FPIES (Food Protein-Induced Enterocolitis Syndrome)

What is FPIES (Food Protein-Induced Enterocolitis Syndrome)?

FPIES is short for "Food Protein-Induced Enterocolitis Syndrome" and is a type of food allergy.

However, the mechanism is different from common food allergies (the type that causes hives or difficulty breathing). In FPIES, a strong reaction primarily occurs in the digestive tract (stomach and intestines) after consuming specific foods.

Symptoms

after eating the food that caused it 1 to 4 hours later You will experience the following symptoms:：

  • Repeated severe vomiting(Most characteristic symptoms)
  • To look pale
  • to become sluggish
  • My body temperature is dropping.
  • In severe cases, blood pressure can drop, leading to shock.
  • Diarrhea may also occur 4 to 6 hours after vomiting.

Unlike common food allergies, hives, skin rashes, and difficulty breathing are not typically seen.

Prevalence rate

  • FPIES was once considered very rare, but recent studies suggest 0.015–0.71 TP3T for infants reported to develop
  • In Japan's large-scale birth cohort study (Echofil Study), the prevalence based on parent reports 0.69%the prevalence diagnosed by physicians 0.06% It was.
  • In reality, more babies may be experiencing FPIES, but it is thought to be often overlooked because the symptoms are easily mistaken for gastroenteritis or sepsis.

recently increasing

The number of FPIES reports is increasing globally. There are two possible reasons for this:

  1. Increased awarenessIn 2017, international diagnostic guidelines were published, enabling physicians to correctly diagnose FPIES.
  2. Early introduction of complementary foodsIn recent years, early introduction of allergenic foods such as eggs and peanuts has been recommended for the prevention of IgE-mediated food allergies. In Japan, the Ministry of Health, Labour and Welfare's complementary feeding guidelines were revised in 2019, recommending the early introduction of eggs. It has been pointed out that this early introduction period may overlap with the "window of susceptibility" during which FPIES is more likely to occur.

Peak age

  • The peak onset is 4-7 months after birth.is
  • A child with 95% By the time they are 1 year old You experience the first symptoms.
  • FPIES due to cow's milk often occurs relatively early (3-4 months of age), while FPIES due to solid foods (eggs, fish, etc.) often appears after the introduction of solid foods (5-7 months of age).
  • There is almost no gender difference.

Common food ingredients in Japan

  • Chicken eggs (including yolks)
  • Milk
  • Soybeans
  • Grains such as rice and wheat

Differences from common food allergies

ItemCommon food allergiesFPIES
MechanismIgE antibodyNon-IgE (Innate Immunity)
Onset timeA few minutes to 2 hours1-4 hours
SymptomsHives and difficulty breathingVomiting, lethargy
InspectionThere are many positivesUsually negative

Can it change to immediate food allergy (IgE-positive)?

FPIES typically yields negative results on common allergy tests (blood tests and skin prick tests). However, it has been reported that approximately one-quarter of children may test positive for IgE antibodies to the causative food during the course of the condition. Particularly when milk is the cause, some patients who test positive for IgE antibodies may transition to a type that exhibits immediate allergic symptoms such as hives.

In FPIES caused by eggs, IgE sensitization has been observed in approximately 9–371 TP3T, and reports indicate that about 411 TP3T of IgE-positive cases involving cow’s milk progressed to immediate-type allergy.Given this background, it is considered important to conduct follow-up evaluations, including assessment of IgE antibodies, even in cases diagnosed with FPIES.

Will it be cured (resistance acquisition)

FPIES often improves naturally with growth, but the timing varies depending on the causative food. It is said that many cases develop tolerance to milk and soy by around 3 to 5 years of age.
On the other hand, if fish are the cause, it may take 5 to 10 years or more for improvement.
Regarding eggs, it is generally said that tolerance is acquired by around age 4 in many cases, but it is important to note that there are significant individual differences.

How to respond

Daily management

When diagnosed with FPIES, the basic treatment is to completely eliminate the causative food for a certain period. Generally, elimination for about 12-18 months from the last symptom onset is recommended.
Unlike IgE-mediated allergies, FPIES is not typically treated with an epinephrine auto-injector (like an EpiPen) because it is not effective. It is also important to pay attention to nutritional balance and seek professional nutritional guidance as needed.

