Ankylosing spondylitis (AS) is a chronic inflammatory condition primarily affecting the axial skeleton, leading to inflammatory back pain and, in severe cases, spinal fusion. Classified under spondyloarthritis (SpA), AS shares characteristics like peripheral arthritis, enthesitis, and uveitis. Understanding the epidemiology, etiology, clinical presentation, and particularly the Ankylosing Spondylitis Age Of Diagnosis is crucial for early intervention and management.
Epidemiology and Age of Onset
The prevalence of ankylosing spondylitis in the United States ranges from 0.2% to 0.5% of the population. Globally, the incidence rate varies, with age- and sex-adjusted figures between 0.4 and 14 per 100,000 person-years. A significant correlation exists with the HLA-B27 gene, as prevalence increases to approximately 5% in HLA-B27 positive individuals. Men are diagnosed with AS more frequently than women, at a ratio of approximately 2:1.
The ankylosing spondylitis age of diagnosis is a key epidemiological feature. The onset of AS symptoms typically peaks during the second and third decades of life. Notably, about 80% of individuals with AS experience their first symptoms before the age of 30. Late-onset AS, with symptom presentation at age 45 or older, is less common, accounting for only about 5% of cases. This early age of onset underscores the importance of considering AS in younger individuals presenting with chronic back pain.
Etiology and Genetic Predisposition
While the exact cause of ankylosing spondylitis remains largely unknown, genetic factors play a significant role. Heritability is strongly implicated, with major histocompatibility complex (MHC) alleles, especially HLA-B27, contributing substantially to genetic susceptibility, potentially accounting for up to one-third of the genetic component. Other MHC alleles like HLA-B60 and HLA-DR1 may also have minor roles.
Recent advancements in genetic research, particularly genome-wide association studies (GWAS), have identified additional susceptibility loci beyond MHC, including genes such as IL23R, ERAP1, and IL1R2. These genetic findings are crucial for understanding the pathogenesis of AS and may offer targets for future therapeutic interventions. Environmental triggers are also suspected to play a role in individuals with genetic predisposition, but these are still under investigation.
Clinical Manifestations and Progression
The hallmark clinical manifestation of ankylosing spondylitis is inflammatory back pain, stemming from sacroiliitis and axial arthritis. This is often accompanied by peripheral arthritis affecting joints other than the spine, enthesitis (inflammation at tendon and ligament insertion points), and acute anterior uveitis (eye inflammation). Less frequently, cardiac involvement such as aortitis and arrhythmias can occur.
Inflammatory back pain in AS is characterized by stiffness, soreness, and pain that is typically worse in the morning and after periods of rest, often causing sleep disturbance. A key differentiating feature from mechanical back pain is that inflammatory back pain improves with physical activity and stretching.
The natural course of AS can lead to structural changes in the spine. Chronic inflammation can result in the formation of syndesmophytes, bony growths that bridge vertebrae and reduce spinal mobility. Over time, this process can lead to spinal fusion, often described as “bamboo spine.” While traditionally thought to progress in an ascending pattern from the lumbar to cervical spine, recent evidence suggests spinal fusion may occur in a more discontinuous, or saltatory, pattern. The rate of progression and severity of ankylosis vary significantly among individuals, highlighting the heterogeneous nature of the disease. Early diagnosis, within the typical ankylosing spondylitis age of diagnosis window, can be critical in managing the disease course and mitigating long-term complications.
Diagnosis and Classification Criteria
Diagnosing ankylosing spondylitis can be challenging, especially in early stages before radiographic changes are evident. The 1984 Modified New York classification criteria have been widely used for research and clinical diagnosis. These criteria require both clinical and radiographic evidence, specifically:
- Clinical criteria:
- Inflammatory back pain for at least 3 months, improved by exercise and not relieved by rest.
- Limitation of lumbar spine motion in both sagittal and frontal planes.
- Limitation of chest expansion compared to normal values adjusted for age and sex.
- Radiographic criterion:
- Sacroiliitis of grade 2 or more bilaterally, or grade 3-4 unilaterally.
However, recognizing that radiographic sacroiliitis may not be present in early AS, the Assessment of SpondyloArthritis International Society (ASAS) developed criteria for axial spondyloarthritis. These criteria allow for diagnosis earlier in the disease course. The ASAS criteria for axial SpA include:
Set 1:
- Sacroiliitis on imaging (MRI evidence of active inflammation or definite radiographic sacroiliitis based on Modified New York criteria)
- AND at least one SpA feature: inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn’s disease/ulcerative colitis, good response to NSAIDs, family history of SpA, HLA-B27 positivity, elevated CRP.
Set 2:
- HLA-B27 positivity
- AND at least two SpA features (listed above).
These newer criteria are particularly helpful in diagnosing axial SpA in patients who present within the typical ankylosing spondylitis age of diagnosis range but do not yet meet the stricter Modified New York radiographic criteria.
Treatment Strategies and Management
Treatment for ankylosing spondylitis is tailored to the predominant symptoms, whether axial arthritis, peripheral arthritis, or enthesitis. Physical therapy is a cornerstone of management for all patients, aimed at maintaining spinal mobility and physical function.
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used alongside physical therapy to manage inflammatory back pain. While various NSAIDs can be effective, indomethacin has historically been considered a preferred option, although evidence is largely anecdotal. For patients who do not respond adequately to NSAIDs for sacroiliitis, intra-articular corticosteroid injections into the sacroiliac joints may be considered.
The advent of TNF inhibitors, such as etanercept, infliximab, adalimumab, and golimumab, has significantly improved the management of axial arthritis in AS. Clinical trials have demonstrated that TNF inhibitors effectively reduce inflammatory back pain and improve physical function, fatigue, and quality of life. However, it is important to note that, like other treatments for AS, TNF inhibitors have not been shown to prevent spinal fusion progression.
For peripheral arthritis symptoms, disease-modifying antirheumatic drugs (DMARDs) like sulfasalazine and methotrexate are often effective. Leflunomide, while effective in rheumatoid arthritis and psoriatic arthritis, has not shown significant efficacy in AS.
Prognosis and Long-Term Outlook
The prognosis for ankylosing spondylitis is variable. Some individuals may experience complete spinal ankylosis over time, while others have a more intermittent course with flares and remissions. The primary long-term goals of AS treatment are to preserve physical function, minimize work absenteeism, and maintain a good quality of life. Early diagnosis, especially considering the typical ankylosing spondylitis age of diagnosis, and consistent management are crucial for achieving these goals and improving long-term outcomes for individuals living with AS.
References
- Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369(9570):1379-90.
- Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci 2011;341(4):284-6.
- Dillon CF, Hirsch R. The United States National Health and Nutrition Examination Surveyand the epidemiology of ankylosing spondylitis. Am J Med Sci 2011;341(4):281-3.
- Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68(6):777-83.
