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.

The Diagnostic Delay and the Increase of New Diagnoses: Is It a Contradiction?

Ernst's story shows how a delay in FPIES identification, until a third episode, is not so rare. Fortunately, in the last 5 years there has been more information about this syndrome, so that doctors are more aware of it. In our experience, 10% of children presented almost four episodes before the diagnosis was made and a few of them had even ten adverse reactions before a solution was found. A few years ago, we ourselves were wrong, and you will read about what happened to Katie in 2004 below.

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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].