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Food Allergy and Intolerance
 

Up to 8% of children less than 3 years and approximately 2% of the adult population experience food-induced allergic disorder.

Hippocrates, often hailed as the "Father of Medicine", first described adverse reaction to food over 2000 years ago, but it is only recently that the medical community has accepted and started investigating these disorders.

What do we mean by the term "food allergy"?

Here are some common terms used relating to food allergy, and what they should mean:

Adverse reaction to foods: any abnormal response to a food or food additive, whether caused by allergic or non-allergic mechanisms.

Food allergy, hypersensitivity or sensitivity: an immunologic reaction that involves the body’s immune system overreacting to ordinarily harmless substances. The word "allergy" is frequently overused and misused to include any irritating or uncomfortable symptom after eating. Strictly speaking the term should only be used for the immediate symptoms that develop after eating foods like, milk, egg, peanut, wheat & seafoods. It involves IgE antibodies and is easily confirmed with a positive skin prick test or RAST to that food. An example of true food allergy is hives that develop after eating peanuts or fish or wheezing after drinking milk.

Food Intolerance: a physical response to a food or food additive. This response is not necessarily immunologic, e.g., lactose (a milk-sugar) intolerance, which occurs when an individual lacks the enzymes to break down the milk sugar for proper digestion.

Food Anaphylaxis: the most severe allergic reaction following food that can be fatal. The commonest food causing fatality is peanuts.

Food poisoning, toxicity: an adverse reaction that does not involve the immune system. It can be caused by food that has been contaminated with toxins (poisons or bacteria), microorganisms or parasites. An example is scombroid fish poisoning, which can mimic anaphylaxis, but is due to excessive histamine in spoilt fish.

Pharmacologic food reaction: an adverse reaction in which a chemical found in a food or food additive produces a drug-like (pharmacologic) effect e.g., caffeine causing "the jitters".

Food Aversion: A psychologically based food intolerance, where a conditioned response is elicited by the recognition, appearance, smell or taste of a particular food. Panic Attacks is an example of food aversion presenting as anaphylaxis.

Natural History of Food Allergy

The natural history of food allergy depends on three principal factors: age at onset, type of food(s) involved, and severity of the initial reaction. As a rule, the later the onset of food allergy, the less likely that clinical sensitivity will be lost. Up to 85% of infants sensitive to cow's milk can tolerate reintroduction by 3 years and up to 80% of infants with egg allergy are able to consume egg by 5 years of age. Children diagnosed as having a food allergy after the age of 3 years are less likely to outgrow the problem. Children are more likely to outgrow milk, eggs, soy, and wheat before the age of 5, whereas reactions to peanut and fish are more often severe and persistent. In a recent study 21.5% of peanut allergic children appeared to have lost their sensitivity over time. Most of the patients who outgrew their peanut allergy had milder reactions to begin with.

Food Allergens

Those parts of the food causing allergic reactions are usually proteins and are called allergens. Most of these allergens can still cause reactions even after they are cooked or have undergone digestion in the intestines. Exceptions are fruits & vegetables, which seem to be more allergenic when fresh. Numerous food proteins have been studied to establish allergen content.

The most common food allergens – responsible for up to 90% of all allergic reactions – are the proteins in cow’s milk, eggs, peanuts, wheat, soy, fish, shellfish and tree nuts.

All foods come from either a plant or animal source, and foods are grouped into families according to their origin. Peanut, peas, beans & Soya are some of the members of the legume family. In some food groups, especially tree nuts and seafood, an allergy to one member of a food family may result in the person being allergic to all members of the same group. This is known as cross-reactivity. However some people will be allergic to peanuts & tree nuts, which are from different food families: these allergies are called coincidental allergies, because they are not related.

Symptoms of IgE mediated "true" Food Allergy

Skin: The most common allergic skin reaction to a food is hives (urticaria). Hives are red, very itchy, swollen areas of the skin. They arise suddenly and can disappear quickly.

  Hives can occur alone or
with any of the symptoms
listed under anaphylaxis.

Foods most commonly incriminated in adults include fish, shellfish, nuts, and peanuts, and those in children include eggs, milk, and peanuts, although reactions to various seeds (eg, sesame, and poppy) and fruits (eg, kiwi) are becoming more common.

