Understanding Food Protein Induced Enterocolitis Syndrome – a potentially severe sensitivity affecting infants.
Dr Marie Wheeler MB ChB,MRCP,DCH

Many acute allergic reactions (which are called type 1 or IgE reactions) are fairly easy to spot with symptoms such as an urticarial (hive) rash, eye swelling (periorbital oedema), facial oedema (swelling) and a close temporal relationship to the food ingested. There are also a group of foods which are the most common offenders including cows milk protein within dairy products, egg, nuts, fish and seafood, and some less common such as soya, peas and seeds, and celery.

Food protein induced Enterocolitis syndrome (FPIES), however, is a little bit different so making the diagnosis more difficult. Because of this, and because it is much less common than the reactions described above, many families with babies or infants with this condition can feel unsupported and with a lack of information.

Hopefully this article may go some small way to provide further understanding and recognition of the condition .I will outline some of its characteristics and some information on management and re-introduction of foods, using a case to illustrate some of the points raised.

Causes – milks and solid foods
FPIES can be a potentially severe food hypersensitivity affecting the gastro-intestinal system i.e. the gut, found in babies less than one year of age mainly. This means that it usually presents with symptoms related to ’digestion’ including vomiting, diarrhoea, abdominal pain or discomfort and sometimes with blood in the stool. Poor weight gain and growth (failure to thrive or faltering growth in babies) may also be a feature if the condition is ongoing and not recognised.

In its most acute presentation a baby can become unwell very rapidly and the condition can mimic a severe infection with profuse vomiting, floppiness and collapse requiring emergency hospital admission and the need for rapid treatment with fluids intravenously. As one can see, these symptoms are not the usual allergic constellation of symptoms as outlined in the introduction.

FPIES is commonly caused by cows milk protein (and often soya proteins) in formula-fed infants during the first year of life. In breast fed babies where cows milk or soya is introduced later, the onset of FPIES is therefore usually later too. About a third of infants who have FPIES to cows milk or soya initially also develop similar symptoms with rice and oats. It is a far less common condition than cows milk protein (IgE mediated) allergy, though it is probably under diagnosed.

FPIES may also be induced by solid foods, often with a later age at onset, than seen with the milk proteins above, because solids are introduced into the infant diet later, typically at 4-7 months of age. Rice is the most common FPIES-inducing solid, followed by oats, barley, chicken, turkey, egg white, green pea, peanut, sweet potato, white potato, corn, fruit protein and fish, Because quite a few of these foods are used as first ‘weaning’ foods, e.g. in baby rice, rusks, baby porridge etc. it can, understandingly, be very alarming for families, as they begin to wean their baby on to solid food, for the infant to experience symptoms of FPIES. At these early stages of weaning, families understandably begin to worry that the baby won’t be able to tolerate any solid food, partly because the offending solid food list above is usually well recognised to be ‘safe’ (have a low risk of causing allergic symptoms usually).

Anxiety can be compounded by the fact that the condition may not be easily and quickly diagnosed at this time. Because of the known high rate of intolerance of multiple foods, within similar groups, in solid-food FPIES, it may be beneficial to avoid these foods in the first year of life. If there is tolerance to a single food within a ‘high risk group’ for example chicken in the poultry group, it is likely that other foods within this group will be tolerated without a problem, which is reassuring and can help to encourage a mixed, less limited and nutritionally balanced diet.

Not uncommonly, a baby may present in the first six months of life with severe and persistent vomiting, sometimes with diarrhoea, which, in severe cases, may lead to dehydration and lethargy in the acute form often to the extent, that they present as emergencies to Emergency Department, where the baby shows signs of having a severe infection (sepsis). 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. It can also cause failure to thrive (faltering growth) in a chronic form.

The diagnosis is also not straightforward because the child will generally not have food-specific IgE antibodies (blood tests raised in allergy) so the blood tests don’t give any clues that this condition is an ‘allergy’. Skin prick testing to cows milk protein, soya or the implicated foods are also usually negative. If the child remains well once the implicated food is eliminated 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, though rarely, and this kind of challenge would usually be performed with an intravenous line in place, in case rapid vomiting ensues during the challenge.

Hospital based food challenges, too, are necessary during follow-up to determine when a child has “outgrown FPIES.”

Management and Treatment
As with other food allergy, the cornerstone of therapy is strict avoidance of the offending food or milk protein. Any food already tolerated by an infant does not need to be restricted. If there were an acute reaction, the management relies on vigorous rehydration (as discussed above) and not on the use of antihistamines or intramuscular adrenaline, as in other acute reactions with food allergies.

Extensively hydrolysed formula milk (e.g. Nutramigen Lipil or Pepti) or an essential amino acid milk (Neocate LCP or Nutramigen AA) are recommended rather than soy-based formula, partly due to frequent concomitant cows milk as well as soya FPIES. In severe cases, temporary bowel rest and intravenous fluids may be necessary.

It is also very helpful to provide children and their families with an emergency treatment letter that describes the symptoms and management of acute episodes, as, because it is an uncommon diagnosis, some health providers may be unfamiliar with its emergency management.

Referral to a Paediatric allergy clinic and a Paediatric dietician with expertise in this area is essential for ongoing management, support and information.

Predicting the outcome with testing?

Because most children with FPIES have negative skin-prick testing and undetectable serum food-specific IgE (allergy blood test) at diagnosis, repeating these tests generally doesn’t give many answers, though in children with FPIES who do have detectable food-specific IgE, there is a tendency for this group to have a more protracted course and to be at a higher risk of developing IgE-mediated immediate-type symptoms, so food challenges would be delayed in this group.

In most studies, FPIES to milk and soy resolves by three years of age. Studies of solid-food FPIES in the United States have reported resolution by age three years that varied for different foods with resolution occurring in 67% of cases of FPIES induced by vegetables, 66% of those related to oat, and 40% of children with solid-food FPIES (usually rice).

Hospital based oral food challenges, too, are necessary during follow-up to determine when a child has “outgrown FPIES ” before the food is reintroduced into the diet at home. Recommendations include follow-up 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 two hours later, to the extent that 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 three days. A single blood-tinged diarrhoea was noted in one stool on admission only. At discharge after three days, she had negative blood cultures (i.e. no signs of a bug or infection growing in the blood) 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 120mls, 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 (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, 30mls/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. Solid foods including rice and oats were introduced into the diet , cautiously, but without any problems.

By age two and a half years 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.

1. FPIES: The ‘Other’ Food Allergy. Medscape. Apr 03, 2013. Other references on request.

This article first appeared in Allergy Newsletter no. 109, Winter 2013.