Version May 2024
INTRODUCTION — Food allergies are adverse reactions to foods due to immunologic mechanisms. Most adverse food reactions in adults are due to various forms of food intolerance, which are nonimmunologic reactions. This topic provides an overview of the most common forms of food allergies seen in adults and briefly outlines the many different forms of food intolerance. Childhood food allergy is presented elsewhere in detail, as are specific food allergy syndromes. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution" and "Clinical manifestations of food allergy: An overview".)
NONALLERGIC ADVERSE FOOD REACTIONS — Nonallergic adverse food reactions can arise from gastroesophageal reflux disease (GERD), gastrointestinal infections, deficiency of digestive enzymes, disorders resulting from anatomic and neurologic abnormalities, metabolic diseases, toxin-mediated reactions, and a host of other processes (table 1) [1-5].
Food intolerance — Food intolerance refers to difficulty digesting or metabolizing a particular food. Food intolerance disorders are a subset of all adverse food reactions and are reported by 15 to 20 percent of the population [6]. Food intolerances are even more common among patients with irritable bowel syndrome and other functional gastrointestinal disorders, with 50 to 80 percent reporting consistent problems with certain foods [7-9]. (See "Pathophysiology of irritable bowel syndrome", section on 'Food sensitivity'.)
Comparison with food allergy — Food intolerances are not immunologic allergies and do not carry the same risk, although patients may not appreciate this distinction. A simple way to explain the difference is that food intolerance generally involves the digestive system, the amount of food ingested is directly related to the severity of symptoms, and the food causes similar symptoms with each exposure. In contrast, food allergies involve the immune system, and with immunoglobulin E (IgE)-mediated food allergies, even tiny amounts of the food can cause severe reactions. Finally, IgE-mediated, food-allergic reactions are unpredictable and have the potential to progress to a serious or life-threatening reaction called anaphylaxis.
Clinical features of food intolerance — Clinical features of food intolerances traverse a spectrum of organ systems and vary among different disorders, although most involve prominent gastrointestinal symptoms. Excessive intestinal gas, bloating, abdominal pain, and diarrhea are common symptoms.
With food intolerances, the amount of the food ingested tends to be more directly related to the severity of symptoms, compared with immunologic food allergies, in which even trace amounts of the food can trigger an explosive reaction. As an example, a patient who can eat one or two strawberries without symptoms but develops erythema and irritation around the mouth with an entire bowl of strawberries likely has an intolerance to strawberries, rather than an IgE-mediated allergy. A possible explanation for such symptoms is that some berries (eg, strawberries and blueberries) contain natural histamine-like or histamine-releasing compounds and can cause minor skin eruptions, itching, or urticaria in some children and adults. Other foods that naturally contain relatively high amounts of "biogenic amines" include chocolate, tomato, and banana [10].
Specific disorders — Examples of well-described food intolerances include:
●Lactase deficiency (also known as lactose intolerance) – Lactose intolerance presents as bloating, flatulence, abdominal cramping, and/or diarrhea after consumption of lactose in dairy products. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)
●Fructose malabsorption (or fructose intolerance) – Fructose intolerance presents with bloating, flatulence, or diarrhea after ingestion of fruit and fruit-based sweeteners (including high-fructose corn syrup). (See "Overview of the treatment of malabsorption in adults", section on 'Specific dietary restriction in selected patients'.)
●Aldehyde dehydrogenase deficiency – Deficiency of aldehyde dehydrogenase presents as flushing after alcohol and is more prevalent in people of Asian descent. (See "Approach to flushing in adults", section on 'Alcohol'.)
●Glucose-6-phosphate dehydrogenase (G6PD) deficiency – G6PD deficiency presents with hemolysis (usually in males) after ingestion of fava beans, red wine, legumes, blueberries, soy, tonic water, or certain medications (eg, nitrofurantoin, dapsone). (See "Diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency".)
