Ankylosing Spondylitis (AS) – Definition, Pathophysiology, and Causes.


Ankylosing spondylitis or AS, is a form of arthritis that primarily affects the spine, although other joints can become involved. It causes inflammation of the spinal joints (vertebrae) that can lead to severe, chronic pain and discomfort. The disease leads to calcification of the spine’s ligaments and discs and causes these soft structures to harden and fuse together with the joints and vertebral bodies. The spine becomes hard, brittle and susceptible to fracture.

In some people, AS can also affect the shoulders, ribs, hips, knees, and feet. It can also affect areas where the tendons and ligaments attach to the bones. Sometimes it can affect the eyes, bowel, and very rarely, the heart and lungs.

Pathophysiology of ankylosing spondylitis

There are no single agents that have been associated with the causation of ankylosing spondylitis. There seems to be a complex interaction between raised serum levels of IgA (Immunoglobulin A) and acute phase reactants of inflammation, the body’s immune system and the HLA-B27 gene.

A typical histological finding is called Enthesitis. Enthesis is the insertion of a tendon, ligament, capsule, or fascia into bone. Typically in ankylosing spondylitis, this enthesis is inflamed at the vertebrae.

Studies show that the entheseal fibrocartilage is the major target of the immune system and inflammation in ankylosing spondylitis. Enthesitis was originally considered as the hallmark of ankylosing spondylitis.

In addition, there is seen to be mild and destructive synovitis or inflammation of the synovium that forms a cushion in the joints. The myxoid subchondral bone marrow is also affected.

As the disease progresses it destroys the nearby articular tissues or joint tissues. The original and new cartilages are replaced by bone through fusion. This causes fusion or joining up of the joint bones and stiffness and immobility. This is the hallmark symptom in the spine in ankylosing spondylitis.

Causes of ankylosing spondylitis

  • The cause of ankylosing spondylitis is unknown.
  • The disorder does tend to run in families, so genetics probably play a role. If your parents or siblings have ankylosing spondylitis, you are 10 to 20 times more likely to be diagnosed with the disease than someone with no family history.
  • The main gene associated with the risk of AS is called HLA-B27. Scientists recently discovered two more genes (IL23Rand ERAP1) that, along with HLA-B27, make it more likely you will get AS.
  • Other immune system-related genes associated with ankylosing spondylitis include endoplasmic reticulum aminopeptidase 1 (ERAP1), interleukin 1 alpha (IL1A), and interleukin 23 receptors (IL23R). However, it is not clear how these gene variations affect a person’s risk of developing AS.

Risk factors

  • Men are as much as 3 times likelier to develop AS than women
  • The biggest risk factor for developing a severe form of AS is smoking
  • Age: Onset generally occurs in late adolescence or early adulthood
  • Family history

Clinical manifestations

  • Constant pain and stiffness in the low back, buttocks, and hips that continue for more than three months
  • Pain in ligaments and tendons
  • Eye inflammation such as redness and pain occurs in some people with spondylitis
  • You may also experience pain in the large joints such as the hips and shoulders.
  • Early morning stiffness
  • Loss of appetite
  • Low-grade fever
  • Weight loss
  • Fatigue
  • Anaemia or low iron

Because ankylosing spondylitis involves inflammation, other parts of your body can be affected as well. Patients may also experience:

  • Inflammation of the bowels
  • Mild eye inflammation
  • Heart valve inflammation
  • Achilles tendonitis

Complications of ankylosing spondylitis

  • Ankylosing spondylitis can cause an overgrowth of the bones, which may lead to the abnormal joining of bones, called “bony fusion.” Fusion affecting bones of the neck, back, or hips may impair a person’s ability to perform routine activities
  • Heart problems. Ankylosing spondylitis can cause problems with your aorta, the largest artery in your body. The inflamed aorta can enlarge to the point that it distorts the shape of the aortic valve in the heart, which impairs its function.
  • Eye inflammation like uveitis
  • Compression fractures in bones of people with AS
  • A hunched posture. A curled forward, chin-to-chest stance can occur if the spine fuses together in a hunched forward position.

  • Cauda equina syndrome. This rare condition involves extreme pressure and swelling of the nerves at the end of the spinal cord.
  • In this condition, one or more intervertebral discs or disc spaces become infected.

Diagnosis and Test

A medical history

A patient will be asked to describe:

  • When and how the joint pain or other symptoms first occurred
  • If pain improves or worsens with exercise
  • If joint pain has changed in severity or location
  • If any treatment has provided pain relief

A physical exam

A doctor will ask you for details about the pain and the history of your symptoms.

Images of your bones and joints

  • X-ray. An X-ray of your spine and any painful joints will show erosion. The erosion may not be detected if the disease is in the early stages. An MRI study may also be done, but the results are often difficult to interpret.
  • An MRI provides more-detailed images of bones and soft tissues. MRI scans can reveal evidence of ankylosing spondylitis earlier in the disease process but are much more expensive.
  • CAT scans (CT scans), and ultrasound can provide more accurate and detailed images, helping doctors identify earlier changes in the joints. These medical imaging techniques are more expensive and time-consuming than x-rays, so they are only done if needed.

