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.

At Last…FPIES Register

We hope you would not miss the chance to suspect an FPIES diagnosis when you meet a patient suffering from it. To do this, the only things you need to know are the main FPIES diagnostic criteria, as for example the first four ones we discussed before (see Table 2); an allergist will take care of all the other specialist aspects of this syndrome such as the consequent diagnostic work-up, the definitive diagnosis and the correct dietary management. As often happens in medicine, there is still a gray zone in FPIES, including different methods of performing OFCs. Some authors, ourselves included, disagree a little with published methods:^[24] oral challenge involves the administration of food protein, 0.15–0.3 g protein/kg body weight, up to a maximum of 10 g, in three doses over 30−45 min. For example, we do not understand why the established dose should be administered three times in 30−45 min if vomiting usually occurs 2 h after the beginning of ingestion. However, this is a very specialist aspect, which should interest only allergists, those few who are used to performing OFC in their daily clinical practice. Anyway, you will find some hints about this problem in our case review.^[5] All the things we ignore about FPIES are inversely proportional to all we learnt about this syndrome. After all, the number of cases published at the end of 2012 do not exceed 400 units and this is not only due to the fact that FPIES is an uncommon disease (Katz et al.^[4] registered CM-FPIES in 0.5% of newborns), but because it is not well-known and studied. To remedy this situation, we are going to set up the Italian FPIES Register. Our aim is to collect a significant number of cases to throw light on new aspects of this syndrome; thanks to information gathered, a FPIES guideline could be outlined to follow in clinical practice. That's the meaning of 'from practice to theory'.

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].