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.

Sometimes You Need to Be Lucky – Bridget's Story

Since her birth Bridget had almost always been breast-fed; she drank cow's milk (CM) formula only during the first week after birth and at the 45th day of life, without showing any adverse reaction. When she was 4 months old, Bridget drank 120 ml of CM formula and then fell asleep for approximately 90 minutes. A few minutes after she woke up, she started to vomit repetitively and became hyporeactive, pale, hypotonic and so sleepy that her parents could not wake her up completely. Worried about her condition, Bridget's parents drove her to the nearest first aid station, where doctors monitored the baby's vital signs, including oximetry, blood pressure and heart rate, and found they were normal. A few hours later Bridget felt better and acted as though nothing unpleasant had happened. Doctors interpreted this episode as a vagal reaction associated with vomiting and suspected a probable diagnosis of gastroesophageal reflux disease (GERD), on the basis of the clinical history which reported sleep difficulties and opisthotonos. Therefore Bridget returned home with the suggestion of a gastroenterological consultation. At the end of the same day, she had a huge evacuation of liquid and acrid-smelling feces. Following the doctor's suggestion Bridget went to the pediatric gastroenterologist. He told Bridget's mother that her child had no gastroenterological problem and that she did not need to change anything in the baby's diet. In spite of that, Bridget's mother decided that exclusive breast-feeding would have been the safest solution, so she did not feed the child with artificial milk anymore. One day she met a young resident and told her her daughter's story. She was fortunate in that this young doctor attended the pediatric allergic center, so she suspected an allergy and planned a specialist examination for the baby. During the visit, skin prick tests (SPT) were performed and tested negative for CM proteins. An oral food challenge (OFC) was scheduled and performed in a day-hospital (DH) regimen, one month after the critical episode. During that day, the baby drank 60 ml of CM in one dose, which was half of the quantity that caused the previous reaction. Two hours after the ingestion, Bridget started to vomit and became pale and hyporeactive, but blood pressure was normal. These symptoms continued for 4 h and blood pressure decreased, especially the diastolic parameter, to below the physiological range (81/35 mmHg). The child received intravenous (iv.) fluids, hydrocortisone and intramuscular (im.) epinephrine. Six hours after CM ingestion Bridget was fine and returned home with the diagnosis of food protein-induced enterocolitis syndrome (FPIES) caused by CM, and the young resident's suspicion was confirmed. Bridget had to eliminate CM from her diet and, in case of lack of breast milk, she would have to replace it with a extensively casein-hydrolyzed formula. It was also suggested to perform two other OFCs in day-hospital regimens. The first one had to be performed soon with a mixture of cereals, legumes (including soy) and poultry, and the second at the age of 18 months with CM, to verify the possible achievement of tolerance.

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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].