Food Allergy and Additive Intolerance.
An Overview for Health workers
by Dr Adrian Morris
Food Allergy has always been a bit of a Cinderella Science often the topic of Media Fads and Fringe Medicine. It is falsely perceived to be the domain of controversial alternative medical practitioners and as a result is generally frowned upon by mainstream academic medicine. However, there can be some very serious and life threatening consequences of food allergy. Consider the dire results of Fish and Peanut Anaphylaxis.
At our Allergy Clinics at the Guildford Nuffield Hospital and at the London Medical Centre, 90% of our referrals are for suspected food allergy. Patients are very aware of the symptoms of food allergy, which can be quite alarming. The prospect of a life-threatening anaphylactic reaction is always a major public concern. Patients may present with urticaria that they attribute to food allergy. An increasingly common food allergic presentation are oral symptoms such as itching and swelling of the mouth and throat obstruction with respiratory difficulties.
Successful testing for allergy can be very difficult without a clear history implicating a particular food. The tests we have available are often not 100% specific. We see both false negative and false positive skin and blood tests and then fresh food challenge testing may be necessary.
Classification of Food Allergy and Adverse Reactions
The subject becomes less confusing if we use asimple classification for all Adverse Reactions to Food This Food Hypersensitivity includes all reproducible food related reactions and may be both Allergic and Non-allergic. I however divide Adverse Reactions to Food into four distinct groups.
Firstly, classicalTrue Food allergy, as in Peanut anaphylaxis - where we have an immediate catastrophic IgE immune mediated reaction. This will require emergency adrenaline injections and medical resuscitation.
Next is the group ofFood Intolerance which are not immune mediated but may be due to enzyme deficiencies, and other mechanisms that mimic true allergic reactions.
Biological contaminants or poison present in the food causesFood Toxicity, which then cause recognisable toxic reactions.
Finally, there isFood Aversion where the patient is convinced that they are allergic to a food, but when challenged with the food, fail to have any reaction.
True Food Allergy
True Food Allergy, is an Immediate IgE Mediated Allergic Hypersensitivity reaction, which involves antibodies that cause tissue Mast Cells to release histamine, resulting in tissue inflammation and swelling. A small protein particle called an allergen is responsible for triggering the antibody response. The antibody called Immunoglobulin E (IgE) accounts for 90% of True Food Allergic reactions. A reaction can occur to minute traces of the offending allergen and in exquisitely sensitive individuals, even airborne food allergen can trigger anaphylaxis - as in fish and peanut allergy.
Increasingly we see Delayed T-cell mediated food allergic reactions - these take over 24 hours to evolve and are typically seen with Contact Dermatitis in adults and Coeliac Disease in children. We refer to these as Non-IgE Allergic Hypersensitivity reactions
Classical IgE Mediated food allergy presents with immediate Urticarial rashes, tissue angioedema of the face and neck and even anaphylaxis with shock and circulatory collapse. In adults, the foods commonly implicated in anaphylaxis are Peanuts, Tree nuts, Shellfish, Fish and Egg.
Another interesting immediate food allergic phenomenon is that of the Oral Allergy Syndrome. Here the allergic reaction is localised to the mouth and throat and is triggered by allergy to Fruit and Vegetables such as Apple, Peach, Celery, Tomato and Cherry.
In adults we also see exacerbations of eczema and rhinitis in food allergy but rarely isolated asthma due to food allergy. Other manifestations involving the lower GI tract are vomiting and diarrhoea. Food-induced Oesophagitis and Enteropathy is more common in children. Frequently patients think they are allergic to one food but may end being allergic to 3 or more foods after evaluation.
Food Intolerance (Non-allergic food Hypersensitivity)
Food Intolerance(or Non-Allergic Hypersensitivity) is an adverse reaction that is not immune mediated and generally doesn’t lead to anaphylaxis as no specific IgE response is generated. Reactions are dose-dependant - smaller amounts of the offending food are tolerated, but at a certain dietary threshold a clinical response will occur.
