November 2013 Issue

Food Protein–Induced Enterocolitis Syndrome — The Hidden Scourge of GI Food Allergies
By Judith C. Thalheimer, RD, LDN
Today’s Dietitian
Vol. 15 No. 11 P. 12

A mother’s 6-month-old son eats rice cereal for the first time. Shortly after, he lies limp in her arms as his skin turns blue. Another mom’s 3-month-old daughter, who was thriving on an exclusively breast milk diet, begins supplemental formula for the first time. Hours of vomiting and diarrhea follow as well as signs of severe dehydration.

These infants were tested for food allergies, but the results came back negative. It turns out that both children had a rare food allergy called food protein–induced enterocolitis syndrome (FPIES), for which there’s no laboratory test.

FPIES Explained
It’s estimated that food allergies affect 6% of children in the first two years of life. About 40% of these children have non–immunoglobulin E (IgE)-mediated reactions, mostly involving the gastrointestinal (GI) tract.1 FPIES is one of these non–IgE-mediated GI food allergies, which also includes food protein–induced proctocolitis and food protein–induced enteropathy.2

When dietitians think of a food allergy, they typically picture an immediate reaction, with symptoms such as hives, itching, wheezing, swelling, and possibly anaphylaxis. These rapid-onset symptoms are a result of the release of histamine and indicate IgE antibodies in the bloodstream rushing to attack a supposed invader.3 Allergists can use skin-prick testing, oral challenges, or blood tests to diagnose these IgE-mediated allergies.4

Unlike these more commonly recognized allergies, non–IgE-mediated reactions associated with FPIES involve different, less understood immune mechanisms. Onset of symptoms is delayed by several hours from ingestion of the allergen, making identification of the trigger difficult. There’s no rise in IgE levels in the blood, making existing allergy tests useless. Nevertheless, these conditions are reproducible, consistent, specific immune responses and are therefore considered allergies as opposed to intolerances (lack of a particular enzyme necessary for digestion) or sensitivities (an unpleasant reaction to foods that doesn’t involve the immune system).3

Since standard allergy testing can’t be used to diagnose FPIES and related conditions, clinicians must rely on recognizing symptoms. Unfortunately, typical presenting symptoms of FPIES, such as repetitive vomiting, diarrhea, and dehydration, mimic GI viruses. More severe FPIES symptoms of lethargy, low blood pressure, and pale or blue skin easily are mistaken for sepsis. In the long term, undiagnosed FPIES can result in failure to thrive, hypoalbuminemia and, in rare instances, reintroduction of the offending food can cause shock.1,5

“Health professionals need to understand that FPIES isn’t black and white,” says Joy Meyer, DTR, cofounder and executive board chair of the FPIES Foundation. “There’s a spectrum of symptoms, and each case needs to be treated individually. Many of the things we hear about in support groups for FPIES families aren’t even mentioned in the literature.”

The absence of diagnostic tests for FPIES and related conditions, combined with a general dearth of knowledge in the nonspecialist community leads to underdiagnosis, unnecessary testing, prolonged suffering of infants and young children, and frustrated, frightened families.

Best Tool for Diagnosis
The gold standard for diagnosing non–IgE-mediated food allergies (NFAs) is resolution of symptoms when the offending food is removed from the diet. Typically, all GI symptoms resolve three to four weeks after implementing the elimination diet. The diagnosis is confirmed if symptoms return when the suspected allergen is reintroduced.2 Identifying allergens can be difficult, since reactions can be delayed for hours after ingestion.

Dairy and soy are the most common triggers of FPIES and other NFAs. Since standard formulas are dairy or soy based, formula-fed babies will become ill from the start. Breast-fed infants aren’t entirely protected from FPIES, as dairy and soy proteins in the mother’s diet pass into her breast milk.

