Food Protein-Induced Enterocolitis Syndrome

Food protein induced enterocolitis syndrome is a non-IgE-mediated gastrointestinal food allergy that causes repetitive vomiting and, in severe cases, shock. It usually presents in infancy after a first or early exposure to the trigger food.

Cow's milk, soy, rice, oat, egg and fish are common triggers. Estimated cumulative incidence in infants is around 0.3 to 0.7%, with onset in the first year. Acute disease follows intermittent ingestion, and chronic disease follows regular ingestion, usually of cow's milk or soy formula in young infants.

Most children develop tolerance by 3 to 5 years, though persistence is longer for some triggers. The condition is often misdiagnosed as gastroenteritis or sepsis.

Pathophysiology.

The mechanism is not fully understood. T-cell-mediated and innate immune activation produces cytokine release, increased intestinal permeability and fluid shift into the gut, which causes hypovolaemia.

No specific IgE to the food is present in typical disease, and skin prick tests are usually negative.

• Acute: repetitive projectile vomiting 1 to 4 hours after ingestion, with pallor, lethargy and hypotonia. Diarrhoea follows in 5 to 10 hours in up to half.
• Severe episodes: hypotension, hypothermia, dehydration and metabolic acidosis with methaemoglobinaemia, in about 15% of cases.
• Chronic: intermittent vomiting, watery diarrhoea with mucus or blood, poor weight gain and hypoalbuminaemia. Symptoms resolve on elimination and recur with re-exposure.
• Infant is well between episodes in acute disease.

Red flags.

• Shock, hypotension, cyanosis or marked lethargy.
• Fever, blood in stool or failure to thrive requiring exclusion of infection, intussusception and surgical disease.
• Anaphylaxis features (urticaria, wheeze, angioedema), suggesting IgE-mediated allergy.

• Diagnosis is clinical, on a history of repetitive vomiting 1 to 4 hours after the food, without IgE-mediated skin or respiratory signs, and with resolution on avoidance.
• Supportive tests in acute episodes: neutrophilia peaking at 6 hours, thrombocytosis, raised methaemoglobin, acidosis, and raised CRP.
• Supervised oral food challenge when the diagnosis is uncertain or to test for tolerance, performed in a unit with resuscitation facilities.
• Allergy tests (specific IgE, skin prick) do not diagnose but identify coexisting IgE-mediated allergy.

Differential diagnosis. Infective gastroenteritis, sepsis, intussusception, pyloric stenosis, malrotation with volvulus, metabolic disease, eosinophilic oesophagitis, food protein induced allergic proctocolitis and IgE-mediated food allergy.

Acute episode.

• Mild: oral rehydration and ondansetron 0.15 mg/kg orally or IV (maximum 16 mg).
• Moderate to severe: IV access, 0.9% sodium chloride 10 to 20 mL/kg bolus, repeated as needed, with ondansetron 0.15 mg/kg IV (maximum 16 mg).
• Methylprednisolone 1 mg/kg IV (maximum 60 mg) is often given for severe episodes, but evidence is limited.
• Monitor blood pressure, glucose, acid base state and methaemoglobin. Treat methaemoglobinaemia and acidosis if severe.
• Adrenaline is not indicated unless features of IgE-mediated anaphylaxis occur.

Long term care.

• Strict avoidance of the trigger food. For infants with milk or soy triggers, use extensively hydrolysed formula, or amino acid formula if hydrolysed formula is not tolerated or in severe reactions.
• Breastfeeding can continue, with maternal avoidance only if the infant reacts through breast milk.
• Introduce solid foods one at a time, starting with low risk foods. Dietitian review for nutrition and growth.
• Give parents a written emergency plan for acute reactions.
• Re-test tolerance by supervised challenge every 12 to 18 months, or earlier for foods with a shorter course.

Monitoring. Growth, nutritional state and feed tolerance. Review at 3 to 6 months.

Referral and escalation. Refer to a paediatric allergist and dietitian. Admit children with moderate or severe reactions or persistent vomiting.