Summary

Maize or corn (Zea mays L.) is a high-yielding and an essential food crop after wheat and rice, available globally. Maize is widely cultivated throughout the world, including countries such as northern Europe, Russia, South Africa, East Asia, the Himalayas, China, Southeast Asia, the Pacific Islands, Chile, and Canada. Allergy to maize has commonly been reported in countries, such as southern Europe and Mexico, where its consumption is popularly high. Oral ingestion of maize can lead to IgE-mediated allergic reactions, like oral food allergy syndrome and even severe reactions, like anaphylaxis. Additionally, inhalation of maize flour at work, can lead to occupational asthma and rhino-conjunctivitis, while skin contact with it, can provoke allergic reactions, such as contact urticaria. Five allergenic components of maize, such as Zea m 1, Zea m 8, Zea m 12, Zea m 14, and Zea m 25 have been identified; among them Zea m 1 and Zea m 14 are the major allergens. Zea m 14 (non-specific lipid transfer protein) is a highly resistant protein, capable of withstanding heat, enzymatic, and chemical treatments. Maize has been found to cross-react with other cereals, such as rice, wheat, barley, etc. Besides this, maize has also shown to cross-react with fruits, such as peach, cherry, cowpea, apricot, grapes as well as pollens, such as grass and Platanus pollens.

Epidemiology

Worldwide distribution

Allergy to maize has commonly been reported in countries, such as southern Europe and Mexico, where the consumption of maize is popularly high. However, presently maize allergy has been receiving large attention, following its use as a genetically-modified crop in human food.

Prevalence of maize allergy was identified in a study that involved 24 Italian and 3 Swiss patients (n=27) with suspected allergy to maize. All the patients (100%) confirmed positive result to skin prick test (SPT) and also showed specific immunoglobulins E (sIgE) for maize.

In a study conducted on 661 Mexican patients with a history of allergy, 56 patients (8.7%) reported allergy to maize.

Racial and ethnic differences in food allergy phenotype, among children with food allergy in the US have been characterized. A large, retrospective cohort study conducted in US, involved 285 African American (AA), 99 Hispanics, and 433 white children (age range: 0 to 17 years) with a history of food allergy. According to the results, the prevalence of allergy to corn, shellfish, and fish was significantly higher (p<0.01) in AA and Hispanics than in whites. Furthermore, the prevalence of corn allergy in whites, AA, and Hispanics was found to be 2.1%, 15.1%, and 7.1%, respectively.

In a survey conducted among school children in France, the prevalence of food allergy was studied using questionnaires. Out of 3500 questionnaires being distributed in 150 classes in 8 schools, 2716 (77.6%) responses were obtained. It was reported that only two out of 244 cases (0.8%) showed allergy to corn, carrots, grapes, and mussels.

National Health and Nutrition Examination Survey (NHANES) conducted a periodic survey on the prevalence of different food allergies among 20,686 US children and adolescents. The prevalence of corn allergy obtained in the study was 0.28% among children and 0.22% among adults.

An extensive study was conducted on 145 children with atopic dermatitis (AD), who showed positive SPT result to one or more cereal grains, such as corn, wheat, rye, barley, oats, rice. Among 145 patients subjected to food challenges, 21.3% showed positive reactions (31 out of 145 patients), while 25 of these 31 patients (80%) reported positive challenge responses to single grain. Further, it was found that 12% of patients showed a positive response to only corn (3 out of 25 patients).

In a study conducted on 689 allergic patients in Pakistan (Rawalpindi and Islamabad), 16% of patients reported sensitization to corn, based on SPT (110 out of 689 patients).

Risk factors

Respiratory allergic symptoms, such as acute rhinitis and asthma may occur due to occupational exposure to corn flour, in millers, food workers, and homemakers. Moreover, the major maize allergen, 9 kDa LTP, shows a high level of sequence homology with the LTP of rice, which attributes to a higher risk of co-sensitization between the individuals with maize allergy and rice-induced allergy.

Route Of Exposure

Main

Oral ingestion of maize can lead to IgE-mediated allergic reactions, like oral food allergy and even severe reactions like anaphylaxis.

Secondary

Inhalation or handling of maize flour at work can lead to occupational asthma and rhino-conjunctivitis. Moreover, skin contact with maize can provoke allergic reactions, such as AR and contact urticaria.

Clinical Relevance

Oral allergy symptoms and Anaphylaxis

Food allergy symptoms, such as OAS, urticaria, and anaphylaxis, following consumption of maize, have been reported in some countries, especially in Italy, where polenta (cooked maize flour) is popularly consumed.

