Food allergy and food intolerance

Introduction

Some people have an adverse reaction on exposure to certain foods that can make them unwell. This can be a recurring reaction, happening each time that person ingests the food. Symptoms depend on the mechanism of reaction; however, they range from vomiting and diarrhoea and skin reactions such as eczema and urticaria to dramatic angio-oedema, severe respiratory distress and anaphylaxis.

Food anaphylaxis is a severe, potentially life-threatening, systemic hypersensitivity reaction¹ .

Foods commonly involved (there may be allergy to multiple food proteins)² :

• Cows' milk.

• Hen's eggs.

• Peanuts and other legumes - eg, soybean, pea, and chickpea.

• Tree nuts - eg, walnut, almond, hazelnut, pecan, cashew, pistachio and Brazil nuts.

• Crustacean shellfish (eg, shrimp, crab, and lobster), and fish.

• Wheat.

One way to classify adverse reactions to foods is as either³ :

• Immunological reactions - both IgE (acute, often rapid, onset) and non-IgE-mediated (delayed and non-acute reactions).

• Non-immunological reactions.

Food allergy should be reserved for immunologically mediated reaction to food allergens. Food intolerance is a rather vague term and needs a fuller explanation specifying whether immunologically mediated or not.

Epidemiology

• Levels of food allergy seem to be rising. Reasons for this are unclear but it may be connected with the processed nature of the western diet and its effects on the gut microbiome⁴ .

• It is difficult to find accurate numbers for prevalence of food intolerance or allergy. Some studies have shown that self-reporting of food-related symptoms may not be confirmed in food challenge studies.

• Cow's milk allergy is one of the most common presentations of food allergy seen in early childhood, second to egg allergy. Almost all cases present before one year of age, with a prevalence of between 1.8-7.5% of infants during the first year of life⁵ .

History³

When presented with a case of possible food allergy or intolerance, a careful symptom history is essential. This should seek to identify possible allergens and whether the reaction is likely to be IgE-mediated and thus the patient may be at risk of anaphylaxis.

• Why is a food allergy suspected?

• What foods do they feel are implicated? A complete list is needed, including how the food has been prepared, to try to identify the likely ingredient.

• What are the symptoms that occur after eating the food?

• At what age did the symptoms start?

• How much food is needed to cause symptoms?

• Do symptoms occur every time the food is eaten?

• How long does it take for symptoms to occur?

• How long do the symptoms last?

• Do the symptoms follow a particular pattern or sequence?

• Frequency of occurence - does it happen every time after exposure?

• Setting of reaction (eg, home, school, anywhere)?

• What is the worst reaction that the person has had?

• Is there a personal or family history of allergy?

• Feeding history, age of weaning, formula-fed or breastfed (in which case, consider the mother's diet)?

• Previous treatments. Have any exclusion diets been tried?

• Is their diet nutritionally adequate?

Symptoms Suggestive of IgE and Non-IgE-mediated Food Allergy³

Differential diagnosis²

• Acute spontaneous urticaria and angio-oedema, which often occurs following viral infection.

• Carcinoid syndrome.

• Food intolerance. Non-immune, nonspecific food reactions which may be related to enzyme deficiencies such as:

  • Lactase deficiency. See the separate Lactose Intolerance article for further details.

  • Pharmacological causes - eg, caffeine or tyramine in cheeses, monosodium glutamate (causing flushing, headache and abdominal symptoms), sulphites, artificial food colours, preservatives, vasoactive amines, salicylates, flavour enhancers, alcohol, artificial sweeteners.

  • Histamine intolerance is a reaction to histamine which is present in many foods, including alcoholic drinks, pickled and cured foods, mushrooms and Quorn®. Histamine-induced symptoms include rashes, headaches and abdominal symptoms. Some foods, including a range of fruits and vegetables, can stimulate the release of histamine from mast cells in susceptible individuals.

