Management of IgE-mediated food allergy: An overview

INTRODUCTION — 

Management of immunoglobulin E (IgE) mediated food allergy consists of avoidance of the food allergen, attention to nutrition and psychologic issues, treatment of accidental exposures with medications, and the additional option of treatment with therapies that may increase the reaction threshold [1]. The ultimate goal of immunotherapeutic approaches to food allergy is to induce permanent tolerance to the food, where allergic reactions will not recur upon reexposure to the food in any amount after stopping the therapy. However, none of the available treatments or those under investigation appear to achieve permanent tolerance in a substantial number of treated patients. Rather, in most cases, they temporarily desensitize or protect patients, requiring continued treatment to maintain efficacy [2]. (See "Management of food allergy: Avoidance" and "Food-induced anaphylaxis" and "Anaphylaxis: Emergency treatment" and "Prescribing epinephrine for anaphylaxis self-treatment".)

Novel therapeutic approaches to food allergy can be classified as food allergen specific (eg, immunotherapy with native or modified recombinant allergens) or food allergen nonspecific (eg, anti-IgE, other monoclonal antibodies, small-molecule inhibitors, or microbial therapies) [3]. (See "Food allergy management: Allergen-nonspecific therapies" and "Food allergy management: Allergen-specific immunotherapy".)

The general approach to management of IgE-mediated allergy is reviewed here. The specific aspects of management are reviewed in greater detail separately. (Refer to appropriate see links in sections below.)

IgE-MEDIATED FOOD ALLERGY — 

IgE-mediated food allergic reactions are referred to as "immediate" or "acute" allergic reactions because they are rapid in onset, typically beginning within seconds to minutes from the time of ingestion, although reactions up to two hours or more after exposure can occur [4]. One exception to the typical temporal pattern is IgE-mediated reaction to carbohydrate allergens in meats, which usually begins four to six hours after ingestion (see "Allergy to meats"). Signs and symptoms can involve the skin, respiratory and gastrointestinal tracts, and cardiovascular system (table 1 and table 2) and are caused by mediator release from tissue mast cells and circulating basophils (figure 1). (See "Clinical manifestations of food allergy: An overview" and "Food-induced anaphylaxis" and "Pathogenesis of food allergy".)

Two unique and distinct presentations are pollen-food allergy syndrome/oral allergy syndrome, in which symptoms are limited to in and around the oropharynx, and food-dependent, exercise-induced anaphylaxis (FDEIAn), in which reactions to foods only occur in association with exercise. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis" and "Anaphylaxis: Acute diagnosis", section on 'Diagnostic pitfalls'.)

Most patients react to one or two specific foods/food groups, although an increasing number of patients react to multiple foods. Allergies to certain foods, such as hen's egg and cow's milk, tend to be outgrown during childhood, whereas allergies to other foods, such as shellfish and nuts, are much more likely to persist. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution" and "Food intolerance and food allergy in adults: An overview".)

TERMINOLOGY — 

Various terms are used to describe goals and outcomes in patients treated for food allergy (table 3 and figure 1):

●Reaction threshold – The lowest amount of ingested food that causes allergic symptoms [5].

●Tolerance – "Tolerance" is a permanent state, which means that there is no recurrence of clinical reactivity upon reintroduction of a full, age-appropriate serving of the food after a period of abstinence and interruption of therapy [6].

●Sustained unresponsiveness or remission – Permanent tolerance is difficult to confirm, particularly in a shorter-term clinical trial. Thus, the term "sustained unresponsiveness" (SU) was coined to describe the lack of a reaction to ingestion of a full challenge dose after therapy was discontinued for weeks to months.

●Desensitization – "Desensitization" is a temporary state of protection through increased reaction threshold. Patients can be fully desensitized to a food, such that they can ingest a normal serving size without having a reaction, or partially desensitized, such that the reaction threshold (eliciting dose) is raised but they still react to an amount less than a normal serving size. Partially desensitized patients, in theory, should be less likely to have a reaction to an accidental exposure because of the increased reaction threshold. An increased reaction threshold can be achieved through continued low-dose exposure to the allergen to maintain the protective state or without exposure to food (eg, as a result of anti-IgE monoclonal antibody or small-molecule drugs).

