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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0000000000000051
Original Clinical Articles

Tissue Studies in Screened First-degree Relatives Reveal a Distinct Crohn's Disease Phenotype

Sorrentino, Dario MD*,†; Avellini, Claudio MD; Geraci, Marco PhD§; Dassopoulos, Themistocles MD; Zarifi, Dimitra MD*; Vadala' di Prampero, Salvatore Francesco MD*; Benevento, Gianluca MD*

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Abstract

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.

Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

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