that also contribute to the cause of AS: ARTS-1 and IL23R. The findings were published in the November 2007 edition of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. 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.
The major types of medications used to treat ankylosing spondylitis are pain-relievers and drugs aimed at stopping or slowing the progression of the disease. Pain-relieving drugs come in two major classes:
- 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 patients with elevated acute phase reactants seem to benefit most from continuous treatment with NSAIDs.
- Opioid analgesics, which are addictive and not generally prescribed.
Drugs used to treat the progression of the disease include:
- Disease-modifying antirheumatic drugs (DMARDs) such as cyclosporin, methotrexate, sulfasalazine, and corticosteroids, are used to reduce the immune system response through immunosuppression;
- Tumor necrosis factor-alpha (TNFα) blockers (antagonists), such as the biologics etanercept, infliximab, golimumab and adalimumab, have shown good short-term effectiveness and trials are ongoing to determine their long-term effectiveness and safety. One drawback is the cost. Another drawback is that TNF inhibitors, like all immunosuppressing drugs, have a risk of allowing suppressed infections to become active again, and reduce the body's ability to resist new infections.
- Anti-interleukin-6 inhibitors such as Tocilizumab, currently approved for the treatment of rheumatoid arthritis, and rituximab, a monoclonal antibody against CD20, are also undergoing trials.
In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky.
In addition, AS can have some manifestations which make anaesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anaesthesia may be difficult owing to calcification of ligaments, and a small number of patients haveaortic insufficiency. The stiffness of the thoracic ribs results in ventilation being mainly diaphragm-driven, so there may also be a decrease in pulmonary function.
Some of the therapies that have been shown to benefit AS patients include:
- Physical therapy/osteopathy/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 stretching, yoga, climbing, t'ai chi, Pilates method, etc.
Moderate-to-high impact exercises like jogging are generally currently not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some patients.