Ankylosing Spondylitis

What is Ankylosing Spondylitis?

Ankylosing spondylitis is a long term painful disease that affects the spine, bones, muscles and ligaments that connect bones. There is presence of joint pain and inflammation akin to arthritis in this condition.

Causes of ankylosing spondylitis

This condition is caused when there is inflammation of the joints between the vertebrae in the spine, or in the ligaments and the joints at the base of the spine.

The inflammation leads to pain and stiffness in the neck and back and inflammation of the joints at the base of the spine or sacroiliac joints leads to pain in the lower back.

There is a genetic link that is associated with this condition. A gene known as HLA-B27 has been found to be associated with ankylosing spondylitis.

Symptoms of ankylosing spondylitis

The condition is characterized by pain and inflammation of the spine, surrounding muscles, ligaments and sacroiliac joints. The inflammation may affect the ankles, knees, and other organs such as eyes as well.

Ankylosing spondylitis epidemiology

Ankylosing spondylitis may affect people at any age beyond adolescence. It usually begins between ages 15 and 35 years (average 26 years).

About 80% of patients develop the condition before they are 30 years of age and less than 5% present with the symptoms at an age above 45 years.

Men are around two to three times more likely to suffer from this condition.

HLA B27 is the genetic link with the disease and is seen mostly among northern countries and some tribes. It is highest in Inuit populations and Haida Indians.

Overall, the prevalence of ankylosing spondylitis is between 0.1% and 1.4%. In mid-Europe the prevalence is 0.3–0.5%. The incidence of new cases of ankylosing spondylitis is between 0.5 and 14 per 100 000 people per year worldwide.

Treatment of ankylosing spondylitis

There is no cure for ankylosing spondylitis. Treatment aims at relief of pain and stiffness.

Long term treatment goals include maintaining optimum flexibility and movement of the spine in order to retain functioning.

Treatment involves regular physiotherapy that includes physical methods, such as massage and manipulation.

Medications including pain medications and those that relieve inflammation may help. Several lifestyle changes that improve the symptoms also help in treatment of this debilitating condition.

Eye involvement including inflammation of the uvea or uveitis is a complication sometimes associated with ankylosing spondylitis. This needs urgent attention failing which vision may be lost.

Ankylosing Spondylitis Diagnosis

There are no single tests that can confirm the diagnosis of ankylosing spondylitis. It is diagnosed mainly on the basis of symptoms as well as some tests.

Pain of ankylosing spondylitis is usually typical, worsening after rest usually in the second half of the night or early morning.

Complete blood count including ESR (erythrocyte sedimentation rate)

ESR denotes the level of blood cells after an hour of standing in a tube. High ESR is usually a marker of an inflammatory condition.

ESR may be raised in several conditions and thus this test is not specific for ankylosing spondylitis.

Blood tests also reveal mild anemia called normochromic normocytic anaemia meaning there is little change in appearance of Red blood cell size or colour.

A raised alkaline phosphatase level may be present in severe disease. Above normal serum IgA (Immunoglobulin A) levels are common.

C-Reactive protein

This is yet another marker of inflammation and is raised in several inflammatory conditions. However, only 50–70% of patients with active disease will have an increased level of C reactive protein and a raised ESR.

Imaging studies

Imaging studies like an X ray of the spine and lower back is then performed. X rays reveal damage to the joints at the base of the spine and formation of tiny new bones between the vertebrae (bones that form the spine). These new bones can press of surrounding structures and cause pain.

An X ray is followed up with a magnetic resonance imaging (MRI) scan to look at details of the damage to the spine, vertebrae and the sacroiliac joints (joints at the base of the spine).

MRI also reveals damage and inflammation of the ligaments in the spinal column. An ultrasound scan is sometimes performed to detect inflammation of the tissues.

These imaging studies can often confirm ankylosing spondylitis since they reveal characteristic inflammatory changes.