This may be due to an enzyme deficiency as in Lactose Intolerance. Here the enzyme Lactase is depleted resulting in cramps, flatulence and frothy diarrhoea after drinking cows milk. It is an inherited trait and affects up to 10% of the population, beginning in teenage years and gets worse with advancing age. Lactose Intolerance is commoner in Afro-Americans, Hispanics, Asians and Mediterranean populations. Lactose intolerance is reliably diagnosed with a "hydrogen breath" test or reducing sugars measured in the diarrhoeal stool. Intolerance to Sucrose in table sugar and fruit can lead to similar symptoms if there is a deficiency of the intestinal enzyme which breaks sucrose down to absorbable fructose and glucose.
Food additives such as colourants and preservatives may trigger pseudo-allergic reactions. These are not IgE mediated, but possibly involve direct Mast Cell and Basophil Histamine Release. Histamine may even occur naturally in foods and when absorbed in the GI tract, the histamine content triggers an allergic-like reaction. A similar reaction can also be seen with naturally occurring dietary salicylate in aspirin sensitive people. Other chemicals found in food can cause ill effects such as caffeine induced palpitations. Capsaicin in chilli’s induces a typical "hot curry" burning oral sensation. While alcohol induced flushing and nasal congestion due to local vasodilatation.
Food Toxic Reactions
Food Toxicreactions have no immune basis, but are due to bacterial endotoxins and contaminants. This results in vomiting, diarrhoea, flushing and certain neurological symptoms in all individuals who consume the food.
Other biologically active toxins include algae that infest shellfish with paralytic neurotoxins, glyco-alkaloids in potatoes and amatoxin in mushrooms. Mycotoxins in grain produce such as wheat, rye, barley and oats can cause Ergotism with gangrene and convulsions. Scromboid toxicity occurs when fish putrefies and releases histamine causing allergy-like reactions.
Food aversion is diagnosed when the patient is psychologically convinced that they are food allergic. They might have had a viral illness with vomiting, thought it was an allergy and then blames a specific food. But if we disguise the food and then give it to them, they fail to react adversely.
Often their symptoms will be quite bizarre and not match any particular clinical picture. It can be very difficult to convince these patients that they are not food allergic or intolerant, and often "Alternative" practitioners will have reinforced their food aversion.
The Lay media tends to promote and popularise what we call "Populist" Medicine. Conditions that have no scientific basis become common place and are slowly accepted as actual disease entities. People are constantly being diagnosed with Chronic candidiasis, Yeast allergy or Sugar allergy. Sugar is not an allergen. An allergen has to be a protein or a protein-binding hapten. Reactive hypoglycaemia is often brandished about, but random blood glucose levels are inevitably normal. Clinical Ecologists talk about Multiple Chemical Sensitivities which really have no pathologic basis and are diagnosed from the most bizarre and vague symptom complexes. Then conditions such as Hyperactivity, Chronic post viral fatigue and Autism are blamed on food intolerance with no convincing research or evidence based studies.
Allergy is often diagnosed using Vega electro-magnetic fields, Kinesiology or muscle strength testing or even worse - with Hair Analysis. There are pseudo-scientific tests such as the Nutron and ALCAT test or leucocytotoxic test that has never been found to be accurate ever since it was first developed in 1956. No wonder food allergy is on shaky ground with conventional practitioners!
Typical IgE Mediated Allergy.
This usually presents with an acute urticarial rash that starts on the face and neck then spreads to the rest of the body. Angioedema with or without the rash may be a striking feature. Another manifestation in Silver Birch pollen allergic people is the Oral Allergy Syndrome. Patients may experience diffuse itching, even experience throat tightening with oedema and wheezing after eating fruit and nuts.
True IgE mediated food allergy occurs within minutes and most reactions will have evolved within one hour of contact with the triggering food. While minute traces of the food ingested will trigger a reaction, even inhalation of food essence or skin contact with the food can trigger life-threatening anaphylaxis. This may occur in aeroplanes when peanuts are handed out to other passengers as snacks or in a restaurant when the person at the next table is eating fish.
