Silent Crohn's Disease Predicts Increased Bowel Damage During Multiyear Follow-up: The Consequences of Under-reporting Active Inflammation.

BACKGROUND: Patients with Crohn's disease (CD) in clinical remission with elevated C-reactive protein (CRP) have been labeled "silent CD" and have increased 2-year hospitalization rates when compared with asymptomatic patients with no biochemical evidence of inflammation. The risk of cumulative bowel damage in patients with silent CD is unknown. METHODS: Observational study of patients with CD prospectively followed in a tertiary referral natural history registry. Consecutive patients with CD in clinical remission (Harvey-Bradshaw Index ≤ 4) with good quality of life (short inflammatory bowel disease questionnaire score ≥ 50), and same day CRP measurement at first encounter, followed for a minimum of 4 years formed the study population. Disease trajectory was determined using change in Lémann Index as a measure of bowel damage. RESULTS: A total of 185 patients with CD (median age 42 years; 51.4% men) were included in the study. CRP elevation was observed in 43 (23%) patients (Silent CD cohort). Majority of them showed worsening disease trajectories based on change in Lémann Index when compared with asymptomatic patients with normal CRP (65% versus 36%, P < 0.0001). Multinomial logistic regression analysis demonstrated that elevated CRP was independently associated with 7-fold higher odds (odds ratio = 6.93, P < 0.0001) of having worse disease trajectories when compared with stable disease trajectories. CONCLUSIONS: Two-thirds of patients with CD in clinical remission, while demonstrating elevated CRP, will develop bowel damage over the ensuing years, despite feeling well. These patients with silent CD are an "at-risk" group who warrant further investigation to prevent development of disease-related complications.

Genetic Predictors of Benign Course of Ulcerative Colitis-A North American Inflammatory Bowel Disease Genetics Consortium Study.

BACKGROUND: A subset of patients with ulcerative colitis (UC) have a benign course and an overall favorable prognosis. Early identification of these low-risk patients may allow for a less aggressive therapeutic approach and possible reduction of therapy-associated risks. The aim of this project was to identify the genetic predictors of benign UC phenotype. METHODS: UC patients were selected from the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium. Benign phenotype was defined as no need for immunomodulatory or biological therapy, hospitalizations, or colectomy. The association between benign UC phenotype and known loci linked to the risk of inflammatory bowel disease (IBD) was evaluated. The results for 156 index single-nucleotide polymorphisms (SNPs) from the known IBD loci were extracted for the main analysis. The association of the benign phenotype to a genetic burden score was also evaluated. RESULTS: None of the index SNPs from the IBD loci reached the predefined threshold of 1 × 10. In the exploratory analysis of the remaining Immunochip SNPs and imputed major histocompatibility complex data, 5 distinct suggestive association signals are identified (rs1697950, rs2523639, rs17836409, rs11742854, and rs75001121). CONCLUSIONS: No SNPs from IBD susceptibility loci were found to be associated (at our predefined threshold of 1 × 10) with a benign UC disease course. The rs11742570 variant on chromosome 5 was the one with the greatest association to benign disease although the association did not reach the predefined significant threshold. Given the modest power of our study, the findings suggested on the exploratory analysis merit extension to larger discovery cohorts.