Food Protein-Induced Enterocolitis Syndrome (FPIES) is a serious, delayed food allergy that primarily affects the gastrointestinal system, most often seen in infants and young children. Unlike the immediate, hives-and-swelling-type allergies, FPIES is classified as a non-immunoglobulin E (non-IgE) mediated immune reaction, meaning it does not involve the antibodies typically measured in standard allergy tests. Diagnosing FPIES presents a challenge because there is no single, simple blood or skin test that can definitively confirm the condition. The specialized approach to diagnosis relies heavily on a detailed medical history and, ultimately, a closely supervised procedure to confirm the link between the food and the reaction.
Recognizing the Clinical Presentation
The initial step in diagnosing FPIES is establishing a high index of clinical suspicion based on the patient’s symptoms and the timing of their reactions. The hallmark of an acute FPIES reaction is the characteristic delayed onset, with symptoms typically beginning between one and four hours after the ingestion of the trigger food. This delay is a major reason the condition is often initially misdiagnosed as an infectious gastrointestinal illness or “stomach bug”.
The specific symptoms are almost exclusively gastrointestinal, usually beginning with profuse, repetitive vomiting, which can become projectile. This severe fluid loss can rapidly lead to dehydration, noticeable pallor (paleness), and a significant decrease in energy, known as lethargy. While vomiting is the most common symptom, diarrhea may also develop, often occurring within five to ten hours after the exposure.
In the most severe acute cases, the resulting dehydration and fluid shifts can lead to hypovolemic shock, requiring immediate emergency medical intervention. Patients are typically well and symptom-free in between these acute episodes, which helps to differentiate FPIES from chronic gastrointestinal diseases. Chronic FPIES is a less common presentation that occurs with the daily or frequent ingestion of a trigger food, such as a formula.
Chronic FPIES presents with milder, intermittent vomiting and diarrhea, which can lead to poor weight gain and failure to thrive in infants. Symptoms resolve within three to ten days once the offending food is completely removed from the diet. Because of the non-specific nature of these chronic symptoms, a thorough medical history documenting the relationship between food intake and clinical signs is the critical starting point for an accurate diagnosis.
Distinguishing FPIES from Other Allergies
The complex nature of FPIES means that the standard tools used for most food allergies are ineffective, complicating the diagnostic process. Most common food allergies, such as those to peanuts or shellfish, are IgE-mediated, meaning they involve the production of Immunoglobulin E antibodies that cause immediate reactions. These immediate reactions typically present as hives, swelling, or difficulty breathing, usually within minutes of eating the food.
FPIES is a non-IgE-mediated, cell-mediated disorder, meaning the immune reaction is driven by different types of immune cells, primarily T-cells, rather than IgE antibodies. Therefore, the results of standard skin prick tests and IgE blood tests for the suspected FPIES trigger food are typically negative.
The failure of these standard tests to identify FPIES means that a negative allergy test result cannot be used to rule out the condition. This fact is a major point of confusion for many parents and general practitioners, often leading to a delayed diagnosis. A small percentage of patients have “atypical FPIES,” where they present with the classic delayed FPIES symptoms but also have detectable IgE antibodies to the trigger food.
Therefore, the diagnosis of FPIES is often a diagnosis of exclusion, where physicians must first rule out other possible conditions that share similar symptoms, such as infectious gastroenteritis, metabolic disorders, or other non-allergic causes of vomiting and diarrhea. The lack of a simple biomarker necessitates a more intensive, direct method to confirm the diagnosis.
The Supervised Oral Food Challenge
The definitive and most accurate method for diagnosing FPIES is the Supervised Oral Food Challenge (OFC). This procedure involves the controlled reintroduction of the suspected trigger food to confirm that it causes the characteristic FPIES reaction. Because of the risk of a severe reaction, which can involve profound dehydration and shock, the challenge must be conducted in a specialized clinical setting, such as a hospital or a dedicated allergy center.
Prior to the challenge, the suspected food must have been completely removed from the patient’s diet, and the patient must be completely healthy, without any intercurrent illness. The procedure begins with the administration of a calculated dose of the suspected food, which is typically divided into three equal portions.
These portions are given over a short period, often within an hour, and the patient is then monitored closely for a minimum observation period of four hours after the final dose. The total amount of food administered is standardized, often based on the patient’s weight, with guidelines suggesting a dose of 0.06 to 0.6 grams of protein per kilogram of body weight. The medical team watches for the onset of repetitive vomiting, lethargy, or pallor, which confirms a positive diagnosis.
If a reaction occurs, treatment is initiated immediately, which often includes the use of IV fluids to rapidly correct dehydration and the administration of the antiemetic medication ondansetron to stop the vomiting. In cases of a severe reaction, steroids may also be necessary. The supervised OFC is considered the gold standard because it provides a definitive answer while mitigating the risk of a life-threatening event.