Table of Contents  

Green: Food allergy

Introduction

Adverse reactions to food are common in the general population. However, amongst the community of health professionals, there is still widespread uncertainty about criteria for diagnosis and correct management. There is a vast amount of research in this area, indicative of how the pathogenesis and the best ways for diagnosis and management of these conditions are still being developed. This review focuses on the epidemiology, pathogenesis, diagnosis and management of food allergy.

Definition

The National Institute of Allergy and Infectious Diseases has defined food allergy as an ‘adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food’.1 This can be either an IgE-mediated or a non-IgE-mediated immune response. The term ‘food hypersensitivity’ is also used to refer to food allergies.2 In general, any food can trigger an allergic response. The most common allergens are cow’s milk, hen’s eggs, peanuts, tree nuts, wheat, soya, fish and shellfish.3 Food intolerance, on the other hand, is a non-immune, adverse reaction to food. This can be caused by different mechanisms, including metabolic disorders that affect the digestion or absorption of food (e.g. lactose intolerance due to lactase deficiency), reactions to a pharmacologically active component, such as vasoactive amines (e.g. caffeine and tyramine from aged cheeses), reactions to toxins, such as food poisoning, and undefined mechanisms (Figure 1).1

FIGURE 1

Classification of adverse reactions to food.

8-3-6-fig1.jpg

Prevalence

The prevalence of food allergies is around 8% in children and 5% in adults. There has been a tendency for this to increase over the last three decades.4 In the United States of America (USA), a population-based data trial of clinical food allergy showed an estimated prevalence of 2.5% in young children (e.g. milk, 2.5%; egg, 1.3%; peanuts, 0.8%; fish, 0.1%).5 In Australia, in a population-based sample of 2848 12-month-old infants, the prevalence of challenge-proven peanut allergy, raw egg allergy and sesame allergy was 3.0%, 8.9% and 0.8%, respectively.6 In the United Kingdom (UK), in a cohort study of 757 11-year olds and 775 15-year olds, the prevalence of food allergy, confirmed using open food challenges and positive skin prick test (SPT) responses, plus a history of adverse reactions, was 2.3% in both the 11- and 15-year-old cohorts.7 In general, food allergies appear to be more common in children than in adults. Allergies to egg, cow’s milk, soya and wheat tend to fade away after a few years of food avoidance, but allergies to peanut, tree nuts, fish and shellfish tend to be for life.8

A multicentre, European case series in IgE-mediated food allergy, the EuroPrevall project, is aiming to provide data on different phenotypes of food allergy. These include milk, egg, fish, shrimp, peanuts, hazelnut, celeriac, apple and peach and all will be confirmed by double-blind, placebo-controlled food challenges (DBPCFCs). The plan is also to validate new in vitro diagnostic tests, to find out threshold values for diagnosis and to examine the socioeconomic impact of food allergy in the community.9

Risk factors

Generally speaking, patients most at risk of developing a food allergy are those with a biological parent or sibling with a history of food allergy, allergic rhinitis, eczema or asthma.1

However, other risk factors have been associated with increased likelihood of food allergies. Food allergy seems to be common in males, black children, people with low consumption of omega-3 polyunsaturated fatty acids or low consumption of antioxidants and those who are obese.10 Several studies have shown that vitamin D deficiency is associated with increased risk of food allergy. Sharief et al.11 performed a study with 3136 children and adolescents. They found increased risk for sensitization to peanuts in those with vitamin D levels of less than 15 ng/ml, in comparison with those having vitamin D levels greater than 30 ng/ml.11 Osborne et al.,12 in Australia, have shown that people who live further from the equator are more likely to have a food allergy. They believe that this might be related to having the lowest exposure to ambient ultraviolet radiation.12

Eczema in early childhood seems to be a strong risk factor for developing IgE-mediated food allergy. To determine the relationship between eczema and food allergies, Martin et al.13 performed a population-based study on 4453 1-year-old infants with eczema and assessed their risk for food allergy. Those children with eczema undertook skin prick testing to egg, peanuts and sesame. Those with a detectable weal of any size for any of the allergens underwent an oral food challenge. They found that the risk for peanut and egg allergy was, respectively, 11 times and 6 times higher in children with eczema than in those without eczema. Of the infants who developed eczema that required treatment with topical corticosteroid during the first 3 months of life, some 50.8% developed food allergy. This suggests that the more severe the eczema, the higher the risk of developing food allergies.13