Atopic dermatitis is an occasionally transient, but more likely chronic, itchy inflammation of the skin often occurring in individuals with personal or family histories of allergic rhinitis or asthma. Eczema is usually the first manifestation of Allergies & it usually starts about 4 – 6 months of age, around the time of weaning onto milk formulae. Cow’s milk is the commonest food allergen causing eczema, closely followed by eggs. In a recent study 35% to 40% of children with moderate- to-severe atopic eczema first seen by a university-based dermatologist were found to be allergic to food.

It is important to know that food allergens from the mother's diet are passed into breast milk and can cause eczema during breast-feeding.

Respiratory Reactions caused by foods

Both upper (allergic rhinoconjunctivitis) and lower (bronchospasm and asthma) respiratory reactions have been provoked in blinded food challenges, although respiratory symptoms in the absence of skin or gastrointestinal symptoms appear to be rare. In a survey of 323 patients with chronic rhinitis attending an allergy clinic, only 2 patients (0.6%) had nasal symptoms reproduced during blinded food challenges. Despite the belief that milk ingestion " is mucous producing" and frequently leads to nasal congestion, only 0.08% to 0.2% of infants in 3 epidemiologic surveys were found to have nasal symptoms after a milk challenge. In one study by Bock of 480 children referred for evaluation of adverse food reactions, about 16% experienced respiratory symptoms (sneezing, runny nose, nasal obstruction, wheezing, cough or eye signs) during DBPCFCs, but only 2% of symptoms were confined to the respiratory tract. Approximately 25% of 112 patients with histories of adverse food reaction starting after 10 years of age were found to develop respiratory symptoms after oral challenge, with the majority being nasal symptoms caused by fruit or vegetable sensitivities. In surveys of children with asthma attending chest clinics, food-induced respiratory reactions were demonstrated in about 6% to 8% of children. Bock found that 25% of 279 children referred for evaluation with histories of food-induced wheezing/asthma actually experienced wheezing as one of their symptoms during DBPCFCs.

In Hugh Sampson’s studies of children with atopic dermatitis, nasal symptoms typically developed within 15 to 90 minutes of initiating the DBPCFC and lasted about 0.5 to 2 hours. Itchy nose & itchy eyes are commonly followed by prolonged bursts of sneezing and profuse runny nose. Similarly, a study with 88 children with atopic dermatitis and asthma revealed acute bronchospasm (dyspnea, cough and wheezing) in 15% of patients during DBPCFCs, with 8% demonstrating greater than 20% fall in FEV1.

Asthmatic reactions caused by airborne food allergens have been reported in cases where susceptible individuals are exposed to vapours or steam emitted from cooking food (eg, fish, molluscs, crustacean, eggs, and garbanzo beans). Symptoms include rhino-conjunctivitis, urticaria, laryngeal oedema, bronchospasm, and rarely hypotensive shock.

Gastrointestinal food hypersensitivity (IgE) reactions

Symptoms caused by immediate gastrointestinal hypersensitivity typically develop within minutes to 2 hours of eating the responsible food allergen and consist of nausea, abdominal pain, colic, vomiting, and/or diarrhoea. In young infants immediate vomiting is not always a consistent finding, and some infants are first seen with intermittent vomiting and failure to thrive. In children with atopic dermatitis and food allergy, the repeated ingestion of a food allergen induces partial desensitisation of gastrointestinal mast cells, resulting in subclinical reactions. Generally these children are seen with complaints of poor appetite, poor weight gain, and intermittent abdominal pain.

The oral allergy syndrome (OAS) appears to have become more prevalent in the past decade, but this may be due to increased awareness. It is estimated that OAS affects up to 40% of adults with pollen allergy, especially to birch pollens.

OAS is a form of contact allergy that is confined almost exclusively to the inside of the mouth (oropharynx) and rarely affects other target organs. Local IgE-mediated mast cell activation provokes the rapid onset of pruritus (itching); tingling and swelling of the lips, tongue, palate, and throat; and occasionally a sensation of pruritus in the ears, tightness in the throat, or both. Symptoms are generally short-lived and are most commonly associated with eating various fresh fruits and vegetables. Patients allergic to birch pollen may have symptoms after eating raw potatoes, carrots, celery, apples, hazelnuts and kiwi. Cross-reactivity between birch pollen and various fruits and vegetables is due to homology among various pathogenesis-related proteins, which are important in the defence against plant diseases. For example Mal d 1, the major apple allergen, is 63% homologous to the major birch pollen allergen, Bet v 1. Oral allergy syndrome has been described among several fruits in the Prunoideae subfamily (peach, apricot, cherry, and plum) and Brazil nuts. Patients with OAS generally can eat these foods in the cooked form without difficulty.

