Substance Info: (and synonyms)

Background Info:

Citrus sinensis - sweet variety
Citrus aurantium - sour variety

Oranges, with orange-coloured peels and juicy fruit in separable quarter-moon-shaped sections, come from an evergreen tree growing to 9m. Oranges are the most important commercial citrus fruit. They were cultivated over 3,000 years ago in China. They now also thrive around the world in warm-climate areas including Portugal, Spain, North Africa and in the United States (the world's largest producer). Spain and Israel are leaders in orange exports. The many varieties (Mardarin, Tangerine, Blood Orange, etc.) fall under the basic categories of loose-skinned and tight-skinned, and sweet and bitter (the latter not eaten raw and on its own but used as a flavoring in processed foods).

The fruit is often eaten fresh and raw. The juice is also extracted and sold fresh and as frozen concentrate, or employed as flavouring in jellies, ice cream etc. The rind serves as flavouring in cakes, marmalade and other sweets. The flowers are cooked as a vegetable or made into a tea. Oranges are high in vitamin C and flavanoids. They contain thiamin, folate and pectin, which may lower blood cholesterol levels. The fruit, juice and rind are folk remedies for many ailments.

An essential oil from the peel is used as a food flavouring and also in perfumery and medicines. Some of the plants’ more recent applications are as sources of anti-oxidants and chemical exfoliants in specialised cosmetics.


Adverse Reactions:


[ 1 / 30 ]

This study reports an unusual case of repeated anaphylactic episodes to orange and apple without clinical evidence of primary sensitization to peach LTP (a 38-year-old man who suffered from 5 repeated anaphylactic episodes, 3 to orange and 2 to apple). In vitro and in vivo tests revealed heat stability of the implicated allergens and also provided new evidence of differences in allergenicity among apple varieties and strong cross reactivity of citrus fruits. 'Prick-to-prick' method with fresh fruits proved to be a quick and advantageous tool in investigating allergy to fresh fruits. He reported having developed itching of the palms and face, flushing, facial angioedema, hoarseness, dyspnoea and dizziness within 20 to 60 minutes after the ingestion of a raw orange a year before. He also experienced oral allergy syndrome to peach, grapes, wine and bell pepper. Prick-to-prick tests (4) with fresh, raw and boiled (isolated entire fruit at 100ºC for 30 minutes) 4 apple cultivars were positive for raw and boiled Granny Smith and Starking Delicious, raw Jonagold and Royal Gala but negative for boiled Jonagold and Royal Gala. Prick to prick tests with fresh, raw and boiled, orange and 3 other citrus fruits (lemon, mandarin, grape fruit), all induced strong skin reactivity. Commercial orange juice elicited a positive response too. Skin prick tests (SPTs) with commercial extracts provided positive results for orange, peach, apricot, marginally positive for apple and negative for grapes. (Tsiougkos 2013 ref.29135 5)

Tsiougkos N, Vovolis V. Repeated anaphylactic episodes to orange and apple. Eur Ann Allergy Clin Immunol 2013 May;45(3):113-115

[ 2 / 30 ]

Food protein-induced enterocolitis syndrome triggered by orange juice. a 2-year-old white boy with repetitive emesis, dehydration, and lethargy occurring on 5 separate occasions. His ?rst reaction occurred at 10 months of age with approximately 10 episodes of emesis with no fever, diarrhea, rash, angioedema, or respiratory symptoms. on further history taking, the possibility of orange juice as a trigger for his reactions was identi?ed. Emesis had occurred 1 to 2 hours after ingestion of orange juice in most of his reactions. negative skin prick testing to orange extract and fresh orange juice. Additionally, speci?c IgE to orange was less than 0.1 kU/L. Oral challenge with orange juice to a dose of 0.06 g protein/kg divided into 3 feedings over a total of 45 minutes with a 4-hour observation time was conducted. Consequently, he received 10 mL orange juice every 15 to 20 minutes, with a total of 30 ml given. One hour and 30 minutes after the ?nal dose, he developed repetitive emesis every 10 to 15 minutes lasting 2 hours. No urticaria, rhinorrhea, nasal congestion, wheezing, diarrhea, or other symptoms of anaphylaxis occurred during the challenge. (Federly 2012 ref.28521 5)

Federly TJ, Ryan P, Dinakar C. Food protein-induced enterocolitis syndrome triggered by orange juice. Ann Allergy Asthma Immunol 2012 Dec;109(6):472-473

[ 3 / 30 ]

Induced bronchospasm after handling of orange flavedo (zest). (Felix 2012 ref.28465 5)

Felix R, Martorell C, Martorell A, Pineda F, Cerda JC, De LM. Induced bronchospasm after handling of orange flavedo (zest). J Allergy Clin Immunol 2012 Nov 10;

