Grain allergy: Clinical features, diagnosis, and management

INTRODUCTION — Grain allergies are common food allergies that are typically seen in individuals with other food allergies. The immunologic responses to grain proteins can be immunoglobulin E (IgE) mediated and/or non-IgE mediated. Food allergy to wheat is best known and manifests with a variety of symptoms and a wide range of clinical syndromes, such as atopic dermatitis exacerbations, exercise-induced anaphylaxis, eosinophilic esophagitis (EoE), baker's asthma, and celiac disease. This topic review highlights wheat and also covers other cereal grains including rye, barley, oat, rice, corn, sorghum, and millet, as well as noncereal grains including quinoa, amaranth, and buckwheat (figure 1).

The epidemiology, clinical features, diagnosis, and management of grain allergy are presented in this topic review. An overview of grains and their classification, as well as the major grain allergens, are discussed in detail separately. (See "Grain allergy: Allergens and grain classification".)

General discussions of food allergy are presented separately in other topic reviews.

Wheat allergy related to occupational exposure is presented separately, as is food-dependent (including wheat) exercise-induced anaphylaxis and celiac disease (gluten-sensitive enteropathy):

●(See "Occupational asthma: Definitions, epidemiology, causes, and risk factors" and "Occupational asthma: Pathogenesis" and "Occupational asthma: Clinical features, evaluation, and diagnosis" and "Occupational asthma: Management, prognosis, and prevention".)

●(See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis" and "Exercise-induced anaphylaxis: Management and prognosis".)

●(See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children" and "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Diagnosis of celiac disease in adults" and "Management of celiac disease in children".)

EPIDEMIOLOGY

General population — Wheat allergy is the most common of the cereal grain allergies. It usually begins in early childhood and is outgrown by adolescence, although some retain it beyond the teenage years [1]. IgE-mediated wheat allergy is reported to affect 0.2 to 1.3 percent of children in Europe [2] and 0.4 percent of children in the United States [3]. Onset of wheat allergy in adulthood is typically not seen unless it is related to an occupational exposure or due to sensitization to omega-5-gliadin (see 'Baker's asthma' below and 'Wheat-dependent exercise-induced anaphylaxis' below). Epidemiologic data for the other grains are sparse.

Referral populations — Wheat allergy was reported in 18 percent of patients seen in a university-based pediatric allergy outpatient clinic focusing on food allergies [4]. It was among the most common reported triggers of anaphylaxis, following cow's milk, peanut, and tree nuts. Thirty-seven percent of children with atopic dermatitis referred to a university-based dermatology clinic had clinically significant IgE-mediated food hypersensitivity; of them, 13 percent had wheat allergy [5]. Other grain allergies are less common. (See "Role of allergy in atopic dermatitis (eczema)".)

Oat sensitization is relatively common in patients with atopic dermatitis, particularly in those with wheat allergy, but clinical allergy is rare. In one series of children with atopic dermatitis, oat sensitization was seen in 19 percent of cases, and, of those, oral food challenge (OFC) was positive in only 16 percent [6]. In another series of patients with atopic dermatitis evaluated in a university-based clinic, oat sensitization was seen in one-half of the cases with confirmed wheat allergy, but clinical oat allergy was confirmed in less than one-third of those [7]. Likewise, corn (maize) allergy was confirmed by OFC in only 5 of 145 children (3 percent) with atopic dermatitis and sensitization to one or more cereal grains (wheat, rice, rye, barley, oat, corn) [8].

CLINICAL FEATURES — Patients with grain allergy present with a wide range of IgE-mediated and non-IgE-mediated clinical syndromes. (See "Grain allergy: Allergens and grain classification", section on 'Grain allergens' and "Clinical manifestations of food allergy: An overview".)

IgE-mediated reactions — IgE-mediated food-triggered reactions generally occur immediately, within minutes to two hours after ingestion. These reactions can present with skin, oropharyngeal, upper and lower respiratory tract, gastrointestinal tract, and/or cardiovascular signs and symptoms. Reactions can vary from mild cutaneous reactions to life-threatening anaphylaxis (table 1). IgE-mediated food allergy is more common in children than adults. Occupational and household exposures involving inhalation of cooking or processing vapors containing grain proteins may cause respiratory symptoms. Casual contact by touching can cause localized urticaria. (See "Clinical manifestations of food allergy: An overview", section on 'IgE-mediated reactions' and "Respiratory manifestations of food allergy".)

