Latin name: Lycopersicon esculatum
Source material: Whole freeze-dried tomato
Common names: Tomato, Garden Tomato, Love Apple
Tomato is a vine fruit of the Nightshade family. Tomatoes were used for food by the Indians of Peru before the arrival of Europeans. Tomato is the most universally accepted vegetable among all cultural groups, and second only to Potato as a vegetable in world food production. A great variety of cultivars exist, from the tiny Cherry tomato to giant prize varieties the size of Grapefruit; and though the sterotyped colour is red, colours can range from green to purple, and some varieties have stripes. Many wild forms are found, including a closely related species called Currant tomato (L. pimpinellifolium).
Wild forms are found, but are generally not good to eat. Tomato can be eaten raw or cooked, but is mostly processed into juice, canned goods, etc. It can be used as a savoury vegetable, especially in salads, and as a flavouring in soups and other cooked foods. The fruit can also be dried and ground into a powder to serve as a flavouring and thickening agent in soups, breads, pancakes, and so on. An edible oil can be obtained from the seed. The fruit is rich in vitamins A and C, calcium and potassium.
The skin of Tomato fruits is a good source of lycopine. Tomato is used as a herbal remedy for a variety of conditions. The pulped fruit is a wash for oily skin. The oil can be used in making soap.
All green parts of the plant are poisonous. A spray made from Tomato leaves is an effective but very toxic insecticide.
Allergens began to be isolated around 4 decades ago (1) but have only recently been characterised.
In a study of 2 patients with significant immediate hypersensitivity reactions to Tomato, proteins similar to each other were detected in skin and seed extracts, with protein bands discernible at molecular weights of 21, 33, and 43 kDa. One band appeared to be a heat-stable allergen, as both patients in the study developed severe allergic reactions to both cooked and fresh Tomato. One patient reacted specifically to a 43 kDa protein band on IgE immunoblot (2).
The following allergens have been characterised:
Lyc e 1, a 14-16 kDa protein, a profilin (3-10).
Lyc e 2, a 50 kDa protein, a beta-fructofuranosidase (3,9,11-13).
Lyc e 3, a 8-10 kDa protein, a lipid transfer protein (3,8,14-17).
Lyc e Chitinase, a 31 kDa protein (18).
Lyc e Glucanase, a 55 kDa protein (19-21).
Lyc e Peroxidase, a 45 kDa protein (22).
Lyc e PME, a pectin methylesterase inhibitor (23).
Lyc e LAT52 from pollen (24).
Lyc e 1, a profilin, appears to be a minor allergen in Tomato. The recombinant Tomato profilin rLyc e 1 demonstrated high sequence identity to other allergenic food and pollen profilins and was reactive with 22% (11/50) of Tomato-allergic patients (5).
In another study of patients with adverse reactions to Tomato, 44% presented IgE antibodies to Tomato profilin and 35.5% to Cross-reactive Carbohydrate Determinants (CCDs). Two patients were sensitised to the lipid transfer protein Lyc e 3 (8).
Lyc e 3, a lipid transfer protein (LTP), is a potentially severe food allergen, in particular due to its extreme resistance to pepsin digestion. Cross-reactivity among foods containing LTPs is often accompanied by clinical food allergy, frequently including systemic reactions (17).
Specific allergens may be involved in specific adverse reactions. For example, Lyc e 3, a lipid transfer protein, appears to be involved in severe systemic reactions (17). In patients with oral allergy syndrome (OAS), 4 proteins binding with IgE from more than half of the patients’ sera were found to be polygalacturonase 2A (Lyc e 2), [beta]-fructofuranosidase, superoxide dismutase (SOD) and pectinesterase (PE). The concentrations of PG2A, [beta]-fructofuranosidase and PE were highest in the red ripening stage (11).
The allergenicity of Tomato appears to be influenced by hormone treatment with ethylene and salicylic acid. In a report on 8 patients who experienced anaphylaxis after eating raw Tomato, the wheals obtained in prick tests were significantly more severe with the extracts of Tomato treated with ethylene and salicylic acid, and the patients who presented greater wheal diameters in skin tests were those who had more-severe episodes of anaphylaxis. Neither the protein stain nor the IgE immunodetection patterns clearly varied between the untreated and the hormone-treated samples. The study concluded that treatment with plant hormones induced a more intense cutaneous response (25).