●Intolerance of short-chain fermentable carbohydrates – Flatulence, abdominal pain, bloating, or diarrhea after foods containing fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) (table 2) is variably referred to as carbohydrate intolerance and is believed to be more prevalent in patients with irritable bowel syndrome. (See "Pathophysiology of irritable bowel syndrome", section on 'Carbohydrate malabsorption'.)
●Migraine headaches may be considered a manifestation of food intolerance if it is triggered by certain foods in a specific patient, and foods with high biogenic amine content have been implicated (table 3). Biogenic amines increase with food ripening, aging, and spoilage [11]. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults".)
●Mast cell activation – Patients with mast cell disorders may experience episodes of mast cell activation in the absence of IgE-mediated food allergy. Episodic symptoms may include flushing, pruritus, urticaria, diarrhea, or abdominal cramping after spicy or aged foods, as well as alcohol. This disorder is believed to be rare, although prevalence data are lacking. (See "Mast cell disorders: An overview".)
●Sulfite sensitivity – Sensitivity to ingested sulfites is believed to disproportionately affect patients with severe asthma who can experience wheezing in response to dietary sulfites. True allergic reactions are believed to be rare. (See "Allergic and asthmatic reactions to food additives".)
Unproven syndromes of food intolerance — There are other food intolerance syndromes that are not well-substantiated.
●"Histamine intolerance" – The term "histamine intolerance" first appeared in the medical literature in the 1980s and is increasingly discussed in the lay press as a verified disorder. However, no pathophysiologic mechanism, such as deficiency in one of the enzymes that appear to degrade histamine (eg, diamine oxidase [DAO] or histamine-N-methyltransferase [HNMT]), has been demonstrated in prospective, controlled studies [12]. Symptoms attributed to this syndrome include flushing, itching, headache, nausea/vomiting, and diarrhea. A trial on nonsedating H1 antihistamines and H2 antihistamines for gastrointestinal symptoms is reasonable, although there are no rigorous trials evaluating these agents specifically in patients presumed to have this disorder. We have had some limited success with the mast cell stabilizer cromolyn in an oral solution (100 to 200 mg) taken 20 to 30 minutes before meals.
●Problems with additives and food coloring agents – Although the vast majority of food additives and preservatives are well-tolerated, there are rare cases of true IgE-mediated allergy to these substances, as discussed separately. (See 'Causative foods and allergens' below and "Allergic and asthmatic reactions to food additives".)
DEFINITION OF FOOD ALLERGY — A food allergy may be defined as an adverse reaction to a food due to an abnormal immunologic response following exposure (usually ingestion) [13]. The terms "allergy" and "hypersensitivity" are often used interchangeably in the literature, although the term "allergy" is preferred in this topic review.
There are multiple types of food allergy, each with distinct clinical and pathophysiologic features. Food allergies are broadly categorized into either IgE-mediated or non-IgE-mediated processes (eg, food protein-induced enterocolitis, cell-mediated contact dermatitis to foods) [14]. Some disorders, such as eosinophilic gastrointestinal disorders, have characteristics of both mechanisms (algorithm 1).
IMMEDIATE (IgE-MEDIATED) FOOD ALLERGY — IgE-mediated reactions are referred to as "immediate" because signs and symptoms typically develop rapidly after ingestion of the culprit food (ie, within seconds to minutes). Uncommonly, reactions up to two hours and beyond can also occur. The pathophysiology involves the sudden, widespread activation of mast cells and basophils, as reviewed separately. (See "Food-induced anaphylaxis", section on 'IgE-mediated anaphylaxis'.)
Epidemiology — Food allergy had previously been estimated to affect up to 5 percent of adults, compared with 8 percent of children [14-17]. However, subsequent studies have documented higher rates in adults [18,19]. In a cross-sectional survey of over 40,000 adults in the United States conducted between 2015 and 2016, the estimate of convincing food allergy was significantly higher, at 10.8 percent, with a self-reported prevalence of twice that [20]. In this study, self-reported food allergy cases were deemed convincing if symptoms matched those of IgE-mediated reactions.