Implicated grains — IgE-mediated reactions have been reported to all of the cereal grains (wheat, rye, barley, oat, rice, corn, and millet) except sorghum, as well as the noncereal grains (quinoa, amaranth, and buckwheat). Wheat is the most common grain to trigger these types of reactions, which include food-dependent exercise-induced anaphylaxis and baker's asthma. Rice is an uncommon cause of IgE-mediated allergies, particularly with ingestion, but is a reported cause of occupational allergy with respiratory symptoms developing upon inhalation of raw rice dust or rice vapor when rice is boiled [9]. Oral allergy syndrome (food-pollen syndrome) has not been reported with grains, presumably because they are consumed in cooked forms rather than raw. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis" and "Occupational asthma: Definitions, epidemiology, causes, and risk factors", section on 'High-molecular-weight' and "Respiratory manifestations of food allergy" and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)".)

A study using double-blind, placebo-controlled food challenges (DBPCFCs) confirmed corn allergy, although rare, resulting in various symptoms including anaphylaxis [10]. Anaphylaxis to millet has been reported in sporadic case reports [11]. In addition, millet is a potential inhalant allergen for atopic bird keepers in whom millet may subsequently also elicit food allergy [12,13]. Sensitization but not confirmed clinical allergy to sorghum has been reported [14].

There are case reports of IgE-mediated allergy to the noncereal grains. Several cases of buckwheat allergy have been described, including occupational allergy in patients working in the production of buckwheat-containing foods and food allergies [15,16]. Manifestations include anaphylaxis confirmed by DBPCFCs [17,18]. Anaphylaxis to quinoa has been described in two case reports from France and the United States [19,20]. One single case of food anaphylaxis to amaranth seed has been described [21].

Mixed IgE-mediated and non-IgE-mediated reactions — The mixed reactions may have either humoral and/or cell-mediated mechanisms and may present with acute and/or chronic symptoms. (See "Clinical manifestations of food allergy: An overview", section on 'Mixed IgE- and non-IgE-mediated reactions'.)

Atopic dermatitis (eczema) — Food allergy plays a pathogenic role in a subset of patients, primarily infants and children, with atopic dermatitis. Wheat is the third most common allergy (after hen's egg and cow's milk) reported in infants and young children with moderate-to-severe atopic dermatitis [5]. The role of food allergy in atopic dermatitis is discussed in detail separately. (See "Role of allergy in atopic dermatitis (eczema)".)

Allergic eosinophilic gastrointestinal disorders — Wheat is also among the major allergenic foods, following cow's milk, in allergic eosinophilic esophagitis (EoE), a disorder characterized by eosinophilic inflammation of the esophagus in both children and adults [22-24]. Other grain allergies reported in patients with EoE include corn and rice. Patients with this disorder have symptoms suggestive of gastroesophageal reflux but are unresponsive to conventional reflux therapies. Other presenting symptoms include feeding disorders, vomiting, abdominal pain, dysphagia, and food impaction. Patients with allergic eosinophilic gastroenteritis (eosinophilic gastroenteropathy of the stomach and intestines) may have symptoms of abdominal pain, nausea, vomiting, diarrhea, or weight loss. The role of food allergy in eosinophilic gastroenteritis is less clear than in EoE. These disorders are discussed in greater detail separately. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Allergy testing in eosinophilic esophagitis" and "Dietary management of eosinophilic esophagitis" and "Eosinophilic gastrointestinal diseases".)

Non-IgE-mediated reactions — The non-IgE-mediated reactions usually have a delayed onset beyond two hours of ingestion and typically present with gastrointestinal symptoms. (See "Clinical manifestations of food allergy: An overview", section on 'Non-IgE-mediated reactions'.)

Food protein-induced enterocolitis syndrome — Grains, especially oat and rice, and occasionally wheat, barley, and corn are among the most commonly reported triggers after cow's milk and soy in food protein-induced enterocolitis syndrome (FPIES), typically seen in young children, which can present in one of two ways [25]. The typical presentation is that of severe vomiting and diarrhea within two to four hours after ingestion of the offending allergen, causing profound dehydration, lethargy, and sometimes shock. The acute phase can be the first manifestation of FPIES or can occur when the allergen is removed from the diet and then reintroduced. Chronic exposure to the offending allergen may present with vomiting and diarrhea, failure to thrive, and hypoalbuminemia. FPIES is discussed in greater detail separately. (See "Food protein-induced enterocolitis syndrome (FPIES)".)

