A. Case study
An 11-month-old boy was seen for eczema. Since birth he had been given cow's milk-based formula, until he developed eczema at the age of 3 months. He was put onto a soya formula, and his symptoms resolved. The mother began to give him solid foods at age 5 months. She started him on rice and maize cereals and gradually introduced a variety of fruits and vegetables, as well as rice, potato, chicken and beef. At the age of 9 months, he developed severe eczema again. He was drinking about 800ml of soya formula per day at this stage. The general practitioner requested some blood tests, with the following results (in KU/L):

Total IgE: 300 (High)
Soya: 9.47 (Class 3)
Rice: 0.39 (Class 1)
Maize: <0.35 (Class 0)
Potato: <0.35 (Class 0)
Phadiatop: 0.46 (Class 1)

(This last is a screening test that measures the level of IgE to a combination of the common inhalant allergens. A positive result indicates that the subject is sensitized to 1 or more of these inhalants, but does not indicate which. From there one can test for specific allergens.)

The mother was asked to stop feeding with the soya formula, but the symptoms improved only slightly. (She was, importantly, sent to a dietitian to ensure that the child's diet would be nutritionally adequate.) The mother returned to the doctor when the child was 11 months old. He still had chronic eczema, but he also seemed to have severe "flare-ups" now and again. The mother could not establish what the cause was.

THOUGHT PROCESS:
Apart from reacting to something in his everyday environment or diet that produced constant eczema, the child must have been exposed to something causing the "flare-ups." What were the possibilities?
a. He was reacting to something (environmental or dietary) that he was exposed to only occasionally.
b. He was sometimes being exposed to a higher dose of the allergen (environmental or dietary) that was causing his constant eczema.
c. He was reacting to varying "hidden" sources of cow's milk and/or soya in his diet.
d. In a patient with eczema, one should consider stress and other non-food factors (e.g., exposure to house dust mite, pets, smoke, perfumes and fabric softeners) that could aggravate eczema.

DISCUSSION:
a-b. These will be discussed below.
c. A detailed dietary history was taken to determine whether hidden allergens were present. But because the mother was very careful, she gave only plain food (no processed foods or added flavorants). No hidden allergens could be identified.
d. Even though the serum-specific IgE to Phadiatop was quite low, the child could have been reacting to an environmental allergen not tested for in the Phadiatop mix. No association could, however, be drawn between any environmental allergen and his symptoms. The boy was not exposed to smoke, perfumes or fabric softeners, and stress was not a factor.

THOUGHT PROCESS:
What could be the next step?
a. Do more serum-specific IgE tests to other foods.
b. Ask the mother to keep a food-symptom diary.
c. Do an elimination diet and oral challenges.

DISCUSSION:
a. There was no clear indication of which food could be a cause of the reaction, and it would therefore have been difficult to suggest which foods to test for. But testing for the most common allergens can be helpful in such circumstances, as the chance of a child reacting to one of these is better than to uncommon foods. The tests were done and were negative.
b. The purpose of keeping a diary is to detect a pattern in what is eaten and the development of symptoms. Because the child experienced constant eczema, the diary would probably not have assisted in identifying the general cause; but it was potentially helpful for identifying the allergen causing the "flare-ups." But it was decided to do an elimination diet with challenges, which could be useful in both areas.
c. Because there was no clear indication of which food could be the cause of the reaction, an elimination diet was singled out as an approach. The mother was asked to allow only rice and rice products, maize and maize products, potato (as the IgE levels of all of these were 0 or low), banana, pear and chicken (as these are low-allergenic foods) in her son's diet. The plan was to keep him on this diet until his symptoms disappeared, and then challenge him with the foods that were excluded, to see which provoked a reaction. After 1.5 weeks, the symptoms had not improved. The mother did, however, pick up that her son's symptoms got worse ("flared up") after he ate sweet corn. She was asked to exclude all sources of maize, including the maize cereal, while still following the rest of the elimination diet. This was done, and his symptoms improved dramatically. Upon a rechallenge (with a double-blind method), the symptoms flared again. This supports a recent finding that skin-specific IgE and serum-specific IgE to maize have little, if any, clinical significance for most patients studied (discussed below).