A 2S storage albumin, named Lec2SA, has been isolated from the seed of Tomato. The sequence of Lec2SA was similar to that of 2S albumins from different plants, such as Brazil nut and castor beans (26). The allergenic potential of the protein was not evaluated.
A cDNA clone encoding profilin from pollen grains (not fruit) of Tomato has been isolated (the clinical significance of this has not yet been determined). Sequence analysis of the insert shows 87% similarity to Tobacco, 78% to Timothy grass profilin, 77% to Arabidopsis profilin, 77% to Maize ZmPro3, and 73% to Birch profilin (27).
An extensive cross-reactivity among the different individual species of the genus could be expected, as well as to a certain degree among members of the family Solanaceae (28). This has been shown in IgE antibody inhibition experiments, where Tobacco, Mugwort pollen, and Tomato extracts inhibited the binding of a Tobacco-allergic patients’ serum to Tobacco leaf. Tobacco (Solanaceae family) is often used as a contact insecticide in gardens (29).
In patients with Tomato allergy and multiple sensitisation to other foods and Birch pollen, IgE directed against Tomato profilin showed a strong cross-reactivity with profilins from plant food sources and Birch pollen (5). Bell pepper profilin (Cap a 2) and the Tomato profilin Lyc e 1 display 91% identity, whereas Tomato profilin from pollen shares only 75% identity with Tomato fruit profilin (6-7). Eleven out of 34 food-allergic patients (32%) display IgE binding to both purified profilins (6). An Italian study found that hypersensitivity to the profilin Bet v 2 was strongly associated with clinical allergy to citrus fruit (39% in patients monosensitised to Bet v 2), Melon or Watermelon (67%), Banana (66%), and Tomato (33%). The sensitivity of a history of allergy to gourd fruit, citrus fruit, Tomato, Banana, or a combination thereof as a means to detect profilin-hypersensitive patients was 85% (41/48). The authors suggested that in clinical settings in which laboratory investigations are not easily accessible, allergy to Melon, Watermelon, citrus fruit, Tomato, or Banana can be used as a marker of profilin hypersensitivity once a sensitisation to Latex and lipid transfer protein is ruled out (30).
Many earlier studies reported that patients with grass pollen-allergic respiratory disease report adverse food reactions more frequently than do patients allergic to House dust mite (31-32), probably as a result of the profilin panallergen. Positive SPT to food allergens was shown to be more frequent in children with allergy to grass pollen (59.8%) than in children with allergy to Dermatophagoides (9.4%). A considerably high frequency of positive reactions to Tomato (39.2%), Peanut (22.5%), Green pea (13.7%), and Wheat (11.7%) was observed in children with allergy to grass pollen (33). Other foods included Garlic, Onion, and fruits such as Peach (31-32). Whether this is due to a panallergen was not clearly established, but in inhibition studies with Tomato and extract from Birch pollen, Mugwort pollen, Apple, and Celery, significant inhibitions among all of these allergens were found. Epitopes exclusive to grass pollen and Tomato were not detected. Cross-reactivity between Tomato fruit and grass pollen allergens was confirmed by the EAST inhibition assay, the structures responsible being a 16 kDa protein, which was identified as profilin (9). Tomato profilin has also been shown to have a high degree of identity with profilin from Goosefoot pollen (34).
Other studies have reported an association between grass pollinosis and sensitisation to Tomato, Potato, Green pea, Peanut, Watermelon, Melon, Apple, Orange and Kiwi (35). A high frequency (50%) of food hypersensitivity occurs in patients with allergic rhinoconjunctivitis. Food allergens seen more frequently were shellfish, Tomato, Rice, and Peanut (36). A Polish study reported that 10-20% of children sensitised to grass pollens were also sensitised to Carrot, Celery, Apple, Tomato and nuts (37).