Protein-induced proctitis/proctocolitis — Protein-induced proctitis/proctocolitis usually presents by six months of life with bloody-streaked, mucousy, loose stools and occasionally diarrhea in breastfed or standard formula-fed infants who are otherwise well appearing. Cow's milk and soy are the major causative foods, and elimination of milk and soy from maternal diet has resulted in resolution of symptoms in some but not all infants, suggesting a role for other food allergens, although wheat is not among the most commonly implicated foods [26]. (See "Food protein-induced allergic proctocolitis of infancy".)

Food protein-induced enteropathy — Infants with this disorder have malabsorption, failure to thrive, anemia, diarrhea, vomiting, and hypoproteinemia. It is usually caused by cow's milk protein, but rice is one of the reported solid food triggers [27]. Food protein-induced enteropathy is discussed in greater detail separately. (See "Food protein-induced allergic proctocolitis of infancy".)

Celiac disease — Celiac disease (also known as gluten-sensitive enteropathy or nontropical sprue) is an immune-mediated inflammation of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. The grains that contain the triggering proteins are wheat, barley, and rye. Patients usually have gastrointestinal manifestations, which may include diarrhea with bulky, foul-smelling, floating stools and abdominal distension and pain, as well as weight loss from malabsorption. There are also numerous nongastrointestinal manifestations (table 2 and table 3). The diagnosis is made by finding characteristic histologic changes on small intestinal biopsy and symptom resolution on a gluten-free diet. The range of clinical presentations of celiac disease and nonceliac gluten sensitivity are discussed in detail separately. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children" and "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Diagnosis of celiac disease in adults".)

DIAGNOSIS OF WHEAT ALLERGY — A general discussion of the diagnosis of food allergy is presented elsewhere. A summary of this information, with a focus on those aspects that are most relevant to the diagnosis of wheat allergy, is provided below. (See "History and physical examination in the patient with possible food allergy" and "Diagnostic evaluation of IgE-mediated food allergy".)

The diagnosis of grain allergy is based upon the history and laboratory testing when available. The gold standard for diagnosis is a clinician-supervised double-blind, placebo-controlled oral food challenge (DBPCFC), although an open challenge will often suffice. Measurement of grain-specific IgE can aid in the diagnosis of IgE-mediated allergy and may eliminate the need for oral food challenges (OFCs). (See "Oral food challenges for diagnosis and management of food allergies".)

With the exception of in vitro immunoassays for specific IgE, other diagnostic allergy procedures, including skin testing and food challenges, should be performed by allergy specialists with training in the management of serious allergic reactions. (See "Overview of skin testing for IgE-mediated allergic disease" and "Oral food challenges for diagnosis and management of food allergies".)

Component-resolved diagnosis to help determine when sensitization is clinically relevant may become more widely available in the future [8,28-30]. (See "Future diagnostic tools for food allergy", section on 'Component-resolved diagnosis'.)

IgE-mediated presentations — Wheat allergy can present similarly to other food allergies or with the specific presentations of wheat-dependent exercise-induced anaphylaxis (WDEIAn) or baker's asthma.

Classic food allergy — Allergy to ingested wheat most often presents as a typical food allergy. It usually affects young children and is outgrown by adolescence, although some retain it into adulthood. The history of an immediate reaction consisting of typical allergic symptoms, supported by positive tests for specific IgE antibodies, is sufficient to establish a presumptive diagnosis for suspected IgE-mediated reactions. Skin prick tests (SPTs) with a commercial wheat extract and/or in vitro tests for wheat-specific IgE are usually performed initially. Higher concentrations of food-specific IgE and larger skin test wheals generally correlate with an increased likelihood of a reaction upon ingestion, although these findings are based upon a limited number of clinical studies and the positive predictive values for wheat are low. In addition, these values are not predictive of the nature or severity of a reaction. Elimination of wheat, followed by an OFC, can help confirm the diagnosis in unclear cases. (See "History and physical examination in the patient with possible food allergy" and "Diagnostic evaluation of IgE-mediated food allergy" and "Oral food challenges for diagnosis and management of food allergies".)