●Response – Specific studies may define the "rate of response" or "responders" in a variety of ways. As an example, a study participant who reacted at an amount of peanut equivalent to less than or equal to half of peanut kernel (100 mg peanut protein) might be considered a responder if they could ingest the equivalent of three or more peanut kernels (600 mg peanut protein). Alternatively, a responder might be defined as a study participant who reacted to the baseline challenge but is able to ingest a full serving of peanut (6 to 8 grams of peanut protein) after treatment.

GOALS — 

The ultimate goal of treatment for food allergy is to induce permanent tolerance to the food so that it can be eaten ad libitum. Additional goals are prevention of reactions, prompt treatment of acute reactions to prevent morbidity and mortality, and mitigating the impact of food allergies on nutrition and overall health [7]. Most treatments typically only improve (increase) the threshold of reaction. However, an increased threshold may prevent reactions from accidental ingestions, reduce quality-of-life burdens and anxiety, and, if the food can be included in the diet, improve nutrition as well. Important goals for patients and their parents/caregivers are reduction of anxiety related to food allergies and improvement in quality of life [8]. (See "Management of food allergy-related anxiety in children and their parents/caregivers" and "Management of food allergy: Nutritional issues".)

TREATMENT OF ACUTE IgE-MEDIATED REACTIONS — 

Treatment of acute IgE-mediated food reactions depends upon the type and severity of symptoms as well as past history of reactions and additional factors (eg, use of beta blockers or medications that can increase adverse effects of epinephrine) [9]. (See "Anaphylaxis: Confirming the diagnosis and determining the cause(s)", section on 'Concurrent medications and other substances' and "Food-induced anaphylaxis", section on 'Epinephrine' and "Food-induced anaphylaxis", section on 'Areas of uncertainty'.)

Manifestations of an IgE-mediated food reaction can range from mild, isolated symptoms (eg, nasal or oral pruritus, sneezing, limited urticaria, mild nausea/gastrointestinal upset) to varying degrees of anaphylaxis including anaphylactic shock (table 2 and figure 2). (See "Clinical manifestations of food allergy: An overview" and "Food-induced anaphylaxis", section on 'Clinical features' and "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Clinical manifestations'.)

The first and most important therapy in anaphylaxis is epinephrine (table 4 and table 5). There are no absolute contraindications to epinephrine in the setting of anaphylaxis. Treatment of anaphylaxis with epinephrine and adjunctive therapies is discussed in greater detail separately. (See "Anaphylaxis: Emergency treatment" and "Food-induced anaphylaxis", section on 'Epinephrine' and "Prescribing epinephrine for anaphylaxis self-treatment".)

Mild, localized symptoms can be managed by close observation with or without treatment of the specific symptom (eg, antihistamine for oral pruritus or a few hives). However, there are certain situations in which treatment with epinephrine in the absence of clear anaphylaxis may be advised. These scenarios and management of isolated symptoms are reviewed separately. (See "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Patients with oral symptoms to low-risk foods' and "New-onset urticaria (hives)", section on 'H1 antihistamine therapy for all patients' and "Food-induced anaphylaxis", section on 'Areas of uncertainty'.)

ANTICIPATION OF FUTURE REACTIONS (EMERGENCY ACTION PLAN) — 

Clinicians should ensure that patients with food allergies and their caregivers have a plan in place for management of food allergy reactions if they occur. This plan includes written instructions and prescription of self-administered epinephrine for treatment of anaphylaxis. (See "Food-induced anaphylaxis", section on 'Preparation for recurrent reactions' and "Prescribing epinephrine for anaphylaxis self-treatment".)

