Food allergies are caused by a reaction of the body’s immune system to food proteins. There are several types of allergic reactions, depending on the immune players involved (i.e. IgE and/or cell-mediated: e.g. T-cells, mast cells, IgG, etc), and they give rise to different clinical manifestations.
The IgE-mediated reactions are the commonly described food allergies. However, other less well understood and often more delayed reactions also exist. These are often collectively referred to as non-IgE- or cell-mediated allergies.
Genetic and acquired immune disorders, increased passage of proteins through the gut wall (increased intestinal permeability, “leaky gut”), the airways or skin predispose to the development of allergies. The immune, nervous and endocrine (hormonal) systems interact extensively in the intestinal wall and throughout the body, explaining the multidirectional integration of immune, pain and psychological reactions. The organisms resident in and on our bodies (microbiome: bacteria, fungi, viruses, protozoa, archaea) are increasingly shown to communicate with our own organ systems and control mechanisms. All these factors play a role in the development and maintenance of allergies and also determine the balance between food tolerance and allergy.
The exact sequences of food protein structures responsible for allergies are increasingly recognized, allowing prediction of allergic reactions and cross-reactions, for example between food and pollen.
Exercise, stress, alcohol, antibiotic use and certain painkillers can induce allergic reactions in at-risk individuals. Reduced vitamin D, zinc and other micronutrients also appear to favor the development of allergies. Changes in lifestyle, hygiene, habitat and nutrition over the last decades are increasingly likely to have substantially contributed to the currently experienced increase in allergies.
Frequency in population and natural history
- Adults: 1-4%; Children: 5-8% (based on currently accepted test techniques)
- Geographic differences: the most frequent allergies differ according to eating habits and lifestyle.
Self-reported food allergies are six times more common than those confirmed by testing. Most food allergies present in early childhood, but adults can develop new food allergies, especially allergies to fruit and vegetables. The natural history varies with the individual food allergy, however many allergies eventually fade away in later childhood, e.g. by school age. The food allergies most likely to resolve include soy, wheat, egg and cow’s milk, although the last two are recently becoming more persistent into adulthood. Food allergies that typically persist include fish, peanut, shellfish and tree nuts. Overall, the frequency of food and other allergies is increasing.
Individual types of allergy
Allergies to almost any food component have been reported.
The following constitute 90% of the most common so-called IgE-mediated allergies in the developed Western world: Milk, peanut, egg, soy, wheat, tree nut (including, but not limited to: walnut, almond, hazelnut, cashew, pistachio, and Brazil nuts), fish, seafood (crustaceans and shellfish), vegetables (e.g. carrot, celery, tomato, bean, mustard), and meat (e.g. beef, pork).
Besides specific allergies to one type of food, cross-allergies, i.e. allergies to either different classes of food or affecting different organs (e.g. skin, intestines or airways), are common. Important cross-allergies are latex-fruit allergy and pollen-associated allergies (e.g. oral allergy syndrome or pollen food syndrome).
Allergic reactions involving the alimentary tract can result in a wide range of symptoms, stretching from harmless tingling in the mouth to life-threatening shock reactions, and from lasting a few hours to many days.
At least 30% of sufferers will have symptoms resembling functional gastrointestinal disorders, such as irritable bowel syndrome, functional diarrhea or functional dyspepsia, with nausea, vomiting, bloating, abdominal cramps and pain, diarrhea, swallowing problems or reflux. Tingling, swelling, itching of the mouth, lips, tongue and throat are frequent allergic signs relating to the oral allergy syndrome (see Latex fruit and allergy cross-reactions), which is the commonest food allergy in teenagers and adults. Other possible manifestations of food allergies are skin reactions, such as itching (urticaria), rash, hives, edema or swelling, and respiratory problems, such as runny nose, sneezing, sinusitis, difficulty in breathing, cough and asthma or bronchitis. Nervous system reactions, such as tiredness, chronic fatigue, loss of ability to concentrate, migraine headaches and psychiatric disturbances, and musculoskeletal symptoms, including joint and muscle pain, are increasingly recognized. At the extreme end of the spectrum life-threatening anaphylactic shock can ensue. These reactions are most common in adolescents with co-existing asthma and with peanut allergies.
