Route Of Exposure

The name Millet is used to describe seeds from several taxonomically divergent species of grass. They are grown mostly in marginal areas and under agricultural conditions in which major cereals fail to give sustainable yields.

Common millet and the other Millets are not closely related to Wheat. Common millet was grown in prehistoric Europe. Because of its ability to mature quickly, it is often cultivated by nomads. This shallow-rooted plant varies in height between 30 and 100 cm. The grain contains a comparatively high percentage of indigestible fibre because the seeds are enclosed in the hulls and are difficult to remove by conventional milling processes.

The Millets are important sources of food for humans and animals. But in the West, with the exception of natural food stores, Millet is sold mainly as bird feed.

Clinical Relevance

Allergen description

No allergens from this plant have yet been characterised.

In a study of 7 patients who experienced allergic symptoms after ingestion of Millet, immunoblotting detected 3 major allergens in Millet extract, directed to serum IgE antibodies of 6 of the patients. In the control group, 10 of 16 (63%) of Millet-exposed atopic bird keepers were shown to have IgE antibodies directed at allergens in Millet extract. A protein of approximately 36 kDa was recognised by 94% of the patients. An allergen of approximately 70 kDa was recognised by 62% of the patients, and an allergen of approximately 90 kDa by 75% of the patients.

In a study, the antigenic relationships among "minor Millets" (Barnyard, Little and Foxtail millets) and other cereals (Wheat, Maize, Rice, Sorghum, Finger millet and Pearl millet) were evaluated using an antibody raised against a 20 kDa prolamin from Kodo millet. It was demonstrated that this prolamin was related to the prolamins from the other foods. Rice was the only common cereal that did not cross-react immunologically with the 20 kDa prolamin of Kodo millet. Common millet was not assessed, and it is possible that a similar protein is present in Common millet.

A Rice protein of 16 kDa was reported to be involved in cross-allergenicity among antigens in Rice, Wheat, Corn, Japanese millet and Foxtail millet. This protein was subsequently shown to have sequence homology to Wheat alpha-amylase inhibitor and Barley trypsin inhibitor. Common millet was not assessed, and it is possible that a similar protein is present in Common millet.

A beta-amylase of 58 kDa, belonging to a protein family that has allergenic members, was isolated from germinating Common millet seed. The allergenicity of this protein was not evaluated.

Potential Cross Reactivity

Studies have not reported cross-reactivity between Millet and Barley, Maize, Oats, Wheat, or grass pollen (Rye, Orchard, and June grass). A study found that though cross-reactivity to these cereals may be suggested by the presence of IgE antibodies directed to them, this was not clinically relevant.

A Rice protein of 16 kDa has been shown to be involved in cross-allergenicity among antigens in Rice, Wheat, Maize, Japanese millet and Foxtail millet. However, Common millet was not assessed, and whether a similar protein can be found in this Millet is unknown.

Clinical Experience

Hypersensitivity to cereals may occur via inhalation or ingestion. But in spite of Common millet being regarded as a potent allergen, allergy is uncommon, with reports generally confined to case studies. With the increasing popularity of "natural foods", Millet is more frequently included in various dishes, which might raise the incidence of Millet-related allergic reactions. Patients with adverse effects to Gluten may substitute Millet for gluten-containing cereals. Allergic reactions have been described after ingestion of Millet, and after inhalation of bird seed dust by people who keep caged birds. Case reports of asthma and/or anaphylaxis after ingestion of food containing Millet have been documented.

Individual cases are most instructive.

The first report of an adverse reaction to Common millet was described in a 25-year old clerk who developed anaphylaxis after the ingestion of Millet seed. Symptoms developed approximately 30 minutes after a "natural food" dinner, which included a Date-Millet pudding. The symptoms included periorbital angioedema, ocular injection, tightness of the throat, shortness of breath, wheezing, intense generalised pruritus, and lower abdominal distress. Significant intradermal skin-test reactivity to Millet extract was shown. IgE antibodies to Millet were elevated. Histamine release tests were positive. No cross-allergenicity between Millet seed and other grains and grasses (Rye, Orchard, and June grass pollen; Wheat, Oat, and Barley grain) was shown.

A meal containing Millet triggered an anaphylactic reaction in a young woman who kept a Parrot in a cage in her bedroom. Millet seeds were major constituents of the bird's feed.

A few minutes after ingestion of a cookie containing Millet, a 32-year-old woman developed laryngeal pruritus and oedema with stridor, tightness of the throat, pruritus of the palms and soles, conjunctivitis, facial swelling, and, a few minutes later, bronchospasm and hypotension. She had previously complained of laryngeal itching after ingestion of a pastry containing Millet, as well as of an episode of swelling of the tongue in her childhood related to ingestion of a particular but unidentified cereal. No adverse effects were reported to other common cereals, including Barley and Wheat. Skin reactivity was determined for Barley seed and Wheat flour, but was negative for Barley flour, Maize seed and flour, and Oat seed and flour. Skin reactivity was present for fresh Millet seed extract. IgE antibody determination for Barley, Maize, Oats, and Wheat were negative but raised for Common millet (1.7, class 2). The authors highlighted the fact that, although skin reactivity was found for Wheat and Barley seed, she tolerated them well.

Anaphylaxis after ingestion of food containing Millet was reported in a 51-year-old woman who, after ingesting a Millet dumpling, immediately developed generalised urticaria, mucosal swelling, shortness of breath, and "hypotonic" reactions. She had not eaten Millet before. She had kept a Budgerigar years before and described having had asthmatic attacks while cleaning the bird cage. Skin reactivity was found only to Millet, which was strongly positive. Intradermal testing was positive for Rye, Oats, Maize, and Barley. SPT for Budgerigar allergens was negative. IgE antibody levels were raised for nearly all the cereals evaluated and in particular for Millet.

A study evaluated 7 individuals who all kept caged birds and had experienced allergic reactions after ingestion of Millet-containing food, with adverse reactions ranging from oral allergy syndrome to anaphylaxis. Symptoms included conjunctivitis (n=1), collapse (n=1), dyspnoea (n=3), hypotension (n=2), nausea (n=2), oral allergy syndrome (n=2), rhinitis (n=2), and urticaria (n=3). The individual profiles of these patients were the following: a 13-year-old male (nausea, hypotension), a 28-year-old female (oral allergy syndrome), a 32-year-old female (conjunctivitis, dyspnoea, urticaria), a 46-year-old female (rhinitis, dyspnoea, urticaria), a 62-year-old female (nausea, dyspnoea, urticaria, hypotension), a 30-year-old female (rhinitis), and a 40-year-old female (oral allergy syndrome). IgE antibody levels varied from ImmunoCAP classes of 2 to 4. As all of these subjects kept birds at home and used Millet as birdseed, the authors assumed that the sensitisation to Millet occurred via the inhalant route. Sixty-three percent of the bird keepers had IgE antibodies directed at Millet. Several patients reported respiratory symptoms while cleaning the bird cage. The authors suggested that sensitisation to Millet may subsequently also elicit food allergy. Anaphylaxis was described in a bird-keeper sensitised to Millet via inhalation; the anaphylaxis occurred after oral ingestion

Other reactions

Crude extracts of Millet may contain aflatoxins. Some varieties of Millet appear to contain cyanide. Fonio millet (Digitaria exilis) contains flavanoids with antithyroid properties and was reported to have resulted in an epidemic of severely iodine-depleted goiter, as a result of the presence of apigenin and of luteolin. Other Millets contain C-glycosylflavones. Millet diets rich in C-glycosylflavones are goitrogenic. Jimson weed poisoning due to contamination of Millet porridge with this seed has been reported.