Oral Allergy Syndrome
Dr Janice Joneja investigates this conditon which plagues so many people early in the year.
Oral Allergy Syndrome (OAS), which is also known as pollen-food allergy syndrome, should not be confused with the type of food allergy that can cause anaphylaxis. OAS symptoms occur in the mouth and throat of someone primarily allergic to inhaled pollen allergens (usually tree, weed or grass pollens) with typical respiratory symptoms of hay fever, who reacts to specific food allergens which contain structures indistinguishable from those of the pollen (1) . Symptoms only occur when they eat those foods and the foods come into direct contact with the lining of their mouths and throats (2).
There are no authoritative data on how common OAS may be as there can be significant geographical and climatic differences in cross reactivity depending on where you live (3) For example, in central and northern Europe, allergies to fruits such as apples and stone fruits (eg, peach, apricot, cherry) of the Rosaceae family are closely associated with birch tree pollinosis, but in North America they are also associated with grass or ragweed pollen, in Europe with wormwood, and in Japan with cedar (4)
Symptoms of OAS
Symptoms include itching, tingling, and irritation of the inside of the mouth; swelling, and sometimes blistering, of the lips, palate and tongue; occasional sensation of tightness in the throat; and rarely systemic (whole body) symptoms (5). Most people with this allergy exhibit symptoms within 5 minutes of eating the offending food, and almost all individuals show symptoms within 30 minutes after contact with the food (1).
Although there are reports of OAS resulting in anaphylaxis, most experts agree that anaphylaxis to a food should not be considered as OAS but should be treated as classic food allergy that triggers symptoms in the mouth in addition to other organs (6,7).
Oral symptoms following eating fruits, vegetables, and nuts have been described in individuals with coexisting allergy to trees of the birch/alder group, (5,8–17) weeds such as mugwort, (18,19) ragweed, (20,21) grasses, (22,23) and other pollens (24)
Table 1 provides a summary of frequently reported pollen and food associations.
Cause of OAS
OAS symptoms are caused by a rapid response of the mast cell–bound IgE to allergens released from raw fruits and vegetables as the allergens enter the mouth and come into contact with saliva. There are unusually high concentrations of the mast cells that trigger the symptoms of the allergy in the oral and pharyngeal tissues. It is thought that the high reactivity of these mast cells results from continual exposure to the pollen allergens as they are inhaled (8).
As defined, the syndrome has two important aspects:
1. Symptoms appear in the mouth and adjacent tissues and occur immediately on contact with the allergenic food.
2. The sufferer must also have an allergy to inhaled plant materials, usually pollens (pollinosis). The pollinosis will usually be long-standing, often having been present before the symptoms of OAS appear.
The type of allergy in which the individual is sensitised to the food secondarily to inhaled pollens, is called class 2 food allergy. In a class 2 food allergy the sensitising allergen is something other than a food; the food reaction is a result of a structurally similar molecule in the food being recognised by the antibody to the non-food allergen. In a class 1 food allergy the sufferer is sensitised primarily to the food to which IgE antibodies are produced. (25)
Characteristics of Allergenic Food Protein in Relation to OAS
Analysis of many food proteins at the molecular level has made it much easier to recognise the clinical signs and symptoms of food allergy, especially in the case of OAS (1,8,26).
OAS is due to similarities between amino acid sequences in the food protein allergens (eg, apple, carrot, or hazelnut) and the allergenic pollen proteins (eg, birch pollen). A match of over 70% of the amino acid sequence is generally needed for cross-reactivity to occur. Other syndromes due to cross-reactivity between non-food allergens and foods include the latex food syndrome, the house mite/seafood syndrome, and the bird/egg syndrome (27). In investigations of OAS, birch pollen and its associated food allergens have been the most extensively studied.
Birch Pollen Allergens and OAS
At present, at least seven birch pollen antigens (molecules which can trigger an allergic response) have been well identified (designated Bet v 1 through Bet v 7) (28) Bet v 1 was the first of these allergens to be identified and is thought to be the most significant in birch pollen allergy (29) There is a considerable degree of similarity between the structure of Bet v 1 and the main apple allergen (Mal d 1), which is why raw apple appears to trigger OAS symptoms so often in individuals with birch allergies.
Bet v 2 and Bet v 4 are two other allergens that seem to be involved in the birch pollen–associated OAS (but at probably lower reaction levels) (28). Bet v 2 has lower allergenicity than Bet v 1 (ie, has a reduced tendency to cause allergic reactions, and the allergy it triggers is less severe).
