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Allergic and asthmatic reactions to food additives

Allergic and asthmatic reactions to food additives
Literature review current through: Jan 2024.
This topic last updated: Apr 14, 2021.

INTRODUCTION — The list of additives used in the food industry is extensive and includes thousands of natural and synthetic substances used as flavorings, coloring substances, preservatives, sweeteners, antioxidants, thickeners, etc. However, only a small number of additives have been implicated in immunoglobulin E (IgE)-mediated or other (immunologic or nonimmunologic) adverse reactions.

Food additives that have been linked to urticaria/angioedema, asthma, and anaphylaxis will be discussed here. Food additives that cause asthma/rhinitis in food industry workers and testing and challenge procedures for food additives are mentioned briefly here and reviewed in more detail separately. (See "Occupational asthma: Pathogenesis" and "Occupational rhinitis" and "Testing and challenge procedures to evaluate allergic and asthmatic reactions to food additives".)

Issues surrounding food additives that are not discussed in this topic review include the following:

Hyperactivity and behavioral changes in children (see "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis")

Oncogenic potential of food additives (see "Risk factors for gastric cancer")

Dietary factors and headache (see "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults")

OVERVIEW — Food additives may be classified by function. Additives that affect the chemical or structural characteristics of foods include emulsifiers, acidulants, buffers, raising agents, and enzymes. Shelf-life extenders include preservatives, antioxidants, and curing/pickling agents. Thickeners, colors, gelling agents, and non-nutritive sweeteners are added to alter the sensory characteristics of foods. Food additives are identified in the United States by their English names or, in the European Union, by a unique identifying number, the "E number" [1,2].

Epidemiology — Patients and parents of young children suspect allergy and intolerance to food additives far more often than it can be verified [3]. The prevalence of a reaction to food additives was only 0.23 percent in a population-based study [3,4]. Many of the cases of adverse reactions attributed to food additives that are reported in the medical literature are either anecdotal or characterized by poorly-controlled challenge procedures. In reality, relatively few food additives have been convincingly demonstrated to cause reactions, such as urticaria, angioedema, asthmatic reactions, or anaphylaxis [5-10].

Allergic reactions to nutritive foods (eg, tree nuts or seafood) are far more prevalent than reactions to food additives, and food allergy must always be considered first in the differential diagnosis. (See "Clinical manifestations of food allergy: An overview".)

Clinical manifestations — Food additives should be considered as a possible cause of allergic or asthmatic reactions when signs/symptoms occur in association with meals or other ingestions (candy, etc).

Clues that the patient may be reacting to a food additive include [7]:

Allergic or asthmatic reactions that occur in timely association with meals or other ingestions (ie, usually within minutes to a few hours of eating).

A convincing history of symptoms to several apparently unrelated foods.

Reactions to commercially prepared forms of foods that are tolerated when prepared at home.

The following types of allergic and asthmatic reactions to food additives have been reported:

Anaphylaxis – Classic immunoglobulin E (IgE)-mediated allergic reactions most commonly involve one or more of the following signs and symptoms: flushing, urticaria, pruritus, angioedema, bronchospasm, nausea, vomiting, or throat tightness (table 1). Anaphylaxis is the most severe form of an IgE-mediated allergy. Diagnostic criteria for anaphylaxis are shown in the figure (figure 1).

Isolated asthmatic reactions in people known to have asthma.

Urticaria and angioedema, alone or in combination.

In contrast, there are no known associations between food additives and other chronic atopic conditions, such as atopic dermatitis or eosinophilic esophagitis [11].

Reactions to multiple additives — When patients do have a true adverse or allergic reaction to a food additive, it is generally caused by a single agent. The medical literature does not support the notion of patients being broadly "chemically-sensitive." The evaluation of patients with apparent "multiple chemical sensitivity" is discussed separately. (See "Idiopathic environmental intolerance (multiple chemical sensitivity)".)

Other types of reactions — There are many nonallergic reactions that also need to be considered in the patient presenting with reactions related to food ingestion (table 2). These are mentioned separately. (See "Clinical manifestations of food allergy: An overview", section on 'Differential diagnosis'.)

