Cow’s milk tops list of most common FPIES triggers
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Key takeaways:
- Most patients only had one food protein-induced enterocolitis syndrome trigger, though many had a co-association of triggers.
- Accurate FPIES diagnoses at first contact were seen in about half of patients.
Peanut and egg were found to be new triggers for food protein-induced enterocolitis syndrome, and milk and oat surpassed rice as the most common triggers, according to a study in The Journal of Allergy and Clinical Immunology: In Practice.
“FPIES is a non-IgE food allergic reaction presenting with delayed severe vomiting, diarrhea and dehydration,” Sara Anvari, MD, MSc, associate professor in the division of allergy and immunology and director of clinical trials in the food allergy program, FPIES clinic and penicillin allergy clinic at the Baylor College of Medicine and Texas Children's Hospital, told Healio.
“FPIES typically starts within the first year of life,”. she continued. “Currently, there are no diagnostic tests for FPIES, and the immune basis of FPIES is poorly understood.”
Anvari said patients with FPIES reported a reduced quality of life due to disease burden, lack of testing and treatments.
Anvari and colleagues examined and compared their recent FPIES cohort (2018 to 2022) with a previous FPIES cohort (2015 to 2017) to identify changes occurring in the age of onset, presentation, duration and common food triggers of FPIES. They also examined whether guidelines and practice changes have had any impact on FPIES since 2017.
Methods
This retrospective study reviewed electronic medical records of patients aged up to 18 years with a new FPIES diagnosis between January 2018 to March 2020 from the Texas Children’s Hospital allergy and immunology clinic. A diagnosis of atypical FPIES was founded on clinical history that was consisted with FPIES symptoms and sensitization evidence based on skin prick testing (SPT) or IgE testing. Family history on seasonal allergies, food allergy, eosinophilic gastrointestinal disease, atopic dermatitis, asthma or FPIES was also documented.
Results
Among the 210 patients included in the analysis, most were male (54.3%), white (73.8%), and non-Hispanic (71.4%) and had private health insurance (77.6%). Researchers estimated FPIES incidence within their clinic’s network as 0.53%.
The group’s comorbidities included eczema (47.6%), allergic rhinitis (18.5%), IgE-mediated food allergy (16.7%), asthma (12.4%), food protein-induced allergic proctocolitis (6.2%), and eosinophilic gastrointestinal disease (1%). Drug allergy was listed by six (2.9%) patients, and a family history of atopy was found in 63.3% of patients.
The age of the index FPIES reaction had a median of 6 months (range = 1-168 months; interquartile range [IQR] = 4-8), and the median age at diagnosis was 9 months (range = 1-204 months; IQR, 7-16).
The food allergen with the earliest presentation was cow’s milk (CM) with a median onset age of 5 months (IQR, 7-17.5) and a median age of diagnosis of 9 months (IQR, 7-17.5), whereas shellfish FPIES had a median age of onset of 24 months (IQR, 23-36) and a median age of diagnosis at 30 months (IQR, 29-79).
Researchers found that most patients had an FPIES trigger of CM (35.2%), followed by oat (19%), egg (17.6%), rice (17.6%), avocado (11.4%), and sweet potato (11.4%). Among those that had a CM trigger, 14.9% reported a reaction to baked dairy products while 8.1% of those with an egg trigger reported reactions to baked egg products.
Most commonly, patients only had one FPIES trigger (53.3%) while 27.1% had two triggers and 19.5% had three or more. Among the patients who had reactions to CM, 30% also experienced reactions to soy. A total of 96% of patients who reacted to soy also had reactions to CM.
Among patients with reactions to rice, 33% reacted to oat, and of those who reacted to oat, 30% also reacted to rice. Exactly 50% of patients with wheat reactions also reacted to oat, and 12.5% of those reacting to oat also reacted to wheat. Among patients with reactions to banana, 36% also reacted to avocado, while 33% of those reactive to avocado also reacted to banana.
All the 210 FPIES patients included in the data presented with delayed vomiting 1 to 4 hours after food allergen ingestion. Almost half of the patients (49.5%) also reported lethargy along with vomiting. The other reported symptoms were diarrhea (44.3%), pallor (20.5%), hypotonia (9.1%), dehydration (17.6%), hypotension (2.4%) and hypovolemic shock (2.4%).