• Food poisoning and toxic reactions, including:

  • Scombroid poisoning, which may present with paraesthesia, burning sensations, headaches, and itch after spoilt food ingestion. Scombroid poisoning is due to bacterial production of excess amines, particularly histamine, on food. Most cases derive from tuna, mackerel, herring, marlin, anchovy, or mahi-mahi fish.

  • Foods contaminated by toxins, or by viruses, bacteria or parasites - eg, lectins found in undercooked beans can cause gastrointestinal symptoms.

• Food refusal or aversion. However, food allergy in young children may present as food refusal due to unarticulated symptoms such as oral tingling and burning, difficulty swallowing, abdominal pain, or nausea.

Investigations^{3 6}

Food diary - this simple activity may be helpful in some cases. It involves noting what foods are eaten and any reaction to them. It is cheap but often not diagnostic.

If an IgE-mediated food allergy is suspected:

• Arrange a skin prick test and/or blood tests for specific IgE antibodies to the suspected foods and likely co-allergens, depending on which is more acceptable to the patient or on which is available for a given food.

• Both skin prick tests and IgE testing measure sensitisation to an allergen, rather than clinical food allergy.

• Atopy patch testing or oral food challenges should not be used to diagnose IgE-mediated food allergy in primary care or community settings³ .

• Skin prick tests⁷ :

  • Must be done where there are facilities to deal with a possible anaphylactic reaction and the expertise to interpret the results.

  • A drop of liquid or solid food is placed on the skin of the forearm. A lancet or needle is used to prick the skin through the allergen solution.

  • A saline-based control solution is also used at a separate site on the forearm.

  • The reaction is usually 'read' after 15-20 minutes. The result should be interpreted with referral to the history.

  • Note that food extracts are not available and skin prick testing has not been validated, for all foods.

• Serum allergen-specific IgE⁸ :
  

  • Blood tests for serum allergen-specific IgE are considered to be more specific but are more expensive than skin prick tests, and results are not immediate.

  • Specificity and sensitivity both vary according to test manufacturer and allergen.

  • There may be clinically insignificant cross reactions with other allergens, so results must be interpreted with caution and always in conjunction with the clinical history.

  • However, this test is safe and can be used in people who have widespread skin disease or a history of severe anaphylactic reaction.

• Oral food challenge² :

  • If the results of allergy testing do not correspond with the clinical history, an oral food challenge may be needed to confirm the diagnosis.

  • Oral food challenge is the gold standard for diagnosis of food allergy, and is an accurate and sensitive test.

  • Increasing quantities of the food allergen are used under medical supervision, starting with direct mucosal exposure (contact with the lips) and then titrated oral ingestion as tolerated.

  • If symptoms are not provoked, the test is negative and clinical allergy can be excluded.

  • If there has been a previous severe reaction to a known food, a repeat challenge is not usually arranged for at least two years.

If a non-IgE-mediated food allergy is suspected:

• When the allergen is clear, arrange a trial elimination diet (normally for between 2-6 weeks) to see if symptoms improve, and then reintroduce after the trial to see if symptoms return. Seek advice from a dietician to ensure adequate nutrition during the trial and to provide dietary follow-up. Examples are:

  • Food protein-induced enterocolitis - presents with projectile vomiting, diarrhoea and failure to thrive in the first few months of life. Cow's milk and soy protein formulas are usually responsible, although it can also be triggered by solid foods.

  • Eosinophilic oesophagitis and gastroenteritis - there can be nausea, abdominal pain, reflux, and failure to thrive. There is no response to antacids. Eosinophilia may be found on FBC in some or at gastrointestinal biopsy.

  • Coeliac disease - this is not strictly an allergy but occurs because of an immune response induced by exposure to gluten in genetically predisposed individuals.

Management⁶

Current best management is directed at educating patients, families and caregivers on food allergen avoidance and how to treat food allergy emergencies⁹ .

The management of an anaphylactic reaction is discussed in the separate Anaphylaxis and its Treatment article.

