Summary

Rice (Oryza sativa) is an essential food crop cultivated and routinely consumed globally and is regarded as a staple food for ~50% of the total world’s population. It is extensively cultivated in Asian countries, such as India, China, Japan, Indonesia, Myanmar, Cambodia, Nepal, the Philippines, Bangladesh, Pakistan, Thailand, the Republic of Korea, Srilanka, and Vietnam. Hence allergy to rice is predominantly reported from these countries. Oral ingestion of cooked/boiled rice, inhalation of uncooked, steamed rice, raw rice husk/dust, or direct skin contact with rice (sorting/handling rice or washing rice before cooking) have been considered as important routes of exposure causing rice allergy in individuals. Ingestion of rice may induce IgE-mediated food allergy symptoms, such as oral allergy syndrome or even anaphylaxis. Inhalation of rice husk/ raw rice powder could lead to respiratory symptoms (such as asthma, allergic rhinitis, and rhino-conjunctivitis), while direct contact with rice may cause skin symptoms (such as generalized urticaria/angioedema, and atopic dermatitis). Ory s 14 (a 14-kDa lipid transfer protein) is an important food allergen present in rice seed, that is found to be heat stable and resistant to pepsin digestion. Besides, Ory s 1 and Ory s 12 are rice pollen allergens responsible for causing respiratory allergic symptoms. Rice has been found to cross react with other cereals, such as barley, oats, wheat, rye, soybean, and corn, with fruit such as peach, and also with grass pollens.

Epidemiology

Worldwide distribution

Despite high consumption of rice globally, prevalence of rice allergy is considered low. It is a staple food, mostly in the Eastern Asia; hence allergy to rice is predominantly reported from Asian countries.

In Western countries, rice allergy is rarely reported with varied prevalence, ranging between 0.7 and 2% in these population, although the true prevalence rate is unclear. This is probably because in these regions rice is considered mainly as a cereal-related allergen source. Furthermore, rice allergy has also been found in countries, such as Russia, Denmark, France, Estonia, Lithuania, and Sweden.

In Thailand, the rice ranked 4th among the list of important food allergens, post shellfish, peanut, and soy, while in Japan it ranked 5th and in Indonesia 6th.

In Japan, the estimated prevalence of IgE-mediated rice allergy was found to be ~10% in atopic individuals.

A survey was conducted in India to determine the rice allergy in 1200 AR and bronchial-asthmatic patients aged between 5 and 60 years. Among these patients, 165 were found to have a prior history of rice allergy. It was reported that 12.1% of patients (20 out of 165) were found positive to skin prick test (SPT) result (n=20), 65% of patients (13 out of 20) showed increased-specific (s)-IgE for raw rice, whereas 60% of patients showed it against boiled rice. Furthermore, according to double blind placebo-controlled food challenge (DBPCFC), 60% of patients demonstrated allergy to rice (6 out of 10). Overall, rice was considered to be an essential allergen source, with IgE-mediated rice allergy affecting 0.8% of AR and bronchial-asthmatic patients. Furthermore, in a cross-sectional study conducted in India, allergy to rice was reported to be greater among patients of age group>40 years in comparison to patients<40 years.

In a study conducted in Malaysia, 148 adult patients (>17 years) having symptoms of AR (rhinorrhoea and nasal congestion) were compared to 113 subjects without AR, who acted as controls. The study revealed that, among 11 food items tested, 48% of AR patients (71 out of 148) showed positive SPT reactivity for food, in comparison to 4.4% (5 out of 113) among controls. Moreover, compared to other food allergens, rice (30.4%; 45 out of 148) and shrimp (47.9%; 71 out of 148) demonstrated greater reactivity to SPT among AR patients.

Risk factors

Risk of asthma and contact dermatitis might occur as a result of occupational exposure to rice, among food workers and bakers. Moreover, the LTP allergen of rice (Ory s 14) shares high-sequence similarity with major maize allergen, a 9 kDa LTP, attributing to high risk of co-sensitization in individuals having these allergies.

