FPIES is a rare non-IgE mediated food allergy triggered by the ingestion of certain food proteins. The symptoms are solely gastrointestinal, vomiting with or without diarrhoea leading to hypotension and lethargy [
FPIES is diagnosed on the basis of history and typical symptoms that improve with avoidance of the culprit food. Oral food challenge (OFC) remains the gold standard of diagnosis [
This is a case history of a two-year-old boy who presented to a Paediatric Allergist at six months of age following three episodes of severe reaction to cow’s milk at various stages.
The infant was born by normal delivery following an in vitro fertilization pregnancy and weighing 3.2 kilograms. He was exclusively breast-fed since birth with the mother consuming a normal diet inclusive of dairy, soy, and egg. The infant first direct exposure to cow’s milk was at the age of four months when he was fed a cow’s milk formula feed. Two hours following this feed, he developed profuse vomiting, which lasted for an hour. He then developed lethargy and an unusual deep sleep for several hours following this episode and it was difficult for him to rouse from sleep. The episode resolved after he had slept for a long time. He was managed at home by parents and taken to primary care practitioner the following day.
This reaction was reproduced again at the age of five months when he was fed a different cow’s milk formula feed. At the age of six months, when given a baby porridge containing cow’s milk, a similar reaction was noticed. There was no associated diarrhoea with either of the episodes and stools were otherwise normal.
He had been weaned onto solids at the age of six months and tolerated various products such as eggs, fish, wheat, rice, oats, beans, lentils, poultry, and sweet potato without any problems. He did not have any symptoms suggestive of gastroesophageal reflux.
The infant also developed eczema at the age of three months, which was initially treated with mild topical corticosteroids followed by a brief period of usage of potent corticosteroids. He did not have any signs of asthma, allergic rhinitis, or any other allergies. Mother had eczema and an immediate egg allergy as a child. Father had eczema when he was young.
A diagnosis of FPIES to cow’s milk protein was made on the basis of history, clinical examination, and skin prick testing as shown in Table
Skin prick testing at six months of age.
Allergen being tested | Size of wheal (in millimetres) | Allergen being tested | Size of wheal (in millimetres) |
---|---|---|---|
Positive control (histamine) | 3 | Negative control (normal saline) | 0 |
Cow’s milk | 0 | Egg | 0 |
Soy | 0 | Wheat | 0 |
Shrimp | 0 | Peanut | 0 |
Hazelnut | 0 | Sesame | 0 |
Cashew nut | 0 |
Parents were thereafter advised to avoid any form of cow’s milk products in his diet. Mother was advised to continue breast-feeding if she wished to without the need to exclude dairy in her diet. At the age of nine months, he was commenced on an extensively hydrolysed formula milk as mother wanted to discontinue breast-feeding.
At the age of twelve months, he had an OFC to soy milk in hospital, which he passed. He was then transitioned from EHF to soy milk.
At the age of 2 years and 6 months, the child was challenged with fresh cow’s milk. This was done as a high-risk OFC in hospital with an intravenous cannula placed before the beginning of the procedure. The protocol used for OFC to cow’s milk in hospital to check if tolerance had developed is elaborated as follows [
He was given cow’s milk in two stages:
Observe the child for 45 minutes and do a full set of observations (blood pressure, respiratory rate, pulse, oxygen saturations, PEFR (if applicable), and chest auscultation) and clinical assessment every 15 minutes. If there was no reaction after 45 minutes, proceed to the next stage.
Observe the child for 4 hours. For the initial hour do a full set of observations (blood pressure, respiratory rate, pulse, oxygen saturations, PEFR (if applicable), and chest auscultation) and clinical assessment every 15 minutes. For the remaining 3 hours do a full set of observations and clinical assessment every 30 minutes.
The underlying pathophysiology is not well understood and is thought to be a cell mediated food hypersensitivity [
Current understanding is that ingestion of food allergens causes T cell activation and local inflammation and hence leads to increased intestinal permeability and rapid fluid shifts and causing typical symptoms of FPIES [
There is some suggestion that this inflammation may be mediated by TNF-
Leucocytosis with left shift is also a common finding in patients with acute FPIES [
There are two types of FPIES described in literature, acute and chronic [
The most common offending foods are cow’s milk followed by soya [
A large retrospective study in America showed cow’s milk (67%) as the most common trigger for FPIES followed by soya (41%) and then followed by grains (34.6%) and egg (11%) [
Apart from cow’s milk and soy, other foods reported to cause FPIES are rice, grains (oat, barley, and wheat), poultry (chicken and turkey), legumes (green peas, lentils, string beans, and peanut), sweet potato, squash, egg white, fruit, white potato, lamb, and fish [
FPIES is a clinical diagnosis [
Powell’s criteria [ Less than 9 months old at initial reaction. Exposure to the culprit food resulting in profuse vomiting and lethargy and/or diarrhoea within 4 hours. Symptoms limited to the gastrointestinal tract. Elimination of the culprit food from the diet resulting in resolution of symptoms. An OFC or isolated reintroduction of the culprit food eliciting the typical symptoms.
