Disease location, anti‐Saccharomyces cerevisiae antibody, and NOD2/CARD15 genotype influence the progression of disease behavior in Crohn's disease

• Published in: Inflammatory bowel diseases Vol. 10; no. 5; pp. 521 - 528
• Main Authors: Smith, Ben R. K., Arnott, Ian D. R., Drummond, Hazel E., Nimmo, Elaine R., Satsangi, Jack
• Format: Journal Article
• Language: English
• Published: Philadelphia Lippincott Williams & Wilkins, Inc 01.09.2004
• Subjects: Adult; Antibodies, Fungal - analysis; ASCA; Carrier Proteins - genetics; Crohn Disease - genetics; Crohn Disease - immunology; Crohn Disease - microbiology; Crohn Disease - pathology; Crohn's disease; Disease Progression; Female; Follow-Up Studies; Humans; Ileal Diseases - pathology; Intracellular Signaling Peptides and Proteins; Male; Nod2 Signaling Adaptor Protein; NOD2/CARD15; perianal Crohn's disease; Phenotype; Saccharomyces cerevisiae - immunology; Severity of Illness Index
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/00054725-200409000-00005

Background: Crohn's disease (CD) is characterized by heterogeneity of phenotype. The Vienna classification can be used to classify CD, and recent data illustrate that behavior evolves over the course of the disease. Clinical and biological influences on disease progression remain unclear. We examined the associations of CD disease progression at diagnosis and for up to 20 years of follow‐up. Methods: Two hundred thirty‐one well‐characterized CD patients were studied. Demographic, clinical, and NOD2/CARD15 data were collected. Disease behavior according to the Vienna classification was assessed at diagnosis and for up to 20 years following diagnosis. Results: At diagnosis, 70% of patients had inflammatory disease, 9% stricturing, and 21% penetrating. Early age at diagnosis was associated with ileocolonic and upper GI disease (p = 0.015), and positive anti‐Saccharomyces cerevisiae antibody (ASCA) was associated with ileal invovement (p = 0.008). Smoking was relatively protective against colonic, rather than ileal involvement at diagnosis (p < 0.02). At 20 years, 92% had progressed to a more severe disease type. Patients who progress to a more severe disease type require more frequent surgery (p < 0.00001). Multivariate analysis found disease progression to be associated with ileal disease location (p = 0.001) and positive ASCA (p = 0.003). Variant NOD2/CARD15 alleles were protective against rapid progression of disease phenotype (p = 0.04). The presence of perianal disease was independent of intestinal penetrating disease. Conclusions: The progression of disease type in CD is associated with the need for more frequent surgery. Rapid progression is associated with ileal disease and positive ASCA, and delayed progression is associated with variant NOD2/CARD15 alleles. Consideration should be given to a separate Vienna classification for perianal disease.