Ankylosing spondylitis (AS) is a chronic inflammatory disease predominantly affecting the axial skeleton, characterized by persistent back pain and progressive spinal stiffness. Recognizing AS is crucial for timely intervention, yet its symptoms can overlap with other conditions, posing diagnostic challenges. This article delves into the differential diagnosis of ankylosing spondylitis, highlighting key distinctions to aid in accurate diagnosis and patient management.
Introduction to Ankylosing Spondylitis and Diagnostic Challenges
Ankylosing spondylitis (AS) is a systemic inflammatory condition primarily impacting the spine and sacroiliac joints. While chronic back pain and spinal rigidity are hallmark features, AS can also manifest with peripheral arthritis, enthesitis, and extra-articular manifestations such as uveitis and inflammatory bowel disease. Accurate diagnosis of AS is paramount to initiate appropriate treatment, alleviate symptoms, and prevent disease progression. However, the clinical presentation of AS can be heterogeneous, and several other conditions can mimic its symptoms, leading to potential diagnostic confusion. Therefore, a thorough understanding of the Ankylosing Spondylitis Differential Diagnosis is essential for clinicians. This article aims to provide a comprehensive overview of conditions that should be considered in the differential diagnosis of AS, emphasizing the distinguishing features that help differentiate these conditions from AS.
Etiology of Ankylosing Spondylitis
The exact cause of ankylosing spondylitis remains elusive, but genetic predisposition plays a significant role. The strongest known genetic association is with the HLA-B27 gene. While not everyone with HLA-B27 develops AS, its presence significantly increases the risk. In individuals carrying the HLA-B27 gene, the prevalence of AS ranges from 5% to 6%. The prevalence of HLA-B27 varies across different ethnic populations, with higher rates observed in non-Hispanic Whites compared to other groups in the United States. Environmental factors and triggers are also suspected to contribute to the development of AS in genetically susceptible individuals, but these are still under investigation.
Epidemiology of Ankylosing Spondylitis
Ankylosing spondylitis typically manifests in younger individuals, with the majority of patients experiencing symptom onset before the age of 30. Approximately 80% of AS patients develop symptoms before the age of 30, and diagnosis after 45 is uncommon, occurring in less than 5% of cases. AS has a higher prevalence in males compared to females. Furthermore, there is a familial component to AS, with an elevated risk of developing the condition among relatives of affected individuals, underscoring the genetic influence.
Pathophysiology of Ankylosing Spondylitis
Ankylosing spondylitis is characterized by chronic inflammation, primarily targeting the entheses, which are sites where tendons and ligaments insert into bone. This inflammatory process, known as enthesitis, is a key feature of spondyloarthropathies, including AS. The inflammatory infiltrate in entheses involves immune cells such as CD4 and CD8 T lymphocytes and macrophages. Key cytokines, including tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β), play crucial roles in mediating the inflammation, fibrosis, and eventual ossification observed at entheseal sites in AS. This chronic inflammation and subsequent structural changes in the spine and sacroiliac joints lead to the characteristic symptoms of pain, stiffness, and reduced mobility in AS.
History and Physical Examination in AS Diagnosis
A comprehensive history and physical examination are critical in evaluating suspected ankylosing spondylitis. Given the systemic nature of AS, assessment should encompass all body systems. Back pain is a predominant complaint, and the nature of this pain is typically “inflammatory.” Inflammatory back pain, suggestive of AS, is characterized by:
- Onset before age 40
- Gradual onset
- Improvement with exercise
- No relief with rest
- Nocturnal pain that improves upon waking
Spinal stiffness, limited spinal mobility, and postural changes such as hyperkyphosis are also commonly observed. The physical examination should assess spinal mobility, peripheral joints, and entheseal sites for tenderness. A detailed medical history should explore associated conditions like psoriasis, inflammatory bowel disease, and uveitis, which can coexist with AS and provide further diagnostic clues.
Evaluation and Diagnostic Modalities for Ankylosing Spondylitis
Laboratory tests in ankylosing spondylitis are often non-specific but can provide supportive evidence. Elevated acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are seen in 50% to 70% of patients with active AS, indicating inflammation. However, normal ESR and CRP levels do not exclude AS.
Imaging plays a crucial role in AS diagnosis. Sacroiliitis, inflammation of the sacroiliac joints, is a key diagnostic criterion. Radiographic imaging and magnetic resonance imaging (MRI) are used to assess sacroiliitis. Plain radiographs can detect sacroiliitis based on a grading scale:
- Grade 0: Normal
- Grade I: Suspicious
- Grade II: Sclerosis and erosions
- Grade III: Severe erosions, pseudo-widening of joint space, partial ankylosis
- Grade IV: Complete ankylosis
Early radiographic changes in sacroiliac joints may be subtle, becoming more evident over time. Characteristic radiographic features in AS include subchondral erosions, sclerosis, and joint fusion, typically symmetrical in both sacroiliac joints. Later in the disease, spinal radiographs may reveal “squaring” of vertebral bodies, Romanus lesions (“shiny corner signs”), facet joint ankylosis, syndesmophytes, and calcification of spinal ligaments, including the “dagger sign” and “bamboo spine” appearance in advanced stages.