Theories about why food allergy may be increasing in adults includes aging of the generation of children in which food allergy incidence increased, or the presence of factors that are predisposing both children and adults to the development of food allergy. The pathogenesis of food allergy is reviewed separately. (See "Pathogenesis of food allergy", section on 'Factors influencing sensitization or tolerance'.)
Onset — Food allergies can develop at any age, although most first appear in childhood. In a retrospective chart review, approximately 15 percent of patients with an initial food allergy diagnosis developed the problem as an adult [21]. The same study found that age at first reaction peaked during the early 30s, although there was a wide range, with initial onset as late as 86 years of age. Of note, older age was associated with a higher risk for severe reactions [21].
Predisposing factors — There are several factors that may lead to the development of sensitization (ie, the formation of IgE to a specific substance) and subsequent food allergy in an adult, although in many cases, no predisposing exposures can be identified:
●Pollen exposure and sensitization is present in most patients with oral allergy syndrome (OAS), and most have concomitant allergic airway disease (rhinitis or asthma). (See 'Oral allergy syndrome' below.)
●Occupational exposures (eg, inhalation or contact) can lead to sensitization and subsequent reactions to food. (See 'Seafood allergies' below and 'Occupational food allergy' below.)
●Repeated tick bites or jellyfish stings can cause sensitization to red meats and certain soybean products, respectively. (See 'Delayed allergy to red meat' below and 'Natto allergy' below.)
●Cutaneous exposures to hydrolyzed wheat protein in face soaps has been linked to wheat-dependent, exercise-induced anaphylaxis in Japanese women. (See 'Food-dependent, exercise-induced anaphylaxis' below.)
●Sudden dietary changes for weight loss or with protein supplementation in conjunction with a new exercise regimen have been noted anecdotally in the months preceding onset of food allergy, particularly wheat and cow's milk (author's personal cases).
The use of acid suppressive medications has been suggested to predispose toward food sensitization [22], although a study found that current prescription of antacid therapies was seen in 19 percent of all adult patients with food allergy [21], a rate that is not different from estimates of the incidence of gastroesophageal reflux disease (GERD) in the United States [23]. Thus, the role of acid suppression remains unclear.
Signs and symptoms — Combinations of the following signs and symptoms are typical: Pruritus; urticaria; flushing; swelling of the lips, face, or throat; nausea; vomiting; cramping; diarrhea; wheezing; lightheadedness; syncope; or hypotension (table 4). Acute urticaria is probably the most common cutaneous manifestation of IgE-mediated food reactions, generally appearing within minutes of ingestion of the causative food. By comparison, food allergies are rarely an underlying cause of chronic urticaria (defined as greater than six weeks of regular outbreaks). (See "Anaphylaxis: Emergency treatment" and "Food-induced anaphylaxis", section on 'Clinical features'.)
The severity of IgE-mediated reactions are variable and unpredictable, such that the individual may develop hives on one occasion but life-threatening anaphylaxis with the next ingestion (table 5). Even tiny amounts of the food can cause severe reactions. Factors that can make an allergic reaction more severe include:
●Concomitant asthma: Patients with asthma are at higher risk for food-induced anaphylaxis (see "Food-induced anaphylaxis", section on 'Risk factors')
●Agents that increase intestinal permeability, such as alcohol and aspirin
●Certain medications: Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, which can impair the body's compensatory responses to hypotension and interfere with the actions of epinephrine, respectively
●Exercise, exertion, or stress
●Concomitant illness (viral infections, etc)
●Lack of sleep [24]
●Menstruation
Food can also cause acute contact urticaria. In this condition, urticaria develops only on skin that was in direct contact with the food. In addition to the common allergens, raw meats, seafood, raw vegetables and fruits, mustard, rice, and beer are among the foods that have been implicated in this form of reaction [25-27].
