Ankylosing Spondylitis

Ankylosing Spondylitis (AS) is a painful condition caused by inflammatory arthritis of the joints and ligaments of the spine (a form of spondyloarthritis – read more here). AS primarily affects the axial skeleton, which includes the entire spine, pelvis, rib cage and skull. The word “ankylosis” means abnormal stiffness and immobility of a joint due to bone fusion, and “spondylitis” means inflammation of the bones of the spine (vertebrae). Approximately 2% of Australians are affected, more males than females. AS usually begins before the age of 40.

Symptoms

The most common symptoms are aches and stiffness of the spine and hips that can extend to the neck, shoulders, rib cage and other joints over time. Pain and stiffness are worse in the morning or after rest and improve with activity or exercise.

In severe, long-standing cases, the vertebrate may fuse together and lead to a bent forward posture. The fused spine seen in AS patients is sometimes referred to as “bamboo spine”. Bone fusions can occur in other areas, such as the rib cage, which can affect breathing. In approximately 25% of affected people, the inflammation spreads to the eyes, causing pain and redness.

Diagnosis

Diagnosis is based on symptoms, physical examination, blood tests and medical imaging.

  • Blood tests such as CRP and ESR/SED rate are performed to assess levels of inflammation.
  • X-rays may show bone abnormalities and/or damage due to inflammation, such as erosion. A key sign of AS is erosion and fusion of the joints linking the base of the spine and pelvis (the sacroiliac joints).
  • MRI can detect early signs of the disease that cannot be seen on an X-ray, such as changes in bone marrow, excess fluid in the bone (oedema) and abnormal bone growth. Disease progression and inflammation may also be assessed with MRI technologies. Clinical trials will often involve MRI scans.

What Causes Ankylosing Spondylitis?

The symptoms of AS are due to inflammation in the ligaments and joints. This damaging inflammation leads to erosion of bones and joints and abnormal bony growths, which can lead to vertebrae fusing together.

By http://en.wikipedia.org/wiki/User:Senseiwa [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons

The actual disease itself is caused by a combination of things, the most significant of these, but not always the underlying cause, is genetics.

Genetics

Numerous genes have been linked to AS, with most of those having roles in inflammation or regulation of the immune system, such as Human Leukocyte Antigens (HLAs) and Interleukins (ILs).

  • HLAs are expressed on the surface of immune cells and instruct the immune system to identify what is self-tissue versus foreign cells or substances. There are two major classes of HLAs and 1000’s of variations that exist in humans. HLA-B27 is the most strongly associated genetic risk factor for AS. It can cause the immune system to attack its own healthy cells and tissues. 90-95% of AS patients have this HLA subtype, compared to around 7% of the healthy population.
  • ILs are signalling proteins released by immune cells. They include pro- and anti-inflammatory ILs. High levels of pro-inflammatory ILs have been found in AS patients, such as IL-17 and IL-23.

Other Risk Factors

  • Smoking is a major risk factor and can accelerate disease progression and rates of spinal fusion;
  • Inactive lifestyle and poor posture;
  • Gut inflammation (i.e. inflammatory bowel disease);
  • Bacterial infection may also increase the risk of developing AS.

Current Treatment Options

Unfortunately, there is no cure for AS, however it can be well controlled with the right treatment and management plan. Early diagnosis and treatment are key to improving symptoms and preventing advanced disease outcomes.

Non-Steroidal Anti-Inflammatory Drugs

NSAIDs (i.e. ibuprofen, naproxen, diclofenac, celecoxib) may reduce inflammation and improve pain and stiffness.

Disease-Modifying Anti-Rheumatic Drugs

DMARDs can be trialled if NSAIDs aren’t useful. They are designed to treat the underlying issues and may relieve arthritis symptoms and prevent joint damage. There are synthetic (conventional) and biological DMARDs. Biologics are recommended for AS and include the following:

  • Anti-TNFα Drugs – Tumor Necrosis Factor Alpha is a major immune regulator and is pro-inflammatory. Too much is produced in various inflammatory/immune diseases. TNFα inhibitors are highly effective in reducing disease activity and symptoms of AS and are therefore strongly recommended in treatment of AS. Some examples are etanercept and infliximab.
  • Interleukin Inhibitors – Inhibition of key pro-inflammatory ILs reduces inflammation and AS symptoms. The IL-17 inhibitor secukinumab is approved for AS. Ustekinumab is an inhibitor of IL-12 and Il-23. It is currently approved for treatment of psoriasis and psoriatic arthritis, but not AS. It is being trialed in patients with AS and the results are promising.

Physical Therapy

An active lifestyle and regular exercise improves the symptoms and outcomes of AS. Studies have shown that regular exercise may reduce pain and disease activity and can help to prevent spinal fusions.

Surgery

Joint replacement surgery (namely the hips) may be performed to restore functioning that has been lost due to inflammed and damaged joints.


Clinical Trials

Genesis Research Services is currently recruiting participants with Ankylosing Spondylitis for a trial involving an investigational medication. To register your interest and see if you qualify for this study, click here or call us on (02) 4985 1860.


References & Resources:

  1. Arthritis Foundation. “Ankylosing Spondylitis”: https://www.arthritis.org/about-arthritis/types/ankylosing-spondylitis/
  2. Empowered – Arthritis Australia. “Ankylosing spondylitis”: http://empowered.org.au/ankylosing-spondylitis
  3. Dashti N, et al. “HLA-B*27 subtypes and their implications in the pathogenesis of ankylosing spondylitis”. Gene 2018;670:15-21. https://www.ncbi.nlm.nih.gov/pubmed/29803000
  4. Dülger S, et al. “How Does Smoking Cessation Affect Disease Activity, Function Loss, and Quality of Life in Smokers With Ankylosing Spondylitis?”. Journal of Clinical Rheumatology 2018;Jul 10. https://www.ncbi.nlm.nih.gov/pubmed/29994796
  5. Lata M, Hettinghouse AS & Liu CJ. “Targeting tumor necrosis factor receptors in ankylosing spondylitis”. Annals of the New York Academy of Sciences 2018;Jul 15. https://www.ncbi.nlm.nih.gov/pubmed/30008173
  6. Østergaard M & Lambert RGW. “Imaging in ankylosing spondylitis”. Therapeutic Advances in Musckuloskeletal Disease 2012;4:301-311. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403247/
  7. Ranganathan V, et al. “Pathogenesis of ankylosing spondylitis – recent advances and future directions”. Nature Reviews. Rheumatology 2017;13:359-67. https://www.ncbi.nlm.nih.gov/pubmed/28446810
  8. Regel A, et al. “Efficacy and safety of non-pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis”. RMD Open 2017; 3:e000397. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28176966
  9. Sieper J & Poddubnyy D. “New evidence on the management of spondyloarthritis”. Nature Reviews. Rheumatology 2016;12:282-295. https://www.ncbi.nlm.nih.gov/pubmed/27052489
  10. Sundström B, Ljung L & Wållberg-Jonsson S. “Exercise habits and C-reactive protein may predict development of spinal immobility in patients with ankylosing spondylitis”. Clinical Rheumatology 2018;Jul 18. https://www.ncbi.nlm.nih.gov/pubmed/30022369
  11. Toussirot E. “New treatment options and emerging drugs for axial spondyloarthritis: biological and targeted synthetic agents”. Expert Opinion on Pharmacotherapy 2017; 18:275-282.
    https://www.ncbi.nlm.nih.gov/pubmed/28099816
  12. Spinal process image by http://en.wikipedia.org/wiki/User:Senseiwa [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons
August 8th, 2018|