Ankylosing spondylitis

Ankylosing spondylitis (AS) is a type of

About 0.1% to 0.8% of the population are affected, with onset typically occurring in young adults.[4]^[2] While men and women are equally affected with AS, women are more likely to experience inflammation rather than fusion.^[9]

Signs and symptoms

The signs and symptoms of ankylosing spondylitis often appear gradually, with peak onset between 20 and 30 years of age.

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.^[10] 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.^[12] In prepubescent cases, pain and swelling may also manifest in the ankles and feet where heel pain and enthesopathy commonly develop.^[12] Less common occurrences include ectasia of the sacral nerve root sheaths.^[13]

About 30% of people with AS will also experience anterior

Ankylosing

Ankylosing spondylitis is a member of the more broadly defined disease axial spondyloarthritis.^[22][23] 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).^[22]

While AS can be diagnosed through the description of radiological changes in the

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

If these criteria still do not give a compelling diagnosis magnetic resonance imaging (MRI) may be useful.^[22][24] MRI can show inflammation of the sacroiliac joint.

Imaging

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.^[25]

Options for earlier diagnosis are

• 
  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.^[26]

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).^[27]

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.^[28] 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.^[29] 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.

The Schober's test is a useful clinical measure of flexion of the lumbar spine performed during the physical examination.^[30]

Treatment

There is no cure for AS,^[31] but treatments and medications can reduce symptoms and pain.

Medication

Medications for AS may be broadly considered either "disease-modifying" or "non-disease-modifying". Disease-modifying medications for ankylosing spondylitis aim to slow disease progression and include drugs like tumor necrosis factor (TNF) inhibitors. Non-disease-modifying medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), primarily address symptoms like pain and inflammation but do not alter the course of the disease.^[32]

NSAIDs

Unless otherwise contraindicated, all people with AS are recommended to take non-steroidal anti-inflammatory drugs (NSAIDs). The dose, frequency, and specific drug may depend on the individual and the symptoms they experience. NSAIDs, such as ibuprofen and naproxen, are used to alleviate pain, reduce inflammation, and improve joint stiffness associated with AS. These medications work by inhibiting the activity of cyclooxygenase (COX) enzymes, which are involved in the production of inflammatory prostaglandins. By reducing the levels of prostaglandins, NSAIDs help mitigate the inflammatory response and relieve symptoms in individuals with ankylosing spondylitis.^[8][33]

TNF inhibitors

Tumor necrosis factor inhibitors (TNFi) are a class of biologic drugs used in the treatment of ankylosing spondylitis. TNFi drugs, such as

Non-TNFi "biologic" drugs used in the treatment of ankylosing spondylitis include drugs that target different pathways involved in the inflammatory process. Two of the most important drugs in this class target IL-17, an important part of the inflammatory system: secukinumab and ixekizumab. They are often considered in cases where TNFi drugs are not effective or cause too many side effects. Additionally, they may sometimes be used as an adjunct to a TNFi when symptoms persist, but improve, while the patient is on the TNFi. The choice of a specific non-TNFi biologic depends on various factors, including the patient's medical history, preferences, and the recommendations of the healthcare provider.^[8]

Biosimilar drugs are biological products that are highly similar to an already approved biologic drug, with few or no clinically meaningful differences in terms of safety, purity, and potency. These drugs are developed to be equivalent to the reference biologic, often at a lower cost, providing alternative treatment options. In the context of ankylosing spondylitis, biosimilars are typically used as alternatives to the original biologic drugs. Biosimilars for ankylosing spondylitis may include versions of tumor necrosis factor inhibitors or other biologics commonly used in the treatment of the condition. When possible, physicians are recommended to use the original drugs over the biosimilar versions. Even biosimilars with perfect replication of the quality, composition, and other properties of the original drug are susceptible to nocebo effects.^[8][36]

csARDs

Conventional synthetic antirheumatic drugs (csARDs) are a class of disease-modifying medications. Unlike biologics or targeted synthetic drugs, which act on specific pathways in the immune system, csARDs have a broader effect on the immune system and are often considered traditional or conventional treatments. The most common drugs in this class are methotrexate and sulfasalazine. These medications are only used when others fail, or when certain specific conditions are met, and are often discontinued if a patient's symptoms become manageable with just a TNFi or other medication. Conventional DMARDs such as leflunomide are also considered to be part of this class.^[8]

Concerns exist about a possible lack of efficacy of some drugs in this class.^[37]

Corticosteroids

Glucocorticoids, such as prednisone or methylprednisolone, are sometimes used in the treatment of ankylosing spondylitis to manage acute flares and provide short-term relief from inflammation and symptoms. They are powerful anti-inflammatory medications that can help reduce pain, swelling, and stiffness associated with AS. However, glucocorticoids are generally not recommended for long-term use. They are more commonly used as localized injections when someone with AS has a temporary pain flare in a particular joint or area.^[8]

