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Whole Allergen

f208 Lemon

f208 Lemon Scientific Information

Type:

Whole Allergen

Display Name:

Lemon

Family:

Rutaceae

Latin Name:

Citrus limon

Route of Exposure

Lemon is the fruit of the lemon tree. The true home of the lemon is unknown, though some have thought it to be north-western India. (1)

The lemon tree grows 3 to 6 m in height. It usually has sharp thorns on the twigs. The alternate leaves, reddish when young, later become dark green above and light green below. They are oblong, elliptic or long-ovate, 6 -11 cm long, finely-toothed, and with slender wings on the petioles. The mildly fragrant flowers may be solitary, or there may be 2 or more clustered in the leaf axils. The buds are reddish; the opened flowers have 4 or 5 petals, 2 cm long, white on the upper surface and purplish beneath. They have 20 to 40 more or less united stamens with yellow anthers. (1)

The fruit is oval and 7 to 12 cm long, with a nipple-like protuberance at the apex. The peel is usually light yellow, though some lemons are variegated with longitudinal stripes of green and yellow or green and white. The skin is 6 to 10 mm thick and aromatic, being dotted with oil glands. The pulp is pale yellow, formed in 8 to 10 segments, juicy and acid. Some fruits are seedless, but most have a few seeds, elliptic or ovate, pointed, smooth, 9.5 mm long, and white. Lemons for export may be harvested early and naturally ‘cured’ in transit. (1)

Several lemon cultivars of true lemons and/or lemon-like fruits are accepted as lemons in home or commercial usage.

The lemon is used for culinary and non-culinary purposes throughout the world. The fruit is used primarily for its juice, though the pulp and rind (‘zest’) are also used, primarily in cooking and baking. Lemon juice is about 5% citric acid, which gives lemons a tart taste and a pH of 2 to 3. (1)

Lemon is also a preservative of colour. Oils from the skin are used in perfume-making, and to flavour drinks and other foods.

Clinical Relevance

Allergen Description

The following allergen has been characterised:

Cit l 1, a germin-like protein. (2)

Cit l 3, a lipid transfer protein. (3, 4)

The major protein component of citrus seeds is the globulin seed storage protein citrin. Albumin seed storage proteins have also been described as components of citrus seeds. (5) Citrus seed extracts display similar antigenic profiles, indicative of close phylogenetic relationships. Protein bands between 9 and 61 kDa have been demonstrated, with strong bands at 9, 14, 15, and 27 kDa. The bands between 9 and 15 kDa may represent the panallergens profilin and lipid transfer protein. (6)

Potential Cross Reactivity

Cross-reactivity within the Rutaceae family (lemon, lime, orange, tangelo, grapefruit) can be expected, but has not been documented to date.

Both orange and lemon lipid transfer protein has been shown to display cross-reactivity with the major peach allergen Pru p 3, a lipid transfer protein. (7) In a patient with anaphylaxis from mandarin (Citrus reticulata), a lipid transfer protein was isolated from mandarin fruit. Analysis of the patient's serum also demonstrated sensitisation to the lipid transfer protein Cit s 3, from orange, as well as to Cit s 1, a germin-like allergen. (4) Whether similar allergens occur in grapefruit, a closely-related family member, was not assessed.

Latex allergy has been reported to be associated with allergy to a number of other foods, including avocado, banana, kiwi, papaya, chestnut, peach and grapefruit. (8) A 34-year-old female with asthma and atopic dermatitis was described who developed severe anaphylaxis to latex; she was shown to have serum-specific IgE directed against latex, banana, kiwi, grapefruit, and avocado. Skin-specific IgE was also detected to banana, grapefruit, avocado, and latex extract. (9)

Molecular Aspects

Clinical Experience

IgE-mediated reactions

Ingestion of lemon may result in allergic reactions, including food allergy, allergic rhinoconjunctivitis, atopic dermatitis and anaphylaxis. (10, 11, 12) Citrus fruit such as lemon is one of the most common causes of atopic dermatitis. (13, 14, 15) IgE antibodies to lemon have been detected using the Pharmacia CAP System in food-allergic children, (16) and in children with atopic dermatitis and respiratory disease. (17) Lemon-dependent, exercise-induced anaphylaxis has been reported. (18)

