I recently evaluated a 6 month old male for possible "food allergy"- for whom I am considering diagnosis of FPIES. My questions are regarding the likelihood of this as dx but more so approach for evaluation and treatment at this time ( ie challenges, avoidance) as there are certain atypical points in history which make the diagnosis I think suggestive for FPIES but unclear.

This essentially exclusively breast fed male (tolerates breast milk very well) had no issues until 4 months of age when given rice cereal (although took it well 2 times) was noted to have "explosive vomiting" without diarrhea or lethargy or dehydration, about 2-4 hours after ingestion. Mom tried rice cereal again one week later with same response and again x 1 after that with same response. Pt had similar rxn with first trial of sweet potato. He tolerates fruits, squash. Never given poultry or other grains.

He was not ill and at this point no vomit without those two foods. He had no hives, swelling, pruritus, choking.

Skin test negative to milk, soy, wheat, egg, rice, turkey, barley and oat. Has not had cows milk or soy based formulas.

My questions are:
1. Likelihood of diagnosis without diarrhea, other sxs.
2. When to challenge to foods - ie cows milk, soy- as although has never had either as they are most likely culprits in FPIES, I believe physician supervised challenges would be needed.

3. At this time I told mom to avoid grains, poultry and legumes (potato too). I am concerned about avoiding above if diagnosis likelihood is weak-would be difficult to do challenges to multiple foods but realize it may be necessary.


Thank you for your inquiry.

I am going to ask Dr. Dan Atkins, who is an authority in food allergy, to respond to your question. As soon as I receive Dr. Atkins’ response, we will forward it to you.

Thank you again for your inquiry.

Phil Lieberman, M.D.

We received a response from Dr. Dan Atkins to your Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Phil Lieberman, M.D.

Response from Dr. Dan Atkins:
As you know, FPIES is a rare (incidence of 0.34% reported in Israel) non-IgE mediated condition (negative skin tests and immunoCAPs) that is often seen in breast fed infants with the first 6 months of life. The timing of symptom onset is 2-6 hours after ingestion of the offending food. Observed symptoms include profuse vomiting, lethargy, pallor and diarrhea (not all go on to develop diarrhea). Severe reactions are associated with hypotension. Treatment of acute episodes is fluid resuscitation rather than the administration of epinephrine and diphenhydramine.

The mechanism of FPIES remains undefined, although tumor necrosis factor alpha is thought to play a role. Unfortunately, there is no diagnostic test such as skin testing, serum food-allergen-specific IgE testing or patch testing that predicts or identifies offending foods. Thus, feeding the child the food is currently the only way to tell if a child will react. Although milk and soy are the most common foods that cause reactions (usually offered in the liquid form in the target age group), rice (given as rice cereal) is likely the most common solid food trigger, particularly in young infants. A number of other foods have been implicated including grains and meats.

FPIES has been reported to vegetables and fruits, but these are less frequent triggers. Reactions to sweet potato (as in your patient) have been observed. Although the majority reacts to only a couple of foods, a small proportion of these patients (less than 10%) can react to multiple foods. Reactions to both milk and soy are common, as are reactions to more than one grain. In most infants the introduction of most vegetables and fruits is well tolerated. Obviously, parents are often anxious about the introduction of new foods after their child has reacted to a common food in this manner. Fortunately, most children outgrow FPIEs by 3 years of age, although a small percentage can have disease that persists into adolescence. Obviously, some can outgrow FPIES before 3 and are usually discovered by accidental ingestion of significant amounts of the previously offending food without the expected reaction.

In response to your questions:
1. Likelihood of diagnosis without diarrhea, other sxs.

a. I agree that this child has FPIES to rice and likely to sweet potato. It is difficult to know whether other foods are triggers without feeding them to the child.

2. When to challenge to foods - ie cows milk, soy- as although has never had either as they are most likely culprits in FPIES, I believe physician supervised challenges would be needed.

a. I would continue with the introduction of vegetables and fruits, as these are often well tolerated. The introduction of soy and/or milk will likely depend upon when the mother wants to wean the child. You can try hydrolyzed formulas, but might want to challenge to milk or soy first because of the additional cost. I agree with you that these challenges should be physician-supervised with the ability to rapidly provide fluid resuscitation if necessary.  

3. At this time I told mom to avoid grains, poultry and legumes (potato too).

a. I agree with continuing with the addition of vegetables and fruit (obviously other than sweet potato and potato for now). I would suggest physician observed challenges to a grain and either soy or milk depending upon how the child tolerates the introduction of other fruits and vegetables and when the mother wants to wean the child. Challenges to suspected triggers (rice and sweet potato) could be performed when the child is about 3 years of age unless there is a history of an accidental exposure resulting in a reaction to suggest continued sensitization. Waiting until a year to 18 months after the last reaction to challenge again is reasonable.

There are numerous references in the literature, but 3 I find helpful follow:

1. Sicherer SH. Food protein-induced enterocolitis syndrome: case presentations and management lessons. J Allergy Clin Immunol 2005;115:149-56.

2. Nowak-Wegrzyn A, Muraro A. Food protein-induced enterocolitis syndrome. Curr Opin Allergy Clin Immunol 2009;9:371-7.

3. Leonard SA, Nowak-Wegrzyn A. Clinical diagnosis and management of food protein-induced enterocolitis syndrome. Curr Ipin Pediatr 2012;24:739-45.

Dan Atkins

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