[ 4 / 30 ]

Anaphylaxis due to orange soft drinks. A 23-year-old woman experienced an episode of anaphylaxis 10 minutes after handling sweet oranges in a fruit warehouse where she had been working for a month. Because of this episode, she left the job and some months later experienced contact urticaria when squeezing an orange; she also experienced oral allergy syndrome after drinking several orange soft drinks that she had previously tolerated. She had not eaten sweet oranges for 15 fifteen years. SPTs with the soft drink extracts were negative but the corresponding intradermal tests were positive. 1 hour after the intradermal test with orange extract (pulp and peel), the patient developed facial edema, dyspnea, and wheezing that required urgent medical attention. Total serum IgE was 6.7 IU/mL and serum specific IgE against orange peel and pulp extracts was
<0.35 kU/L (class 0). IgE immunoblotting with the patient’s serum revealed IgE-binding bands of approximately 75 kDa, 66 kDa, 57 kDa, 28 kDa, 22 kDa, and 18 kDa. The immunoblotting profile of 3 orange soft drink extracts showed a strong band of 28 kDa. The 28-kDa IgE binding protein was identified as Cit s 1. Oral provocation test was refused. The authors conclude that this nonatopic patient showed clinically relevant monosensitization to Cit s 1, a sweet orange allergen, which appeared as an active allergenic component in orange soft drinks.

Navarro LA, Pastor-Vargas C, Liñana JJ, Martínez I, Maroto AS, Vivanco F, Bartolomé B. Anaphylaxis due to orange soft drinks. J Investig Allergol Clin Immunol 2012;22(4):297-9.

[ 5 / 30 ]

Orange seed has increased allergenicity compared with juice extract,(Zhu 1989 ref.582 65) and patients allergic to citrus seeds but tolerant of pulp have been described.(Zhu 1989 ref.582 65) (Wang 2008 ref.22731 5) (In: O'Sullivan 2011 ref.26839 5)

O'Sullivan MD, Somerville C. Cosensitization to orange seed and cashew nut. Ann Allergy Asthma Immunol 2011 Sep;107(3):282-283

[ 6 / 30 ]

Anaphylaxis to apple and orange seed. There are a limited number of reports of patients reacting to citrus seeds in the absence of clinical reactivity to fruit pulp/peel (Wang 2008 ref.22731 5) (Zhu 1989 ref.582 36), but there are no previous reports of apple seed allergy. This study reports on 3 children with anaphylactic reactions to fruit seeds, all of whom could tolerate the fruit pulp.
A 6-year-old girl experienced a generalized non-anaphylactic reaction to an unknown constituent of a fruit salad and had a positive skin prick test (SPT) response to orange seed (9.5 mm), and also to fresh mango (5 mm), kiwi fruit (9 mm), and lemon seed (10 mm) but negative to orange pulp. An open food challenge (OFC), resulted in anaphylaxis (abdominal pain, urticaria, and shortness of breath with oxygen desaturation) after ingestion of a single orange seed.
The second child, a 5-year-old girl, had anaphylaxis after ingestion of a cut slice of orange but had a negative SPT response to orange pulp and tolerated a full seedless orange at a subsequent OFC. The SPT response was positive to fresh orange seed (15 mm) and mandarin and grapefruit seeds.
Both children had coexisting peanut allergy. They were also sensitized on SPTs to cashew and pistachio, a finding consistent with the few cases of citrus seed allergy previously reported in the literature.
The third child, a 15-month-old boy with previous anaphylaxis to kiwi fruit and a history of perioral erythema after exposure to banana and strawberry, presented with anaphylaxis on first exposure to commercially produced apple and oatmeal baby food (containing apple puree, apple juice, oats, and cinnamon extract). Within minutes of ingesting 2 teaspoons, he vomited, became lethargic, and had cyanosis with drooling, requiring multiple (3) doses of intramuscular adrenaline. He was subsequently noted to have facial angioedema and wide- spread urticaria by the attending medical staff. SPT responses were positive to the ingested baby food (5 mm), apple seed (4 mm), and orange seed (4 mm) and negative to fresh apple, cinnamon, and oats. He also had positive SPT responses to kiwi, strawberry, peanut, cashew, pistachio, and sesame.
Protein bands were visible between 9 and 95 kDa for the apple seed extract, with strong bands at 9, 28, 36, 40, and 49 kDa. The patient’s serum IgE bound to proteins from the apple seed extract, with particularly strong binding at 49 and approximately 70 kDa. The authors speculate that the apple seed proteins on immunoblotting represent novel allergens because they do not correspond to characterized allergens of apple, sesame, or peanut.