The common offending foods in paediatric practice that account for 90% of paediatric food allergy are Cows milk protein, Hen’s egg white, Wheat, Peanuts, Cod fish and Soya bean. A person will react to specific allergens in the offending food. For instance in Cow's milk, one may react to the Whey constituents (either a-lactglobulin or b-lactoglobulin) or less commonly to the Curd (Casein) which is used to make cheese. Children who are allergic to the whey only will usually tolerate heated (denatured) and "long life" UHT cow's milk (and even goats milk). In hypoallergenic milk formulas such as Nutramigen, these constituents will be extensively modified so as not to cause an allergic reaction. 20% of cow's milk allergic people will also develop allergy to soya milk.
In adults, the common food allergens causing severe allergic reactions tend to be peanuts, Tree-nuts such as Brazil nut, hazelnut and almond, Bony fish and Shellfish, followed by Tomatoes and various fruits such as apple, peach and cherry.
The natural history of food allergy
The natural history of food allergy in adults is slightly different from that in children, who tend to rapidly outgrown their allergies. As a result food allergy is more common in children but most will outgrow it before the age of 10 years. Up to 6% of children suffer with true food allergy, while only 1-2% of adults have true IgE mediated food allergy.
If foods are completely avoided, up to 30% of adults will become clinically non-reactive to an offending food over a 2-year elimination period. They will however remain atopic - that is maintain a positive Skin Prick Test or retain specific IgE antibodies to the food, but have no reaction if they eat the food. Certain foods are highly allergenic and allergy to them is unlikely to be outgrown - these are usually foods with heat resistant allergens. Peanuts, Nuts, Shellfish and Fish fall into this category. Food allergy also varies from country to country depending on local eating habits - the more a food is consumed in a country - the higher the incidence of allergy to it. In the USA we see plenty of Peanut allergy, In Scandinavia we see predominantly fish allergy, in Eastern Europe it's Poppy Seed allergy, Sesame allergy in the Middle East, while in Japan, Rice allergy is a significant problem.
Cases of suspected Nut allergy and anaphylaxis are frequently referred to the allergy clinic. It is becoming more and more common and is a serious cause of fatal and near-fatal allergic reactions.
Once sensitised in childhood allergy is usually life long and rarely decreases in severity. Only 10% will outgrow nut allergy, while 80% or more will outgrow egg allergy. There is a great deal of cross-reactivity between the various nuts and several nut allergens are often implicated.
The oils of nuts contain very little protein of the nut allergen, and are often safe to consume in nut allergic people. However beware of low quality cold pressed oils that may contain nut allergen. Roasting and processing of nuts paradoxically increases their allergenicity.
The major nut culprits are predominantly Peanuts, Brazil nuts, Almond, Hazelnuts, and then to a lesser extent Walnuts, Cashew, Pecan, Coconut, Pistachio, Chestnut, Poppy and Sesame seeds.
The rapid increase in nut allergy has been quite alarming especially when one considers that Dr Hide described the first case of Brazil nut anaphylaxis in the UK as recently as 1983.
The aim of nut anaphylaxis management is to clearly identify the culprit nut by skin testing, RAST testing or provocation testing. Once identified, strict avoidance is the main strategy - Patients are particularly at risk when eating out in restaurants, at children’s birthday parties, school dinners and processed ready to eat warm up meals from supermarkets. Holidays to Thailand and Far East are particularly fraught as nuts make up a major part of the diet in these countries. Nut allergy support groups can be particularly helpful and supportive. The Anaphylaxis Campaign has been excellent in this regard. While a dieticians input on food label reading and avoidance will be invaluable. All nut allergic patients and especially those with anaphylaxis should be fitted with a Medic Alert bracelet, clearly identifying the nature of their allergy.
Nut allergic patients should always have an in-date Epipen adrenaline auto-injector available. We usually recommend one at home and one in the workplace. The patient should be familiar with how to use it and use it early in anaphylaxis when it is most effective. The patient should also carry oral antihistamine such as Piriton 8mg and Prednisilone 40mg. The withdrawal of the adrenaline inhaler- Medihaler Epi was a tragic loss to anaphylaxis management.
