Orthopaedic Surgery - Ankylosing Spondylitis

Basics

Ankylosing spondylitis (AS) is a seronegative spondyloarthritis characterized by chronic inflammation affecting the axial skeleton and, to a lesser extent, peripheral joints.

The disease primarily involves the spine and sacroiliac (SI) joints, although the hips and shoulders may also be affected. Any level of the spine can become involved as the disease progresses.

AS affects both synovial and fibrous joints. Persistent inflammation can produce chronic synovitis, erosions, sclerosis, fibrosis, and ultimately ankylosis, resulting in progressive loss of joint and spinal mobility.

Extra-articular manifestations may involve the eyes, cardiovascular system, lungs, skin, and mucous membranes.

Epidemiology

Ankylosing spondylitis most commonly becomes symptomatic in young adults, particularly during the third and fourth decades of life.

The disease has traditionally been recognized more frequently and often more severely in males, although both males and females can be affected.

Initial manifestations developing after the age of approximately 40 years are relatively uncommon.

The precise cause remains unknown, but there is a strong association with genes of the major histocompatibility complex, particularly HLA-B27.

Incidence

The reported frequency of ankylosing spondylitis in North America is approximately 0.1–0.3% of the population.

The likelihood of disease is substantially increased among individuals carrying the HLA-B27 gene.

However, genetic susceptibility alone is insufficient to cause disease, and the majority of HLA-B27-positive individuals never develop ankylosing spondylitis.

First-degree relatives of affected patients also have a significantly increased risk compared with the general population.

Prevalence and HLA-B27

Although ankylosing spondylitis is strongly associated with HLA-B27, fewer than approximately 5% of individuals carrying the gene ultimately develop the disease.

Therefore, the presence of HLA-B27 supports the diagnosis in the appropriate clinical setting but does not by itself establish the diagnosis.

Risk Factors

The principal recognized risk factors are HLA-B27 positivity and a positive family history of ankylosing spondylitis or related spondyloarthritis.

An earlier age of onset is often associated with a more severe disease course.

Genetics

Ankylosing spondylitis has a strong hereditary component.

The concordance rate is substantially higher in identical twins than in fraternal twins, supporting an important genetic contribution.

The strongest association is with HLA-B27, although other major histocompatibility complex genes, including HLA-DRB1 and HLA-B60, have also been implicated.

Additional genetic associations have been reported involving genes such as CYP2D6 and IL-1B.

Despite this strong genetic contribution, environmental and immune factors are also believed to influence whether disease develops.

Pathophysiology

Ankylosing spondylitis is a chronic inflammatory arthropathy that characteristically involves the sacroiliac joints, often bilaterally.

Both synovial and fibrous joints of the axial and peripheral skeleton may become inflamed.

Inflammation can also occur at the sites where tendons and ligaments attach to bone, known as entheses.

Persistent inflammation leads to erosion and structural damage, followed by fibrosis and new bone formation. Over time, this may result in progressive ankylosis of the affected joints and spine.

Disease Course

The onset is usually gradual and insidious.

Patients commonly experience periods of worsening symptoms followed by partial improvement or remission.

Although both sexes are affected, disease has historically been observed to be more severe in males.

Earlier onset is also associated with a greater likelihood of significant structural and functional impairment.

Etiology

The exact cause of ankylosing spondylitis remains unknown.

Genetic susceptibility appears to interact with immune and environmental factors.

Various infectious triggers have been investigated. Klebsiella species have been proposed as a possible contributor, although studies have not established a definitive causal relationship.

There is also evidence of an association between ankylosing spondylitis and inflammation of the small intestine, supporting a possible relationship between intestinal immune responses and axial inflammation.

Associated Conditions

Enthesopathy is common and may present as plantar fasciitis or Achilles tendinitis.

Extra-articular manifestations include acute anterior uveitis and cardiovascular abnormalities such as aortic insufficiency, cardiomegaly, and cardiac conduction disturbances.

Pulmonary abnormalities may develop in advanced disease.

