Rice

Allergen Exposure

In Rice allergy, proteins with molecular masses of 14-16, 26, 33, and 56 kDa have been demonstrated to be potentially allergenic. The 33 kDa allergen was identified as a novel type of plant glyoxalase I that is expressed in various plant tissues, including maturing seeds. (1) The majority of the allergic components are albumins with molecular weights between 14 and 16 kDa (2). The 16 kDa Rice protein has been reported to be a major allergen and responsible for cross-allergenicity between cereal grains in the Poaceae family (3). A 19 kDa globulin protein has also been isolated (4).

Other allergens partially characterised have been designated RAP, RAG 1, RAG 2, RAG 5, RAG 14, and RAG 17. RAG 17 is a 16 kDa protein, a member of the alpha-amylase/trypsin inhibitor protein family (5-6). Although raw Rice is more allergenic than cooked, some of the allergens are probably heat-stable and resist proteolysis  (7).

In a more recent study that evaluated Rice allergy in Indian patients, in sera of individuals allergic to Rice, 14-16, 33, 56 and 60 kDa proteins were shown to be major IgE-binding components in Rice. Boiled Rice retained 4 IgE-reactive proteins of 16, 23, 33 and 53 kDa (8).

The following allergens have been characterised:

• Ory s LTP, a 14 kDa lipid transfer protein. (9-13).
   
• Ory s aA/TI, a 16 kDa alpha-amylase/trypsin inhibitor. (5-6,14-20).
   
• Ory s Glyoxalase I, a glyoxalase (1,3,12,21).
   
• Ory s 12, a profilin (22-23).

Ory s 1, Ory s 2, Ory s 3, Ory s 7, Ory s 11, Ory s 12 and Ory s 13 have been characterised in Rice pollen and contribute to asthma, allergic rhinitis and allergic conjunctivitis as a result from exposure to Rice pollen. Ory s 12, a profilin, has been detected in both Rice seed and Rice pollen (22,24).

Rice also contains a lipid transfer protein (9 10). LPTs are heat-stable proteins and may play a role in allergy to cooked Rice. A report was made of 3 individuals who developed rhinoconjunctivitis and asthma as a result of exposure to the lipid transfer protein of raw Rice thrown at weddings, but who could tolerate cooked Rice. This may indicate some modification of Rice lipid transfer protein during cooking (12).

At least 5 alpha-amylase/trypsin inhibitors have been isolated from Rice, including Ory s aA/TI. Patients may react with all 5 proteins, whereas others specifically react with individual proteins only (16). This family of allergens is highly resistant to digestive enzymes (20) and is heat-stable (6). There is a suggestion that some epitopes of recombinant versions of these proteins are still immunoreactive when they are expressed as their fragments (18).

Although Rice seed contains the panallergen profilin, the levels of this are much lower than those in foods commonly known to contain profilin, e.g., Celery (22).

A chitinase has been isolated from Rice. The substance accumulates to a high level in the roots of the plant, but only low levels are found in stem and leaf tissue (25). Whether the chitinase is found in the seed, and whether this chitinase has allergenic potential, are questions that have not yet been evaluated.

Potential cross-reactivity

An extensive cross-reactivity among pollen of the different individual species and tribes of the Poaceae family could be expected and in fact does occur frequently. (26) Although similar patterns of cross-reactivity may occur among the seeds/grains of the family, this has not been as well determined as in the case of pollen. In vitro cross-reactivity has been demonstrated among IgE binding proteins of Corn, Rice, Soybean and Peanut. A high degree of cross-reactivity between Rice and Corn was thought to be due to the fact that they both belong to the same botanical family. The authors state that the clinical significance of these cross-reactivities is not yet known and that clinical studies will be required to put these findings into perspective (27).

Cross-allergenicity among the cereal grains Rice, Wheat, Corn, Japanese Millet and Italian Millet was examined by RAST inhibition assay, and significant close correlations in every combination of IgE antibody values for the 5 grain extracts were found (3).

