Is it worth already in the first step exceeding the 3‐g protein limit for the oral food challenge for food protein‐induced enterocolitis syndrome?

To the editor:

Food protein‐induced enterocolitis syndrome (FPIES) is a non‐immunoglobulin E‐mediated food allergy that is characterized by repetitive vomiting within 1–4 h of eating the trigger food and may be associated with lethargy, pallor, and diarrhea. The diagnosis is in most cases anamnestic. ¹ In a few cases, it is necessary to perform the oral food challenge (OFC). There are some protocols for the OFC methodology that propose different ways of dividing the total amount of challenge food. ¹ , ² , ³ On the other hand, there is an agreement in following the indications provided by the International Consensus Guidelines (ICG) regarding how to calculate the total dose to administer. ¹

The ICG recommends “… not to exceed a total of 3 g of protein … for an initial feeding”, and “When a very low dose of food protein is administered and there is no reaction, some experts advocate that the patient ingest a full age‐appropriate serving of the food. ¹ ” In this regard, Bird et al., ⁴ in the position paper on OFC of the American Academy of Allergy, Asthma, and Immunology specify: “When a very low dose OFC is performed and tolerated, a second OFC with a higher dose (e.g., 3 g of food protein) is to be undertaken within 2–3 h of the first feeding before declaring the child is no longer reactive to the food of concern.”

These two important papers give us the impression that 3 g of protein of the challenge food is a sufficient quantity to perform an OFC for FPIES, at least for the majority of experts. ¹ , ⁴ Therefore, a child who does not have adverse reactions after ingesting the above quantities of protein from the challenge food can be considered tolerant. A case we have observed raises doubts about this aspect.

A 7‐year‐old female patient received an anamnestic diagnosis of fish FPIES at the age of 1 year. In fact, between 10 and 11 months of age the patient presented with 3 acute episodes fully compatible with the diagnosis of FPIES according to the ICG criteria, ¹ after 2 h from the ingestion of cooked place. The patient came to our attention at the age of 6 years, her weight was 28 kg. During the last 5 years she had never ingested fishes, coelenterates, crustaceans, molluscs. We performed a first OFC with a mixture of coelenterates, crustaceans and molluscs. She assumed 30 g of each component, which is 4 g of mussel protein, 5 g of cuttlefish protein, and 7 g of shrimp protein. ⁵ This OFC was passed. A second OFC with plaice was performed 3 months later. The patient took about 50 g of plaice, containing 11 g of protein. ⁵ The patient showed no reaction and the OFC was considered passed. However, 5 days later the patient ingested a portion of pasta with tomato sauce and plaice fillets (from the same package as the one used for the OFC and prepared in the same way), ingesting an unknown quantity of plaice but according to the parents lower than that ingested during the OFC. After 3 h, she presented with a single episode of vomiting with no other manifestations. Since then, she had not ingested sea fish. Another OFC with plaice was performed 3 months later. The patient ingested a total of 130 g of plaice, a normal portion for her age. ⁶ After 3 h from the start of the ingestion she presented with 4 vomiting associated with pallor. After obtaining parental consent, 4 mg of ondansetron was administered intramuscularly and the emesis stopped. Since the last OFC the patient avoids any type of sea fish.

The case we have described offers the opportunity to reflect on the quantities of challenging food that the patient with FPIES has to ingest without presenting adverse reactions in order for the OFC to be defined as passed. The patient during her first OFC ingested about 50 g of plaice, which corresponds to about 11 g of protein, ⁵ beyond the maximum quantity suggested by the ICG which is 3 g of protein of challenge food and had no adverse reactions. ¹ We considered the OFC passed, but the subsequent episode of vomiting occurred at home created some doubts. Some patients need more trigger food proteins to develop an adverse reaction, as Christensen et al. ⁷ reported that in patients with wheat‐dependent exercise‐induced anaphylaxis. This is likely to be true for our patient as well, although this possibility has never been described for non‐IgE‐mediated food allergies, including FPIES. We also believe that the evaluation made by the parents regarding the quantity of plaice ingested by the patient at home, which induced a single vomiting, was inaccurate. We think that the quantity was larger than that ingested during the first OFC.

In conclusion, we propose to increase the quantities of challenge food, by eliminating the maximum limit of 3 g of total protein of the challenge food, ¹ , ² and to administer a dose of challenge food equal to that of a normal portion for age in a single dose. We propose that it is always necessary to test an age‐appropriate portion of challenge food, right at the first step, not only when very low doses of challenge food are tolerated, as suggested by the ICG. ¹ To give an idea of the difference, for the most frequent foods involved in FPIES, Table 1 shows the amounts of food containing 3 g of protein and the normal portions for various age groups.

TABLE 1.

Amounts of food containing 3 g of proteins and normal portions for various age groups

Food	Quantity that contains 3 g of proteins (g)	NP for ages 2–3 years (g) †	NP for ages 4–6 years (g) †	NP for ages 7–10 years (g) †	NP for ages 11–14 years (g) †
Cow milk	91	200 ‡	200 ‡	200 ‡	200 ‡
Hen egg	24	50	50	50	50
Plaice	19	50	60	80	150
Codfish (frozen)	19	50	60	80	150
Codfish	18	50	60	80	150
Shrimp	22	50	60	80	150
Soy	8	30	60	90	120
Rice	45	40	50	70	100
Oatmeal	38	20	30	40	40
Chicken	15	35	45	80	100

The quantities refer to raw food, net of waste. Nutripiatto 2.0 2019 provides two estimates for fish (ages 7–9 years): lean fish (cod, trout, plaice) 130 g and fatty fish (salmon, mackerel) 60 g. ^†Ref. 8. ^‡The cow milk is 200 mL. Abbreviation: NP, normal portion.

We do not believe that this increases the risk of a serious adverse reaction, especially since the use of ondansetron was endorsed. ¹ , ² , ⁹ Patients with specific IgE positive for challenge food should receive a total amount of challenge food equivalent to a normal portion for age, but divided into at least two doses. ³

CONSENT FOR PUBLICATION

Written informed consent was obtained from the children's parents.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Mastellone F, Bersani G, Sinatti D, Gelsomino M, Sopo SM. Is it worth already in the first step exceeding the 3‐g protein limit for the oral food challenge for food protein‐induced enterocolitis syndrome? Pediatr Investig. 2023;7:54–56. 10.1002/ped4.12351