Pathogenesis

The mucosal immune system of the gastrointestinal tract is continuously in contact with environmental antigens such as bacteria and food proteins. To avoid the development of an allergic reaction to food, the mucosal immune system must develop oral tolerance, which is the capacity to suppress immune reactivity to foreign proteins and harmless bacteria.14

The intestinal epithelial cell barrier, formed by a simple, columnar epithelial cell layer, separates the internal environment from the lumen to prevent absorption of antigens. The presence of tight junctions between adjacent enterocytes, the mucus layer that covers the epithelium (glycocalyx), the intestinal microvillus, luminal enzymes and pH are all features of the intestinal mucosa that avoid the passage of particles though the epithelium.3

The gut-associated lymphoid tissue lies below in the lamina propria and forms the immunological barrier that differentiates organisms and food proteins that are potentially harmful from those that are not. This immunological barrier consists of an innate system (macrophages, polymorphonuclear leucocytes, natural killer cells and Toll-like receptors) and an adaptive immune system (intraepithelial and lamina propria lymphocytes, secretory immunoglobulin A, Peyer’s patches and cytokines).14

When food proteins enter the body – by skin penetration, inhalation or ingestion – they are encountered by the antigen-presenting cells (APCs), which present them to the T-helper (Th) cells. Th1 response is a cell-mediated response, directed towards intracellular bacteria and protozoa. On the other hand, Th2 response is directed against parasites and involves the stimulation of basophiles, eosinophils, mast cells and IgE-producing B cells, which is a type 1 hypersensitivity response and IgE-mediated food allergy.10

Oral tolerance requires the development of an active immune response, mediated by regulator T (Treg) cells with increased production of interleukin 10 (IL-10). IL-10 prevents Th1 production of interferon gamma and IL-2 and reduces Th2 production of IL-4 and IL-5.10

The physiological digestion of dietary proteins by proteolitic enzymes, as well as the presence of gastric acid, seems to reduce protein immunogenicity by destruction of conformational epitopes.15 Gastric digestion seems to decrease the possibility of food proteins binding to IgE, which, in turn, increases the amount of protein necessary to trigger an allergic reaction (Figure 2).16

FIGURE 2

Pathogenesis of food allergies. Some food proteins can cross the epithelial barrier and encounter APCs. In tolerant responses, the production of IL-10 and transforming growth factor beta stimulates Treg cell proliferation. By contrast, IgE-mediated food allergy occurs when a Th2 response (which releases IL-4 and IL-13), directed against a food protein, induces IgE-producing B cells with stimulation of eosinophils, basophils and mast cells.

8-3-6-fig2.jpg

Clinical manifestations

IgE-mediated reactions

Signs and symptoms of IgE-mediated (Table 1) allergic reactions to food typically involve the skin (urticaria, angioedema, pruritus and erythema), respiratory system (wheeze, stridor, persistent cough, hoarse voice, nasal congestion and respiratory distress), gastrointestinal tract (vomiting and abdominal pain) and, less commonly, the cardiovascular system (hypotension, pale and floppy infant or collapse). Typically, the onset of symptoms is acute, beginning within minutes or taking up to 2 hours after ingestion of the allergen.

TABLE 1

Clinical manifestations of IgE-mediated food allergy (modified from Sicherer and Sampson3)

Acute urticaria/angioedema Oral allergy syndrome Anaphylaxis
Typical age Children > adults Adult > young child Any
Key features Triggered by ingestion or direct skin contact Pruritus, mild oedema confined to mouth Rapidly progressive, multiple organs reaction
Most common causal food Egg, milk, peanuts, tree nuts, soy, wheat, fish, shellfish Raw fruit/vegetables; cooked forms tolerated Any. Most commonly egg, milk, peanuts, tree nuts, fish, shellfish
Natural course Depends on food Might be long-lived Depends on food

Acute urticaria and angioedema

Acute urticaria and angioedema are common cutaneous manifestations of food allergy. Around a fifth of cases of acute urticaria are caused by food allergy. However, food allergy is rarely the cause of chronic urticaria.17

Contact urticaria

Contact urticaria can be seen on skin that has been in direct contact with food. Common allergens can induce this reaction, as well as raw vegetables, fruits, raw meats, seafood, rice and beer.18

