Background: First-degree relatives of patients with Crohn's disease (CD) are at risk of developing the disease with 5% to 15% reported to be affected over time. Yet, a much greater proportion of them (>40%) shows features of “subclinical inflammation” with elevated intestinal inflammatory markers such as fecal calprotectin. The meaning of these findings is unclear in the absence of tissue data.
Methods: Thirty-eight asymptomatic first-degree relatives of patients with CD underwent ileocolonoscopy and other tests including fecal calprotectin. All known causes of intestinal inflammation were carefully excluded. Age and gender-matched controls consisted of 10 individuals who underwent colonoscopy for other reasons. Histology was scored based on known methods.
Results: Compared with controls, the relatives had significantly greater median values for fecal calprotectin and histological scores. In relatives, endoscopy identified 3 different phenotypes: (1) normal, (2) with minor lesions (aphthae or small superficial erosions), and (3) with typical CD inflammation. Based on the histological scores, the clustering analysis produced 3 corresponding highly separated clusters (61%, 26%, and 13% of the total, respectively) with divisive coefficient D = 0.94. When followed up (on the average for 53 mo), individuals in the second cluster had histological scores similar to baseline values (P = 0.12).
Conclusions: Tissue studies in first-degree relatives of patients with CD reveal 3 distinct groups: normal, with minimal inflammation, and with frank disease. The second cluster represents a novel phenotype, which does not seem to develop the disease over time. These findings explain previous observations of “subclinical inflammation” in such population.
Article first published online 30 April 2014.
*Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy;
†IBD Center, Division of Gastroenterology, Virginia Tech-Carilion School of Medicine, Roanoke, Virginia;
‡Department of Pathology, University of Udine School of Medicine, Udine, Italy;
§Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, United Kingdom; and
‖IBD Center, Division of Gastroenterology, Washington University in St. Louis, St. Louis, Missouri.
Reprints: Dario Sorrentino, MD, Division of Gastroenterology, Virginia Tech-Carilion School of Medicine, 3 Riverside Circle, Roanoke, VA 24016 (e-mail: firstname.lastname@example.org).
The authors have no conflicts of interest to disclose.
Received March 16, 2014
Accepted March 19, 2014