Food Protein-Induced Enterocolitis Syndrome (FPIES) is a delayed-onset food allergy affecting the gastrointestinal tract, primarily striking infants and young children. Unlike common immediate allergies, FPIES is not mediated by IgE antibodies; it involves a non-IgE, cell-mediated immune response. This reaction leads to severe gastrointestinal symptoms, such as repetitive vomiting and diarrhea, which are sometimes mistaken for an infection. Recent research suggests FPIES is more common than once believed.
Understanding FPIES Prevalence Rates
Determining the exact global frequency of FPIES has been challenging, but scientific estimates are becoming more refined. The reported cumulative incidence is estimated to range widely from 0.015% to 0.7% in infants across different populations. For example, an Australian study reported an incidence of approximately one in 10,000 infants younger than two years, while studies in Israel and Spain estimated the cumulative incidence between 0.34% and 0.7% in infants. In the United States, prevalence has been estimated at about 0.51% in children and 0.22% in adults.
The wide variation in these figures highlights the difficulty in securing precise, universal statistics. This uncertainty is partly due to a lack of mandatory reporting and the absence of a universally accepted definition for FPIES until recently. Although historically regarded as rare, the latest evidence shows FPIES is more common than previously assumed. The data suggests FPIES is likely the most frequent non-IgE-mediated food allergy worldwide.
Factors Influencing Reported Frequency
The reported frequency of FPIES is significantly influenced by challenges in its diagnosis, often leading to underestimation. The delayed onset of symptoms, typically occurring one to four hours after food ingestion, means the link to the specific trigger food is not always obvious to caregivers or medical professionals. This time lag distinguishes FPIES from immediate-type allergies.
The symptoms are non-specific and can mimic other severe conditions, often presenting as profuse vomiting, lethargy, and sometimes shock. This frequently leads to misdiagnosis as severe gastroenteritis or sepsis. Furthermore, the absence of a simple blood or skin prick test complicates diagnosis, as these tests are typically negative in non-IgE-mediated reactions. Diagnosis relies heavily on observing clinical features and a patient’s history of reproducible symptoms following food exposure.
Definitive diagnosis frequently requires a medically supervised oral food challenge, which is a resource-intensive procedure. When diagnosis is not confirmed in a specialized setting, cases may be categorized incorrectly or remain entirely undiagnosed, particularly among general practitioners who lack awareness of the condition. The lack of a specific international disease code until 2015 also previously hindered accurate data collection and tracking.
Demographics and Susceptibility
FPIES typically presents in infancy, with the age of onset dictated by when the food protein is first introduced into the diet. Acute FPIES is most often seen in young infants between four and six months old, corresponding to the typical introduction of solid foods. Cow’s milk and soy FPIES tend to present earlier, often in neonates, due to their introduction via formula.
While some studies report a slight male predominance (approximately 50% to 60% of cases), the gender difference is not substantial. A family history of atopy is frequently present in children with FPIES. Having a first-degree relative with FPIES is also associated with an increased likelihood of developing the condition.
The most common food triggers vary geographically, but generally include cow’s milk, soy, and grains such as rice and oats. Cow’s milk is the most frequent trigger in many regions, though rice is often the most common single solid food trigger. Most children with FPIES react to only one or two foods, but reaction to multiple food groups is possible.
Contextualizing FPIES Against Common Pediatric Allergies
Understanding the commonality of FPIES requires comparing it to widely recognized IgE-mediated food allergies, such as those to peanut or egg. IgE-mediated allergies cause immediate symptoms like hives or anaphylaxis and are significantly more frequent in the pediatric population. The prevalence of IgE-mediated food allergy to common triggers like peanut and tree nuts is substantially higher than FPIES.
FPIES remains less common than these immediate-type allergies, though it is considered the most common non-IgE-mediated gastrointestinal food allergy. The difference in prevalence is linked to the underlying immune mechanisms. IgE-mediated reactions are immediate, while FPIES is a delayed, cell-mediated response. This fundamental difference often leads to distinct clinical presentations and different rates of recognition.
The estimated pediatric prevalence of FPIES (around 0.5% in the US) is considerably lower than the overall prevalence of IgE-mediated food allergy, which is much higher. This comparison helps place FPIES within the landscape of pediatric food hypersensitivities. While FPIES is not rare, its overall frequency is lower than the more prevalent, immediate-type allergic conditions.