Buckwheat

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Code: f11
Latin name: Fagopyrum esculentum
Source material: Whole seed
Family: Polygonaceae
Common names: Buckwheat, Beechwheat, Fagopyrum, French wheat, Garden buckwheat

Allergen Exposure

Geographical distribution
Buckwheat is grown almost worldwide, but is especially common in China and Iraq. Its original habitat is obscure. It is a member of the Polygonaceae group of weeds. In China another type of Buckwheat, Tartary buckwheat (Fagopyrum tartaricum) is grown and consumed (1). Buckwheat is consumed mainly in Asian countries, in particular in Japan, where it is a major food allergen due to the popularity of soba (Buckwheat noodles).

Buckwheat is a large-leafed, herbaceous species and not a grass, and thus not a true cereal. The only other common food plant in this family is Rhubarb. Buckwheat is useful as a substitute for Wheat and other small grains (Rice, Barley, Oats, Rye), in particular as an alternative for people allergic to Wheat.

Environment
Buckwheat grows in cultivated beds and, where it has escaped from cultivation, on waste ground. Buckwheat flour is used for bread and other baked products. The seed is processed to make noodles (termed “soba” in Japan) and is used in soups, cakes, biscuits, etc. The grain can produce edible sprouts and excellent beer. The leaves can be eaten raw or cooked like Spinach. Buckwheat is high in fibre, minerals, vitamins and essential amino acids, especially lysine. It also contains rutin, which is believed to improve cardiovascular health by dilating the blood vessels, reducing capillary permeability, and lowering blood pressure.

Buckwheat is used internally in the treatment of high blood pressure, gout, varicose veins, chilblains, radiation damage, etc. It is best used in conjunction with vitamin C, since this aids absorption. Often combined with Lime flowers (Tilia species), it is a specific treatment for haemorrhage into the retina. A poultice made from the seeds has been used for restoring the flow of milk in nursing mothers. An infusion of the herb has been a treatment of erysipelas (an acute infectious skin disease). A homeopathic remedy has been made from the leaves and used in the treatment of eczema and liver disorders.

Unexpected exposure
The hulls of Buckwheat are used as cushion fillings in some Asian countries. A blue dye is obtained from the stems, while a brown dye is obtained from the flowers.

Allergens

Buckwheat is a very potent allergen, causing both food and inhalant allergy. Approximately 30% of total Buckwheat proteins are 2S albumins. These polypeptides range from 8 to 16 kDa, and are water-soluble. (2) However, the allergenicity of these proteins was not evaluated. Using sera from 9 Buckwheat-allergic subjects, major IgE-reactive bands of 73, 70, 62, 58 and 54 kDa were isolated under non-reducing conditions. Under reducing conditions, the 73, 70, 62 and 58 kDa bands split to 56 and 24, 52 and 24, 45 and 24, and 43 and 24 kDa molecules, respectively. The 24 kDa molecule was the most prominent band recognised with IgE as well as IgG and IgA  (3).

In a study of 19 Buckwheat-allergic subjects with symptoms after Buckwheat ingestion, and 15 asymptomatic control subjects with positive SPT to Buckwheat, the prevalence of IgE binding to 24 kDa (Fag e 1), 16kDa (Fag e 16kD), and 9 kDa (presumably now recognised as Fag e TI) allergens was assessed. IgE antibodies to split 19 kDa allergens was more often found in Buckwheat-allergic patients than in asymptomatic subjects (78% vs. 7%). The amino acid sequence of the 19 kDa and 16 kDa allergens showed moderate and weak homology to the 19 kDa globulin protein of Rice and the alpha-amylase/trypsin inhibitor of Millet, respectively. The 9 kDa isoallergens were similar to each other and were identified as trypsin inhibitors. The authors concluded that the allergens of 24, 19, 16, and 9 kDa were strong major allergen candidates for Buckwheat, and that the 19 kDa allergen was relatively specific for Buckwheat-allergic patients (4). Studies by other researchers have suggested that 14 and 18 kDa Buckwheat allergens are major allergens (5), and an earlier study reported the isolation of 22 kDa, 36 kDa, 39 - 40 kDa and 70 - 72 kDa allergens that were identified from water-soluble fractions of Buckwheat (6).