The client’s 6-month-old son in the case study above didn’t show signs of allergy until his first taste of rice cereal, though. “Grains that are typically considered safe first foods for infants, such as rice and oats, are triggers in many FPIES patients I’ve seen,” says Bailey Koch, RD, CSP, LD, president of Atlanta Pediatric Nutrition and a member of the medical advisory board of the FPIES Foundation. “I see reactions to other common grains, such as corn, wheat, and barley; chicken and turkey; and various vegetables, including peas, green beans, sweet potatoes, and squash. While fruits usually are safe, I have even treated patients with reactions to apples and bananas.” Rice is known to be a common FPIES trigger, and children who react to rice frequently are allergic to multiple food proteins.5

RDs as Huge Assets
Dietitians often are on the front lines of diagnosing NFAs. “As a pediatric nutritionist, I’ve gotten referrals for feeding difficulty or GI disorders that turn out to be FPIES. Sometimes I see children referred by an allergist because they tested positive for one food allergy, but find out they have non–IgE-mediated reactions to other foods,” says Koch, who works as a team with a pediatric gastroenterologist and a pediatric allergist to diagnose and treat FPIES patients.

“In my practice,” she continues, “I figure out triggers then help parents with things such as label reading, food alternatives, and the order of introduction of new foods. The help of a dietitian is essential to make sure the child’s nutritional needs are being met for normal growth and development.”

Koch recommends that nutrition professionals interested in these conditions educate themselves as much as possible about pediatric nutrition and food allergies. “Order of introduction of new foods is particularly critical,” she says. “Children who have too many bad experiences with new foods can become food averse, potentially severely compromising their nutritional intake.”

Need for Greater Awareness
In a 2012 study, author Harumi Jyonouchi, MD, discussed recent advances in understanding the mechanisms and clinical presentations of NFAs.5 “NFA has begun to attract more attention in allergy/immunology and pediatric gastroenterology disciplines,” Jyonouchi wrote, “although awareness of NFA in the general population still remains dismally low.”

The FPIES Foundation was launched to address this lack of awareness. “Our mission is to offer tools for education, support, and advocacy to empower families and the medical community to overcome the challenges of FPIES,” Meyer says.

Non–IgE-mediated GI food allergies such as FPIES once were considered benign conditions easily corrected by avoiding the offending food. But families who have struggled to find help for violently ill infants and children would certainly disagree. The more that’s learned about NFA reactions, the less straightforward they appear to be. New findings are beginning to show a complex interplay of environmental issues such as gut flora and dietary factors affecting intestinal mucosal homeostasis.5 Educated nutrition professionals are an integral part of the health care team needed to accurately diagnose and treat these disorders.

The 6-month-old baby presented in the case study was rushed to the hospital lethargic and unresponsive. After doctors ruled out sepsis, he was referred to several specialists, including an allergist. Although his allergy tests were negative, the mother felt strongly that the rice cereal was to blame and refused to introduce any solid foods. The family was sent to a pediatric nutritionist to deal with “feeding issues.”

The nutritionist worked extensively with the family to introduce new foods in a safe, controlled way and to construct family-friendly meal plans that avoided even trace amounts of rice products. The child outgrew his allergy by the age of 3.

The 3-month-old’s pediatrician suspected a reaction to the dairy-based formula and suggested soy-based instead. When the child began vomiting several hours after trying the soy formula, her mother contacted a lactation consultant and negotiated with her employer to pump breast milk several times per day while at work.

With the advice and support of a dietitian, the mother removed dairy and soy from her own diet to avoid passing any proteins to her daughter through her breast milk. When the mother introduced her daughter to solid foods, she gave her no dairy or soy, and the child had no adverse reactions to other foods. A food challenge at the age of 18 months showed that the daughter had outgrown her dairy and soy protein allergy.

Both children are healthy and doing well.

— Judith C. Thalheimer, RD, LDN, is a freelance nutrition writer and community educator living outside Philadelphia.


1. Sampson H. Non-IgE mediated food allergy: new diagnostic challenges. J Pediatr Gastroenterol Nutr. 2004;39:S549-S550.

2. Sampson HA, Sicherer SH, Birnbaum AH. AGA technical review on the evaluation of food allergy in gastrointestinal disorders. American Gastrological Association. Gastroenterology. 2001;120(4):1026-1040.

3. Woznicki K. Food allergies: 5 myths debunked. WebMD website. Updated May 21, 2010. Accessed August 29, 2013.

4. Allergy testing: tips to remember. American Academy of Allergy, Asthma and Immunology website. Updated 2013. Accessed September 3, 2013.

5. Jyonouchi H. Non-IgE mediated food allergy — update of recent progress in mucosal immunity. Inflamm Allergy Drug Targets. 2012;11(5):382-396.