One in five asymptomatic relatives of people with Crohn's disease had persistently raised faecal calprotectin

Design

Cross-sectional screening stage of a prevention trial, with endoscopic evaluation of those with raised calprotectin

Population

331 asymptomatic first-degree relatives of people with Crohn's disease, aged 6 to 38 years

Primary outcome

Persistent calprotectin elevation (above 70 µg/g twice) and endoscopic presymptomatic Crohn's disease

Effect

19% persistently raised; calprotectin above 225 µg/g, AUC 0.97, sensitivity 89%, specificity 94%

This is the screening stage of the PIONIR trial, which tests whether a diet can reduce the risk of Crohn's disease in first-degree relatives. Faecal calprotectin was measured in asymptomatic relatives aged 6 to 38 years; those with levels above 70 µg/g on at least two tests were offered capsule endoscopy or ileocolonoscopy.

Of 950 relatives approached, 331 (35%) agreed to screening, and 63 (19%) had persistently raised calprotectin. Of 42 who underwent further evaluation, 9 (2.7% of those screened) had appearances compatible with presymptomatic Crohn's disease, 22 had non-specific mucosal changes and 11 had normal-looking mucosa. The 33 in the latter two groups were labelled potential pre-Crohn's (17.9% of those screened after adjustment). A calprotectin above 225 µg/g discriminated presymptomatic disease (area under the curve 0.97; sensitivity 89%, specificity 94%). Among those with a single raised value, 22% normalised on repeat testing.

The study aimed to define a population for a prevention trial, not to recommend screening. Only 35% agreed to take part, the numbers are small and the long-term meaning of these findings is unknown.

• This is a research framework; do not screen asymptomatic relatives with calprotectin outside a study.
• A single raised calprotectin normalised on repeat in 22%, so repeat before acting.
• Persistent elevation (above 70 µg/g twice) was found in 19% of those screened.
• Symptomatic relatives should still be evaluated in the usual way.

Why it matters

It shows that a sizeable minority of relatives carry silent inflammation, which matters for designing prevention trials.

Don't overread it

Only 35% of invited relatives took part, nine had presymptomatic disease, and no one knows whether acting on these findings changes outcomes.

The statistics, in plain English

An AUC of 0.97 means the test separated presymptomatic Crohn's from others very well in this sample. With only nine confirmed cases, though, the estimate is imprecise and may be too optimistic.

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