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Food allergies have long been a grey area for GPs, with a great deal of scepticism about their role in many complaints. But allergies are increasing, and as Dr Helen Cox outlines, a step- wise approach to management is possible
as Dr Helen Cox
outlines, a step-
wise approach to
Few GPs need to be told about the current allergy epidemic in the UK. Prevalence rates for eczema, asthma and allergic rhinitis have trebled in the past 20 years. Food allergy currently affects 6-8 per cent of young children and has become the leading cause of anaphylaxis presenting outside the hospital.
Yet there is still considerable confusion and indeed scepticism among health professionals as to the diagnosis and management of food allergy.
Considerable progress has been made in the understanding of food-based allergic disorders with characterisation of many of the food allergens at the molecular level.
This has increased our understanding of the immunopathogenesis of allergic responses and may soon lead to novel immunotherapeutic approaches.
What do we mean by food allergy?
Food allergy is defined as an adverse immunologic response to a food, which occurs when oral tolerance fails to develop normally or 'breaks down' in genetically susceptible individuals.
Broadly speaking, food allergic reactions may be immediate or delayed. Reactions mediated by IgE are typically immediate, occurring within minutes to two hours of ingesting an allergen and vary in severity from trivial to life-threatening.
By contrast, delayed type reactions occur within hours or days of being exposed to a food, are largely T-cell mediated and are rarely life-threatening. Mixed IgE and cell-mediated reactions to foods occur in certain conditions.
What are the main foods associated
with allergic reactions?
Despite the enormous diversity of the human diet, relatively few foods cause allergic reactions. In children 85 per cent of all allergic reactions to foods are caused by eight foods.
Sensitisation is frequently 'occult' with reactions occurring on first known exposure.
There is considerable homology due to the existence of cross-reacting proteins (panallergens) between various plant and animal proteins. While some cross-reacting proteins are clinically important others are not.
The homology between peanuts and tree nuts is relevant with 30-50 per cent peanut allergics reacting to tree nuts. Most children with cow's milk allergy will be unable to tolerate goat's milk.
On the other hand the cross-reactivity between peanuts and other legumes is clinically irrelevant with 95 per cent of peanut allergic individuals being able to tolerate a variety of other legumes.
Some patients (mostly hay fever sufferers) develop localised oral symptoms of burning, itch and tingling following the ingestion of certain raw (but not cooked) fruits and vegetables (ie apples, carrots, celery and hazelnuts).
These patients have the oral allergy syndrome (OAS or pollen-food allergy syndrome) which develops as a result of cross-reacting proteins between various inhalant allergens (birch, ragweed and mugwort) and a variety of plant-derived proteins. These proteins are highly unstable and susceptible to heat degradation, which accounts for the absence of symptoms when eating the cooked rather than raw food. These reactions rarely progress to more severe reactions.
Who outgrows their food allergies?
Fortunately most children lose their sensitivity to allergenic foods within the first three to five years of life. Infants with non-IgE mediated allergy to milk and soya typically achieve tolerance during the second year of life. In infants with IgE mediated allergies to milk, egg, soya and wheat, tolerance is achieved slightly later with 85 per cent of children outgrowing their allergies by the age of five1. Induction of tolerance is accompanied by a fall in food-specific IgE concentrations.
Allergy to nuts and seafood is rarely lost with persistence of immediate hypersensitivity into adult life. In the 20 per cent who outgrow their allergy to nuts, most are younger than two years at presentation, have few additional food allergies, mild initial reactions, declining specific IgE and a long (>3 year) interval since the last reaction10.
Diagnosis of food allergy
The diagnosis of food allergy depends on a good clinical history, specific IgE tests, elimination diets and food challenges. In suspected immediate (IgE mediated allergy) skin prick tests and radioallergosorbent test (RAST) may be used to identify food specific IgE antibodies.
A wheal diameter of at least 3mm greater than the negative control is considered positive with an overall positive predictive accuracy of approximately 50 per cent. The obvious caveat to this is at least 50 per cent of patients testing positive will have falsely positive responses. A negative skin test on the other hand has a high negative predictive accuracy excluding immediate food allergy in >95 per cent of cases.
Studies using higher cut-off values for skin testing have shown certain wheal diameters to be 100 per cent predictive of a positive food challenge to these foods.
