Common silver birch

Synonym: B. pendula

Allergen Exposure

• Bet v 1, a 17 kDa protein, a ribonuclease and a PR-10 protein (8-17).
• Bet v 2, a 15 kDa, a profilin  (11,15-25).
• Bet v 3, a 24 kDa calcium-binding protein (19,26).
• Bet v 4, a 9 kDa calcium-binding protein (20,27-29).
• Bet v 5, a 35 kDa isoflavone reductase-related protein (30-32).
• Bet v 6, a 30-35 kDa protein, PCBER (Phenylcoumaran benzylic ether reductase) (33).
• Bet v 7, a 18 kDa protein, a cyclophilin (34).
• Bet v 11 (39).

The following recombinant allergens have been expressed:

• rBet v 1 (35).
• rBet v 2 (25,36-38).
• rBet v 3 (19,26).
• rBet v 4 (20,28-29).
• rBet v 5 (30).
• rBet v 6 (11).

Bet v 1 displays a considerable degree of heterogeneity and consists of at least 20 isoforms (Bet v 1a to Bet v 1n), which differ in their IgE-binding capacity (8,17,30,39). Although the major allergen Bet v 1 recognises serum-IgE antibodies in up to 95% of Birch pollen-allergic indivuals (30), studies among patients from 6 countries report highly variable IgE sensitisation profiles in Birch pollen-allergic patients from various countries and regions (40).

Bet v 2, a profilin, has been reported as being recognised by IgE from about 10% to 38% of Birch pollen-allergic patients from Central Europe (41-42.) The percentage affected clearly depends on the geographic area; in Swedish and Finnish patients, approximately 5-7% were sensitised to Birch profilin, compared to 20-38% of patients in Central and Southern Europe (42). Similarly, in a study that reported that few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, Bet v 2 reactivity was found to be more common in the other populations (20% to 43%) (40).

Bet v 3 is recognised by IgE from about 10% of Birch allergic patients (30).

Bet v 4 reacts with serum IgE from approximately 20% of individuals allergic to pollen (8,19-20,30,43).

rBet v 5 bound IgE from 32% (9/28) sera from Birch pollen-allergic patients with an IgE antibody level of at least 3.50 kU/l (30).

Bet v 7, a cyclophilin, was recognised by IgE antibodies in up to 20.8% of Birch pollen-allergic patients (34).

Significantly, Birch pollen-allergic individuals may not be sensitised to any of the major Birch pollen allergens.

Potential cross-reactivity

Cross-reactivity between pollens from species within the Betulaceae family or belonging to closely related families can be expected (44-47). Fagales pollens, e.g., Birch (Betula verrucosa), Alder (Alnus glutinosa), Hazel (Corylus avellana), Hornbeam (Carpinus betulus) and Oak (Quercus alba), all contain 1 major Birch pollen-related allergen (43). Amino acid sequence identities between the Cor a 1 isoforms from Hazel and Bet v 1 were between 71% and 73% (80.5-83% similarity); between Cor a 1 isoforms and Aln g 1 from Alder, there was 75.5-76.7% identity (83.6-85% similarity); and between Cor a 1 isoforms and Car b 1 from Hornbeam, 83.6-89.9% sequence identity (89.3-95% similarity) (48). Cas s 1 from European Chestnut shows significant amino acid sequence similarity and is antigenically closely related to Bet v 1 (49). Cross-reactivity has also been reported between Birch tree and other members of the Fagales family (such as Beech), and partial cross-reactivity between Birch and Ash pollens (50).

The most common manifestation of allergy to food in Birch pollen-allergic individuals is oral allergy syndrome and typically occurs in Birch tree pollen allergic individuals in Central and Northern Europe. Symptoms elicited are usually limited to the oropharyngeal system and are called “oral allergy syndrome”. This is discussed in detail below.

Cross-reactivity has also been noted between Mugwort, Birch pollen allergy, and Celery (51-53), a phenomenon often referred to as “Birch-Mugwort-Celery syndrome” (54), or ”Celery-Carrot-Birch-Mugwort-spice syndrome” when Carrot and Spices are included (55-59). Spices involved included Anise, Fennel, Coriander, and Cumin, all members of the Apiaceae family (60).