Allergens of 14 and 18 kDa have been isolated from Buckwheat and shown to be major proteins. These were found to share some homology with Rice proteins associated with Rice allergy, and cross-allergenicity with Buckwheat proteins was postulated (28). However, some Buckwheat-allergic subjects do not develop immediate adverse reactions after ingesting Buckwheat, despite high levels of Buckwheat-specific IgE antibodies. Further investigation has led to the conclusion that there is IgE antibody cross-reactivity between Buckwheat and Rice, and that IgE antibodies from immediate hypersensitivity reaction-negative subjects might recognise the epitopes on Buckwheat antigens that cross-react with Rice antigens, whereas IgE antibodies from immediate hypersensitivity reaction-positive subjects might bind to Buckwheat-specific epitopes (29-30). Thus, in spite of cross-allergenicity between Buckwheat and Rice, Rice ingestion only uncommonly induces immediate hypersensitivity reactions, even in subjects with high IgE for Rice; this is not the case for Buckwheat-induced immediate hypersensitivity reactions (31).

Approximately 86% of Maize-allergic patients were shown to have allergen-specific IgE to a 9 kDa protein, shown to be a lipid transfer protein. Immunoblotting inhibition showed that this LTP cross-reacts completely with Rice and Peach LTPs but not with Wheat or Barley LTPs. A 16 kDa allergen was also isolated (recognised by 36% of patients) and shown to be the Maize inhibitor of trypsin. This protein cross-reacts completely with grass, Wheat, Barley, and Rice trypsin inhibitors (2,32). Other studies have confirmed the high degree of cross-reactivity between Rice and LTPs from other foods (10). Cross-reactivity has been demonstrated between Rice lipid transfer protein and those from Peach and Apple (11). The 3-dimensional structure of Rice lipid transfer protein closely resembles the published structures of Wheat, Barley and Maize LTPs (13).

Clinical Experience

IgE-mediated reactions
Rice may uncommonly induce symptoms of food allergy, asthma, rhinitis, eczema and urticaria in sensitised individuals; however, in communities where Rice is a staple food, e.g., in the Far East, reactions may be more frequently encountered (33-40). With the increase of Rice consumption in the West, the prevalence of allergy to Rice may increase. Symptoms reported in Rice-allergic individuals include abdominal cramping and similar pain, nausea, vomiting, rhinitis, rhinoconjunctivitis, dyspnoea, asthma, contact urticaria, atopic dermatitis, dermatitis, angioedema and anaphylaxis. Individuals may be sensitised without being symptomatic (41-43). A high percentage of this sensitisation may be of this kind (9).

In 148 Malaysian adults with symptoms of nasal congestion and rhinorrhoea and 113 control subjects without rhinitis symptoms, SPT evaluation of 11 foods common in the Malaysian diet showed that 48% of the patients with rhinitis had skin reactivity to food, compared with 4.4% of control subjects. The most commonly implicated foods were Shrimp (48%) and Rice (30%), both of which are common in the Malaysian diet (34).

In a study that evaluated Rice allergy in Indian patients, of 1,200 patients screened, 165 presented with a history of Rice allergy, and of these, 20 (12.1%) demonstrated marked skin reactivity and 13 showed significantly raised IgE antibodies to Rice. DBPCFC confirmed Rice allergy in 6/10 patients. The authors concluded that IgE-mediated Rice allergy affects approximately 0.8% of Indians with asthma and rhinitis (8).

Rhinoconjunctivitis, asthma and contact urticaria from handling Rice and other cereals were reported in a housewife. She tolerated cooked cereals. SPT with a Rice extract and cutaneous challenge with raw Rice were positive. Raw Rice produced immediate and late clinical effects, and objective lung function tests confirmed the symptoms of asthma (44). Other studies have also reported Rice-induced asthma in adults (45-46). The allergen-specific IgE level may be raised in these individuals (46). In addition, a high frequency of food hypersensitivity may occur in individuals with allergic rhinoconjunctivitis (47).

A 9-year-old girl seen during a follow-up visit for asthma (perennial symptoms) reported that she "disliked" foods with Rice and had avoided eating them for the last 3 years. Attempts to feed her with Rice had resulted in immediate nausea, abdominal pain and diarrhoea. On one occasion, she had suffered urticaria-angioedema in the kitchen while her mother was sorting Rice. She had previously been found allergic to grass pollens through intradermal but not epidermal tests. Skin prick tests and prick-prick tests with various cereals, including Rice, Wheat, Barley, Oat and Lentil, demonstrated a marked wheal and flare reaction only to Rice with both tests. Total IgE was 165 kU/l, and Rice-specific IgE was 13.2 kUA/l. A double-blind, placebo-controlled food challenge resulted in nausea, abdominal pain and diarrhoea within 10 minutes of ingestion. She had no problems when eating other cereals. She therefore demonstrated allergy to the ingestion of cooked Rice and to inhalation of raw Rice proteins (48).