Turner PJ, Gray PE, Wong M, Varese N, Rolland JM, O'Hehir R, Campbell DE. Anaphylaxis to apple and orange seed. J Allergy Clin Immunol 2011 Dec;128(6):1363-1365

[ 7 / 30 ]

Allergic contact dermatitis due to citrus fruits is rare, but has been reported in cooks and bartenders. A bartender with hand dermatitis who had an allergic contact sensitivity to lime peel, fragrance mix I, and fragrance mix II. Most reported cases of citrus peel allergy are due to d-limonene, which makes up the majority of the peel oil. However, this patient had an allergic reaction to geraniol, which is a minor component of the peel oil and is present in fragrance mix I. It is important to consider a contact sensitivity to citrus in patients who have positive reactions to fragrance mix I and II and who are occupationally exposed to citrus fruits. (Swerdlin 2010 ref.28299 0)

Swerdlin A, Rainey D, Storrs FJ. Fragrance mix reactions and lime allergic contact dermatitis. Dermatitis 2010 Aug;21(4):214-6.

[ 8 / 30 ]

A 28-year-old man with anaphylaxis induced by fresh orange juice. The reaction was dose-dependent and could only be confirmed by challenge test, as specific IgE to orange was undetectable by skin prick test and CAP immunoassay. He had experienced identical anaphylactic reactions on 2 occasions within 20 minutes after consumption of 300 mL of fresh orange juice. The symptoms were feeling of heat, flushing, itching on the palms and head, rhinitis, and generalized urticaria. He did not experience symptoms when he ate 2 oranges or drank 300 mL of a commercial orange juice product. SPT with commercial extract and fresh juice of all citrus family members (orange, lemon, mandarin, and grapefruit) were also negative, as was intradermal test with filtered orange juice. Specific IgE to orange, lemon, mandarin, rPru p 3 (lipid transfer protein) and profilin was not identified. A challenge test was performed with fresh orange juice administered at increasing doses (50, 100, 150, 200, 300 mL) every 30 minutes. Within 20 minutes of drinking 150 mL of fresh orange juice the patient experienced an anaphylactic reaction with generalized urticaria similar to that reported in his history. The same reaction also appeared after 30 minutes with 150 mL of lemon, mandarin, and grapefruit juice. An oral challenge test with 2 commercial orange juice products was positive at 600 mL and 800 mL, respectively. A provocation test with fresh orange juice boiled for 2 minutes induced a mild anaphylactic reaction at 500 mL, thus demonstrating that the offending allergen is heat-labile but not completely inactivated by boiling. This allergen does not belong to any of the 3 recently identified major orange allergens–profilin (Cit s 2), germin-like protein (Cit s 1), and lipid transfer protein (Cit s 3) - because these are heat-resistant. The culprit allergen is likely to be uncovered after proteolytic degradation of certain unknown orange proteins (pro-allergen) during digestion. (Vovolis 2009 ref.24685 5)

Vovolis V, Koutsostathis N. Dose-dependent anaphylaxis to orange juice without detectable specific immunoglobulin E. J Investig Allergol Clin Immunol 2009;19(6):508-509

[ 9 / 30 ]

Immunological contact urticarial and/or protein contact dermatitis. Classically, the protein sources are divided into 4 main groups: group 1: fruits, vegetables, spices, plants, and woods; group 2: animal proteins; group 3: grains and group 4: enzymes. Taking into account the nature of the causal proteins, a wide variety of jobs can be affected. (Amaro 2008 ref.20923 7)

Amaro C, Goossens A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review. Contact Dermatitis 2008 Feb;58(2):67-75.

[ 10 / 30 ]

A 38-year-old woman who presented with a 10-year history of painful ulcerations on her tongue. She reported that she drank large quantities of diet cola and some orange juice daily and that she used cinnamon-flavored toothpaste and mouthwash nightly. Patch testing elicited positive reactions to balsam of Peru (a fragrance as well as a flavoring agent put in cola drinks that cross-reacts with orange juice) and cinnamic aldehyde. She was diagnosed with allergic contact dermatitis. She was put on a restricted diet and a fragrance-free regimen, and her condition resolved. (Jacob 2007 ref.21515 7)

Jacob SE, Steele T. Tongue erosions and diet cola. Ear Nose Throat J 2007 Apr;86(4):232-3.