Management of food allergy and intolerance may include one or more of the following:

• Food avoidance: the only real treatment for food allergy and intolerance is food avoidance. This is particularly crucial in the case of a previous anaphylactic reaction to a food substance and can prove very difficult when eating out and when buying food, as cross-contamination can occur. Food labelling is also an issue and laws on this are being tightened.

• Dietician referral should be considered. Patients should be taught to read food labels carefully. Detailed written advice on avoidance strategies can be helpful. Dietary deficiencies can be anticipated and prevented. The possibility of allergen cross-reactivity should also be discussed. Advice about possible sources of contamination should be given.

• Antihistamines: if symptoms are less severe (for example, just pruritus or urticaria), antihistamines can be helpful. However, caution should be used as they may mask more serious reactions and the patient's degree of sensitivity can increase over time.

• Adrenaline (epinephrine): if respiratory symptoms or severe anaphylactic reactions have occurred, or the allergy is to foods such as peanuts that commonly cause severe reactions, or there is a history of asthma, the need for adrenaline (epinephrine) - eg, EpiPen® - should be considered. Advise that this is to be carried at all times and give full instructions for use.

• Medical emergency identification bracelet or similar: should be worn by people at risk of anaphylaxis.

• Patient and parent, relatives, schools and carer education: anyone closely involved with the person who has the food allergy, particularly if there is risk of an anaphylactic reaction, should be informed and educated about what to do if a reaction occurs. A written emergency plan is helpful.

• Support groups: there are many groups available for patients and their families.

Injection immunotherapy (desensitisation) has been used with some success to treat pollen and insect venom allergies but, at present, is not used to treat food allergy other than peanut allergy¹ . However, studies looking at oral desensitisation may be effective in some situations¹⁰ .

Prognosis

• The prognosis of food allergy depends on age, comorbidities and specific food allergen. Most children outgrow their food allergy over time. However some food allergies are more likely to persist - eg, peanuts, tree nuts, fish and shellfish² .

• Adults with food allergy can develop tolerance after appropriate food elimination diets have been implemented. One third of all adults and children lose their clinical reactivity to food allergens after 1-2 years of food elimination diets.

• Peanut allergy in teenagers and adults rarely resolves The quality of life of the affected patients and their families is decreased because of the need for constant vigilance over food choices and the perceived likelihood of anaphylaxis, alongside the dietary and social restrictions that accompany food allergy⁹ .

• Sensitivity to seafood, fish and tree nuts also rarely resolves.

Prevention

There are a number of unanswered questions about how to prevent allergies developing. The guidance has changed several times over recent years, causing some confusion, and new research often reaches surprising conclusions.

Breastfeeding is promoted as a way to prevent food allergy and atopy but there has been some controversy surrounding this¹² .

Delayed introduction of solid foods until the child is 6 months old, as an allergy prevention measure, is also controversial. Studies have demonstrated that delayed exposure to allergenic foods do not reduce the risk of food allergy, leading to guidelines which recommend against delaying the introduction of solid foods after 4-6 months of age, both in high- and low-risk infants¹³ .

However it is recommended in the UK that babies be exclusively breastfed until around 6 months of age and continue to be breastfed for at least the first year of life. Additionally, solid foods should not be introduced until around 6 months to benefit the child’s overall health¹⁴ .

Some Cochrane reviews on allergy prevention have concluded that:

• There is no evidence to support short-term or prolonged feeding with a hydrolysed formula compared with exclusive breastfeeding for prevention of allergic disease¹⁵ .

• Likewise, soy formula cannot at present be recommended for prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance. However, further research is needed to look at the role of soy formulas for the prevention of allergy or food intolerance in infants unable to be breastfed who have a strong family history of allergy or cow's milk protein intolerance¹⁶ .

• There is insufficient evidence to determine the role of prebiotic or probiotic supplementation of infant formula for prevention of allergic disease and food hypersensitivity. Studies have shown some possible positive outcomes regarding reduction in eczema but more research is needed^{17 18} .