Excerpt from Ankylosing Spondylitis

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Background

Ankylosing spondylitis (AS) is a chronic, progressive inflammatory disorder primarily affecting the axial skeleton. AS is one of the seronegative spondyloarthropathies, a group of multisystem inflammatory diseases that affects the spine, peripheral joints, adjacent soft tissues, and extra-articular structures. Most of these disorders are associated with the human leukocyte antigen B27 (HLA-B27) antigen.

In addition to AS, the seronegative spondyloarthropathies include the following:

• Reactive arthritis (also referred to as Reiter syndrome)
• Inflammatory bowel disease associated arthritis
• Psoriatic arthropathy
• Juvenile spondyloarthropathy
• Undifferentiated spondyloarthropathies

Several of these disorders share some clinical features, such as sacroiliitis, spondylitis, asymmetric peripheral arthritis, aortitis, clinically evident or occult bowel lesions, and uveitis. On the other hand, some clinical features are more disease specific, such as the urethritis or cervicitis of reactive arthritis or the skin lesions and nail changes in psoriatic arthritis.

Diagnosis of AS is established by clinical and radiographic criteria. The Modified New York Criteria require 1 of 3 clinical features, as well as characteristic radiographic features, to diagnose AS. Clinical criteria for diagnosis of AS include the following: lower back pain greater than 3 months in duration that improves with activity but is not relieved by rest, limited lumbar spine motion in the sagittal and frontal planes, and decreased chest expansion. Characteristic radiographic findings include the following: pseudowidening of the sacroiliac joints, sclerosis, narrowing, and ankylosis.

HLA-B27 typing is not necessary to establish the diagnosis, although it is a useful prognostic indicator in patients with uveitis.

Pathophysiology

Acute anterior uveitis occurs in as many as 30% of patients with AS, particularly in those with the HLA-B27 allele. The exact role of HLA-B27 in the pathology of uveitis is not precisely known, but several theories for its role in disease exist. The oldest theory is that of molecular mimicry, in which an infectious agent triggers an immune response against autoantigens. The HLA-B27 antigen shares some amino acid homology with proteins from several gram-negative bacteria, including Yersinia enterocolitica, Shigella flexneri, and Chlamydia trachomatis, as well as gram-negative bacteria found in the GI tract.

Other theories include the arthritogenic peptide theory, in which the immune response is directed against a peptide presented by HLA-B27; the altered self theory, in which a reactive sulfhydryl group on the HLA-B27 molecule interacts with other self peptides, thereby inducing antigenicity; and, finally, the theory that the HLA-B27 allele confers an altered immune response that directly relates to the disease.

Frequency

United States

Anterior uveitis occurs in 25-30% of patients at some time during the course of the AS.

Mortality/Morbidity

Patients with AS and the HLA-B27 antigen tend to develop uveitis at a younger age, have a longer duration of ocular disease, and have more recurrences. Additionally, patients who are HLA-B27 positive appear to have more severe disease in terms of anterior chamber inflammation and vitritis, resulting in a higher incidence of complications and the requirement for more aggressive therapy.

Age

Uveitis is seen at an earlier age than with idiopathic uveitis.

Please click here to view the full topic text: Ankylosing Spondylitis