Bet v 1, the major allergen in Birch pollen, is a member of a group of defence proteins (PR-10) (61), which behave as major allergens in patients from Northern and Central Europe with allergy to plant foods associated with Birch pollen allergy. In these patients, the primary sensitisation seems to be produced through the inhalation route on exposure to Birch pollen. The most characteristic set of symptoms associated with sensitisation is oral allergy syndrome (OAS) (62). The major allergens in Apple, Pear, Apricot and Sweet Cherry are structural homologues to the Birch pollen major allergen Bet v 1 (63).

Bet v 2, a profilin, may result in cross-reactivity with other profilin containing pollens or food, including Hazelnut, Ragweed pollen, Mango, Mugwort pollen, Timothy grass pollen, Celery, Carrot, Peanut, Paprika, Anise, Fennel, Coriander, Cumin, Tomato and Potato (64-65).

Furthermore, profilin is present in Birch pollen, Peach and Apple, and this may result in cross-reactivity among these, even though the patients in question have never been exposed to Birch (66).

Bet v 3 and Bet v 4 are calcium-binding proteins, may result in cross-reactivity with other plants containing these panallergens.

Bet v 5, an isoflavone reductase-related protein, is a minor Birch pollen protein and may be responsible for pollen-related oral allergy to specific foods in a minority of patients with Birch pollen allergy (30,32).
Bet v 6, a pectin esterase (67), affecting approximately 10-15% of Birch pollen-allergic individuals, was reported to be cross-reactive with proteins of comparable size from Lychee, Mango, Banana, Orange, Apple, Pear and Carrot (68).

Clinical Experience

IgE-mediated reactions
Birch pollen is highly allergenic and is a significant cause of immediate hypersensitivity, in particular asthma and rhinoconjunctivitis, not only in Scandinavia, Europe, Canada, and the northern part of the United States but also in Japan, resulting in allergic reactions such as asthma, allergic rhinitis and conjunctivitis in adults and children (45-46,69-85).

Birch pollen is a significant cause of immediate hypersensitivity among susceptible subjects in temperate climates, affecting 5-54% of the population in Western Europe (86). The number of individuals allergic to plant pollen has been on a constant increase, especially in large cities and industrial areas. For example, in a Belgian study of patients suffering from respiratory allergy, the frequency of Birch pollen sensitisation significantly increased, from 13% in the period 1975-1979 to 34% in the period 1992-1995. In contrast, the frequency of house dust mite, Timothy grass pollen, and Mugwort pollen sensitisation remained almost unchanged. The increase was not associated with an increase in the Birch pollen count (87). An increased sensitisation to Birch has also been reported in the Netherlands (88).

Both adults and children may be affected. Immune response to Birch has been reported to occur in all children during the first 7 years of life, regardless of atopic status (89). It was documented that children exposed to high Birch pollen levels at 1 year were more likely to be sensitised to Birch pollen than those born in a year with a lower exposure, and more likely to have allergic asthma (90). Furthermore, exposure of the mother during pregnancy to high levels of Birch pollen was reported to result in a tendency towards increased risk of sensitisation to the same allergen, and increased symptoms of atopic disease in children with atopic heredity (91-92).

Furthermore, sensitisation to Birch may occur in new immigrants residing in an area highly populated with Birch trees. For example, among immigrants to Sweden, sensitisation to Birch, as documented by serum IgE antibodies and SPT, increased from 16% within 2.5 years to 53% after more than 10.5 years. More than 40% of the immigrants who had asthma, rhinoconjunctivitis, eczema, and urticaria were allergic to only Birch pollen, and 19% had oral allergy syndrome, suggesting that environmental factors rather than hereditary differences determine the IgE state (76).

Sensitisation to Birch tree pollens are heterogenous in character with individuals being sensitised to one or more Birch tree pollen allergens. In a retrospective Spanish study of pollen allergy caused by Betula in the area of Ourense, out of 222 patients diagnosed with pollen allergy, 41.89% were shown to have skin reactivity to Betula alba (10.75% were monosensitised); 30% suffered from an oral allergy syndrome to fruits; 41.93% of the patients with skin reactivity to Betula pollen had asthma, in comparison with 23.25% of the those with no sensitisation to Betula (93).

Because of the close relationship shared between Betula species, similar inferences can be drawn in countries where these species occur. For example, atmospheric surveys carried out in different parts of India showed that the closely related Betula utilis produced allergenically important pollen (94).

In Sapporo, Japan, the most common allergen responsible for pollen allergy was Birch, affecting 54 of 87 patients (62%) (95). In 392 patients with nasal allergy attending a clinic in Sapporo, 74 (18.9%) were Birch pollen-allergic. The authors reported that there had been a significant increase in Birch pollen allergy, compared with previous reports (96). A study reported that allergy to Japanese White Birch (Betula platyphylla var. japonica) is gradually increasing; this was especially marked in Sapporo and its neighborhood (97).