LONG-TERM MANAGEMENT STRATEGIES

Choosing a strategy — For patients with IgE-mediated food allergy, some degree of avoidance of culprit food allergens is a required component of therapy. It is particularly essential for those at risk of anaphylaxis. The benefits, costs, and risks of additional management options should be discussed as part of a shared decision-making approach, but avoidance alone is appropriate for most patients [10]. A decision support tool is available for the patients and caregivers who are considering oral immunotherapy (OIT) [11]. These approaches are discussed below and in greater detail separately. (See "Management of food allergy: Avoidance" and "Food allergy management: Allergen-specific immunotherapy" and "Food allergy management: Allergen-nonspecific therapies".)

The US Food and Drug Administration (FDA) approved therapies that raise the reaction threshold include omalizumab (an anti-IgE monoclonal antibody) and peanut allergen oral immunotherapy powder. However, these therapies have substantial costs and burdens that may outweigh the benefits for many patients. Additional strategies include office-based OIT with commercial food products and sublingual immunotherapy (SLIT) with aqueous solutions.

Additional management options may include graded oral food challenges (OFCs) to determine if extensively heated, baked foods containing hen's egg or cow's milk may be tolerated and added to the diet, as is the case for many children with these food allergies. (See "Egg allergy: Management" and "Milk allergy: Management".)

Most reactions can be prevented with careful avoidance, but accidental exposures and reactions can still occur. Thus, patients and caregivers must be prepared to treat reactions regardless of the approach taken. (See 'Treatment of acute IgE-mediated reactions' above and 'Anticipation of future reactions (emergency action plan)' above.)

Avoidance — Avoidance of culprit food allergens to decrease the risk of reactions is the preferred strategy for nearly all patients with food allergy and is essential for those at risk for anaphylaxis. Options range from strict avoidance of all foods that may contain even trace amounts of the allergen to less restrictive avoidance.

Strict avoidance — Strict avoidance is simple in theory but difficult in practice and imposes real burdens, including nutritional restrictions, impaired quality of life, and loss of "food freedom" [12]. (See "Management of food allergy: Avoidance".)

Food-induced reactions including anaphylaxis can still occur despite patients' best efforts at avoidance. In addition, avoidance can restrict daily activities and impact social interactions, reducing quality of life. Fear and anxiety around the possible risk of a reaction from an accidental exposure can also negatively affect quality of life. Furthermore, avoidance of multiple food allergens, particularly those that are staples in the diet, can lead to deficits in nutrition and growth in children if not carefully managed. Avoidance of food allergens and the impact of food allergies on patients and caregivers are discussed in greater detail separately. (See "Management of food allergy: Avoidance" and "Management of food allergy-related anxiety in children and their parents/caregivers" and "Food allergy: Impact on health-related quality of life" and "Management of food allergy: Nutritional issues".)

Less restrictive avoidance based upon history, food, and/or testing — There are several situations in which less strict avoidance is reasonable:

●Pollen-food allergy syndrome – Patients with pollen-food allergy syndrome to a low-risk plant food (raw fruit or vegetable) can eat cooked forms of these foods. In addition, patients who have had mild symptoms localized to the oropharynx with ingestion of the raw food may not need to avoid the food because the risk of anaphylaxis is low. However, oral symptoms to peanut and tree nuts may represent a spectrum of a systemic allergy to peanut and tree nuts, especially in children who are not sensitized to pollen. Evaluation using a commercially available component-based test can identify patients with symptoms to peanut and tree nuts caused by cross-reactivity with pollen (eg, Bet v 1 cross-reactive peanut Ara h 8, hazelnut Cor a 1) versus those who are primarily sensitized to nut-specific seed storage proteins (eg, Ara h 1,2,3 or Cor a 9, 14) [13]. (See "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Patients with oral symptoms to low-risk foods' and "Component testing for pollen-related, plant-derived food allergies".)

●Food-dependent exercise-induced anaphylaxis – Patients with food-dependent exercise-induced anaphylaxis (FDEIA) can eat the food when ingestion is not associated with exercise. (See "Exercise-induced anaphylaxis: Management and prognosis", section on 'Food avoidance in patients with FDEIA'.)

