Route Of Exposure

Allergen Exposure

Strawberry plants make up about 12 species of low, runner-bearing perennial herbs. The strawberry is the sweet red fruit borne on the runner. Most are native to northern temperate regions. Strawberry plants are cultivated as ornamentals and – especially – for their fruit. Strawberry was cultivated in the days of the Greeks and Romans, and commercial cultivation began about 250 years ago in France. Most cultivated Strawberries are derived from crosses between F. chiloensis and F. virginiana.

Both cultivated and wild strawberries are eaten raw and used in desserts. They are often used to make preserves, and are even dried. The leaves are eaten raw or cooked, and used as a tea substitute. The root is a coffee substitute in India.

The fruits contain salicylic acid. Both the fruits and leaves are used in a variety of herbal remedies. Externally applied, strawberry is a remedy for chilblains and sunburn.

The fruit is also an ingredient in skin-care creams and tooth-whiteners. The flowers sometimes serve as a compost activator.

Clinical Relevance

Allergen Description

A number of allergenic proteins have been detected, including a 30 kDa cross-reactive protein.

The following allergens have been characterised from F. ananassa:

Fra a 1 has been shown to vary among different strawberry varieties. For 153 other proteins, biological variation is affected more by different growth conditions than by different taxonomical varieties. The allergen content was found to always be lower in colourless (white) strawberry varieties than in the red ones.

Fra a 3 LTP gene expression in strawberry is stimulated by wounding and repressed by cold stresses. Examination of strawberry allergy in the Mediterranean area showed that although strawberry LTP (Fra a 3) is present in strawberry extracts, and is capable of eliciting histamine release in peach LTP (Pru p 3)-sensitised patients, the concentrations needed are much higher than for Pru p 3, such that these patients do not show clinical strawberry allergy; therefore, Fra a 3 does not seem to be clinically relevant.

A Bet v 6-related food allergen, PCBER (phenylcoumaran benzylic ether reductase), has been detected.

A beta-1,3-glucanase gene has been isolated from strawberry; this enzyme has been shown to have allergenic potential in other plants. Its allergenic potential in this instance was not evaluated.

The pectolytic enzymes polygalacturonase, pectate lyase and pectin methylesterase (PMEs) have been isolated from strawberry and are partly associated with a decrease in fruit firmness observed during ripening. Maximum PME activity was detected in green fruits, and decreased steadily to a minimum in senescent fruits. Although these enzymes may be allergenic in other plants, their allergenic potential was not evaluated in the case of this one.

The white variety of strawberries, known to be tolerated by individuals affected by allergy, were found to be virtually free from strawberry allergens. Also, several enzymes in the pathway for biosynthesis of flavonoids, to which the red color pelargonidin belongs, have been shown to be down-regulated in these strawberries.

Potential Cross Reactivity

Extensive cross-reactivity among the different individual species of the genus could be expected. Extensive cross-reactivity occurs among various members of the Rosaceae family, but to date, the amount of cross-reactivity between strawberry and other members of the family has not been evaluated.

Fra a 1 has a 54-61% and a 77-78% sequence identity with Bet v 1 and the homologous apple allergen Mal d 1, respectively. Cross-reactivity with other plants containing a Bet v 1 homologue is therefore possible.

Allergy to Rosaceae fruit is frequently associated with birch pollinosis in central and northern Europe, and with grass pollen allergy in central Spain. The main cross-reactive structures involved in individuals who have birch pollen allergy are Bet v 1 and profilin; in grass pollen-allergic individuals, profilin and carbohydrate determinants. Rosaceae fruit allergy can occasionally occur in patients without pollinosis. Eleven patients from central Spain allergic to apples, peaches, and/or pears, but not to pollen, were compared with 22 control subjects with combined grass pollen and fruit allergy. Rosaceae fruit allergy without pollinosis was reported to be severe, with 82% of patients reporting systemic symptoms, mainly anaphylaxis (73%), whereas oral symptoms were less frequent (64%). Anaphylaxis was seen in 36% of patients. The fruit allergens involved showed cross-reactivity between Rosaceae species, but were not related to profilin or Bet v 1. Ninety-one per cent of patients with combined grass pollinosis and fruit allergy reported oral allergy, 45% reported systemic symptoms, 18% reported anaphylaxis, and 9% reported anaphylactic shock. The study concluded that allergy to Rosaceae fruits in patients without a related pollen allergy is a severe clinical entity. Profilin- and Bet v 1-related structures are not involved in Rosaceae fruit allergy without pollinosis.