Surgery

In severe cases of AS, surgery can be an option in the form of joint replacements, particularly in the knees and hips. Surgical correction is also possible for those with severe flexion deformities (severe downward curvature) of the spine, particularly in the neck, although this procedure is considered very risky. In addition, AS can have some manifestations that make anesthesia more complex. Changes in the upper airway can lead to difficulties in intubating the airway, spinal and epidural anesthesia may be difficult owing to calcification of ligaments, and a small number of people have

Physical therapy

Though physical therapy remedies have been scarcely documented, some therapeutic exercises are used to help manage lower back, neck, knee, and shoulder pain. There is moderate quality evidence that therapeutic exercise programs help reduce pain and improve function.^[38] Therapeutic exercises include:^[39][40]

• Exercise programs, either at home or supervised
• Low intensity aerobic exercise, e.g. Pilates
• Spa-exercise therapy
• Aquatic physical therapy^[41]
• Proprioceptive neuromuscular facilitation
  (PNF)
• Heat therapy
• Cryotherapy in conjunction with exercise^[42]

Moderate-to-high impact exercises like jogging are generally not recommended or recommended with restrictions due to the jarring of affected vertebrae that can worsen pain and stiffness in some with AS.^{[medical citation needed]}

Diet

Research by Alan Ebringer at King's College in London, beginning in the 1980s, implicates overgrowth of the bacterium Klebsiella pneumoniae in the symptoms of ankylosing spondylitis. The body produces antibodies that attack Klebsiella pneumoniae. Enzymes made by the bacterium resemble human proteins, including three types of collagen (I, III, IV) and the HLA-B27 complex of glycoproteins. The antibodies therefore attack these human proteins, producing the symptoms of ankylosing spondylitis. Ebringer and others recommend low-starch or no-starch diets.^[43]

Prognosis

Prognosis is related to disease severity.^[10] AS can range from mild to progressively debilitating and from medically controlled to refractory. Some cases may have times of active inflammation followed by times of remission resulting in minimal disability while others never have times of remission and have acute inflammation and pain, leading to significant disability.^[10] As the disease progresses, it can cause the vertebrae and the lumbosacral joint to ossify, resulting in the fusion of the spine.^[44] This places the spine in a vulnerable state because it becomes one bone, which causes it to lose its range of motion as well as putting it at risk for spinal fractures. This not only limits mobility but reduces the affected person's quality of life. Complete fusion of the spine can lead to a reduced range of motion and increased pain, as well as total joint destruction which could lead to a joint replacement.^[45]

Osteoporosis is common in ankylosing spondylitis, both from chronic systemic inflammation and decreased mobility resulting from AS. Over a long-term period, osteopenia or osteoporosis of the AP spine may occur, causing eventual compression fractures and a back "hump".^[46] Hyperkyphosis from ankylosing spondylitis can also lead to impairment in mobility and balance, as well as impaired peripheral vision, which increases the risk of falls which can cause fracture of already-fragile vertebrae.^[46] Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. In compression fractures of the vertebrae, paresthesia is a complication due to the inflammation of the tissue surrounding nerves.

Organs commonly affected by AS, other than the axial

Mortality is increased in people with AS and circulatory disease is the most frequent cause of death.[49] People with AS have an increased risk of 60% for cerebrovascular mortality, and an overall increased risk of 50% for vascular mortality.^[50] About one third of those with ankylosing spondylitis have severe disease, which reduces life expectancy.^[51]

As increased mortality in ankylosing spondylitis is related to disease severity, factors negatively affecting outcomes include:^[49][52]

• Male sex^[53]
• Plus three of the following in the first two years of disease:
  • Erythrocyte sedimentation rate (ESR) >30 mm/h
  • Unresponsive to NSAIDs
  • Limitation of lumbar spine range of motion
  • Sausage-like fingers or toes
  • Oligoarthritis
  • Onset <16 years old

Gait

The hunched position that often results from complete spinal fusion can have an effect on a person's

Ankylosing spondylitis was distinguished from rheumatoid arthritis by Galen as early as the 2nd century AD.^[58] Skeletal evidence of the disease (ossification of joints and entheses primarily of the axial skeleton, known as "bamboo spine") was thought to be found in the skeletal remains of a 5000-year-old Egyptian mummy with evidence of bamboo spine.^[59][60] However, a subsequent report found that this was not the case.^[61]

The anatomist and surgeon

In 1858, David Tucker published a small booklet which clearly described the case of Leonard Trask, who had severe spinal deformity subsequent to AS.^[65] In 1833, Trask fell from a horse, exacerbating the condition and resulting in severe deformity. Tucker reported:

It was not until he [Trask] had exercised for some time that he could perform any labor ... [H]is neck and back have continued to curve drawing his head downward on his breast.

The account of Trask became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS.

In the late nineteenth century, the

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

References