●More cooked/processed forms of food – As an example, children tolerant to baked forms of cow's milk and/or hen's egg avoid lightly cooked/processed versions of these foods while safely ingesting baked versions [14]. Similarly, some patients with fish allergy may tolerate canned/tinned tuna, and some with meat allergy can ingest well-cooked or baked beef. (See "Milk allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Egg allergy: Management", section on 'Monitoring for resolution and reintroduction'.)

●Specific forms or amounts of a food – Whole sesame seeds, for example, may pass through the digestive tract intact and therefore not trigger a reaction in patients with sesame allergy who would react to ground sesame (tahini) [15-18]. Similarly, some patients with sesame allergy have a longstanding history of tolerating sesame oil as an ingredient in processed foods. These forms of sesame can be consumed ad libitum in small amounts in these patients but ground sesame avoided.

●Threshold identification to reduce dietary restrictions – Identification of tolerance to a small amount of an allergenic food or certain forms of a food through an OFC can impact management and quality of life in several ways [19-24]. It can help identify patients who are likely at lower risk for a reaction triggered by a trace or small amount of allergen and decrease patient and caregiver concerns about such reactions [5]. It may also allow for consumption of products with advisory labeling for the allergenic food and may also enable the introduction of a small amount of the food ad libitum [25]. A low-dose OFC can be performed if this is the primary goal of the OFC. It can also be used to identify the starting point for OIT, as discussed below. (See 'Threshold-based treatment options' below and "Oral food challenges for diagnosis and management of food allergies".)

However, it is important that patients/caregivers understand that an OFC is not an exact replica of what can happen with food ingestion in a normal setting, as there are other factors in addition to the quantity of food consumed that can impact the occurrence and severity of a reaction (eg, exercise, illness). In addition, OFCs are time consuming, there are limited resources for performing them, and they can trigger allergic reactions including anaphylaxis, although performing a low-dose OFC can minimize these limitations and risks. (See "Food-induced anaphylaxis", section on 'Risk factors' and "Food-induced anaphylaxis", section on 'Factors affecting presentation'.)

Threshold-based treatment options — An OFC can be used to identify the starting point for OIT, a treatment that involves stepwise reintroduction of a food with supervised up-dosing. Patients with higher thresholds may need less frequent up-doses compared with patients who have lower thresholds who are treated with standard OIT approaches. Whether regular ingestion of small amounts of the allergen in the diet enhances and/or accelerates resolution of the allergy in younger children is also under investigation. OIT is discussed briefly here and reviewed in greater detail separately. (See "Oral food challenges for diagnosis and management of food allergies", section on 'Determine the reaction threshold' and "Food allergy management: Allergen-specific immunotherapy", section on 'Overview of OIT'.)

Raise the reaction threshold — An ideal alternative to avoidance is a treatment that induces permanent tolerance to the food. However, none of the available treatments achieve permanent tolerance in a substantial number of treated patients. Rather, they offer the possibility of temporary protection from reactions to accidental exposures by raising the threshold for a triggering exposure (partial desensitization) [5]. In addition, patients require continued treatment to maintain efficacy and ongoing avoidance of the culprit food(s) in the case of therapies with maintenance doses that are lower than anticipated accidental exposures in the real world.

Anti-IgE — Omalizumab increases the reaction threshold to food allergens (a surrogate for protection against reactions due to accidental exposures) for many patients and theoretically should work for any food [26]. However, anti-IgE therapy has not been shown to induce permanent tolerance, is costly, and protection requires administration at regular intervals indefinitely. An ongoing food allergen avoidance is necessary, unless a reaction threshold is established through supervised testing and can inform the level of avoidance. There are additional limitations and uncertainties, including which patients may benefit most from therapy [27]. Omalizumab for food allergy is discussed in greater detail separately. (See "Food allergy management: Allergen-nonspecific therapies", section on 'Omalizumab (anti-IgE)'.)