URTICARIA/ANGIOEDEMA

Patients with chronic urticaria — Chronic urticaria (CU) is defined as the presence of urticaria (hives) most days of the week for a period of six weeks or longer. CU is inherently variable, and when the disorder first develops, many patients will try to make an association with specific foods or food additives. However, clinically relevant allergies to foods or food additives are rare in patients with CU. Clinicians should not routinely advise patients with CU to avoid food additives [5].

Although allergies rarely cause this disorder, a subset of patients with CU will notice that symptoms are exacerbated (not caused) by foods that have high levels of natural histamine-like chemicals. The relationship between diet and symptom severity in CU is reviewed in more detail separately.

The most accurate means to assess a possible adverse reaction is to utilize double-blind, placebo-controlled challenge protocols, as is done with food challenges [12,13]. However, challenges are particularly difficult to perform in patients with CU, because, on one hand, withdrawal of antihistamines can result in increased symptoms that can be misinterpreted as a positive challenge. On the other hand, the patient is unlikely to react to challenge if full doses of antihistamine are continued, yielding false-negative results.

In a study of 100 patients with CU evaluated at the author's center over a 10-year period, subjects were challenged with 11 common food and drug additives. Forty-three percent of the group reported suspected reactions to additives. Prior to challenge, antihistamines were tapered to the "minimal effective dose" that allowed patients to be comfortable, but not hive-free. Subjects were then given a single-blind challenge consisting of multiple opaque capsules containing the following additives [14]:

Monosodium glutamate (MSG)

Sodium benzoate

Methyl paraben

Butylated hydroxyanisole (BHA)

Butylated hydroxytoluene (BHT)

Tartrazine (FD&C Yellow #5, E102)

Sunset yellow (FD&C Yellow #6, E110)

Sodium nitrate

Sodium nitrite

Aspartame

Potassium metabisulfite

Criteria for a positive challenge used "skin scores" of urticarial lesions. Skin scores for several hours after the challenge were compared with scores from the previous three days. Two patients had an increase of 30 percent in their skin scores following the initial challenge [14]. After two weeks, these two patients underwent double-blind, placebo-controlled challenges with each additive separately on 11 different days. Neither patient reacted to any additives. Thus, none of the 100 patients was sensitive to any of the additives tested, suggesting that reactivity to food additives in patients with CU is rare, if it occurs at all. The multiple-additive challenge protocol used in this study is reviewed separately. (See "Testing and challenge procedures to evaluate allergic and asthmatic reactions to food additives", section on 'Mixed additive challenge'.)

Additives implicated in case reports — BHA, BHT, aspartame, and lysozyme have been implicated in causing urticaria or angioedema in isolated case reports.

BHA and BHT — Butylated hydroxyanisole (BHA) (E320) and butylated hydroxytoluene (BHT) (E321) are antioxidants commonly used in breakfast cereals and other grain products to maintain crispness and prevent rancidity. There is one well-documented report of CU, confirmed by double-blind, placebo-controlled challenges, exacerbated by these agents [15]. Sensitive subjects exhibited improvement in urticaria after elimination of BHA and BHT from the diet.

Aspartame — Aspartame (NutraSweet), a dipeptide, is a low-calorie artificial sweetener [16]. Two cases of aspartame-induced urticaria, confirmed by placebo-controlled, double-blind challenge, have been reported [17], and additional cases by the same author have also been described [18]. However, other investigators have encountered difficulty recruiting subjects with adverse reactions to aspartame and have found that such subjects do not have reproducible reactions [19,20].

Lysozyme — Lysozyme in egg, aged cheeses, and pharmaceuticals was implicated in a case report of recurrent angioedema [21].

ASTHMATIC SYMPTOMS — Sulfites are the only compounds that have been convincingly demonstrated to provoke asthmatic reactions in a small subset of asthmatic patients [5]. Affected patients typically have severe, steroid-dependent asthma [22,23]. The evidence that other additives can provoke asthma, especially benzoate, monosodium glutamate (MSG), and tartrazine, is limited to case reports and has not been supported by rigorous double-blind, placebo-controlled challenges.