However, during initial stages of the disease, damage to the spine may not yet be visible making diagnosis difficult. To confirm a diagnosis of the condition some features must be present and these include presence of inflammation of the sacroiliac joints on X ray in a person with:-

  • at least three months of lower back pain that gets better with exercise and becomes worse with rest
  • restricted movement of the lower spine or the lumbar spine
  • restricted movement of the chest for breathing according to normal as per age and sex

In persons with all 3 features without sacroiliac inflammation the diagnosis of “probable ankylosing spondylitis” is made. An MRI can help detect the condition early.

HLA-B27 gene

The HLA-B27 gene is present in about 90–95% of white patients with ankylosing spondylitis in central Europe and North America. This is one of the confirmatory tests.

Ankylosing Spondylitis Symptoms

The symptoms of ankylosing spondylitis may differ among individual sufferers. Usually the disease is progressive and slow in onset and development.

Sometimes the symptoms may take years to manifest and develop.

Age of onset

Symptoms usually start during later teenage years or during young adulthood. The symptoms vary in intensity over the years and may improve or get worse over many years.

It usually begins between ages 15 and 35 years (average 26 years). About 80% of patients develop the condition before they are 30 years of age and less than 5% present with the symptoms at an age above 45 years.

Men are around two to three times more likely to suffer from this condition. The initial symptom is typically a dull pain that is insidious or slow in onset.

Symptoms of ankylosing spondylitis

  • Back pain and stiffness of the back – typically pain of the ankylosing spondylitis gets better with exercise and worsens on rest. A person often complains of a stiff and painful back early in the morning after a night’s rest. The pain and stiffness may last longer than 30 minutes after getting up and moving about in the morning. The pain may also worsen in the second half of the night after sleeping well the first half.
  • Pain in the lower back and buttocks – there may be pain in the lower back and the buttocks if the lower part of the spinal column or the lumbar spine is affected. Commonly the sacroiliac joint of the hip joint is affected. This also causes pain in the lower back and the buttocks. 
  • Inflammation, pain and swelling of the joints – apart from the spine, other joints may also be affected. Commonly hips, knees, wrists, shoulders and ankles may be affected. The main symptoms associated with arthritis include painful and restricted movement of the joint, swelling and warm joints are tender or painful on examination.
  • Inflammation and pain at the site where the tendons or ligaments attach to bone (enthesitis) – tendons are tough cord like connections between the muscles and bones while a ligament is band of tissues that connect the bones to bones. Site of enthesitis include the top of the shin bone, the Achilles tendon or behind the heel, under the heel and the ends of the ribs. The ankle may be painful if the tendons and ligaments around the ankle is affected. If the ends of the ribs are affected, there is chest pain.
  • Extreme fatigue and weakness
  • If the eyes are affected with anterior uveitis there may be symptoms of pain in the eye, increased tears formation, redness, pain on light being shown in the eyes (photophobia) etc.
  • Associated irritable bowel disease - around 60% of patients with ankylosing spondylitis also have IBD.

Ankylosing Spondylitis Treatment

Ankylosing spondylitis has no cure. Most of the treatments aim to relieve symptoms and delay the progress of the disease and prevent the spinal deformities and disability.

Treatment involves:-

Physiotherapy

Physiotherapy and keeping active helps in maintaining the flexibility of the spine and delays the progress of the disease. Stiffness and pain in the spine are also prevented with regular sessions of physiotherapy.

Physiotherapy is the cornerstone in treating ankylosing spondylitis. A physiotherapist advises the most effective exercises that are suitable for the patient and helps draw a plan for treatment of the condition with exercises.

Exercises prescribed may be performed in a group exercise programme or an individual exercise programme. Massage is also advised in some cases. Here the muscles and other soft tissues are manipulated to relieve pain and improve movement. This needs to be done by experts to prevent injury to the bones and muscles.

Another form of therapy suggested is hydrotherapy. Here the exercises are usually performed under water. The water is warm and shallow and may be a special hydrotherapy bath. Here the weight of the water helps improve blood flow, relaxes the muscles and relieves pain.

