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.

Micol: The Chameleon FPIES

Since her birth, Micol had taken CM four-times. The first time, when she was ten days old, she vomited twice. Then, three times within the third and fourth months of life, 3 h after the ingestion of 30 ml of formulated milk, the baby started to vomit repetitively and presented with pallor, lethargy and diarrhea. 6−8 h after the symptoms started, Micol was fine. SPTs performed with casein, β-lactoglobulin and lactalbumin were negative, while fresh CM SPT was weakly positive (mean wheal diameter: 4 mm). We diagnosed atypical FPIES and from the age of 8 months, Micol consumed an extensively hydrolyzed formula of casein instead of CM as breast milk was terminated. At the age of 16 months, a year after the last adverse episode, Micol performed and passed an OFC, ingesting 200 ml of CM without showing any symptoms, so we suggested to reintroduce CM into the child's diet. However, after 5 days of ingestion of CM without any other problems except a slight erythema in the perioral region, Micol presented with cough and vomiting 20 min after drinking 200 ml of CM. On the 7th day, 40 min after she finished her CM meal, the child presented with vomiting without coughing, and hives and rash appeared on the anterior surface of the body, which was the skin area that came in contact with vomit. Eating parmesan did not, however, cause symptoms. So, eight days after the first OFC, a second one was performed; SPTs were positive for fresh CM (mean wheal diameter: 5 mm), β-lactoglobulin (mean wheal diameter: 3 mm) e lactalbumin (mean wheal diameter: 4 mm), while the one with casein was negative. Micol consumed 220 ml of CM in one dose; some hives showed on the perioral area where some drops of milk dripped. 20 min after the child finished the CM meal, she presented with cough and vomiting; hives and erythema appeared also on the body surfaces that came in contact with vomit. In conclusion, in Micol's case, we observed a shift from FPIES to an IgE-mediated generalized reaction,^[11] where, however, the involvement of the GI tract remains important. This means that Micol was cured of FPIES – that is, she no longer presented symptoms compatible with FPIES when she ate CM again. Only a few days later the symptoms of IgE-mediated allergy appeared. And before 16 months of age, symptoms compatible with an IgE-mediated form had never presented. The two clinical expressions have never been contemporaneous. Similar stories were also reported by Katz et al.^[24] and Kessel et al.^[25] Micol's story can support, according to us, the hypothesis that there are different phenotypes of FPIES; in some cases the role of specific IgE becomes more important. But we want to emphasize once again that there is controversy surrounding this idea and mention that some researchers may not agree with this concept.

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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].