Non–IgE-mediated severe gastrointestinal food hypersensitivity, typically presents in early infancy with repeated vomiting, dehydration, lethargy, metabolic acidosis (even mimicking sepsis). Watery diarrhoea (sometimes with blood and/or mucus) can develop in some cases. The severity is really what makes it worthy of a distinct name, debatable if it is actually distinct from other non-IgE mediated food allergy.
Probably underdiagnosed.
A few unusual features cf type 1 allergy.
The most common offending foods are cow’s milk and soy in young infants; in older infants, there are a range of food triggers including some foods usually not considered allergenic eg rice, oat, chicken, sweet potato! Egg an unusual cause in some countries! Cases in breastfed infants have been reported, even severe hypotension requiring intensive care.
Acute symptoms occur 1 to 5 hours after ingesting the offending food. Lasts up to 24 hours. Not always consistent, which might suggest co-factors important.
In Europe, rare to get multiple food FPIES but in UK/US/Australia about 25% (English speaking!?).
Diagnosis
Diagnosis is based, predictably for a non-IgE condition, on clinical history and food challenges. Leucocytosis and methaemoglobinaemia are associated but low specificity/sensitivity.
2017 Consensus out of date but diagnostic criteria still used –
- Major – vomiting at 1-4 hours in absence of type 1 skin/resp symptoms.
- Minor – at least 3 minor criteria eg second episode of repetitive vomiting after same food; extreme lethargy; hypotension; need for hospital care or IV fluids; etc
Probably mild, mod and severe! Proposed BIO-FPIES criteria includes abdominal pain, nausea, increase in neutrophil count (but 3 points for second episode of repetitive vomiting after same food).
Phenotype switching
Egg and nut FPIES often go on to develop IgE sensitisation (about 20%), less for others. Of those, about 30% of milk FPIES will switch to type 1 phenotype, 15% for egg, less for other foods. But overall, unlikely to make much of a difference to care (and doesn’t help predict resolution).
Management
No role for antihistamine/adrenaline!
Family support at www.fpiesuk.org.
For introducing weaning foods, when known FPIES to one food, start with low risk foods, supervise common triggers eg rice/egg.
Challenge
Challenge is necessary to decide whether things are getting better or not. Consensus is that 12-18 months after last reaction is a good balance between chances of things being better, and risk of causing severe reaction.
50% milk/soya resolve by age 3-4, more like 4-5 years for other foods.
Traditional protocol is 0.3g/kg protein, divided into 3 doses over 30 mins. But unrealistic for low protein foods eg fruit. And doesn’t really make sense to split dose when you don’t expect a reaction for hours (but risk of switch to type 1 allergy for egg/nuts).
2 day protocol (25% portion then whole portion next day) had less severe reactions.
25-30% of age appropriate portion triggers reaction in most children. [Baked???] Over 50% react after at least 2 hours.
Beaudoin 2024 has home challenge protocol but brave…
[BSACI FPIES grand round – Marta Vazquez-Ortiz (Imperial/St Mary’s, BIO-FPIES research network)] [2025 Shaker shared decision making] [2024 Anvari]