Apple is a fruit belonging to the Rosaceae family of fruits. This family comprises many of the most widely consumed fruits in the Northern Hemisphere such as pear, strawberry, and the stone fruits peach, apricot, plum and cherry. Apple allergy is a so-called IgE-mediated food allergy. IgE (Immunoglobulin E) is the allergy antibody. Allergy to apple is caused by proteins in the fruit, the apple allergens. The most important apple allergens have been identified. Apple allergy is often seen in patients with hay fever in early spring caused by pollen of birch alder and hazel. The reason that these allergies frequently go together is that pollen from these trees contain similar allergens as those present in apple. On the basis of this similarity, IgE antibodies of patients with tree pollen allergy also recognize apple allergens. This is called cross-reactivity. The allergens involved in this phenomenon are called Bet v 1 and Bet v 2 in birch pollen and Mal d 1 and Mal d 4 in apple. Bet v 2 and Mal d 4 are so-called profilins. This cross-reactive syndrome only occurs in areas with significant exposure to birch pollen, i.e. in Northern and Central Europe. Allergy to apple however, also occurs in Mediterranean countries like Spain, Italy and Greece where exposure to birch pollen is absent. Cross-reactivity with grass pollen which also has a similar profilin allergen can be the cause apple allergy in these areas. Often however, apple allergy in the Mediterranean area is seen independently from pollen allergies. In these cases, another allergen is responsible for the reactions. This allergen is called lipid transfer protein (LTP), but is also referred to as Mal d 3. LTP is an extremely stable protein that is resistant to food processing and to gastro-intestinal digestion.
Most apple allergic patients notice itching of mouth and throat, and itching, redness and swelling of the lips, within the 5-15 minutes after eating the fruit, or even while chewing and swallowing it. These symptoms disappear 15 to 60 minutes later. This is known as the “oral allergy syndrome”. Some patients present more serious reactions after apple intake, preceded or not by the oral symptoms, and with a variable involvement of the skin, the gastrointestinal and respiratory tracts, and/or the vascular system. At the skin, patients develop nettle rash (urticaria) with or without swelling (angioedema). When present, swelling most frequently affects face, lips and eyelids. The gastrointestinal involvement manifests as stomach burning or pain, cramps, vomiting, and/or diarrhoea. The respiratory tract is less frequently involved, but patients can present with itching of the nose, sneezing, a runny nose (rhinitis) and/or cough, chest tightness, wheezing and short breath (asthma). Some apple allergic patients may develop generalised reactions with involvement of the skin together with other organs. These generalised allergic reactions are known as anaphylaxis and are a medical emergency. Fortunately, only a minority of patients with anaphylaxis present a decrease in blood pressure (hypotension). This is the most severe and life threatening allergic reaction known as anaphylactic shock. Other life threatening reactions such as severe asthma attack or laryngeal or glottis oedema (swelling in throat) are exceptionally observed.
There are regional differences in the manifestations of apple allergy within Europe. In North and Central Europe apple allergy is observed in patients allergic to birch pollen. The allergens involved are easily destroyed by digestion in the gut, and thus can only induce local contact reactions in the mouth and throat where they are still intact. This explains why oral symptoms are for most of the patients the unique manifestation of this food allergy. The lability of these allergens also explains why reactions are only induced by fresh apple while processed foods containing this fruit, including apple juices, are generally well tolerated. In contrast, in Mediterranean areas without birch trees, apple allergy is caused by LTP and is often severer. The majority of patients also have oral symptoms, but generalised reactions such as urticaria and anaphylaxis appear in more than 1/3 of patients. All the patients react to fresh apple, although some of them can tolerate the ingestion of the peeled fruit. The explanation for this is that LTP is more abundant in the peel of apple. Foods containing processed apple commonly induce allergic reactions.
Related foods (cross-reactions)
Allergy to apple in patients with birch pollen allergy frequently goes together with allergy to other related fruits, like pear, peach, cherry, apricot, plum and strawberry. Those patients often also have allergy to tree nuts like hazelnut and to a lesser extent almond and walnut. These types of birch pollen related fruit and nut allergies are exclusively seen in areas with exposure to tree pollen from birch, alder and hazel. Mainly in the Central European part of this area, some vegetables like carrot and celery have also been linked to this syndrome. Peanut allergy can also be a part of it. All these combined reactivities can be explained by the presence of similar allergens. As said, this phenomenon is called cross-reactivity. Grass pollen allergic patients with cross-reactive fruit allergies are common in the Mediterranean area. The spectrum of fruits that is potentially involved in allergic reactions is overlapping with the birch pollen related foods but is even broader. In Spain melon and banana have been shown to be among the foods that are frequently linked to grass pollen fruit cross-reactivity.