Other than urticaria, isolated dermatitis is an uncommon presentation of IgE-mediated food allergy in adults. In contrast, among children with severe eczema (atopic dermatitis), food allergy was found to exacerbate eczema and cause other symptoms in up to one-third of subjects in some studies. (See "Role of allergy in atopic dermatitis (eczema)".)
Causative foods and allergens — Although any food can cause IgE-mediated allergy, a few foods cause most of these reactions. Fish/seafood and peanuts/tree nuts are the two food groups that cause the majority of adult food allergies, both of which are estimated to affect up to 2 percent of the United States population. The other foods that cause allergy in adults vary around the world, probably reflecting the prominence of that food in the diet.
Most food allergens are proteins. Occasionally, carbohydrate allergens have been implicated in allergic reactions to certain meats (eg, beef, pork, and lamb). (See 'Delayed allergy to red meat' below.)
Pesticides, additives, artificial colors, and antibiotics in animal feeds are often suspected by the patient to be the cause of an allergic food reaction, but in reality, these substances are rare causes of allergy. Patients may also ask whether organic foods are less allergenic that nonorganic foods. There is no difference in allergenicity because both contain the same proteins, and most food allergens are proteins. The small number of additives that have been implicated in IgE-mediated reactions are often derived from natural substances, such as carrageenan (from seaweed), lupine flour, pectin (from fruits and vegetables), gelatin, annatto (a red dye produced from the seeds of the achiote tree), and carmine red (derived from insect bodies). Allergic reactions to food additives are discussed separately. (See "Allergic and asthmatic reactions to food additives".)
Common types of IgE-mediated food allergy — The most common types of IgE-mediated food allergy in adults are OAS and isolated allergies to fish/seafood or peanuts/tree nuts.
Oral allergy syndrome — Oral allergy syndrome (OAS), or pollen-food allergy syndrome (PFAS or PFS), is the most common form of food allergy in adults, affecting up to 5 percent of the general population in some studies [28]. It is a generally mild form of food allergy that is caused by contact of the mouth and throat with raw fruits and vegetables and sometimes nuts. The most frequent symptoms of OAS are itchiness or mild swelling of the mouth, face, lip, tongue, and throat, generally developing within minutes after eating raw fruits or vegetables. Cooked fruits and vegetables typically do not elicit the symptoms, and this is an important question in the clinical history. Tree nuts and peanuts (raw and cooked) can also cause isolated oral symptoms, although these foods can also cause more serious systemic reactions. It is appropriate to refer all nut reactions to an allergy specialist. (See 'Referral' below.)
OAS is IgE-mediated and considered a form of contact allergy that develops in patients sensitized to pollens. Most patients also report seasonal allergic rhinitis or conjunctivitis. Common examples include the following (figure 1):
●Birch-allergic patients may develop itching of the lips or mouth upon eating fresh apple, pear, cherry, carrot, celery, or handling raw potato
●Ragweed-allergic patients may react to melons and banana
●Mugwort-allergic patients may react to raw celery
OAS is caused by the presence of heat-labile proteins (eg, profilins) within these foods that are cross-reactive with allergenic pollen proteins. Patients may suspect that these reactions are caused by pesticides, fungicides, waxes, or other chemicals on the fruits or vegetables, but this is not the case. The allergenic proteins cause mild symptoms in the mucosal surfaces of the mouth and throat and are then destroyed by the acid pH in the stomach (or by heat during cooking), so the reaction typically does not present with gastrointestinal or systemic symptoms. However, a small minority of patients (ie, <2 percent) report systemic symptoms, and these patients should be evaluated by an allergist for more serious forms of food allergy and supplied with an epinephrine autoinjector. Referral is also appropriate if the diagnosis is unclear. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Prescribing epinephrine for anaphylaxis self-treatment".)
Management of OAS primarily involves avoiding raw forms of the fruits and vegetables in question. Cooked forms can be eaten as tolerated. In straightforward cases of OAS, patients do not need to be referred to an allergist. Other management options are discussed separately. (See "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)".)
