Dr Joanne Walsh shares some key points on diagnosing and managing IgE-mediated and non-IgE-mediated food allergy

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Read this article to learn more about:

  • the distinction between IgE-mediated and non-IgE-mediated allergy, and what tests can be done in primary care
  • the importance of taking an allergy-focused clinical history
  • who should be referred to secondary or specialist care.

1 Know the difference between allergy and intolerance

Food hypersensitivity is the broadest term for symptoms caused by a food. If the immune system is involved, the reaction to the food is termed a food allergy, and if the immune system is not involved, the term food intolerance should be used.1,2

Understanding the differences between food allergy and intolerance is important in determining which (if any) tests will be helpful and how the symptoms are best managed.

For example, in lactose intolerance there is difficulty digesting the sugar, lactose. This may occur for several reasons, such as a decrease in the production of lactase (the enzyme that digests lactose) as the diet becomes less reliant on milk; this presents as loose stools and abdominal pain in adolescents, and particularly affects those of an Asian or African-Caribbean ethnic background.3 Alternatively, temporary damage to the bowel wall may occur following a severe gastrointestinal infection or when there is unrecognised or poorly managed coeliac disease or milk allergy. Once the bowel wall repairs itself, lactose can again be tolerated.

Milk allergy, however, is caused by an immune reaction to the protein in milk.4

2 Food allergy can be IgE-mediated or non-IgE-mediated

The immune system may respond to a food with immediate symptoms. These symptoms usually occur within minutes to 2 hours and are caused by an immunoglobulin E (IgE) antibody-mediated reaction.5

Some symptoms of food allergy develop >2 hours or even days after ingestion.5 The mechanism is not entirely understood, but it is referred to as non-IgE-mediated disease.

The presentations of IgE-mediated disease are often easily recognised as allergy, and include:2

  • acute urticaria
  • acute angioedema
  • immediate vomiting
  • collapse and anaphylaxis.

Non-IgE-mediated disease can be more difficult to diagnose as the symptoms may not be directly associated with consumption of a particular food. These symptoms include:2

  • loose and frequent stools or constipation (often straining but a soft stool)
  • abdominal pain
  • eczema.

Non-IgE-mediated disease may present in infants as persistent crying, back arching, and even less obviously allergic symptoms.

Food allergy should be considered if symptoms occur in more than one organ system (gastrointestinal, skin, or respiratory) or if a person does not respond to usual treatments.2

Table 1 (below) provides a list of signs and symptoms of possible food allergy for both IgE- and non-IgE-mediated reactions; however, this list is not exhaustive and the absence of these symptoms does not exclude food allergy.

Table 1: Signs and symptoms of possible food allergy2
The skin
Acute urticaria—localised or generalisedAtopic eczema
Acute angioedema—most commonly of the lips, face, and around the eyes 
The gastrointestinal system
Angioedema of the lips, tongue and palateGastro-oesophageal reflux disease
Oral pruritusLoose or frequent stools
NauseaBlood and/or mucus in stools
Colicky abdominal painAbdominal pain
VomitingInfantile colic
DiarrhoeaFood refusal or aversion
Perianal redness
Pallor and tiredness
Faltering growth in conjunction with at least one or more gastrointestinal symptoms above (with or without significant atopic eczema)
The respiratory system (usually in combination with one or more of the above symptoms and signs)
Upper respiratory tract symptoms (nasal itching, sneezing, rhinorrhoea, or congestion [with or without conjunctivitis]) 
Lower respiratory tract symptoms (cough, chest tightness, wheezing, or shortness of breath)
Signs or symptoms of anaphylaxis or other systemic allergic reactions 
Note: this list is not exhaustive. The absence of these symptoms does not exclude food allergy
National Institute for Health and Care Excellence (2011). Food allergy in under 19s: assessment and diagnosis. NICE Clinical Guideline 166. Available from: www.nice.org.uk/cg116.
NICE has not checked the use of its content in this article to confirm that it accurately reflects the NICE publication from which it is taken.

3 Take an allergy-focused clinical history

As well as healthcare professionals suspecting food allergy when patients present with a collection of symptoms and/or signs, people will commonly present to primary care thinking that they may have a food allergy.

In order to explore this further, an allergy-focused history must be taken.2,6 The purpose of the history is to determine:

  • is allergy likely or not?
  • what is the likely mechanism of the reaction (IgE- or non-IgE-mediated)?
  • how severe was the reaction?

The answers to these questions will determine any future management.

