The development of a standardised diet history tool to support the diagnosis of food allergy

The characterization of symptoms is an essential first step when taking a history from someone presenting with adverse reactions to foods.

A number of guidelines have summarised these symptoms [1,11-13], primarily those seen in children, which can be skin related (pruritus, erythema, acute urticaria, acute angioedema), gastro-intestinal (anal pruritus, colicky abdominal pain, diarrhoea and vomiting) or upper and lower respiratory symptoms. In adults, skin reactions are also associated with IgE-mediated food allergy [16], but gastrointestinal symptoms are predominant especially dysaesthesia of the tongue, oro-pharyngeal pruritus and vomiting [17-20]. Rhinitis, conjunctivitis and asthma are also presenting features of adult food allergy [5,15] Tachycardia, hypotension, throat tightness, bronchospasm, laryngeal oedema, shortness of breath, syncope and anaphylaxis can affect all ages [21,22].

Proctocolitis [23] is characterised by blood and mucous in the stools and occasional diarrhoea, although the infant appears well. The symptoms of food protein-induced enterocolitis syndrome (FPIES) include late onset gastro-intestinal symptoms of profuse vomiting, diarrhoea, pallor and occasionally hypovolemic shock [24]. Children and infants with Eosinophilic Oesophagitis (EoE) often show signs of chronic vomiting, abdominal pain, poor appetite, food refusal, other feeding refusal behaviours as well as dysphagia [25]. Up to one third of young children with Atopic Dermatitis (AD) may present with a FA, particularly those with moderate to severe eczema unresponsive to topical treatment [26,27]. Adults have less well documented non-IgE-mediated food allergies, but dysphagia and oesophageal food impaction are particularly associated with adult-onset EoE [28].

Sometimes symptoms of an allergic disorder can resemble those due to non-immune mediated adverse reactions to foods, thus complicating the diagnostic process. For example, dietary histamine has been reported to provoke rhino-conjunctivitis, flushing, pruritus, urticaria, asthma, hypotension and abdominal cramping [29]. The food additive sodium metabisulphite has been linked to symptoms of rhinitis, nasal blockage, wheeze and abdominal pain [30]. Abdominal symptoms are a notable feature of Irritable Bowel Syndrome (IBS), a diagnosis which is positively associated with pain in the lower abdomen, pain relieved by bowel movements, frequent pain and abdominal bloating [31].

It is important to establish the temporal relationship between eating a food and the onset of symptoms. It is generally agreed that the sooner the symptoms occur after eating, the greater the likelihood that an IgE-mediated mechanism is provoking the reaction [1,12]. Non-IgE-mediated FA symptoms are usually delayed; children with FPIES typically experience severe vomiting 1–4 hours after ingestion of the suspect food [32]. However occasionally symptom speed of onset does not provide such clear signposting; co-factors such as exercise can mislead if the symptoms only occur during exercise, but the food involved could have been eaten up to 2 hours earlier [33]. Another example is delayed anaphylaxis to red meat occurs in relation to IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) generated by tick bites [34]. Conversely, some non-immune-mediated adverse food reactions may manifest soon after eating, i.e. gastrointestinal symptoms triggered by lactose intolerance [35], or wheeze provoked by the food additive sodium metabisulphite [30].

Other important factors relating to symptoms include ascertainment of the quantity of food required to trigger symptoms, frequency and reproducibility of the reactions and the interval since the last reaction [1,11-13]. The age of onset of symptoms, feeding/diet history, history of any food elimination and any previous therapeutic interventions are also significant.

For children, in addition to a physical examination focusing on growth and development, any allergy related co-morbidities and family history of atopy should be ascertained [1,11]. The likelihood of food allergy is enhanced in children with moderate to severe eczema [26]. For adults, a physical examination is also helpful, but it is also vital to establish atopic status due to the strong association between atopic disease and the manifestation of food allergy in adults [36]. Allergic rhinitis is increasingly prevalent in food allergic adults, reportedly affecting 41% of UK adults suffering from adverse reactions to foods in 2009, compared to 25% in 1991 [37,38]. Asthmatics with food allergy are also more likely to have severe and uncontrolled asthma [39] and suffer from fatal or near fatal food anaphylaxis [22].