An 8S storage globulin from Buckwheat, with the structure common to the vicilin-like family of seed storage proteins, was isolated; its increase precedes that of the 13S globulin (the main Buckwheat storage protein) and starts from an early stage of Buckwheat seed development, continuing to accumulate throughout seed development to contribute approximately 7% of total seed proteins. A 13S Buckwheat legumin of 23-25 kDa, reported to be a major Buckwheat allergen, was also isolated. A partial cDNA showed high homology with cDNAs coding for vicilin-like storage proteins from various plant species (7).

The following allergens have been characterised:
  • Fag e 1, previously known as BW24KD, a 22 - 24 kDa protein, an 11S Globulin-like legumin (3,6,8-11).
     
  • Fag e 10kD, a 8-17 kDa protein, a 2S albumin (12-13).
     
  • Fag e 16kD, a 16 kDa protein, a 2S Albumin. (9,12,14-15).
     
  • Fag e 19kD, a 19 kDa vicilin-like protein. (9,15).
     
  • Fag e TI, a trypsin inhibitor (4,16-17).

Studies have elaborated on the characterised allergens, and a number of other proteins have been isolated but not characterised.

Fag e 10kD is also a major allergen of Buckwheat and was reported to sensitise approximately 57% of Buckwheat-allergic patients (13). Interestingly, not all species of Buckwheat contain the major allergen found in F. esculentum. F. lineare and F. urophyllum have been shown to lack the 22 kDa major allergenic protein (18).

The 16 kDa protein of Buckwheat, also a major allergen, has 50% homology to the reported 8 kDa Buckwheat allergen which is a 2 S storage albumin. Using a re-combinant 16 kDa allergen, it was found that approximately 77.8% of 18 patients with Buckwheat allergy had raised IgE antibody level to this allergen, compared to none of 20 asymptomatic Buckwheat-sensitised subjects (14).

In an assessment of the 19 kDa allergen, about 83.3% of Buckwheat-allergic patients were shown to have IgE antibodies raised to the recombinant 19 kDa protein, compared to only 1 of the 19 asymptomatic Buckwheat-sensitised subjects, suggesting that the 19 kDa Buckwheat allergen may be a major allergen (15).

Allergens of 14 and 18 kDa have been isolated and shown to share some homology with Rice proteins. Both are major allergens (5). Another major allergen, a 24 kDa protein, bound to IgE antibodies in sera from every Buckwheat-allergic patient in a study (1,19).

A16 kDa Buckwheat protein that was isolated has been shown to be resistant to pepsin digestion and was reported to be responsible for immediate hypersensitivity reactions, including anaphylaxis. Allergen-specific IgE was detected to a pepsin-sensitive 24 kDa protein but was not thought to play a role in immediate hypersensitivity reactions. However, the 24 kDa protein, previously reported to be a major allergen and now recognised as Fag e 1, reacted to IgE antibodies present in sera from almost all subjects (19/20) regardless of symptoms. On the other hand, 16 and 19 kDa proteins bound with IgE antibodies present in sera from 9 of the 10 patients with immediate hypersensitivity reactions, including 8 patients with anaphylaxis; but not with sera from Buckwheat-specific IgE-positive subjects without immediate hypersensitivity reactions. After pepsin treatment, the 16 kDa protein but not the 19 and 24 kDa proteins remained undigested and preserved the capacity of IgE binding (9).

In an analysis of Buckwheat-specific IgE antibodies in an 8-year-old with fatal food-dependent exercise-induced anaphylaxis, 7 protein bands were found that reacted with the IgE of the patient's serum. Four bands of 16, 20, 24, and 58 kDa were specific to the patient, compared to subjects not allergic to Buckwheat (20).