MRI is more sensitive than plain radiography, particularly in early AS. MRI can detect bone marrow edema (BME) in the sacroiliac joints, indicative of active inflammation. However, BME can also be seen in mechanical back pain and healthy individuals, so clinical correlation is important.
Treatment and Management Strategies for Ankylosing Spondylitis
The goals of AS treatment are to reduce pain and stiffness, maintain spinal mobility and function, and prevent complications. Non-pharmacological approaches include regular exercise, postural training, and physical therapy.
Pharmacological management typically starts with non-steroidal anti-inflammatory drugs (NSAIDs) as first-line therapy. If NSAIDs are insufficient, tumor necrosis factor inhibitors (TNF-Is) such as adalimumab, infliximab, or etanercept may be used. Response to NSAIDs should be assessed within 4-6 weeks, and TNF-I response within 12 weeks. Systemic glucocorticoids are generally not recommended, but local steroid injections may be considered for specific issues. Referrals to specialists such as rheumatologists, dermatologists, ophthalmologists, and gastroenterologists may be necessary based on individual patient needs and extra-articular manifestations.
Ankylosing Spondylitis Differential Diagnosis: Mimicking Conditions and Distinguishing Features
Accurate diagnosis of ankylosing spondylitis requires careful differentiation from other conditions that can present with similar symptoms, particularly back pain and stiffness. The ankylosing spondylitis differential diagnosis includes:
1. Mechanical Low Back Pain vs. Ankylosing Spondylitis
Mechanical low back pain is a common condition that, like AS, can cause back pain. However, key differences help distinguish these conditions:
| Feature | Mechanical Low Back Pain | Ankylosing Spondylitis |
|---|---|---|
| Age of Onset | Any age | Typically before age 40 |
| Pain Pattern | Variable, often related to activity | Inflammatory back pain pattern |
| Effect of Rest | Improves with rest | No improvement with rest, worsens at rest |
| Effect of Exercise | May worsen with exercise | Improves with exercise |
| Morning Stiffness | Mild and short-lived | Prolonged, often > 30 minutes |
| Peripheral Arthritis | Absent | May be present |
| Extra-articular Features | Absent | May be present (uveitis, IBD, psoriasis) |
| Sacroiliitis | Absent | Present on imaging |
Mechanical back pain often arises from muscle strain, ligament sprains, or disc issues. The pain is typically localized and can be related to specific movements or postures. Unlike AS, mechanical back pain is generally relieved by rest and may worsen with activity. Morning stiffness, if present, is usually brief. Systemic features and sacroiliitis are absent in mechanical back pain.
2. Lumbar Spinal Stenosis vs. Ankylosing Spondylitis
Lumbar spinal stenosis (LSS) is a condition characterized by narrowing of the spinal canal, which can compress the spinal cord and nerves. LSS shares some symptoms with AS, such as back pain and stiffness, but there are important differentiating factors:
| Feature | Lumbar Spinal Stenosis | Ankylosing Spondylitis |
|---|---|---|
| Age of Onset | Typically older than 60 | Typically before age 40 |
| Pain Pattern | Neurogenic claudication, positional pain | Inflammatory back pain pattern |
| Effect of Rest | May improve with rest | No improvement with rest, worsens at rest |
| Effect of Exercise | May worsen with walking/standing | Improves with exercise |
| Morning Stiffness | May be present | Prolonged, often > 30 minutes |
| Peripheral Arthritis | Absent | May be present |
| Extra-articular Features | Absent | May be present (uveitis, IBD, psoriasis) |
| Sacroiliitis | Absent | Present on imaging |
| Neurological Symptoms | Common (leg pain, numbness, weakness) | Less common |
| Response to NSAIDs | Variable | Often effective |
LSS typically affects older individuals and is associated with degenerative changes in the spine. A hallmark symptom of LSS is neurogenic claudication, characterized by leg pain, weakness, or numbness that worsens with walking or standing and improves with sitting or bending forward. While back pain and stiffness can be present, they often lack the inflammatory characteristics of AS. Peripheral arthritis and extra-articular features are not associated with LSS.