There is an increasing level of aeroallergen sensitisation in all age groups, which persists into old age [40,41]. Thus establishing sensitisation to pollens, mites and animal dander is vital when interpreting the history, especially as geographical variation in aeroallergen sensitisation across Europe affects prevalence and foods involved [42]. Positive tests to pollen [15], latex [43] or house dust mite [44], can be linked to homologous reactions to fruits, vegetables, nuts or shellfish. More unusual cross-reactions include sensitisation to bird feathers inducing symptoms to the egg yolk allergen alpha livetin [45], individuals sensitised to galactose-alpha-1,3-galactose (alpha-gal), reacting to beef and pork [34], and reactions to pork associated with sensitisation to cats [46]. The sensitising agent might be a food-related parasite such as cereal mites [47] or the Anisakis nematode worm [48].

In adults, exercise, alcohol, stress, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) can enhance or precipitate an allergic reaction to food [49]. Food-dependant exercise-induced anaphylaxis (FDEIA) is characterised by a lack of reaction to the trigger food unless it is consumed in close proximity to taking exercise [50]. Wheat, crustaceans, tomatoes, celery, strawberries, cheese have all been implicated [33,49-53]. Alcohol can also act as a co-factor, but symptoms to alcohol could also be due to an allergy to grapes or barley [54,55], sensitivity to vasoactive amines or sodium metabisulphite [29,30], or caused by a congenital deficiency of the enzyme alcohol dehydrogenase [56]. Food additives have also been shown to act as co-factors in cases of anaphylaxis [53]. Co-factors may be less relevant in children [57], but exposure to allergens other than via the oral route require consideration in both children and adults; these include inhalation of aerosolized allergens, transfer of allergens during cooking or by skin contact [58-60].

Although there are a large range of foods which can be implicated in IgE-mediated FA, only a limited number regularly provoke reactions in most people. Most reactions in children are due to milk, egg and peanut [2], with milk and egg being the most common causes of anaphylaxis [61]. Milk, egg, wheat and soy allergy usually remit in late childhood [62-65], thus a primary allergy to these foods is rare in adults. Wheat allergy in adults is generally associated with FDEIA [52] and adults reporting reactions to soy usually develop symptoms due to homology between soy protein and birch pollen allergens [66]. Peanut and tree nut allergy in adults is usually a persistence of childhood allergy since only 8-10% of cases are newly diagnosed in adolescence or adulthood [67-69]. Up to 30% of adults with a peanut allergy have cross-reactivity to other legumes such as lupine [70]. Lupine allergy also presents in childhood, but is far less prevalent than peanut allergy in the general population, affecting less than 0.3% of patients with reported reactions to foods [71]. Seeds such as sesame and mustard are also a significant cause of IgE-mediated reactions in certain populations [72,73]. Those with a primary allergy to one type of nut, seed or legume can react to other similar foods due to co-sensitisation to homologous allergens [74-79].

Fish and shellfish trigger both paediatric and adult IgE-mediated FA [80,81], often provoking severe reactions [22,82]. Pan allergens in vertebrate fish account for strong interspecies cross-reactivity; thus sensitization to more than one species is common in fish-allergic individuals [80]. The same is true for crustaceans and molluscs, although sensitisation to minor seafood allergens can limit clinical reactivity solely to the seafood which provoked the index reaction [83]. The lack of homology between the pan allergens in vertebrate fish and shellfish usually means fish-allergic individuals can tolerate shellfish and vice versa [80].

Fruits and, to a lesser extent, vegetables, are often the most frequently reported foods to provoke new onset reactions in adults [5,17,18,37]. These reactions are usually due to oral allergy syndrome or pollen-food syndrome (PFS), a common manifestation of cross-reactive plant FA in adults, which can affect 50% or more pollen-sensitized individuals [15,17]. Such reactions are also reported in older children and teenagers, although only limited epidemiological data supports this [84]. Reactions, usually to more than one food, typically occur to tree nuts, apples, peaches and cherries, although peanuts and soy may also be involved [15,17,85-87]. If PFS is suspected then any history of seasonal hay fever should be linked to symptoms to fruits and vegetables, and symptoms may be worse or only occur during the pollen season [61]. Homologous allergens in natural rubber latex (Hevea brasiliensis) can also cross-react with foods, in particular kiwi fruit, avocado, chestnuts and bananas [44]. Lipid Transfer Protein (LTP) allergy should also be considered if plant foods provoke severe reactions [88]. LTP allergy, usually associated with sensitisation to the peach LTP allergen Pru p 3 [88,89], is highly prevalent in southern Europe [90], and associated with presence of co-factors such as alcohol and exercise [19,49].

