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Ankylosing Spondylitis

Humza Khizer

Overview

The National Institute of Health defines ankylosing spondylitis as a type of <a href="https://www.merisehat.pk/disease/arthritis" target="_blank">arthritis </a>that causes inflammation of the spine, including the joints and ligaments<a href="#accordion">[1]</a>. It has even been observed in Egyptian mummies dating back to 5,000 years. Derived from the Greek words ankylos (crooked) and spondylos (joint of the back), the disease is marked by a severe spinal deformity that often leads to a hunched posture.&nbsp;

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A type of seronegative spondyloarthropathy, ankylosing spondylitis (AS) is also known as Bechterew disease. Its global prevalence varies between 0.1-1.4%<a href="#accordion">[2]</a>. The United Kingdom saw a steep rise in AS cases (0.13% to 0.18%) between 1998 and 2017<a href="#accordion">[3]</a>. This increase was most significant among women and patients aged 60 years and above. In the United States, in particular, the disease is more common among non-Hispanic Whites than Mexican-Americans or Black people<a href="#accordion">[4]</a>. Generally, the disease seems to have a higher prevalence among the European population than among Asians and Africans<a href="#accordion">[5]</a>.

The prevalence of ankylosing spondylitis within a population varies depending on the prevalence of the HLA-B27 gene<a href="#accordion">[6]</a>. Approximately 90% of AS patients have the gene<a href="#accordion">[7]</a>. In Pakistan, due to the lack of studies, the exact prevalence of the disease remains unknown. However, previous studies have reported an approximate prevalence of 0.1 per 1000 population in Northern Pakistan and 0.9 per 1000 population in the southern part of the country<a href="#accordion">[8]</a>.&nbsp;

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Juvenile ankylosing spondylitis is a rare form of disease that affects young people, aged 17-35 years. However, it can occur in children as well. Inflammatory arthritis mostly affects the spine, but pain may also occur in the hips, knees, heels, and low back.&nbsp;

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Signs And Symptoms

Approximately 80% of people develop their first symptom before the age of 30 years<a href="#accordion">[4]</a>. The disease typically begins as chronic back pain and stiffness that is worse in the morning and at night. Moreover, this pain tends to improve with physical activity and worsen with rest. Unlike common backaches, the pain in ankylosing spondylitis is more likely to be long-lasting.

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Other signs and symptoms of the disease are:

<ul>
	<li>Pain or stiffness in the neck, shoulders, buttocks, lower back, hips, thighs, hands, feet, or heels</li>
	<li>Fatigue</li>
	<li>Weight loss</li>
	<li>Loss of appetite</li>
	<li>Fever</li>
	<li>Swelling of the joints</li>
	<li>Skin rash</li>
	<li>Postural abnormalities (e.g., hunched posture)</li>
	<li>Difficulty bending or twisting</li>
	<li>Difficulty sitting due to tenderness at the base of the pelvis</li>
	<li>Breathing difficulty</li>
</ul>

&nbsp;

Other than the spine and various joints, other parts of the body can also develop inflammation. Extra-articular manifestations of the disease include:

<ul>
	<li>Psoriasis</li>
	<li>Inflammatory bowel disease (e.g., Crohn&rsquo;s disease and <a href="https://www.merisehat.pk/disease/ulcerative-colitis" target="_blank">ulcerative colitis</a>)</li>
	<li>Acute anterior uveitis</li>
	<li>Pulmonary disease (e.g., lung fibrosis)</li>
	<li>Cardiovascular disease (e.g., inflammation of the aorta)</li>
</ul>

<div>&nbsp;</div>

Causes

The spinal column comprises 33 vertebrae, the spinal joints, intervertebral discs, the spinal cord, and ligaments and muscles that hold the spine in place. Moreover, tendons connect the muscles to the bones and help in spinal movement.&nbsp;

In ankylosing spondylitis, the joints and ligaments can undergo inflammation. As a result, movement becomes painful and stiff. The inflammation also leads to the formation of new bone around the spinal column. This adds to the stiffness in the back and neck.&nbsp;

Moreover, as a result of the inflammation, the body produces extra calcium which causes the bones to fuse together. Thus, adding to the spinal deformity.&nbsp;

Patients with ankylosing spondylitis typically experience flare-ups and periods of remission. The spine and lower back are most commonly affected by pain, stiffness, and a loss of mobility. However, the disease can also affect the neck and other joints in the body.