Buckwheat seed contains a thiamin-binding protein. The protein has homology with the thiamin-binding proteins from Rice seeds and Sesame seeds (21). A 230 kDa thiamin-binding protein has been isolated from Sunflower seeds; its properties are similar to those in proteins from Buckwheat seeds, but not to those from Rice seeds and Sesame seeds; and similar to those of helianthinin (22). The clinical significance of this protein has not been established. Similarly, the significance of the inhibitor of trypsin and chymotrypsin is unknown (23).

Potential cross-reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected (24). Importantly, Buckwheat is not taxonomically closely related to Wheat or other cereal grains. The 24 kDa allergenic protein in Tartary buckwheat shares a greater than 93% homology with the allergenic storage protein and a legumin-like protein from Common buckwheat (25).

Immediate hypersensitivity reactions induced by the ingestion of Buckwheat are considered to be IgE-mediated. In 28 subjects without immediate hypersensitivity reactions to Buckwheat ingestion, out of 46 subjects in whom IgE antibodies to both Buckwheat and Rice allergens were detected, results led to the conclusion that there is cross-reactivity with IgE antibodies between Buckwheat and Rice and that IgE antibodies from subjects without immediate hyper-sensitivity reactions might recognise the epitopes on Buckwheat antigens which cross-react with Rice antigens, whereas IgE antibodies from subjects with immediate hypersensitivity reactions might bind to Buckwheat-specific epitopes (26-27).

Cross-reactivity between Buckwheat and Natural rubber latex has been reported; therefore, allergy to fruits and vegetables that cross-react with Latex should be considered in patients who are proven to be allergic to Buckwheat (28-29). Immuno-chemical cross-reactivity between the globulins from Buckwheat and Indigo seeds has been documented (30).

The 19 kDa Buckwheat allergen has a weak homology to the vicilin-like allergens of Cashew (Ana o 1), English walnut (Jug r 2) and 7 S globulin from Sesamum indicum. (15) Cross-sensitisation of Poppy seed with Buckwheat has been reported (31).

Clinical Experience

IgE-mediated reactions
Buckwheat has been recognised as a common food allergen in Korea, Japan, and other Asian countries, but not in Taiwan (32-33). In these countries, Buckwheat may frequently induce sensitisation or symptoms of food allergy or inhalant allergy in sensitised individuals (3,34-43). Approxi-mately 5% of Korean children were reported to have IgE antibodies to Buckwheat (44).  Similarly, food allergy was noted in 5.2% of Japanese students, with a higher prevalence in female students. Buckwheat was reported to be the second-most-frequent cause after Egg, followed by Shrimp, Crab, Mackerel and Cow's milk (33). In a study of the incidence of anaphylaxis in a Korean tertiary care hospital, radio-contrast media and Buckwheat were respectively the leading causes of drug and food anaphylaxis (45).

Despite being a potent allergen when ingested or inhaled, Buckwheat has been increasingly popular, in particular as a health food, in the United States, Canada, and Europe (46-47). Researchers have suggested that allergy to Buckwheat will become a larger problem as a result of its increased use in the food processing industry. Buckwheat is also used as a substitute cereal for children with coeliac disease (43).

Some authors have stated that Buckwheat can cause allergic reactions much more severe than Wheat and its relatives do, and that allergy to Buckwheat should therefore be considered in patients with classic symptoms of food allergy, where the signs are often severe (43). Symptoms include gastrointestinal distress, urticaria, Quincke oedema (angioedema), dyspnoea, rhinorrhoea, wheezing, asthma, rhinitis, anaphylaxis and shock (48-51).