The lipid transfer protein (LTP) panallergen in Tomato (Lyc e 3) may result in cross-reactions with other foods containing this panallergen, e.g., Rosaceae fruit, tree nuts, Peanut, beer, Maize, Mustard, Asparagus, Grape, Mulberry, Cabbage, Date, Orange, Fig, Kiwi, Lupine, Fennel, Celery, Eggplant, Lettuce, Chestnut and Pineapple (17,38-39).
Approximately 50% of patients who are sensitised to Latex also show sensitisation to foods, most commonly fruit. These foods include Avocado, Potato, Banana, Tomato, Chestnut, and Kiwi (40-44).These individuals may report symptoms of oral allergy syndrome after ingestion of these foods (45). In a study of food allergy in Latex-allergic individuals, 18.4% (93 out of 505) were positive, and 69.9% of these positive cases were seen in a group of children with Latex-specific IgE antibodies, most frequently to Potato, Tomato, Sweet pepper, and Avocado (46). In 137 patients with Latex allergy, 49 potential allergic reactions to foods in 29 (21.1%) patients were reported. Foods responsible for these reactions included Tomato in 3 (6.1%) (47). Class I chitinases appear to be the relevant cross-reacting proteins in Latex-fruit allergy involving Cherimoya, Passion Fruit, Kiwi, Papaya, Mango, Tomato or Wheat. These allergens are activated by stress to the plant (18).
Tomato, Potato, and Latex contain a common protein of 44-46 kDa, probably corresponding to the proteins called patatins. Patatins are storage proteins found in plants such as Potato and Tomato. This protein could be implicated in the high degree of cross-reactivity among Tomato, Latex, and Potato observed in immunoblot and CAP inhibition studies (48). A 43 kDa Latex allergen, Hev b 7, has been purified from Hevea brasiliensis and shown to be highly homologous to patatins.
Tomato also contains a 1,3-beta-glucanase, which may result in cross-reactivity with other foods or plants containing this panallergen, e.g., Potato, Bell pepper, Banana, Latex and Olive tree pollen (Ole e 9) (20-21).
Japanese cedar (Cryptomeria japonica) pollinosis is among the most widespread diseases in Japan. Cross-reactivity between Japanese Cedar pollen and Tomato fruit could be demonstrated using RAST and immunoblot inhibition tests. IgE binding to Japanese cedar pollen in the sera of 4/5 subjects was inhibited by more than 50% by preincubation of the serum with Tomato fruit extracts. Likewise, IgE binding to Tomato fruit discs was inhibited by more than 50% by Japanese cedar pollen extracts in 3/5 sera (49).
Cha o 2 from Japanese cypress (Chamae-cyparis obtuse) has been shown to share significant identity with polygalacturonases of Avocado, Tomato, and Maize, as well as with Cry j 2 from Japanese cedar (Cryptomeria japonica) (50).
Clinical ExperienceIgE-mediated reactions
Tomato is a common cause of symptoms of food allergy in sensitised individuals (2,5,13 51-60). For instance, the most common allergenic foods for 866 Finnish children aged between 1 and 6 years were citrus fruit, Tomato, Hen’s Egg, Strawberry and fish (61). In Mexico, in 1,419 allergic patients aged between 1 year and 18 years, 442 (31%) had positive SPT to some 33 tested foods. Fish, milk, seafood, beans, Orange, Onion, Tomato, Chicken, nut, Lettuce and Strawberry were responsible for 58% of the total of allergic reactions (51).
In a study conducted at 17 clinics in 15 European cities to evaluate the differences between some Northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms, it was reported, after evaluation of questionnaires of food-allergic individuals concerning 86 different foods, that the foods most often reported as eliciting symptoms in Russia, Estonia, and Lithuania were citrus fruits, chocolate, honey, Apple, Hazelnut, Strawberry, Fish, Tomato, Egg, and Milk, which differed from Sweden and Denmark, where Birch pollen related foods, such as nuts, Apple, Pear, Kiwi, stone fruits, and Carrot, were the most common perceived causes. The most common symptoms reported were oral allergy syndrome and urticaria. Birch pollen-related foods apparently dominate in Scandinavia, whereas some Mugwort-related foods seemed to be of more importance in Russia and the Baltic States. Among 1,139 individuals, Tomato was the 8th most reported food, resulting in adverse effects in 29% (58).