The other foods were put back into his diet without adverse effects.

TIP for Allergy Advisor users: Allergy Advisor contains a guide to elimination diets under the "Assessment" bar, under "Assessment Forms & Guides". It contains examples of few foods diets for different age groups as well as a step-by-step guide to oral challenges. The "Challenge Vehicles" provides ideas for vehicles that can be used to disguise foods during challenges.

B. More information:

Corn and maize are terms used for the same plant, with the Latin name Zea mays. For the purpose of this review, the term "maize" will be used. Maize allergy can occur to the ingestion of maize or maize derivatives, or to the inhalation of maize flour or maize pollen. A true allergy to maize has been said to be uncommon,1 but recent studies have shown that diagnostic methods used in the past may not have been accurate, so that maize allergy was underdiagnosed. Also, the prevalence of this allergy may be higher in countries such as Africa and Central and South America, where maize is a staple cereal.2,3,4,5,6,7,8

An allergy to maize may result in mild to severe reactions. Although anaphylactic reactions to maize are uncommon, they can occur.^9,10 An anaphylactic reaction has even occurred during double-blind, placebo-controlled maize challenges.¹¹ One of the allergens in maize, Lipid Transfer Protein (LTP, a panallergen), is reported to be responsible for this severe form of allergic reaction.¹² Food-dependant exercise-induced anaphylaxis to maize has also been described.¹³ In a study reporting on 7 cases of food-dependant exercise-induced anaphylaxis, responsible foods were wheat (2 cases), maize, barley, shrimp, apple, paprika and mustard.¹⁴

Anaphylaxis to maize starch glove powder has been described in 2 nurses. The authors suspected that cornstarch was the responsible allergen.¹⁵ Other adverse reactions that have resulted from cornstarch surgical glove powder include contact urticaria, oculorhinitis, angioedema, asthma and intermittent episodes of dyspnoea.^16,17,18 Cornstarch powder in medical gloves also plays an important role in latex-induced hypersensitivity, as an allergen carrier by the inhalation route, by skin contact or by direct contact with mucous membranes, so that the powder can enhance latex-induced hypersensitivity.¹⁹

Allergic reactions, including dermatitis, have been described with maize by-products, corn syrup, corn dextrimaltose, corn invert sugar, corn isomerised dextrose and corn D-psicose.^20,21,22 This demonstrates that one or more allergens remain in maize throughout processing and are still present in maize derivatives. Intravenous administration of a maize-derived dextrose solution has resulted in anaphylaxis. Symptoms included oro-facial swelling, difficulty in breathing, hypotension, cardiac arrhythmia, voice hoarseness, total body warmth and flushing. These reactions occurred within 8 minutes of initiation of a 5% dextrose Lactated Ringer's solution.²³

There has been a report of hypersensitivity reactions to the ceremonial use of oral maize pollen among Native Americans. The symptoms included various combinations of oral and ear itching, sneezing, cough, and wheezing.²⁴

Other allergic symptoms from oral ingestion that have been reported include abdominal pain, nausea, vomiting, atopic dermatitis,³ oral allergy syndrome⁴ and recurrent serous otitis media.²⁵ Maize has also been reported to cause migraine.²⁶

In the occupational setting
Occupational exposure to maize, maize flour or maize dust may result in occupational asthma or rhinitis, in particular in bakery workers, mill workers and those working in the animal feed industry.^{3,27,28,29,30} As discussed above, contact urticaria and anaphylactic reactions can occur from cornstarch surgical glove powder.¹⁵ Whether atopy may play a role in the development of grain dust-induced airway disease has not been fully evaluated yet.²⁷ In a group of 35 men working in an animal food processing plant, the most frequent positive skin prick reactions occurred to the following occupational allergens: fish flour (82.9%), carotene (77.1%), maize (65.7%), four-leaf clover (62.9%), sunflower (54.3%), chicken meat (31.4%), soy (28.6%), and yeast (22.7%).²⁹

