Food Protein Induced Enterocolitis syndrome – FPIES

Dr Marie Wheeler, Consultant Paediatrician, MB ChB MRCP DCH, at Gloucestershire Royal Hospital, explains.


Many acute allergic reactions to food (Type 1 or IgE reactions) are fairly easy to spot with symptoms such as an urticarial rash (hives), eye or facial swelling (periorbital or facial oedema) occurring very soon after the food was eaten.

There are also a group of foods that are the most common offenders including cows milk protein, egg, nuts, fish and seafood; less common offenders include soya, peas and seeds, and celery. Food Protein Induced Enterocolitis Syndrome (FPIES) however is rather different, making its diagnosis more difficult.

Causes – Milks and solid foods
FPIES is a potentially severe, non-immunoglobulin (IgE), cell-mediated, gastrointestinal food hypersensitivity – so a ‘sort of ’ allergy. Symptoms are usually related to the gastro-intestinal tract including vomiting, diarrhoea (some times with blood in the stool), abdominal pain and, only occasionally in my experience, poor weight gain. They do not include the usual allergic constellation of symptoms as outlined above. FPIES is most commonly caused by cow’s milk (CM) and soya proteins in formula-fed infants early on, very soon after introduction. In American studies up to 50% of children with FPIES reacted to both. In breast fed babies where cows milk or soya are introduced later, the onset of FPIES is therefore later too.

FPIES may also be caused by solid foods which can almost be more worrying. The symptoms will then appear as solids are introduced into the infant diet, usually in the UK from 4-6 months of age.

Rice is the most common FPIES-inducing solid food, with other unexpected foods including  oats, chicken, turkey, egg white, green pea, peanut, sweet potato, white potato, corn, fruit protein and fish. Symptoms tend to be unexpected as some of these are foods are commonly used in the first 6 months of weaning because they are well recognised to be ‘safe’ (have a low risk of causing allergic symptoms; excluding egg, peanut, fish). About a third of infants who have FPIES to cow’s milk or soya develop similar symptoms with rice and oats. FPIES to solid foods, though, is probably under diagnosed.


A baby may present in the first 6 months of life, with severe vomiting and sometimes with diarrhoea. In severe acute cases this may lead to dehydration and lethargy/floppiness and the child may finally be taken to an emergency department because he/she is showing signs of having a severe infection. It is not uncommon for a baby to be admitted once or even twice with a likely diagnosis of a severe infection before the diagnosis of FPIES is considered, partly because the symptoms are not particularly indicative of an ‘allergy’. Chronic FPIES can cause poor weight gain so occasionally presents in this way.

The diagnosis is also not straightforward because there is no blood test for FPIES as there is for allergy. If the child remains well once the implicated food is removed from the diet, the diagnosis of FPIES can usually be established on clinical grounds. At times, it can be difficult to know if the suspected food really is the culprit, so in these rare cases a food challenge in the hospital setting may be required. This kind of challenge may be performed, under observation within the hospital setting, sometimes with an intravenous line in place, in case of rapid vomiting during the challenge.

Hospital based food challenges, however, are necessary during follow-up to determine when a child has ‘outgrown FPIES’, especially as some children seem to go on to develop the more classical food allergies, to the foods that caused their FPIES.

The differential diagnosis of FPIES is wide and includes other allergic food disorders, infectious disease, severe gastroesophageal reflux disease, less commonly anatomical intestinal obstruction as well as others including metabolic diseases.

Management and Treatment

The mainstay of management is strict avoidance of the offending food or milk protein, as in other allergic conditions. Any food already tolerated by an infant can continue to be given. Dietician input is really important to ensure that sufficient Vitamin D and Calcium are still present in sufficient quantities in the diet. Supplementation may be required.

If there were an acute reaction, the management relies on rehydration (sometimes requiring intravenous fluids) and not on the use of antihistamines or intramuscular adrenaline, as in acute food allergy reactions.

It is also very helpful to provide children and their families with an emergency ‘action plan’ detailing the symptoms and management of acute episodes, as, because it is an uncommon diagnosis, some health providers may be unfamiliar with its emergency management.

Extensively hydrolysed formula milks (Nutramigen Lipil or Pepti) or essential amino acid milks (Neocate LCP or Nutramigen AA) are recommended rather than soy-based formula, in part, because many babies with cow’s milk FPIES will also have soya FPIES. In 10%-15% of infants, an amino acid formula (e.g. Neocate LCP or Nutramigen AA) is needed. In severe cases, temporary bowel rest as well as IV fluids may be necessary.