Oral allergy syndrome (pollen-associated food allergy syndrome)

Oral allergy syndrome (pollen-associated food allergy syndrome) is caused by a reaction to food proteins that have cross-reacted with pollen proteins. The syndrome is more common in patients who present allergic rhinitis to pollen. Symptoms include pruritus and mild swelling, confined to the oropharynx.19

Food-associated, exercise-induced anaphylaxis

Food-associated, exercise-induced anaphylaxis is a disorder characterized by the onset of an allergic reaction during or immediately after physical exercise. The symptoms can be urticaria, angioedema, gastrointestinal and even anaphylactic shock. Symptoms do not develop if the patient does not exercise within 4 or 5 hours after the ingestion of the allergen. Crustaceans and wheat flour seem to be the most common foods that trigger the allergic reaction.20

Anaphylaxis

Anaphylaxis is a severe allergic reaction that progresses rapidly, affecting multiple organs. Patients may present a combination of symptoms, including reactions on the skin and in the respiratory and gastrointestinal systems. They may also present cardiovascular symptoms, including hypotension, cardiac arrhythmia, vascular collapse and death. Food-induced anaphylaxis is the most common single cause of anaphylaxis occurring outside the hospital. In the USA, fatal cases of anaphylaxis are mainly triggered by peanuts and tree nuts; most of these victims are teenagers or young adults with a previous history of asthma.21

Non-IgE-mediated reactions

Symptoms related to non-IgE-mediated food allergies (Table 2) typically affect the gastrointestinal tract (abdominal pain, vomiting, diarrhoea and bloody stools) and skin. They have a subacute (several hours after the ingestion of the food) or chronic onset of symptoms. There are three main clinical disorders, which are described in the sections that follow.

TABLE 2

Clinical manifestations of non-IgE-mediated food allergy (modified from Sicherer and Sampson24)

Food protein-induced enterocolitis syndrome Food protein-induced proctitis and proctocolitis Food protein-induced enteropathy
Typical age Predominantly affects infants Otherwise healthy neonate Infants (< 3 months old)
Key features Vomiting, diarrhoea, failure to thrive, lethargy Bloody stools with mucus Chronic diarrhoea or steatorrhoea
Most common causal food Mainly related to cow’s milk, soy, rice, oats and meat Mainly triggered by cow’s milk through breast-feeding Gluten
Natural course Symptoms resolve after avoidance of allergen Symptoms disappear with elimination diet Symptoms disappear with elimination diet

Food protein-induced enterocolitis syndrome

Food protein-induced enterocolitis syndrome (FPIES) mainly affects infants. Chronic exposure can lead to emesis, diarrhoea, poor growth and lethargy. Re-exposure after restriction produces emesis, diarrhoea and hypotension 2 hours after ingestion.22

Food protein-induced proctitis and proctocolitis

Food protein-induced proctitis and proctocolitis (FPIAP) involves the passing of mucus and bloody stools in infants. The most common trigger is cow’s milk through breast-feeding. Usually, this affects infants of between 2 and 8 weeks old. It settles after a few days of an elimination diet.22

Food protein-induced enteropathy

Food protein-induced enteropathy (FPE) is a disorder that presents with diarrhoea (steatorrhoea) and poor growth, usually during the first months of life. An intestinal biopsy shows villous atrophy with prominent mononuclear cell infiltrate.23

Heiner syndrome

Heiner syndrome is a rare infantile disorder characterized by the presence of pulmonary infiltrate, iron deficiency anaemia and failure to thrive triggered by milk protein.3

Mixed IgE-/non-IgE-mediated reactions

The allergic eosinophilic disorders are characterized by eosinophilic infiltration of the oesophagus, stomach and/or intestinal walls. The eosinophilic infiltrate can affect the mucosa, muscularis propria and/or serosa.

Eosinophilic oesophagitis

Eosinophilic oesophagitis is a condition that can affect children and adults. Multiple allergens have been associated with this condition; the most common are eggs, cow’s milk, wheat and soya.

