Suspecting that your child has a food allergy or sensitivity can cause parents immense concern and worry.Dr Lisa Waddellhelps clarify the correct diagnosis, management and support procedures within the community following the latest NICE guidelines allergy1 

Dr Lisa Waddell,BSc (Hons), RD, Dip ADP, PhD Specialist Community Paediatric Dietitian Nottingham CityCare Partnership 

Abstract   
Food allergy is among the most common of the allergic disorders, with a prevalence of 6-8 per cent in children up to the age of three. However, many people self-diagnose, putting their children at risk of malnutrition, possibly as a result of lack of awareness by health professionals of food allergy as a potential cause of conditions such as infantile eczema, chronic diarrhoea, faltering growth and gastrooesophageal reflux. NICE (The National Institute for Health and Clinical Excellence) recently published guidelines, which they hope will help to improve the diagnosis of food allergies within the community9. If food allergy or lactose intolerance is suspected, the mainstay of a diagnostic work up should comprise of a detailed allergy-focused clinical history, part of which will involve determining whether the adverse reaction is typically an immediate (IgE mediated) or more delayed-type (non-IgE mediated) allergic reaction, or whether it may be lactose intolerance; a form of non-allergic hypersensitivity. 

Key Points     
Food allergy is a poorly recognised underlying cause of many conditions such as infantile eczema, chronic diarrhoea, faltering growth and gastrooesophageal reflux    

NICE's latest guidelines can help. Look for the document titled "Diagnosis and assessment of food allergy in children and young people in primary carallergycase1e and community settings"  

A detailed allergy focused clinical history is paramount and should form the mainstay of the diagnostic and assessment process  

Food allergic reactions should be classified as either IgE mediated (immediate) or non IgE mediated (delayed > two hours). The term food intolerance should only be used for conditions which do not involve the immune system; such as lactose intolerance due to lactase deficiency, although the term non immune mediated food hypersensitivity is preferred  

Allergy sensitisation tests should be used as part of the diagnostic process for IgE mediated allergy, whereas a two to six week trial elimination period of suspected allergen, followed by re-introduction is required for non-IgE mediated allergy 

Introduction   

Food allergy is among the most common of the allergic disorders and has been recognised as a major paediatric health problem in western countries. The prevalence of food allergy in Europe and North America has been reported to range from 6 to 8 per cent in children up to the age of three years1-3. Food allergies can place a huge psychological, financial and emotional burden on the family and necessary life style changes can significantly affect the family's quality of life4. Many people self-diagnose and self-manage without any dietetic advice, putting themselves or their children at risk of conditions such as malnutrition (as observed with the use of rice milk for the treatment of constipation and congestion)5. This in part may result from delayed diagnosis by health professionals such as GPs and health visiting team members in the community, due to the lack of awareness of common signs and symptoms of food allergy. Where delayed reactions occur, it can be more difficult to determine what the offending food allergen might be6. This can cause substantial parental stress and is commonly the case for eczema and gut-related allergies associated with symptoms such as gastro-oesophageal reflux (GOR), diarrhoea, constipation, vomiting, faltering growth, food aversion and infantile colic. It is poorly recognised that just under half of the cases of GOR in infants less than one year of age are likely to have a concomitant cow's milk protein allergy (CMPA)7 and that infantile eczema is a major risk factor for IgE mediated food allergy8.   allergyfig1 

This article aims to expand on the NICE food allergy guidelines and provide some practical tips and tools to support health pallergyt1rofessionals improve their diagnosis of both food allergy and lactose intolerance in infants and children in the community.  

What is food hypersensitivity?   
In 2003, the World Allergy Organisation (WAO) proposed a classification that all non-toxic adverse reactions to foods should be termed food hypersensitivity (FHS); divided into immune-mediated food hypersensitivity (food allergy) or non-immune mediated food hypersensitivity (previously referred to as food intolerance), which includes enzyme deficiencies and pharmacological reactions10 (Fig 1). Food allergy continues to be commonly incorrectly referred to as food "intolerance" by both health professionals and the general public alike. Most people understand the term food allergy to represent an immediate adverse reaction to food (within two hours of ingestion). This type of reaction should be referred to as IgE-mediated allergy, as the reaction involves production of IgE antibodies. However, a substantial number of more delayed reactions (over two hours post-ingestion of food) are seen in infants and children in the community, which nevertheless still involve the immune system, and these type of reactions should be referred to as non-IgE mediated allergy. It is imperative that this type of reaction is not confused with a diagnosis of lactose intolerance resulting from an enzyme deficiency (lactase), with no immune involvement, and for which the management differs markedly from that of a cow's milk protein allergy.    

  

When should food hypersensitivity be considered? 