Oral immunotherapy — Compared with avoidance alone, OIT increases supervised in-clinic food challenge thresholds [9]. However, OIT increases the risk of anaphylaxis and need for epinephrine, and milder reactions (skin, gastrointestinal) are common, particularly during up-dosing [28]. Other burdens associated with OIT include lifestyle restrictions associated with dosing, need to take the dose daily, and additional medical visits [29]. The only US FDA-approved product for OIT is a specific preparation of peanut allergen oral immunotherapy powder containing consistent quantities of the major peanut (Arachis hypogaea, Ara h) proteins. OIT for food allergy is discussed in greater detail separately. (See "Food allergy management: Allergen-specific immunotherapy".)

Introduce less allergenic forms of the food — For most food allergies, patients must completely avoid the food. However, many patients with cow's milk and hen's egg allergy, and some patients with allergy to meats or seafood, tolerate more cooked/processed forms of these foods because some allergenic epitopes are sensitive to heating/processing. For patients with milk and egg allergies, we perform serial monitoring (clinical history and blood and/or skin allergy testing) and offer graded, supervised OFCs to milk or egg in baked goods when test results and history suggest the benefits of introduction of baked milk/egg into the diet are likely to outweigh the risk of a reaction during the challenge [30]. Further gradual introduction is determined on a case-by-case basis. This approach is discussed in greater detail separately. (See "Milk allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Egg allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Food allergy in children: Prevalence, natural history, and monitoring for resolution" and "Oral food challenges for diagnosis and management of food allergies".)

MANAGEMENT OF SPECIFIC FOOD ALLERGIES — 

Management of issues related to specific food allergies (eg, what food products are more likely to contain a given food allergen, management approach for younger siblings, determining whether well-cooked forms may be tolerated), as well as the unique form of oral allergy syndrome (food-pollen syndrome), are discussed in greater detail in topics specific to these food allergens:

●Peanut, tree nut, and seed allergy – (See "Peanut, tree nut, and seed allergy: Management".)

●Cow's milk allergy – (See "Milk allergy: Management".)

●Hen's egg allergy – (See "Egg allergy: Management".)

●Grain allergy – (See "Grain allergy: Clinical features, diagnosis, and management".)

●Seafood allergy – (See "Seafood allergies: Fish and shellfish", section on 'Management'.)

●Meat allergy – (See "Allergy to meats", section on 'Management'.)

●Oral allergy syndrome – (See "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)".)

FOOD ALLERGY-RELATED ISSUES

Nutritional issues — Dietary limitations due to food allergy can lead to malnutrition due to deficits in total energy and/or deficiencies in specific macronutrients and micronutrients. In children, these nutritional deficits can negatively affect growth. The specific impact varies depending on the food or foods avoided. A registered dietitian familiar with food allergies can help patients avoid nutritional deficiencies and optimize nutrition within the context of the allergen-restricted diet. (See "Management of food allergy: Nutritional issues".)

Food allergy-related anxiety — Food allergy-related anxiety in the patient and caregiver(s) is common. An appropriate degree of anxiety can lead to safer practices related to food allergy. Psychoeducation and facilitation of self-management can help decrease food allergy-related anxiety [12]. Consultation with a mental health professional is warranted if the anxiety seems excessive and is causing substantial distress and dysfunction (eg, an anxiety disorder may be present). (See "Management of food allergy-related anxiety in children and their parents/caregivers".)

Natural history and monitoring for resolution — Certain food allergies are more likely to resolve in childhood (eg, cow's milk, hen's egg, grains), while others are more likely to persist or develop later in life (eg, peanut, tree nuts, seafood). The natural history of food allergies and monitoring for resolution and reintroduction are discussed in detail separately. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

SPECIAL CIRCUMSTANCES

Management at schools and camps — Food allergy in school-age children is common. Policies to keep food-allergic children safe often affect all members of the student body and staff within a given setting [31]. The food allergy management plan of a school or camp should include policies regarding where food is allowed, where medications are stored, and protocols for contacting emergency services and parents/caregivers during a reaction. Specific strategies can be implemented to minimize the risk of food allergy reactions in school and camp settings. (See "Food allergy in schools and camps".)