Sulfites and related compounds — Sulfites have been widely used for centuries to freshen and prevent oxidative discoloration (browning) of foods. Sulfites are also used as sanitizers and to inhibit the growth of undesirable micro-organisms in the fermentation industry. Sulfiting agents include sulfur dioxide, sodium potassium sulfite, bisulfite, and metabisulfite. Foods containing sulfites are listed in the table (table 3). The highest levels of sulfites are found in commercially prepared dried fruits (such as apricots), potatoes, wines, and some seafood items [24].

Sulfiting agents can cause serious and potentially life-threatening asthmatic reactions in patients with asthma, as demonstrated in double-blind controlled studies [22,23,25]. As many as 5 percent of the asthmatic population may experience adverse reactions from mild wheezing to severe bronchospasm following ingestion of sulfite-containing foods or beverages [23,26,27]. Asthmatic reactions in patients without underlying asthma appear to be uncommon.

While any asthmatic may develop sulfite sensitivity, many sulfite-sensitive asthmatics have more severe asthma and are steroid-dependent. Therefore, one should consider sulfite sensitivity in moderate/severe or steroid-dependent asthmatics who give a history of reacting to foods/beverages likely to contain moderate-to-high levels of sulfites (table 3).

Tartrazine (FD&C Yellow 5) — Tartrazine (FD&C Yellow #5 or E102) is an acidic dye derived from coal tar that is used as a colorant in foods and medications. It was reported to provoke bronchospasm in patients with asthma, although the studies that supported this conclusion in the 1960s and 1970s lacked adequate controls by modern standards [28-31]. It was also believed by some clinicians at the time that tartrazine "cross-reacts" with nonsteroidal anti-inflammatory drugs (NSAIDs) and should be avoided by patients with aspirin-exacerbated respiratory disease (AERD). However, tartrazine is not a cyclooxygenase-1 (COX-1) inhibitor like NSAIDs, and subsequent studies have shown it is well-tolerated in patients with AERD. Well-controlled studies have also suggested that tartrazine sensitivity in other asthmatic patients is rare.

Two double-blind, placebo-controlled studies each found no tartrazine-sensitive subjects among approximately 50 adult and pediatric subjects with chronic, frequently steroid-dependent asthma [32,33].

Double-blind, placebo-controlled challenge protocols in aspirin-sensitive asthmatics found no adverse reactions in 165 patients challenged to a dose of 50 mg of tartrazine [34].

A 2001 systematic review identified six randomized trials examining the effects of tartrazine in patients with asthma, both with and without aspirin sensitivity. Only three included analyzable data, and these were not comparable, so no formal conclusions were drawn [35]. However, tartrazine challenges or tartrazine avoidance were not found to affect asthma symptoms in any of the six trials.

In a study of 26 atopic patients with either asthma, allergic rhinitis, urticaria, or pseudoallergic reactions to NSAIDs, subjects underwent double-blind, placebo-controlled challenge with 25 mg of tartrazine and demonstrated no increase in symptoms [36].

Therefore, based on the available evidence, avoidance of tartrazine in patients with asthma is not justified.

Sodium benzoate — Sodium benzoate (E211) is used as an antimicrobial preservative in foods. There has been only one subject in the medical literature shown to have benzoate-provoked asthma, as reported in a double-blind, placebo-controlled study [37]. This patient was not aspirin-sensitive and did not experience amelioration of asthma symptoms while on a benzoate-free diet.

Spearmint, peppermint, and menthol — The flavorings spearmint (Mentha spicata), peppermint (Mentha piperita), and menthol (Mentha labiatae) used in chewing gum and toothpaste have been confirmed by challenges in two cases to have triggered asthma [38,39]. Anaphylaxis was described in another case report [40].

ANAPHYLAXIS — Several natural food additives have been implicated in causing anaphylaxis, and reports have become more common as consumer preference for products containing only "natural" ingredients has increased. Over the past decades, food manufacturers have been replacing synthetic food additives with compounds derived from plant, insect, and animal products. Because most immunoglobulin E (IgE)-mediated allergy is caused by proteins from other living organisms, this switch to natural agents has been associated with an increase in IgE-mediated allergies to these substances. As examples, case reports have described the potential for anaphylaxis with annatto, carmine, psyllium, and guar gum [41-44]. IgE-mediated allergy to spices also occurs.