Rice thrown at weddings may result in rhinoconjunctivitis and asthma. Three patients are described who experienced asthma or rhinoconjunctivitis to raw Rice by inhalation of Rice dust at these events. All were able to tolerate Rice by ingestion, but were allergic to Peach. IgE antibodies to Rice and Peach were detected in all 3 patients. Recombinant Pru p 3, as well as Rice seed lipid transfer protein, bound IgE from sera of 2 patients whose sera were available for testing. SPT was positive for natural Pru p 3. The authors suggest that, as lipid transfer proteins are purported to be heat-stable, the fact that these patients could tolerate cooked Rice may indicate some modification of Rice lipid transfer protein during cooking (12).

Anaphalaxis and anaphalactoid reactions have also been reported in adults and children (49-50). Food-dependant exercise-induced anaphylaxis (FDEIA) may occur (51), as well as FDEIA related to multiple food intake (52). The observed recurrence of FDEIA following intervention may be a result of concomitant ingestion of other foods such as Rice and Peanut (53). Anaphylaxis has also been reported to the inhalation of Rice dust (54).

Allergy to Rice dust was also reported in 2 children. A 7-year-old girl with asthma was able to eat cooked Rice, but she was found to have IgE antibodies to Rice of 38.3 kUA/l. It was thought that her asthma was exacerbated by Rice powder inhalation, as the family milled Rice. Her symptoms improved greatly when she was away from the business. The second patient, a 3-year old boy with atopic dermatitis whose family brewed sake (made from Rice), was shown to have allergen-specific IgE of 2.21 kUA/l to Rice. The dermatitis improved when Rice was removed from his diet, but a flare occurred once when he came near Rice-threshing or milling machinery (55).

Three individuals who experienced severe allergic reactions to Rice, including anaphylaxis, were reported. The severity of the allergic response was related to the presence of the lipid transfer protein allergen in Rice. A 50-year-old woman with a history of grass pollen hypersensitivity and oral itching following the ingestion of many kinds of fruits and tree nuts experienced generalised urticaria and angioedema associated with dyspnoea about 30 minutes after eating a “risotto” dish (boiled Rice with mushrooms), and about 2 months later she experienced oral allergy syndrome followed by generalised urticaria and collapse following the ingestion of a risotto with saffron. A 25-year-old woman with grass pollen allergy and oral allergy to a number of fruits and nuts had experienced generalised urticaria and angioedema associated with dyspnoea about 1 hour after eating a risotto dish (boiled Rice with saffron). A 30-year-old man with a history of grass pollen allergy, and oral itching following the ingestion of fruits and nuts, experienced several urticaria reactions following the ingestion of risotto dishes (Rice with Chicory) and Onion. In vitro inhibition studies using lipid transfer protein purified from both Rice and Apple, as well as whole Peach extract, demonstrated that the lipid transfer protein was the relevant allergen in these patients, and demonstrated cross-reactivity between Rice lipid transfer protein and those from Peach and Apple (11).

Children may also develop allergy to Rice, although anaphylaxis appears to be uncommon. Three admissions of a 6-month-old girl due to the sudden onset of respiratory and gastrointestinal symptoms, paleness and a reduced level of consciousness following ingestion of Rice flour have been reported. A provocation test resulted in an anaphylactic reaction (56). A similar report of anaphylaxis to Rice flour in a 6-month-old girl has been documented (57).

The effect of Rice allergy on the skin has been documented by many studies. In 200 of 226 patients (90.5%) with atopic dermatitis visiting a Japanese hospital, oral food challenge tests showed that food allergy was involved, and Rice allergy affected 2.5% (58). In a study of 1006 Japanese patients with typical and atypical lesions of atopic dermatitis, who were analysed statistically by correlating the clinical severity to serum IgE antibody values, the suggestion was supported that Rice allergy strongly contributed to the development of the severity of this condition. Of 25 patients with severe atopic dermatitis and a IgE antibodies to Rice who were treated by a Rice exclusion diet, 9 were remarkably improved, 10 were moderately improved, and no effect was seen in 6 (37). The results of a study suggested that ocular-type atopic dermatitis belongs to the most severe end of the spectrum of atopic dermatitis, and that Rice and Wheat may contribute to the pathogenesis of severe atopic dermatitis, resulting in ocular complications (47,59).

