Ankylosing Spondylitis

Introduction, Etiology, and Pathophysiology

Introduction and Epidemiology

• Ankylosing spondylitis (AS) is a chronic, multisystem inflammatory disorder that primarily affects the axial skeleton, including the sacroiliac joints and the spine. It is classified as a radiographic axial spondyloarthritis (r-axSpA).¹
• The prevalence of AS in North America is estimated to be between 0.2% and 0.5% of the population.¹ Symptoms typically manifest in early adulthood, with a peak onset between the ages of 20 and 30; diagnosis is often delayed by several years due to the insidious nature of the symptoms.²
• Historically, the disease was thought to predominantly affect males; however, recent data suggest a more balanced sex distribution, although radiographic progression is frequently more severe in male patients.^1,2

Etiology and Genetics

• A complex interaction between environmental factors and genetic predisposition may contribute to the etiology of AS.³
• A strong genetic association has been established with the human leukocyte antigen (HLA) class I molecule B27 (HLA-B27). It is reported that approximately 90% of patients with AS are HLA-B27 positive.³
• However, the presence of HLA-B27 is not sufficient for disease development, as only a small percentage of HLA-B27 carriers develop AS. Other genetic loci, such as ERAP1 and IL23R, and environmental triggers, including gut microbiome dysbiosis, are implicated in the pathogenesis.^1,3

Pathophysiology

• The primary pathological lesion in AS is enthesitis, which is defined as inflammation at the insertion sites of tendons, ligaments, and joint capsules into bone.³
• The inflammatory process is driven by the interleukin-23/interleukin-17 (IL-17) axis and tumor necrosis factor (TNF), leading to a sequence of osteitis, erosion, and aberrant new bone formation.²
• Syndesmophytes form when the outer fibers of the annulus fibrosus ossify; these bony growths eventually bridge the vertebral bodies.³
• Progression of the disease leads to the ossification of the supraspinous and interspinous ligaments, the ligamentum flavum, and the apophyseal joints, resulting in a fused, rigid spine classically known as a “bamboo spine.”^2,3

Clinical Presentation and Diagnosis

Musculoskeletal Manifestations

• Inflammatory Back Pain: The hallmark symptom is inflammatory back pain, which is characterized by an onset before 45 years of age, a duration of longer than three months, morning stiffness lasting more than 30 minutes, and improvement with exercise but not with rest.^2,3
• Spinal Deformity: As ankylosis progresses, the normal lumbar lordosis is lost and thoracic kyphosis is exaggerated. In severe cases, the cervical spine may become fixed in a flexed position, resulting in a “chin-on-chest” deformity that severely limits the visual field and neck extension.^3,4
• Peripheral Arthritis: Asymmetric oligoarthritis affecting the lower extremities, particularly the hips and knees, is observed in up to 50% of patients.¹

Extra-Articular Manifestations

• Ocular: Acute anterior uveitis is recognized as the most common extra-articular manifestation and is seen in 25% to 40% of patients.³
• Cardiovascular: Aortitis affecting the ascending aorta and aortic valve can lead to aortic regurgitation. Fibrosis may extend into the interventricular septum, leading to conduction disturbances, such as atrioventricular blocks.⁴
• Pulmonary: Involvement of the costovertebral and costosternal joints results in limited chest wall expansion and a restrictive ventilatory defect.⁴ Rare complications include apical pulmonary fibrosis and cavitation.⁴
• Neurological: The fused, osteoporotic spine is highly susceptible to fractures even after minor trauma. The cervical spine is the most commonly fractured segment, which can lead to devastating spinal cord injuries.⁴

Diagnosis

• Diagnosis Criteria: Diagnosis is based on a blend of clinical features, laboratory testing (including HLA-B27 status and C-reactive protein), and imaging.²
• Radiographic Findings: Radiographic evidence of sacroiliitis is required for the diagnosis of AS (r-axSpA); however, magnetic resonance imaging (MRI) can detect active inflammation (osteitis) before structural changes appear on plain radiographs.²
• Classic Signs: Advanced disease may present with classic radiographic signs such as the “bamboo spine” (diffuse syndesmophytic ankylosis) and the “dagger sign” (a central dense line on AP radiographs due to ossification of the supraspinous and interspinous ligaments) (Figure 1).⁵

