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Ankylosing spondylitis
This long-term autoimmune disorder can cause inflammation in the joints and ligaments of the spine, and sometimes in other parts of the body. It generally affects young adults, with symptoms often starting in late adolescence or early adulthood.
Overview
Ankylosing spondylitis (AS) is a type of arthritis that mainly affects the spine. The condition can cause inflammation in the vertebrae (the small bones of the spine), which can eventually lead to severe, chronic pain and discomfort [PMID:33675037]. In advanced cases, this inflammation can cause new bone formation on the spine, leading to sections of the backbone fusing together. This fusion can result in a rigid, inflexible spine, sometimes described as a 'bamboo spine'.
While the spine is the primary area affected, AS can also cause inflammation in other joints, such as those in the hips, knees, or shoulders. It can also affect ligaments and tendons, and sometimes other organs like the eyes. The exact prevalence of AS in the UK and globally varies, with estimates typically ranging from 0.1% to 1.4% of the population, and it is observed more frequently in men than in women [PMID:35773919].
Symptoms & clinical features
The hallmark symptoms of ankylosing spondylitis include persistent pain and stiffness in the lower back and hips, especially in the mornings or after periods of inactivity. This pain often improves with exercise and worsens with rest. Many individuals experience sacroiliitis - inflammation of the joints between the base of the spine and the pelvis (sacroiliac joints).
Other symptoms can include pain and stiffness in the neck, chest, or heels. Some people may develop enthesitis, which is inflammation where tendons or ligaments attach to bones. Fatigue is also a common symptom, as the body uses energy to fight ongoing inflammation. In some cases, individuals may experience inflammatory eye conditions such as uveitis (inflammation of the middle layer of the eye), which can cause eye pain, redness, and sensitivity to light.
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Affected organs
The primary organs affected by ankylosing spondylitis are the joints of the axial skeleton, particularly the spine and the sacroiliac joints. Chronic inflammation in these areas can lead to structural changes over time.
Beyond the spine, AS can affect other systems. The peripheral joints, such as the hips, knees, and shoulders, may experience inflammation. Ligaments and tendons, especially where they connect to bone (entheses), can also become inflamed. Less commonly, AS can impact the eyes, causing uveitis, and in rare instances, it may affect the heart, lungs, or kidneys, though these are not typical primary features of the condition.
Risks & severity
Ankylosing spondylitis typically presents in late adolescence or early adulthood, with symptoms often beginning before the age of 45. The severity of AS can vary significantly between individuals; some may experience only mild, intermittent symptoms, while others face chronic pain and significant spinal rigidity.
Over many years, severe AS can lead to fusion of the vertebrae, resulting in a loss of spinal flexibility and potentially a stooped posture. This can impact daily activities and quality of life. The risk of certain complications, such as inflammatory bowel disease, psoriasis, and acute anterior uveitis, is increased in individuals with AS. Spinal fractures are also a concern in those with advanced spinal fusion due to increased bone fragility [PMID:35773919].
Genetic causes
Ankylosing spondylitis is considered a complex or polygenic condition. This means that a combination of multiple genetic variations, along with environmental factors, contributes to an individual's susceptibility. This is different from conditions caused by a single gene mutation.
While many genes are thought to play a role, specific genes, such as *ERAP1* (endoplasmic reticulum aminopeptidase 1) and *IL23R* (interleukin 23 receptor), have been identified as contributing to AS risk [PMID:24177724]. *ERAP1* is involved in processing peptides for presentation to the immune system, and variations in this gene can influence how effectively the immune system responds. *IL23R* encodes a receptor for interleukin-23, a cytokine that plays a key role in inflammatory and autoimmune responses. Variant forms of these genes, particularly in combination with specific types of the *HLA-B* gene (especially *HLA-B27*), have been associated with an increased risk of developing AS.
Inheritance pattern
Ankylosing spondylitis has a polygenic or complex inheritance pattern. This means there isn't a single gene that causes the condition. Instead, it is thought to be influenced by multiple genes acting together, alongside environmental factors that are not yet fully understood.
If you have a close relative with AS, you may have a slightly increased risk of developing the condition compared to the general population, but it's not a certainty. The presence of certain genetic markers, such as *HLA-B27*, can increase risk, but many people with this marker never develop AS. Because of this complex inheritance, predicting precisely who will develop AS within a family is very difficult, and genetic testing is not typically used for predictive purposes in relatives.