Mixed IgE- and non-IgE mediated disorders of the GIT due to foods

Allergic eosinophilic esophagitis, gastritis, or gastroenteritis are characterized by infiltration of the oesophagus, stomach, and/or intestinal wall with eosinophils and increased eosinophils in the blood in 50% of patients. The eosinophilic infiltrate leads to thickening and rigidity of the bowel walls.

Allergic eosinophilic oesophagitis is seen most frequently during infancy through adolescence and presents with chronic reflux (gastrointestinal reflux), intermittent vomiting, food refusal, abdominal pain, difficulty swallowing, irritability, sleep disturbance, and failure to respond to conventional reflux medication. One study of children less than 1 year of age with gastrointestinal reflux found 40% had a cow’s milk-induced reflux.

Allergic eosinophilic gastroenteritis may occur at any age and may appear with symptoms similar to oesophagitis, gastritis, or both. Weight loss or failure to thrive is a hallmark of this disorder. Up to 50% of these allergic eosinophilic disorders are atopic, and food-induced IgE-mediated reactions have been implicated in a minority of patients.

Non-IgE-mediated disorders

Dietary protein enterocolitis syndrome is a disorder most frequently seen in the first several months of life in which infants are first seen with irritability, protracted vomiting, and diarrhoea, not infrequently resulting in dehydration. Vomiting generally occurs 1 to 3 hours after feeding and continued feeding may result in bloody diarrhoea, anaemia & failure to thrive. Symptoms are most commonly provoked by cow’s milk or soy formulae but occasionally result from food protein passed in maternal breast milk. A similar enterocolitis syndrome is seen in older infants and children, which is caused by egg, wheat, rice, oat, peanut, chicken, and fish sensitivity.

In adults shellfish (eg, shrimp, crab, and lobster) sensitivity may provoke a similar syndrome with severe nausea, abdominal cramps, and protracted vomiting. Stools often contain occult blood. Skin prick Test responses to the suspected foods are negative.

Coeliac disease is a T cell-induced inflammation of the small intestines, due to gliadin present in wheat, oats, barley & rye. The severity varies from a debilitating malabsorption syndrome to a "silent" subclinical disorder.

Life-threatening Food Allergy or Anaphylaxis

Food allergies are the single most common cause of generalized anaphylaxis seen in hospital emergency departments. It is estimated that about 100 fatal cases of food-induced anaphylaxis occur in the USA each year (compared to about 50 cases from bee sting). In addition to the skin, respiratory, and gastrointestinal symptoms mentioned earlier, patients might have cardiovascular symptoms, including hypotension and vascular collapse, caused by massive mast cell mediator release. However, most food-induced anaphylactic reactions are not associated with major increase in serum tryptase.

In a series of 12 fatal or near-fatal anaphylactic reactions, all patients experienced severe respiratory compromise, 10 of 12 experienced nausea and vomiting, and only 7 of 12 patients experienced skin symptoms. About one-third of patients had a biphasic reaction and one quarter experienced prolonged symptoms (eg, up to 3 weeks)

Factors associated with severe reactions include, concomitant asthma, history of previous severe reactions, denial of symptoms, and failure to give adrenaline early.

Food-associated exercise-induced anaphylaxis

This is an increasingly recognized form of anaphylaxis. It occurs only when the patient exercises within 2 to 4 hours of eating a food, but in the absence of exercise the patient can eat the food without any apparent reaction. Patients are usually atopic and have a positive skin prick test response to the food that provokes their symptoms. Occasionally they have a history of reacting to the food when they were younger. This disorder appears to be more prevalent in the late teens to mid-thirties. In my experience, males are more commonly seen with this disorder, but other studies report females to be affected twice as commonly as males. The exact mechanism(s) involved in this disorder are unknown. It is speculated that the food hypersensitivity is subthreshold for the mast cells to degranulate & exercise is required as a co-factor to achieve the correct threshold. Wheat is the most common food (in my experience) associated with this disorder, however several others have been implicated, including shellfish, fish, celery, fruit, and milk.

This is a very controversial area at the present time, as there are conflicting reports on the effects of maternal diet during pregnancy & breast-feeding in preventing allergies.