All patients who experience anaphylaxis should still present to A&E or contact their GP for assessment. Ideally blood should be taken after the reaction for Tryptase estimation. Tryptase taken at 1 to 2 hours after the event is a reliable confirmatory test that anaphylaxis has actually taken place. Occasionally patients panic with the fear of anaphylaxis during mild urticarial reactions, hyperventilate and pass out with vaso-vagal syncope - and medical personnel think they have had anaphylaxis.
Who is a risk for anaphylaxis
Who is at risk for anaphylaxis and which patients should we be more vigilant with? A previous severe anaphylactic reaction is always an indicator of possible future anaphylaxis. Highly atopic individuals with Total IgE exceeding 1000KU/L are at risk. Poorly controlled brittle asthmatics with food allergy are at risk. Patients with peanut, nut, fish and shellfish allergy are particularly at risk. Those on Beta blocker and ACE inhibitor medication are a special risk, as adrenaline used in treatment of anaphylaxis may not reverse the reaction and this group may need to be treated with Glucagon. For whatever reason females are statistically more at risk for life-threatening anaphylaxis.
Oral Allergy Syndrome
The Oral Allergy Syndrome is a fascinating disease entity. It has more recently been renamed Pollen-Food allergy syndrome. In this condition, Hayfever patients sensitised to pollen develop oral allergic symptoms to certain fruits and vegetables. This occurs in up to 40% of all Hayfever sufferers who are allergic to birch or grass pollen. Once sensitised to the pollen, they develop allergy to similar allergens found in fresh fruit and vegetables.
Symptoms occur within a few minutes of contact and are almost always localised to the mouth and oro-pharynx with lip and oral itching. Oral swelling with occasional glottic oedema may ensue. Patients do not react to cooked fruit or vegetables. The Birch pollen-Apple Oral Allergy syndrome is the commonest seen in the UK.
Other Food-Pollen Allergic Reactions
As mentioned, the Birch pollen-Apple oral Allergy Syndrome is commonly seen in the UK. The major Birch Pollen pan-allergen Bet V 1 has a very similar structure to the major allergens in Apple, Hazelnut, Carrot, Cherry, Pear, Tomato, Celery, Potato and Peach. Hence we find Birch Pollen sensitised individuals have oral allergy to any one or combination of these fruits and vegetables.
Other pollen-food allergic syndromes include Grass pollen allergic rhinitics who have oral allergy to Melon, Orange. Tomato and wheat. Ragweed allergic people may react to Melon and Banana, While Mugwort allergic react to Apple, Carrot, Celery and Melon. People who are sensitised to natural latex in rubber gloves, catheters etc may react in a similar way to Avocado, Banana, Chestnut and Kiwi fruit and may even develop anaphylaxis to these foods.
A certain amount of cross-reactivity occurs between foods of similar classes and this should be borne in mind if symptoms recur on specific food avoidance. For example if allergic to peanuts, then there is a high risk of being allergic to beans, peas, lentils, carob, senna and liquorice (all members of the legume family). But foods from divergent food families may cross react such as "celery-spice-carrot-mugwort syndrome". This may be due to the presence of similar pan-allergens called Profilin and Lipid Transfer Protein (LTP) common to fruit, grass and vegetables and which accounts for the cross-reactivity we see between unrelated foods. It would appear that allergic reactions to fruit and vegetables, which often coexist with pollen allergy, are on the increase. These pan-allergens seem to play a protective role in plants and are induced by environmental stress such as plant infections, soil conditions, changes in weather and storage conditions. Birch pollen allergic people can have cross-reactions to apples and other fruit, grass pollen allergic people may react to melon, cereals and tomatoes, while those allergic to latex, react to avocado, chestnut, banana and kiwi-fruit. Profilin generally causes milder reactions and is destroyed by heat and cooking. Lipid transfer Protein (LTP) is heat and digestion resistant and can cause more severe systemic allergic reactions. Hidden allergen sources also need to be identified as processed foods are notoriously inadequately labelled.
Sometimes the apparent allergy provoking food is not the cause but another co-existent allergy, such as allergy to the Cod Worm parasite in fish mimicking a typical fish allergy, or allergy to the red spider mite on tomatoes or grapes being the allergen and not that food.