Allergens that have been identified
Many allergens have been isolated from maize, but the majority of them have not been clinically evaluated for their allergenic potential. The most researched allergen is Zea m 14, a LTP, that was isolated from maize flour.^{2,9,12,31,32,33} It is a major maize allergen.⁹ Maize LTP maintains its IgE-binding capacity after heat treatment, which makes it the most likely allergen responsible for severe anaphylactic reactions to both raw and cooked maize.³⁴

Other allergens present in maize (but with allergenic potential not yet evaluated) are the following:

The prolamin protein (the protein found in cereals that causes the same intestinal damage in Celiac Disease that gliadin, found in wheat, causes) in maize is called zein. Prolamin contributes 55% to the grain's protein content, but the ingestion of maize is considered safe in Celiac Disease.3,38 There are two basic types of maize, namely sweet corn and field corn. Sweet corn is distinguished from field corn by the high sugar content of the kernels at the early "dough" stage and by wrinkled, translucent kernels when dry.However, cultivars of maize may also be divided into six types: popcorn (everta), flint corn (indurata), dent corn (indenta), flour corn (amylacea), sweet corn (saccharata) and pod corn (tunicata). Even though they may look different, cultivated hybrids of maize are from the same species and there are no differences in their protein profile and allergenic properties.34

Potential Cross-reactivity
Individuals with allergy to maize pollen may also demonstrate allergy to maize seed, as both contain similar allergens.^32,39 In a group of 56 children with hay fever as a result of maize pollen, more than half were sensitized to maize seed allergens.³⁹

Maize belongs to the family Poaceae (Gramineae); other members include sorghum, oats, rice, barley, rye, wheat and various grasses. One would expect there to be an extensive cross-reactivity among these individual species of the genus, but there appears to be a low degree of cross-reactivity between maize and other cereals.40 However, by using RAST inhibition tests, the degree of cross-reactivity between cereal grains was shown to closely parallel their taxonomic relationship and appeared to be in the following order of decreasing closeness: wheat, triticale, rye, barley, oat, rice and corn.41 Another study showed that there were significant close correlations between every combination of RAST values for rice, wheat, corn, Japanese millet and Italian millet.42

Also, in vitro cross-reactivity among the IgE binding proteins of maize, rice, soybean and peanut has been demonstrated,⁴³ and the maize inhibitor of trypsin cross-reacts with grass, wheat, barley, and rice trypsin inhibitors.⁹ The relevance of these cross-reactions (above) still needs to be established from a clinical perspective. Cross-reactions in foods (including maize) containing LTP have been reported to be more clinically relevant. A high degree of cross-reactivity has been demonstrated among the LTP's of maize, peach, apple, walnut, hazelnut, peanut, rice, and apricot.^9,44,45 Not all LTP's from plants are, however, closely related.⁴⁶ For example, maize LTP was shown to cross-react completely with rice and peach LTP but not with wheat or barley LTP. Overall, there is a low cross-reactivity between maize LTP and the LTP's of other cereals.⁹

There appears to be an unidentified but common allergen in birch pollen and apple, pear, carrot, banana and other exotic fruits. The clinical relevance, again, has not been established.³⁶

What diagnostic methods can be used?
Traditionally, skin-specific and serum-specific IgE tests to maize are used to diagnose maize allergy. It is generally assumed that a negative result indicates the absence of maize allergy. However, it was recently shown that a negative skin-specific IgE and serum-specific IgE to maize flour had no clinical significance for most of the patients studied, and that food allergy to maize has to be proved by double-blind placebo-controlled food challenge studies.³

