Ankylosing Spondylitis - USMLE Guide

Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton, resulting in inflammation, pain, and stiffness of the spine. It belongs to a group of conditions known as spondyloarthropathies. AS commonly affects young males and is characterized by progressive spinal fusion, leading to reduced mobility and functional impairment.

Etiology and Pathophysiology

The exact cause of AS remains unknown; however, a combination of genetic and environmental factors is thought to play a role. The HLA-B27 gene is strongly associated with AS, with approximately 90% of affected individuals being positive for this gene. Environmental triggers such as infections (e.g., gastrointestinal or genitourinary) may initiate an immune response in genetically susceptible individuals, leading to chronic inflammation.

The pathophysiology of AS involves inflammation primarily at the entheses, which are the sites where tendons and ligaments attach to bone. This inflammation leads to the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23). These cytokines promote further inflammation, bone remodeling, and new bone formation, ultimately leading to ankylosis (fusion) of the affected joints.

Clinical Presentation

1. Back pain and stiffness

The hallmark symptom of AS is chronic back pain and stiffness that worsens with rest and improves with exercise. The pain is typically located in the sacroiliac joints and lumbar spine and is worse in the morning or after periods of inactivity.

2. Limited spinal mobility

As the disease progresses, ankylosis of the spine can occur, resulting in reduced spinal mobility. This can lead to a stooped posture and difficulty with activities requiring spinal flexibility.

3. Extra-articular manifestations

AS can also affect other organs and systems, resulting in various extra-articular manifestations. These may include uveitis (inflammation of the eye), enthesitis (inflammation at tendon and ligament insertions), dactylitis (swelling of fingers or toes), and inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).

Diagnosis

1. Clinical evaluation

A thorough history and physical examination are crucial for the diagnosis of AS. The presence of chronic back pain and stiffness, especially in young males, should raise suspicion for AS. Examination may reveal limited spinal mobility and signs of extra-articular involvement.

2. Imaging studies

X-rays of the sacroiliac joints and spine are commonly used to evaluate for characteristic findings of AS, such as sacroiliitis and syndesmophytes (bony outgrowths). Magnetic resonance imaging (MRI) can provide early evidence of inflammation before radiographic changes are visible.

3. Laboratory tests

Although there is no specific diagnostic test for AS, certain laboratory findings can support the diagnosis. These may include elevated inflammatory markers (e.g., erythrocyte sedimentation rate and C-reactive protein) and the presence of HLA-B27 antigen.

Treatment

1. Non-pharmacologic interventions

• Regular exercise: Physical therapy and exercise programs aimed at improving posture, flexibility, and spinal mobility can help manage symptoms and prevent further functional impairment.
• Heat and cold therapy: Application of heat or cold to affected areas can help alleviate pain and stiffness.
• Patient education: Providing information and support to patients regarding the nature of the disease, self-management strategies, and the importance of compliance with treatment is essential.

2. Pharmacologic interventions

• Nonsteroidal anti-inflammatory drugs (NSAIDs): These medications are the first-line treatment for AS due to their anti-inflammatory and analgesic properties. They can help reduce pain and stiffness.
• Disease-modifying anti-rheumatic drugs (DMARDs): In cases of severe or refractory disease, DMARDs such as sulfasalazine or methotrexate may be prescribed to control inflammation.
• Biologic agents: Tumor necrosis factor inhibitors (e.g., etanercept, adalimumab) are effective in reducing inflammation and slowing disease progression in patients with moderate to severe AS.

Prognosis

AS is a chronic disease with a variable course. Early diagnosis and appropriate management can help control symptoms, maintain spinal mobility, and improve quality of life. However, severe cases may lead to significant disability and functional limitations. Regular follow-up and close monitoring of disease activity are essential to optimize treatment outcomes.

Conclusion

Ankylosing spondylitis is a chronic inflammatory disease primarily affecting the axial skeleton. Understanding the etiology, pathophysiology, clinical presentation, diagnosis, and treatment options for AS is crucial for medical professionals. By recognizing