Non-IgE mediated food allergy

  • PIC logo
    PIC Endorsed
  • See also

    IgE-mediated food allergy
    Unsettled or crying babies
    Gastro-oesophageal reflux disease in infants
    Slow weight gain

    Key points

    1. Non-IgE-mediated food allergies are delayed immune-mediated reactions to food
    2. Non-IgE-mediated allergies are diagnosed on the basis of clinical history and do not require allergy testing
    3. Treatment is based on elimination of the trigger food(s), there is no need for adrenaline or antihistamines
    4. FPIES can lead to dehydration and shock, and may need acute treatment


    • Food allergies are mediated through the immune system and can be classified as IgE-mediated, non-IgE-mediated, or mixed IgE/non-IgE-mediated
    • IgE-mediated reactions are characterized by stereotypical signs and symptoms that develop usually within 60 minutes of ingestion eg urticaria, angioedema, airway compromise (see IgE-mediated food allergy)
    • Non-IgE-mediated food allergies are characterised by a delayed onset of signs and symptoms, usually over hours to days following ingestion
      • The exception is FPIES (Food Protein Induced Enterocolitis Syndrome), which occurs on average 2-4 hours after ingestion of the offending allergen
    • Non-IgE food allergies are common in the first 1-2 years of life, with most resolving by early childhood
    • They commonly involve the gastrointestinal tract
    • Non-IgE-mediated allergies do not cause anaphylaxis and therefore are not treated with adrenaline

    • CMPI (Cow’s Milk Protein Intolerance) is an umbrella term still used by many clinicians, which encompasses the non-IgE-mediated allergic conditions Food Protein-Induced Allergic Proctocolitis and Food Protein-Induced Enteropathy


    Food Protein-Induced Allergic Proctocolitis (FPIAP): delayed, non-IgE-mediated inflammation of the rectum, commonly presenting in first few months of life. Stools with blood +/- mucous. Infant usually well and thriving

    Food Protein-Induced Enteropathy: delayed, non-IgE-mediated inflammation of the small intestine, commonly presenting in early infancy. Persistent loose stools, vomiting is common and there may be poor weight gain. Child can be unsettled and may have secondary lactose malabsorption, leading to bloating and peri-anal excoriation

    Food Protein-Induced Enterocolitis Syndrome (FPIES): delayed onset of repeated vomiting, on average 2-4 hours after ingestion of trigger food. May be associated with pallor, lethargy and may have loose stools. Usually presents in first year of life following introduction of solid foods. The most common trigger foods in Australia are rice, cow milk, soy or oats, however it can be caused by any food. See ASCIA: Food Protein-Induced Enterocolitis Syndrome (FPIES)



    • Food exposure and timing of reaction (note food may have been ingested directly by the child or through maternal ingestion via breastmilk in FPIAP and enteropathy)
    • Has this food been eaten in past, how often, any prior reactions?
    • Details of reaction and duration
      • Vomiting
      • Diarrhoea
      • Stool description, including presence of mucous or blood
      • Delayed presentations of lethargy, pallor
      • Unsettled behaviour
      • Rash (morphology and duration)
    • Age at time of initial reaction, timing of other reactions
    • Dietary history: breastfeeding (noting any maternal dietary exclusions), formula (including types)
    • Growth trajectory, taking note of slow weight gain
    • Associated eczema
    • Infectious contacts


    • Assess for dehydration
    • Abdominal examination:
      • In non-IgE-mediated food allergy presentations, the abdomen should be soft and non-tender
      • Consider other causes for presentation if abdomen is distended or tender
      • Perianal examination for rash or fissures
    • Growth parameters: weight, length, head circumference
    • Skin: assess for rashes, ie eczema, petechiae in the setting of bloody stools (consider thrombocytopenia), haemangiomas (may also be present in GI tract and present with rectal bleeding)

    Summary of conditions





    Average age

    <6 months

    <6 months

    <12 months


    Usually not prominent

    May be present

    Profuse +++


    Blood, mucous usually present

    Mucous +/- blood may be present

    May have loose stools



    Can be present










    Weight gain

    Not affected

    Can be affected

    Rarely affected

    Timing of reaction after ingestion

    >few hours-days

    >few hours -days

    Average 2-4 hours

    Improvement of symptoms

    Over few days to weeks after eliminating trigger food

    Over few days to weeks after eliminating trigger food

    Once vomiting ceases and fluids tolerated, improvement seen after few hours

    Unsettled behaviours

    Usually not present

    May be present

    Not a prominent feature

    Common food triggers

    Cow milk, soy

    Cow milk, soy

    Rice, oats, cow milk, soy, eggs

    Less common food triggers

    Others not common

    Others not common

    Avocado, chicken, sweet potato, legumes (many others possible)

    Differential diagnoses

    • Infectious gastroenteritis
    • Early onset inflammatory bowel disease
    • Bleeding disorder


