Axial Spondyloarthritis (Ankylosing Spondylitis)

Axial spondyloarthritis (SpA) is a general term for arthritic conditions that affect the spine and sacroiliac joints. There are two types: radiographic, which shows changes on X-rays, and nonradiographic. Ankylosing spondylitis is a common type of radiographic axial SpA. It is a chronic inflammatory condition that causes pain and gradual fusion of the spine. It usually starts in the late teens or early 20s and is more common in males than females.

Diagnostic Essentials

Axial Spondyloarthritis is a seronegative spondyloarthropathy that typically presents with complaints of chronic low backache (and stiffness) in a young adult. It’s described as being worst in the morning, with progressive limitation of back motion and chest expansion. Other important findings include peripheral arthritis (50% transient; 25% persistent) and anterior uveitis (20-25%).

Diagnostic radiographic changes are seen in the sacroiliac joints.

Serologic tests for RF and anti-CCP antibodies are negative.

If there is an intermediate probability of disease, HLA-B27 testing is helpful.

Clinical Findings

Symptoms and Signs

The onset is usually gradual, with intermittent bouts of back pain that may radiate into the buttocks. The back pain is worse in the morning and associated with stiffness that lasts hours. Pain and stiffness improve with activity, in contrast to back pain due to mechanical causes, which improves with rest and worsens with activity. As the disease advances, symptoms progress in a cephalad direction and back motion becomes limited, with the normal lumbar curve flattened and the thoracic curvature exaggerated.

Costovertebral joint involvement often leads to the limitation of chest expansion — and In advanced cases, the entire spine can become fused, allowing for no motion in any direction.

Transient acute arthritis of the peripheral joints occurs in about 50% of cases, and permanent changes in the peripheral joints—most commonly the hips, shoulders, and knees—are seen in about 25%.

Enthesopathy, a hallmark of the spondyloarthropathies, can manifest as swelling of the Achilles tendon at its insertion, plantar fasciitis (producing heel pain), or dactylitis, which is fusiform “sausage” swelling of a finger or toe.

Anterior uveitis is associated in up to 25% of cases and may be a presenting feature of ankylosing spondylitis.

Cardiac involvement, characterized by atrioventricular conduction defects, aortic regurgitation, or aortic root widening, occurs in 3–5% of patients with longstanding severe disease.

Pulmonary fibrosis of the upper lobes, with progression to cavitation and bronchiectasis mimicking tuberculosis, may rarely occur, characteristically long after the onset of skeletal symptoms.

Laboratory Findings

The ESR is elevated in 85% of cases, but rheumatoid factor and anti-CCP antibodies, which are usually positive in rheumatoid arthritis, are negative. The presence of elevated ESR or CRP conveys increased risk of disease progression and accumulation of damage.

Anemia of chronic disease may be present but is often mild.

HLA-B27 is found in 90% of White patients and 50% of Black patients with ankylosing spondylitis. Because this antigen occurs in 8% of the healthy White persons and 2% of healthy Black persons, it is not a specific diagnostic test but is most useful when there is intermediate probability of disease.

Imaging

The earliest radiographic changes are usually in the sacroiliac joints. In the first 2 years of the disease, sacroiliac changes may be detectable only by MRI. Indeed, patients who have symptoms and findings of ankylosing spondylitis and sacroiliitis evident by MRI but not by conventional radiographs are classified as having nonradiographic axial spondyloarthritis.

With disease progression, erosion and sclerosis of the sacroiliac joints become evident on plain radiographs. The sacroiliitis of ankylosing spondylitis is bilateral and symmetric.

Inflammation where the annulus fibrosus attaches to the vertebral bodies initially causes sclerosis (“the shiny corner sign”) and then characteristic squaring of the vertebral bodies.

The term “bamboo spine” describes the late radiographic appearance of the spinal column in which the vertebral bodies are fused by vertically oriented, bridging syndesmophytes formed by the ossification of the annulus fibrosus and calcification of the anterior and lateral spinal ligaments.

Differential Diagnosis

Low back pain due to mechanical causes, disk disease, and degenerative arthritis is very common.

Onset of back pain before age 30 and an “inflammatory” quality of the back pain (ie, profound morning stiffness and pain that improve with activity) should raise the possibility of ankylosing spondylitis.

In contrast to ankylosing spondylitis, rheumatoid arthritis predominantly affects multiple, small, peripheral joints of the hands and feet. Rheumatoid arthritis spares the sacroiliac joints and only affects the cervical component of the spine.

Bilateral sacroiliitis indistinguishable from ankylosing spondylitis is seen with the spondylitis associated with IBD.

Sacroiliitis associated with reactive arthritis and psoriasis, on the other hand, is often asymmetric or even unilateral.

Osteitis condensans ilii (sclerosis on the iliac side of the sacroiliac joint) is an asymptomatic, postpartum radiographic finding that is occasionally mistaken for sacroiliitis.

Diffuse idiopathic skeletal hyperostosis (DISH) causes exuberant osteophytes (“enthesophytes”) of the spine that may be difficult to distinguish from the syndesmophytes of ankylosing spondylitis. The enthesophytes of DISH are thicker and more anterior than the syndesmophytes of ankylosing spondylitis, and sacroiliac joints are normal in DISH.

Treatment

NSAIDs remain first-line treatment of ankylosing spondylitis.

TNF inhibitors have established efficacy for NSAID-resistant axial disease; responses are often substantial and durable. TNF inhibitors may also have disease-modifying effects and slow radiographic progression.

Secukinumab and ixekizumab inhibit the proinflammatory cytokine IL-17A; these agents are highly effective and FDA-approved for the treatment of ankylosing spondylitis.

Corticosteroids have minimal impact on the arthritis—particularly the spondylitis—of ankylosing spondylitis and can worsen osteopenia.

All patients should be referred to a physical therapist for instruction in postural exercises and a safe exercise program.

Prognosis

Most patients have persistent symptoms over decades; rare individuals experience long-term remissions.

The severity of disease varies greatly, with about 10% of patients having work disability after 10 years.

Developing hip disease within the first 2 years of disease onset presages a worse prognosis.

Biologic agents provide symptomatic relief, improve quality of life, and may slow disease progression for many patients with ankylosing spondylitis.