Annatto — Annatto (E160b) is a yellow food coloring used to color a variety of foods, including cereal, cheese, ice cream, margarine, oils, and beverages. Annatto dye extract is produced from the pericarp of the fruit of the annatto tree, Bixa orellana. Anaphylaxis to annatto has been reported [43,45].

Carmine — Carmine (E120), or cochineal extract, is a red food dye derived from the dried bodies of female Dactylopius coccus Costa insects [46]. Carmine is used in foodstuffs, such as candy, ice cream, yogurt, cookies, pastries, syrups, liqueurs, vinegar, cheese, butter, delicatessen meats, jam, and caviar, as well as in cosmetics. It has been implicated in anaphylaxis as well as occupational asthma [44,47]. (See "Occupational asthma: Pathogenesis".)

Allergic symptoms following carmine ingestion appear rapidly in some individuals but are delayed by several hours in others, for reasons which are not clear [46]. Skin testing is informative, although positive results may appear after 30 minutes, rather than the usual 15 minutes [48].

Erythritol — Erythritol (ERT; 1,2,3,4-butanetetrol) is a 4-carbon sugar alcohol prepared from glucose by fermentation that is used as a sweetener [42]. It may also occur naturally in foods, such as wine, beer, soy, cheese, mushroom, grape, and watermelon. Anaphylaxis has been reported after ingestion of ERT-containing foods [42].

Guar gum — Guar gum (E412) is a galactomannan derived from the guar bean, which is used as an emulsifier and binder in foods and pharmaceuticals. Guar gum has been implicated in severe anaphylaxis, as well as occupational rhinitis/asthma [49-52].

Psyllium — Psyllium is a source of soluble dietary fiber derived from the husks of Plantago ovata seeds. Psyllium is commonly used in bulk laxatives and fiber-enriched breakfast cereals. Allergic reactions, including severe anaphylaxis, have been reported [53]. Psyllium can also be a source of occupational asthma/rhinitis [54-56]. Health care workers who have prepared and handled psyllium-containing bulk laxatives appear to be at particular risk [53].

Sulfites — A small number of cases of anaphylaxis related to sulfite ingestion with positive skin tests have been reported [41,57]. One patient had monoclonal mast cell activation syndrome [58]. In addition, three reports assessed sulfite sensitivity in subjects with idiopathic anaphylaxis. In one report, 1 subject among 130 challenged was found to be sulfite-sensitive [59]. In another report, one subject experienced a systemic reaction following a sulfite skin test [60]. A third report found no sulfite sensitivity [61].

Epinephrine autoinjectors contain small amounts of sulfite, although this is not a contraindication to their use. This is discussed below. (See 'Patients with anaphylaxis' below.)

Other additives — Several other additives have been implicated in anaphylaxis, including the following:

Carrageenan is a gelatinous polysaccharide derived from seaweed, which is used as a stabilizer and thickener. It has been implicated in anaphylaxis caused by a barium enema solution [62].

Lupine flour is an inexpensive flour extender that has been implicated in allergic reactions [63,64]. Lupine may have some cross-reactivity with peanut. (See "Food allergens: Clinical aspects of cross-reactivity", section on 'Peanut'.)

Pectin, a jelling agent and thickener, has been reported to cause anaphylaxis upon ingestion and occupational asthma upon inhalation [65]. Pectin may cross-react with cashew [65].

Gelatin in gummy candies and fruit chews has caused anaphylaxis [66,67]. Gelatin in vaccines (particularly in Japan) has been more frequently implicated in anaphylaxis. (See "Allergic reactions to vaccines".)

Mycoprotein is fermented fungus (Fusarium venenatum) bound with egg albumin. It shares common allergenic determinants with other molds. Mycoprotein is used as a meat substitute (marketed as Quorn in the United States). Allergic reactions, including anaphylaxis, have been reported, mainly in patients with inhalant mold allergy [68-70].

