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Understanding Food Protein Induced Enterocolitis Syndrome


Food Protein Induced Enterocolitis Syndrome or FPIES is a form of non-immunoglobulin E (IgE) mediated food allergy that mainly presents in infancy. It occurs in around 0.35% of infants (although estimates of prevalence vary widely) and it is thought to be T cell-mediated, with the release of cytokines leading to increased intestinal permeability and inflammation. 

There are two main phenotypes of FPIES – acute and chronic. Some patients also develop allergic sensitisation to the FPIES trigger, which is termed atypical FPIES.

  • Acute FPIES typically occurs in older infants or young children, often around the time of solid food introduction. Individuals typically experience repetitive, profuse vomiting 1-4 hours after ingestion of the culprit food. The vomiting may be accompanied by pallor and lethargy, with diarrhoea that may contain blood and/or mucus occurring 5-10 hours after ingestion. Symptoms often resolve completely within hours although diarrhoea may be a delayed symptom. A detailed history is often enough to identify trigger foods, although food challenges can be used as necessary.
  • Chronic FPIES is mainly seen in young infants, often triggered by feeding cow’s milk or soya infant formulas. Symptoms include watery diarrhoea, mucous and blood in stools and intermittent emesis (not necessarily associated with ingestion). Onset is within 1-4 weeks of infant formula introduction. In chronic FPIES the diagnosis can be unclear and so a supervised food challenge is recommended. During these challenges, infants present with acute FPIES symptoms, which confirms an FPIES diagnosis.
  • Atypical FPIES describes individuals with a compelling history of FPIES who also have evidence of allergic sensitisation to the trigger food. It is estimated that atypical FPIES may occur in 5-25% of FPIES cases, and it is thought to be more common for cow’s milk and egg. Atypical FPIES has been associated with a more prolonged course, with persistence of FPIES reactivity even into adulthood. 



A recent webinar on FPIES prompted many questions about the causes and management of the condition. Here Dr Carina Venter answers some of the questions received.

Q.  FPIES is a complex area. How do you make it easier for parents to navigate?

A.  For the first few appointments, concentrate on what the child can eat, adding maybe 2–3 new foods each time. When the child has a few different foods for breakfast, lunch and dinner and a few snacks, you can then start to consider what to avoid (around appointment 4 or 5). FPIES is often driven by the non-typical foods and so food labels are not particularly helpful (e.g. rice is not listed as an allergen) and this can increase parental anxiety even more. Better to look at the positives ‘what we can eat’ rather than what to avoid. Regular follow ups are useful; a phone call every two weeks, particularly at the beginning, is reassuring for parents/carers and helps monitor progress.

Q.  Should we delay the introduction of peanut in children with FPIES?

A.  In short, no we shouldn’t delay. Children with FPIES and other non-IgE mediated allergies such as food protein induced proctocolitis (FPIAP) have a higher risk of developing other food allergies and so we should try to get peanut into the diet from an early stage. Once a variety of fruits, vegetables and meat (for iron) have been introduced, we should then consider peanut.

Q.  I have seen the FPIES weaning ladder mentioned in various forms by many hospitals. It is my understanding that this ladder is created using the foods statistically least likely to cause a reaction. However, I am obviously concerned about the development of an IgE reaction if parents take too long to introduce foods. What are your thoughts on free feeding foods unrelated to a child's first trigger food?

A.  Research has shown that children who have a greater variety of foods during the first year of life are less likely to develop food allergies later on. The American Academy of Pediatrics suggests introduction of one new food every 3–5 days, but for non-high-risk foods, every other day tends to work well. If a child has IgE-mediated food allergy, I suggest waiting 3 days after separately introducing egg and peanut and some of the other allergenic foods. In children with FPIES, I would also wait 3 days between introducing rice and oat and perhaps other high-risk foods after consultation with the physician. 

Q.  What is your opinion on chronic FPIES? I have seen parents blaming every symptom their baby exhibits on chronic FPIES, but the literature seems to point to a fairly specific set of symptoms for this.

A.  Believe the parents/carers and work with them. It is very hard to manage a baby with FPIES and the parents/carers need to feel supported. A careful clinical history is essential to help better understand the individual child’s condition.

If a child has chronic FPIES they will have acute symptoms when we introduce the food in hospital, so bring the child in and do an open food challenge in hospital. If they don’t react, continue to introduce the foods at home. Often a negative food challenge gives the parents/carers confidence that it isn’t chronic FPIES and encourages them to help with the introduction and reintroduction of foods. If the child has acute FPIES then there are more food challenges to do. Many children only have FPIES to one food and food challenges can help to confirm if you are dealing with single or multiple FPIES. 

Q.  At what age do you step up from a formula to a plant-based milk? 

A.  The Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guidelines suggest that children with FPIES should continue with elemental formulas until 2 years of age. However, clinical practice is starting to change as we see more plant-based fortified milks (for example milks fortified with pea protein). 

Assess the child’s intake and if >50% is from formula, I would recommend continuing with an elemental formula. Look at diet variety and intake of protein, iron, vitamin D and zinc and if the diet is varied, there are no concerns about micronutrient deficiencies and they are growing well, then consider suitably fortified milk. If not, continue with formula for older children until at least 2 years of age and reassess. Dietetic assessment is really key in these cases. Cost is also an issue as many of these plant-based products are expensive.


Useful resources

Go to ANHI.org/uk for further information & education.

To view this webinar on demand, click here 


UK-N/A-2100237. Date of preparation: June 2021.