Whilst children might have a reaction to a food soon after the first exposure, older children and adults may suddenly develop symptoms to foods consumed for many years. However, foods habitually eaten are mostly considered as safe and should not be tested. If the reactions are to multiple foods and PFS is not suspected, then a ‘hidden’ allergen used as an ingredient in composite dishes may be implicated, such as legumes, seeds, celery and natural food colourings.

FPIES typically occurs in response to milk or soy proteins in infant formula, and more rarely to food proteins in breast milk [91,92]. The common provoking allergens in FPIES are milk, rice and soy, but reactions have also been reported to oats, fish, egg and some fruit and vegetables [93]. Although eosinophilic gastrointestinal disorders are seen in both adults and paediatrics, offending foods may differ [94]. In children, milk, egg, wheat and soy have been found to be most relevant, although in some cases fish, nuts and peanuts also play a role, although meat proteins (including, beef, lamb, chicken and pork), carrots, potato, maize and peanuts may also be causative foods [95]. Wheat and milk appear to be major allergens in adults although other triggers could include corn, rice and legumes [96].

Milk is most frequently linked to non-immune mediated conditions in adults including lactose intolerance [35], IBS [97], and some respiratory conditions [98]. In the absence of IgE-sensitisation to wheat, coeliac disease [99] should be excluded prior to considering differential diagnoses such as non-coeliac gluten sensitivity [100] and IBS [101]. There is some evidence that foods containing high levels of oligo-, di-, mono-saccharides and polyols carbohydrates (FODMAPS™) could provoke some or all of the gut symptoms experienced by IBS sufferers [102]. Oligosaccharides (wheat, rye, onions, garlic, artichokes and legumes) probably affect the majority of IBS sufferers, 45% of whom will also be intolerant to foods high in fructose (honey, apples, pears, watermelon and mango) [103]. Reported reactions to multiple foods in the absence of IgE-sensitisation can indicate a non-immune mediated reaction. Potential mediators may include food additives (azo dyes, benzoates, sulphites and mono-sodium glutamate) [30,104], or naturally-occurring substances such as vasoactive or biogenic amines (fish, pork and fermented or aged meat products, strong cheeses, red wine, spinach, aubergine and yeast extract) [29], or salicylates (coffee, dried herbs and spices, cherries, strawberries and certain apple varieties) [105] although robust evidence on the prevalence of these types of reactions is lacking.

Nutritional impairment is a tangible risk in those with suspected FA; the elimination of food allergens often entails the exclusion of foods that contribute essential nutrients for growth and development (Table 2) [9,10]. Poor growth and stunting has been shown to occur in children with IgE-mediated FA who are on exclusion diets [10,110], with the number of foods excluded linked to a low weight for age and height for age in such children [10]. Feeding difficulties may also occur as clinical features of non-IgE mediated FA. Adults generally are not in danger of developing major nutritional deficiencies although individuals avoiding multiple foods can be at risk [111]. Therefore both tools contain a nutritional assessment section which, on completion, should indicate whether onward referral for specialist nutritional intervention is required. A dietitian can ascertain and interpret the diet history to ensure normal growth and development, employing a variety of measures to determine dietary intake [112,113]. The nutritional analysis can signpost the requirement for nutritional supplements and give expert advice to ensure a healthy, regular and varied diet is taken as this has been shown to be of importance in the development of allergy [114,115] It is important that the user take into account the important role of under-nutrition in paediatric and adult food allergy since poor nutritional status may aggravate symptoms and a healthy diet could be important in the prevention of allergic disease [10,116,117].