Allergy to apple caused by IgE antibodies against LTP is almost exclusively seen in patients with peach allergy. This suggests that peach is the cause of the allergy. There is some evidence now that other fruits like grape (Greece) can also cause LTP allergy. The spectrum of foods that can cause reactions in LTP patients is very similar to those involved in the birch pollen apple syndrome: peach, pear, cherry, apricot, plum, nectarine, hazelnut, walnut, and almond. In some cases, allergy to LTP can be linked to symptoms induced by other plant foods like peanuts, string beans, salad, corn, grapes including wine and barley and wheat including beer.
Who, when, how long and how often?
Apple is most frequently involved in food allergic reactions in adolescents and adults. Females are affected twice more frequently than males. Apple allergy is the most frequent food allergy in Central and Northern Europe in areas rich of birch trees, whereas peach is the food most frequently involved in allergic reactions in the Mediterranean area in countries such as Spain, Italy and Israel. Allergy to birch in areas with significant exposure to birch pollen is observed in around 10% of the population. Of these patients up to half will have allergy to apple. This means that up to 5% of the population is affected by apple allergy. Apple allergy in areas without birch pollen is much rarer. The exact frequency has not been established.
Birch pollen related apple allergy comes up after the occurrence of hay fever. In general, hay fever develops in the school age (roughly between 5 and 15 years), usually followed by apple allergy several years later. In practice this means that apple allergy develops in the teenager years or later. Birch pollen allergy is usually not outgrown, and consequently apple allergy is life-long as well.
Apple allergy related to LTP usually develops around puberty. In most cases, peach allergy precedes the occurrence of apple allergy. As far as known now, this form of apple allergy is not outgrown.
How much is too much?
There are no studies available that have reliably established how much apple is enough to trigger an allergic reaction. It is expected that this quantity will be different in patients with birch pollen related and LTP-related apple allergy. In a small group of patients with birch pollen related apple allergy it was shown that 5 grams of an apple gave a reaction during a challenge. This is a small bite of apple (an average apple is 200-250 grams). Differences in allergenicity between apple varieties have been demonstrated.
Apple allergy is suspected on the basis of the medical history which establish the relationship between the contact with the fruit and the appearance of symptoms, it is supported by the demonstration of specific IgE by means of skin and blood tests, and it is confirmed by an oral challenge. The best test to demonstrate a sensitisation (presence of specific IgE) to apple is the prick-prick test with fresh apple. In this test the lancet is plunged several times into the fruit immediately before pricking the patient’s skin with it. The sensitivity of this test (the frequency of positive results in allergic patients) is high, generally over 80%. Peel and pulp can be tested separately. False negative skin tests are frequently found with commercial apple extracts, especially in patients sensitised to labile allergens which can be modified during the extract preparation. This factor can also reduce the diagnostic performance of the commercially available blood tests for the detection of serum IgE to the fruit.
In the clinical practice it is rarely indispensable to make oral challenges to confirm the clinical suspicion if the symptoms are unequivocal (which is almost always the case), and the patient presents specific IgE to apple. In those patients with anaphylaxis in whom specific IgE is demonstrated, oral challenges should not be performed.
Where do I find apple?
Apple is of course primarily eaten fresh as a whole fruit. It is also a major component of fresh fruit salads. Dried apple is used in products like candy bars, breakfast cereals, and tuti fruti. Apple is used in yoghurts and deserts, fruit juices and apple sauce. Apple is frequently used in cakes, pies and other pastries. For those patients that have apple allergy as a result of their pollen hay fever, only fresh fruit is causing symptoms, processed apple has lost its allergen activity. For patients with LTP-related apple allergy, processed apple is causing symptoms as well. It is important to realize however, that patients with pollen allergy can at the same time also have LTP-related apple allergy.
Apple is not a common ingredient in non-food products. It is however used in some hygiene products like shower gels, soaps and shampoos.
The only recommendation to apple allergic patients is the strict avoidance of the fruit. This is especially important in the population from the Mediterranean area sensitised to LTP that is at risk of severe reactions. They should avoid fresh apple as well as apple processed products. Certain patients with previous anaphylaxis or anaphylactic shocks should be trained in the early recognition and treatment of reactions in case of accidental ingestion, and given rescue medication including adrenaline (epipen). Patients with apple allergy linked to birch pollinosis should avoid fresh apple. Avoidance of apple processed products is generally unnecessary, but if their tolerance is unknown it should be assessed at the allergy clinic before allowing their ingestion. If the tolerance to a related cross-reactive food (such as other Rosaceae fruits) is not known or has not been assessed after a confirmed diagnosis of apple allergy, patients should avoid it. This is again especially important in patients sensitised to LTP who have had serious reactions with apple.
The effect of birch pollen immunotherapy on the linked apple allergy has been investigated. Some investigators have found a beneficial but seemingly transient effect. Three years after birch pollen immunotherapy is stopped half the patients are again reactive to apple.
Apple is not included in the list of foods of the recent new legislation of the EU on food labelling (EU Labelling Directive 2003/89/EG and list of Codex Alimentarius Commission on mandatory labelling of pre-packaged food). This means that patients can not completely rely on food labels if searching for the presence of apple.