[ 11 / 30 ]

A report on 16 cases of childhood OAS in a Japanese study. The rate of sensitization against four major pollens (Japanese cedar, orchard grass, short ragweed, alder) among 1067 pediatric patients with allergic diseases was investigated. OAS in childhood differs from that in adulthood in some ways. One is that childhood OAS does not always accompany with pollinosis. The most frequent allergen in this study was kiwi fruit followed by tomato, orange and melon. The sensitization rate against alder was equivalent as that against orchard grass and short ragweed, but less than that against Japanese cedar. The study concludes that Childhood OAS may have different mechanisms from adulthood OAS which almost always accompanies with pollinosis or latex allergy. (Sugii 2006 ref.16084 3)

Sugii K, Tachimoto H, Syukuya A, Suzuki M, Ebisawa M. Association between childhood oral allergy syndrome and sensitization against four major pollens (Japanese cedar, orchard grass, short ragweed, alder). [Japanese] Arerugi 2006 Nov;55(11):1400-1408

[ 12 / 30 ]

Of 56 subjects with self-reported reactions to orange, 23 were classified as orange allergic showing mainly an oral allergy syndrome. Of 23 subjects classified as orange allergic, 22 were sensitized to profilin, Cit s 2. In patients with mono-sensitization to profilin in vitro histamine releases up to 75% from basophils were induced using orange extract and purified plant profilins. Of the allergic patients 78% were sensitized to germin-like protein, Cit s 1. Both allergens showed retained IgE reactivity in heat-processed orange juice. Interestingly, subjects with and without clinical allergy showed a comparable sensitization profile. Profilin and germin-like proteins are major orange allergens. However, a predominant sensitization to both allergens in subjects without symptoms also indicates a high frequency of clinically insignificant sensitization. (Crespo 2006 ref.13811 3)

Crespo JF, Retzek M, Foetisch K, Sierra-Maestro E, Cid-Sanchez AB, Pascual CY, Conti A, Feliu A, Rodriguez J, Vieths S, Scheurer S. Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits. Mol Nutr Food Res 2006;50(3):282-290

[ 13 / 30 ]

Twenty nine orange allergic patients, aged 6 months to 29 years, mainly with symptoms of oral allergy syndrome, but also eyelid edema, sneezing, epigastralgia, vomiting, generalised urticaria, throat swelling, atopic dermatitis and chest tightness. Specific IgE to Cit s 1, an Orange allergen, was detected in 62% of 29 individual sera from orange-allergic patients, whereas positive SPT responses to the purified allergen were obtained in only 10% of such patients. The study concludes that over 60% of patients with allergy to oranges show specific IgE to Cit s 1 but that the purified allergen exerts a low in vivo reactivity. False positive diagnosis could occur if the diagnosis of allergy to oranges is mainly based on in vitro specific IgE determination. (Ahrazem 2005 ref.13135 7)

Ahrazem O, Ibáñez MD, López-Torrejón G, Sánchez-Monge R, Sastre J, Lombardero M, Barber D, Salcedo G. Orange germin-like glycoprotein Cit s 1: an equivocal allergen. Int Arch Allergy Immunol 2006;139(2):96-103.

[ 14 / 30 ]

Multiple allergy syndrome in a 24 years old female, who suffered several episodes of gastrointestinal complaints after eating fish since 9 months and nasal symptoms after inhaled fish allergens since 2 years. At 2 years she developed atopic dermatitis (extensive after fish and chocolate ingestion), at 6 years rhinoconjunctivitis and at 7 years itching of the hands after peeling orange, oral allergy syndrome associated with peach ingestion and contact dermatitis with peach peel. Total IgE 2819 U/ml, positive SPT and serum specific IgE to mites, cockroach, dog dander, alternaria, grasses, birch pollen, mugworth, pellitory, plantago, peach, apple, tomato, onion and several fish species (commercial extracts, raw and cooked fresh fish): cod, pollack, salmon, sole, tuna, horse-mackerel, sardine and trout. Immunoblotting to cod, salmon, tuna and sardine showed that these species of fish share antigenic and allergenic determinants, namely Gad cI and Gad mI (except tuna). Tests for Anisakis simplex were negative. Positive patch test to balsam of Peru (included in chocolate and orange peel). Specific immunotherapy to dust mites worsened her dermatitis. Unintentional inhalation fish allergens and voluntary fish ingestion induce symptoms. Hypersensitivity reactions type I and IV to a different allergens can appeared in the same person and the food allergy can persist to adult age worsening the quality of life. (Costa 2006 ref.23502 7)

Costa A, Santos M, Santos A, Pedro E, Pereira-Barbosa M. Multiple allergy syndrome - Case report. EAACI Congress, Vienna-Austria. 2006 Jun; Oral Abstract 1553.

[ 15 / 30 ]

Twenty-seven patients, showing mainly oral allergy syndrome after orange ingestion, as well as positive prick responses and serum-specific IgE levels to orange, were evaluated. (Ahrazem 2005 ref.11867 7)

Ahrazem O, Ibáñez MD, López-Torrejón G, Sánchez-Monge R, Sastre J, Lombardero M, Barber D, Salcedo G. Lipid transfer proteins and allergy to oranges. Int Arch Allergy Immunol 2005 Jul;137(3):201-10.