Latex allergy is a relatively newly described phenomenon and is most predominantly seen in medical theatre staff and patients who have had numerous surgical procedures such as in Spina Bifida. Some people are so exquisitely sensitive, that inhalation of traces of the powder from the surgeons gloves can trigger anaphylaxis.
The Rising Incidence of Food Allergy – Why?
We have seen a rapid rise in the incidence of food allergy in recent years - mainly nut allergy due to the increased consumption of tropical nuts in the UK. Peanuts and Brazil nuts seem to be leading the pack. Oral allergy syndrome is now the commonest food allergic manifestation in adult and parallels the rising incidence of pollen allergic Hayfever. This may be due to increased planting of Birch trees in suburban Britain and a particular enthusiasm to grow Male trees, as they look attractive and are less messy and do not drop fruit. However, their prolific pollen producing catkins are a distinct social and health disadvantage. Some recent studies on Birch pollen immunotherapy in Hayfever sufferers have shown very good desensitising results and symptom control. An unexpected but valuable spin-off has been that up to 80% of their Oral Allergies also resolved.
Exercise Induced Anaphylaxis
Another interesting allergic manifestation seen in adults is that of Exercise Induced Anaphylaxis. In this condition, patients develop itching, urticaria, angioedema and upper airway obstruction with bronchospasm during or shortly after strenuous exercise taking place within a few hours of eating certain foods. This allergic condition may occur up to 12 hours after eating wheat, celery and shellfish especially prawn. These patients have no reaction to the foods if at rest. It is most commonly seen in female athletes usually under the age of 30years.
Food Induced Rhinitis
Rhinitisis a frequent problem in adults and 30 to 50% of adults have allergic rhinitis - mainly triggered by inhalant allergens. However foods and food additives can induce rhinitis. Adults may occasionally have IgE mediated allergy to dairy produce or eggs which manifests with rhinitis.
But non-immune mediated rhinitis is a larger clinical entity. Alcohol can cause vasodilatation and nasal obstruction. Preservatives and colorants can trigger mast cell histamine release. Certain fermented foods such as cheese, wine and sauerkraut contain histamine and can cause nasal symptoms when consumed. Hot spicy foods precipitate local nasal irritation and rhinorrhoea. Aspirin or acetylsalicylic acid (ASA) sensitive individuals that develop asthma, rhinitis and nasal polyposis can have their rhinitis exacerbated by intake of natural salicylate in certain fruits and vegetables.
Scromboid Toxicityis an interesting condition, which we included under food toxicity. It is often confused with true fish allergy, but is due to histamine released from the fish flesh. Here we see an adverse food reaction to fish in a person who has previously tolerated fish all their life. The reaction typically occurs when eating Scromboid fish, which include Tuna and Mackerel but can also occur in non-Scromboid dark meat fish such as Herring and Sardine.
The person experiences intense flushing, headaches, palpitations, sweating, vomiting and cramps within one hour of eating the fish. This reaction is due to rapid absorption of histamine from the putrefying flesh of the fish. The fish usually has a telltale metallic or peppery taste due to the high histamine content. Histidine is metabolised to histamine by bacteria. On allergy testing, these patients have no specific IgE antibodies to fish antigens and can tolerate fresh fish on other occasions.
Another fish linked phenomenon seen mainly in Mediterranean Europe is that of fish infestation with the ubiquitous parasite Anasakis Simplex (Codworm). This parasitic worm infects fish flesh. If eaten by humans in lightly cooked fish or raw Sushi this parasite can trigger an anaphylactic reaction which is often mistaken for fish allergy.
Pseudo-allergic food reactions
Pseudo-allergic food reactions or food intolerant reactions are not IgE mediated, but clinically mimic true food allergy. As they are not IgE mediated they rarely cause life-threatening anaphylaxis - with the exception of the preservative sodium sulphite.
Reactions include those to the common Food Additives and Preservatives. Foods that cause direct Histamine Liberation from tissue mast cells. Foods containing high levels of natural histamine or so-called Vaso Active amines, and those foods containing natural salicylate which cause adverse reactions in aspirin sensitive individuals.