Route Of Exposure

Main

Oral ingestion of cooked/boiled rice or inhalation of uncooked, steamed rice, raw rice husk/dust have been considered as important routes of exposure causing rice allergy in individuals. It has been reported that oral ingestion of rice could lead to IgE-mediated and rapid hypersensitivity reactions, such as oral allergy syndrome (OAS), anaphylaxis, asthma, allergic rhinitis (AR), atopic dermatitis, and rhino-conjunctivitis. Similarly, inhalation of rice dust, husk or flour as well as rice vapors during cooking could induce asthma, AR, rhino-conjunctivitis, anaphylaxis, and in some cases generalized urticaria/angioedema.

Direct skin contact with rice (sorting/handling rice or washing rice before cooking) is another important route of exposure that may cause allergic reactions, such as contact urticaria and angioedema.

Clinical Relevance

According to published literatures, it has been reported that rice allergy may cause severe allergic reactions in individuals, leading to respiratory (asthma, AR, rhino-conjunctivitis), GI (vomiting, abdominal pain, diarrhea), skin (atopic dermatitis, angioedema, urticaria), and systemic symptoms (anaphylaxis).

Oral allergy symptoms and Anaphylaxis

Ingestion of rice or inhalation of rice dust/flour may induce IgE-mediated food allergy symptoms, such as OAS or even anaphylaxis. This has been documented in several case reports, mentioned below.

In a case series involving three LTP-allergic patients (25-, 30-, and 50-year-old patients), anaphylaxis induced by rice was reported. All the three cases were presented with dyspnea, generalized urticaria or angioedema on consumption of risotto (cooked rice and mushrooms) and/or rice along with chicory. The results showed positive SPT for commercial rice extract with high rice sIgE.

A case of repeated anaphylactic episode, following oral ingestion of rice with symptoms, such as angioedema, pruritis, generalized urticaria, bronchospasm, and dysphagia was reported. The results revealed that IgE reactivity was confirmed (detected by SPT) for various rice extracts (both raw rice and cooked boiled rice).

Gastrointestinal reactions, such as pain in the abdomen, nausea, vomiting and diarrhea on consumption of rice was reported in a 9-year-old girl. The SPT and prick-prick tests showed a noticeable wheal and flare response with rice. Furthermore, a double-blind, placebo-controlled, food challenge test performed on the patient reported GI symptoms within 10 mins of eating rice; however, it was observed that she didn’t show any allergic reaction while consuming other cereals.

Rice flour-induced anaphylaxis was reported in a 6-month-old girl who was admitted in the hospital thrice as a result of immediate onset of respiratory as well as GI symptoms, pale skin, and decreased responsiveness. Anaphylaxis has also been reported due to inhalation of rice proteins in a 11-year-old-boy with atopic dermatitis.

Allergic rhinitis, rhino-conjunctivitis, and asthma

Inhalation of rice dust/pollen may induce AR, and this could be considered as one of the factors for the development of asthma in individuals.

It has been reported that allergy to rice pollens may induce these respiratory symptoms among rice farmers and people living near rice farms during the flowering season of rice plants. A cross-sectional study conducted among 464 rice farmers (mean age 48.3± 15.2 years) in California (USA) reported AR (25.7%), persistent wheeze (8.8%), asthma and severe cough (7.1% each), and bronchitis (6.3%), due to burning of rice stubble in the agricultural fields.

In a study conducted in Taiwan, 9.3% of asthmatic children showed positive response to rice pollen extract (n=312), and it was reported that sensitization to rice pollen might be one of the important factors for eliciting IgE-specific responses in the patients.

In a case series of four patients, it was reported that inhalation of raw rice (while throwing rice in wedding ceremony) may have led to respiratory-allergic symptoms (rhino-conjunctivitis and asthma).

A case of AR was identified in a 31-year-old male who worked in a grain industry and showed a prior history of runny nose, blockage, sneezing and itchy/burning eyes at work, while being exposed to rice powder. His symptoms aggravated at workplace. The SPT was found positive for rice extracts, the serum-IgE level for rice was reported high, and the nasal provocation test with rice extract showed development of AR. The findings indicated that inhalation of rice flour at workplace may have led to AR.

Atopic Dermatitis

Allergic reaction induced by rice could be IgE mediated in cases of AD and bronchial asthma. Few studies have been reported, which suggest that exacerbation of AD may be caused by rice.