Seafood allergies — Of reported food allergy among adults, seafood (ie, fish, shellfish, and mollusks) allergy is the next most common, with an estimated prevalence of 1 to 2 percent both in the United States and internationally. One study suggested that 40 to 60 percent of seafood allergies developed in adulthood, rather than in childhood [29].
Most seafood-allergic patients are allergic to either one or more finned fish or one or more shellfish/mollusks. Only 10 percent of allergic patients are reactive to foods in both groups. Thus, a person with allergy to one specific type (eg, shrimp) can often safely continue to eat other types of seafood (eg, fish and possibly some mollusks), and referral to an allergist can be helpful for determining which types are tolerated. Seafood allergies are discussed in detail separately. (See "Seafood allergies: Fish and shellfish".)
Seafood allergy is unrelated to radiocontrast allergy. Individuals with allergic disease (ie, those with asthma, allergic rhinitis, atopic dermatitis, or food allergies) as a group are three times more likely than individuals without these conditions to have a severe adverse reaction to intravenous iodinated contrast media, although no special precautions are indicated prior to radiographic studies aside from controlling asthma symptoms as well as possible. Most of this increased risk is believed to be related to asthma. There is no additional risk associated with seafood allergy specifically. This misconception is discussed separately. (See "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Patients with past reactions to contrast'.)
Peanut and tree nut allergies — Peanuts and tree nuts are also commonly implicated in adults with food allergy, although in most cases, the nut allergy developed in childhood and persisted into adulthood, unlike the situation with seafood allergies. Because peanut and tree nut allergies can range from mild to severe and can be difficult to categorize, we suggest referring all nut-allergic patients to an allergy specialist for evaluation. (See 'Referral' below.)
Cow's milk and 'dairy' allergies — Allergic reactions to cow's milk proteins in adults is complicated by lactose intolerance, which increases with age. However, recent large population-based phone survey data suggest that cow's milk allergy may be as common in adults as peanut allergy but less associated with severe reactions and less frequently physician-diagnosed [20].
Uncommon types — There are several uncommon presentations of IgE-mediated food allergy, such as food-dependent, exercise-induced anaphylaxis, delayed allergy to red meat, occupational food allergies, allergies related to latex allergy, and natto allergy (Japan).
Food-dependent, exercise-induced anaphylaxis — Food-dependent, exercise-induced anaphylaxis is a form of food allergy in which the patient only develops symptoms when ingestion of the culprit food is followed within a few hours by exertion or exercise. Symptoms do not develop if the food is eaten at rest or if the patient exercises without first eating the food. Thus, the connection between the food and exertion may not be recognized for some time. In addition, the reactions are unpredictable, which further complicates recognition. Diagnosis can be difficult, because commercial skin test reagents and in vitro testing may not as reliably detect the underlying food allergy. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis" and "Exercise-induced anaphylaxis: Management and prognosis".)
Occupational food allergy — Occupational food allergy most often develops in patients who work in food processing. Common causes include fish, shellfish, wheat, other grains, fruits, and vegetables. Patients may present with respiratory allergy (ie, asthma, allergic rhinitis), anaphylaxis [30,31], and/or contact urticaria [32,33]. A history of symptoms occurring predominantly in the work environment is suggestive. Occupational asthma and rhinitis are discussed elsewhere. (See "Occupational asthma: Definitions, epidemiology, causes, and risk factors", section on 'High-molecular-weight' and "Occupational rhinitis", section on 'Immunologic occupational rhinitis'.)
Food allergies related to latex allergy — Latex allergy peaked in the 1990s in the United States and Europe due to the introduction of "universal precautions," then declined again as hospitals and other work environments switched to nonlatex alternatives. However, rates of latex glove use and associated latex allergy remain high in some countries and in certain occupations, such as health care workers, food handlers/restaurant workers, and housekeeping staff. Among patients with latex allergy, 30 to 50 percent of individuals who are allergic to latex show an associated hypersensitivity to some plant-derived foods, such as avocado, banana, kiwi, chestnut, peach, tomato, white potato, and bell pepper (figure 2). (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis".)