For children, NICE Clinical Guideline 116 lists questions to ask (see Box 1, below),2 as does the Royal College of Paediatrics and Child Health pathway project.7

A detailed history is often unrealistic in an initial primary care consultation, so patients may need to return in order for a complete history to be taken. Primary care-focused questionnaires could also be used, but it is important to ensure that enough information is obtained to determine the next steps.2

Box 1: What to include in an allergy-focused clinical history2

  • any personal history of atopic disease (asthma, eczema, or allergic rhinitis)
  • any individual and family history of atopic disease (such as asthma, eczema, or allergic rhinitis) or food allergy in parents or siblings
  • details of any foods that are avoided and the reasons why
  • an assessment of presenting symptoms and other symptoms that may be associated with food allergy (see Table 1, above), including questions about:
    • the age of the child or young person when symptoms first started
    • speed of onset of symptoms following food contact
    • duration of symptoms
    • severity of reaction
    • frequency of occurrence
    • setting of reaction (for example, at school, or home)
    • reproducibility of symptoms on repeated exposure
    • what food and how much exposure to it causes a reaction
  • cultural and religious factors that affect the foods they eat
  • who has raised the concern and suspects the food allergy
  • what the suspected allergen is
  • the child or young person's feeding history, including the age at which they were weaned and whether they were breastfed or formula-fed—if the child is currently being breastfed, consider the mother's diet
  • details of any previous treatment, including medication, for the presenting symptoms and the response to this
  • any response to the elimination and reintroduction of foods.

National Institute for Health and Care Excellence (2011). Food allergy in under 19s: assessment and diagnosis. NICE Clinical Guideline 166. Available from: www.nice.org.uk/cg116
NICE has not checked the use of its content in this article to confirm that it accurately reflects the NICE publication from which it is taken.

4 How to test for IgE-mediated disease

If IgE-mediated disease is suspected from the history, specific IgE blood tests or skin prick tests are needed to confirm the diagnosis.2 Blood tests can be requested for specific IgE antibodies to individual foods, such as egg, and if required, can be even more specific (e.g. egg white). In allergy clinics, further detailed tests can be performed to look for reactions to specific parts of a protein.

Skin prick tests should only be undertaken where there are facilities to deal with an anaphylactic reaction.2 This includes primary care settings where immunisations are given (as immunisations carry a risk of anaphylaxis). Currently, skin prick tests are rarely performed in primary care, but in order to manage food allergy more effectively this may need to be reconsidered, and the competencies of healthcare professionals likely to be requesting tests improved, so that more testing can be performed in the community.

5 How to confirm a diagnosis in non-IgE-mediated disease

No blood or skin prick tests are needed if the mechanism of the food allergy symptoms is thought to be non-IgE mediated. Instead, a trial elimination of the suspected allergen from the person's diet (normally for between 2–6 weeks), followed by a reintroduction of the allergen to confirm diagnosis, is recommended.2,6 It is important to confirm the diagnosis, otherwise patients may be on restricted diets unnecessarily, which can cause stress for them and their families (and in the case of infants with suspected milk allergy, be costly to the NHS when alternative formulas are prescribed unnecessarily). NICE recommends involvement of a dietitian (with appropriate competencies) for advice when elimination diets are undertaken.2

There is little published literature on confirming the diagnosis in non-IgE-mediated allergy in primary care, but the Milk Allergy in Primary Care (MAP) guideline8 suggests that after 2–4 weeks of an exclusion diet, milk should slowly be reintroduced to see if symptoms recur (for further information on cow's milk allergy and the MAP milk allergy guideline, see the Guidelines in Practice article). If the symptoms return, then the diagnosis is confirmed. If there are no further symptoms, a diagnosis of milk allergy is unlikely and the infant can return to an unrestricted diet.8

This home challenge/reintroduction to prove the diagnosis underpins one of the statements in NICE Quality Standard (QS) 118 on Food allergy6 (see the Guidelines in Practice article covering NICE QS118).

It is important to note that elimination and reintroduction of a suspected allergen is not recommended in people who have experienced severe delayed reactions; they need to be referred to secondary or specialist care.6

6 Who should be referred

The NICE Quality Standard on Anaphylaxis9 reiterates the recommendations of the NICE guideline on anaphylaxis:10 following suspected anaphylaxis, a person should be referred to an allergy clinic, preferably one that is age appropriate. Pathways for this referral route may need to be established.

While waiting for the appointment, those individuals with suspected anaphylaxis to a specific food (or if appropriate, their parent/carer) should be:

  • given advice on avoiding that trigger10
  • prescribed an adrenaline device and trained in when and how to use it10
  • provided with information about patient support groups,10 such as the Anaphylaxis Campaign and Allergy UK (see tip 9).

Following an allergy-focused clinical history, some other patients with suspected food allergy should be referred before any testing occurs in primary care. The only national guidance on referral for food allergy is from NICE CG116, which covers those aged 19 years and under. NICE recommends referral for children or young people:2

  • who have:
    • had one or more acute systemic reactions or severe delayed reactions
    • faltering growth in combination with one or more of the gastrointestinal symptoms listed in Table 1 (see above)
    • significant atopic eczema where multiple or cross-reactive food allergies are suspected by the parent or carer
  • where there is:
    • persisting parental suspicion of food allergy, despite a lack of supporting history
    • clinical suspicion of multiple food allergies.

Children or young people who will need to be referred following testing or initial work-up in primary care include:2

  • those who have not responded to a single-allergen elimination diet
  • any child with asthma who has confirmed IgE-mediated food allergy, even if there was only a mild localised reaction to food
  • those with a strong clinical suspicion of IgE-mediated food allergy but allergy test results are negative.

