Future trends in Food Allergy

Academy for Paediatric Gastoenterology – March 2015

Notes on the presentations by Michelle Berriedale-Johnson

Cow's Milk Allergy – the complexities and the guidelines – Dr Trevor Brown

Future trends in Food Allergy for IgE and non-IgE – Dr Adam Fox

Hypo-allergenic formulae – Natalie Yerlett

Weaning your child: can we develop new guidance – Dr Rosan Meyer

FPIES: diagnosis and management – Louise Littler

Quality of Life in food allergy – Dr Rosan Meyer


Cow's Milk Allergy – the complexities and the guidelines

Dr Trevor Brown, Consultant Pediatrician, Ulster Hospital, Belfast

Dr Brown is one of the UK's leading experts on cow's milk allergy (CMA) and has been intimately involved in the creation of the four guidelines that now exist for its management. He described some of the background and the difficulties in the area.

Cow's milk allergy is the most complex of the common food allergies. It normally involves other allergies and is, very often, non IgE mediated so very much harder to diagnose. Some figures:

2-4% of formula-fed UK infants are cow's milk allergic
0.5% of UK breast fed infants are cow's milk allergic

There is a ten-fold discrepancy between parent-reported allergy and diagnosed allergy but that is mainly because non IgE CMA is not included in the diagnosed figures.

Figures from the 2010 UK GP's database suggest that 1% of infants are diagnosed by the age of three months but that it takes a further three months and 4.2 visits to the GP for the other 3-4% to be diagnosed.

86% of cow's milk allergic infants are diagnosed in primary care with 42% being referred on, although they may have to wait up to three months for a specialist appointment. Less than 10% of these families are referred to a dietitian.

Over 90% of these children have mild to moderate, non IgE cow's milk allergy.

There are now four diagnosis and management guidelines available:

2013 EAACI Diagnosis of food allergy

2014 BSACI Cow's Milk Allergy – designed for specialist use.

2011, updated 2014, NICE Diagnosis and assessment of food allergy in children and young people in primary care and community settings.

2014 MAP Guideline - A primary care guide to the diagnosis and management of cow's milk allergy in the first year of life

Notes on the individual guidelines:

• A skin prick test advised for initial diagnosis. It is very quick although not totally reliable is 95% predictive for IgE.
Food challenges are advised but only under supervision followed by conservative 'milk ladder'.

• Initial diagnosis of allergy through a history and examination taking the skin, gut and respiratory systems into consideration and being aware of the distinction between IgE and non IgE allergy.
• Further investigation through skin and blood tests and food challenge, but the latter only under specialist care and where resuscitation facilities are available. (NICE recognises that these are rarely available in Primary Care.)
• Suspected non-IgE – home exclusion and challenge, with dietetic support, advised.
• Suspected severe IgE – referral to emergency and then specialist care. Children should be referred if food allergy is only suspected, even if there is no clinical evidence or history beyond parental belief.

MAP Guidelines:
Drawn up by specialist group covering every aspect of allergy.
'Walks' GP through the signs and symptoms of both IgE and non-IgE cow's milk allergy with clear algorithms for further treatment and management.

Severe forms of non IgE mediated cow's milk allergy

FPIES (Food protein-induced enterocolitis syndrome). See Louise Littler's presentation below but cow's milk is the commonest trigger for FPIES.
Diagnosis is slow because it is a little recognised condition – usually only diagnosed on the third or fourth emergency admission.

EGIDS (Eosinophilic Gastrointestinal Disorders). Management is usually a six food elimination although milk is by far the commonest trigger.

Future Trends in Food Allergy for IgE and non-IgE

Dr Adam Fox, Consultant Paediatric Allergist, St Thomas' Hospital, London

In approaching allergy there are two issues:
• Preventing the onset of allergy
• Inducing tolerance


• Eczema.
Work in Australia has showed a very clear relationship between the seriousness of infant eczema and the onset of food allergy. The earlier the eczema starts, the higher the likelihood of food allergy developing. So if an infant has serious eczema at under three months it has a 50% risk of developing food allergy.
Mutation in the filaggrin gene (which provides the 'cement' to stick cells together and prevent allergic proteins breaching the skin barrier) have been shown to be associated with persistent eczema.

So could early and aggressive treatment of eczema prevent the development of food allergy?

