The male-to-female ratio is approximately 3 to 1, with prevalence from 0.1% to 6.0% across different populations. The onset of clinical manifestations usually occurs in young adults.

Pathology. The primary pathologic change is an inflammatory process in the apophyseal and costovertebral articulations of the spine and the sacroiliac joints. Initially, the sacroiliac joints become inflamed bilaterally, and the disease can eventually spread up the spine. The speed of progression varies considerably from patient to patient, and the inflammation may stop at any spinal level or encompass the entire spine.

The presence of HLA-B27 in 80% to 90% of patients with ankylosing spondylitis suggests a direct and dominant genetic component. However, only a small group of people who carry the HLA-B27 (5% to 6% in white people) actually develop the disease, which means additional factors may be important. Advances in the genetics of spondyloarthritis have shown that disease association is more complex than with HLA-B27 alone and that there are non–HLA-B27 major histocompatibility complex (MHC) and non-MHC genes important in susceptibility to this disease. Over the past decade, almost 60 subtypes of HLA-B27 have been distinguished, but this has not been accompanied by a great deal of epidemiologic data to evaluate associations with the disease. Understanding of genetics (HLA-B27), the pathophysiology of inflammation (e.g., lesions on magnetic resonance imaging [MRI]), and structural damage is an area of active research and may evolve into new definitions of classification and diagnosis of spondyloarthropathies in the future.

Clinical Manifestations. In the early stage of the disease, patients complain of low back pain, which indicates inflammation of the spine and the sacroiliac joints; this can be accompanied by constitutional symptoms as well. The low back pain is typically worse in the morning and better with activity. Other early signs and symptoms include difficulty in arising from bed because of pain and muscle spasm in the low back, tenderness on pressure and percussion of the sacroiliac joints and lumbar spine, painful restricted motion of the low spine, and flattening of the normal lumbar lordosis (see Plate 5-29). If the cervical spine becomes affected, movement of the head and neck also becomes painful and limited. Chest expansion may be restricted as the costovertebral joints become involved. Some studies show that half of the patients with ankylosing spondylitis reported temporomandibular joint symptoms when specifically questioned about them. Pain, stiffness, and swelling of peripheral joints may also occur. Enthesitis (inflammation of the enthesis) and dactylitis (diffuse swelling of digit[s] of hands or feet) can also be clinical manifestations of ankylosing spondylitis.

After years of disease activity, the inflammation may subside and pain abate, but because the ankylosis is irreversible, the spine remains rigid with limitation in spine mobility. In advanced disease, the thoracic spine may become kyphotic and the neck and head assume a fixed forward position. Affected hips are also painful, and movement is restricted; a complete, incapacitating ankylosis may result.

The most common extra-articular involvement is acute anterior uveitis. Iridocyclitis in one or both eyes may result in synechiae and impaired vision if it is severe and untreated (see Plate 5-30). Cardiac involvement in ankylosing spondylitis can also occur in two distinct ways. First, there is an increase in subclinical atherosclerosis in patients with ankylosis spondylitis compared with controls, and early monitoring of possible cardiac involvement along with cardiac risk factor stratification may be helpful. Second, disturbances in cardiac conduction, usually first-degree atrioventricular block, are detected in about 10% of patients and dilatation of the aortic ring and insufficiency of the aortic valve may develop (see Plate 5-30). Less common extra-articular manifestations include pulmonary (apical fibrosis), renal, and bowel mucosal ulcerations.