Similar 95 per cent diagnostic predictive values for immediate food allergy have been delineated using a quantitative measurement of food-specific IgE antibodies (CAP system FEIA; pharmacia-Upjohn Diagnostics).
Strongly positive tests, therefore, make the diagnosis of food allergy more likely. They do not predict the severity of clinical reactions.
In the absence of an absolute test, however, the oral food challenge test remains the gold standard. This is usually a hospital-based test and is used to confirm a diagnosis when there is discrepancy between the clinical history and specific IgE and skin prick tests or when wishing to assess whether or not a child has 'outgrown' their food allergy3.
Oral food challenges in children with a previous history of immediate food allergy should not be done at home because a respiratory reaction risk.
Role of food allergy in eczema
is there one?
A number of well-designed studies in unselected populations have shown the prevalence of food allergy in eczema patients to be 30 per cent7. In populations selected for eczema severity the prevalence of food allergy rose to 60-80 per cent2,8, and was greatest in young children and infants.
Specific IgE tests can therefore be extremely helpful in identifying food allergens as a trigger for eczema. It is important, however, to concentrate efforts on the major allergens together with known allergens causing reproducible, identifiable reactions, as opposed to testing for numerous minor allergens.
Around 10-25 per cent of food associated reactions in children with eczema, however, are non-IgE mediated8,9. A high index of suspicion of non-IgE mediated allergy to foods should be entertained in the infant (<6 months)="" with="" moderate="" to="" severe="" eczema,="" especially="" if="" the="" onset="" of="" eczema="" occurred="" during="" a="" period="" of="" exclusive="">6>
A six-week trial of milk and egg exclusion from the maternal diet (if breast-feeding) or infant diet, monitoring for improvement on exclusion and deterioration on reintroduction, will usually clarify the matter.
Role of cow's milk allergy in infantile colic and gastro-oesophageal reflux
The symptoms which characterise infant cow's milk allergy can be indistinguishable from gastro-oesophageal reflux with selected studies reporting improvement in 50 per cent of infants with vomiting +/- irritability when cow's milk was eliminated from the diet6.
Similar improvements in infant crying have been noted in studies examining the benefits of hypoallergenic milks in infants with colic4. There is, therefore, evidence to support a one- to two-week trial of an extensively hydrolysed protein formula (eHF) in formula-fed infants with vomiting or excessive irritability or crying.
Infant diets what are the alternatives?
The options vary depending on whether you are attempting to prevent the development of allergy in a high-risk infant (primary prevention) or whether you are treating a child with clinical signs of food allergy (tertiary prevention). In primary prevention, both exclusive breast-feeding for four months and the delayed introduction of solid foods after four to six months are associated with a lower cumulative incidence of cow's milk allergy (CMA) and eczema. There is currently no convincing evidence for a preventive effect of maternal diets during pregnancy or lactation.
The European and American Academy of Paediatrics recommends the following for the primary prevention of allergy5:
Primary prevention of allergy
No special diet during pregnancy or to the lactating mother.
Exclusive breast-feeding preferably for six months but at least for four months. If supplement is needed conventional cow's milk formula is recommended.
Avoidance of solid foods until six months (preferable) but at least four months.
For high-risk infants (one parent or sibling with allergic disease)
If supplement is needed an extensively hydrolysed protein formula is recommended
until four months of age. After the age of four months high-risk infants who have no signs of allergic disease can be nourished like normal infants.
Tertiary prevention of allergy
Treatment of established food allergy (tertiary prevention) requires removal of the causal allergen from both the infant and maternal diets (if breast-feeding). In CMA, an extensive protein hydrolysate (eHF) or amino acid formula is recommended during the first year.
In infants who fail to tolerate an eHF or in infants with multiple food protein intolerances an amino acid formula (eg Neocate) is recommended. Soy formula is poorly tolerated in delayed type CMA but well-tolerated in immediate CMA when the specific IgE to soy is negative.
Unfortunately soy is no longer recommended as the sole protein source in any infant <12 months="" following="" recent="" concerns="" from="" the="" department="" of="" health="" regarding="" the="" phyto-oestrogen="" content="" of="" soy="" and="" possible="" links="" with="" male="">12>
In infants with immediate CMA, consideration can be given at 12 months of age to changing
to a calcium-enriched soy formula (provided specific IgE to soy negative), or calcium-enriched rice milk. Involvement of a paediatric dietitian is essential.
