One in five healthy relatives of Crohn's patients had persistently raised calprotectin

Design

Screening cohort within a prevention trial (pre-PIONIR)

Population

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

Primary outcome

Persistent raised calprotectin and endoscopic findings

Effect

19% persistently raised; 2.7% presymptomatic Crohn's; >225 µg/g AUC 0.97, sensitivity 89%, specificity 94%

Before enrolling a Crohn's disease prevention trial, investigators measured faecal calprotectin in asymptomatic first-degree relatives aged 6 to 38. Those with values above 70 µg/g on at least two tests were offered capsule endoscopy or ileocolonoscopy. It was published on 7 October.

Of 331 relatives screened, 63 (19%) had persistently raised calprotectin and 42 were examined. Nine (2.7% of all screened) had appearances compatible with presymptomatic Crohn's disease; 22 had non-specific mucosal changes and 11 normal mucosa despite raised calprotectin, together labelled 'potential pre-Crohn's'. A calprotectin above 225 µg/g identified presymptomatic disease with sensitivity 89% and specificity 94%. Of single raised values, 22% normalised on repeat testing.

This is a screening framework for research, not a recommendation to screen relatives in clinic. There is no proven prevention yet; the trial it feeds is testing a diet. The clinical lessons are about calprotectin itself: a single raised value is unreliable, and a high, persistent value in a relative with symptoms deserves investigation.

• Do not screen asymptomatic relatives of Crohn's patients with calprotectin outside research; no prevention is yet proven.
• Repeat a single mildly raised calprotectin before acting on it, since about a fifth normalise.
• Investigate promptly when a first-degree relative with gut symptoms has a persistently high calprotectin.
• Offer interested families information about prevention trials where available.

Why it matters

It shows Crohn's disease is detectable before symptoms, which is the first step towards preventing it.

Don't overread it

Only nine presymptomatic cases were found, and there is no evidence yet that early detection changes outcomes.

The statistics, in plain English

An AUC of 0.97 means the 225 µg/g threshold separated presymptomatic Crohn's from other results very well, but it was based on only nine cases, so the estimate is fragile. An intraclass correlation of 0.72 means repeat values agreed only moderately.

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