A recent study concluded that in pollen-allergic patients who frequently present with allergic symptoms after ingestion of any of several kinds of plant-derived foods, the majority of these reactions are caused by 4 distinct cross-reactive structures that are present in birch pollen. Proteins that share epitopes with Bet v 1, the major birch pollen allergen, occur in pollens of several tree and other species: apple, stone fruits, celery, carrot, nuts, and soya beans. Approximately 70% of patients who are allergic to birch pollen may experience symptoms after consumption of foods from these groups. In contrast, 2 minor allergenic structures, profilins and cross-reactive carbohydrate determinants (CCD), which sensitise approximately 10-20% of all pollen-allergic patients, are also present in grass pollen and weed pollen. IgE-binding proteins related to the birch pollen minor allergen Bet v 6 (PCBER) are found in apple, peach, orange, lychee, strawberry, persimmon, zucchini, and carrot. However, the occurrence of cross-reactive IgE antibodies often does not correlate with the development of clinical food allergy. For example, in a DBPCFC study, reactions to peach occurred in 22 patients, in 6 to apple, and in 5 to apricot. The authors concluded that the presence of skin- or serum-specific IgE should not be taken as the only guide for multi-species dietary restrictions. Nevertheless, the possibility of clinical allergy to other Rosaceae should not be neglected. If the reported reaction is confirmed, current tolerance to other Rosaceae should be precisely established, unless there has been ingestion without symptoms after the reaction.

IgE antibodies were found to peach, guava, banana, mandarin and strawberry in a patient experiencing anaphylaxis after eating peach. The cross-reactive protein was identified as a 30 kDa protein occurring in all of the fruits.

In a study of 61 patients with a documented history of IgE-mediated reactions to grape or its products (wine, juice, and wine vinegar), it was found that 82% were co-sensitised to apple, 71% to peach, 48% to cherry, 33% to strawberry, 49% to peanut, 43% to walnut, 31% to hazelnut, 26% to almond, and 29% to pistachio. The high prevalence of concomitant reactivity to other fruits elicits interest in the clinical relevance of these findings among the grape-allergic population.

A Mexican retrospective review of 232 patients with pollen allergy, among whom sensitisation to olive tree pollen was found in 41.5%, found that 16.6% experienced symptoms of oral allergy syndrome, mainly related to apple and strawberry.

Clinical Experience

IgE-mediated reactions

Strawberry may commonly induce symptoms of food allergy in sensitised individuals, and was reported to be a common cause of allergy in children. Birch pollen-related foods appeared to dominate in Scandinavia, whereas some mugwort-related foods were of more apparent importance in Russia and the Baltic States. Among 1 139 individuals, strawberry was the 7th-most-reported allergenic food, resulting in adverse effects in 31%. According to a Polish study, most positive skin-specific IgE reactions to food allergens occurred with nuts, celery, rye flour, carrot, strawberry, pork, and beans. In a Mexican study, among 1 419 allergic patients aged between 1 and 18 years, 442 (31%) had positive skin-specific IgE tests to 33 tested foods. Fish, cow’s milk, seafood, soya, beans, orange, onion, tomato, chicken, nut, lettuce and strawberry were together responsible for 58% of all the allergic reactions.

A cross-sectional, descriptive, questionnaire-based survey was conducted in Toulouse schools to determine the prevalence of food allergies among schoolchildren. Of 2 716 questionnaires returned, 192 reported a food allergy. Eight reported allergy to strawberry.

A study was conducted to evaluate the differences between some northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms: 1 139 patients with a history of food hypersensitivity filled out a questionnaire in which 86 different foodstuffs were listed. The foods reported as eliciting symptoms differed among countries. In Russia, Estonia, and Lithuania, citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, hen’s egg, and cow’s milk were most often reported as causes of hypersensitivity. In Sweden and Denmark, birch pollen-related foods, such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common reported causes. In all countries, children (more often than adults) had symptoms of allergic reaction to citrus fruits, tomato, strawberry, cow’s milk, hen’s egg, and fish. Most patients (95%) reported hypersensitivity to several foodstuffs (median: 8 foods). The most common symptoms were oral allergy syndrome and urticaria.

Reactions reported include symptoms of food allergy (abdominal pain and cramping, nausea and vomiting), atopic dermatitis, asthma, rhinitis, and symptoms of oral allergy syndrome. Allergy to strawberry has also been reported as part of a true multi-food allergy in a 4-year-old child.

A study evaluating the role of profilin and lipid transfer protein was conducted; the subjects were 28 patients recruited from Spain and Italy who had a reported history of strawberry allergy. Reported symptoms were oral allergy syndrome (n=26), asthma (n=1), generalised urticaria (n=1), and pruritus (n=1). Serum-specific IgE was detected in 9, but was evaluated only in 16. Sixteen of the 17 skin-prick tests performed were positive.

Food-dependent, exercise-induced anaphylaxis attributed to strawberry has been reported.

Contact urticaria to strawberry has been documented. Contact urticaria to cucumber pickle and strawberry has been reported. A fixed-food-eruption to strawberry was also reported.

Allergic contact dermatitis to strawberry lip salve has been reported.

Other reactions

Strawberry contains a variety of aromatic and vasoactive substances, e.g. histamine, that may result in non-IgE-related reactions. For example, urticaria may occur as a result of excess production of histamine triggered by the fruit.

Unripe strawberry fruit may produce a triterpene phytoalexin, which appears to be involved in the resistance of strawberry to a particular fungus. Phytoalexin may result in photosensitivity dermatitis.