However, persons who are sensitized to Bet v 1 and to Bet v 2 are more likely to develop OAS (28). This may be true of other birch allergens, such as Bet v 4, that have a tendency to trigger a reaction in individuals allergic to birch while they are undergoing birch pollen immunotherapy by desensitisation injections. (30)
There are indications that the severity of an allergic reaction to a food depends on the allergen responsible for the sensitisation. By studying the IgE reactivity profiles against hazelnut extract of individuals with severe anaphylactic reactions, Pastorello (31) showed that anaphylactic subjects reacted only to an allergenic hazelnut lipid transfer protein (see below). On the other hand, individuals sensitised to the major hazelnut allergen (Cor a 1), which is 70% similar to birch pollen (Bet v 1), only had OAS reactions (32,33). In the same context, the major allergen responsible for cross-reactivity between birch ad cherry has been identified as Pru av 1 ( 34).
Allergenicity of Plant-derived ProteinsOne of the most important groups of plant-derived proteins that are responsible for allergies are the pathogenesis-related (PR) proteins. PRs are proteins that are created when the plant suffers some sort of environmental stress such as an infection, a wound, dehydration, pollution, or comes into contacts with noxious chemicals such as pesticides (27).
Pathogenesis-related proteins have been classified into 14 families. Examples of plant food allergens similar in structure to PR proteins include:
Properties of Plant-Derived Proteins and Associated Food AllergyThe different properties of these groups of plant-derived proteins may account for differences in symptoms observed in individuals with food allergies. Classification of allergens into groups with structural similarities may help to predict cross-reactivities, thus providing useful information to individuals with food allergies.
To distinguish between those causes of oral symptoms not definable as OAS and those fitting the definition of OAS, it is essential that the allergen responsible be identified and its presence established in each of the allergenic materials (7,35,36).
Ideally, each molecule that could be responsible for apparent cross-reactivity between a substance that is breathed in and one that is eaten should be isolated and identified to confirm exactly what elements are cross-reacting (37).
Management of Oral Allergy Syndrome
A list of the foods that most frequently trigger symptoms of OAS in individuals allergic to pollen is provided in Table 1.
Individuals allergic to pollen who do not show symptoms of OAS should not restrict their diet in order to avoid the possibility of developing OAS. It is unnecessary for a person with OAS to avoid other pollen-associated foods if they have not become sensitised to them (38). Over time a person with OAS may develop oral symptoms to other foods on the list of those that cross-react with their particular allergenic pollen. In these cases the onset of the reaction is usually a mild tingling rather than an overt OAS reaction. The person will thus be alerted to the possibility of a reaction and should thenceforth avoid that food in its raw form.
In many cases, the allergen responsible for OAS is a class 2 allergen (see above). An important characteristic of Class 2 allergens is that most of them are sensitive to heat (in scientific terms, they are heat-labile)(25). This means that individuals with OAS can usually eat the plant foods with impunity after the foods have been cooked. Cooking the food frequently allows a person to eat the food without a reaction even when symptoms develop in contact with the raw food.
Identification of the Foods That Cause Symptoms
Very often it is clear which foods trigger OAS, because the reaction is immediate on contact with the raw food. Individuals often report exactly which foods cause a problem and record the reaction in their food and symptom records. However, when the foods responsible are not obvious, or if the list of suspect foods is extensive, an OAS elimination diet is useful. This would then be followed by challenge to identify the foods responsible.
Open Food Challenge
In most cases, open food challenge with gradually increasing doses of the test food will identify the foods that need to be avoided. Gradually increasing doses of the troublesome food (known as incremental dose challenge or SIDC) is a method of challenge in which a small quantity of the test food is consumed and symptoms monitored for an initial 4-hour period. If no symptoms develop, the test dose of the food is doubled, and again symptoms are monitored for another 4 hours. If symptoms again do not occur, a further doubled dose of the food is consumed. This method of challenge is usually very effective in demonstrating food allergy when symptoms occur in the mouth and as well as elsewhere in the body, and when the quantity of food is an important factor in triggering a response.
Topical Application of the Food
When the symptoms occur predominantly in the mouth and on immediate contact with the food, applying a little of the test food to the lip may be all that is needed to trigger a symptom. The site of application is observed for the development of obvious symptoms, such as itching, reddening, blistering, or swelling. Twenty minutes is usually a sufficient length of time for the reaction to develop. If topical application does not trigger any symptoms, then the incremental dose challenge (SIDC) should confirm whether the food is indeed responsible for symptoms.
The Final Diet
When the culprit foods have been identified by challenge, they should be carefully eliminated from the diet. Complete balanced nutrition must be supplied from alternate foods, especially when the foods restricted are important sources of essential nutrients.