In children, the most common symptoms include feeding disorders, reflux, food refusal, early satiety, vomiting and failure to thrive. Patients may have a history of food allergy with proved sensitization to the food. In adults, the main symptoms are reflux, chest pain, dysphagia and food impaction. Patients with no pathological acid reflux and with symptoms that do not respond to a high dose of proton-pump inhibitors should undergo an endoscopy with multiple oesophageal biopsies. The presence of more than 15 eosinophils per high-power field infiltrate in the oesophageal mucosa confirms the diagnosis.25,26

The management of eosinophilic oesophagitis includes elimination diets to one (targeted elimination diet) or several suspected food allergies (six-food elimination diet). In cases of severe gastrointestinal symptoms and failure to thrive, an elemental diet can be considered. Treatment with dilatation of oesophageal strictures or with topical steroids can alleviate the symptoms.22,27

Eosinophilic gastroenteritis

Eosinophilic gastroenteritis refers to a group of gastrointestinal diseases, including eosinophilic gastritis, eosinophilic enteropathy and eosinophilic colitis. The symptoms include nausea, vomiting, chronic abdominal pain, ascites, weight loss, oedema and obstruction.28 This is dependent on the location within the gastrointestinal tract and the degree and depth of the eosinophilic inflammation within the intestinal wall. The majority of patients have a history of atopy, including asthma, eczema, food allergy, and present peripheral eosinophilia. The current management of this condition is based on an elimination diet and topical or systemic steroids.29

Cow’s milk protein allergy

Cow’s milk protein allergy (CMPA) is common disorder in infants, affecting between 2% and 7% of children younger than 12 months old. It presents either with clinical features of IgE-mediated allergy symptoms (acute onset of symptoms and anaphylaxis) or with features of non-IgE mediated allergy [persistent crying, eczema, diarrhoea, gastro-oesophageal reflux disease (GORD) and constipation]. We may suspect the presence of CMPA in an infant with other features of atopy, such as eczema or GORD, which do not respond to conventional therapy, or where the infant has symptoms affecting several systems or where the symptoms are dose dependent (Table 3).30

TABLE 3

Clinical manifestations of non-IgE-mediated food allergy (modified from Sicherer and Sampson24)

Eosinophilic oesophagitis Eosinophilic gastroenteritis Atopic dermatitis (eczema)
Typical age Children and adults Children and adults Infant > child > adult
Key features Feeding disorders, reflux symptoms, vomiting, dysphagia, food impaction Vary on site(s)/degree eosinophilic infiltration: abdominal pain, ascites, weight loss Associated with food allergy in around 35% of children with moderate to severe rash
Most common causal food Multiple Multiple Mainly egg and milk
Natural course Likely to be persistent Likely to be persistent Typically resolves

Diagnosis of IgE-mediated food allergy

The diagnosis of food allergy requires a thorough, clinical history and physical examination, followed by the measure of sensitization, by either a SPT or allergen-specific IgE (sIgE) testing. If the diagnosis is still uncertain, a DBPCFC is the gold-standard test.

History

Food allergy symptoms are clearly related to the ingestion of the trigger food and are reproducible. The case history should reveal the allergen that causes the reaction, the quantity ingested and the form of its ingestion (raw, baked or cooked). Typically, IgE-mediated food allergy occurs at first exposure with the allergen and the symptoms appear in less than 1 hour. Only around half of food allergy cases can be diagnosed based on history alone. Therefore, SPTs or sIgE levels are necessary for an accurate diagnosis.31

Investigations

Once the clinical history suggests IgE-mediated food allergy, the next step is to detect sIgE. The most common tests used in clinical practice are the SPT, the measurement of serum food-specific IgE and, in some cases, atopy patch testing.32

The presence of sIgE in food allergens, without clinical symptoms after exposure to those foods, is called (allergic) sensitization1 and does not equate to allergy. SPTs have the advantage of being inexpensive and the results are available immediately. However, performing this test requires skilled staff and the food extracts are not well standardized. The measurement of sIgE has the advantage of being commonly accessible to health professionals and allows an ample variety of allergens to be tested at the same time.31

Food allergen-specific serum IgE

The level of sIgE can predict the chances of a given food leading to an allergic reaction, though it cannot predict severity. Factors that can help to predict the severity of the allergic reactions are patient age, the amount of food ingested, details of food preparation (whether it is raw, cooked or processed), the combination with other foods and the presence of comorbidities (e.g. asthma or eczema).8

