Ankylosing Spondylitis

Eric S. Schned

KEY POINTS

The diagnosis of ankylosing spondylitis (AS) should be strongly considered if four or more of the following clinical features are present: age of onset of back pain less than 40 years; insidious onset; low back pain lasting longer than 3 months; association with morning stiffness; improvement with exercise.
Radiologic imaging is the key to the accurate diagnosis of AS. Investigation should start with x-rays; if these are not diagnostic, computed tomography (CT) scans or magnetic resonance imaging (MRI) may be more sensitive and specific.
Spinal fracture is a serious complication of AS. Risk of fracture is increased by the presence of ankylosis of the spine, osteoporosis, and trauma. Acute back pain in a patient with AS after minor trauma should raise concern regarding a possible fracture.
Common disorders that need to be distinguished from AS are lumbosacral disc disease, degenerative arthritis of the spine, diffuse idiopathic skeletal hyperostosis (DISH), and osteitis condensans ilii.
Tumor necrosis factor-α (TNF-α) inhibitors are important to provide relief of symptoms in patients with AS who are unresponsive or inadequately responsive to nonsteroidal anti-inflammatory drugs (NSAIDs). Early evidence suggests that they may modify the outcome of AS.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown etiology that primarily affects the spine, axial skeleton, and large proximal joints of the body. Distinctive features of the disease are the striking tendency toward ossification and ankylosis of the spine and involvement of entheses. There is a spectrum of clinical severity, ranging
from asymptomatic sacroiliitis to immobilizing spinal encasement. The most common manifestations of the disease are back pain and stiffness. Genetic and environmental factors play key roles in the pathogenesis of all the spondyloarthropathies, including AS.

Table 39-1 Proposed Classification Criteria for Ankylosing Spondylitis

Clinical criteria

Low back pain and stiffness for more than 3 mo duration, improved by exercise, unrelieved by rest
Limitation of motion of the lumbar spine in both sagittal and frontal planes
Limitation of chest expansion relative to norms corrected for age and sex

Radiologic criteria

Sacroiliitis with more than minimum abnormality bilaterally or
Sacroiliitis of unequivocal abnormality unilaterally

Diagnosis
Definite AS is present if one of the radiologic criteria is associated with at least one clinical criterion
Probable AS is present if 3 clinical criteria are present or if one of the radiologic criteria is present without any signs or symptoms satisfying the clinical criteria

From van der Linden S, Valkenburg HA, Cats A, et al. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:366, with permission.

Classification criteria have been developed for AS (Table 39-1). These are employed in epidemiologic studies in an attempt to standardize AS diagnosis.

ETIOPATHOGENESIS

I. GENETIC ASPECTS

Human leukocyte antigen (HLA)-B27 association. In 1973, Schlosstein and Brewer independently reported a strong association of HLA-B27 with AS. The prevalence of AS has been shown to vary in populations based on the frequency of HLA-B27 in those populations. Recent estimates suggest that HLA-B27 contributes only 16% to 50% of the total genetic risk for AS, which probably helps explain why only a small percentage of individuals with the HLA-B27 allele develop AS.
Family history. A positive family history of AS is found in approximately 15% to 20% of cases. The risk of development of AS in an HLA-B27 relative of an index case is approximately 20%.
Sex distribution. AS is identified more commonly in men than in women by a ratio of 3:1. However, the diagnosis in women may be overlooked or missed for various reasons, such as attribution of symptoms to other causes, or reluctance to perform a radiologic examination of the pelvis in young women.
Environmental aspects. When the HLA-B27 gene and human α are introduced into rats, a Reiter’s-like syndrome develops. However, if the same molecules are introduced into rats in a germfree environment, disease does not occur. These experiments suggest a role for “pathogens” in the pathogenesis of AS and other spondyloarthropathies.

However, to date, there is no clear evidence for a specific environmental trigger for AS.

II. THEORIES OF PATHOGENESIS

How does the HLA-B27 gene contribute risk for AS? The answer is not yet known, but structural features of the B27 molecule may offer some clues (see Chapter 6). A leading theory is that the HLA-B27 molecule may present antigenic peptides to T cells, triggering an inflammatory response.

III. PATHOLOGY

Skeletal sites of inflammation in AS include: sacroiliac joints, intervertebral disc spaces, and apophyseal joints; anterior central joints such as the manubriosternal
joint, sternoclavicular joints, symphysis pubis; and large proximal joints (hips and shoulders). The presence of peripheral joint inflammation such as in the hands or feet should cause the diagnosis of AS to be questioned and raise the possibility of psoriatic arthritis or reactive arthritis.
Extraskeletal sites of inflammation include the uveal tract, aortic root wall, lung apices, and the heart valves.
Pathologic findings. In AS, inflammation occurs in the annulus fibrosis of the intervertebral disc, subchondral bone (osteitis), the entheses (the insertion areas of tendons and ligaments into bone), and synovium (synovitis). Inflammation of subchondral bone leads to erosion and sclerosis, which later becomes replaced by fibrocartilage and then becomes ossified.

PREVALENCE

In white Americans, the HLA-B27 gene occurs in approximately 8% of the population and the prevalence of AS is estimated to be approximately 0.1% to 0.2%. The risk of AS is much higher in native American populations such as the Haida who have a 50% prevalence of HLA-B27, and is very low in native South American and Bantu populations of Africa who have very low HLA-B27 prevalence.
AS typically affects young adults in their 2nd through 4th decades. The risk of developing AS in a random population of HLA-B27–positive persons is approximately 2%.

CLINICAL MANIFESTATIONS