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A 6-month-old male is brought to ED by his mother with multiple episodes of profuse vomiting after eating lunch. No diarrhoea, fevers or unwell contacts. He is usually a well child and had a normal neonatal period.

He is immunised and otherwise thriving from a growth and developmental perspective. The mother, a nurse, reports that the infant was mottled, pale and lethargic at home but began to pick up whilst being triaged in ED.

What is FPIES?

Food hypersensitivity can be classified into food allergy and non-allergic food intolerances. Food allergy can be further subdivided into IgE-mediated and non-IgE-mediated food allergy.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity that can be severe and lead to shock.

FPIES represents the severe end of the spectrum of food protein-induced gastrointestinal disease and most cases present <12 months of age when foods/formula are first being introduced. There is a rarer chronic form of FPIES which occurs with daily ingestion of the food and presents with chronic diarrhoea, intermittent vomiting and failure to thrive. This article refers to acute FPIES.


What are the clinical findings of FPIES?

FPIES is a spectrum and the presentation can vary from mild to severe

It usually occurs in infants less than 12 months of age. Commonly it presents with profuse/projectile protracted vomiting, which has an onset 1-3 hours after ingestion. The child can develop diarrhoea (watery or bloody) about 5-10 hours after ingestion. Other symptoms include lethargy, pallor, haemodynamic instability and hypotension (15% cases), and abdominal distension. Severe cases may progress to hypothermia.

The symptoms of FPIES usually resolve within 24 hours after food ingestion, and the child is well in between episodes with normal growth.


What are the investigation findings in FPIES?

Bloods will show

  • Elevated neutrophil count
  • Thrombocytosis
  • Severe cases can progress to methaemoglobinaemia and acidaemia mimicking sepsis


N.B. the following findings may be present but these tests are not recommended in routine work-up:

  • Stool may be positive for frank or occult faecal blood, leucocytes, eosinophils, and increased carbohydrate content
  • Negative IgE test to the triggering food in most cases
  • Intramural gas and air fluid levels are sometimes seen on abdominal radiograph


What is the proposed pathophysiology of FPIES?

The pathophysiology of FPIES is not well defined and is thought to involve antigen-specific T cells, antibodies, and cytokines as a cause of the gastrointestinal inflammation. This inflammation is thought to cause an increased intestinal permeability and fluid shift into the gastrointestinal lumen.


What are the common food triggers in FPIES?

The most commonly reported triggers are cow’s milk, soy protein and grains (rice and oats). Any food can trigger FPIES including meat, poultry, eggs, vegetables, fruit, legumes and seafood. Approximately 60% of patients react to the first exposure of the food.


How is FPIES diagnosed?

FPIES is a clinical diagnosis based on history, typical clinical findings and improvement following withdrawal of the suspected causal food. There is no current validated diagnostic criteria and there are no laboratory or diagnostic procedures specific for FPIES. Rarely an oral food challenge is needed to confirm diagnosis.


How common is FPIES?

There is limited epidemiologic information and reports of prevalence vary widely. One study, Katz et al reported a cumulative incidence of infants with cow’s milk induced FPIES of 3 per 1000 newborns over a 2 year period at one hospital (0.34%).


What are the associations with FPIES?

Although FPIES is distinct from IgE mediated disease, many children have comorbid atopy with eczema and food IgE sensitisation.

Most children in Australia have FPIES to one food only. If multiple foods are suspected then referral to a clinical immunology/allergy specialist is recommended to guide safe introduction of foods.

Risk factors for FPIES have not been assessed.


How is FPIES managed?

Acute FPIES is managed with aggressive fluid resuscitation, approximately 15% of patients can have hypovolaemic shock. Dietary elimination of the offending food is recommended. Some children have cross reactivity e.g. 20-50% of children with cow’s milk FPIES have soy FPIES. FPIES rice and oats may also cross react (<20%). Children with chicken FPIES should avoid all poultry and children with fish FPIES should avoid all fish.

If the infant is breastfed, it is recommended that this continue and there is no need for a maternal exclusion diet (NB it is very rare to have acute FPIES following a breastfeed). If cow’s milk/soy induced FPIES, extensively hydrolysed milk formula is usually tolerated. If FPIES reaction to extensively hydrolysed milk formula, then use amino acid based formula.

An emergency management plan should be provided to the family.

Patients should be seen by a dietitian to provide guidance on complementary food introduction, to ensure nutritional adequacy, and manage potential oral aversion. Growth parameters should be monitored at regular intervals. Reintroduction of the foods triggering FPIES should occur under medical supervision.


What are the long-term outcomes?

Most cases of FPIES resolve by age 3-4 years but this varies widely with the population studied and the food triggering FPIES.


Where to from here?

We still do not completely understand the prevalence, risk factors and pathogenesis of FPIES. There is no validated proposed diagnostic criteria and no protocols guiding need for oral food challenge and long-term management of FPIES. There are no known therapeutic approaches to accelerate FPIES resolution and no good longitudinal cohort studies determining natural history and outcomes.



  • Clementine David is a trainee in Clinical Immunology and Allergy with an unrivalled affiliation for gelato. While an Aussie at heart, she is currently residing as an expat in Hong Kong’s Happy Valley, balancing her time between antigens and Octonauts.


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