In infants, food protein-induced inflammation of the colon (proctitis, colitis or enteropathy) can be a serious disease, related predominantly to cow’s milk and soy allergy. Characteristic symptoms and signs are protracted diarrhea, vomiting, bloody stools, pain, and malabsorption.
A careful history and observation of food-related reactions are most important.
The food history should include:
- Identification of suspect food
- What is the time lag between eating and development of symptoms?
- What types of symptoms ensue?
- What amount of food is required to cause reaction?
- Does the reaction occur with every ingestion of the food?
- Does the reaction only occur under certain circumstances, e.g. exercise or stress?
- When did the last reaction occur?
- Are there other known allergies, e.g. hay fever, asthma, eczema?
- Do other family members have asthma?
The following tests can be helpful in determining sensitization (reaction of immune system), but are inaccurate in the diagnosis of food allergies.
Skin prick testing
A negative test excludes an allergy with a certainty of approximately 90% (sensitivity). However, a positive test confirms a specific allergy only in 50% of cases. The quality and standardization of tests differs widely and these tests only apply to IgE mediated allergies. The use of these tests together with a careful medical history can lead to accurate diagnosis in approximately 70% of patients. Strong reactions to skin testing may occur in highly sensitive individuals.
Serum-specific IgE blood levels can be measured, for example using the radio-allergo-sorbent-test (CAP RAST). However, IgE produced in the intestines in response to ingested food may not lead to raised blood IgE levels. Similar to the skin tests, a negative test excludes an allergy with a certainty of approximately 90% (sensitivity), but a positive test is more difficult to interpret. However, newer tests may allow a better predictability of positive results in egg, fish, milk protein, peanut and tree nut allergies. Threshold values are being defined for clinical use. IgE-independent measures, such as ECP and EPX in the blood or stool can be helpful in supporting a suspected diagnosis of food allergy.
Basophil activation tests (BAT)
These newer tests measure the expression of particular activation markers on specific cells involved in IgE-mediated allergies (basophils). They have been validated in various food allergies and complement the above conventional tests. The exciting promise of these tests, however, is that they can discriminate between sensitization (a laboratory phenomenon demonstrated by IgE and skin tests) and clinical allergy. Further testing is required to confirm the place of BAT tests in clinical practice.
Food challenge testing
A useful but cumbersome form of testing is the double-blind, placebo-controlled food challenge by a specialist. Increasing doses of the suspected food or a placebo are given at intervals and the patient is observed for signs of food allergy. As these challenges carry a small risk of severe reactions (anaphylaxis), they should be performed under adequate medical supervision. Food challenge testing does not reliably distinguish between intolerances and allergies and tests are not well standardized. Open food provocation tests carry similar risks, but are less conclusive.
Sequential elimination of specific food groups from the diet may allow identification of the offending food. Standardized elimination diets are available, with stepwise introduction of new foods every 2-3 days and documentation of food reactions and symptoms using a food diary. Such diets are best performed under the guidance of an experienced dietician.
New endoscopic allergy testing is being pioneered, but is not validated enough for clinical use. If the above tests do not lead to a clear diagnosis, exclusion of other diseases is warranted.
The most important aspect of allergy management is accurate recognition of the offending food(s) or other agent(s).
Important questions are: which food causes symptoms (allergens)? What is the timing, duration, severity, type and reproducibility of symptoms? Are there known risk factors (e.g. exercise), family history, co-existing medical problems including other allergic diseases?
Permanent exclusion of even small amounts of the recognized component(s) from the diet is still the cornerstone of allergy management for prevention of occurrence and escalation of symptoms (see Tests above). An elimination diet is often difficult, depending on the food component(s), frequently requiring expert dietary advice and a great deal of personal motivation and discipline. Careful reading of food, drug and in some cases household and cosmetic product labels is advised. Advice on food substitution from an experienced dietician is crucial in the case of fruit or vegetable allergies to prevent deficiencies.
