Food Protein-Induced Enterocolitis Syndrome

From Practice to Theory

Stefano Miceli Sopo; Monica Greco; Serena Monaco; Salvatore Tripodi; Mauro Calvani

Expert Rev Clin Immunol. 2013;9(8):707-715.

Most Frequent Culprit Foods

Bridget suffers from CM FPIES, Ernst and Katie from fish FPIES, Victor from rice FPIES. These four stories present us with the three most frequent culprit foods of FPIES. The predominant food is CM, with the exception of Australia, where rice is the most frequent. The latter is also the most commmon solid culprit food worldwide, unless in Italy where fish is the most relevant one. In the United States some studies were published reporting a double reactivity to CM and soy in 50% of patients and this fact has led the suggestion for preventive dietary therapies^[17] (we will discuss about this aspect next in the article). On the contrary, in Israel none out of 44 children affected by CM FPIES had any problem with soy.^[4] In summary, there are some FPIES geographical differences, so that clinical approaches cannot be always the same. Some prudent dietetic attitudes that can be suitable in a particular geographical area could be wrong elsewere. In addition to rice and fish, among some solid culprit foods identified were oat, barley, poultry, turkey, egg, peas, peanut, potatoes, fruits and shellfish. Recently, we also detected an episode of FPIES caused by corn,^[18] so this food can be added to the list.

In our study,^[5] CM was the culprit food in 67% of cases. Fish was involved in 12% of cases. Approximately three out of eight children suffering from fish FPIES also performed an OFC with types of fish different from the culprit one (the remaining children did not agree with this proposal) with the following results:

A child affected by sole FPIES tolerated codfish and tuna;
A child affected by codfish and sole FPIES tolerated salmon and swordfish;
A child affected by trout and sole FPIES tolerated seabream, codfish and perch.

In summary, as happens in IgE-mediated fish allergy,^[19] it is possible that even in fish FPIES the patient is able to tolerate other types of fish and this fact is very important as, together with the baked food mentioned before, it can help improve patients' quality of life by expanding their food choices and making their diet less limited. So, it's now the time to discuss one of the most important management aspect of FPIES, the diet therapy.

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Table 1. Acute and chronic FPIES clinical manifestations.
Acute FPIES	Chronic FPIES
Important and repetitive vomiting (constant)	Regurgitation, small amounts of vomit
Lethargy (frequent)	Lethargy
Hyporeactivity (frequent)	Failure to thrive
Pallor (frequent)	Dehydration
Diarrhea (inconstant and tardive)	Diarrhea, sometimes bloody
Dehydration (rare)	Abdominal distention
Hypothermia (rare)	Hypotension (rare)

Table 2. Diagnostic criteria of FPIES.
Powell, 1986²	Leonard et al., 2012¹	Miceli Sopo et al., 2013
Less than 9 months of age at initial presentation (reaction)	Less than 9 months of age at initial diagnosis	Less than 2 years of age at first presentation (frequent feature but not mandatory)
Exposure to the incriminated food elicits repetitive vomiting and/or diarrhea within 4 h without any other cause for the symptoms	Repeated exposure to causative food elicits gastrointestinal symptoms without alternative cause	Exposure to the incriminated food elicits repetitive and important vomiting, pallor, hyporeactivity and lethargy within 2–4 h. Diarrhea may be present, much less frequently and later. The symptoms last a few hours, usually less than 6 h
Symptoms limited to the GI tract	Absence of symptoms that may suggest an IgE-mediated reaction	Absence of symptoms that may suggest an IgE-mediated reaction
Avoidance of the offending protein from the diet results in resolution of symptoms	Removal of causative food results in resolution of symptoms	Avoidance of the offending protein from the diet results in resolution of symptoms
A standardized food challenge or isolated re-exposure elicits the typical symptoms	Re-exposure or oral food challenge elicits typical symptoms within 4 h	Re-exposure or oral food challenge elicits typical symptoms within 2−4 h. Two typical episodes are needed to deliver the definitive diagnosis

Box 1. Clues in favor of a specific IgE role in food protein-induced enterocolitis syndrome pathogenesis.
There are some cases with positive specific IgEs against the culprit food, even if their levels are low. In one child,, during an episode of acute FPIES caused by rice, a plasmatic cytokinic trend similar to those of IgE-mediated allergic reactions was observed, with an increase of IL-4 and a decrease of IFN-γ [10]. The fact that symptoms arise 2 h after the ingestion of the culprit food is not a typical feature either of classical IgE-mediated forms (the reaction usually appears long before 2 h) or of classical non-IgE-mediated forms (which usually manifest long after 2 h). Few patients (with positive specific IgE research) present a shift in symptoms from those of FPIES to those of gastrointestinal anaphylaxis [11]. Regarding CM FPIES, there is a report about the capability of tolerating the culprit food if well-cooked (baked) [12].