Ankylosing spondylitis

Ankylosing spondylitis is a chronic inflammatory disease primarily affecting the axial skeleton, leading to pain, stiffness, and progressive spinal fusion. It is a type of spondyloarthritis that can significantly impact mobility and quality of life. Early recognition and management are essential to prevent long-term complications.

Etiology and Risk Factors

Genetic Factors

Genetic predisposition plays a major role in the development of ankylosing spondylitis.

• HLA-B27 association: The presence of the HLA-B27 gene is strongly linked with increased risk of developing the disease. Around 80-90% of patients with ankylosing spondylitis are HLA-B27 positive.
• Other genetic predispositions: Additional genes related to immune regulation may contribute to susceptibility.

Environmental Factors

Environmental triggers can influence disease onset and progression.

• Infections and microbial triggers: Certain bacterial infections may activate immune pathways that contribute to inflammation in genetically susceptible individuals.
• Lifestyle factors: Smoking and physical inactivity may exacerbate disease severity and progression.

Demographic Factors

Certain demographic features are associated with higher risk of ankylosing spondylitis.

• Age of onset: Typically occurs in late adolescence or early adulthood, often between 15 and 30 years of age.
• Sex differences: More common in males, with men generally experiencing more severe spinal involvement.

Pathophysiology

Ankylosing spondylitis is characterized by chronic inflammation of the axial skeleton, leading to structural changes and functional impairment.

• Inflammatory processes: Inflammation primarily affects the sacroiliac joints, vertebral bodies, and entheses, resulting in pain and stiffness.
• Role of cytokines: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-17 (IL-17) are key mediators driving the inflammatory response.
• Sacroiliitis and vertebral involvement: Early inflammation at the sacroiliac joints progresses to vertebral inflammation, causing characteristic radiographic changes.
• Progressive ossification: Chronic inflammation leads to the formation of syndesmophytes and eventual fusion of vertebral bodies, limiting spinal mobility.

Clinical Features

Musculoskeletal Manifestations

The hallmark symptoms of ankylosing spondylitis involve the axial skeleton, with additional involvement of peripheral joints and entheses.

• Chronic back pain and stiffness: Typically worse in the morning or after periods of inactivity and improves with exercise.
• Peripheral arthritis: Involvement of hips, shoulders, and knees can occur, often asymmetrical and mild compared to axial symptoms.
• Enthesitis: Inflammation at tendon, ligament, and joint capsule insertions, commonly affecting the Achilles tendon and plantar fascia.

Extra-Articular Manifestations

Ankylosing spondylitis can affect organs and systems beyond the musculoskeletal system.

• Uveitis: Acute anterior uveitis occurs in approximately 25-40% of patients, causing eye pain, redness, and photophobia.
• Cardiovascular involvement: Aortic regurgitation and conduction abnormalities may develop in long-standing disease.
• Pulmonary complications: Restrictive lung disease can result from reduced chest expansion due to spinal rigidity.
• Gastrointestinal manifestations: Patients may have an increased risk of inflammatory bowel disease and associated symptoms.

Diagnosis

Clinical Assessment

Diagnosis is based on a combination of patient history, physical examination, and clinical criteria.

• History and symptom evaluation: Chronic inflammatory back pain, improvement with activity, and onset before 40 years of age are key indicators.
• Physical examination findings: Tests such as the Schober test and measurement of chest expansion help assess spinal mobility and involvement.

Laboratory Investigations

Laboratory tests support diagnosis and help monitor disease activity.

• Inflammatory markers: Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) indicate active inflammation.
• HLA-B27 testing: Presence of HLA-B27 gene supports diagnosis, especially in patients with typical clinical features.

Imaging Studies

Imaging is essential for detecting structural changes and early inflammation.

• X-rays: Sacroiliac joint changes and syndesmophytes are visible in established disease.
• MRI: Detects early sacroiliitis and spinal inflammation before radiographic changes appear.
• CT scans: Used selectively for detailed evaluation of complex spinal involvement.

Differential Diagnosis

Several conditions can mimic the clinical features of ankylosing spondylitis. Accurate differentiation is essential to ensure appropriate management.

• Mechanical back pain: Degenerative spinal changes or muscle strain causing non-inflammatory pain.
• Psoriatic arthritis: May involve the spine and peripheral joints, often with skin and nail changes.
• Reactive arthritis: Post-infectious arthritis that can involve axial and peripheral joints, usually acute and self-limiting.
• Rheumatoid arthritis: Typically affects small joints symmetrically and rarely involves the sacroiliac joints.

Management

Non-Pharmacological Treatment

Non-drug therapies play a central role in preserving function and reducing symptoms.

• Physical therapy and exercise: Regular stretching and strengthening exercises improve spinal mobility and reduce stiffness.
• Posture and ergonomics: Maintaining proper posture and using supportive furniture helps prevent deformities.
• Patient education and lifestyle modifications: Smoking cessation, weight management, and activity modification are important for disease control.

Pharmacological Treatment

Medications aim to reduce inflammation, relieve pain, and prevent structural damage.

• NSAIDs: First-line treatment to control pain and stiffness.
• TNF inhibitors: Biologic agents targeting tumor necrosis factor-alpha, effective in reducing inflammation and slowing disease progression.
• IL-17 inhibitors: Biologics targeting interleukin-17, beneficial in patients with inadequate response to TNF inhibitors.
• Other immunosuppressive agents: Used selectively for refractory peripheral arthritis or extra-articular manifestations.

Surgical Intervention

Surgery is reserved for patients with severe structural damage or complications.

• Spinal surgery: Corrective osteotomies may be performed for severe kyphosis or spinal deformity.
• Joint replacement: Hip or knee replacement may be indicated for advanced peripheral joint destruction.

Prognosis

The prognosis of ankylosing spondylitis varies depending on disease severity, early diagnosis, and treatment adherence. With appropriate management, many patients maintain functional independence and quality of life.

• Long-term functional outcomes: Early intervention and regular exercise can preserve spinal mobility and reduce disability.
• Impact on quality of life: Chronic pain, fatigue, and mobility limitations can affect daily activities, work, and social participation.
• Factors influencing disease progression: HLA-B27 positivity, male sex, smoking, and early onset are associated with more aggressive disease and higher risk of spinal fusion.

Complications

Ankylosing spondylitis can lead to multiple complications affecting the musculoskeletal system and other organs.

• Spinal deformities and fractures: Progressive kyphosis and increased risk of vertebral fractures due to rigidity and osteoporosis.
• Cardiovascular complications: Increased risk of aortic regurgitation, conduction abnormalities, and ischemic heart disease.
• Osteoporosis and bone loss: Chronic inflammation and reduced mobility contribute to decreased bone density.
• Vision and eye problems: Recurrent anterior uveitis can lead to visual impairment if untreated.

References

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