Performing a sIgE test can detect the presence of circulating sIgE antibodies in the serum. The Phadebas radioallergosorbent test (RAST®; Pharmacia Diagnostics AB, Uppsala, Sweden) was the first assay for the detection of sIgE antibodies. Currently, there are different autoanalyser-based, sIgE antibody assays, such as ImmunoCAP® (Pharmacia Diagnostics AB, Uppsala, Sweden), IMMULITE systems (Siemens Healthcare, Erlangen, Germany) and the HYTEC™ 288 system (Hycor Biomedical, Inc., Garden Grove, CA, USA). These assays use non-isotypically labelled, antihuman IgE and are calibrated using the same reference data. There is enough evidence to identify values of sIgE that have a positive predictive value (PPV) of 95% to assess whether or not a child has an allergy to cow’s milk, egg, fish, peanuts or tree nuts, using DBPCFCs as the gold standard (Table 4).31

TABLE 4

The 95% PPVs for serum-specific IgE for various allergens (modified from Stiefel and Roberts31)

Specific IgE levels (IU/ml) associated with 95% PPV
Egg ≥ 7
Egg (infants ≤ 2 years) ≥ 2
Milk ≥ 15
Milk (infants ≤ 2 years) ≥ 5
Peanuts ≥ 15
Peanuts (infants ≤ 2 years)
Tree nuts ≥ 15
Fish ≥ 20

IU, international unit.

The results of sIgE tests must be interpreted in the context of the clinical history only. The larger the sIgE, the greater the likelihood that a child has an IgE-mediated allergy. However, the severity of the allergic reaction does not correlate with the results of the sIgE test. A pre-test probability (the possibility of a patient having a clinical allergy) could be estimated from the clinical history before the sIgE test is performed. Stiefel and Roberts31 designed a three-by-three table, combining clinical history and sIgE results, to predict the probability of clinical allergy, segmented into high, intermediate and low (Table 5).

TABLE 5

Schema to use when considering food allergy in children and teenagers (modified from Stiefel and Roberts31)

Likelihood of clinical allergy from specific IgE (kU/l)
Low (< 0.35) Intermediate (0.35 to < 15) High (≥ 15)
Likelihood of clinical allergy from history High, e.g. urticaria and wheeze on two exposures Possible allergy Probable allergy Allergy
Intermediate, e.g. urticaria in a single exposure Possible allergy Possible allergy Probable allergy
Low, e.g. non-IgE symptoms No allergy Possible allergy Possible allergy

Most recently, allergen component proteins have been used to increase the accuracy of predicting food allergy and to differentiate more effectively between sensitization and clinical allergies.33

Skin prick test

The SPT involves puncturing the skin with a lancet to apply food extracts and controls. After 15 minutes, a weal of 3 mm or more is considered a positive result.34 It has been shown that using the weal size and skin index when testing allergy to hen’s eggs and cow’s milk can predict a positive outcome for the food challenge. However, the sensitivity and specificity of this test is poor, if one simply categorizes it as a positive or negative result.35

Double-blind, placebo-controlled food challenge

If the diagnosis remains uncertain, the gold-standard test to confirm the diagnosis of food allergy is the DBPCFC, though some evidence suggests that open food challenges can give the same results.36 During DBPCFC, patients will receive the allergen and placebo on separate, randomized days, while being monitored for clinical reactions. This test has several disadvantages. It requires specialized staff, it has to be carried out in an inpatient setting and it has the risk of anaphylaxis. Further, some reactions are considered positive, even if the patient has received a placebo. Ahrens et al.37 retrospectively analysed positive placebo reactions in a cohort of 740 placebo challenges. Of all placebo challenges, 2.8% were positive. Compared with those children classified with negative placebo reactions, children with positive placebo challenges were younger (less than 18 months old), had a higher level of total IgE and had a worsening of atopic eczema as the most common clinical reaction.37

A clinical case report suggested cross-contamination or inadvertent transfer of the allergen from another person during challenge observation periods as a cause of positive placebo challenges.38 Although there are no well-accepted criteria for diagnosis of food allergy, experts in the field still consider DBPCFC necessary to confirm diagnosis.39

Figure 3 shows a general approach to diagnosis.

FIGURE 3

General approach to diagnosis of adverse reactions to food (modified from Sicherer and Sampson24).