Spices — The term "spice" is often used to describe a variety of flavoring agents. Items that can be considered spices include allspice (a type of pepper), basil, cardamom, celery, chives, cinnamon, coriander, cumin, dill, fennel, garlic, ginger, marjoram, nutmeg, onion, oregano, parsley, pepper, peppermint, rosemary, saffron, sage, savory, star anise, tarragon, tumeric, and vanilla. Seeds (eg, poppy, sesame, caraway, mustard) are sometimes considered spices within the food industry.

Many types of pepper are used for spice (eg, bell, red, cayenne). In addition, many spices that are "hot" or "spicy" contain a chemical, capsaicin, which triggers burning sensations in normal individuals that could be misinterpreted as an allergic reaction, especially in a child.

Allergic reactions and anaphylaxis to a variety of spices have been reported and usually affect adults. In a French study, allergy to spices was estimated to account for approximately 2 percent of adults with food-allergic reactions and was rare in children [71]. The most allergenic groups of spices were those of the Apiaceae family (coriander, caraway, fennel, celery, chervil, and dill) and Liliaceae family (garlic, onion, chive, shallot, and saffron). Most individuals allergic to spices have concomitant allergy to inhaled pollens (especially birch and mugwort) and experience allergic reactions upon ingesting spices that contain proteins with homology to pollen proteins. Spice allergy is discussed in more detail separately. (See "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)".)

REACTIONS TO MSG — Monosodium glutamate (MSG) is a nonessential dicarboxylic amino acid that is a normal constituent of food protein. Additional MSG is added to food as a flavor enhancer, particularly in Asian food. A variety of nonallergic symptoms have been attributed to MSG, while allergic and asthmatic reactions are only rarely reported and generally not well-substantiated.

MSG symptom complex — Perhaps the best known adverse reaction to a food additive is the MSG symptom complex. This is not an allergic reaction.

The MSG symptom complex typically appears 1 to 14 hours after ingestion. Reported symptoms include headache, myalgia, backache, neck pain, nausea, diaphoresis, tingling, flushing, palpitations, and chest heaviness [72]. Children have been reported with shivering, chills, irritability, screaming, and delirium.

The mechanism of these reactions has been proposed to involve an exaggerated sensitivity to this compound, which is metabolized after ingestion to glutamate, a major excitatory amino acid neurotransmitter.

The MSG symptom complex has not been reproduced in controlled challenges, and symptoms were not consistently inducible in 130 patients who were self-identified as sensitive to MSG and challenged in a double-blind manner. Those patients who inconsistently experienced symptoms most often did so only when MSG was ingested in quantities larger than those that would be encountered in a normal diet and without accompanying food [73]. Thus, MSG is regarded as a safe food additive [74,75]. Still, a patient suffering from these symptoms who believes that MSG is the cause can be advised to avoid foods containing added MSG, since this is relatively simple to do. Such patients should particularly avoid liquid foods (such as wonton soup), from which high levels of MSG can be rapidly absorbed.

Allergic and asthmatic reactions — A small number of case reports have implicated MSG in causing urticaria and angioedema [74,76,77]. As an example, one case described delayed angioedema beginning 16 hours after ingestion of 250 mg MSG, which was reproduced by single-blind, placebo-controlled challenge [77].

Although MSG has been implicated in provoking asthma [78,79], this association has not been supported in studies characterized by double-blind, placebo-controlled MSG challenges in high-risk asthmatic subjects (aspirin-sensitive or history-positive) [80-82].

One group of researchers reported a small number of subjects with perennial rhinitis attributed to MSG ingestion and positive responses to double-blind, placebo-controlled oral challenges [83,84]. However, this hypothesis requires further investigation, as MSG could aggravate rhinitis through its vasoactive properties, and the implication that it is a cause of rhinitis has not been established [74].

EVALUATION AND DIAGNOSIS — An evaluation for allergy to a food additive involves a detailed and focused clinical history, a physical examination, possibly skin testing with foods or isolated food additives, and possibly a supervised challenge [5].

Clinical history — The clinician should review each reaction that the patient can clearly recall in detail. (See 'Clinical manifestations' above.)