Diagnosis

Signs and Symptoms

Diagnosis is based on the combination of clinical features and imaging findings.

Typical symptoms usually persist for at least 3 months and are characteristic of inflammatory rather than mechanical back pain.

Pain and stiffness generally improve with exercise and do not improve significantly with rest.

Morning stiffness is common and may be prolonged.

Common Clinical Features

Patients may develop progressive restriction of spinal movement, fatigue, and reduced chest expansion.

Weight loss can occur in patients with active systemic inflammation.

Inflammation of the costosternal or costovertebral joints may cause chest discomfort.

Progressive disease can lead to thoracic kyphosis and loss of the normal lumbar lordosis.

Upper-extremity peripheral joint involvement is less common than involvement of the hips and lower limbs.

Pulmonary Manifestations

Advanced disease may be associated with apical pulmonary fibrosis.

Restricted mobility of the costovertebral and costosternal joints can also reduce chest expansion and contribute to restrictive respiratory mechanics.

History

The history often reveals a gradual onset of discomfort involving the lumbosacral spine, buttocks, or hips.

Symptoms commonly begin before the age of 40 years and persist for longer than three months.

A characteristic feature is morning stiffness that improves with physical activity.

Pain frequently improves during exercise but returns after prolonged inactivity.

Physical Examination

Patients may have relatively few abnormal findings early in the disease.

A comprehensive examination should include the musculoskeletal, neurologic, pulmonary, and ocular systems.

Careful assessment of spinal posture and mobility is essential.

Lumbar Spine Examination

Reduced lumbar flexion and extension are common as the disease progresses.

Loss of normal lumbar movement may be subtle initially but becomes more evident with increasing structural involvement.

Spinal stiffness should be compared with age-appropriate expectations.

Sacroiliac Joint Examination

Tenderness may be present over the SI joints.

Provocative maneuvers that stress the sacroiliac region may reproduce the patient’s typical buttock or low-back pain.

However, physical examination alone is not sufficiently specific to confirm sacroiliitis.

Chest Expansion

Chest expansion should be assessed because involvement of the costovertebral and costosternal joints may progressively restrict thoracic excursion.

Decreased expansion can contribute to reduced pulmonary function in advanced disease.

Neurologic Examination

A complete neurologic examination is important, particularly in patients with advanced spinal deformity or suspected fracture.

Any new weakness, numbness, gait disturbance, or bowel or bladder abnormality requires urgent evaluation.

Ocular Examination

Patients should be questioned about eye pain, redness, photophobia, and visual disturbance because these symptoms may indicate acute anterior uveitis.

Recurrent uveitis is a well-recognized extra-articular manifestation of ankylosing spondylitis.

Laboratory Tests

HLA-B27

Testing for HLA-B27 can support the diagnosis in a patient with compatible clinical findings.

However, because many healthy individuals carry the gene without developing disease, it should not be interpreted in isolation.

Inflammatory Markers

The erythrocyte sedimentation rate (ESR) may be elevated and can reflect inflammatory activity.

Other inflammatory markers such as C-reactive protein may also be elevated.

However, normal inflammatory markers do not exclude ankylosing spondylitis.

Rheumatoid and Antinuclear Antibodies

Rheumatoid factor and antinuclear antibodies are generally not useful for diagnosing ankylosing spondylitis.

The condition is classified as a seronegative spondyloarthritis, meaning rheumatoid factor is typically absent.

Imaging

Plain Radiographs

Radiographs may remain normal during the early stages of disease.

As ankylosing spondylitis progresses, characteristic abnormalities develop, particularly around the sacroiliac joints.

Sacroiliac Joint Findings

Radiographic changes of the SI joints are central to the diagnosis of established ankylosing spondylitis.

Changes are typically bilateral and relatively symmetric.

Early abnormalities include erosions and subchondral sclerosis, producing irregular or poorly defined joint margins.

Apparent widening of the SI joint may occur because erosions create a pseudo-widened appearance.