If the causative ingredient is egg yolk/egg white

Egg yolk and egg white are not the same. In FPIES, instead of broadly saying "egg allergy,"It is important to consider egg yolk and egg white as separate causative ingredients.between 27 and 36 weeks of pregnancy.

Egg yolk FPIES and egg white FPIES are separate conditions.

  • Egg yolks and egg whites contain different proteins, respectively,They might react separately.
  • Actual research has also reported these figures separately: egg yolk as the cause: 32.91 TP3T; egg white as the cause: 20.51 TP3T.
  • It doesn't necessarily mean "all eggs are bad" (Metbulut AP et al. Int Arch Allergy Immunol. 2022)

The yolk is often the sole cause.

In Japan, egg yolk is introduced first for baby food, so FPIES is often triggered by egg yolk alone. is considered

Egg whites can sometimes be eaten.

In a study, children who reacted to egg yolk tried egg whiteI was able to eat about 881 TP3T without any problems.It has been reported that (only 12% tested positive). Egg yolk and egg white areIt is not always necessary to remove them simultaneously.(Ocak M et al. Allergy Asthma Proc. 2021)

However, in actual practice, we often instruct people to "eliminate all eggs."

In theory, they are considered separately, but in reality, the yolk and egg whiteComplete separation is difficult.Even with a small amount of contamination, there's a possibility of symptoms appearing. Due to the difficulty in managing this in home cooking and school lunches, prioritizing safety,Once the entire egg is removed, it will be cleared after confirmation by a medical institution.This is a commonly used method.

Summary

  • Yolk and egg whiteEvaluate separately
  • It's not always necessary to "eliminate all eggs."
  • However, in real life, it's often completely removed for safety reasons.
  • Reintroduction is essentialConfirmed by oral food challenge (OFC) at a medical institution

How to respond to FPIES symptoms

If vomiting repeatedly occurs after consuming a suspect food and the person is listless, seek immediate medical attention.
The cornerstone of acute FPIES treatment is hydration, and intravenous fluid replacement may be necessary.

Reintroduction (Confirmation of edibility)

The evaluation of whether causative foods can be consumed again must be performed at a medical institution.
Self-reintroduction at home based on your own judgment is not recommended as it can cause severe reactions.
Generally, an oral food challenge is performed under medical supervision 12-18 months after the onset of the last symptom to confirm safety.

School/Daycare Response

When children with FPIES participate in group activities, complete elimination of the trigger food is the basic principle.
Also, since symptoms appear 1 to 4 hours after ingestion, you should be mindful of changes in your condition some time after a meal.
It is important to share in advance with caregivers and school staff that the main signs are recurring vomiting, poor complexion, and listlessness, rather than hives or difficulty breathing, and that prompt medical attention is necessary in such cases.

Summary

FPIES is a special type of food allergy that develops through a different mechanism than common immediate food allergies, and it is mainly seen in infants and young children during the weaning period. With appropriate elimination and follow-up at a medical institution, many children acquire tolerance as they grow.
It is important to proceed cautiously with the timing and method of reintroduction, always in consultation with a specialist.

References

Anvari S, Gupta M, Nicolaides R, et al.
The Evolution of Food Protein-Induced Enterocolitis Syndrome (FPIES): Global Trends, Emerging Triggers, and Natural History.

Caubet JC, Ford LS, Sickles L, et al.
Clinical Features and Resolution of Food Protein-Induced Enterocolitis Syndrome: 10-Year Experience.
The Journal of Allergy and Clinical Immunology. 2014.

Nowak-Węgrzyn A.
Food Protein-Induced Enterocolitis Syndrome and Allergic Proctocolitis.
Allergy and Asthma Proceedings. 2015.

Ullberg J, Fech-Bormann M, Fagerberg U.
Clinical Presentation and Management of Food Protein-Induced Enterocolitis Syndrome in 113 Swedish Children.
Allergy. 2021.

Lange L, Gernert S, Berger M, et al.
Different Patterns of Foods Triggering FPIES in Germany.
The Journal of Allergy and Clinical Immunology: In Practice. 2022.