Electrotherapy is also tried by some sufferers. Small electric currents or impulses are passed though the muscles to ease pain and promote healing.

Other exercises like swimming and yoga may also be performed. All sports and exercises need to be cleared by the attending physiotherapist or rheumatologist before they are attempted to prevent injury and damage to the spine.

Pain relievers or NSAIDs (Non steroidal anti-inflammatory drugs)

The NSAIDs help in two ways – they relieve the pain and ease the inflammation. The commonest agents prescribed include Ibuprofen, diclofenac, naproxen etc. These however are fraught with side effects like gastric ulcers, kidney damage etc. Long term continued use is thus unadvisable.

In some individuals pain relief may be inadequate with NSAIDs and paracetamol. They may require opioid analgesics or Codeine. Codeine and other opioids however may cause side effects such as constipation, nausea, drowsiness and may lead to dependence and abuse.

Biologicals like tumour necrosis factor (TNF) blockers

These agents target the actual pathology of the condition rather than its symptoms. TNF is a chemical produced by cells when tissue is inflamed. TNF blockers or inhibitors help curb this TNF mediated inflammation.

Examples of TNF blockers include adalimumab, etanercept, golimumab etc. These agents are relatively new in ankylosing spondylitis though they have been used extensively in rheumatoid arthritis.

These may be used only if the diagnosis of ankylosing spondylitis is confirmed and level of pain is assessed twice 12 weeks apart to note no improvement with other therapies.

After 12 weeks of treatment with TNF blockers the pain scores and other scores are tested to check for improvements.

Calcium replenishing and bone forming agents like bisphosphonates

These agents are valuable in treatment of osteoporosis. Osteoporosis may develop as a complication of ankylosing spondylitis. Bisphosphonates may also be effective in treating ankylosing spondylitis.

Bisphosphonates including Alendronate, resedronate, zoledronate etc. can be taken by mouth as tablets or given by injection.

Disease-modifying anti-rheumatic drugs or DMARDs

These agents are useful in rheumatoid arthritis. DMARDs may be prescribed for ankylosing spondylitis but benefit those with involvement of peripheral joints such as knees, hips, shoulders, ankles and wrists. The ones that may be used include methotrexate and sulfasalazine.

Corticosteroids

Corticosteroids are anti-inflammatory agents that can be taken as injections (in acute cases) or as tablets. In case of inflamed joints the drug may also be given directly into the joint by injection. This is called intra-articular injections.

Ankylosing Spondylitis Pathophysiology

The cause of ankylosing spondylitis is not clearly understood. However, a genetic association is clear. Pathogenesis of this condition has clear associations with the HLA-B27 gene.

The HLA-B27 gene

Persons who suffer from ankylosing spondylitis seem to carry a particular gene known as human leukocyte antigen B27 (HLA-B27).

Nearly 90% of individuals with the condition test positive for this gene. However, having the gene along may not predict with 100% certainty that a person with get the disease.

Around 8% individuals in the general population have the HLA-B27 gene but do not have ankylosing spondylitis.

Persons who have a close relative who has ankylosing spondylitis, such as a parent or a sibling, the risk of developing ankylosing spondylitis is increased. This again could be due to presence of the HLA-B27 gene.

Underlying mechanisms 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 anklylosing 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.

Genetic and environmental factors

There is probably an interaction between the class I MHC molecule HLA-B27 and the T cell immune response. The HLAB27 presents an antigen to the CD8+ T cells and this in turn activates the immune system to attack the fibrocartilage or cartilage.

Bacterial infections are suggested to be triggering events in some cases and thus the environment may also play a part. Patients with the condition also have a higher production of IL10 (Interleukin 10) by CD8+ T cells. They have low levels of TNFα and interferon.

Ankylosing Spondylitis 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 that are 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 syndesmophytes 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, colon, and kidney. 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.

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