Treatment

• Nonpharmacologic Management: Physical therapy and regular exercise are recommended as first-line strategies to maintain spinal mobility and function.¹
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line pharmacologic therapy for symptomatic relief.^1,2
• Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): In patients with persistent disease activity despite NSAID therapy, biologic disease-modifying antirheumatic drugs are indicated. TNF inhibitors (TNFi) and IL-17 inhibitors are commonly used to reduce inflammation and improve quality of life.^1,2
• Surgery: Total hip arthroplasty may be required for patients with severe hip involvement. Spinal surgery, such as osteotomy, is reserved for the correction of severe kyphotic deformities.¹

Anesthetic Considerations

Airway Management

• Preoperative Assessment: A meticulous airway examination must be performed to evaluate cervical spine mobility, as the presence of bridging syndesmophytes and facet joint ankylosis can lead to a rigid cervical spine (Figure 2), making direct laryngoscopy severely challenging.⁴
• Direct Laryngoscopy Challenges: The classic “chin-on-chest” deformity creates a fixed flexion angle that can render alignment of the oral, pharyngeal, and laryngeal axes nearly impossible during direct laryngoscopy.⁴
• Intubation Techniques: Awake fiberoptic intubation is commonly regarded as the gold standard for airway securement in patients with predicted difficult airways due to AS.⁵
• Video Laryngoscopy: Advanced video laryngoscopes have been successfully used in patients with AS. However, care must be taken to avoid forceful manipulation, which could result in iatrogenic cervical spine fractures.^6,7
• Supraglottic Airways: The laryngeal mask airway has been utilized successfully for airway maintenance or as a conduit for intubation in selected cases, though its placement may be hindered by limited mouth opening.⁷

Neuraxial Anesthesia

• Technical Difficulties: Neuraxial blockade is complicated by the ossification of the midline ligaments (supraspinous, interspinous, and ligamentum flavum), which obliterates the acoustic window for ultrasound and the physical path for needle insertion.^4,8
• Paramedian Approach: A paramedian approach is often a useful alternative to the median approach because it can bypass the calcified midline ligaments. Ultrasound guidance is recommended to identify the vertebral level and assist in needle trajectory planning.⁴
• Epidural Failure Rates: A high rate of failed or patchy epidural blocks has been reported in parturients and surgical patients with AS.9 This failure is attributed to the restricted spread of local anesthetic within a fibrosed epidural space or the presence of dorsal epidural diverticula (dural ectasia) associated with the disease.⁹
• Hematoma Risk: The risk of spinal epidural hematoma may be increased due to technical difficulties necessitating multiple attempts and the concurrent use of NSAIDs.⁸

Regional Anesthesia

• Peripheral Nerve Blocks: Regional anesthesia techniques are valuable alternatives when neuraxial blockade is contraindicated or technically impossible.
• Cervical Plexus Blocks: Bilateral superficial or intermediate cervical plexus blocks have been successfully employed for neck surgeries, such as thyroidectomy, to avoid airway manipulation in high-risk AS patients.¹⁰
• Fascia Iliaca and Sciatic Blocks: For hip surgeries, which are common in this population, combined fascia iliaca and sciatic nerve blocks can be utilized to provide effective anesthesia and analgesia, thereby avoiding the risks associated with general and neuraxial anesthesia.¹¹
• Erector Spinae Plane (ESP) Blocks: The ultrasound-guided ESP block has been successfully used as a sole anesthetic technique for truncal and abdominal surgery in patients with severe AS, providing complete surgical anesthesia without airway instrumentation.¹²

Systemic and Positioning Considerations

• Positioning: Extreme care must be taken during positioning. The head and neck should be supported in their neutral (often flexed) position to prevent vertebral fractures; gaps between the mattress and the patient’s head or back should be filled with padding.⁴
• Cardiovascular Monitoring: Vigilance for bradycardia and heart block is required, especially during anesthesia induction, given the increased prevalence of conduction system disease.⁴
• Respiratory Function: Postoperative respiratory function should be monitored closely, as chest wall rigidity renders respiration dependent on diaphragmatic excursion.⁴
• Pain Management: Nerve blocks can help reduce opioid use, but they are not always feasible due to technical challenges. A multimodal approach combining careful doses of NSAIDs and opioids is recommended. Since these patients are at higher risk for respiratory compromise, opioids should be used cautiously and under close monitoring.