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.

Diet Therapy, Single and Multiple

To date, nobody doubts that the culprit food has to be always and strictly eliminated from the patient's diet up to the spontaneous achievement of tolerance. This is a difference between FPIES and IgE-mediated FAs: the management of FPIES does not provide, as happens for some common IgE-mediated FAs, the possibility of initiating oral immunotherapy (OIT) in order to actively induce tolerance or at least desensitization.^[20] OIT was never performed for FPIES, as spontaneous tolerance is achieved relatively soon, usually within the first 5 years of life: it's not worth exposing patients to the risks of OIT for such a short wait. So, patients cannot ingest even small amounts of culprit food, as the minimum quantity which can cause an acute episode is still unknown, and it's very difficult to obtain this information due to the latency period of the symptoms; the patient always has the time to finish the meal before symptoms arise. We also do not know if small and frequently ingested amounts of food can cause chronic FPIES. So in case of FPIES, diet concerning the culprit food must be very strict and has no alternative.

Moreover, Sicherer has also proposed the elimination from the diet of other foods in addition to the culprit. In fact, this author suggests,^[17] in case of CM FPIES, to avoid ingesting soy and cereals and to delay the introduction of other solid foods, at least until the baby is one year old. In case of FPIES induced by solid food, he proposes avoiding the ingestion of cow milk, cereals, legumes and poultry, at least until the baby is 1-year-old. Of course, the preventive diet will be implemented only if the foods in question, at the time of diagnosis of FPIES, have not already been eaten without problems by the child. The suggestion is born from the observation of a clinical reactivity to these foods in children with CM FPIES or solid food FPIES in the USA in a series composed of 30−50 individuals.^[21,22] However, Sicherer precises:^[17] "These strategies represent only one of many possible courses of action and would require alterations in approach depending on numerous factors, including severity of previous reactions, clinical judgment, nutritional needs and patient preferences. Foods that are clinically tolerated should not be removed from the diet". When the Italian,^[5] Australian^[3] and Israeli^[4] clinical series (a little less than 150 cases total) were published, it was observed that the occurrence of FPIES caused by many different foods in the same child ('multiple FPIES') was infrequent; in our experience this event happens at most in 2% of cases. In light of this recent information, we think that the probability of a multiple FPIES is too low to suggest multiple dietary restrictions for all children with FPIES to their debut.

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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].