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Ankylosing spondylitis usually has an impact on:

<ul>
	<li>Hip and shoulder joints</li>
	<li>Lower back vertebrae</li>
	<li>Point of attachment of tendons and ligaments to the bones (mainly in the spine)</li>
	<li>The joint between the spine and pelvis (sacroiliac joint)</li>
</ul>

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The exact pathogenesis of ankylosing spondylitis is unclear. However, researchers predict that the human leukocyte antigen (HLA-B27) gene may be linked to the disease. Mutations in the gene can increase the risk of disease.&nbsp;

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There are no specific screening tests for ankylosing spondylitis.

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Diagnosis

Since ankylosing spondylitis begins with back pain, it is easily confused with several other diseases. It&rsquo;s also difficult to diagnose the condition because the disease progresses slowly. Moreover, there is no single, definitive test for ankylosing spondylitis, and so doctors may require a combination of blood tests and imaging scans to reach a diagnosis.

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<h5>History</h5>

Initially, a complete history is taken from the individual. During the history taking, the doctor will focus on questions relating to the person&rsquo;s location and characteristics of pain. They will also make it a point to ask whether the pain wakes the patient up from sleep at night.&nbsp;

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<h5>Physical Examination</h5>

During a physical exam, the doctor checks the patient&rsquo;s range of motion in the spine. Moreover, a person&rsquo;s chest expansion is tested to assess breathing difficulty.&nbsp;

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<ul>
	<li>Schober Test: It measures the extent of lumbar flexion as the person bends over in a toe-touch position. A limited motion is considered diagnostic of ankylosing spondylitis.&nbsp;</li>
	<li>Chest Expansion: The patient&rsquo;s chest expansion is measured from full inspiration to deep expiration. A measurement of less than 1 inch indicates reduced chest expansion. Thus, suggesting a diagnosis of ankylosing spondylitis.&nbsp;</li>
</ul>

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<h5>Lab Tests&nbsp;</h5>

Blood tests can help confirm whether the patient has the HLA-B27 gene. However, not everyone who tests positive for the gene will go on to develop ankylosing spondylitis. Other tests, such as the erythrocyte sedimentation rate and levels of C-reactive protein, can help assess inflammation.

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<h5>Imaging Studies</h5>

<ul>
	<li>X-ray: An X-ray demonstrates any joint damage within the spine and joints. A widening of the joint space, the presence of a bony spur, and a change in spinal curvature can be seen in the imaging study. In the radiograph of the lumbar spine &ldquo; a trolley-track sign&rdquo; can be seen which is characteristic of ankylosing spondylitis.&nbsp;</li>
	<li>Magnetic Resonance Imaging (MRI): An MRI of the sacroiliac joints helps reveal any early signs of disease not commonly visible on X-rays.&nbsp;</li>
</ul>

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Imaging abnormalities help assess damage in the spine and sacroiliac joints. Evidence of sacroiliitis is typically included in the inclusion criteria for ankylosing spondylitis diagnosis. Based on the imaging abnormalities, sacroiliitis can be classified into the following grades:

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<ul>
	<li>0: This grade denotes a normal sacroiliac joint with sharp joint margins</li>
	<li>I: The findings are termed suspicious</li>
	<li>II: Sclerosis and some erosions are visible&nbsp;</li>
	<li>III: Severe erosions are seen in the scan, along with partial ankylosis and pseudo-dilation of the space between the joints</li>
	<li>IV: This is the most severe grade and is characterized by complete ankylosis</li>
</ul>

<div>&nbsp;</div>

Treatment

Currently, there is no cure for ankylosing spondylitis. However, treatment can help manage pain, slow disease progression, prevent complications, and improve the person&rsquo;s overall quality of life.&nbsp;