Food allergy   
Food allergy should be considered in infants and children who have one or more of the signs and symptoms illustrated inFig 1, as described by NICE (2011)9. Food allergy should also be considered in infants and children who do not respond adequately to treatment for atopic eczema, GOR and chronic gastrointestinal symptoms including chronic constipation9.   
Lactose intolerance     
Non-immune food hypersensitivity other than lactose intolerance is uncommon in children and hence will not be addressed in this article. Lactose intolerance however, is more common and can occur after an episode of viral gastroenteritis and in conditions such as untreated coeliac or Chron's disease, when damage to bowel mucosa causes a deficiency in lactase; the enzyme responsible for lactose digestion (known as secondary lactose intolerance)11. Malabsorbed lactose produces an osmotic load that draws fluid into the gut, producing symptoms of loose, watery stools, abdominal bloating, flatulence and pain (Fig 1). This is usually reversible and secondary lactose intolerance should be suspected in all children who have loose stools for more than two weeks post gastroenteritis. 

Primary lactose intolerance is also quite common, although rarely before two to three years of age, and tends to become apparent later, as the ability to produce lactase reduces over time. This tends to run in families and is more common in certain ethnic groups, such as Asian people and varying levels of lactose will be tolerated in the diet. Congenital lactose intolerance is very rare and is a lifelong disorder.   
How can food hypersensitivity be allergyt2assessed?     
If food allergy or lactose intolerance is suspected, it is vital that a detailed allergy-focused clinical history is taken, tailored to the presenting symptoms and age of the infant or child12. This should form the mainstay of the diagnostic work up and part of this will involve determining whether the adverse reaction is typically an immediate (IgE-mediated) or more delayed-type allergic reaction (non-IgE mediated), or whether it may be simply lactose intolerance, as this will indicate whether allergy sensitisation tests or possible tests for lactose intolerance are required.Table 1details the questions that should be asked during the allergy-focused clinical history, which supports the recommendations by NICE, (2011)9. If there are signs of atopy in the family or child, the likelihood that the child has a diagnosis of food allergy is increased. It has been shown that nearly one third of children with atopic eczema have cow's milk protein allergy (CMPA) and about 40-50 per cent of children under one year of age with CMPA have atopic eczema13. The role of food allergy as a trigger for an eczema flare is greatest in infants, with up to 64 per cent of infants with onset of atopic eczema under three months of age demonstrating high risk IgE food sensitisation to egg, and/or cow's milk and/or peanut8. 

Based on the findings of the allergy-focused clinical history, a physical examination should be taken, paying particular attention to growth, which should be plotted on the appropriate growth chart for age and sex and a Body Mass Index calculated and plotted on the appropriate chart in children over two years of age. Physical signs of allergy-related comorbidities (atopic eczema, asthma and allergic rhinitis) should be identified9,14,15. The examination however, may reveal symptoms more suggestive of a non-allergic disorder that would require further investigation and tests15.    
How can a diagnosis of food allergy or lactose intolerance be confirmed? 
Lactose intolerance     
Diagnosis of lactose intolerance can be confirmed if the diarrhoea resolves within two weeks of exclusion of lactose from the diet11. A low lactose diet should only be required for a period of six to eight weeks, until lactase activity is fully re-established and then lactose should be gradually re-introduced over a period of one to two weeks to enable the body to adapt to the increasing lactose load.   

While on a diet containing lactose, stools can be tested for i) reducing substances which if positive indicate undigested lactose in the stools, ii) stool pH (more sensitive but less specific), where a low pH (< 5.0-5.5)indicates bacterial fermentation of lactose and other carbohydrates in the gut, which produce fatty acids that lower fecal pH. Alternatively, a lactose hydrogen breath test can be undertaken in hospital, which detects hydrogen from undigested lactose. However, these tests allergyt3are not necessary if dietary avoidance of lactose resolves the symptoms and reintroduction of dairy foods causes recurrence11. 
Food allergy     

Based on the results of the allergy-focused clinical history: 

If non-IgE mediated allergy is suspected, a trial elimination of the suspected allergen for between two to six weeks should be undertaken, followed by re-introduction after the trial9. A firm diagnosis can only be made if the symptoms resolve following the elimination period and re-occur on re-introduction of the allergen.    

If IgE-mediated allergy is suspected, the infant or child should be offered a skin prick test and/ or blood test for specific IgE antibodies to the suspected foods and likely co-allergens. Skin prick tests however, are generally not available in the community and hence usually require referral to a specialist allergy clinic. If specific IgE antibody testing is undertaken in the community, it is paramount that the health care professional is able to interpret the results in the context of information from the allergy focused clinical history, as the test alone is just a measure of sensitisation and therefore does not guarantee that a reaction will occur or how severe that reaction might be11. If the test is positive, alongside a positive clinical history, there is no need to undertake a food challenge to confirm the diagnosis17. A negative test suggests that the symptoms are not IgE-mediated, but it cannot rule out a diagnosis of non IgE-mediated food allergy or non-immune-mediated food hypersensitivity. Competencies required by health professionals to diagnose, treat and optimally manage food allergy are described by the Royal College of Paediatrics and Child Health (RCPCH) care pathway for food allergy18. 
How can parents be supported?   
If a diagnosis of food allergy has been made, parents or carers should be offered a wide range of information relevant to the type of allergy (Table 2), tailored to parental needs, provided at specific times and in various formats to optimise retention of information9,19. Follow up is therefore required, to check parental understanding of dietary advice or skin prick test results for example, and to continue to be able to offer relevant information at appropriate times.Table 3lists all the suitable hypoallergeallergycase2nic formulas (HAF) available, those that are soya-based and also those for the treatment of lactose intolerance and GOR, with indications as to which you might use and when.   

