Review article: joint involvement in inflammatory bowel disease

Area of Science:

• Gastroenterology and Rheumatology
• Genetics and Immunology

Background:

• 10-20% of inflammatory bowel disease (IBD) patients exhibit peripheral joint involvement, such as synovitis and enthesiopathy, often recurring with intestinal flare-ups.
• Axial involvement, including sacroiliitis and ankylosing spondylitis (AS), is under-reported but present in 20-25% (sacroiliitis) and 3-10% (AS) of IBD patients.
• IBD-associated AS may have a different genetic basis than classic AS, with lower prevalence of human leucocyte antigen B27 (30% vs. 90%).

Purpose of the Study:

• To investigate the genetic and clinical links between inflammatory bowel disease and spondyloarthropathy.
• To explore the role of CARD15 polymorphisms and tumor necrosis factor-alpha in the pathogenesis of IBD-associated joint disease.

Main Methods:

• Analysis of human leucocyte antigen B27 prevalence in IBD patients with AS.
• Genotyping for CARD15 polymorphisms in IBD patients with and without sacroiliitis.
• Review of clinical outcomes, including response to infliximab, in spondyloarthropathy patients.

Main Results:

• CARD15 mutations are more prevalent in Crohn's disease patients with sacroiliitis (78%) compared to controls (48%).
• Patients with spondyloarthropathy and gut inflammation likely to develop Crohn's disease show higher rates of CARD15 mutations (42%) than those with normal histology (7%).
• Treatment with infliximab led to rapid and sustained symptom improvement in spondyloarthropathy, implicating tumor necrosis factor-alpha.

Conclusions:

• CARD15 gene polymorphisms are associated with sacroiliitis in Crohn's disease patients.
• A shared pathophysiology exists between IBD and spondyloarthropathy, potentially mediated by tumor necrosis factor-alpha.
• Genetic and clinical evidence supports a strong relationship between gut inflammation and joint involvement in IBD.