Late Sacroiliac Changes

With progression, fibrosis and new bone formation lead to narrowing and eventually complete osseous bridging or ankylosis of the SI joints.

These findings indicate advanced structural disease.

Spinal Radiographic Findings

Inflammation at the vertebral margins and outer annulus fibrosus leads to erosive changes followed by new bone formation.

Bridging syndesmophytes may progressively connect adjacent vertebral bodies.

When extensive, this produces the characteristic radiographic appearance known as a “bamboo spine.”

Bamboo Spine

The bamboo-spine appearance results from progressive ossification and syndesmophyte formation across multiple vertebral levels.

The spine becomes increasingly rigid and behaves biomechanically more like a long bone than a flexible segmented column.

This rigidity substantially increases the risk of unstable spinal fractures.

Imaging for Suspected Fracture

Fractures in ankylosed spines can be difficult to identify on standard radiographs.

Anteroposterior, lateral, and appropriate additional views should be examined carefully.

When fracture is suspected, CT with multiplanar or 3D reconstruction is highly useful because it is more sensitive for detecting fracture lines and defining their extent.

MRI

MRI is particularly valuable when neurologic symptoms are present or when an occult fracture or soft-tissue complication is suspected.

It can identify epidural hematoma, spinal cord compression, ligamentous injury, and other neural abnormalities.

MRI is also useful for detecting active inflammatory sacroiliitis before structural radiographic changes become obvious.

Differential Diagnosis

The differential diagnosis includes other seronegative spondyloarthropathies.

Important conditions include reactive arthritis, psoriatic arthritis, and inflammatory bowel disease-associated arthritis related to Crohn disease or ulcerative colitis.

Additional Differential Diagnoses

Other conditions that may resemble ankylosing spondylitis include septic sacroiliitis, osteoarthritis, rheumatoid arthritis, and lumbar disc herniation.

Clinical history, imaging findings, laboratory studies, and the distribution of joint involvement help distinguish these disorders.

Treatment

Initial Management

The foundation of treatment is regular exercise and maintenance of spinal mobility.

Back exercises and flexibility training help reduce pain, maintain function, and limit progressive loss of motion.

Exercise should begin early and continue throughout the course of the disease.

General Measures

Patients should be encouraged to maintain an active and healthy lifestyle whenever possible.

Regular recreational activity helps preserve cardiovascular fitness, muscle strength, posture, and spinal mobility.

Prolonged inactivity should be avoided because stiffness often worsens when movement is reduced.

Posture

Postural training is important because progressive ankylosis may fix the spine in a kyphotic position.

Patients should be encouraged to maintain an upright posture during daily activities and sleep.

Appropriate exercises can help preserve extension and limit progressive flexion deformity.

Physical Therapy

Physical therapy is a central component of management.

Programs should focus on spinal flexibility, posture, chest expansion, strengthening, and maintenance of functional mobility.

Hyperextension exercises may help reduce the tendency toward progressive thoracic kyphosis.

Flexibility Training

Regular stretching and mobility exercises can decrease stiffness and improve functional ability.

Consistent flexibility training may also improve quality of life by helping patients maintain independence and activity.

Medication

First-Line Therapy

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as first-line pharmacologic treatment.

They can reduce pain and stiffness and improve function.

Selection is largely based on patient response and tolerance because no single NSAID, including selective COX-2 inhibitors, has consistently demonstrated clear superiority.

Additional Medical Therapy

Other medications may be considered when symptoms remain inadequately controlled.

Historically, agents such as corticosteroids and sulfasalazine have been used in selected cases, particularly when peripheral joint disease is present.

Systemic corticosteroids are generally not preferred for routine long-term axial disease because of their adverse-effect profile.

Biologic Therapy

Biologic agents that inhibit tumor necrosis factor-alpha (TNF-α) can substantially reduce disease activity in patients with persistent active disease despite conventional treatment.

These medications have become an important treatment option for moderate-to-severe ankylosing spondylitis.

Other targeted biologic therapies may also be used depending on disease characteristics and response.