A total of 36.7% of the patients presented to the ED for an acute FPIES reaction and 11.4% ended up being hospitalized. Most commonly, patients were treated with ondansetron (24.3%) in the ED for acute reactions. This was followed by oral rehydration treatment in 19.5% of patients and IV fluid resuscitation in 17.1% of patients. Corticosteroids were given to 3.7% of patients and IM epinephrine was given to 2.4% of patients.
FPIES was correctly diagnosed in 54.3% of patients at the initial medical contact for a reaction. The most common diagnoses given at presentation for an acute FPIES reaction were IgE-mediated food allergies (34.3%), unspecified vomiting (31.9%), gastroesophageal reflux/colic (12.8%) and sepsis (3.3%).
Within an outpatient setting, 167 patients (79.5%) had IgE sensitization testing performed to the FPIES trigger. Among them, 23 patients tested positive to an FPIES trigger, giving an overall IgE sensitization or atypical FPIES rate of 13.8%.
IgE sensitization was found in 25% of shrimp FPIES, 17.2% of egg FPIES and 16.7% of peanut FPIES. The atypical FPIES rate of CM and banana were 13.3%, soy (11.8%), wheat (11.1%), sweet potato (7.1%), avocado (5.9%), and oat at 4%.
“Our findings revealed that cases of FPIES nearly doubled every year since 2018,” Anvari said. “The time between receiving an FPIES diagnosis following an initial reaction had reduced compared to patients diagnosed before 2018. Peanut and egg emerged as new FPIES triggers, and the rates of atypical FPIES (IgE sensitization to the FPIES trigger) had increased since 2018.”
Ondansetron was prescribed to 43.8% of patients for the management of FPIES reactions. An epinephrine autoinjector prescription was given to 20% of patients for an FPIES trigger; among them, 28.6% of patients had evidence of IgE sensitization. Diabetic consultation was given to 49% of patients.
Patients were offered an oral food challenge (OFC) within 12 to 24 months after their last FPIES reaction. Forty-nine OFCs were performed in 37 (17.6%) of patients during the study, and 36 (73.5%) successfully passed.
Challenges were given to CM (n = 9), rice (n = 7) and avocado, egg, oat and sweet potato (n = 4 for each). The highest OFC pass rate at 100% was seen in egg, followed by 89% in CM. The youngest mean age at OFC administration was 30 months for CM, while the oldest median age at OFC was 41 months for avocado. Most underwent one OFC challenge (57.4%).
Trigger resolution was found in 115 (54.8%) of patients, with the median age of resolution being 27 months (IQR, 22-36). Most patients (76%) saw resolution by age 36 months. The highest resolution rates were seen in sweet potatoes (42%) at a median age of 24 months (IQR, 19-48), with 60% resolution at that age. CM had a resolution rate at 28% at a median age of 27 months (IQR, 13-36), with 48% resolution by 24 months.
“The implementation of the 2017 FPIES International Consensus Guidelines has increased awareness about FPIES within the medical community,” Anvari said. “Prior to 2018, we had not observed peanut or egg FPIES at our institution. We hypothesized that the emergence of peanut and egg FPIES at our institution was likely correlated with the increased uptake of the early peanut and egg introduction guidelines for infants. This finding, however, should not halt the clinical efforts in preventing IgE food allergies in high-risk infants.”
Authors noted that were was no statistically significant difference in the age of resolution and the type of food allergen triggers, calling for future research into the subject.
“Our findings should raise the question about identifying the risk factors to developing egg or peanut FPIES and proposing larger multi-center studies to examine these questions further,” Anvari said.
She further added that findings from this study provide insight into the changing landscape of FPIES and the importance of dietetic guidance on high-risk foods in early introduction. Additionally, she said, as FPIES awareness increases, medical providers should provide emergency action plans for their FPIES patients to help caregivers recognize and manage reactions promptly and safely.
“This study will continue to raise awareness about FPIES within the medical community,” Anvari said.
She noted that the study has alrady inspired additional multicenter research initiatives designed to investigate clinical correlates that identify patients who are at risk for developing FPIES as well as how to guide them in early food allergen introduction.
“These research initiatives will aim to further examine clinical correlates associated with the development and resolution of FPIES, which will facilitate guideline updates in the prevention of food allergies such as FPIES,” Anvari said.