8-3-6-fig3.jpg

Management of food allergy

Avoidance and emergency treatment

The current management of IgE-mediated food allergies relies on dietary restrictions, and medication in the case of accidental allergic reactions. Therefore, education of patients and relatives is crucial to avoid exposure to allergens. Education includes recognizing the presence of the allergen when buying meals in the shop (label reading) or in restaurants. It is also necessary to recognize the symptoms of allergy. In the case of severe reaction, patients need to have emergency treatment, using self-injectable adrenaline. Other medications such as H1 and H2 antihistamines and glucocorticoids may help to relieve mild symptoms.3

Early introduction of food in infants

Over the last 20 years, the National Institute for Health and Care Excellence (NICE) guidelines in the UK have recommended delayed weaning in infants (after 6 months of age) and the introduction of potentially allergenic food only after 1 year of age.40 Owing to the lack of evidence, this approach has been withdrawn.8 Indeed, current evidence suggests that early introduction of allergenic food can avoid the development of allergy, probably by inducing immune tolerance.

In the UK, the prevalence of peanut allergy in Jewish children is 10-fold higher than it is in Jewish children in Israel. At the time of this study, the advice from UK government was to delay the introduction of peanuts until after the age of 3 years. Conversely, Israeli children start eating food that contains peanuts early in life, consuming it more frequently and in higher doses than children in the UK.41

The LEAP (Learning Early About Peanut Allergy) study randomized 640 infants, aged between 4 and 11 months, with high risk for peanut allergy, based on sensitivity to peanut extract.42 Infants with eczema and/or allergy to egg, assessed by SPT, were assigned to avoid or consume peanuts until they were 5 years old. The study found that none of the infants with mild eczema or no egg allergy was sensitized to peanut allergy. In infants with either severe eczema or egg allergy and 0 mm peanut SPT weal response, some 17% had peanut-specific IgE sensitization (≥ 0.35 kU/l). Some 56% of infants with either severe eczema or egg allergy, and 1 to 4 mm peanut SPT weal response, had peanut sIgE sensitization and 91% of the infants with > 4 mm peanut SPT had sIgE sensitization.42

A population-based, cross-sectional study (HealthNuts) included 2589 infants to assess whether the duration of breast-feeding and the age of introducing egg and solids might account for the development of egg allergy at 12 months of age.43 The study found a higher risk for egg allergy in infants that avoid eating egg during the first 6 months of age, compared with those who ingested egg at 4 to 6 months. The duration of breast-feeding and the age of introduction of solids did not seem to be related to egg allergy.43

A prospective study including 13 000 infants assessed the risk factors for the development of cow’s milk allergy. The study has shown that the incidence of cow’s milk allergy was significantly higher in children who consumed cow’s milk after the age of 4 to 6 months than those who had consumed cow’s milk in the first 2 weeks of life.44

Anticipatory testing

Multiple food allergies in a single individual are common. Current NICE guidelines recommend testing for the allergen that causes the index reaction, as well as for known coallergens.40 This approach allows the identification of food allergies that have not been revealed, avoiding unexpected severe reactions to foods and unnecessary dietary restrictions.4 The presence of moderate to severe eczema is a risk factor for developing food allergies. Therefore, anticipated testing for food allergy could be beneficial in this population.

Immunotherapy

The use of allergen-specific immunotherapy has been tested to induce desensitisation of food allergies, induce tolerance and allow the consumption of the allergen without triggering an allergic reaction.4,45 This therapy is performed by the administration of small doses of an allergen in increasing amounts, usually twice a week. Subsequently, a maintenance dose is given for a number of weeks or up to 1 year. In some cases, a food challenge is performed after the maintenance phase.46 Although this therapy can reduce the severity of reactions to accidental exposure, there are still concerns about safety because of the high number of allergic reactions during the installation phase. It is also necessary to eat the allergen regularly in order to maintain clinical tolerance, since discontinuation of the immunotherapy can cause loss of desensitization.4 Currently, there are several routes of administration, such as oral, sublingual and epicutaneous immunotherapy, which are under investigation in several clinical trials.

Conclusion

Given that the management of food allergy is an area that is still developing, there is uncertainty about identifying the best approaches for prevention, diagnosis and management of the condition. There is a need to distinguish between those patients who may be at risk of life-threatening conditions and those who are affected by less severe conditions. Incorrect diagnosis of food allergy may lead to unnecessary dietary restrictions that may adversely affect nutrition, social interaction and quality of life.

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