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.

FPIES Definition and Diagnostic Criteria

FPIES is an important cell-mediated food hypersensitivity, probably non-IgE-mediated and most commonly caused by CM and soy.^[1] There could be other culprit solid foods, such as fish, rice, egg, legumes, poultry, but they are less frequent. Acute FPIES (the most frequent form) is characterized by repetitive and severe vomiting, pallor, hyporeactivity and is less frequently accompanied by diarrhea that can lead toward dehydration and shock in a 10−20% of patients. FPIES clinical findings are listed in Table 1. FPIES can also manifestate itself in a chronic form. This was most frequent in the past years, when it was used to be called 'CM protein intolerance' and it was often diagnosed by gastroenterologists. Nowadays the chronic form is very rare; our clinical records of 55 children report that only three patients are affected by the chronic form.

In FPIES some typical laboratory findings such as neutrophilia and thrombocytosis can be found, especially in the acute form, but their documented presence is not indispensable for the diagnosis. This last one is based on five clinical criteria, which must be fully satisfied to make the diagnosis. They were already listed by Powell in 1986^[2] and recently Leonard et al.^[1] reviewed them and submitted a new version. These criteria are very important and it is necessary to understand their relevance. Now we would like to briefly make some comments concerning the original criteria of Powell^[2] and the changes proposed by Leonard et al.;^[1] Table 2 summarizes the above criteria and our proposal.

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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].