If symptoms persist there is some evidence that certain types of anti-allergic medication may be helpful. These include cromoglycate, ketotifen (mast cell stabilizers), antihistamines and probiotics. There is currently insufficient evidence to support the use of steroids or more novel agents, except in the case of eosinophilic intestinal disease. Allergic reactions to food may be very severe, even life-threatening. Medical diagnosis and management advice are important.
Emergency treatment injectors (adrenaline, e.g. Epipen™) should be carried in case of severe allergic reactions, especially those involving the airways.
Antihistamines can be used for acute treatment in less severe allergies. Steroid treatments have a slower onset and are sometimes used in chronic allergies. Immunotherapy for some allergies, especially the pollen-associated food allergies, may be successful in a subset of individuals, however even then the effect is often not long-term. New data show ingestion of small amounts of allergen in egg or milk allergy may in the long term diminish allergic reactions. Sublingual immunotherapy (SLIT) and epicutaneous immunotherapy (EPIT) are two relevant methods showing promise in the desensitization of allergies, but research is needed to define optimal doses and administration protocols. Other treatments in development include vaccination, anti IgE and other antibodies, toleragen peptides, recombinant epitopes for hyposensitization, anti-mast cell drugs, as well as molecular modification of the offending food protein.
The recommendations for the prevention of allergy by the American Academy of Pediatrics, the American Academy of Allergy, Asthma and Immunology and European Academy of Allergy and Clinical Immunology have recently been revised and now conclude, that
current evidence does not support a role for maternal dietary restriction of highly allergenic foods during pregnancy or lactation in the reduction of allergies.
There is evidence that exclusive breastfeeding for at least 4 months and up to 6 months, compared with feeding formula made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood. At present, there are insufficient data to document a protective effect of any dietary intervention beyond 4 to 6 months of age for the development of atopic disease.
Processing may alter the allergenic properties of food proteins.
Extensive heating decreases the allergenicity of egg white proteins and the majority (50–85%) of egg allergic patients are tolerant to heated egg products. Milk pasteurization may increase allergenicity. Heating of food by microwave or cooking will eliminate or reduce allergic reactions to many foods, but not peanuts, tree nuts or mustard. Roasting may increase peanut allergenicity. Heating wheat at high temperature or acid hydrolysis may induce allergenicity.
- In oral allergy syndrome peeling of the fruit or eating freshly picked or unripe fruit may reduce allergic reactions.
- In highly allergic individuals inhalation of the food allergen may be sufficient for even strong allergic reactions. Examples are flour, egg white or crustaceans.
- Immunotherapy (‘allergy shots’) of hay fever may reduce the intensity of associated food allergies.
- Seek medical treatment if a severe food allergy requiring use of the emergency injector occurs, as usually a second, delayed reaction can occur 4 to 12 hours after the first reaction.
- Intestinal malabsorption (e.g. lactose or fructose) and slow clearing of intestinal content may predispose to food allergy.
- Food allergies and food intolerances (reactions to food not mediated by immune system) may co-exist. If conscientious exclusion of one type of food does not result in major symptom relief, consider having other intolerances or allergies excluded.
- Skin prick and blood IgE tests correlate incompletely with intestinal allergic reactions. These results therefore never exclude food allergies. They can, however, provide some useful guidance.
- Although currently not accepted by most allergy specialists, food IgG4 blood tests have been shown to result in significant and useful symptom improvements in some patients with functional bowel disorders, when identified foods were excluded from the diet.
- Food additive allergies are rare, but may be severe (e.g tartrazine, monosodium glutamate, “natural food additives”). This can be suspected if symptoms occur after food or beverages some, but not all of the time, suggesting the reaction only occurs in the presence of the additive.
- Food allergies and anaphylaxis may be provoked by exercise, which do not occur otherwise. This is especially common with wheat allergy.