Based on a statistical analysis of the correlation between Rice-specific IgE score and clinical severity in atopic dermatitis patients, the probable involvement of Rice allergy in many severe cases was postulated (60-61).

Contact urticaria from Rice has also been reported (62). Similar allergic effects were recorded in a 17-year-old female presenting with acute erythema of the hands, oedema of the eyelids, dyspnoea and cough following contact with raw Rice, which occurred from throwing raw Rice during a wedding. She was able to tolerate cooked Rice by ingestion. The authors suggested that the adverse respiratory and skin reactions resulted from Rice dust (63). Further insight into this condition comes from a report on a 30-year-old man with atopic dermatitis who experienced erythema, itching and urticarial erythema of the hands several minutes after washing Rice in water, though he had always eaten cooked Rice without problems. SPT with water used to wash regular Rice was markedly positive, but only mildly positive with water used to wash allergen-reduced Rice. Total serum IgE was 4,200 kU/l, and serum Rice-specific IgE was reported as class 2. Immunoblotting analysis of 3 atopic dermatitis patients with high IgE antibody levels to Rice detected several polypeptides, but none for this patient. The authors concluded that these findings suggest that the allergen responsible for contact urticaria in this patient might be water-soluble, heat-unstable, and not contained in allergen-reduced Rice (61).

Occupational contact dermatitis and/or asthma may occur in Rice workers and occasionally in bakers (64,66).

Other reactions
Food protein-induced enterocolitis syndrome, a symptom complex of severe vomiting and diarrhoea occurring in infants several hours after the ingestion of particular food proteins, has been reported to be caused by Rice in some instances (67). Although food-sensitive enteropathy is more often caused by milk, Rice and ground Rice may also temporarily damage the small intestinal mucosa in infancy (68-69). Reactions may be severe. Shock, nausea, vomiting, and diarrhoea have been reported in 4 infants. Occult blood in stools of these infants was positive. All immunologic tests were negative. Nevertheless, the authors conclude that, based on the clinical findings in these patients, the adverse effects were probably allergic in nature (70).

Red yield rice (Cholestin) is produced from the fermentation of Rice with the mould Monascus purpureus went, a traditional oriental food commonly known as Hongqu in China and as Red yeast rice in the United States and said to have health-enhancing qualities. A 26-year-old butcher was investigated following a severe anaphylactic episode, with sneezing, rhinitis, conjunctivitis, and generalised pruritus followed by widespread urticaria, angioedema and dyspnoea, after preparing sausages containing Red yield rice (71). Although uncommon, anaphylaxis to Red yield rice has been reported in other studies (72).

A distinct clinical syndrome seems to be associated with exposure to Rice husk dust. The manifestations of this “Rice millers' syndrome” include acute and chronic irritant effects on the eyes, skin, and upper respiratory tract; and allergic-like responses such as rhinitis, dyspnoea, bronchospasm, and eosinophilia. Radiological opacities in the chest, probably representing early silicosis or extrinsic allergic alveolitis, have been reported (73). Similarly, findings suggesting increased asthma prevalence among California Rice farmers and workers have been reported. Radiologic findings were consistent with dust or fibre exposure, although no association with specific farming activities was identified (74).

Individuals working with Rice may in fact be allergic to Rice pollen and not Rice per se (75). Among 260 Costa Rican patients with asthma and 100 non-atopic subjects studied with skin prick tests for all Poaceae tribes, 51.2% were positive to at least 1 tribe. The pollen of the Oryzeae tribe (Rice) showed the highest positivity among asthma patients of the province producing most of the country's grains (76-77).

Contact dermatitis from Rice leaf has been reported (78).

Talc-coated Rice (clearly labelled as such) is available only in a few markets, usually those specialising in South American foods. It must be thoroughly rinsed before cooking, as the talc can be contaminated with asbestos.

Compiled by Dr Harris Steinman, harris@zingsolutions.com

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