Newly propped criteria have been suggested in a recent review and are listed below [
Repetitive vomiting or diarrhoea within 6 hours of food ingestion. Absence of cutaneous and respiratory symptoms suggestive of an IgE mediated allergy. Removal of causative food which results in resolution of symptoms. Reexposure or a food challenge eliciting the typical symptoms.
Hypotension. Lethargy, pallor, or hypotonia. Negative skin prick test and undetectable specific IgE level. Absence of fever or hypothermia (less than 36 degrees Celsius).
The child in this case had a delay in diagnosis of two months and had multiple presentations to the primary care physician before an allergist finally saw him. This observation is in keeping with the findings of a large UK retrospective study [
Management of acute reactions in FPIES involves treating the episode once recognized. Most episodes will resolve with fluid rehydration and may even be self-resolving [
Steroids (single dose of methylprednisolone) are recommended in cases with more severe symptoms [
Ondansetron has been shown to be effective in the resolution of symptoms in acute FPIES in some studies on a small number of patients during OFC. A complete resolution of symptoms was within 10–15 mins of administering ondansetron (intravenous or intramuscular) [
Long-term dietary management consists of removing the offending food from the diet with careful advice and use of action plans [
It is well reported that most infants with acute FPIES will tolerate breast milk from an unrestricted maternal diet. Two large studies have reported that infants with FPIES did not seem to react to allergens in breast milk [
As the diagnosis of chronic FPIES may overlap with other gastrointestinal conditions, no clear link has been established between the symptoms and maternal milk intake when breast-feeding. However if the child is failing to thrive, a trial of exclusion diet for mother under the guidance of a dietician may be recommended [
Some large studies from Australia [
The Australian and American consensus guidelines also recommend EHF for treatment of FPIES [
The choice of formula recommended for IgE mediated cow’s milk allergy is EHF [
The usual age for presentation of FPIES is between 4 and 6 months [
OFC can be used either to establish the diagnosis or to test the achievement of tolerance. However, most clinicians and parents would not be willing to challenge for diagnosis confirmation as the child has usually had a few serious episodes by the time the diagnosis is made.
Various studies have looked at the age of challenging for achievement of tolerance. For cow’s milk, the age at which tolerance was regained is somewhere in the second year of life. One study reported that 60% of children had developed tolerance to cow’s milk at age of 3 years [
FPIES is a high-risk challenge and should be performed in a setting where the resuscitation facilities are present. This would mostly be an in-patient setting. There are several protocols documented for performing an FPIES challenge. The protocol described by Leonard and Nowak-Węgrzyn [
In this case, the local protocol was used to do an OFC which has been written as per guidance by Powell [
Prognosis for FPIES is favourable with overall 85% patients having resolution of their reactions by 5 years of age [
Positivity for food specific IgE remains a poor prognostic marker for outgrowing the hypersensitivity [
To summarise, “FPIES is not an apple pie” and diagnosis and management can be quite challenging. It is a rare condition and is often underrecognized. The patient has usually had multiple presentations before being diagnosed. Diagnosis is clinical with allergy tests often being negative. Once recognized, management involves removing the causal food protein from the diet and this results in dramatic improvement. Breast-feeding is mostly well tolerated and most patients do not react to the food protein in breast milk. The first choice of formula milk for non-breast-feeding infants is EHF. OFCs are important in determining if tolerance to the offending food has developed. For cow’s milk, OFC can be performed after the age of 18 months. This involves giving the food in 2-3 stages with the last stage being an age appropriate serving followed by a period of observation for several hours. Prognosis is usually good but age of resolution varies with populations with a small percentage developing IgE mediated food allergy.
Food protein-induced enterocolitis syndrome
Oral food challenge
Extensively hydrolysed formula
Tumour necrosis factor-alpha
Transforming growth factor-beta
Millilitres.
The authors declare that they have no competing interests.