[ 16 / 30 ]

Six patients with orange allergy (type 1 hypersensitivity after ingestion of orange juice and a positive skin prick test on at least two occasions). Dose eliciting symptoms was between 20 and 100 g. Three patients tolerated small quantities of lemon juice. One patient tolerated tangerine but 2 patients had oral allergy syndrome to this fruit. 2 main IgE-binding components were seen - a 25 kDa in all patients and a 13 kDa. Skin prick test was positive to both pulp and peel. OAS was reported in all patients. One reported OAS, atopic dermatitis and general discomfort and another reported OAS and generalised urticaria. Serum specific IgE was raised in all ranging from 0.76 to 6.04 kU/L. Specific IgE was raised for tangerine in 5 patients (highest 6.04) and for lemon in 6 patients, ranging from 0.67 to 5.37 kU/L, and for grapefruit in 5. Bet v 2 was raised in 4 patients (8.81 to 39.2). These 4 patients had symptoms with pollen and the two with <0.35 for Bet v 2 did not. Cross-reactivity was not evaluated. (Ibanez 2004 ref.8941 5)

Ibanez MD, Sastre J, San Ireneo MM, Laso MT, Barber D, Lombardero M. Different patterns of allergen recognition in children allergic to orange. J Allergy Clin Immunol 2004;113(1):175-7

[ 17 / 30 ]

Food-dependent exercise-induced anaphylaxis due to ingestion of orange described in an 18-year-old Japanese woman. She had a history of recurrent redness and swelling of the face with irritation accompanied by dyspnea and abdominal distress. She was able to ingest citrus fruit without symptoms. Serum specific IgE for orange was 0.83 U/ml. After orange ingestion followed by exercise, she developed redness and swelling on her face, and mild dyspnea and abdominal distress 30 mins after onset of exercise. Plasma histamine was raised. (Morimoto 2004 ref.11622 5)

Morimoto K, Tanaka T, Sugita Y, Hide M. Food-dependent exercise-induced anaphylaxis due to ingestion of orange. Acta Derm Venereol 2004;84(2):152-3

[ 18 / 30 ]

In 2002, 107 cases were reported to the French Allergy Vigilance Network of which 59.8 % were cases of anaphylactic shock (one being fatal), 18.7% systemic reaction, 15.9% laryngeal angio-edema, 5.6% serious acute asthma (one fatal). Adults represented 69% of cases (74 cases). The most frequent causal allergens were peanut (14), nuts (16), shellfish (9) latex group fruit (9 patients), and most often in-patients allergic to latex: avocado (4), kiwi (2), fig (2), and banana (1). Next came lupine flour (7), wheat flour (7), celery (5) and snails (5), sesame (4), milk (3), buckwheat (3), fish (3), peach (2), chicken (2). Single observations included sulfites, quinine (an additive in a tonic drink), mustard, lentils, kidneys, pork, melon, grapes, pears, chicory, artichokes, oranges and Anisakis simplex. Four patients had an immediate post-prandial shock and were reported as idiopathic shock. The allergen was present in a masked form in 13% of cases: peanut (6 - with one fatal), lupine (4), sesame (3), and hazelnut (1).
In 4 cases of which one lethal a severe anaphylactic reaction occurred after consumption of macaroon in which the almonds have been replaced by peanuts paste without an adequate labeling. Two cases of anaphylactic shocks in hospitalized children were due to chocolate drink containing lupine flour. Both children were allergic to peanuts and AS occurred by cross allergy. A case of food allergy to hazelnuts is due to a mislabeling on chocolate packaging at Halloween. Two cases of severe anaphylaxis by proxy are reported: the incriminated allergenic peanuts. The patient presented the allergic reaction by contact with another person eating peanuts. (Moneret-Vautrin 2004 ref.10176 0)

Moneret-Vautrin DA, Kanny G, Morisset M, Rance F, Fardeau MF, Beaudouin E. Severe food anaphylaxis: 107 cases registered in 2002 by the Allergy Vigilance Network. Allerg Immunol (Paris) 2004;36(2):46-51

[ 19 / 30 ]

True multifood allergy in a 4-year-old child: A 4-year-old male with urticaria and asthma clearly related to the ingestion of eggs at the age of 2. In the subsequent years, rhinitis, angioedema, headache, gastroenteritis appeared. These symptoms were variously associated and started between few minutes and 2 h after the ingestion of numerous foods. SPT with fresh food gave a 4-mm wheal for fig, asparagus, cherry and walnut; a 5-mm wheal for medlar and orange; a 6-mm wheal for chicory and strawberry; a 7-mm wheal for fish and peanuts; a 8-mm wheal for peach; and a 9-mm wheal for egg. The RAST assay confirmed the presence of specific IgE to egg, fish, peanuts, walnut, fig, orange, strawberry, peach and cherry. The total serum IgE was 730.6 kU/L. The DBPCFC was positive, at various degrees, for all the tested foods according to skin sensitizations. (Pajno 2002 ref.13783 5)

