Ankylosing Spondylitis

Definition

Ankylosing spondylitis is classified along with the seronegative spondyloarthritic diseases. Ankylosing spondylitis is a chronic, systemic, inflammatory disease that affects primarily the sacroiliac joints and spine. Certain peripheral joints and tendons can also be affected, and extra-articular manifestations may be present. The disease typically affects young adults, and there are strong genetic features.

The spondyloarthritides, as a subset, have several distinguishing features that are shared among them. The diseases are seronegative by definition. There are common genetic factors including the human leukocyte antigen (HLA) B27 gene. Axial involvement, including sacroiliitis, can be seen in all and is essential for the diagnosis of ankylosing spondylitis. Enthesitis, or inflammatory changes of the tendon and ligament attachment to bone, is the primary pathologic phenomenon. The spondyloarthritides share many extra-articular features including uveitis, dermatitis, and colitis.

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Etiology

The etiology of ankylosing spondylitis remains unclear. There is solid evidence pointing to a genetic component and risk. The HLA B27 gene is commonly present, and there is a strong familial association. Infective mechanisms have been proposed but seem less evident than in the reactive arthritides.

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Prevalence and Risk Factors

The prevalence of ankylosing spondylitis is 0.1% to 1.4%, depending on the population studied.1 The disease is more common in Caucasians than in other races. Typically, but not universally, the prevalence reflects the associated prevalence of the HLA B27 gene in that population.2 Ankylosing spondylitis is discovered to be the etiology in 4% to 5 % of patients with chronic low back pain.3

In North American Caucasians, the HLA B27 gene is found in 7% of the normal population and in more than 90% of patients with ankylosing spondylitis.2 A person who is HLA B27 positive has a 5% to 6% chance of developing the disease.4 There is a fivefold to 16-fold increase in having ankylosing spondylitis if a first-degree relative has the disease.5 The HLA B27 factor makes up about a third of the overall genetic risk.

In the past, ankylosing spondylitis was thought to be an overwhelmingly male disease, but the actual male-to-female ratio is closer to 3:1. The median age of onset is 23 years. Ankylosing spondylitis rarely has its initial manifestation after age 40 years; however, there can be a delay in diagnosis.

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Pathophysiology and Natural History
Pathogenesis

The pathogenesis of ankylosing spondylitis remains unclear to date. It is assumed to be immune mediated. There is an obvious cytokine role, because patients show improvement with anti–tumor necrosis factor α (anti–TNF-α) agents. As discussed earlier, there is also a genetic component, and the HLA B27 gene is found in more than 90% of patients with ankylosing spondylitis, although the incidence varies some depending on the population studied. Familial aggregation is seen even without the HLA B27 gene. An infectious trigger for the disease remains an intriguing hypothesis. Studies with animal models show that rodents that have HLA B27 and are raised in a germ-free environment do not develop disease; however, in a regular environment, they develop a disease similar to ankylosing spondylitis.6 To date however, no infectious trigger has been unequivocally established, as with reactive arthritis.
Pathology

Enthesitis, in both the axial and the appendicular skeleton, is the primary pathologic feature of the spondyloarthritides.7 The enthesis is where the tendon or ligament attaches to bone. The progression is typically edema of bone followed by erosion, then ossification, then finally ankylosis. The sacroiliac joints exhibit inflammation followed by ankylosis. In the spine, one can see inflammation at the junction of the annulus fibrosis of the disk cartilage with the margin of vertebral bone. Ultimately, this leads to formation of syndesmophytes, with bridging that leads to the radiographic appearance of a bamboo spine (see the discussion of imaging, later). The spinal facet joint can exhibit synovitis followed by ankylosis. In the peripheral skeleton, one sees synovitis and enthesitis.

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Signs and Symptoms
Symptoms

Spinal and sacroiliac symptoms are typically early and the most prominent. Low back pain is the first symptom in more than 75% of patients. In some patients, the symptoms are more in the buttock. Over time, the patient experiences limited spinal mobility. One of the keys to the diagnosis of ankylosing spondylitis is identifying features of inflammatory low back pain.3, 8 This includes onset before the age of 40 years, insidious onset, chronic (>3 months) pain, morning stiffness for longer than 30 minutes, improvement with exercise, awakening with pain in the second half of the night, and alternating buttock pain (Box 1).
Box 1 Diagnosing Inflammatory Low Back Pain
Onset before the age of 40 years
Insidious onset
Greater than 3 months in duration (chronic)
Morning stiffness >30 minutes
Improvement with exercise but not with rest
Awakening with pain in the second half of the night
Alternating buttock pain

Enthesopathic symptoms can be spinal or peripheral. Axial enthesitis includes costovertebral, manubriosternal, sternal clavicular, and costochondral. Some patients experience decreased chest expansion. Examples of extraspinal enthesisits include dactylitis (sausage digit), Achilles tendinitis, and plantar fasciitis.

Inflammatory arthritis likewise can be axial or appendicular. The hips and shoulders are commonly involved. In the peripheral skeleton, patients typically experience lower extremity and asymmetric patterns of involvement.

Finally, extra-articular manifestations may be present (Box 2). Eye involvement is the most common, with anterior uveitis (or iritis) seen in 25% to 40% of patients who have ankylosing spondylitis.9 This precedes the spinal symptoms in some cases.