Tissue studies in screened first-degree relatives reveal a distinct Crohn's disease phenotype.

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.

Diagnosis and assessment of Crohn's disease: the present and the future.

Diagnosis of Crohn's disease (CD) is often challenging and requires the utmost precision and perseverance in defining location, extent, severity and type of disease (inflammatory vs stricturing/penetrating), as well as in excluding septic complications and extraintestinal manifestations. Endoscopy and histology remain, as of today, the best tests for initial diagnosis of CD. Increasingly important roles are played by imaging techniques (small bowel MRI, computed tomographic enterography and intestinal ultrasound) and noninvasive markers of disease such as fecal calprotectin and specific autoantibodies. Here, we will review the main tools presently available to make the initial diagnosis of intestinal and perianal CD, to evaluate the response to treatment and to diagnose disease recurrence after surgery. Finally, we will discuss some of the future diagnostic challenges in CD.