Because maize is eaten in various ways (as a vegetable, or as derivatives of maize in the form of corn oil, corn syrup, cornstarch, corn flour, and cornmeal) and the specific allergen profile of various maize derivatives is not known, it may be necessary to challenge each derivative separately. Each derivative may have a different potential for triggering adverse reactions. It is therefore useful to assess a person's tolerance of each component. If some maize derivatives are proven to be safe, it will improve dietary variety, especially in severely allergic individuals.⁴⁷

Management
Maize elimination diets are very difficult to manage because maize and maize products constitute ingredients in a large number of processed food products, especially snack foods.^1,47

Maize is likely to be present in foods containing the following ingredients: corn, cornmeal, cornflakes, cornmeal, corn sweetener, corn syrup solids, corn flour, corn starch, caramel corn, maize, corn alcohol, baking powder, dextrates, dextrins, flavouring (caramel, both natural and artificial), maltodextrins, marshmallow, powdered sugar, hominy, grits, popcorn, vegetable gum, vegetable paste, food starch, modified starch, vegetable starch, vegetable protein and starch. Hydrolysed plant protein (HPP), hydrolysed vegetable protein (HVP) and textured vegetable protein (TVP) may also be made from maize. Even though, as with similar products derived from wheat, it is known that the hydrolysis process breaks down proteins to the point where they are unlikely to be allergenic,^1,47 insufficient knowledge about the allergens in maize makes it impossible to ensure that all allergens will be broken down to the point at which a substance may be freely included in the diet.

In the processing of maize oil, the protein is removed. The oil could therefore be seen as safe for consumption.¹ However, the product may become contaminated with protein from maize during manufacturing. It is probably not necessary to restrict maize oil as an ingredient in foods, as maize protein is an uncommon cause of anaphylaxis and the quantity likely to be present in the oil depends on the processing and might be very small.⁴⁷

In the highly maize-allergic individual, eliminating maize entirely from the diet would require the exclusion of a variety of foods, including non-alcoholic beverages, candy, canned fruits, cereals, cookies, jams, jellies, lunch meats, snack foods, syrups, convenience foods and infant formulas.^1,3,47 Whiskey, beer, and other alcoholic beverages may also have to be excluded, as they may be produced using maize. It has been demonstrated that LTP in barley is one of the main allergens responsible for allergic reactions to beer.⁴⁸

In spite of the wide use of maize in food manufacturing, eliminating maize from one's diet would not normally lead to nutritional deficiencies. Exceptions would occur in countries where maize is a staple food and alternatives are too expensive or not available. Normally, if a person's usual diet contains many maize-containing convenience foods, alternative maize-free products can be suggested.1,47 The following ingredients can be used (probably more commercially than domestically) as alternatives to maize derivatives: Sweeteners: fruit juice, honey, beet sugar, cane sugar and maple syrup; Thickeners: rice starch, potato starch, tapioca and wheat starch; Leavening agents: baking soda and cream of tartar (5 ml or 1 tsp baking powder can be replaced by 1 ml or ¼ tsp bicarbonate of soda and 2 ml or ½ tsp of cream of tartar).1

For more information on this subject and other allergy and intolerance related topics, visit:
http://www.allallergy.net
http://www.allergyadvisor.com
http://users.bigpond.net.au/allergydietitian