Among adult asthmatics in a Japanese study, 625 of 3102 (20.1%) had a positive test to 1 or more food allergens, according to skin-specific IgE evaluation. The commonest food allergens were Shrimp (27.7%), Crab (27.7%), Yeast (23.8%) and Buckwheat (15.8%). Positive food challenge responses occurred in 30/60 subjects (50%). The foods which most often provoked a reaction were Buckwheat, Shrimp, Crab and Bread (52). In a Japanese study, more severely asthmatic children had a higher incidence of positive intracutaneous skin tests to house dust, molds, Japanese cedar tree, Ragweed, Cat dander, Silk and Buckwheat (53). An earlier study reported the opposite in children with asthma (54).

From the results of a questionnaire sent to 341 elementary school nurses in Yokohama, the incidence of Buckwheat allergy in of 92,680 children was determined to be 0.22% (140 boys and 54 girls). Symptoms were urticaria (37.3%), skin itching (33.3%), and wheezing (26.5%). Anaphylaxis was reported in 4 children (3.9%). The incidence of anaphylaxis due to Buckwheat was higher than that due to Egg and Milk allergy. Seven pupils had allergic reactions to Buckwheat noodle served at school lunch (55).

The French Allergy Vigilance Network, which monitors adverse allergy reactions in that country, reported that in 2002, 107 cases were reported, of which 59.8% were cases of anaphylactic shock, 18.7% of systemic reactions, 15.9% of laryngeal angioedema, and 5.6% of serious acute asthma. The most frequent causal allergens were Peanut (n=14), Nuts (n=16) and Shellfish (n=9). Severe adverse reactions to Buckwheat were reported in 3, in contrast to 4 to Sesame, 3 to Cow's milk, and 3 to Fish (56).

In 34 Finish children with atopic dermatitis, 33 were SPT positive to Wheat and 18 to Oats, whereas Rice, Maize, Millet or Buckwheat was positive in 16/34 patients (57).

Inhalation of very small amounts of Buckwheat allergen can initiate severe allergic symptoms (19). A 20% reduction in lung function after inhalation of aerosolised Buckwheat allergens has been documented (58). In 12 children with IgE-mediated food allergy who developed asthma on inhalational exposure to food, the implicated foods were Fish, Chick pea, Milk, Egg and Buckwheat. Bronchial food challenge resulted in 5 children showing objective clinical features of asthma and 2 developing late-phase symptoms (59). An interesting report described a young woman who experienced anaphylaxis after entering a pancake restaurant but before consuming any food or drink. Investigation demonstrated sensitisation to both Dust mites and Buckwheat, and airborne Buckwheat allergens were incriminated in the anaphylactic reaction, with a Buckwheat 2S albumin implicated as the responsible allergen (60).

In Switzerland reactions to Buckwheat are uncommon and reported to be mostly due to ingested Buckwheat in the form of pizoccheri (dumplings) and Buckwheat bread. A study described 6 individuals who experienced allergic reactions due to Buckwheat. Symptoms of urticaria were experienced by 6, angioedema in 4 and asthma in 5. Four patients reacted to ingestion of Buckwheat and 2 to inhaled Buckwheat allergens in an occupational setting. All were shown to have positive SPT and raised allergen-specific IgE to Buckwheat (49).

Exposure to Buckwheat may also result in anaphylaxis (61-62). An anaphylactic reaction was reported in a 19-year-old-man after he ate "poffertjes" (small Dutch pancakes), the principal ingredient being Buckwheat. The authors suggest that it was highly likely that this patient had been sensitised to Buckwheat by sleeping on a pillow stuffed with Buckwheat husk (63). Similarly, an individual developed asthma and worsening allergic rhinitis after exposure to Buckwheat present in his pillow. SPT and IgE in vitro test were strongly positive, and the later was reported to be class 4 (64). Indeed, nocturnal asthma from sleeping on Buckwheat chaff-stuffed pillows, a common type in Korea, has been reported as a result of Buckwheat allergy (65-66). However, House dust mite (D. farinae) may also be an important allergenic substance in Buckwheat-husk pillows (67).

A woman with asthma is described who had anaphylaxis, generalised urticaria, and an acute exacerbation of asthma 5 minutes after ingesting Buckwheat. She was markedly SPT positive for Buckwheat, and serum Buckwheat-specific IgE was reported as class 6 (32).

