January 10, 2024
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Key takeaways:
- The clinic had no reported cases before 2014, but cases more than doubled during the last two years.
- Children with delayed vomiting after peanut ingestion despite prior tolerance may be cases.
Cases of food protein-induced enterocolitis syndrome induced by peanuts increased at a pediatric allergy practice between 2015 and 2023, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Multiple reports describing increases in food protein-induced enterocolitis syndrome [FPIES] cases have emerged since widespread adoption of recommendations to introduce peanut into infant diets early, Mary Grace Baker, MD, MS, and colleagues wrote.
The median age of first peanut ingestion among children in the study was 6 months, and median age for the first reaction was 6.5 months. Image: Adobe Stock
“A few years ago, our group noticed that we were seeing an increasing number of infants with FPIES to peanut (PN-FPIES),” Baker, who is an assistant professor of pediatrics at the Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, told Healio.
“We also observed that many children with PN-FPIES continued to be reactive to peanut, even years after their initial reaction,” Baker continued. “In this study, we aimed to characterize our sample of children with PN-FPIES and describe the natural history of PN-FPIES in this cohort.”
Study design, results
A chart review identified 45 patients (58% boys) with a clinical history of PN-FPIES or a FPIES reaction following an oral food challenge to peanut between January 2015 and April 2023.
Mary Grace Baker
Charts indicated that these patients also had atopic dermatitis (58%), IgE-mediated food allergy (38%) and FPIES due to other foods (18%), with a median of one other food or food group trigger for FPIES (range, 1-2).
With first peanut ingestion occurring at median age 6 months, first PN-FPIES reactions occurred at median age 6.5 months with PN-FPIES diagnosis at age 8 months. Also, 27 patients (60%) tolerated peanut ingestion before the index reaction, including 18 (40%) who tolerated three ingestions or more.
“These results highlight that in a child who presents with signs/symptoms of a possible FPIES reaction to peanut, prior tolerance does not exclude the possibility that FPIES could have developed, especially if weeks or months have passed since the last ingestion,” Baker said.
All 45 patients experienced vomiting, 25 (56%) experienced lethargy, eight (18%) experienced diarrhea and six (13%) experienced pallor. Also, 10 (22%) had visited the ED because of their PN-FPIES reaction.
Clinicians performed skin prick testing on 43 patients, with 79% yielding negative results and a median wheal size of 0 mm (range, 0-6 mm).
When clinicians drew serum IgE for 21 patients, nine (43%) had undetectable peanut specific IgE. The overall median was 0.11 kU/L, with a range of less than 0.1 kU/L to 7.3 kU/L.
Also, 20 patients (44%) participated in 25 FPIES OFCs, including 11 OFCs that generally were used in IgE-mediated allergy assessment and 14 that were used in assessing PN-FPIES resolution.
The patients who participated in the diagnostic OFCs were diagnosed with PN-FPIES after they experienced delayed vomiting following the challenge. When five of these patients had an OFC to assess them for PN-FPIES resolution, they all reacted as well.
Noting that most children outgrow FPIES over time, Baker said that eight children (57%) reacted with delayed vomiting during the OFCs for PN-FPIES resolution, including one patient who also experienced lethargy, despite a median age of 52.5 months (range, 22-120 months) and a median interval of 38 months (range, 17-60) since their last reaction.
“This overall number of OFCs is still pretty small, but these results suggest that the resolution of PN-FPIES may be delayed compared to other FPIES trigger foods,” she said.
The other six patients (43%; median age, 21.5 months) who passed the resolution OFC had not had a reaction for a median of 13.5 months.
Conclusions, next steps
Based on these findings, Baker said that PN-FPIES appears to be increasing.
For example, she said, PN-FPIES only represented less than 2% of cases in one large series of FPIES patients from 2013. Also, PN-FPIES was not even mentioned in a large 2014 cohort study at her institution.
“In our practice, we evaluated no child with PN-FPIES prior to 2014,” she said.
But with a trend toward cases increasing over time and cases more than doubling during the last 2 years of the study period, the researchers called peanut an emerging major trigger.
“As such, it is important to consider the possibility of PN-FPIES in the differential diagnosis of a child presenting after a reaction to peanut,” she said.
Baker noted that FPIES commonly presents in infancy approximately at the time when solid food is introduced into the infant’s diet.
“Although we have much to learn about why and how FPIES develops, it is thought that there may be a window of susceptibility when infants are predisposed to develop FPIES,” Baker said.
Possibly, Baker said, the introduction of potential FPIES food triggers during this period of susceptibility may make a baby more likely to develop FPIES to these foods.
“In 2015, the LEAP study was published, which demonstrated that early introduction of peanut to high-risk infants could help decrease the likelihood of developing IgE-mediated peanut allergy,” Baker said.
This finding led to guidelines that encouraged parents of select infants to introduce peanuts early into their diets as well as widespread awareness about the potential benefits of doing so.
“Interestingly, this coincides with the increase of PN-FPIES, although we do not know if there is a cause-effect relationship,” Baker said.
This increase also indicates a need for larger studies of heterogenous populations to better understand the natural history of PN-FPIES, the researchers continued, as well as a need for allergists and pediatricians to be aware of this increase.
The researchers additionally advised physicians to consider PN-FPIES when there is delayed vomiting after peanut ingestion, even if these children had previously tolerated peanut, while advising families that PN-FPIES may be prolonged compared with other food triggers.
“Since FPIES is a clinical diagnosis, awareness of PN-FPIES is a critical first step for accurate diagnosis,” Baker said. “I think it is important for physicians, care teams and even families to consider the diagnosis of PN-FPIES in a child experiencing delayed vomiting after eating peanut, even if peanut was tolerated a handful of times prior.”
In the short term, Baker said that she and her colleagues will continue to monitor this trend at their institution and in OFC outcome data to better understand the epidemiology and natural history of PN-FPIES.
“On a grander scale, research efforts continue to learn more about the pathophysiology of FPIES in the hopes of identifying ways to better diagnose and manage this condition,” she said.
References:
For more information:
Mary Grace Baker, MD, MS, can be reached at [email protected]
Perspective
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Victoria M. Martin, MD, MPH
These findings are certainly significant. Clinicians at many sites, ours included, are anecdotally seeing this increase in what appears to be PN-FPIES, and it was not necessarily a change we anticipated.
It also seems quite likely that these increases and recommendations for early introduction of peanut into infant diets are related. FPIES is a condition often of the very young. Before 2014, few children were being exposed to peanut during those ages. Thus, it makes sense that earlier exposure would be associated with incidence of PN-FPIES going up, in retrospect.
But I do not think these increases change the importance of early introduction. As this paper shows, many children outgrow FPIES relatively quickly, compared with IgE-mediated peanut reactions, which this early introduction aims to prevent.
Still, physicians need to be aware of this entity and how to distinguish an IgE-mediated from an FPIES reaction. We need more mechanistic studies to better understand the pathophysiology behind PN-FPIES and FPIES reactions.
Victoria M. Martin, MD, MPH
Co-director, GI Section, Food Allergy Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General for Children
Associate Program Director, Fellowship in Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General for Children
Assistant Professor in Pediatrics, Harvard Medical School
Disclosures: Martin reports consulting for Harmony Baby Nutrition.
Sources/Disclosures
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Disclosures:
Baker reports receiving research support from DBV Technologies, the Louis and Rachel Rudin Foundation, NIH/NIAID and Pfizer. Please see the study for all other authors’ relevant financial disclosures.
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