    • Infectious gastroenteritis
    • Early onset inflammatory bowel disease
    • Coeliac disease (if age > 6 months and child has started solids)
    • Underlying immune-deficiency


    • Infection (sepsis, meningitis, UTI, gastroenteritis) Pyloric stenosis
    • Intussusception
    • Bowel obstruction (suspect with bilious vomiting)



    • Not routinely required; diagnoses of non-IgE-mediated allergies are made clinically
    • If persistent blood in stools, check FBE for anaemia or thrombocytopaenia
    • If there are petechiae, suggest urgent FBE looking for thrombocytopenia
    • Can consider stool testing for MCS and viral PCR to exclude infectious causes for presentation
    • Allergy testing with skin prick tests or allergen-specific IgE testing is not indicated for suspected non-IgE-mediated food allergies
      • Allergy testing will not assist with a diagnosis of non-IgE food allergies, and may even cause harm by driving unnecessary food eliminations
      • If there is doubt about the diagnosis at the time of an acute presentation and thought to be an allergic cause, discuss with Allergy & Immunology


    Proctocolitis and Enterocolitis

    Food elimination of suspected trigger

    • If cow milk is the suspected trigger, start with cow milk elimination first, noting improvement may not be seen until two weeks
    • Includes maternal elimination if child is breast-fed
    • If nil or sub-optimal improvement, then also eliminate soy
    • It is unusual to need multiple (>2) food eliminations, in which case, a dietitian review is strongly suggested
    • Suggest calcium supplements for breastfeeding mother if she is needing to eliminate cow milk and soy


    • If formula is required, suggest trialling an extensively hydrolysed formula (EHF) or rice formula in the first instance
    • Recommend two-week trial to begin with
    • If no improvements after two weeks of EHF, then change to an amino acid-based formula in consultation with a specialist
    • There are a number of over-the-counter formulas available, however some extensively hydrolysed formulas and all amino acid-based formulas require a prescription
    • If no improvements on amino acid-based formula, re-evaluate for alternative diagnosis
    • Ongoing monitoring of weight gain is important

    Re-introduction of foods

    • Consider re-introduction of trigger foods, one at a time, around 12 months of age
    • Recommend at least 2-3 week interval between each food introduction
    • For cow milk re-introduction, suggest a graded approach starting with processed milk (eg milk in baked goods), then hard cheese, yoghurt and then finally fresh milk
    • If any delayed reactions occur, cease introduction and re-try in another few months
    • Most children will improve by 1-2 years of age


    Acute management:

    • Treat vomiting
    • Suggested ondansetron doses (oral):



    8-15 kg

    2 mg

    15-30 kg

    4 mg

    >30 kg

    6-8 mg

    • Fluid resuscitation (see Intravenous fluids)
    • In an unwell child, or if not improving with initial management, have a low threshold to investigate and treat for other possible causes, such as sepsis
    • Any bilious vomiting requires an urgent surgical opinion

     Long term management

    • Prior to discharge, the family should be given an FPIES Action Plan and a script for ondansetron
    • Food elimination of suspected trigger
    • Suggest referral to a paediatric allergist
    • Most cases resolve by 2-3 years of age
    • A paediatric allergist usually manages re-introduction of trigger foods, as some of these need to be done under medical supervision

    Consider consultation with local paediatric team when

    • If no improvements in symptoms with common food eliminations, then refer to general paediatrician, paediatric gastroenterologist or paediatric allergist/immunologist
    • If poor weight gain, loose stools and eczema, and not responding to treatment, consider referral to Immunology to exclude other causes (an underlying primary immune-deficiency, eg SCID, may present in this way)

    Consider transfer when

    Any child requiring care beyond the level of comfort of the treating hospital

    For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services

    Consider discharge when

    Parental education has occurred and written/printed advice provided. See Parent Information (below)
    Appropriate follow-up has been arranged
    For FPIES: when the child is tolerating oral fluids and appears well

    Parent information

    ASCIA: Food Protein-Induced Enterocolitis Syndrome (FPIES)
    ASCIA: Food Protein-Induced Allergic Proctocolitis (FPIAP)

    Additional resources

    ASCIA: FPIES Action Plan
    ASCIA: Guide for Milk Substitutes in Cow’s Milk Allergy


    Last updated October 2022

  • Reference List

    1. ASCIA (viewed March-April 2022)
    2. Barrera, E et al. Nutritional management of cow's milk allergy in infants: A comparison of DRACMA, ESPGHAN, and AAP guidelines. The Open Nutrition Journal. 2021. 15, p1-9. doi:10.1097/MOP.0000000000000688
    3. Smart, J & Tey, D. Allergy. In Harding, K et al (Ed) Paediatric Handbook 10th edition. 2021. Wiley Blackwell