A 36-year-old man is described who experienced nausea, vomiting, urticaria, a sensation of throat closing, inability to speak, dyspnoea, and dizziness shortly after ingesting a large portion of Buckwheat. In the previous 2 years, he had experienced asthma, contact urticaria, allergic conjunctivitis, and allergic rhinitis from sleeping with a Buckwheat pillow. Six months after the first ingestion reaction, the patient again experienced anaphylaxis requiring emergency treatment when he accidentally ate crackers with a small amount of Buckwheat in them. SPT and IgE in vitro test were markedly positive for Buckwheat. The authors postulated that inhaled Buckwheat, provoking asthma, had sensitised the patient prior to the 2 episodes of ingestion anaphylaxis (46).

A 37-year-old woman twice developed a life-threatening anaphylactic reaction after eating galettes, a special French pancake from Brittany. She had tolerated ordinary pancakes and crêpes for many years. Investigation confirmed Buckwheat as the causative allergen, and found it in the galettes. SPT and IgE in vitro test was positive for Buckwheat. The authors suggested that whenever a patient experiences allergic reactions due to pastries, Buckwheat allergy should be considered (68).

Food-dependent exercise-induced anaphylaxis caused by Buckwheat may also occur, as reported in an 8-year-old girl. The patient consumed Buckwheat noodles called “zaru soba” and swam vigorously immediately thereafter. Approximately 30 minutes later, she complained of abdominal pain, vomiting, coughing, and chest discomfort, followed 10 minutes later by a deterioration of consciousness and cardiorespiratory arrest. An exaggerated hematemesis that occurred immediately after hospital admission indicated an inflammatory condition of the digestive tract that was caused by Buckwheat. Marked ulceration accompanied with hemorrhage and necrosis was noted at the ileum. Extensive hemorrhage involving the endotracheal pulmonary field and lymphocyte infiltration of the alveolar space likely appeared after the inflammation. The serum IgE antibody level was raised for Buckwheat  (20).

Buckwheat may also be a "hidden" allergen. Anaphylaxis as a result of Buckwheat used as filler in pepper has been reported (69); and to “hidden” Buckwheat in a Wheatburger (70).

Occupational rhinitis, conjunctivitis, asthma or urticaria may occur to Buckwheat or Buckwheat dust in animal husbandry and other food industry workers (1). These symptoms have occurred after exposure to comparatively low levels of Buckwheat dust resulting from the grinding and packaging of Buckwheat  (71-72), to Buckwheat flour (73), and in a noodle maker (74-75). Occupational asthma has also been reported in an individual working in a pancake restaurant, and was confirmed by specific bronchial challenge with aerolised Buckwheat (39,50).

 

Other reactions
Pulmonary haemosiderosis as a result of non-immediate Buckwheat protein hypersensitivity has been reported. The patient had no skin reactivity or IgE antibodies, but was positive to a patch test (76).

Immediate hypersensitivity reactions induced by Buckwheat ingestion are considered to be IgE-mediated. Some subjects, however, develop no immediate adverse reactions after Buckwheat ingestion, despite high levels of Buckwheat-specific IgE antibodies. To elucidate the possible mechanisms, RAST inhibition between these antigens were performed using sera from 23 Buckwheat-sensitive subjects and 30 Buckwheat-tolerant subjects who had IgE antibodies for both Buckwheat and Rice. The authors report that there was cross-reactivity with IgE antibodies between Buckwheat and Rice, and that IgE antibodies from Buckwheat-tolerant subjects with high levels of IgE antibodies to Buckwheat might recognise the epitopes on Buckwheat antigens which cross-react with Rice antigens, whereas IgE antibodies from the Buckwheat-sensitive subjects might bind to Buckwheat-specific epitopes. (77).

Compiled by Dr Harris Steinman, harris@zingsolutions.com

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.