7 Test for tolerance—have they outgrown the allergy?

If there have never been any immediate (i.e. presumed IgE-mediated) reactions to a food and there is no active eczema,* the suspected food can be reintroduced at home. Tolerance is usually acquired to well-cooked forms of a food (e.g. milk and egg in a cake) before it is tolerated uncooked.11 This is due to the proteins being changed during preparation so they are no longer acted on by the body as though they are an allergen.

This forms the reasoning behind food ladders such as the milk ladder produced by MAP.8 This is only for use in mild to moderate non-IgE-mediated food allergy. Tolerance to milk is usually considered in infants after 6 months on a milk exclusion diet, usually around the age of 9–12 months.8 Specific IgE blood tests or skin prick tests can aid decisions on whether to reintroduce a food. The MAP guideline suggests these tests are undertaken in those who have had IgE-mediated symptoms and those with eczema.8 If specific IgE tests are positive, or even negative in those with a previous history of acute reactions, it is best to discuss any reintroduction with a specialist in allergy.8 Controlled challenges in a secondary care setting are often necessary.

With the exception of the NICE Clinical Knowledge Summary on cows milk allergy,12 there is currently (October 2016) no national guidance on primary care management of food allergy in children or in adults. The British Society for Allergy and Clinical Immunology has produced guidance on managing specific food allergies, but its guidance on milk, egg, and nuts is aimed at allergy specialists.

* although eczema is a symptom of non-IgE-mediated disease and can flare on exposure to allergens, it can also be a risk factor for IgE-mediated reactions.

8 Don't forget pollen–food syndrome

Sometimes when a food is eaten, symptoms associated with immediate IgE-mediated reactions occur but are limited to the oral area (e.g. itching of the mouth and swelling or redness around the lips). In these cases, pollen–food syndrome or oral allergy syndrome should be considered. The symptoms occur because the proteins in the food are very similar to another allergen—usually pollen—to which the person is able to produce an immune response.13

For example, the body may react to apple, which has similar areas in its proteins to those that cause hay fever in someone with birch pollen sensitivity. A careful clinical history is needed, and testing may help confirm the diagnosis. Fruits and vegetables causing pollen–food syndrome symptoms can often be tolerated in their cooked, but not raw forms.13 In apples, peeling may help and sometimes reactions will vary between the varieties. It may also be that during the winter and outside of the birch pollen season, foods can be tolerated. A specialist allergy dietitian or allergist can be helpful in managing these cases.

9 Learn about the role of patient support groups

Patients with suspected food allergies and their families often have many questions and concerns.

NICE recommends signposting patients to patient support groups following suspected anaphylaxis.10 The Anaphylaxis Campaign a charity for those at risk of severe allergic reactions, and Allergy UK, a charity that provides information on allergies and intolerances are both useful resources. They provide information leaflets, run help lines, and can provide education and support to patients and their families.


  1. Johansson S, Bieber T, Dahl R et al. Revised nomenclature for allergy for global use: report of the nomenclature review committee of the world allergy organization, October 2003. J. Allergy Clin Immunol 2003; 113 (5): 832–836.
  2. NICE. Food allergy in under 19s: assessment and diagnosis. NICE Clinical Guideline 116. NICE, 2011. Available at: nice.org.uk/cg116
  3. NHS Choices. Lactose intolerance. www.nhs.uk/Conditions/lactose-intolerance (accessed 27 September 2016).
  4. du Toit G, Meyer R, Shah N et al. Identifying and managing cow's milk protein allergy. Arch Dis Child Educ Pract Ed 2010; 95 (5): 134–144.
  5. Leung D, Szefler S, Akdis C et al. Pediatric allergy: principles and practice. In: Leung D, Szefler S, Bonilla F, editors.Allergy in children. Elsevier Health Sciences, 2015: 378.
  6. NICE. Food allergy. NICE Quality Standard 118. NICE, 2016. Available at: nice.org.uk/qs118
  7. Royal College of Paediatrics and Child Health. Care pathways for children with allergies. www.rcpch.ac.uk/allergy (accessed 9 September 2016).
  8. Venter C, Brown T, Shah N et al. Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy—a UK primary care practical guide. Clin Transl Allergy 2013; 3 (1): 23. Available at: www.ctajournal.com/content/3/1/23
  9. NICE. Anaphylaxis. NICE Quality Standard 119. NICE, 2016. Available at: nice.org.uk/qs119
  10. NICE. Anaphylaxis: assessment and referral after emergency treatment. NICE Clinical Guideline 134. NICE, 2011. Available at: nice.org.uk/cg134
  11. Kim J, Nowak-Węgrzyn A, Sicherer S et al. Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol. 2011; 128 (1): 125–131.
  12. NICE. Cow's milk protein allergy in children. Clinical Knowledge Summaries. NICE, 2014. Available at: www.cks.nice.org.uk/cows-milk-protein-allergy-in-children
  13. British Dietetic Association. Pollen-food syndrome (PFS). BDA, 2014. Available at: www.bda.uk.com/foodfacts/PollenFoodSyndrome.pdfG