Both the specific IgE level on blood testing and the skin test wheal size for wheat have poor specificity and sensitivity in predicting OFC outcomes, with most studies showing that even children with high levels of IgE can pass a food challenge to wheat (ie, they are sensitized but not clinically reactive) [31-35]. The low positive predictive value of serum-specific IgE to wheat is mainly due to crossreactivity with grass pollen and to the incomplete representation of wheat proteins in the available diagnostic tests, which do not include all the allergens derived from the three wheat protein fractions with different solubility [36].

Wheat-dependent exercise-induced anaphylaxis — WDEIAn is a rare form of wheat allergy that is most often caused by sensitization to omega-5-gliadin, and "omega-5 gliadin allergy" has been proposed as a more precise term [37]. This type of wheat allergy usually presents in adolescents or adults with severe reactions and anaphylaxis. Reactions occur unpredictably with some but not all wheat ingestions, in part because most patients have one or more cofactors that must be present for a reaction to occur. Exercise or physical exertion is the most common, although concomitant ingestion of alcohol or nonsteroidal antiinflammatory drugs (NSAIDs) is also typical. In some, reactions can be elicited at rest, without cofactors [38]. Omega-5 gliadin sensitization is best demonstrated by immunoassay for IgE specific to the allergen, which is commercially available but is a specialty test [39]. Standard IgE immunoassays for wheat or gluten and skin testing with commercial wheat extracts are less sensitive. WDEIAn is discussed in detail separately. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis", section on 'Wheat-dependent EIA'.)

Baker's asthma — Baker's asthma/rhinitis describes respiratory and naso-ocular reactions to inhaled wheat (or rye) flour caused by sensitization to several different wheat allergens [40]. It is a common cause of occupational rhinitis and asthma. Patients with baker's asthma often tolerate wheat ingestion, which may delay recognition. The gold standard for diagnosis is an inhalational challenge with wheat and rye flours, but this may be difficult in nonspecialty centers or dangerous in patients with severe bronchospasm. In such situations, the combination of serum-specific IgE to wheat and rye and skin testing with whole wheat and rye flour extracts is recommended instead [41,42]. The diagnosis of occupational asthma is discussed more generally elsewhere. (See "Respiratory manifestations of food allergy", section on 'Baker's asthma' and "Occupational asthma: Clinical features, evaluation, and diagnosis".)

Testing for other grains — Patients with wheat are typically tested for sensitization to other grains. We usually test rye, barley, oat, corn, and rice, as well as any other grains the patient is interested in eating. However, there is crossreactivity between grains at the test level that often does not correlate with clinical reactivity, similar to what is seen with other related foods (eg, peanut and other legumes such as soy) [7]. OFCs may need to be performed to other grains to which the patient is sensitized to confirm that there is clinical reactivity. Concomitant clinical reactivity to wheat, rye, and barley occurs more frequently than to oat, corn, and rice. In one series, only 21 percent of patients with a positive SPT to one or more cereals had symptomatic sensitization to cereals, as demonstrated by specific food challenge [8]. Another study assessing crossreactivity between wheat, barley, rye, oat, rice, and corn found a strong correlation between wheat and barley-specific IgE concentrations [43]. Over half of patients with wheat allergy in this study had a positive feeding test to barley, but corn and rice challenges were negative. Component-resolved diagnosis may help determine which "positive" tests to other grains are clinically relevant. As an example, positive tests to certain allergens may help distinguish between baker's asthma, wheat-induced food allergy, and grass pollen allergy [8]. (See "Food allergens: Clinical aspects of cross-reactivity", section on 'Grains' and "Grain allergy: Allergens and grain classification", section on 'Allergenic similarities between cereal grains' and "Future diagnostic tools for food allergy", section on 'Component-resolved diagnosis'.)