D. References
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3. Pasini G, Simonato B, Curioni A, Vincenzi S, Cristaudo A, Santucci B, Peruffo AD, Giannattasio M. IgE-mediated allergy to corn: a 50 kDa protein, belonging to the Reduced Soluble Proteins, is a major allergen. Allergy 2002;57(2):98-106.
4. Enrique E, Cistero-Bahima A, Bartolome B, Alonso R, San Miguel-Moncin MM, Bartra J, Martinez A. Platanus acerifolia pollinosis and food allergy. Allergy 2002;57(4):351-6.
5. Hofman T. Analysis of food allergy incidence in children up to 5 years of age in the Wielikopolska region. [Polish] Pol Merkuriusz Lek 1998;5(30):341-5.
6. Aruin LI, Balabolkin II, Gershman GB, Subbotina OA, Shcherbakov PL, Sofonov AB. Mucous membrane of the jejunum in allergy to cereal protein. [Russian] Arkh Patol 1992;54(6):20-5.
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10. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child 1984;59(10):983-6.
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14. Mathelier-Fusade P, Vermeulen C, Leynadier F. Responsibility of food in exercise-induced anaphylaxis: 7 cases. [French] Ann Dermatol Venereol 2002;129(5 Pt 1):694-7.
15. Seggev JS, Mawhinney TP, Yunginger JW, Braun SR. Anaphylaxis due to cornstarch surgical glove powder. Ann Allergy 1990;65(2):152-5.
16. Crippa M, Pasolini G. Allergic reactions due to glove-lubricant-powder in health-care workers. Int Arch Occup Environ Health 1997;70(6):399-402.
17. Fisher AA. Contact urticaria and anaphylactoid reaction due to corn starch surgical glove powder. Contact Dermatitis 1987;16(4):224-5.
18. Assalve D, Cicioni C, Perno P, Lisi P. Contact urticaria and anaphylactoid reaction from cornstarch surgical glove powder. Contact Dermatitis 1988;19(1):61.
19. Barbara J, Santais MC, Levy DA, Ruff F, Leynadier F. Immunoadjuvant properties of glove cornstarch powder in latex-induced hypersensitivity. Clin Exp Allergy. 2003 Jan;33(1):106-12.
20. Howard W.A, Todd RH, Dalton GL. Studies on the allergenicity of corn products. J Allergy 1959;30:381-386.
21. Nishioka K, Katayama I, Sano S, Numata T, Yamamoto S. Monosaccharides in high fructose corn syrup as an etiologic factor of urticaria. J Derm 1984;11:391-396.
22. Nishioka K, Katayama I, Sano S. Urticaria induced by D-psicose. Lancet 1983;2:1417-1418.
23. Guharoy SR, Barajas M. Probable anaphylactic reaction to corn-derived dextrose solution. Vet Hum Toxicol 1991;33(6):609-10.
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25. Nsouli TM, Nsouli SM, Linde RE, O'Mara F, Scanlon RT, Bellanti JA. Role of food allergy in serous otitis media. Ann Allergy 1994;73(3):215-9.
26. Grant ECG. Food allergies and migraine. Lancet 1979;1:966-968.
27. Park HS, Nahm DH. Identification of IgE-binding components in occupational asthma caused by corn dust. Ann Allergy Asthma Immunol 1997;79(1):75-9.
28. Quirce s, Sastre J. Occupational asthma [Review]. Allergy 1998;53:633-641.
29. Zuskin E, Kanceljak B, Schachter EN, Witek TJ, Maayani S, Goswami S, Marom Z, Rienzi N. Immunological and respiratory changes in animal food processing workers. Am J Ind Med 1992;21(2):177-91.
30. Park HS, Nahm DH, Suh CH, Kwon OY, Kim KS, Lee SW, Chung HK. Occupational asthma and IgE sensitization to grain dust. J Korean Med Sci 1998;13(3):275-80.
31. Pastorello EA, Pompei C, Pravettoni V, Brenna O, Farioli L, Trambaioli C, Conti A. Lipid transfer proteins and 2S albumins as allergens. Allergy 2001;56 Suppl 67:45-7.
32. Heiss S, Flicker S, Hamilton DA, Kraft D, Mascarenhas JP, Valenta R. Expression of Zm13, a pollen specific maize protein, in Escherichia coli reveals IgE-binding capacity and allergenic potential. FEBS Lett 1996;381(3):217-21.
33. Pantoja-Uceda D, Bruix M, Santoro J, Rico M, Monsalve R, Villalba M. Solution structure of allergenic 2 S albumins. Biochem Soc Trans 2001;30(6):919-24.
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35. Huynh QK, Borgmeyer JR, Zobel JF. Isolation and characterization of a 22 kDa protein with antifungal properties from maize seeds. Biochem Biophys Res Commun 1992;182(1):1-5.
36. Vieths S, Frank E, Scheurer S, Meyer HE, Hrazdina G, Haustein D. Characterization of a new IgE-binding 35-kDa protein from birch pollen with cross-reacting homologues in various plant foods. Scand J Immunol 1998;47(3):263-72.
37. Verburg JG, Smith CE, Lisek CA, Huynh QK. Identification of an essential tyrosine residue in the catalytic site of a chitinase isolated from Zea mays that is selectively modified during inactivation with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. J Biol Chem 1992;267(6):3886-93.
38. Pomeranz Y. Wheat: chemistry and technology. American Association of Cereal Chemists, Inc., USA, 1988.
39. Buczylko K, Kowalczyk J, Zeman K, Kardas-Sobantka D, Fiszer A. Allergy to food in children with pollinosis. Rocz Akad Med Bialymst 1995;40(3):568-72.
40. Yman L. Botanical relations and immunological cross-reactions in pollen allergy. 2nd ed. Pharmacia Diagnostics AB. Uppsala. Sweden. 1982.
41. Block G, Tse KS, Kijek K, Chan H, Chan-Yeung M. Baker's asthma. Studies of the cross-antigenicity between different cereal grains. Clin Allergy 1984;14(2):177-85.
42. Urisu A, Yamada K, Masuda S, Komada H, Wada E, Kondo Y, Horiba F, Tsuruta M, Yasaki T, Yamada M, et al. 16-kilodalton rice protein is one of the major allergens in rice grain extract and responsible for cross-allergenicity between cereal grains in the Poaceae family. Int Arch Allergy Appl Immunol 1991;96(3):244-52.
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46. Scheurer S, Pastorello EA, Wangorsch A, Kastner M, Haustein D, Vieths S. Recombinant allergens Pru av 1 and Pru av 4 and a newly identified lipid transfer protein in the in vitro diagnosis of cherry allergy. J Allergy Clin Immunol 2001;107(4):724-31.
47. Joneja JV. Dealing with Food Allergies. A practical guide to detecting culprit foods and eating a healthy, enjoyable diet. Bull Publishing Company, USA, 2003.
48. Garcia-Casado G., Crespo J. F., Rodriguez J., Salcedo G. Identification of beer allergens, protein Z and lipid transfer protein, in patients with positive beer challenges [Poster] 8th International Symposium on Problems of Food Allergy 2001,ch 11-13, Venice.