A study was conducted at 17 clinics in 15 European cities to evaluate the differences between some northern countries regarding which foods, according to the patients, elicit hypersensitivity symptoms. A questionnaire concerning 86 different foods was administered to food-allergic individuals. The foods most often reported as eliciting symptoms in Russia, Estonia, and Lithuania were citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, hen’s egg, and cow’s milk; a profile that differed from that of Sweden and Denmark, where birch pollen-related foods such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common reported causes. The most common symptoms reported were oral allergy syndrome and urticaria. Birch pollen-related foods apparently dominate as culprits in Scandinavia, whereas some mugwort-related foods were of more importance in Russia and the Baltic States. Among 1 139 individuals, lemon was the 16th-most-often-reported culprit food, resulting in adverse effects in 23%. (19)

An Indian study evaluated the effect of a specific elimination diet on symptoms of 24 children aged 3 to 15 years who had documented deterioration in control of their perennial asthma. Specific IgE analysis for a range of food items revealed that 19 (79%) had serum-specific IgE directed at lemon. (20)

A number of case reports describe a range of adverse effects to lemon.

A 26-year-old peanut-allergic man exhibited sensitivity to citrus seed and experienced anaphylaxis to lemon soap (after showering and washing his torso and face with lemon-impregnated soap). Ingestion of whole crushed oranges and citrus seeds, including lemon, orange, and mandarin seeds, had previously resulted in anaphylaxis. Processed citrus fruit juice was tolerated. Symptoms included laryngeal oedema, generalised urticaria, and asthma, and occurred within minutes of ingestion. Serum-specific IgE was raised to peanut (4.0 kUA/L), orange (4.0 kUA/L), lemon (1.1 kUA/L), walnut (15.2 kUA/L), and hazelnut (6.77 kUA/L). (6)

In a study aimed at characterising raspberry allergens, a 25-year-old patient was described who had experienced periorbital oedema and rhinitis from lemon and other citrus fruit. Prick-to-prick tests were positive for peach, lemon, sweet lime, orange, banana, blueberry, tomato, grape and bell pepper. (11)

Eosinophilic gastroenteritis and urticaria following ingestion of citrus fruit was described in a 46-year-old male, who presented with a 2-month history of non-bloody, frequent, loose bowel movements, with abdominal cramping and nausea without emesis. He had been diagnosed approximately 10 years previously with citrus fruit-dependent, exercise-induced anaphylaxis. Lemon or grapefruit consumption followed by exercise caused urticaria and wheezing, but not gastrointestinal symptoms. Lemon-specific serum IgE was >100 kU/L, and Grapefruit 27.4 kU/L. (18)

A cross-sectional, descriptive, questionnaire-based survey was conducted in Toulouse schools to determine the prevalence of food allergies among schoolchildren. Out of 2 716 questionnaires returned, 192 reported a food allergy. Three reported allergy to lemon. (12)

Importantly, individuals allergic to mandarin or other citrus fruit may not necessarily be allergic to all citrus fruits. For example, in a study of 6 patients with orange allergy (type 1 hypersensitivity after ingestion of orange juice and a positive skin-prick test on at least 2 occasions), 3 patients tolerated small quantities of lemon juice, 1 patient tolerated mandarin, but 2 patients experienced oral allergy syndrome to this fruit. Serum orange-specific IgE was raised in all patients, mandarin-specific IgE in 5 patients (highest 6.04), lemon-specific IgE in 6 patients, and grapefruit-specific IgE in 5. (21) Cross-reactivity was not evaluated

Other reactions

Lemon contact with human skin may result in adverse skin reactions, e.g. phytophotodermatitis. (22, 23) A bartender with hand dermatitis was described who experienced allergic contact sensitivity to the skin of lemon, lime, and orange, but not to their juice. The authors pointed out that although most reported cases of citrus-peel allergy are due to d-limonene, in this patient patch tests for geraniol and citral (2 minor components of citrus peel oil) were positive, whereas tests for d-limonene were negative. (24)

Compiled By

Last reviewed: June 2022.