Analysis of causative foods — Allergic reactions to nutritive foods (such as tree nuts or seafood) are far more prevalent than reactions to food additives, and thus, food allergy must always be considered first in differential diagnosis. Ingredient lists of food items that caused adverse reactions should be carefully compared to determine if there is a nutritive food that is present in each item. If not, then food additives should be considered.

In the patient with a suggestive history, in whom a suspect additive can be identified, a trial of avoidance of the suspected additive would be reasonable. If no further reaction occurs, then this may be sufficiently confirmatory, and no further testing may be needed.

In the patient with a suggestive history, in whom a suspect additive cannot be identified, it is not useful or safe to advise patients to "avoid all additives," particularly if the patient experienced anaphylaxis. (See 'Pitfalls of additive-free diets' below.)

In patients with history of repeated anaphylaxis in association with eating that cannot be linked to a food or food additive, differential diagnosis should also include other disorders, such as indolent systemic mastocytosis, clonal mast cell disorder, or idiopathic mast cell activation syndrome. In addition, allergy to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate allergen that can cause delayed anaphylaxis several hours after ingestion of red meat, can evade diagnosis because the reactions occur much later after ingestion than is typical of most food allergies. (See "Mast cell disorders: An overview" and "Allergy to meats", section on 'Alpha-gal' and "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

Indications for allergy referral — Certain groups of patients suspected to have an allergic or asthmatic reaction to a food additive require further evaluation and should be referred to an allergy expert with knowledge about appropriate testing and challenge procedures:

Patients who have experienced anaphylaxis.

Patients with recurrent idiopathic urticaria/angioedema who have refractory or severe symptoms or are dependent upon glucocorticoids to control symptoms.

Patients with chronic persistent asthma or life-threatening asthmatic exacerbations.

Skin testing and challenge procedures may be needed to make the diagnosis and should be carried out by an allergy expert because these techniques require training and experience to interpret properly. In addition, allergic reactions during these procedures are possible (although uncommon). (See "Testing and challenge procedures to evaluate allergic and asthmatic reactions to food additives".)

Common goals of allergy evaluation are:

Proving that a food additive is causing a specific acute reaction, particularly in patients with anaphylaxis.

Excluding reactions to food additives and normalizing the diet in people who are avoiding multiple foods because of concerns about possible reactions to food additives.

Pitfalls of additive-free diets — Additive-free diets are usually not helpful. These diets are sometimes proposed as an initial means of determining that the patient is sensitive to some additive, without implicating a specific one. As an example, patients may be advised to eat a limited number of specified meats, grains, fruits, and vegetables for three weeks, and if the symptoms improve, then it is concluded that the patient is allergic to some additive. However, this approach has several drawbacks. Patients' symptoms often improve initially, but then gradual reintroduction of commercially prepared foods does not lead to identification of a specific culprit. Sometimes patients remain well for a while despite resuming a normal diet, and then their symptoms eventually return and begin to wax and wane again. In addition, it is difficult to adhere to an additive-free diet for any significant period of time, so most people cannot maintain the exercise for very long.

For patients who experienced anaphylaxis and who normally eat commercially prepared or processed foods, additive-free diets are difficult to maintain over time, and the patient is likely to resume his/her prior eating habits over time. This approach puts the patient at risk for future recurrences of anaphylaxis. Whenever possible, patients with anaphylaxis should be referred to an allergy specialist so that the chances of identifying the culprit allergen are maximized.

MANAGEMENT — Management usually consists of avoidance of commercially prepared foods that are likely to contain the additive in question. The patient should be informed of common foodstuffs that contain the additive, as well as all relevant chemical nomenclature and alternative names for that additive. For patients with asthma, good asthma control is an important aspect of care.

Patients with anaphylaxis — Any patient who has suffered anaphylaxis should be supplied with an epinephrine autoinjector, accompanied by verbal and written instructions on how and when to self-administer the drug. Referral to an allergy expert should be arranged when possible. (See "Prescribing epinephrine for anaphylaxis self-treatment".)