Blood tests

  • C-Reactive protein (CRP). A high CRP level indicates an inflammatory condition, including infection. For this reason, a high CRP level does not automatically mean a patient has ankylosing spondylitis. In addition to using this test for diagnosis, doctors often monitor CRP levels to gauge a patients’ response to treatment.
  • Erythrocyte sedimentation rate (ESR). Similar to CRP as an indicator of inflammation, this test is not specific for ankylosing spondylitis and by itself does not diagnose a patient, but it can support the diagnosis. It is also used to see how active the condition is.
  • HLA-B27 gene. A positive test for this gene can help to confirm a suspected case of ankylosing spondylitis, but this test is not required for diagnosis when a patient has several obvious symptoms, or when sacroiliitis can be seen on an x-ray.

Treatment and medications

Exercise: Exercise and stretching may help painful, stiff joints. It should be done carefully and increased gradually.

Diet: A healthy diet is good for everyone and may be very helpful if you have AS. Keeping a healthy weight reduces stress on painful joints. Omega-3 fatty acids, found in cold-water fish (such as tuna and salmon), flax seeds, and walnuts, might help. This is still being studied.

Medicines: Several types of medicines are used to treat AS.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, ibuprofen, and naproxen are examples of NSAIDs.
  • These strong drugs are similar to the cortisone made by your body. They fight pain and swelling.
  • Disease-modifying antirheumatic drugs (DMARDs). These drugs work in different ways to reduce pain and swelling in AS.
  • Biologic agents. These are newer types of medicine. They block proteins involved with pain and swelling. Examples: adalimumab (Humira), adalimumab-atto (Amjevita), a biosimilar to Humira, certolizumab pegol (Cimzia), etanercept (Enbrel), etanercept-szzs (Erelzi), a biosimilar to Enbrel, golimumab (Simponi Aria, Simponi), infliximab (Remicade), and infliximab-dyyb (Inflectra), a biosimilar to Remicade, and secukinimab (Cosentyx) have been FDA-approved for treating ankylosing spondylitis.

Surgery: If AS causes joint damage that makes daily activities difficult, joint replacement may be an option. The knee and hip are the joints most often replaced. In very rare cases, your doctor may suggest surgery to straighten the spin. There are three types of spine surgery that may be used to treat ankylosing spondylitis. Only a surgeon can decide which surgery, if any, is appropriate.

  • Osteotomy of the spine.
  • Spinal fusion instrumentation.
  • Spinal decompression.

Prevention of ankylosing spondylitis

It is not known how you can prevent ankylosing spondylitis because no one knows what causes it in the first place. However, if you have the disease, you can focus on preventing disability by staying active, eating healthy, and maintaining a normal body weight.

  • Stay active. Exercise can help ease the pain, maintain flexibility and improve your posture.
  • Apply heat and cold. Heat applied to stiff joints and tight muscles can ease pain and stiffness. Try heating pads and hot baths and showers. Ice on inflamed areas can help reduce swelling.
  • Don’t smoke. If you smoke, quit. Smoking is generally bad for your health, but it creates additional problems for people with ankylosing spondylitis, including further hampering breathing.
  • Practice good posture. Practising standing straight in front of a mirror can help you avoid some of the problems associated with ankylosing spondylitis.

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  1. please what is the cure for waist pain I had been suffering for the past 6 years now , I need your advise.

  2. please what can be the cure drugs for back pain really? I have been suffering for almost one year now can u help me really.

  3. my mother suffering with back born pain for the couple of years now. she attended to adoctor,given a pills and she asked to attend an exercise but the problem still persist. can i have your help please.

  4. I had a problem of too much pain in my back that was caused by my spine and I would walk like an old woman but I got local medicine made from fruits vegetables and herbs am now very fine am walking normally with no pain

  5. can staph cause back pain?

  6. Good and succinct information/material.

  7. Hassan Kodithadathil

    very good and informative description. Even practising doctors are not fully aware of these details.

  8. Your Name Michael Bliss

    my brother has a disorder at the face region without any pain and doctors and herb men could not diagnosis what the problem is .he has been referred to take an xray . the jour is twisted and the left eye steady without blinking .he feels no pain but looks completely different in appearance .his tongue too is twisted and can’t pronounce words correctly .plz I need immediate help please

  9. my 7years old son suffered stroke and the hip bone of the affected part migrated. doctors tried but his mobility has been affected seriously. can you please help us?

  10. Iam suffering with AS since 4 months and using SAAZ tablets froms 2 months but iam not get rid off from that pain… Severe pain at the neck, knee, ankle…. Can u suggest any solution for it sir……

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