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Pathology - Spondyloarthropathies
I. Definition & Epidemiology:
A. Ankylosing Spondylitis:
I. Definition & Epidemiology:
- Definition: Spondyloarthropathies are inflammatory joint diseases affecting the spine and peripheral joints, characterized by arthritis and enthesitis (inflammation at tendon/ligament-bone insertion sites).
- Epidemiology: These are common diseases (affecting ~1% of the population), predominantly affecting young adults (20-40 years old) with a slight male bias.
- HLA-B27 Association: A strong genetic association exists with the HLA-B27 allele. This is a crucial risk factor.
- Older Theories: Initially, researchers hypothesized that an unidentified "arthritogenic peptide" presented by HLA-B27 to CD8+ T cells triggered inflammation.
- Current Understanding: Recent focus is on HLA-B27 protein itself. The HLA-B27 heavy chain is prone to misfolding, forming abnormal homodimers. Studies (e.g., in transgenic rats) show that this misfolding leads to endoplasmic reticulum stress and IL-23 production via the T-helper 17 pathway, driving inflammation.
A. Ankylosing Spondylitis:
- Prevalence: Affects approximately 0.5% of the population, typically presenting in young adults (20-40 years).
- Presentation: Lower back pain due to sacroiliitis (inflammation of the sacroiliac joints) is the hallmark symptom.
- Extra-articular Manifestations: Inflammation can extend beyond the joints, affecting structures like the eyes (iritis), lungs (pulmonary fibrosis), and aorta (aortitis).
- Onset: Develops within one month of an infection elsewhere in the body.
- Infections: Commonly associated with genitourinary infections (e.g., Chlamydia) or gastrointestinal infections (e.g., Shigella, Salmonella, Campylobacter).
- Mechanism: Possibly due to bacterial antigens or DNA deposition in joints, although this isn't definitively proven.
- Presentation: Pain and stiffness in the lower back, knees, ankles, and feet; enthesitis is frequent.
- Prevalence: Occurs in approximately 5% of patients with psoriasis.
- Joint Involvement: Primarily affects distal interphalangeal joints (joints at the tips of the fingers and toes), potentially causing significant deformity.
- Cause: Currently unknown.
- Prevalence: Found in about 10% of individuals with inflammatory bowel disease.
- Joint Involvement: Typically affects sacroiliac and lower limb joints asymmetrically.
- Cause: Unknown.
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