Babies With Enterocolitis - A Study of Faecal Calprotectin in Hirschsprung Disease (The BEACH Study)

Background:

Hirschsprung's Disease is a rare congenital condition affecting 1 in 5000 children and characterised by an absence of ganglia in the distal bowel(1). Affected infants cannot stool normally and require an intensive treatment programme of regular rectal washouts or a stoma to ensure that their bowel is emptied, and avoid bowel perforation. Once they are a few months old definitive surgery is performed to remove the affected segment of bowel.

Infants with Hirschsprung's Disease have a high (1 in 4) risk of developing Hirschsprung's associated enterocolitis (HAEC), an inflammatory and infective condition of the bowel which can cause severe acute illness and death in 1-10% of affected children(2). Although the incidence of HAEC is reduced by surgery, the risk persists throughout childhood(3). Signs and symptoms are non-specific, including fevers, irritability, poor feeding, abdominal distension and explosive stool, and deterioration can be rapid. The mainstay of treatment is intravenous antibiotic therapy with colonic lavage per rectum. In severe cases, emergency surgery to remove the affected bowel is required, with long term implications for continence. A biomarker to identify children at higher risk of HAEC or its life-threatening complications would enable clinicians to consider employing additional or earlier treatments for these patients.

Faecal calprotectin is a biomarker currently used in both the diagnostic work-up of inflammatory bowel disease (IBD) and to monitor disease progression and remission, adding to the clinical decision making around escalation and de-escalation of IBD treatments(4, 5). Previous studies have demonstrated that faecal calprotectin levels reduce with age and have wide variability in early infancy(6).

Faecal calprotectin has not previously been described as a marker of enterocolitis in infants with Hirschsprung's Disease. We have received written communication of an unpublished retrospective study of single faecal calprotectin measurement in children with Hirschsprung's Disease and suspected HAEC from a UK centre. Using clinical, radiological, haematological and biochemical features this study divided 27 children into "low risk" and "high risk" groups. Faecal calprotectin level was significantly higher in the high risk group (285μg/g) compared to the low risk group (70μg/g) (p <0.01). Whilst these data suggest a potential role for faecal calprotectin assay in the diagnosis of acute HAEC, the difference might simply represent association due to demographics: baseline faecal calprotectin is known to be higher in younger children, likewise HAEC is more common in younger children with Hirschsprung's Disease. Further, it is unknown whether the 'high risk' group had a more profound acute calprotectin rise reflective of acute disease severity or a higher baseline. Serial faecal calprotectin monitoring could benefit children both for earlier diagnosis and earlier initiation of more intensive therapies.