Epinephrine autoinjectors contain metabisulfite. However, the injection of the amount of metabisulfite contained in an epinephrine autoinjector did not trigger any symptoms or change in lung function in a small group of sulfite-sensitive asthmatics [85], and there are no case reports to suggest that autoinjectors are unsafe for sulfite-sensitive patients.

A personalized anaphylaxis action plan is helpful for providing specific instructions to patients about when and how to treat recurrent episodes. Action plan forms are available in English and Spanish from Food Allergy Research and Education (Food Allergy & Anaphylaxis Emergency Care Plan) and the American Academy of Pediatrics (Allergy and Anaphylaxis Emergency Plan English, Spanish). These plans are appropriate for patients with anaphylaxis from any cause. These materials are discussed separately. (See "Anaphylaxis: Emergency treatment", section on 'Discharge care'.)

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: How to use an epinephrine autoinjector (The Basics)")

Beyond the Basics topic (see "Patient education: Using an epinephrine autoinjector (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Of the thousands of food additives in use, only a small number have been implicated in allergic or allergic-like reactions. Symptoms include urticaria and/or angioedema, asthmatic reactions, and anaphylaxis. (See 'Overview' above.)

Clues that a patient may be reacting to a food additive include reactions that occur within minutes to a few hours of eating, a convincing history of similar reactions to several apparently unrelated foods, and reactions to commercially prepared forms of foods that are tolerated when prepared at home. However, allergy to a nutritive food is far more likely than allergy to an additive, so this must be considered first in the differential diagnosis. (See 'Clinical manifestations' above.)

Large series of patients with chronic urticaria/angioedema support the conclusion that symptoms are not caused by food additives, although foods and food additives can aggravate the condition in a minority of patients. Patients with recurrent idiopathic urticaria/angioedema who have refractory or severe symptoms or are dependent on glucocorticoids to control symptoms and appear to have flares in their symptoms after eating should be referred to an allergy specialist for further evaluation. (See 'Urticaria/angioedema' above.)

Sulfites can cause potentially serious asthmatic reactions in as many as 5 percent of patients with asthma, whereas individuals without asthma are rarely affected. Sulfite-sensitive patients more often have severe and/or steroid-dependent asthma. Patients with asthma who experience exacerbations after apparent exposure to sulfites should be counseled to avoid sulfite-containing foods (table 3) and (if possible) referred to an allergy specialist with experience in evaluating for sulfite sensitivity. (See 'Sulfites and related compounds' above.)

Patients with aspirin-exacerbated asthma were advised in the past to avoid foods and medications containing tartrazine (FD&C Yellow #5 or E102), because of a notion that tartrazine was cross-reactive with aspirin, although there is no convincing evidence to support this conclusion. Tartrazine avoidance is not necessary in patients with asthma. (See 'Tartrazine (FD&C Yellow 5)' above.)

The preservative sodium benzoate (E211) and the flavorings spearmint, peppermint, and menthol, have each been implicated in causing asthmatic symptoms in one or two case reports supported by challenge procedures. (See 'Asthmatic symptoms' above.)

Anaphylaxis has been reported to annatto (E160b), carmine (E120), saffron, erythritol (ERT), guar gum (E412), psyllium, carrageenan, lupine flour, gelatin, and pectin. These "natural" additives are derived from plants, insects, or animals, and the reactions are believed to be immunoglobulin (IgE)-mediated. Sulfites have been implicated in a very small number of cases of anaphylaxis. (See 'Anaphylaxis' above.)

An evaluation for allergy to a food additive involves a detailed and focused clinical history, a physical examination, possibly skin testing with foods or isolated food additives, and possibly a supervised challenge. Testing and challenge procedures should be done by an allergy expert, since these techniques require training and experience to interpret correctly and have the potential to cause allergic reactions in very sensitive patients. (See 'Evaluation and diagnosis' above.)

Any patient who has experienced anaphylaxis should be supplied with an epinephrine autoinjector. If the history suggests that a food additive may have been responsible, the patient should be referred to an allergy specialist with experience in performing testing and challenges to food additives. (See 'Patients with anaphylaxis' above.)

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Topic 2405 Version 15.0

References

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