Weaning onto Solids

Introducing vegetables and fruits only and leaving out cereals at 6 months of age may be one initial solution to try. If tolerated, grains, legumes, and poultry can be introduced to the diet. However, because, often, several foods cause symptoms in solid-food FPIES, it may be best to avoid these foods in the first year of life. Tolerance to one food from each high-risk group – for example soy in the legume group, chicken in the poultry food group, or oat from the grains group – gives a good indication that other foods from the same group should be tolerated, making weaning easier, which can be useful to know.

Outcomes and Resolution

Predicting the outcome with testing?

Because most children diagnosed with FPIES have negative skin-prick tests for food allergy, repeating these tests generally doesn’t give many answers. If a child with FPIES does have some positive reactions to food allergy skin prick tests, this may indicate that the FPIES may last longer and they may be at a higher risk of developing IgE-mediated immediate-type allergy later, so food challenges would be delayed in this group.

In most studies, FPIES to milk and soy resolves by 3 years of age. Studies of solid-food FPIES in the United States have reported that 67% of cases of FPIES induced by vegetables, 66% of those related to oat, and 40% of children with solid-food FPIES had resolved by age 3 years….though in a small study of Korean infants with CM FPIES, more than half tolerated cows milk at 10 months, and 92% tolerated soy at 10 months. These investigators recommended follow-up challenge are undertaken sooner: after 12 months of age for CM and at 6-8 months of age for soy. These slightly differing outcome results indicate that further studies are needed to establish the optimal timing of follow-up challenges. My current practice is to offer challenges every 18-24 months in patients without recent reactions.

Case example

A four month old baby girl, born at term, was initially breast fed (Mother had dairy within her usual diet), with a few formula top-ups in the first few days only, until she was given a further cows milk protein formula at 12 weeks of age. She took the feed well but developed profuse vomiting 2 hours later, to the extent where she was beginning to vomit bile (green vomit), with associated pallor and floppiness. An ambulance was called and on examination, at the time, her oxygen saturations were low initially. She had an elevated white blood cell count (consistent with a presumed infection). She received intravenous fluid resuscitation and antibiotics and was observed in hospital for 3 days. A single blood-tinged diarrhoea was noted in one stool on admission only. At discharge after 3 days, she had with negative blood cultures and a presumptive diagnosis of viral gastroenteritis, so it was felt at that time, that she had probably contracted a viral illness (vomiting bug) and there were no indications for further investigations.

A few weeks later, she was given a further cow’s milk protein formula, approximately 4oz, during which she seemed somewhat agitated with pulling up of her legs to her tummy. Again a few hours later, a similar picture of profuse vomiting with pallor and floppiness occurred. By the time emergency help was called she was more responsive and recovering well and it was not deemed necessary to take her to hospital for further review. She had developed a slight red patch around her mouth with the formula feed but no reported obvious urticaria (hive rash), facial oedema (swelling) or respiratory symptoms (cough or wheeze).

On review in the allergy clinic, she was thriving on the 50th centile and did not have any evidence of eczema, nor a personal or family history of atopic disease/allergy, such as viral induced wheeze, or a family history of eczema or hayfever. Skin prick testing was negative (normal) to cows milk protein and soya, though an IgE (blood test) was slightly raised to cows milk protein. A diagnosis of FPIES to cows milk protein was made and an amino acid formula was prescribed as an alternative to breast-feeding for a later date. Breast-feeding was continued (with dairy in maternal diet as this had not caused any prior symptoms) until 8 months of age, when the amino acid formula was tried, initially without success. A soya formula was introduced very slowly, 1 0z/day at a time, but caused eczema and loose stools so was stopped. The amino acid formula was again tried and this time successfully introduced. A follow on amino acid formula was prescribed after age one, and cows milk strictly avoided.

By age 2 1/2 she has successfully incorporated a variety of foods into her diet. However, her parents continued to strictly avoid milk, appropriately, until an oral challenge, within the hospital setting to cows milk was performed before her third birthday with tolerance and no symptoms.

 FPIES: The 'Other' Food Allergy. Medscape. Apr 03, 2013

  • Sicherer SH. Food protein-induced enterocolitis syndrome: case presentations and management lessons. J Allergy Clin Immunol. 2005;115:149-156.
  • Hwang J-B, Sohn SM, Kim AS. Prospective follow-up oral food challenge in food protein-induced enterocolitis syndrome. Arch Dis Child. 2009;94:425-428. 

The FPIES Foundation in the US offers support and further information about the condition.

First published September 2013


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