Early recognition, advice can reduce struggle in FPIES

April 13, 2020

Children who struggle with rare food allergies may have multiple food restrictions, with little understanding as to what really helps.

A team of researchers is working to answer questions about a rare allergy to proteins found in certain foods that is widely misdiagnosed and misunderstood.

In a study published in the Journal of Allergy and Clinical Immunology, researchers investigated the symptoms, diagnosis, and conditions surrounding food protein-induced enterocolitis syndrome (FPIES) by interviewing the caregivers of more than 440 children with the condition.

Food protein-induced enterocolitis syndrome is a non–IgE-mediated food allergy impacting the gastrointestinal system. It typically presents with protracted vomiting followed by watery diarrhea 1 to 4 hours after eating a food that triggers the reaction. In severe cases, symptoms also may include lethargy, hypothermia, hypotension, and 15% of cases result in shock, according to the report.

Typically, FPIES is mistaken for other conditions, such as sepsis or infectious enteritis. Diagnosis can be difficult because there is no blood or skin testing available to confirm FPIES, according to the American College of Allergy, Asthma, and Immunology (ACAAI). Instead, diagnosis is made by noting reaction history and whether clinical improvement occurs through strict avoidance of suspected trigger foods.

Study co-author Theresa A. Bingemann, MD, program director of Allergy and Immunology, and associate professor of Pediatrics and Medicine at the University of Rochester, New York, says FPIES can be both “dramatic and frightening” for caregivers because of the lack of understanding about the condition.

“Despite recent advances in food allergy research, current understanding of FPIES, including food triggers and risk factors, remains low. We found that avoiding multiple food groups due to FPIES was more common than previously reported, with over two-thirds of caregivers reporting their children avoided at least 2 food groups due to FPIES,” Bingemann says. “A large proportion of children in our cohort-20.3%-had a first-degree relative with FPIES, and having a first-degree relative with FPIES was significantly associated with the affected child avoiding multiple food groups.”

Parent-reported triggers

The research team sought to learn more about the disease by polling children and parents about triggers and manifestations about the condition.

Children usually begin to display symptoms of FPIES very early, either after the introduction of milk- or soy-based formulas or when solid foods-especially early grains-are introduced. Often, the first sign that something is wrong is poor growth or a diagnosis of failure to thrive, according to ACAAI. The fact that vomiting and diarrhea occur so many hours after exposure makes it difficult to link the symptom to the food. How rare the condition is also contributes to the lack of understanding of FPIES. According to the study, only 0.015% and 0.7% of children are affected. These small numbers mean there is little information on demographics, comorbidities, food triggers, types of reactions, and risk factors, the researchers note.

In this study, half the children were female, and the majority-86.2%-were white. More than half were atopic, with allergies not associated with the body part in contact with the allergen, says study co-author Lisa Bartnikas, MD, an attending physician in Allergy and Immunology at Boston Children’s Hospital and a pediatric instructor at Harvard Medical School, Boston, Massachusetts.

“Over half of children in our study had parent-reported other atopic conditions including allergic rhinoconjunctivitis, asthma, atopic dermatitis, and immunoglobulin (Ig)E-mediated food allergy,” Bartnikas says. “Pediatricians should be aware of this and ask about relevant symptoms periodically. It is important to be aware that FPIES and IgE-mediated food allergies can co-exist in the same patient, and IgE-mediated food allergy was reported in over a quarter of children in our study. If there are concerns for food allergy in a patient, pediatricians should ask about symptoms of both FPIES and IgE-mediated food allergy.”

In addition to the 54.8% of children in the study who were affected with atopy, 47.4% of their parents were affected as well. Other IgE-mediated food allergies besides FPIES were present in about a quarter of the study group, and 2.5% of parents also had been affected by FPIES. Most of the affected parents were mothers, according to the report. Another familial trait noted was that 8.9% of families had more than one child affected by FPIES. Overall, 20.3% of children in the study had a first-degree relative with FPIES, the report notes.