Patients with latex allergy may react to vaccines drawn by needles through bottles with latex stoppers, although this appears to be rare. Options for vaccination are reviewed elsewhere. (See "Allergic reactions to vaccines", section on 'Latex'.)
Delayed allergy to red meat — One unusual form of IgE-mediated food allergy is caused by sensitization to the allergen galactose-alpha-1,3-galactose (alpha-gal), which is present in tissues from most animals, with the exception of old world primates (and humans). This form of meat allergy is distinguished by a delayed onset, with symptoms appearing three to six hours after ingestion (sometimes in the middle of the night, if meat was eaten for dinner). The symptoms are otherwise typical of IgE-mediated reactions, such as urticaria, angioedema, or anaphylaxis, sometimes with gastrointestinal symptoms or hypotension. Allergy due to sensitization to alpha-gal is described in an increasing number of countries, including the United States, Australia, Spain, Germany, Japan, and Sweden. Patients may become sensitized to alpha-gal through tick bites or exposure to the drug cetuximab, and the role of these factors is discussed elsewhere. (See "Allergy to meats", section on 'Risk factors' and "Allergy to meats", section on 'The role of ticks in red meat allergy'.)
Diagnosis can be difficult because commercial skin test reagents and in vitro testing may not reliably detect the underlying food allergy. (See "Allergy to meats".)
Natto allergy — Reports indicate that surfers in Japan with repeated jellyfish stings are at risk for development of food allergy to fermented soybeans (natto) [34]. The suspected allergen in these cases is the protein poly-gamma-glutamic acid, and both immediate and delayed reactions have been described [35].
Initial management — Initial management for patients with possible IgE-mediated food allergies includes assessing whether the patient requires an epinephrine autoinjector, counseling about avoidance of that food and potentially cross-reactive foods, obtaining initial laboratory tests, and referral to an allergy specialist for further evaluation and management.
Assess the need for an epinephrine autoinjector — We suggest prescribing epinephrine to any patient who may have had an apparent anaphylactic event or an allergic reaction that caused difficulty breathing, throat tightness, or possible hypotension. Such patients should be equipped with two epinephrine autoinjectors, with instructions about how and when to use them.
●Information for clinicians about the different autoinjectors available and key teaching points concerning how and when to use these devices are found separately. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Available devices'.)
●Information for patients about how to use an autoinjector is also provided. (See "Patient education: How to use an epinephrine autoinjector (The Basics)" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)".)
Counsel about avoidance — Patients should avoid the suspect food until further evaluated. In the case of both seafood and tree nut allergy, patients allergic to one food are often allergic to other related foods. Thus, until the patient can be evaluated by an allergy specialist, it is prudent to recommend avoidance of the related foods. One of the goals of an allergy evaluation is clarification of related foods that can be safely ingested. (See "Seafood allergies: Fish and shellfish" and "Peanut, tree nut, and seed allergy: Clinical features".)
Referral — Any patient with suspected IgE-mediated food allergy should be referred to an allergy specialist if possible for definitive diagnosis and further management. A possible exception is the patient with clear clinical symptoms related to a single food and positive IgE immunoassays specific for that food who is content to avoid the culprit food in the future and has no unanswered questions.
Overview of an allergy evaluation — A typical allergy evaluation begins with a detailed history of past reactions to identify likely culprit food and probable mechanism. This is generally done before any testing takes place to determine the pretest probability that will inform interpretation of the results. Testing for IgE-mediated food allergies can be performed with skin testing or in vitro immunoassays for IgE specific to the food in question. Skin testing is the preferred method of diagnosing food allergy in most cases, because it is usually more sensitive and the negative predictive value is high. Skin testing should be performed by allergy specialists. If skin testing or in vitro testing is inconclusive, a graded challenge may be performed. (See "Diagnostic evaluation of IgE-mediated food allergy", section on 'Prick/puncture skin tests' and "Diagnostic evaluation of IgE-mediated food allergy", section on 'Food challenges'.)