Adverse reactions to Food Additives
Everyone is aware of adverse reactions to the food colourant Tartrazine and it has largely been withdrawn as a food colouring. The Azo and non-azo dyes such as Tartrazine, Sunset Yellow and Erythrocine have been found to be quite rare causes of food induced asthma and urticaria. Flavourings such as MSG or Monosodium Glutamate can induce the so-called Chinese Restaurant Syndrome of numbness and burning in the neck, with palpitations and syncope. Occasionally it can induce bronchospasm and urticaria, but the evidence is scanty. Aspartame is a commonly used artificial sweetener, which has been implicated as a trigger for urticaria and angioedema.
As far as Preservatives go, Sulphite used to stop food discoloration or "browning "seems to be major trigger for asthma and even urticaria. Sulphites are found in lemon and lime juices, dried fruit, wine, and sauerkraut and sprayed onto salads to keep them fresh. The Sulphite gas can trigger asthma as a non-specific irritant and up to 20% of asthmatics appear to be sensitive to it. Sulphites foods can induce urticaria, itching and even anaphylaxis has been reported. There may in addition even be an IgE mediated pathway where the sulphite hapten binds to a protein to act as an allergen.
Benzoate’s, Parabens and the antioxidants Butylated hydroxyanisole BHA and Butylated hydroxytoluene BHT have all been implicated as causing bronchospasm, rhinitis and more particularly in triggering urticaria by non-immune mechanisms. An additional food additive is the meat tenderiser Papain, which is actually an allergen. It has triggered anaphylaxis and been implicated as the cause of some suspected meat allergic reactions. This allergen should be borne in mind when evaluating possible allergy to beef and pork meat.
Histamine "Liberator" Foods
Certain non-histamine containing foods can trigger direct histamine release from Mast Cells. These foods directly stimulate the tissue mast cells to release histamine. IgE is not involved in the reaction and specific IgE antibodies to these foods are not elevated. Foods that have been implicated in this type of reaction include Egg white, shellfish, strawberries, chocolate, citrus fruit, tomatoes, fish and pork meat. The histamine liberated in this reaction will cause symptoms that may mimic true food allergy.
Vaso-active amines in food – natural histamine.
Histaminelike substances occur naturally in foods and can trigger symptoms that mimic allergy. This is particularly true of fermented foods that contain high quantities of the vaso-active amines such as Histamine, Phenylethylamine, Serotonin, Tyramine and Dopamine.
Histamine is contained in a number of foods. It occurs in 3 cheeses (Blue, Roquefort and Parmesan), 2 vegetables (Spinach and Aubergine), 2 red wines (Chianti and Burgundy) and yeast extract or Marmite. Tyramine is found in Camembert and cheddar cheese, pickled herring, fermented sauces like bean and Soya, and in chicken livers. Serotonin is in banana, kiwi fruit, pineapple, tomato, walnuts, figs, plum and even seafood such as octopus. Symptoms of vaso-active amine ingestion are cramping, flushing, headache, palpitations and hypotension. The symptoms are usually dose related and occur when the histamine metabolising enzyme diamine oxidase is saturated and cannot metabolise the histamine ingested. Symptoms are most unpleasant but not usually life-threatening.
Natural Salicylate in Food.
Salicylateis a natural aspirin-like substance occurring in certain spices, fruit skins and vegetables. Some Aspirin-sensitive individuals may also be intolerant of salicylate in food and react adversely with oral symptoms. Foods with a high salicylate content are Curry powder, dried thyme and herbs, green apple and potato skins, almonds, tea and certain vegetables.
These foods may occasionally trigger urticaria in aspirin-sensitive people who also react adversely to non-steroidal anti-inflammatory medication. Symptoms may include urticaria, bronchospasm, rhinitis and aggravation of nasal polyposis.
E Numbers as additive labels
E numbers are often branded about in the context of allergy. Most food additives are allocated an E number if approved for use within the European Community. A number of these additives that are implicated with adverse food reactions have already been discussed.
Colourants, flavourings, preservatives and antioxidants all have been allocated E numbers. If the food packaging is labelled with the E number only, the particular additive will not be immediately apparent. Although quite often the label also includes the additive by name.
List of Potential Allergenic Food Ingredients to be labelled in EU countries by 2005
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