There has been very little work done in this area although two studies looking at applying generous amounts of moisturisers to neonates at high risk of allergy, even if they had no symptoms of eczema, reduced the incidence of eczema in that group by 32%.

Inducing tolerance

A high proportion of children do achieve tolerance naturally. Figures from the USA in 2007 show that while 81% of a group of high risk children had Cow's Milk Allergy at 4 years this had reduced to 58% at 8, to 36% at 12 and to 21% at 16 years of age.

However, in 2007 treatment was, essentially, avoidance; in 2015 treatment is a balance between avoidance and measures to promote tolerance through active management:

1. Early introduction of the allergens –.
2. Anticipatory testing for other allergens so that they can be introduced early.
3. Active tolerance induction
4. Active risk assessment re 'may contain'. e.g. Do not always avoid foods with 'may contain' labels but assess how genuine the risk it likely to be depending on the food and taking into account your state of health at the time - run down, tired, suffering from a viral infection etc.

Allergists have had a long standing interest in the possible benefits of probiotics but it is not clear what those benefits may be, nor how the probiotics should be used – what strains? for how long? etc
However, giving maternal probiotics appears to be useful and probiotic supplemented infant formulae have produced significant improvement in the speed at which children outgrow both IgE and non-Ige cow's milk allergy.
The PRESTO study currently ongoing at St Thomas will hopefully shed more light on the usefulness of probiotics.

Heating would appear to change the shape of some epitopes (the part of the allergen that is recognised by the immune system). So, if your child's immune system is reacting to one of the epitopes which changes shape when cooked then they should be able to tolerate baked/cooked milk or egg, for example, with no problem.

In a study at Mount Sinai School of Medicine in New York in 2008 75% of 2-17 year old children with mild to moderate cow's milk allergy could tolerate baked milk.

Oral and epicutaneous desensitisation
Both do appear to induce tolerance, especially for cow's milk allergy, in a significant number of allergy sufferers although tolerance may lapse unless they continue to eat the allergen. There are, however, no guidelines or clinical protocols for the use of OIT.

In management terms, its usefulness depends on whether the patient is more focused on safety or on normalisation of their life. This is probably dependent on the severity of their reactions. If safety, then it should then OIT should be avoided, if normalisation (so that they do not, for example, need to worry about 'may contain' labels) then it is a promising therapy.


Hypo-allergenic formulae

Natalie Yerlett, Specialist Paediatric Dietitian, Great Ormond Street Hospital

In hypoallergenic formulae the protein structure is modified or broken down by heat treatment (hydrolysis) but it is not known where the breaks in the chain may come. In Extensively Hydrolysed Formulae (EHF) less than 1% of the protein remains and that is tolerated by 90% of CMA children. However, 30% of non-IgE cow's milk allergic children do not tolerate EHFs.

Partially hydrolysed formulae may be helpful for infants with eczema and may even be preventative for these babies, but is not appropriate treatment for children with CMA.

Children who do not tolerate extensively hydrolysed formulae will need to have an elemental amino acid-based formula (such as Neocate) although the cost implications are considerable – £2,500 for an amino-acid based formula against £1,000 for an extensively hydrolysed one.

Casein have in vitro the best allergenic potential, but when looking an in vivo studies on children with cow's milk protein allergy, there is absolutely no difference.
If the mother is breast feeding then she must exclude all relevant allergens from her diet and if that includes milk she needs to supplement with calcium and Vitamin D.
Soya-based formulae are not the first option both because of the high proportion of CMA infants who are also soya allergic and because of concern over the high phytate levels in soya.
Follow on formulae are available but you can continue to use hypoallergenic formulae until the child is two. The child can also be given supermarket 'freefrom' milks but may then need extras supplementation.
There are rice based hydrolysate formulas available in mainland Europe as hypoallergenic formulas. These are NOT available in the UK. Although these formulas seem promising, limited large paediatric population studies exist to indicate growth, safety and tolerance in all paediatric allergy patients.

Weaning your child: can we develop new guidance

Dr Rosan Meyer, Principal Research Dietitian, Great Ormond Street Hospital, London

There is very little genuine agreement among health professionals as to the ideal time for weaning in the allergic child. Current guidelines are as follows:
USA AAP – 4–6 months
EAACI (European Academy of Allergy and Clinical Immunology) – 4–6 months
ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) – 4–6 months but not before 17 weeks
Department of Health UK – 6 months for non-allergic babies; not before 17 weeks and not after 26 weeks for allergic babies.

