FPIES: The 'Other' Food Allergy
FPIES is a potentially severe, non-immunoglobulin (Ig)E, cell-mediated, gastrointestinal food hypersensitivity typically provoked by cow's milk (CM) or soy. Less commonly, it may result from solid food ingestion, such as rice, oat, fruits, or vegetables. Prevalence in the United States is not known. However, a study from Israel determined that in a large birth cohort of over 13,000 infants, 0.34% developed FPIES to milk in the first year of life, comparable to the 0.5% of infants who developed an IgE-mediated milk allergy.
FPIES has different manifestations when the food is ingested in a diet on a regular basis vs when it is ingested intermittently or following a period of avoidance. The case presented above included both chronic and acute FPIES caused by CM protein.
What Foods Cause FPIES?
FPIES is commonly caused by CM and soy proteins in formula-fed infants during the first year of life. Delayed introduction of these foods in breastfed infants may result in a later onset. In extremely rare instances, FPIES due to these foods in the mother's breast milk may develop in exclusively breastfed infants, though although only a handful of cases have been reported to date.
FPIES may be induced by solid foods, with a later age at onset than seen with CM- and soy-induced FPIES, a result of the fact that solid foods are introduced later, typically at 4-7 months of age. Rice is the most common FPIES-inducing solid, followed by oats, barley, chicken, turkey, egg white, green pea, peanut, sweet potato, white potato, corn, fruit protein, fish, and mollusks (in adults). The common triggers in FPIES -- rice, oats, and vegetables -- are generally considered to be hypoallergenic and unlikely to cause IgE-mediated food allergy. Thus, they are typically the first solids introduced into an infant's diet.
FPIES to Multiple Foods
In US studies, up to 50% of children with FPIES were found to react to both CM and soy. In contrast, studies from Australia and Israel reported no patients reacting to both of these foods. The differences may be attributed to a more preselected referral population in the US studies and/or delayed introduction of soy formula to the diet of infants reacting to CM.
About one third of infants with CM or soy FPIES develop solid-food FPIES, commonly caused by rice and oat, the grains typically introduced at weaning. The majority of children with solid-food FPIES react to multiple foods. In fact, 80% of infants with solid-food FPIES reacted to more than one food, and 65% were previously diagnosed with CM and/or soy FPIES.
Diagnosis of FPIES is not straightforward because the child will not have food-specific IgE antibodies to aid in the diagnosis. If a small child or infant presents with repeated episodes of severe emesis, with or without hypotension upon ingestion of the food, and is well when the implicated food is eliminated from the diet, the diagnosis of FPIES can be established on clinical grounds and an oral food challenge (OFC) is not necessary. However, OFCs are recommended if the child has chronic symptoms despite dietary restrictions and is not thriving in order to both confirm the diagnosis and identify the offending foods. OFCs are also necessary during follow-up to determine when a child has "outgrown FPIES."
An OFC for FPIES is considered a high-risk procedure because of the potential for hypotension. It is usually performed with secure IV access in place prior to the beginning of the challenge. During a food challenge, a serving of food is fed over 45-60 minutes, usually in 3 equal portions, followed by a minimum of 4 hours of observation prior to discharge. A complete blood count is obtained at baseline, before the start of the challenge, and again 4-6 hours later only if symptoms develop, because an elevation in neutrophil count of > 3500/mL is one of the diagnostic criteria for a positive challenge. It should also be repeated prior to discharge if symptoms are absent.