Non-IgE mediated — IgE tests are expected to be negative if the symptoms do not suggest an IgE-mediated reaction, such as delayed gastrointestinal reactions and some cases of atopic dermatitis. Atopy patch testing may provide additional information in cases of atopic dermatitis [44]. However, there are no standardized reagents, application methods, or guidelines for interpretation for atopy patch testing. Thus, this type of testing cannot be recommended outside of research settings. This method is discussed in greater detail separately, as is diagnosis of wheat allergy in these disorders. (See "Future diagnostic tools for food allergy", section on 'Atopy patch testing' and "Role of allergy in atopic dermatitis (eczema)" and "Allergy testing in eosinophilic esophagitis" and "Food protein-induced enterocolitis syndrome (FPIES)" and "Food protein-induced allergic proctocolitis of infancy".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of wheat allergy includes other food allergies, especially to cow's milk and hen's egg, since these proteins are commonly present in the same foods (eg, pancakes, cakes, cookies, pasta dishes). Other disorders to consider in the differential depend upon age of the patient and the clinical presentation (eg, acute urticaria or anaphylaxis versus chronic gastrointestinal symptoms) and include idiopathic urticaria/anaphylaxis; gastroesophageal reflux disease (GERD); lactose intolerance; toddler's diarrhea; wheat-dependent, exercise-induced anaphylaxis (WDEIAn); celiac disease; irritable bowel syndrome (IBS); and inflammatory bowel disease (IBD). Most of them can be differentiated from wheat allergy based upon clinical history and, when necessary, selective testing. (See "Milk allergy: Clinical features and diagnosis" and "Egg allergy: Clinical features and diagnosis".)

Idiopathic urticaria/anaphylaxis — Idiopathic urticaria and anaphylaxis are diagnoses of exclusion. The diagnosis of idiopathic anaphylaxis is made when a patient has signs and symptoms consistent with anaphylaxis (table 1) but no specific trigger (table 4) can be identified and other diseases have been ruled out (algorithm 1). Acute new-onset urticaria is most often caused by infections, reactions to medications, or food allergy, whereas most cases of chronic urticaria are idiopathic. (see "Anaphylaxis: Confirming the diagnosis and determining the cause(s)" and "Idiopathic anaphylaxis" and "New-onset urticaria" and "Chronic spontaneous urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history")

Gastroesopheal reflux disease — The typical symptoms of GERD include heartburn, regurgitation, and dysphagia. Patients with heartburn as the primary manifestation are typically diagnosed based upon history and are treated empirically, whereas those with regurgitation and/or dysphagia may require additional diagnostic evaluation to rule out other disorders. GERD is common in early infancy but is unlikely to be caused by a grain allergy. The diagnosis of eosinophilic esophagitis (EoE), which can be triggered by grain allergy, should be considered in children and adults with GERD unresponsive to usual therapy. (See "Gastroesophageal reflux in infants" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents" and "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and 'Allergic eosinophilic gastrointestinal disorders' above.)

Lactose intolerance — Lactose intolerance is characterized by abdominal pain, bloating, flatulence, diarrhea (bulky, frothy, and watery stools), and sometimes vomiting, particularly in adolescents, following ingestion of lactose. It can be differentiated from suspected wheat allergy by the presence of characteristic symptoms after dairy ingestion in the absence of concomitant wheat ingestion, in addition to testing for lactose malabsorption, when indicated. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)

Functional diarrhea — Functional diarrhea, also called toddler's diarrhea, is defined as the painless passage of three or more large, unformed stools during waking hours for four or more weeks, with onset in infancy or the preschool years, and without failure to thrive or a specific definable cause. Stools typically become progressively looser as the day progresses. (See "Overview of the causes of chronic diarrhea in children in resource-abundant settings", section on 'Functional diarrhea in young children'.)

Irritable bowel syndrome — Patients with IBS usually present with chronic abdominal pain and altered bowel habits. Some patients also suffer from upper gastrointestinal symptoms such as GERD, bloating and gas, and extraintestinal symptoms. Patients may benefit from exclusion of gas-producing foods such as bagels and wheat germ or a diet low in fermentable sugars (eg, wheat and barley, which are high in oligosaccharides). It is less clear whether a gluten-free diet is effective in decreasing symptoms. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults" and "Treatment of irritable bowel syndrome in adults".)

Inflammatory bowel disease — IBD is comprised of two major disorders, ulcerative colitis (UC) and Crohn disease (CD). Gastrointestinal manifestations include loose stools or bloody diarrhea and abdominal pain/tenderness. Patients may also have weight loss/poor growth and/or extraintestinal findings, such as oral ulcerations, clubbing, rash, uveitis, and arthritis. Some patients with IBD have concomitant features of IBS. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults" and "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

NATURAL COURSE — Wheat allergy has a good prognosis and oftentimes is outgrown by adulthood [1]. In the general population, wheat allergy resolves in most patients by five years of age. However, tolerance appears to develop more slowly in highly atopic populations, with most cases resolving by adolescence, similar to that seen with cow's milk and hen's egg allergies. Food allergies appear to be longer lasting in eosinophilic esophagitis (EoE). Most other grain allergies appear to have a similar natural course to wheat, although data are limited. Food allergies that develop in later childhood to adulthood are unlikely to resolve. The natural history of wheat allergy is reviewed in greater detail separately. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Wheat allergy'.)