References
  1. Morton, J. Lemon. In: Fruits of warm climates. Julia F. Morton, Miami, Florida, USA. 1987:160-8. http://www.hort.purdue.edu/newcrop/morton/lemon.html. Accessed October 2012
  2. Pignataro V, Canton C, Spadafora A, Mazzuca S. Proteome from lemon fruit flavedo reveals that this tissue produces high amounts of the Cit s1 germin-like isoforms. J Agric Food Chem 2010;58(12):7239-44.
  3. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/ Accessed November 2012.
  4. Ebo DG, Ahrazem O, Lopez-Torrejon G, Bridts CH, Salcedo G, Stevens WJ. Anaphylaxis from mandarin (Citrus reticulata): Identification of potential responsible allergens. Int Arch Allergy Immunol 2007;144(1):39-43.
  5. Koltunow AM, Hidaka T, Robinson SP. Polyembryony in Citrus. Accumulation of seed storage proteins in seeds and in embryos cultured in vitro. Plant Physiol 1996;110(2):599-609.
  6. Glaspole IN, de Leon MP, Rolland JM, O'Hehir RE. Anaphylaxis to lemon soap: citrus seed and peanut allergen cross-reactivity. Ann Allergy Asthma Immunol 2007;98(3):286-9.
  7. Ahrazem O, Ibanez MD, Lopez-Torrejon G, Sanchez-Monge R, Sastre J, Lombardero M, Barber D, Salcedo G. Lipid transfer proteins and allergy to oranges. Int Arch Allergy Immunol 2005;137(3):201-10.
  8. Machado M, Sant'anna C, Aires V, Rodrigues PP, Pinheiro MF, Teixeira M. Latex and banana allergies in children with myelomeningocele in the city of Rio de Janeiro. [Portuguese] Rev Assoc Med Bras 2004;50(1):83-6.
  9. Fujie S, Yagami A, Suzuki K, Akamatsu H, Matsunaga K. A case of the latex-induced anaphylaxis by contact with barium enema catheter. [Japanese] Arerugi 2004;53(1):38-42.
  10. Zuidmeer L, Goldhahn K, Rona RJ, Gislason D, Madsen C, Summers C, Sodergren E, Dahlstrom J, Lindner T, Sigurdardottir ST, McBride D, Keil T. The prevalence of plant food allergies: a systematic review. J Allergy Clin Immunol 2008;121(5):1210-8.
  11. Marzban G, Herndl A, Kolarich D, Maghuly F, Mansfeld A, Hemmer W, Katinger H, Laimer M. Identification of four IgE-reactive proteins in raspberry (Rubus ideaeus L.). Mol Nutr Food Res 2008;52(12):1497-506.
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  13. Host A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990;45(8):587-96.
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  15. Stogmann W, Kurz H. Atopic dermatitis and food allergy in infancy and childhood. [German] Wien Med Wochenschr 1996;146(15):411-4.
  16. Matsumaru S, Artia M et al. Clinical evaluation of Pharmacia CAP System new allergens for fish, vegetables, fruits and grains [abstract]. Paper presented at Jap Soc Pediatric Allergology 1992
  17. Yamada M, Torii S. Clinical evaluation of Pharmacia CAP System new food and inhalant allergens [abstract]. Paper presented at Jap Soc Pediatric Allergology 1992.
  18. Kumar A, Teuber SS, Naguwa S, Prindiville T, Gershwin ME. Eosinophilic gastroenteritis and citrus-induced urticaria. Clin Rev Allergy Immunol 2006;30(1):61-70.
  19. Eriksson NE, Moller C, Werner S, Magnusson J, Bengtsson U, Zolubas M. Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and Russia. J Investig Allergol Clin Immunol 2004;14(1):70-9.
  20. Agarkhedkar SR, Bapat HB, Bapat BN. Avoidance of food allergens in childhood asthma. Indian Pediatr 2005;42(4):362-6.
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  22. Weber IC, Davis CP, Greeson DM. Phytophotodermatitis: the other "lime" disease. J Emerg Med 1999;17(2):235-7.
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