Dr Liz Powell, Dr Maeve Kelleher
Food allergies have been increasing in prevalence over the last three decades. In Europe, around 1 in 20 children have allergies to one or more foods. The quality of life and burden of allergic disease is high – even in some cases leading to social exclusion due to fear of exposure to allergens outside of the home. Failure to thrive, nutritional deficiencies and developmental delay can occur as a result of infant food allergy. There is a high public awareness of food allergy, with weekly media attention on the topic. I hope I’ve convinced you this is an important topic and it’s worth reading on….
Firstly, a brief immunology re-cap. Allergy is a hypersensitivity reaction initiated by specific immunological mechanisms. These are either IgE mediated: allergic reactions initiated when an allergen interacts with IgE that is bound to a basophil or mast cell. Or non-IgE mediated: a conglomerate term capturing inflammation in response to an allergen mediated by allergen specific lymphocytes, immune complexes or immunoglobulin G responses.
Immunological bit over, how do we tell the difference clinically?
IgE mediated reactions tend to be immediate (less than an hour), involve skin reactions like urticaria and angioedema, respiratory reactions like rhinitis and wheeze, abdominal reactions such as vomiting and diarrhoea and/or in severe cases, cardiovascular compromise with shock and collapse. Common culprits of IgE mediated reactions? Milk, egg, nuts and fish.
Non-IgE mediated reactions are usually delayed more than 2 hours and can involve skin reactions such as eczema and abdominal symptoms such as pain, diarrhoea and vomiting. Common culprits for non-IgE mediated reactions are milk and wheat.
What tests do we have at our disposal? Specific IgE in bloods or skin prick testing can confirm IgE mediated allergy. But, skin prick tests have their downsides – they are good at ruling out (high sensitivity) but not great at ruling in (low specificity) the diagnosis. So the skin prick test can be positive i.e. there is sensitization without clinical allergy. There is a big hole in available investigations (i.e. there aren’t any good ones…) for non-IgE mediated allergy. Here, the diagnosis relies on exclusion under dietary supervision and reintroduction looking for symptom recurrence.
Cow’s milk protein allergy
Cow’s milk protein allergy is common, affecting 2-3% of 1-3 year olds. It can present as IgE-mediated, non-IgE mediated or just to confuse, a mixed picture. The milder cases of non-IgE mediated allergy are diagnosed and managed in primary care with exclusion of cow’s milk protein and reintroduction from around one year using the iMAP milk ladder. Those with more severe symptoms such as poor weight gain may present to the hospital setting.
The iMAP milk ladder; only to be used in non-IgE mediated Cow’s milk allergy. See Allergy UK for more information
Some severe presentations in infants to bear in mind. From the non-IgE world, FPIES (Food Protein Induced Enterocolitis) which presents with severe vomiting and dehydration. These infants may have been admitted with presumed sepsis or gastroenteritis on one or more occasions before the penny drops. Also a non-IgE mediated milk allergy, allergic proctocolitis, can present as blood in the stool of an otherwise generally well infant. These infants respond to cow’s milk exclusion, either through the removal of milk from mother’s diet while breastfeeding, or (if formula fed), switching to an amino acid formula.
Severe IgE-mediated allergy can present as anaphylaxis in infants – it does happen and can be slightly different in presentation. For example, there might initially be subtle behavioural changes. Respiratory compromise is more likely than hypotension or shock, and where it does occur shock is more likely to manifest as tachycardia than hypotension. Milk and eggs are the most common causes.
Eczema and allergy
There is an increased risk of food allergy in infants who have had severe early eczema – the risk is greater the earlier the eczema (especially if under 6 months old) and the more severe. The theory for this is that in eczema, the skin barrier is leaky. The first introduction of allergens is across this leaky skin barrier rather than orally. This can lead to sensitization to the allergen rather than tolerance – which is what would have happened if the first exposure was by eating it.
The link between food allergies causing eczema flares is less clear. As with most things in medicine, it is important to take a good history. If there are symptoms associated with the flare such as urticaria or angioedema in keeping with food ingestion, this suggests an IgE-mediated component. Skin prick testing should be done and the food should be avoided. If there is a clear history of food triggers with a more delayed response in association with gastrointestinal symptoms or poor weight gain this suggests a non-IgE mediated reaction and an exclusion diet with dietetic support may be worthwhile. Otherwise, in an unselected eczema cohort there is not good evidence for food avoidance.
Be aware that a lot of families whose children have eczema will have tried an exclusion diet so it’s always important to ask about any foods that are being avoided in an eczema consultation. Also be sure the basics of eczema management are being done well, and ensure emollients are applied regularly. Beware the infant who has had allergens removed from their diet at an early age for severe eczema and concern regarding non-IgE allergy – they may develop IgE mediated allergy and subsequently have IgE mediated reactions on reintroduction of these foods.
Food allergy is clearly a big headache for families and there is an ever-increasing demand for allergy services – so how can we avoid the problem in the first place? Treating (or even better, preventing) early eczema is obviously important – as discussed above. The BEEP (Barrier Enhancement for Eczema Prevention) pilot study showed a significant effect (50% relative risk reduction) of emollients once per day in preventing eczema; results from the larger trial are awaited.
The notion that avoiding allergens during pregnancy and early childhood will prevent allergic disease has been quashed. The LEAP (Learning Early About Peanut allergy) study enrolled high risk infants with eczema &/or egg allergy and randomised them to either peanut consumption or avoidance starting at 4-11 months. Those who consumed peanut were significantly less likely to develop allergy – 3% had developed peanut allergy by age 5 compared to 17% in the avoidance group. The EAT (Enquiring About Tolerance) study looked at all infants (not just those at high risk of allergy) and compared early introduction of 6 allergenic feeds from 3 months of age alongside breastfeeding vs standard weaning advice (introduction from 6 months). There was no significant difference in allergy to these foods by 3 years of age in the early introduction vs the standard group. But when the authors looked at those who had adhered to the protocol (only 56%), there was a significant reduction in allergy in the early introduction group. Current UK weaning guidance is to introduce allergenic foods alongside other weaning foods from 4 to 6 months. Watch this space for whether these guidelines change over the next few years – allergy prevention is a very active area of research.
The LEAP study was widely publicised – a lot of parents are aware of it and may ask about it but be concerned about introducing peanut at home. For infants with a high risk of allergies such as severe early eczema, there may be local services available which offer initial assessment for food allergy including skin prick testing and support early introduction of allergenic foods such as peanut.
Key learning points
Food allergy in infants is common, and causes significant burden to families
A good history can suggest IgE mediated versus non-IgE mediated allergy
Skin prick testing and blood tests for specific IgE mediated reactions are available.
Food avoidance with dietetic support is the current standard management of food allergy
Allergy prevention is an active area of research and has a promising future!
Dr Liz Powell, Paediatric Allergy Registrar, Evelina London Children’s Hospital
Dr Maeve Kelleher, Paediatric Allergy Consultant, Evelina London Children’s Hospital
Images of baby enjoying food at the top of the article are pictures of author’s own child, used with permission!