For patients with IgE-mediated allergy, allergists can also provide advice about effective avoidance and ongoing education about anaphylaxis and use of epinephrine autoinjectors, which requires time and can be challenging to do in a busy primary care setting. (See "Management of food allergy: Avoidance".)
Laboratory testing — The presence of food-specific IgE or a positive skin test to a food demonstrates that a patient is "sensitized" to that food and indicates possible allergy. The definitive diagnosis of an IgE-mediated food allergy requires both sensitization and a history of consistent signs and symptoms on exposure to that food. Sensitization alone is not sufficient to diagnose food allergy, because individuals can be sensitized to a food (which is not uncommon) without having clinical symptoms upon ingestion. For example, patients with respiratory allergy to dust mite may have positive serum IgE to shrimp or other shellfish (because the testing cannot differentiate between different allergens within these two phylogenetically-related organisms) but not have shrimp allergy. For this reason, searching for culprit foods with extensive panels of IgE immunoassays when the history is vague is rarely productive and can be misleading.
In contrast, an immunoassay for IgE to the specific food in question can be very helpful if one or a small number of suspect foods are implicated by the history. For example, it is reasonable for the generalist to obtain an immunoassay for IgE to shrimp if a patient developed hives, pruritus, and nausea while eating shrimp cocktail. When the clinical history is highly suggestive of allergy to a specific food (high pretest probability), a positive in vitro test is often sufficient for diagnosis.
Immunoassays for food-specific IgE are widely available and not affected by antihistamines or other medications the patient may be taking. Higher concentrations of food-specific IgE correlate to an increased likelihood of a reaction upon ingestion, although a patient with a significant food allergy can have a high, medium, low, or even negative in vitro test. A patient can also have a low-positive level to a food that is tolerated. The use and interpretation of IgE immunoassays and skin tests to foods is reviewed in detail separately. (See "Diagnostic evaluation of IgE-mediated food allergy", section on 'In vitro testing'.)
Improved forms of IgE immunoassays, called component resolved diagnostics, are being developed for foods that commonly cause IgE-mediated allergies. (See "Future diagnostic tools for food allergy", section on 'Component-resolved diagnosis'.)
Unvalidated forms of testing — There are several types of tests that are not validated in the diagnosis of any type of food allergy and should not be performed [36,37]. Generalists can advise patients against pursuing these tests. These can include food-specific IgG and IgG4 tests, which typically yield multiple positive results and may represent a normal immune response to food [38]. Other types of testing for food allergy that are not supported by scientifically-valid concepts include sublingual or intradermal provocation tests, tests of lymphocyte activation, kinesiology, cytotoxic tests, and electrodermal testing [13]. (See "Diagnostic evaluation of IgE-mediated food allergy", section on 'Unvalidated methods'.)
OTHER TYPES OF FOOD ALLERGY — Eosinophilic esophagitis and food-protein induced enterocolitis syndrome (FPIES) are non-IgE-mediated forms of food allergy. Cell-mediated contact dermatitis to food proteins (usually seen in patients who work in food processing) is another form, although it is believed to be uncommon [39].
Celiac disease is another type of immunologic reaction to food, although it is not generally classified as a food allergy and is discussed in detail separately. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Dermatitis herpetiformis", section on 'Cutaneous manifestations'.)
Eosinophilic esophagitis — Eosinophilic esophagitis in adults typically affects atopic men in their 20s or 30s and appears to be increasing in prevalence. Signs and symptoms are limited to the upper gastrointestinal tract and include dysphagia (initially to solid foods), acid reflux that is refractory to antacids, food impaction, and central chest pain. Eosinophilic esophagitis should be considered in adults with a history of food impaction, with persistent dysphagia, or with gastroesophageal reflux disease (GERD) that fails to respond to medical therapy. The majority of patients have evidence of food allergen and aeroallergen sensitization. Referral to a gastroenterologist for endoscopy is indicated. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Treatment of eosinophilic esophagitis (EoE)".)