In a cross-sectional questionnaire-based survey conducted in Toulouse schools in France, to determine the prevalence of food allergies among schoolchildren, 2,716 questionnaires were returned, of which 192 reported a food allergy. Tomato was implicated in 10 (62).
In a study of food hypersensitivity in Finnish University students, among 172 subjects, the most common foods causing symptoms were Kiwi (38.4%), Milk (32.6%), Apple (29.1%), and Tomato (27.9%) (63).
In a German study of 419 adults with suspected food allergy, 214 (51.1%) were found to have an IgE-mediated food allergy. One hundred and seventeen patients were shown to be sensitised to fruit and vegetables, which included Celery, Tomato, Carrot, Apple, and Banana (64).
In an evaluation of IgE antibody measurement in a Japanese population (n = 4,797,158), Japanese cedar pollen showed the highest number of IgE responses, followed by house dust and Dust mite. Among food allergens, Apple had the highest number of responses, followed by Sesame seed, Egg white, Potato, and Tomato (52).
Other allergic manifestations to Tomato include urticaria/angioedema, dermatitis, perioral dermatitis, oral allergy syndrome, asthma, rhinitis, and abdominal pain. Tomato pollen may trigger rhinitis and/or conjunctivitis (53,65). In particular, OAS appears to be a common symptom (5,53,66-67). Tomato-induced OAS has been reported in 33 of 50 patients with Tomato allergy (5). In a study of the relationship between sensitisation to major pollens (Japanese cedar, Orchard grass, Short ragweed, Alder) among 1,067 Japanese paediatric patients with allergic diseases, and the association with oral allergy syndrome, it was found that childhood OAS does not always accompany pollen allergy. The most frequent allergen responsible for OAS in the study was Kiwi fruit, followed by Tomato, Orange and Melon (68).
A report described a 12-year-old girl with abdominal pain, nausea, and general malaise after eating Tomato, symptoms which remitted completely with antihistamines. SPT and IgE antibody test to Tomato were negative, while the food challenge was positive. Tomato oral rush desensitisation resulted in the patient’s ability to tolerate a maintenance dose of 100 g of Tomato daily with no side effects (69).
A study evaluating the Tomato lipid transfer protein Lyc e 3 the the use of serum from 5 Tomato-allergic individuals, reported that the cohort’s age ranged from 22 to 41 years of age. Five had experienced symptoms of oral allergy syndrome, 4 had skin reactions, 2 had respiratory tract symptoms, 3 had gastrointestinal symptoms, and 1 had cardiovascular symptoms. IgE antibody levels ranged from 1.6 to 51.5 kUA/l. All were shown to have skin reactivity directed at Tomato (16).
Although Tomato is a commonly consumed food, severe allergic reactions to Tomato are unusual or rarely reported. A study reports on 2 adult patients with significant immediate hypersensitivity reactions to Tomato. Both experienced laryngeal oedema, and 1 had anaphylaxis (2). Eight patients aged between 12 and 27 years are described who experienced anaphylaxis after eating raw Tomato. The patients who presented greater wheal diameters in skin tests were those who had had more severe episodes of anaphylaxis (25).
Among 1734 individuals attending 6 allergy clinics in Spain and reporting respiratory and/or cutaneous symptoms, the prevalence of sensitisation to Tomato was 6.52%. The peel extract was positive in 110 of the 113 patients, and the pulp extract in 47 patients; 3 patients were positive exclusively to pulp. Only 1.8% of individuals reported symptoms with Tomato; 44% of them had negative skin tests to both extracts. Among Tomato-sensitised subjects, 16% reported symptoms with Tomato, and 97% were sensitised to inhalant aeroallergens, including 84% to pollens (mainly Artemisia vulgaris and Platanus hybrida), with differences between northern and southern regions. Most of the sensitised subjects were asymptomatic, and some patients reported symptoms without skin test sensitivity. Regional differences may exist, possibly related to the pattern of sensitisation to cross-reacting pollens (56).