In a study conducted in Japan among 1006 patients with AD, it was found that rice may be associated with the severity of AD. Furthermore, excluding rice in the diet of 25 severe AD patients showed good improvement of AD in 9 patients, moderate improvement in 10 patients, and neither aggravation nor any effect in 6 patients

A case of a 3-year-old boy (with AD since the age of 3 months) was reported, who showed worsening of AD symptoms (skin eruptions and rashes) after coming in contact with rice dust.

Urticaria and Angioedema

Direct touching/sorting of raw rice or the water used for washing rice may lead to contact urticaria in certain individuals.

Two case reports have been identified where handling of raw rice led to contact urticaria in hand. The first case was of a 27-year-old housewife who showed positive SPT with flour extract, positive rub test and challenge test with raw rice, and high rice-specific IgE in serum. In the second case of a 17-year-old female, SPT with rice revealed urticaria suggesting raw rice could be the cause of cutaneous reaction in the patient. Furthermore, development of contact urticaria (erythema and itching) after washing rice in water was reported in a 30-year-old male who showed positive SPT with rice allergen, and avoidance of contact with water used for washing rice improved the skin conditions.

Furthermore, occurrence of urticaria and angioedema after inhalation of raw rice has rarely been reported. This was evident in a 9-year old girl who developed urticaria-angioedema after inhaling raw rice.

Urticaria and angioedema of the eyelids, tongue, and lips as a result of consumption of rice has also been reported in a case study of a 33-year-old German patient.

Other diseases

Rice millers’ syndrome

It has been reported that the rice millers’ syndrome might occur as a result of exposure to rice husk powder. The clinical manifestations may include irritation of eyes, skin, and respiratory tract; allergic reactions like nasal discharge, chest tightness, asthma, and high eosinophil counts, along with pulmonary infiltrates, which might represent early silicosis or hypersensitivity pneumonitis. This was evident in a Malaysian study conducted on 122 rice-mill workers.

Prevention And Therapy

Prevention strategies

Avoidance

Individuals who are allergic to rice should generally avoid consumption of this grain completely, along with foods that act as alternatives for rice. Furthermore, certain other foods (barley, oats, wheat, rye, soybean, corn, grass pollen and triticale) that belong to the same family as rice, should also be avoided.

Immediate medical care should be advised to an individual who is allergic to rice, in case if it is accidentally consumed.

Cross-Reactivity

Individuals who are allergic to rice might also show cross-reactivity with other members of the same family, such as barley, oats, wheat, rye, soybean, corn, grass pollen and triticale. The rice proteins with a molecular mass of 15.5, 16, 19, 25, 50, and 90 kDa have been identified as major allergens, developing cross-reactivity among cereal grains in family Poaceae.

Rice LTP is considered as a cross-reacting allergen, with reports of it cross-reacting with LTPs of peach In a study conducted on 148 peach-allergic individuals, 56.8% of patients were found sensitized to rice (IgE test). It was reported that all the patients with symptoms induced by rice were found to be Pru p 3 (a LTP from peach) positive. Furthermore, the major rice allergen identified was 9 kDa (LTP), that showed 53% sequence similarity with Pru p 3. This indicates that rice could lead to allergic reactions in peach-allergic patients.

Furthermore, rice LTP has also shown sequence identity with maize LTP, thus resulting into cross-reactivity between the two. A study revealed that IgE antibodies from 28.5% of patients with maize allergy (n=7) showed cross-reactivity with a 56 kDa rice allergen. In another study, rice extracts completely inhibited all the maize allergens. Moreover, maize LTP was found to have 79% identity and 92% similarity with rice LTP.

In a study it was observed that patients with allergies to food (mostly wheat) and pollens, may often display high levels of IgE-antibodies, particularly to rice.

In another study, based on the radioallergosorbent (RAST) test value (r= 0.56; p<0.01)), 16-kDa rice protein was found to be correlated with Italian millet, however this was not the case with either wheat or corn.

Cross-reactivity between rice and other cereal flour extracts have been noted. This evidence is supported by a case study of a 27-year-old female, who developed rhino-conjunctivitis, asthma as well as contact urticaria, while handling rice and certain other cereals (wheat, rye and corn). Based on the reverse enzyme-immunoassay (REIA) performed, cross-reactivity was reported between rice (75%) and other cereal flour extracts, such as rye (63%), corn (64%), and wheat (51%).