Pajno GB, Passalacqua G, La Grutta S, Vita D, Feliciotto R, Parmiani S, Barberio G. True multifood allergy in a 4-year-old child: a case study. Allergol Immunopathol (Madr) 2002;30(6):338-41

[ 20 / 30 ]

In 25 patients with recurrent otitis media with effusion and food allergy demonstrated by positive skin testing, the most common food found to be associated was milk, egg, beans, citrus, and tomato. The elimination of the food 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 otitis problem. (Arroyave 2001 ref.7020 3)

Arroyave CM. Recurrent otitis media with effusion and food allergy in pediatric patients. [Spanish] Rev Alerg Mex 2001;48(5):141-4

[ 21 / 30 ]

Occupational exposure to latex allergens with a history of anaphylactic reaction to poppy seed and reaction to the antigens of apples, oranges, tangerines, peanuts and bananas, and demonstrated by serum specific IgE. A marked reaction was initiated after the use of a shampoo containing volatile banana oil. (Richter 2000 ref.8754 2)

Richter J, Susický P. Latex allergy. [Czech] Cesk Slov Oftalmol 2000;56(2):129-31

[ 22 / 30 ]

This study investigated the cross-reactivity to non-Rosaceae LTPs. IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods were evaluated in 498 subjects (age > 12 years) with Rosaccae allergy as judged by skin prick test with fresh fruits and (in most cases) clinical history. The majority had OAS (>97%), and only a minority (approximately 10%) showed urticaria/angioedema, gastrointestinal symptoms, food-induced rhinitis, asthma, or anaphylaxis. Sera from 37 patients were available for follow-up studies. Peach was identified most frequently as an offending Rosaceae food (in 30/37 patients), followed by apple (16/37), apricot (11/37), cherry (9/37), plum (8/37), almond (7/37) and pear (6/37). Four patients did not have any clinical symptoms related to Rosaccae fruits, despite a positive SPT with commercial plum extract and peach peel extract. All 37 patients were interviewed for allergies to other foods. Walnut and hazelnut were most frequently reported as offending foods (19/37 and 15/37, respectively), closely followed by peanut (9/37). For the other 33 different foods, the number of patients reporting symptoms ranged from 1 to 5. These foods were found among all major groups of vegetable foods, including cereals (corn, wheat), legumes (soybean, string bean, white bean, chick pea, lentils, lupine), Solanaceae (potato, tomato, eggplant) Brassicaceae (cabbage, mustard), Umbelliferae (celery, fennel), Rutaceae (lemon, orange), and several other plant families. This article contains a table of the 37 patients and the effecting foods and symptoms of each patient.
(Asero 2000 ref.3711 7)

Asero R, Mistrello G, Roncarolo D, de Vries SC, Gautier MF, Ciurana CL, Verbeek E, Mohammadi T, Knul-Brettlova V, Akkerdaas JH, Bulder I, Aalberse RC, van Ree R. Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int Arch Allergy Immunol 2000;122(1):20-32

[ 23 / 30 ]

Atopic dermatitis in children. (Stogmann 1996 ref.7646 7)

Stogmann W, Kurz H. Atopic dermatitis and food allergy in infancy and childhood. [German] Wien Med Wochenschr 1996;146(15):411-4

[ 24 / 30 ]

The presence of specific IgE and IgG antibodies against the oranges Citrus aurantium sinensis and Citrus silension were studied in 41 atopic and 20 non-atopic children aged 8-12 years. The 41 atopic patients were selected as a result of an acute episode of hives and/or sneezing following a provocation test with 150 ml orange juice. Skin prick tests, serum specific IgE and IgG RAST were performed in both groups. 36 of the 41 patients were skin prick test positive to orange. RAST was positive in 34 of the 41. A citrus fruit-exclusion diet was maintained for 180 days. The comparison of the results before and after the diet showed no significant changes in skin reactivity and RAST values, and even a slight increase was recorded in the latter. We have attempted to explain these puzzling findings. (Alonso 1994 ref.1325 5)

Alonso A, Seoane MA, et al. A citrus fruit-exclusion diet in sensitive patients and its influence on specific antibodies. J Investig Allergol Clin Immunol 1994;4(3):146-8

[ 25 / 30 ]

This study shows that ingestion of fresh orange juice per se did not heighten nonspecific bronchial hyperreactivity. (Yap 1990 ref.2667 8)