One allergy, whether IgE mediated or not, suggests that the child may have others. Below are just some numbers from published studies, but these may vary depending on population and type of allergy:
28% Cow's milk allergic babies also have egg allergy
14% Cow's milk allergic babies also have peanut allergy
33% egg allergic babies also have peanut allergy
Allergies may also be mixed – both IgE and non IgE
Testing must be based on a clinical history.

The Infant Nutrition Survey in the UK indicates that normal weaning foods rely heavily rice porridge and often insufficient fruits and vegetables introductions. The most common food allergen in early infancy is cow’s milk. This increases the nutritional pressure to achieve nutrient intake as children that are weaned can not have cheese/yoghurt and other cow’s milk products. It is therefore important that the weaning diet is adequate to achieve normal growth and development.

When weaning atopic babies, start with low allergen foods and add new foods very gradually (one every 2–3 days) and one at a time but cumulative. Try a cooked version first and try them early in the day so you can monitor any reactions. Empower the parents to recognise reactions and to deal with them.

Guidelines badly needed!


FPIES: diagnosis and management

Louise Littler of FPIESUK.org

FPIES (Food Protein-Induced Entercolitis Syndrome) is the most severe form fn non-IgE mediated food allergy. It usually occurs in children under 12 and is often misdiagnosed.

It causes profuse vomiting and lethargy 1–6 hours after the ingestion of the food. In 20% of cases the child MAY also go blue and suffer from hypotension (low blood pressure). The blue tinge may last for up to two weeks. 25% of children may also have diarrhoea. It is not fatal but very scary.

Because it also causes a dramatic increase in neutrophils it is often misdiagnosed as sepsis and sometimes as viral gastroenteritis. (In the FPIES group 25 families had 58 emergency admissions to hospital without a single correct diagnosis. Consultants are unwilling to diagnose while most dietitians are unaware of the condition.)

The only current treatment is the replacement of fluids although anti-emetics seem to be helpful. Provided fluids are replaced the child will recover in 2–3 days, otherwise it may take 2–3 weeks.

Because of the violence of the reaction, FPIES has a dramatic effect on the families' quality of life and can have behavioural effects on the children.

FPIES can be to any foods but is usually to the first weaning foods: milk, soya, poultry, rice, oats, legumes, bananas, sweet potatoes, egg. It is rarely to more than two foods (although often in the same food families) and it often occurs along with other allergies. There appears to be a genetic element in FPIES but the only tests are the normal food challenge tests.

FPIES children usually do well on Amino Acid formula, in a few cases it may not be tolerated. However for those children who do have symptoms on an elemental, amino acid formula: consider it may not be FPIES, it could be other sources of allergens in toothpaste, drugs or in some other disguised form or another medical condition alongside FPIES, Eosinophilic gastroinstestinal Disease for example. And although in FPIES diarrhoea can go along with vomiting, if it is diarrhoea alone, it is not FPIES.

The condition urgently needs more recognition – and a more user-friendly name! – as well as some FPIES specific tests.

FPIES is to non-IgE food allergy what anaphylaxis is to IgE food allergy – the most extreme form of the condition.


Quality of Life in food allergy

Dr Rosan Meyer, Principal Research Dietitian, Great Ormond Street Hospital, London

There are no validated tools with which to assess Quality of Life (QOL) for non IgE food allergy, but there are very good validated tools for for IgE. However, QOL for peanut allergy sufferers compares poorly with QOL of sufferers of rheumatoid arthritis, diabetes and cystic fibrosis. The disruption and anxiety, especially among parents is higher than in other conditions although the children tend to cope relatively well.

Other points:
• Anxiety tends to be lower after a food challenge (no matter what the outcome) and after the prescribing of an Epipen, even when the child did not carry the Epipen!
• A lack of prognosis was felt to be the most distressing element in managing the allergy.
• As children became adolescents and therefore more knowledgeable and competent in managing their own allergy they became more anxious.
• Because management can be so stressful, diagnosis may not significantly improve QOL as it does in other conditions.

In a recent unpublished study carried out at GOSH, the QOLs was worse in children with non-IgE mediated allergy than a matched control group with sickle cell anaemia. The group also found that although the total score for QoL was lower than children with gut failure (short bowel syndrome) this did not reach statistical significance for all categories.

March 2015

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