Provision of Epipens who should get one?
This is an extremely difficult issue, which continues to be hotly debated. It is important to stress that the prescription of Epipens should be seen as part of a management package of allergy care. This includes dietary and community-based advice on allergen avoidance, to minimise the risk of future reactions together with the stepwise approach to the treatment of an allergic reaction.
Within our allergy unit we recommend the prescription of an Epipen to any child who falls into the following categories:
Previous respiratory or cardiovascular reaction
Reaction to trace amount of protein
Co-existent asthma (as risk factor for severe reactions)
Allergy to peanuts or tree nuts (as subsequent reactions may be more severe).
Helen Cox is a consultant in paediatric allergy and immunology at St Mary's Hospital, London
Test for foods commonly associated with allergies rather than many less-likely options
With the exception of nut allergy, most children outgrow their allergies
The food challenge test is still the gold standard for getting a firm diagnosis
Food allergy is common in severe eczema sufferers
Exclusive breast-feeding for at least four months reduces the risk of allergy
If necessary, use an amino acid or protein hydrolysate formula for infants with allergy symptoms
Common foods causing allergic reactions
1 Classification of food allergic reactions
Cutaneous Urticaria, angioedema, erythematous rashes, eczema flare
Gastrointestinal Vomiting, diarrhoea, abdominal pain, oral burning/itching
Respiratory Rhinitis, wheeze, cough, stridor, voice change, dyspnoea
Cardiovascular Hypotension (profound floppiness, collapse, loss of consciousness)
Mixed IgE and non-IgE mediated
Gastrointestinal Allergic eosinophilic oesophagitis, allergic eosinophilic gastroenteritis
Cutaneous Contact dermatitis, dermatitis herpetiformis
Gastrointestinal Food protein-induced proctocolitis, food protein-induced enterocolitis
and enteropathy, coeliac disease
Respiratory Food-induced pulmonary hemosiderosis
Predictive values of skin prick testing2
skin prick testing2
100% predictive level
Allergen Wheal diameter PPV
Milk 8mm 100%
Infants <2 yrs="" 6mm="">2>
Peanut 8mm 100%
Infants <2 yrs="" 6mm="">2>
Egg 7mm 100%
Infants <2 yrs="" 6mm="">2>
Predictive values of food- allergen specific IgE levels
allergen specific IgE levels
95% predictive level
Allergen KU/L PPV
Egg 7 98%
Infants <2 yrs="" 2="">2>
Milk 15 95%
Infants <2 yrs="" 5="">2>
Peanut 14 100%
Fish 20 100%
Tree nuts 15 95%
Soybean 30 73%
Wheat 26 74%
1 Sampson HA. Food allergy. J allergy Clin Immunol 2003;111:S540-7
2 Sporik R et al. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin Exp Allergy 2000;30:1540-6
3 Bock SA et al. Double-blind placebo controlled food challenge (DBPCFC) as an office procedure; a manual. J allergy Clin Immunol 1988;82:987-97
4 Lucassen PLB et al. Effectiveness of treatments for infantile colic: systematic review. BMJ 1998;316:1563-9
5 Muraro A et al. Dietary prevention of allergic disease in infants and small children. Part III: critical review of published peer-reviewed
observational and interventional studies and final recommendations. Paediatr allergy Immunol 2004;15:291-307
6 Rudolph CD et al.Pediatric GE reflux clinical practice guidelines.
J Pediatr gestroenterol Nutr 2001; 32, suppl 2, S1-31
7 Eigenmann PA, Calza AM. Diagnosis of IgE mediated food allergy among Swiss children with atopic dermatitis. Pediatr allergy Immunol 2000 May;11(2):95-100
8 Niggemann B et al. Predictors of positive food challenge outcome in
non-IgE mediated reactions to food in children with atopic dermatitis. JACI 2001 Dec;108 (6):1053-8
9 Roehr CC et al. Atopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis. JACI 2001 Mar;107(3):548-53
10 Hourihane JO et al. Clinical characteristics of peanut allergy.
Clin and Exp Allergy 1997;27:634-9