2. Which of the following is not true regarding anaphylactic reactions to maize?
(a.) They are uncommon.
(b.) They are likely to be caused by Lipid Transfer Protein.
(c.) They can be precipitated by exercise, i.e., as food-dependant exercise-induced reactions.
(d.) They cannot occur due to a double-blind placebo-controlled challenge with maize.

3. Which of the following adverse reactions has been associated with maize starch glove powder?
(a.) Anaphylaxis
(b.) Contact urticaria
(c.) Asthma
(d.) All of the above

4. True or false: Occupational exposure to maize, maize flour, or maize dust may result in occupational asthma or rhinitis, in particular in bakery workers, mill workers and those working in the animal feed industry.
(a.) True
(b.) False

5. True or false: Even though popcorn and sweet corn are from the same species of maize, their protein profile and allergenic properties are different. Their allergenicity in the maize-allergic individual should therefore be evaluated individually.
(a.) True
(b.) False

6. True or false: There is a high degree of clinical cross-reactivity between maize and other cereals.
(a.) True
(b.) False

7. Which is the most accurate method of diagnosis of maize allergy?
(a.) Skin-specific IgE to maize
(b.) Serum-specific IgE to maize
(c.) Double-blind placebo-controlled challenge
(d.) None of the above

8. True or false: Corn oil is likely to be safe for consumption in maize-allergic individuals.
(a.) True
(b.) False