MANAGEMENT — The management of grain allergy does not differ from that of other food allergies. It requires instructions on avoidance and treatment of reactions in the event of accidental exposure. It includes education about grain alternatives. It also includes monitoring for nutritional issues and for the resolution of the allergy. Preliminary data on specific oral tolerance induction to wheat through oral desensitization protocols have shown some promise in children, but it is still considered an experimental therapy [45]. (See "Management of food allergy: Avoidance" and "Anaphylaxis: Emergency treatment" and "Management of food allergy: Nutritional issues" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

The management of food allergy in the specific settings of schools and camps is discussed in detail separately. (See "Food allergy in schools and camps".)

Dietary recommendations

Avoidance — The most straightforward approach in managing any food allergy is complete avoidance of the culprit food. However, eliminating a dietary staple such as wheat from the diet can be difficult and can pose nutritional as well as quality-of-life concerns. Avoidance of other grains may have less of a nutritional impact, depending upon dietary patterns, but can also be challenging since there is not mandatory labeling for grains other than wheat in countries that have enacted food allergen labeling laws. (See "Management of food allergy: Avoidance" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Role of avoidance' and "Management of food allergy: Nutritional issues" and "Food allergy: Impact on health-related quality of life".)

Elimination of wheat includes many processed and manufactured products (Food Allergy Research and Education [FARE]). Wheat is also commonly used as a minor ingredient in other commercial food products. Additionally, it is found in cosmetics and craft items, such as modeling dough. Counseling about avoidance should include discussions about cross-contact and hidden allergens, reading food labels, and eating at restaurants. Food allergen avoidance is discussed in greater detail separately. (See "Management of food allergy: Avoidance".)

Alternatives — Wheat contributes carbohydrates, many micronutrients, and fiber. It is a major constituent of a developing child's diet in many countries, and alternative sources with similar nutrients should be incorporated when avoidance is necessary (table 5). Many alternative flours are available to patients with wheat allergy, including cereal grains, such as oat, corn, rice, millet, and sorghum, and noncereal grains, such as buckwheat, quinoa, and amaranth. These can be used after tolerance has been assessed. In addition, there are a wide variety of products made from these flours. (See "Management of food allergy: Nutritional issues", section on 'Wheat allergy'.)

Management of reactions

Acute IgE-mediated reactions — Identification of individuals with IgE-mediated wheat allergy is important because these patients are at risk for severe reactions. Wheat is one of the major food allergen sources reported in food-induced anaphylaxis [46]. Some patients may react to a relatively low dose of antigen [31,32,47].

As in other forms of food allergy, the severity of symptoms in a given individual with wheat allergy may vary considerably between reactions, and the severity of an initial reaction does not predict the patient's subsequent risk. Thus, we suggest that epinephrine autoinjectors be prescribed for all patients with IgE-mediated reactions to wheat, regardless of the severity of their prior reactions, because wheat allergy is unpredictable. In addition, the patient should have a written anaphylaxis emergency action plan. These measures are discussed in detail separately. (See "Anaphylaxis: Emergency treatment".)

Delayed gastrointestinal reactions — The management of patients with mixed and non-IgE-mediated reactions, such as food protein-induced enterocolitis syndrome (FPIES) and eosinophilic esophagitis (EoE), is presented in the specific topic reviews. (See "Food protein-induced enterocolitis syndrome (FPIES)" and "Food protein-induced allergic proctocolitis of infancy" and "Treatment of eosinophilic esophagitis (EoE)" and "Dietary management of eosinophilic esophagitis".)