There is some evidence to suggest that breast-feeding in infancy, up to 6 months may result in delayed or lower rate of allergies. The nursing mother should probably also avoid foods that may cause her infant to become allergic. However no nursing mother should make alterations in her own diet without first consulting her physician. Unsupervised dietary eliminations could potentially result in nutritional deficiencies, which could affect both the mother and the unborn child.

If breastfeeding is not possible, or if a supplement to breastfeeding is desired, use hypoallergenic formulae. Soy-based formula or goat’s milk formula is not recommended for allergic or potentially allergic infants.

Introducing solids

Care is needed when introducing foods, because the earlier a child is exposed to allergens, the more likely they are to cause an allergic reaction.

Where there is a family history of allergy, solids should not be introduced before 6 months.

Start with the least allergenic food first, such as baby rice, pears and yellow vegetables, introducing 1 new food per week. All foods even fruits should be cooked.

At the age of 9 months – oats, green vegetables & meat may be started.

Do not introduce wheat and soy until 9 months (12 months ideally), cow's milk until 12 months, eggs until 18-24 months and peanuts, nuts, fish and shellfish until 36 months.

Diagnosing Food Allergy

An allergist diagnoses food Allergy by taking a detailed and painstaking medical history. All events surrounding the allergic reactions and everything ingested ("everything that is put inside the mouth") should be recorded, along with symptoms experienced, in a daily diary. The allergist will note the frequency, seasonality, severity and nature of the symptoms. It's important to note the time elapsed between eating a food and the reaction. After a thorough physical examination the allergist decides on the investigations that will confirm his/her suspicions.

Skin Prick Test

In the evaluation of IgE-mediated (true) food allergy, the skin prick test identifies specific IgE antibodies to the suspected food.

The test is usually done on the forearm, after the patient has been off antihistamines for at least 72 hours. It is a very good test for diagnosing allergy to milk, eggs, wheat, peanuts, nuts, seafood, and soy. The test is not very good for fruits & vegetables when commercial extracts are used.

Skin prick tests are most valuable when they are negative because the negative predictive value of these tests is very high (over 95%). Unfortunately, the positive predictive value is in the order of only 50%. Thus, a positive skin test in isolation cannot be considered proof of clinically relevant hypersensitivity, whereas a negative test virtually rules out IgE-mediated food allergy to the food in question.

In Vitro Testing (RAST)

Blood tests for specific IgE (radioallergosorbent test [RAST]) are generally less sensitive than skin prick tests. As with skin tests, a negative result on RAST testing is very reliable in ruling out an IgE-mediated reaction to a particular food, but a positive result has a low positive predictive value.

The CAP-RAST is a newer and more sensitive assay than the RAST. It correlates very well with clinical reactivity to certain foods (milk, egg, peanut, fish).

Because most patients with food allergy are sensitive to only a few foods and a small number of foods are responsible for most reactions, it is usually inappropriate to test for allergies to an extensive number of foods. In the context of a detailed history, selective testing is more likely to reveal causal foods.

Unproven (Unorthodox) Tests for Food Allergy

Measurement of immunoglobulin G4 (IgG4) antibody, provocation-neutralization, cytotoxicity, applied kinesiology, hair analysis and other unproven methods are not useful.

When patients have a history suggestive of food-related illness and tests for IgE antibody to food are positive, the first course of action is to eliminate the food from the diet. Further testing is usually not needed in patients with food-induced anaphylaxis. However, if symptoms are chronic (atopic dermatitis, asthma) and/or many foods are implicated, diagnostic oral food challenges may be necessary.

Double-blind, placebo-controlled food challenges (DBPCFC) are considered the gold standard for diagnosing food allergy. The procedure is labour intensive but can be modified for an office setting. Patients avoid the suspected food(s) for at least 2 weeks, antihistamines are discontinued, and doses of asthma medications are reduced as much as possible. After intravenous access is obtained, graded doses of either a challenge food or a placebo food are administered. The food is hidden either in another food or in opaque capsules.

Medical supervision and immediate access to emergency medications, including adrenaline, antihistamines, inhaled beta agonists (eg, Ventolin nebuliser) and steroid, and equipment for cardiopulmonary resuscitation are required because reactions can be severe. Challenges are terminated when a reaction becomes apparent, and emergency medications are given as needed. Patients are also observed for delayed reactions. If allergy to only a few foods is suspected, single-blind or open challenges may be used to screen for reactivity.

Negative challenges are always confirmed with open feeding of a larger, meal-sized portion of the food. Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction.

 

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