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<h5>Lifestyle Modifications</h5>

Regular exercise, such as swimming, yoga, and walking, can help maintain flexibility and strengthen muscles. It lessens the pain and, coupled with a healthy diet (low in saturated fats products and rich in fruits and vegetables), it can help reduce inflammation.&nbsp;

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<h5>Medications</h5>

<ul>
	<li>
	Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): These are the first-line medications to help manage pain and inflammation in ankylosing spondylitis. Examples include naproxen and ibuprofen.
	</li>
	<li>Tumor Necrosis Factor (TNF) Inhibitors: These drugs block inflammatory markers, such as cytokines, in the body. Examples of the medication include infliximab, adalimumab, and etanercept.</li>
	<li>Corticosteroids: Although systemic steroids are not recommended, injections may be administered locally to the site of inflammation. They can help slow inflammatory damage around the spine.&nbsp;</li>
	<li>Disease-Modifying Antirheumatic Drugs (DMARDs): If NSAIDs do not work, doctors may switch to long-term treatment with DMARDs. Examples include methotrexate and sulfasalazine which prevent joint damage by blocking inflammation.&nbsp;</li>
</ul>

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<h5>Physical Therapy</h5>

Regular physical therapy with experienced professionals stretches the muscles, reduces pain and stiffness, and helps the person maintain a good posture. Moreover, the stretches can also be practiced at home.&nbsp;

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<h5>Surgery</h5>

In case of severe joint damage, doctors may recommend surgery. This may include joint repairs, joint replacements, or even procedures to help correct the spinal curvature.&nbsp;

&nbsp;

<ul>
	<li>Osteotomy: The procedure involves the removal of a portion of the bone to realign the spine. It is typically done to correct kyphosis and improve mobility, but cannot bring back the full range of spinal mobility for the patient.</li>
	<li>Laminectomy: As part of the procedure, the surgeon removes part of the spinal bone to make space for any compressed nerves. It helps relieve pain in the arms and legs, but not the back.&nbsp;</li>
	<li>Spinal Fusion: The surgeon uses wires, rods, and bars to stabilize the spine. It is often conducted in combination with osteotomy or laminectomy.&nbsp;</li>
	<li>Hip Replacement: In case of severe hip joint damage, the surgeon replaces it with an artificial hip. The procedure is not common in ankylosing spondylitis.&nbsp;&nbsp;</li>
</ul>

<div>&nbsp;</div>

If left untreated, the inflammation of the spinal joints can lead to chronic pain and disability. This is due to the fusion of vertebrae in the spinal column. Moreover, the formation of new bone in the spinal regions can lead to immobility.&nbsp;

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Other complications include:

<ul>
	<li>Compression fractures of the spine</li>
	<li><a href="https://www.merisehat.pk/disease/osteoporosis-80" target="_blank">Osteoporosis</a></li>
	<li>Pulmonary fibrosis</li>
	<li>Uveitis</li>
	<li>Cauda equina syndrome</li>
	<li>Aortic regurgitation</li>
	<li>Heart valve disease</li>
</ul>

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The following factors increase one&rsquo;s risk of the disease<a href="#accordion">[5]</a>:

<ul>
	<li>Age: In ankylosing spondylitis, symptoms typically develop before 30 years.&nbsp;</li>
	<li>Gender: Symptoms of the disease can vary according to gender. Moreover, the condition occurs 2-3 times more frequently in men than women.</li>
	<li>Family History: The presence of the HLA-B27 gene has been linked to causing the development of ankylosing spondylitis.</li>
	<li>Medical Diseases: Certain diseases, such as ulcerative colitis, Crohn&rsquo;s disease, or psoriasis, can increase one&rsquo;s risk of disease.&nbsp;</li>
</ul>

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Although genetic factors play a huge role in causing ankylosing spondylitis, certain lifestyle modifications can help prevent the disease from progressing further. Moreover, they can help reduce the risk of postural abnormalities, such as kyphosis, from developing.&nbsp;

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The following can help prevent complications associated with ankylosing spondylitis:

<ul>
	<li>Staying active and exercising regularly</li>
	<li>Maintaining a good posture</li>
	<li>Quitting smoking</li>
	<li>Managing stress</li>
	<li>Eating healthy&nbsp;</li>
	<li>Staying compliant with prescribed medications</li>
</ul>

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Recently, researchers discovered a link between the gut microbiome and ankylosing spondylitis. The observational study evaluated the gut microbiota in 30 patients, before and after administration of adalimumab therapy<a href="#accordion">[9]</a>. After 6 months of treatment, the patient&#39;s microbiome returned to a more normal state, similar to that seen in the control group. Thus, it demonstrates the role of gut bacteria as a potential tool for assessing treatment response in patients with ankylosing spondylitis.&nbsp;

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Key Points

<ul>
	<li>Ankylosing Spondylitis is a chronic inflammatory disease of the spine.&nbsp;</li>
	<li>It is more prevalent in men than women and symptoms typically begin before the age of 30 years.&nbsp;</li>
	<li>A rare, juvenile form of the disease also exists that typically presents in children or people aged 17-35 years.&nbsp;</li>
	<li>The exact cause of the disease is unclear. However, the HLA-B27 gene is associated with causing the disease.&nbsp;</li>
	<li>It is believed that the rare arthritis results from inflammation of the joints and ligaments. As a result, movement becomes painful and stiff.&nbsp;</li>
	<li>The disease typically begins as chronic back pain and stiffness that is worse in the morning and at night. Moreover, this pain tends to improve with physical activity and worsen with rest.&nbsp;</li>
	<li>Other symptoms of the disease include hip pain, fatigue, hunched posture, difficulty breathing, and immobility.&nbsp;</li>
	<li>Compression fractures of the spine, uveitis, pulmonary fibrosis, <a href="https://www.merisehat.pk/disease/osteoporosis-80" target="_blank">osteoporosis</a>, and cardiovascular diseases are common complications of the disease.</li>
	<li>Imaging studies, such as CT and MRI scans, can help assess the joints for damage and inflammation.</li>
	<li>Although ankylosing spondylitis has no cure, current treatment methods can help manage pain, slow disease progression, prevent complications, and improve the person&rsquo;s overall quality of life.&nbsp;</li>
	<li>Lifestyle modifications (physical activity, healthy diet), medications (NSAIDs, DMARDs, TNF inhibitors, steroids), and surgery are common treatment options for the disease.&nbsp;</li>
</ul>

<div>&nbsp;</div>

[1] Ankylosing spondylitis. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

[2] Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology. 2013;53(4):650-657. doi:10.1093/rheumatology/ket387

[3] Crossfield SS, Marzo-Ortega H, Kingsbury SR, Pujades-Rodriguez M, Conaghan PG. Changes in ankylosing spondylitis incidence, prevalence and time to diagnosis over two decades. RMD Open. 2021;7(3). doi:10.1136/rmdopen-2021-001888

[4] Wenker KJ, Quint JM. Ankylosing Spondylitis. [Updated 2022 Apr 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan

[5] Akassou A, Bakri Y. Does HLA-B27 Status Influence Ankylosing Spondylitis Phenotype?. Clin Med Insights Arthritis Musculoskelet Disord. 2018;11:1179544117751627. Published 2018 Jan 8. doi:10.1177/1179544117751627

[6] Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A. Ankylosing spondylitis: An overview. Annals of the Rheumatic Diseases. 2002;61(Supplement 3):8iii-18. doi:10.1136/ard.61.suppl_3.iii8

[7] Chen B, Li J, He C, et al. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep. 2017;15(4):1943-1951. doi:10.3892/mmr.2017.6248

[8] Ahsan T, Erum U, Jabeen R, Khowaja D. Ankylosing Spondylitis: A rheumatology clinic experience. Pak J Med Sci. 2016;32(2):365-368. doi:10.12669/pjms.322.9366

[9] Chen Z, Zheng X, Wu X, et al. Adalimumab therapy restores the gut microbiota in patients with ankylosing spondylitis. Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.700570