Yap JC, Wang YT, Yeo CT, Poh SC. The effect of fresh orange juice on bronchial hyperreactivity in asthmatic subjects. Singapore Med J 1990;31(6):583-6

[ 26 / 30 ]

Food-dependant exercise-induced anaphylaxis in a 12 year-old boy. Angioedema was the main symptom and was accentuated by ingestion of an orange prior to exercise. (Debavelaere 1989 ref.6611 4)

Debavelaere C, De Blic J, Bodemer C, Teillac D, Paupe J, Scheinmann P. Anaphylaxis syndrome induced by exercise. [French] Arch Fr Pediatr 1989;46:281-283

[ 27 / 30 ]

Oranges are considered to be common allergenic fruits in China and may induce severe food allergy in sensitive individuals. In 26 orange-sensitive patients, intradermal tests with extracts of orange juice and seeds were performed in 16 patients. The authors report that the major allergenic components of orange reside in orange seeds instead of orange juice. Systemic reactions developed in 5 patients after intradermal tests with orange seed extracts. The authors conclude that orange seed contains high potent allergens which may induce orange sensitivity due to careless chewing of orange seeds. Many patients in that study were sensitive to other foods, such as walnut, hazelnut, sesame seed, and Chinese prickly ash seed, suggesting that the allergenic determinants in orange seed cross-reacted with those in nuts and seeds. (Zhu 1989 ref.582 65)

Zhu SL, Ye ST, Yu Y. Allergenicity of orange juice and orange seeds: a clinical study. Asian Pac J Allergy Immunol 1989;7:5-8

[ 28 / 30 ]

Contact dermatitis/urticaria. (Kashirskii 1984 ref.2411 7)

Kashirskii IuM. Food allergy in patients with pruritic dermatoses. [Russian] Vopr Pitan 1984;(4):17-20

[ 29 / 30 ]

In a study of fish and citrus allergy these foods were strictly avoided in 177 children up to 1 year of age, whereas 152 children had started taking fish before age 6 months and 145 children had started taking citrus fruits before 3 months. Both fish and citrus allergy, defined by a positive challenge, were found at age 3 years in a similar frequency (about 3%) in children with and without the first-year elimination. The results suggest that food allergy in childhood can be postponed but not prevented by dietary elimination in infancy. (Saarinen 1980 ref.7656 5)

Saarinen UM, Kajosaari M. Does dietary elimination in infancy prevent or only postpone a food allergy? A study of fish and citrus allergy in 375 children. Lancet 1980;1(8161):166-7

[ 30 / 30 ]

Reactions to grapefruit seeds and oranges. (Ratner 1952 ref.224 97)

Ratner B, Untracht S, Malone J, Retsina M. Allergenicity of modified and processed foodstuffs. IV. Orange. J Ped 1952;43:421-428

Non-Immune reactions

[ 1 ]

Oranges are suspected of inducing adverse skin reactions in patients with atopic eczema. 21 adult patients with atopic eczema and a history of adverse reactions to oranges and 10 patients without. 23 patients (74%) had specific serum IgE to orange. Oral provocation testing resulted in pruritic eczematous or maculopapular skin lesions predominantly at the predilection sites in 16 patients (52%). Specific IgE to orange did not correlate with the clinical outcome of the oral provocation test. The negative results in the skin tests and a lack of correlation between specific IgE and oral provocation tests indicate that non-IgE-mediated mechanisms are involved in cutaneous adverse reactions to oranges in patients with atopic eczema. (Brockow 2003 ref.11905 7)

Brockow K, Hautmann C, Fotisch K, Rakoski J, Borelli S, Vieths S, Ring J. Orange-induced skin lesions in patients with atopic eczema: evidence for a non-IgE-mediated mechanism. Acta Derm Venereol 2003;83(1):44-8.

[ 2 ]

Gustatory sweating, and to orange juice. (Freeman 1998 ref.966 10)

Freeman GL. Gustatory sweating in the differential diagnosis of food allergy. Allergy Asthma Proc 1998;19:1-2

[ 3 ]

Orange juice leads to a significant increase of urinary pH and citric acid excretion. (Hesse 1993 ref.1824 6)

Hesse A, Siener R, Heynck H, Jahnen A. The influence of dietary factors on the risk of urinary stone formation. Scanning Microsc 1993;7(3):1119-1127

[ 4 ]

Phytophotodermatitis may result from coumarins such as bergapten contained in the Orange skin. (Egan 1993 ref.1057 6) Bergapten is sometimes added to tanning preparations since it promotes pigmentation in the skin.