Avoidance of certain food groups because of FPIES

The study found that the median age of the participants was 2 years, and most of them-60%-avoided grains. Other foods commonly avoided in the children with FPIES were cow’s milk (52.4%), followed by 42.7% avoiding vegetables, and 38% avoiding fruits. Among fruits avoided, avocados were most common, according to the report, and those who avoided avocado usually avoided bananas, too.

Most children in the study avoided at least 2 food groups because of FPIES, the authors note. Multiple food group avoidance was increased in children who also had a first-degree relative with FPIES. Roughly 20% of the children in the study had first-degree relatives with FPIES, according to the researchers.

“Our study revealed a higher percentage of children with multiple food FPIES than has been previously reported and the most common fruit avoided due to an FPIES reaction was avocado, which was previously thought to be a low-risk food. We also found that avoiding avocado was associated with increased likelihood of avoiding banana,” Bartnikas says. “These findings may reflect the self-reported nature of our study, the fact that caregivers who observed an FPIES reaction to one food, then tried low-risk foods, or a new emerging allergen in FPIES. It is important to recognize that FPIES reactions can be seen with many different foods, even if they were not previously reported.”

Whereas grains overall were most commonly associated with FPIES reactions, the study team uncovered more details. Oat, rice, and wheat were the most commonly avoided grains, according to the report. Avocado, banana, and apple were the most commonly avoided fruits-even though avocados have been deemed a low-risk food. Both bananas and avocados are foods that are introduced early in the solid foods cycle, and the research team says more research is needed to determine why these foods are triggering reactions. Other fruits identified in the study that require further investigation as to whether they are over-avoided or have some role in FPIES reactions include blueberries, strawberries, coconuts, nectarines, honeydew, and cherries. In the vegetable category, sweet potatoes, peas, and corn were avoided most. Beef, chicken, and pork were the most common meats that were avoided. Most children in the study group avoided 3 food groups, with only a third of the cohort eliminating a single food group. Children with family members who had FPIES were more likely to avoid multiple food groups, the study notes.

Symptoms were reported fairly consistently across the study groups, with 94.3% of children in the study having vomiting within 1 to 4 hours of ingesting an offending food as the most common reaction. Lethargy, pallor, a decrease in activity, and diarrhea were other common symptoms. In cases of acute reactions, roughly one-third reported hypotension and another third reported hypothermia. About half of the parents polled reported that their child had met the criteria for a severe FPIES reaction in the past, and 56% reported seeking treatment at the hospital. About 21% of children who sought care at the hospital for severe reactions were admitted, according to the report. When hospital care was required, the study notes that children were most often treated with ondansetron for vomiting, intravenous fluids for hydration, and oral steroids to help control the allergic reaction.

The majority of the participants in the survey were parents, and most reported having an emergency plan written for their child in regard to FPIES. Additionally, the report found that less than half of the children with FPIES attended school or day care, and more than half were kept home over concerns for problems with FPIES.

Bingemann says she hopes the study will offers some answers on FPIES and increase awareness of this condition and the importance of identifying children who struggle with it.

“In FPIES, identifying food triggers and counseling affected families on dietary introduction remains challenging. Our study offers novel insights into the demographics of those affected, association with other atopic conditions, familial predisposition, and reported burden of dietary restriction,” she says. “We hope that the knowledge of the impact of FPIES on caregivers and their children will facilitate early referral to an allergist experienced in FPIES management and this will lead to ‘delabeling’ of some of the allergies if appropriate, increased support and guidance, and improve quality of life.”

References:

1. Maciag MC, Bartnikas LM, Sicherer SH, et al. A slice of food protein-induced enterocolitis syndrome (FPIES): insights from 441 children with FPIES as provided by caregivers in the International FPIES Association. J Allergy Clin Immunol Pract. 2020;pii:S2213-2198(20)30070-30072. doi: 10.1018/jaip.2020.01.030