In a study undertaken to investigate the relevance of Tomato allergy in 32 Birch pollen-allergic patients with a history of adverse reactions to Tomato, Tomato allergy had a prevalence of about 9%. Forty-four percent were sensitised to Tomato profilin, and 35.5% had IgE antibodies to CCDs. Two patients were sensitised to the lipid transfer protein Lyc e 3 (8).
Atopic dermatitis may be precipitated or aggravated by Tomato (70-72), and the condition has been reported to be among the commonest causes of contact dermatitis of the hands (73). In a study of 119 children (1.5 months to 12 years of age) with atopic dermatitis, Tomato was identified as an allergen in 29.4% (74). Urticaria has also been described in a 6 month-old girl (75). Phytodermatitis as a result of contact with green Tomato has been recorded (76).
In 25 patients with recurrent otitis media with effusion and food allergy demonstrated by positive skin testing, the most common foods found to be associated were Milk, Egg, beans, citrus, and Tomato. An elimination diet led to a significant amelioration of the otitis in 22 patients. A subsequent challenge with the suspected offending food provoked a recurrence of the problem (77).
Food-dependant exercise-induced anaphylaxis has also been commonly reported (78-84). Tomato, cereals and Peanuts were said to be the most common foods resulting in this condition (85).
Tomato has also been associated with eosinophilic oesophagitis (86).
Eosinophilic cystitis induced by the ingestion of specific foodstuffs (Tomato, Coffee, Carrot) has been reported (87). Interstitial cystitis has also been reported (88).
Of 26 individuals reporting clinical symptoms induced by Tomato contact or ingestion, 21 (81%) were prick-prick positive to freeze-dried extracts of Canary Islands Tomato. Twenty patients (77%) had positive skin prick test to peel extracts, and 12 (46%) to pulp extracts (55).
A 39-year-old atopic woman with 2-year history of fingertip dermatitis complained that rubber gloves irritated her hands and that handling uncooked Potato and Tomato aggravated her dermatitis. Uncooked but not cooked Tomato resulted in oral tingling and facial erythema. Cooked potato did not affect her. IgE antibody test was positive for Latex, Tomato and Potato (89).
IgE antibodies to Paprika pollen, but not to Tomato pollen, were detected in the sera from 2 greenhouse workers who worked with Paprika plants. A greenhouse worker who cultivated Tomato plants had IgE antibodies against both Tomato and Paprika pollen. The authors claim that the presence of IgE antibodies against Paprika or Tomato pollen is not restricted to workers in horticulture; IgE against this pollen can also be present in food-allergic patients who have serum IgE against Paprika and/or Tomato fruit (90).
In 33 patients with chronic urticaria as a pseudoallergic reaction to food (proved by means of an elimination diet and subsequent re-exposure with provocation meals), oral provocation tests were performed with field-grown Tomato. Of the group, 76% reacted to Tomato. The authors tested with salicylates, histamine, and other components, and attributed the reactions to aromatic volatile ingredients in food, which are novel agents that elicit pseudoallergic reactions. Histamine, salicylates, and a direct mast-cell histamine release proved not to be involved in this reactivity to naturally occurring pseudoallergens (91).
Occupational protein contact dermatitis to Coriander, Carrot and Potato occurred in a 22-year-old chef, who had developed pruritic hand dermatitis from handling raw Potato, Tomato, Carrot, and Curry. Dermatitis developed on his face if juice of these vegetables splashed on it (92).
Auriculotemporal syndrome (or gustatory flushing syndrome), has been reported to masquerade as food allergy (erythema alone) following ingestion of spicy food such as Tomato sauce (93).
Tomato has also been implicated as a factor in irritable bowel syndrome (IBS) (94).
Occupational asthma in greenhouse Tomato growers may occur as a result of Red spider mites, which inhabit the plant (95).
Compiled by Dr Harris Steinman, firstname.lastname@example.org
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