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.

From Practice to Theory

Bridget was lucky, since the story of her first clinical reaction was heard by a young resident pediatrician who knew FPIES and was able to plan a correct work-up to understand the baby's problem. Thanks to that, the second reaction was induced in a safest place which was well equipped and ready to face any harmful situation. Ernst instead wasn't as lucky as Bridget, because nobody considered either the hypothesis of FPIES or even a generic food allergy (FA). The child had three episodes at home without any appropriate assistance, in danger of a more severe outcome. These two stories are suitable for learning a lot about FPIES, as they exemplify some well-known and even uncommon aspects of this syndrome:

FPIES pathogenesis is probably non-IgE-mediated, so culpritfood-specific IgE research is almost always negative;
The period of life during which FPIES appears most frequently is the first 9 months after birth;
The most frequent culprit food (except in Australia) is CM;
The most frequent solid food that induces FPIES in Italy is fish, while worldwide it is rice;
FPIES symptoms are vomiting, hyporeactivity, hypotonia and sometimes diarrhea;
The evolution of FPIES is benign in a few hours;
Diagnostic criteria consist of the occurrence of at least two typical episodes;
There is often a diagnostic delay – as many as six episodes could take place before the situation is clarified;
Acute therapeutical measures are iv. fluids and cortisone;
Dietetic measures consist of eliminating the culprit food from the patient's diet;
As far as prognosis is concerned, there is a good chance of achieving tolerance at 18 months if the responsible food is CM; however, there aren't enough data for other foods.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Next Section

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].