There is no one formula suitable for all elimination trials and hence it is usually necessary to liaise with a dietitian to discuss which one is most appropriate for each individual case. For non-IgE mediated allergy, due to the unpalatable taste of HAF, it is advisable to grade the child onto it in quarter strength increments daily, combining it with their current infant formula/ milk, such that by day 4 the child should be fully converted to HAF (Table 4). 

This is not possible for childrenwith IgE-mediated allergy, where immediate avoidance is imperative.  

In accordance with guidance from the committee on toxicology20, soya based formulas should not be used in infants under 6 months of age, due to their phytooestrogen content potentially carrying a risk to the infant's long-term reproductive health. Of probably greater concern is the chance of cross-reactivity between cow's milk protein and soya allergens, most notably in children with non-IgE mediated gastrointestinal symptoms (Fig 1). Whilst only a small number of children with IgE mediated allergy become sensitised to soya (8 to 14 per cent), up to 67 per cent with non-IgE mediated gut-related CMPA can become soya allergic21. Use of soya formula should therefore be limited to exceptional circumstances in infants under six months of age, eg: in non-breastfed infants from vegan families22. Breastfeeding mothers undergoing a cow's milk protein free diet should continue to take their vitamin D supplement (10mcg/day, as provided in the Healthy Start vitamins for pregnant and breastfeeding mums)23. They are likely to need a supplement providing around 1000mg elemental calcium per day, unless they consume at least one pint of a calcium fortified cow's milk substitute plus at least one calcium fortified dessert or yogurt per day.  

What happens once the trial elimination period has ended?   
After the two to six week trial of complete food allergen elimination, in non-IgE mediated allergy, the allergen should be re-introduced. If an improvement was observed during the elimination period, the timing of the oral food challenge should be considered on a case by case basis, in specialist consultations16. 
Non IgE mediated allergy 
There is a paucity of evidence regarding food rechallenging at home and so the following are suggestions based on personal experience. 

If a clear benefit is observed following elimination, re-introduction could be done gradually, with perhaps 1floz (30ml) daily increments of allergycase3formula per bottle, thereby limiting severe reactions and maintaining the child's familiarity with the HAF. In breastfeeding mothers and older children, re-introduction could be undertaken using gradually increasing amounts of cow's milk protein predominant foods, such as yogurt and cheese, thereby avoiding potentially unnecessary changes to the formula. In breastfeeding mothers on an elimination diet, this could be done in the mother's diet first. 

In some cases, if the benefit of elimination in an infant is irrefutable, such as might be described by parents/ carers reporting "it's as if they have a different baby" or "as if somebody waved a magic wand" and the parents/carers seem to be notably more relaxed, the re-challenge could be delayed until the infant is more settled and weaning established. 

If the benefits are less clear, a direct swap back onto the original formula/milk and normal diet  will help to maximise the contrast following the elimination period and after re-introduction.  

A few children have a severe reaction to food including lethargy, drowsiness and dehydration, and in these cases the challenge should be conducted in hospital, with access to intravenous fluids for possible fluid resuscitation14.IgE mediated allergyAny food challenge undertaken in infants and children with IgE mediated food allergy must be undertaken in a safe and controlled environment, with facility for paediatric resuscitation, due to the potential risk for anaphylaxis and other systemic reactions18. 
When should a referral be made?
All infants and children with a positive food allergy diagnosis (as determined from a positive clinical history and either i) a successful elimination followed by deterioration on re-challenge or ii) a positive serum specific IgE or skin prick tests) should be referred to a registered dietitian. This is necessary to ensure long term nutritional adequacy of their diet and provide on-going support and information, as dietary requirements and patterns change with age and advice on re-challenging is needed at regular intervals (frequency depends upon food allergens implicated)15. 
  

Referral to other specialist or secondary care should be considered when9: 

Symptoms persist, despite food elimination 

Faltering growth present in combination with one or more GI symptoms (Fig 1)  

Had acute systemic reactions or anaphylaxis 

Had a severe non-IgE mediated reaction 

Confirmed IgE mediated food allergy and concurrent asthma  

Significant atopic eczema where multiple or cross-reactive food allergies are suspectedallergyt4 

Persisting parental suspicion of food allergy despite a lack of supporting clinical history 

Strong clinical suspicion of IgE mediated food allergy but sensitisation tests were negative 

Clinical suspicion of multiple food allergies   

Summary     
Food allergy is poorly recognised by health professionals in primary care, and it is hoped that the recent publication of the NICE guidance9 will provide the opportunity to address this. Close liaison with dietitians, alongside extensive training on food allergy for GPs and members of children's health teams will be essential to ensure high quality care for families is provided.