Food protein-induced enterocolitis syndrome — Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that primarily presents in infancy and resolved by three to five years of age. However, it is occasionally reported in adults, in whom mollusks and shellfish can be culprit allergens [40,41]. There are also case reports of FPIES caused by egg in adults [42]. Symptoms usually begin two to four hours after ingestion and are limited to the gastrointestinal tract (ie, nausea, vomiting and nonbloody diarrhea). Episodes usually resolve in a matter of hours, and are often mistaken for food poisoning initially, until a pattern of reactions becomes apparent. It is appropriate to refer patients with suspected FPIES to an allergist, although there is no specific testing that confirms the diagnosis. Testing for IgE-mediated allergy may be performed to exclude immediate allergy. FPIES is managed with avoidance of the culprit food. (See "Seafood allergies: Fish and shellfish", section on 'Gastrointestinal reactions'.)
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 5th to 6th 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 10th to 12th 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 education" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Food allergy (The Basics)")
●Beyond the Basics topic (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Recurrent adverse reactions to specific foods or food groups are reported by up to 20 percent of the general population and by more than one-half of patients with irritable bowel syndrome. Most of these reactions are explained by food intolerances, which are nonimmunologic food reactions. (See 'Nonallergic adverse food reactions' above.)
●Nonallergic adverse food reactions can result from a host of disorders, including gastroesophageal reflux disease (GERD), metabolic diseases, toxin-mediated reactions, gastrointestinal infections, deficiency of digestive enzymes, disorders resulting from anatomic and neurologic abnormalities, and other processes (table 1). In most cases, patients report predominantly gastrointestinal symptoms, and the amount of the food ingested tends to be directly related to the severity of symptoms. (See 'Nonallergic adverse food reactions' above.)
●Food allergy may be defined as an adverse reaction to a food due to an abnormal immunologic response following exposure (usually ingestion). Even tiny amounts of food can cause severe reactions. There are multiple types of food allergy, each with distinct clinical and pathophysiologic features. Food allergies are broadly categorized into either immunoglobulin E (IgE)-mediated or non-IgE-mediated processes, although some disorders (eg, eosinophilic gastrointestinal disorders) have features of both mechanisms. (See 'Definition of food allergy' above.)
●IgE-mediated (immediate) food-allergic reactions, which affect up to 5 percent of adults, present with combinations of the following signs and symptoms: Pruritus; urticaria; flushing; swelling of the lips, face, or throat; nausea; vomiting; cramping; diarrhea; wheezing; lightheadedness; syncope; or hypotension, usually appearing within minutes of ingestion of the causative food (table 4). The severity of the reaction may vary over time, such that the patient may develop hives on one occasion but life-threatening anaphylaxis with the next ingestion (table 5). (See 'Signs and symptoms' above.)
●The most common types of IgE-mediated food allergy in adults are:
•Oral allergy syndrome (OAS), which usually presents as pruritus of the mouth and throat with ingestion of raw fruits and vegetables, with tolerance of cooked forms of those foods. (See 'Oral allergy syndrome' above.)
•Isolated allergies to fish/seafood or peanuts/tree nuts. (See 'Seafood allergies' above and 'Peanut and tree nut allergies' above.)
●Initial management for patients with possible IgE-mediated food allergies include assessing whether the patient requires an epinephrine autoinjector, counseling about avoidance of that food and potentially cross-reactive foods, and possibly obtaining initial laboratory tests. (See 'Initial management' above.)
●Most adults with a suspected IgE-mediated food allergy should be referred to an allergist for definitive diagnosis, if feasible. A possible exception is straightforward OAS. (See 'Referral' above.)
●Eosinophilic esophagitis and food protein-induced enterocolitis syndrome (FPIES) are non-IgE-mediated forms of food allergy that occur in adults. (See 'Other types of food allergy' above.)
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