Monitoring for resolution — Children with grain allergy should be monitored for resolution of the allergy since most will outgrow the allergy in childhood. One exception is that food allergies appear to be longer lasting in EoE. The steps to take to determine if an allergy has resolved are covered in detail separately. (See 'Natural course' above and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

The wheat-specific IgE level or skin prick test (SPT) size that is predictive of clinical reactivity has not been determined, due to poor performance characteristics of the IgE assay and SPT extract for this allergen [32,33]. Proposed challenge decision points range from 20 to 100 kUA/L [34,35]. In one survey, 60 percent of patients with a wheat IgE level <20 kUA/L passed their challenges, and 50 percent of those with a wheat IgE level of <50 kUA/L passed [1]. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Wheat allergy'.)

As such, we typically advise that patients with wheat allergy or sensitization undergo a wheat challenge when wheat-specific IgE is <20 to 50 kU/L. Of note, there are cross-reactive proteins between grass pollen and wheat that can influence IgE tests, but only to a modest degree [48,49].

An alternative approach by another center is to perform serial oral challenges to wheat at least every two years, regardless of specific IgE level, in the absence of an interval history of symptoms triggered by an exposure [1]. Using these general criteria, they have an approximately 40 percent success rate for wheat challenge. Additional variables to take into consideration before proceeding with the challenge include the wheat-specific IgE level and how it compares with the level at the time of the last challenge or reaction due to accidental exposure; the severity of prior reactions and how recent those reactions were; the result of the last challenge (eg, did the reaction occur at the beginning or near the end of the challenge, and what was the severity of the reaction?); and the age of the child (eg, resolution may occur at later ages but is more likely to occur in a two-year time span in a younger child).

Management of younger siblings — Parents often inquire about what measures to take to prevent food allergy in future offspring (eg, maternal avoidance during pregnancy and lactation). Avoidance of wheat or other grains is not recommended for pregnant or nursing mothers, because it has not been shown to prevent food allergies and because grains are an important component of most patients' diets. Delayed introduction of wheat-containing products beyond four to six months of age in asymptomatic infants is generally not recommended. These issues are discussed in greater detail separately. (See "Pathogenesis of food allergy", section on 'Genetics' and "The impact of breastfeeding on the development of allergic disease" and "Primary prevention of allergic disease: Maternal diet in pregnancy and lactation" and "Introducing highly allergenic foods to infants and children", section on 'Introduction in higher-risk populations'.)

FUTURE TREATMENTS — There are no treatments that can cure or provide long-term remission from food allergy. However, several treatment strategies are under investigation. These approaches are either allergen specific or aimed at modulating the overall allergic response. (See "Experimental therapies for food allergy: Immunotherapy and nonspecific therapies".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)" and "Patient education: Food allergen avoidance (Beyond the Basics)")

SUMMARY

●Grain taxonomy – Grains constitute a staple food for most of the world's population. Grains are typically divided into cereal grains that include wheat, barley, rye, oat, rice, teff, corn (maize), millet, and sorghum and the noncereal grains (seeds) that include buckwheat, quinoa, and amaranth (figure 1). (See 'Introduction' above and "Grain allergy: Allergens and grain classification", section on 'Classification' and "Grain allergy: Allergens and grain classification", section on 'Overview of grains'.)

●Epidemiology – Wheat allergy is the most common of the grain allergies, although there are reported allergies to nearly all of the other grains. (See 'Epidemiology' above.)

●Clinical manifestations – Manifestations of grain allergy include immunoglobulin E (IgE) mediated reactions, such as urticaria/angioedema and anaphylaxis; mixed IgE-mediated and non-IgE-mediated reactions, such as atopic dermatitis (eczema) and eosinophilic esophagitis (EoE); and non-IgE-mediated forms of allergy that present with delayed gastrointestinal manifestations, such as food protein-induced enterocolitis syndrome (FPIES). (See 'Clinical features' above.)

●Diagnosis – Diagnosis of IgE-mediated grain allergy is based upon careful history supported by skin prick tests (SPTs) and in vitro tests for specific IgE, although the utility of testing is hampered by poor predictive values. An oral food challenge (OFC) is warranted if the diagnosis is uncertain. Diagnostic testing for non-IgE-mediated manifestations is limited. (See 'Diagnosis of wheat allergy' above.)

●Natural history – Tolerance is achieved by the majority of children with wheat allergy. Allergy to other grains appears to follow a similar pattern. (See 'Natural course' above.)

●Management – Avoidance is the mainstay of management of grain allergy (Food Allergy Research and Education [FARE]). Substitutes for wheat include other cereal and noncereal grains as well as other foods (table 5). (See 'Management' above.)