Other Therapies

A variety of additional agents, including older treatments such as pamidronate and thalidomide, have been investigated.

These are not generally considered routine first-line therapies.

Antibiotics are not routinely indicated because no infectious organism has been established as the direct cause of ankylosing spondylitis.

Surgical Management

Surgery does not treat the underlying inflammatory disease itself.

Instead, surgery is used primarily to manage structural complications that develop as a consequence of long-standing disease.

Total Hip Arthroplasty

Severe hip involvement may lead to painful stiffness and major functional impairment.

Total hip arthroplasty is one of the most commonly performed orthopedic procedures in patients with advanced ankylosing spondylitis.

It can significantly improve pain, mobility, and quality of life.

Spinal Fracture Stabilization

Fractures of an ankylosed spine are often highly unstable.

Because the rigid spine behaves like a long lever arm, even apparently minor fractures may extend through all spinal columns.

Operative stabilization is frequently required to prevent displacement and neurologic deterioration.

Corrective Spinal Osteotomy

Advanced ankylosing spondylitis may produce severe fixed kyphotic deformity.

When deformity markedly limits forward vision, standing balance, or daily function, a corrective spinal osteotomy may be considered.

These procedures are complex and require careful preoperative planning.

Follow-Up

Patients require regular long-term follow-up to assess disease activity, posture, spinal mobility, neurologic function, and extra-articular complications.

Ongoing review also provides an opportunity to reinforce exercise and postural programs and adjust pain medication.

Prognosis

The disease course varies considerably among patients.

Individuals with early-onset disease and prominent peripheral joint inflammation may experience a more severe clinical course.

There is no definitive cure, but modern medical treatment, exercise, and prevention of complications can substantially reduce disability.

Spinal Fracture Risk

One of the most serious complications is spinal fracture after relatively minor trauma.

The ankylosed spine is rigid and brittle and cannot absorb energy in the same way as a normal flexible spine.

As a result, fractures may occur after falls or trauma that would otherwise be considered minor.

Neurologic Complications

Spinal fractures may displace and injure the spinal cord or nerve roots.

Delayed neurologic deterioration can occur if an initially unrecognized fracture subsequently shifts.

Any suspected fracture should therefore be treated as potentially unstable until adequately evaluated.

Epidural Hematoma

Cervical spinal fractures may be associated with an epidural hematoma.

The hematoma can compress the spinal cord and produce rapidly progressive neurologic impairment.

MRI is particularly useful for identifying this complication.

Failure to recognize spinal cord compression may result in permanent paralysis.

Management of Spinal Fractures

Spinal fractures in ankylosing spondylitis require urgent stabilization.

Treatment may involve external immobilization or internal fixation depending on fracture configuration, alignment, neurologic status, and patient factors.

Because these fractures are frequently unstable, surgical fixation is often required.

Uveitis

Acute anterior uveitis develops in a significant proportion of patients, historically reported in approximately 25%.

Symptoms include painful red eye, photophobia, and visual disturbance.

Prompt ophthalmologic assessment is important, and treatment may include topical corticosteroids and other ophthalmic therapies.

Cardiovascular Complications

Potential cardiovascular manifestations include aortic regurgitation, cardiac enlargement, and abnormalities of the cardiac conduction system.

Patients with suggestive symptoms should undergo appropriate cardiovascular evaluation.

Pulmonary Complications

Restrictive respiratory impairment may develop because of reduced chest wall mobility.

Rarely, advanced disease may be associated with upper-lobe pulmonary fibrosis.

Respiratory symptoms should therefore be assessed during long-term follow-up.

Patient Monitoring

Patients should undergo regular review, commonly around every 6 months, although the interval should be individualized according to disease activity.

Monitoring should include posture, spinal mobility, exercise adherence, pain control, and neurologic function.

Patients should also be assessed for extra-articular complications, particularly uveitis and cardiovascular or pulmonary abnormalities.

Early recognition and treatment of complications can substantially reduce long-term morbidity.