In a study conducted on 22 patients (age range: 12 to 50 years), 100% of patients suffered from severe systemic reactions, such as anaphylaxis, after consuming maize in different forms (e.g. popcorn, polenta, crisps, etc.). Nine of these 22 patients (41%) presented with OAS (including 5 with localized OAS), before the onset of systemic symptoms, such as laryngeal edema anaphylaxis, and shock. Further, 3 of the 22 patients (13.6%) presented with food-dependent, exercise-induced anaphylaxis (FDEIA).

In a study conducted on 661 Mexican patients with a history of allergy, 56 (8.4%) patients reported maize allergy. Among them, two patients reported to develop urticaria or even angioedema, upon consumption of maize, in forms such as corn-on-the-cob or popcorn.

A double-blind, placebo-controlled food challenge (DBPCFC) was conducted on 16 corn-allergic patients with positive SPT. It was reported that 37.5% of patients (6 out of 16) showed symptoms of itching and urticaria, upon ingestion of cooked corn.

In another DBPCFC study involving 27 suspected maize-allergic patients, OAS was found to be the most frequent symptom observed in 53.8% of patients (7 out of 13) with positive findings to maize. Other symptoms included generalized and persistent erythema (23%; 3 out of 13), abdominal pain or diarrhea (23%; 3 out of 13), generalized pruritus (15.3%; 2 out of 13), angioedema (15.3%; 2 out of 13), and one case (7.6%; 1 out of 13) each of generalized urticaria, persistent cough, nausea or vomiting, and eczema flare.

A study was conducted on 82 Italian patients (age range: 9 to 47 years) with a history of at least one episode of FDEIA linked with physical exercise (done within 4 hours after a meal), to assess the actual allergenic molecules responsible for FDEIA. Maize and peanut were found to be the most common positive foods (n= 70), followed by apple, peach, onion, lentil and fennel.

Two case studies have been identified that reported allergic reactions, such as OAS and anaphylaxis, after ingestion of corn, in different forms. The first case was of a 44-year-old woman, who had a history of anaphylactic reaction (tingling sensation) post ingestion of corn (licking the cornmeal from fingers). It was further reported that, on subsequent exposure to corn, the women developed urticaria, pruritus, diarrhea, vomiting, and breathlessness. In a two phase, DBPCFC conducted with corn flour, the woman presented with anaphylaxis. In the second case, studied on a 34-year-old male, ingestion of baby cereal formula, containing nongluten rice and corn, led to severe reactions, such as sudden respiratory and gastrointestinal (GI) symptoms, reduced consciousness, and paleness. The patient’s history showed that, although he well-tolerated bread and other cereal-derived products, he experienced OAS after taking beer and mustard. Further, it was reported that the patient suffered from occupational asthma, after coming in contact with the rye flour, that was added in the wood boards. The SPT was found to be positive for mustard and several other food allergens. According to DBPCFC conducted with cereal baby food in lime juice, positive reactions, such as pharyngeal itching, cough, and GI symptoms were noted.

Allergic rhinitis, rhino-conjunctivitis, and asthma

Respiratory symptoms, such as allergic rhinitis (AR), rhino-conjunctivitis and asthma/occupational asthma have commonly been reported in individuals, who either ingest or come in contact with maize.

In a study conducted on 661 adult patients in Mexico, 8.4% (n=56) of patients presented with a history of maize allergy. Of these 56 individuals, 89.3% (n=50) individuals, who worked with the cereal, experienced AR and/or asthma, after coming in contact with maize. The rest of the 10.7% (n=6) individuals, who reported no history of working with the cereal, presented with asthma and/or AR, upon ingestion of maize (popcorn or corn-on-the- cob).

In a case study of a 40-year-old non-smoker male, occupational exposure to maize while working on a maize extrusion process led to rhino-conjunctivitis and asthma. These allergic reactions lasted for around 6 months while at work, however the symptoms reduced, when off-work. The SPT results was found to be positive for maize flour, wheat flour, and beer. Moreover, the specific IgE determinations showed positive result for maize flour extracts, however it was reported negative for other cereal flours.