Diagnosis & testing
Diagnosing ankylosing spondylitis often involves a combination of clinical assessment, imaging studies, and blood tests. A doctor will typically inquire about symptoms, particularly chronic back pain that worsens with rest and improves with exercise. Physical examination may reveal reduced spinal mobility.
Imaging techniques, such as X-rays or MRI scans of the sacroiliac joints, are crucial for identifying inflammation or structural changes characteristic of AS. Blood tests may check for markers of inflammation, such as C-reactive protein (CRP) levels, and sometimes for the presence of the *HLA-B27* gene. However, a positive *HLA-B27* test alone does not confirm AS, as many healthy people also carry this gene. Referral to a rheumatologist, a specialist in joint and muscle conditions, is often necessary for confirmed diagnosis and management. The NHS Genomic Medicine Service (GMS) may offer genetic testing for specific genes associated with AS under R-codes related to inflammatory arthropathies, primarily for diagnostic clarification in complex cases rather than initial screening.
Management & lifestyle
Managing ankylosing spondylitis focuses on relieving symptoms, reducing inflammation, preventing spinal fusion, and maintaining mobility. Treatment plans are individualised and typically guided by a rheumatologist within the NHS.
Non-steroidal anti-inflammatory drugs (NSAIDs) are often the first-line treatment for pain and stiffness. Regular exercise, including physiotherapy, is vital to maintain spinal flexibility and good posture. In some cases, disease-modifying anti-rheumatic drugs (DMARDs) or biologic medications, such as TNF inhibitors, may be prescribed, particularly for those with persistent inflammation or peripheral joint involvement. Genetic counsellors can provide valuable information on the genetic aspects of AS and its implications for family members. Lifestyle adjustments, like avoiding smoking, can also play a role in managing symptoms and reducing disease progression.
UK care pathway
In the UK, individuals suspected of having ankylosing spondylitis are typically referred by their GP to a rheumatologist. The NHS Genomic Medicine Service (GMS) provides a pathway for genetic testing where it is clinically appropriate, often following specialist assessment. Relevant R-codes within the GMS typically relate to inflammatory arthropathies, including specific tests for *HLA-B27* as part of a diagnostic workup. Genetic counsellors are available through clinical genetics services to discuss complex genetic conditions, inheritance patterns, and the implications for families.
Frequently asked questions
Is ankylosing spondylitis an inherited condition?
Ankylosing spondylitis is considered a complex or polygenic condition. This means that multiple genetic factors, rather than a single gene, work together with environmental influences to increase the risk of developing it. It is not inherited in a simple dominant or recessive pattern.
Can ankylosing spondylitis affect parts of the body other than the spine?
Yes, while the spine is primarily affected, ankylosing spondylitis can cause inflammation in other joints like the hips or shoulders. It can also affect where tendons and ligaments attach to bones (enthesitis) and, less commonly, organs such as the eyes (uveitis).
What is the role of the *HLA-B27* gene in ankylosing spondylitis?
The *HLA-B27* gene is strongly associated with an increased risk of developing ankylosing spondylitis. However, many people who carry *HLA-B27* never develop the condition, and some people with AS do not have this gene. Therefore, it is a risk factor, not a diagnostic confirmation.
Can exercise help manage ankylosing spondylitis?
Yes, regular exercise, particularly gentle stretching and strengthening, is a very important part of managing ankylosing spondylitis. It can help improve spinal flexibility, reduce stiffness, and maintain good posture. Physiotherapy often plays a key role in developing an appropriate exercise plan.
References
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- Edavalath M. Ankylosing spondylitis. Journal of Ayurveda and integrative medicine. 2010. PMID: 21547050
- Wei JC, Zhang LJ, Huang JX. Placebo responses in ankylosing spondylitis patients worldwide: variations and possible explanations. Expert review of clinical immunology. 2020. PMID: 32213079
- Braun J. Axial spondyloarthritis including ankylosing spondylitis. Rheumatology (Oxford, England). 2018. PMID: 30445482
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- Chen CW, Wei JC, Gu J. Editorial: Advances in Pathogenesis, Etiology, and Therapies for Ankylosing Spondylitis. Frontiers in immunology. 2021. PMID: 35003143