Birch pollen has been demonstrated to be a significant allergen in Sweden (98-100), Finland (101), Switzerland (102-103), Belgium (104), Austria (74), Germany (105), Spain (106), Greece (107), the Netherlands (108-110) the UK (111) and Japan (112). Birch pollen has been reported to be a major aeroallergen in Fairbanks area, Alaska, from early May to September (113-114).

The most common manifestation of allergy to food in Birch pollen-allergic individuals is oral allergy syndrome (115). Individuals with Birch allergy and oral allergy syndrome are more frequently allergic to Apple than to other foods (116-117). Rhinitis, itching, tingling and other mild reactions on the oropharyngeal mucosa were reported to be the most common complaints after eating raw Apples (in about 30% of patients with hypersensitivity to Birch pollen). Agioedema, urticaria and anaphylaxis were reported to be rare, “but must be noticed” (118). Other studies indicated an association of 70% between oral and pharyngeal reactions to vegetables and fruits on the one hand, and Birch pollen allergy on the other (11,119).

Of 171 Birch pollen-sensitised patients (having IgE antibody levels >0.7 kUA/l), 22 (13%) were hypersensitive to Apple, 11 (6%) to Peach, and 6 (3.5%) to Kiwi fruit. The higher the IgE antibody level to Birch, the higher the prevalence of hypersensitivity to Apple and Peach were found to be (120).

In a study of 283 patients with clinical Birch pollen hypersensitivity, OAS was associated with more severe respiratory symptoms and with higher Birch-specific and total IgE levels; moreover, its onset was clearly related to the duration of Birch pollinosis. Significantly, this study suggests that about 15% of patients with Birch pollen hypersensitivity are not prone to OAS, and that their anti-Birch IgE might be directed against determinants that do not cross-react with food allergens (121). Furthermore, in Mediterranean areas, oral allergy syndrome (OAS) occurs independently of Birch pollinosis; moreover, on occasion it presents with no associated pollinosis (122). Also, IgE antibodies to Birch may be detected in patients with oral allergy syndrome even in geographical areas where Birch pollen is absent. The authors suggest that even in such areas measurement of IgE antibodies to Birch pollen is important for screening and diagnosing patients with oral allergy syndrome (123).

Importantly, allergens present in Peach and Apple may result in cross-reactivity between these 2 foods and Birch, even though patients have never been exposed to Birch (66). Further evidence for the cross-reactive relationship between Birch and Apple is demonstrated by the fact that 56% of patients allergic to Birch pollen and Apple improved in their fruit allergy if desensitised to Birch pollen (124).

Bet v 1 mainly results in mild symptoms of oral allergy syndrome. This is usually caused by Apple, Cherry, Peach and Plum but can also be observed with other allergens giving rise to generalised symptoms. Sensitisation to Bet v 2 is commonly associated with more-generalised symptoms, in particular urticaria and angioedema (55). In allergy that is not related to Birch pollen, oral allergy syndrome to Rosaceae foods may occur as a result of lipid transfer proteins, and, in contrast to the typical experience of Birch-Rosaceae cross-reactive patients, this kind of oral allergy syndrome is frequently accompanied by more severe and systemic reactions (125).

Symptoms of food allergy in Birch pollinosis patients are usually mild and restricted to the oral cavity. On the other hand, while allergy to a food, e.g., Hazelnut, without concomitant pollinosis is less common, symptoms tend to be more severe and are often systemic (116).

Other reactions
Birch pollen-related foods have been reported to trigger atopic dermatitis in patients (126-128). In particular, immediate and delayed hypersensitivity to Birch pollen may result in worsening of atopic dermatitis during the Birch pollen season (77). Adult patients with hypersensitivity to Birch pollen and atopic dermatitis have been shown to have a worsening of their condition after oral challenge with Birch pollen-related foods.
Contact urticaria to fruit related to Birch sensitivity has been reported (129).


Children with Birch pollen-allergic rhinoconjunctivitis have been reported to exhibit an enhanced degree of gingival inflammatory reaction (130). Allergy and sensitivity to Birch pollen (and probably to other kinds of allergens) was reported to be an important risk factor for adenoid hypertrophy in children (131).

Compiled by Dr Harris Steinman, harris@zingsolutions.com.

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