Two more case studies documented about corn-induced occupational asthma. The first case was of a 24-year-old, non-smoker male who reported a history of rhinorrhea, sneezing, and chest tightness, as a result of handling corn dust for making stock feed. The male informed that he did not experience these symptoms in the past, however, his symptoms got worsened on handling the corn dust. The bronchoprovocation test and Enzyme Linked Immunosorbent Assay (ELISA) suggested that corn dust can lead to IgE-mediated bronchoconstriction in an exposed individual. In the second case,a 19-year-old girl, with no prior history of seasonal or perennial allergies, developed erythematous itching rash, on both hands as well as face, along with dyspnea. She worked in a pharmaceutical company that manufactured tablets. Every day, after about 2 hours of working on tablets (containing maize starch, microcrystalline cellulose and lactose), she developed allergic symptoms. A strong positive reaction (including sneezing, conjunctival reaction, and pruritus in nose and eye) was elicited within 6 minutes of nasal provocation test with maize bran. The study revealed that the patient developed allergy to maize through inhalation and cutaneous contact to the allergen, while at work.

Maize has also been reported as a causative agent in baker’s asthma. These patients, however, have never reported problems after consumption of this cereal grain

Atopic dermatitis

A 33-year-old nurse with a history of asthma and seasonal AR, presented with hand dermatitis, since the time she started nursing. She complained of having intermittent, itchy blisters on her hands, which improved when she was off work. She also experienced ‘itchy throat’, when she ate bananas, kiwi, avocado, and cantaloupe. The SPT showed positive response for corn, and the nurse was advised to avoid wearing gloves that contain corn-starch powder. It was reported that her symptoms started improving, after she used a non-cornstarch-based gloves.

Prevention And Therapy

Prevention strategies

Avoidance

Corn allergy can be managed by strictly avoiding the corn ingredients. Moreover, corn is considered as one of the most essential, genetically modified (GM) crops, and hence an appropriate identification of each GM ingredient is needed for GM food labeling as well as monitoring. Furthermore, proper information about the presence of corn in processed foods should be given, so as to make people aware of quality, safety, and food accuracy.

Cross-Reactivity

Maize has been found to cross-react with other cereals, such as rice, wheat, barley, etc. Lipid transfer protein is considered as a major allergen of maize, that has shown sequence identity with LTP of rice, wheat, and barley. 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 has been found to have 79% identity and 92% similarity with rice LTP. The identity was found lower in case of wheat (59%-79%) and barley (57%-78%). Furthermore, the inhibitory potential of wheat, barley, and grass pollen extracts showed complete inhibition to 16 kDa protein and other higher molecular weight protein bands, from the sera of patients allergic to maize. It was demonstrated that these three cereals showed cross-reactivity with trypsin/activated Hageman factor (XIIA) inhibitor and other proteins of maize.

Additionally, maize LTP has shown sequence similarity with certain fruits. In a case report of a 19-year-old boy, peach LTP was found to be cross-reactive to corn, along with rice, apple, walnut, hazelnut, and peanut, with the frequency of cross reactivity being 94%, 93%, 97%, 20%, 66%, and 91% respectively. A study found LTP from maize showing 63% sequence similarity with LTP of apricot (Mr 9000). Another study reported high level of amino acid sequence identity (59.3%) between LTP from cherry and LTP from maize. Cowpea also showed high sequence homology with the LTP from maize (72%).

Besides LTP, another maize allergen also showed sequence homology with cereal allergen, such as wheat allergen. In a study that assessed sequence identity between two maize thioredoxins (Zea m 25 and ZmTRXh2) and wheat thioredoxin allergen (Tri a 25), the analysis showed 74% of sequence identity between Zea m 25 and Tri a 25 allergen. Furthermore, low sequence identity was reported between ZmTRXh2 and Tri a 25 (46%).

The pollen of Platanus aceriflora (P. aceriflora) showed cross-reactivity with certain plant derived foods. Enzyme allergosorbent (EAST) inhibition assays showed 90% inhibition when extracts of corn apple, chickpea, lettuce, peanut or hazelnut were used in solid phase and the inhibitor phase contained P. aceriflora pollen extract.

Furthermore, Zea m 8 (allergenic chitinase from maize) and grape (Class IV chitinase), show about 40-50% of sequence similarity with the class I chitinase, present in foods of plant origin (papaya, avocado, chestnut, kiwi, banana etc.). This may account for high rate of cross-reactivity between maize and grape chitinase allergens, resulting in clinical reactions in patients sensitive to maize and grape. According to a study conducted in almond-allergic patients, high level of co-sensitization or cross-reactivity was reported between 50 kDa γ-zein (maize) and almond major protein (AMP), whereas, low cross-reactivity was found between 27 kDa γ-zein (maize) and AMP.