Egan CL, Sterling G. Phytophotodermatitis: a visit to Margaritaville. Cutis 1993;51(1):41-2

[ 5 ]

Phytophotdermatitis. (Held 1989 ref.9254 4)

Held JL. Phytophotodermatitis. Am Fam Physician 1989;39(4):143-6

[ 6 ]

Nineteen percent of about 490 patients with classical or common migraine reported that headaches can be precipitated by chocolate, 18% by cheese and 11% by citrus fruit, and a highly significant majority of these patients were sensitive to all three foods. (Peatfield 1984 ref.1935 1)

Peatfield RC, Glover V, Littlewood JT, Sandler M, Clifford Rose F. The prevalence of diet-induced migraine. Cephalalgia 1984;4(3):179-183

[ 7 ]

In 60 migraine patients, the commonest foods causing reactions were wheat (78%), orange (65%), eggs (45%), tea and coffee (40% each), chocolate and milk (37%) each), beef (35%), and corn, cane sugar, and yeast (33% each). (Grant 1979 ref.1242 1)

Grant ECG. Food allergies and migraine. Lancet 1979;1:966-968

[ 8 ]

Foods, including orange juice, can cause reflux esophagitis (heartburn). (Price 1978 ref.1023 3)

Price SF, Smithson KW, Castell DO. Food sensitivity in reflux esophagitis. Gastroenterology 1978;75(2):240-3

[ 9 ]

Obstruction of the small intestine due to orange and tangerine. (Skala 1976 ref.8636 3)

Skala J, Komarek J. Obstruction of the small intestine due to orange and tangerine. [Czech] Rozhl Chir 1976;55(4):252-3

[ 10 ]

Anaphylactoid reaction to oranges. (Williamson 1961 ref.581 83)

Williamson JW. Anaphylactoid reaction to oranges. J Florida Med Assoc 1961;Sept:247

[ 11 ]

Anaphylactoid reaction to ingestion of orange. (Bendersky 1960 ref.223 78)

Bendersky G, Lupas JA. Anaphylactoid reaction to ingestion of orange. JAMA 1960;173:255-256

[ 12 ]

See also: Orange (skin)

Editor Comment Editorial comment, common knowledge, or still to add - -

Occupational reactions

[ 1 ]

3 cases of occupational hypersensitivity pneumonitis in citrus farmers. They were admitted with abnormal chest shadows with coughs, fevers and breathlessness, but their symptoms disappeared with isolation from their workplace. Although the pathogenic antigen of this hypersensitivity pneumonitis could not be determined, Aspergillus and Penicillium might be the causative agents, because they were detected in the patients' workplaces and in double immunodiffusion tests. (Yasui 2010 ref.28300 7)

Yasui H, Matsui T, Yokomura K, Nakano Y, Suda T, Chida K. Three cases of hypersensitivity pneumonitis in citrus farmers. [Japanese] Nihon Kokyuki Gakkai Zasshi 2010 Feb;48(2):172-7.

[ 2 ]

Three subjects employed in the preparation of fruit for fruit salads reported work-related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase. Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work-related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma. (Sen 1998 ref.2206 8)

Sen D, Wiley K, Williams JG. Occupational asthma in fruit salad processing. Clin Exp Allergy 1998;28(3):363-367

[ 3 ]

A report on a bartender with hand dermatitis had allergic contact sensitivity to the skin of lemon, lime, and orange but not to their juices. Although most reported cases of citrus peel allergy are due to d-limonene, for our patient, reactions to patch tests for geraniol and citral, two minor components of citrus peel oil, were positive, whereas those for d-limonene were negative. (Cardullo 1989 ref.7732 1)

Cardullo AC, Ruszkowski AM, DeLeo VA. Allergic contact dermatitis resulting from sensitivity to citrus peel, geraniol, and citral. J Am Acad Dermatol 1989;21(2 Pt 2):395-7

[ 4 ]

Foods were tested by the scratch-chamber and open application techniques in 80 hand dermatitis patients, 55 of whom were food handlers. Both immediate and delayed reactions were seen. Most immediate scratch-chamber test reactions were provoked by vegetables and spices in patients with birch pollen allergy, and most delayed reactions from spices in patients with allergy to balsam of Peru, and from onion and leek. The evaluation of allergic and irritant reactions was difficult. Positive open application tests were seen in about 75% of patients with immediate or delayed scratch-chamber reactions. Immediate reactions from vegetables, fish and meat, and delayed reactions from orange and lemon peel and onion showed the best clinical relevance. Wet work, surface active agents and other irritant factors were considered the main causes, and food allergies as contributory factors only in food handler hand dermatitis. (Niinimaki 1987 ref.2344 4) Many cases of dermatitis seen in the industry are due to contact with the peel and oil, and not with the juice.

Niinimaki A. Scratch-chamber tests in food handler dermatitis. Contact Dermatitis 1987;16(1):11-20

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