3. Rheumatoid Arthritis vs. Ankylosing Spondylitis
Rheumatoid arthritis (RA) is another chronic inflammatory arthritis, but it primarily targets the synovial joints, particularly in the hands and feet. While both RA and AS can cause back pain and morning stiffness, several distinctions exist:
| Feature | Rheumatoid Arthritis | Ankylosing Spondylitis |
|---|---|---|
| Joint Involvement | Primarily peripheral joints (hands, feet) | Primarily axial skeleton (spine, SI joints) |
| Back Pain | May be present, often cervical spine | Common, inflammatory back pain |
| Peripheral Arthritis | Highly prevalent | May be present, often asymmetric |
| Rheumatoid Nodules | Pathognomonic, present | Absent |
| Sacroiliitis | Uncommon | Common, often bilateral |
| HLA-B27 Association | Weak | Strong |
| Radiographic Features | Erosions, joint space narrowing in hands/feet | Syndesmophytes, sacroiliitis, bamboo spine |
| Rheumatoid Factor/Anti-CCP | Often positive | Usually negative |
RA predominantly affects the small joints of the hands and feet symmetrically. While back pain can occur in RA, it is less typical and often involves the cervical spine. Peripheral arthritis is a hallmark of RA, whereas in AS, peripheral joint involvement is less frequent and often asymmetric. Rheumatoid nodules are characteristic of RA and absent in AS. Sacroiliitis is less common in RA. Furthermore, serological markers like rheumatoid factor and anti-CCP antibodies are frequently positive in RA but typically negative in AS.
4. Diffuse Idiopathic Skeletal Hyperostosis (DISH) vs. Ankylosing Spondylitis
Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier disease, is a degenerative condition characterized by excessive ossification of ligaments and entheses, primarily in the spine. DISH can mimic AS in terms of postural changes and back pain, but important differences exist:
| Feature | Diffuse Idiopathic Skeletal Hyperostosis (DISH) | Ankylosing Spondylitis |
|---|---|---|
| Nature of Condition | Degenerative | Inflammatory |
| Inflammatory Back Pain | Absent | Present |
| Morning Stiffness | Absent or mild, brief | Prolonged, often > 30 minutes |
| Improvement with Exercise | Absent | Present |
| Sacroiliitis | Absent | Present on imaging |
| Syndesmophytes | Flowing ossification, anterior spine | Syndesmophytes, marginal, vertical |
| Joint Fusion | Less common, primarily ligamentous ossification | Common, bony ankylosis of SI and spine |
| HLA-B27 Association | Absent | Strong |
DISH is a degenerative, non-inflammatory condition, unlike the inflammatory nature of AS. Patients with DISH typically lack inflammatory back pain and significant morning stiffness. Pain in DISH is often activity-related and not relieved by exercise. Sacroiliitis is absent in DISH. Radiographically, DISH is characterized by flowing ossification along the anterior aspect of the spine, whereas AS shows syndesmophytes and sacroiliitis. HLA-B27 association is absent in DISH.
Prognosis of Ankylosing Spondylitis
Earlier onset of ankylosing spondylitis is associated with a potentially poorer functional outcome. However, severe physical disability is not common in AS, and most patients maintain reasonable function and active lives. Patients with severe and long-standing AS have an increased risk of mortality, primarily due to cardiovascular complications linked to chronic systemic inflammation.
Complications of Ankylosing Spondylitis
Ankylosing spondylitis can lead to both articular and extra-articular complications, including:
- Chronic pain and disability
- Aortic regurgitation (cardiac complication)
- Pulmonary fibrosis (lung involvement)
- Cauda equina syndrome (rare neurological complication)
- Mood disorders (depression, anxiety)
Postoperative and Rehabilitation Care in Ankylosing Spondylitis
Exercise programs are crucial in managing AS, improving pain, flexibility, mobility, and overall function. Various exercise approaches, including home programs and group therapy, have shown benefits. Hydrotherapy is particularly helpful for cardiovascular fitness and pain management in AS. Respiratory and postural exercises are important to address potential breathing mechanics and postural issues related to spinal involvement.
Deterrence and Patient Education in Ankylosing Spondylitis
Patient education is vital for successful AS management. Patients need to understand the chronic nature of the disease, medications, and potential side effects. Emphasizing regular exercise, including physical therapy and water therapy, is essential for symptom reduction and functional improvement. Given the risk of pulmonary complications, smoking cessation is critical for patients with AS.
Pearls and Other Important Considerations in Ankylosing Spondylitis
A high index of suspicion for vertebral fractures is necessary in AS patients, even with minor trauma, due to increased fracture risk and potential for neurologic compromise. Early diagnosis and comprehensive management, including exercise, physical therapy, medication, and regular follow-up, are key to preventing disease morbidity and improving patient outcomes.
Enhancing Healthcare Team Outcomes in Ankylosing Spondylitis Management
Ankylosing spondylitis, as a systemic disorder, requires an interprofessional team approach for comprehensive care. The team may include rheumatologists, primary care physicians, gastroenterologists, ophthalmologists, cardiologists, physical and occupational therapists, neurologists, pharmacists, and nurses. Collaborative care improves functional outcomes, pain management, and quality of life for AS patients. Evidence supports the effectiveness of exercise programs and early education in improving patient engagement and treatment outcomes in AS.
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References
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Disclaimer: This rewritten article is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of ankylosing spondylitis or any medical condition.