Management at colleges and universities — Adolescents and young adults are at higher risk for fatal food-induced anaphylaxis due to risk-taking behaviors, including eating unsafe foods and not carrying or appropriately using emergency medications. Additional management issues for college-age students with food allergies include being independently responsible for daily management, living in a social setting with peers, and obtaining meals that are prepared by others. Preparation for college campus management includes addressing proper diagnosis, treatment, and documentation of the allergy, as well as approaches to reduce risky behaviors; meeting with dining and housing services; and discussing any needed accommodations or modifications with the school [32]. Policies and procedures, which may vary by institution and circumstance, should address key factors, including having a confidential process for managing requests for accommodations/modifications, campus emergency response plans, and dining services that can assist the student in obtaining safe meals. (See "Food allergy in college and university students: Overview and management".)

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".)

SUMMARY AND RECOMMENDATIONS

●Management goals – The ultimate goal of immunotherapy for food allergy is to induce permanent tolerance to the food so that it can be eaten ad libitum. Additional goals are prevention of reactions, prompt treatment of acute reactions to prevent morbidity and mortality, and minimizing the impact of food allergies on nutrition, mental health, and overall health. (See 'Goals' above.)

●Treatment of acute reactions – Treatment of acute immunoglobulin E (IgE) mediated food reactions depends upon the type and severity of symptoms, as well as past history of reactions and additional factors. Patients with any degree of anaphylaxis should be treated with epinephrine. The tables provide a rapid overview of the treatment of anaphylaxis in children and adults (table 4 and table 5). Additional details are discussed in greater detail separately. (See 'Treatment of acute IgE-mediated reactions' above and "Anaphylaxis: Emergency treatment" and "Food-induced anaphylaxis", section on 'Epinephrine' and "Prescribing epinephrine for anaphylaxis self-treatment".)

●Long-term management:

•Avoidance alone versus avoidance plus threshold raising therapy – For patients with IgE-mediated food allergy, some degree of avoidance of culprit food allergens is a required component of therapy. It is particularly essential for those at risk of anaphylaxis. A discussion of risks, costs, and benefits of add-on, threshold-raising therapies should be performed, but avoidance alone is appropriate for most patients.

However, strict avoidance is simple in theory but difficult in practice and imposes real burdens, including nutritional restrictions, impaired quality of life, and loss of "food freedom." Omalizumab and oral immunotherapy (OIT) may offer temporary protection from reactions to accidental exposures by raising the threshold for a triggering exposure (partial desensitization), but omalizumab has not been shown to induce permanent tolerance, and OIT is associated with an increased rate of reactions due to treatment. In addition, both therapies require continued treatment to maintain efficacy and ongoing avoidance of the culprit food(s). There may be select patients for whom avoidance plus omalizumab and/or OIT is reasonable. Food allergen avoidance and the nuances of selection of treatments that may raise the reaction threshold are discussed in detail separately. (See 'Choosing a strategy' above and "Management of food allergy: Avoidance" and "Food allergy management: Allergen-nonspecific therapies", section on 'Omalizumab (anti-IgE)' and "Food allergy management: Allergen-specific immunotherapy".)

•Introduction of more cooked/processed forms of the food – For most food allergies, patients must completely avoid the food. However, many patients with cow's milk and hen's egg allergy, and some patients with allergy to meats or seafood, tolerate more cooked/processed forms of these foods. The option of oral food challenges (OFCs) to determine if these forms are tolerated is offered to the patient (and caregivers) if test results and history suggest that the benefits of introduction are likely to outweigh the risk of a reaction during the challenge. (See 'Introduce less allergenic forms of the food' above and "Milk allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Egg allergy: Management", section on 'Monitoring for resolution and reintroduction' and "Food allergy in children: Prevalence, natural history, and monitoring for resolution" and "Oral food challenges for diagnosis and management of food allergies".)

●Specific food allergy issues and special circumstances:

•Nutritional issues (see "Management of food allergy: Nutritional issues")

•Food allergy-related anxiety (see "Management of food allergy-related anxiety in children and their parents/caregivers")

•Natural history and monitoring for resolution and reintroduction (see "Food allergy in children: Prevalence, natural history, and monitoring for resolution")

•Management at schools and camps (see "Food allergy in schools and camps")

•Management at colleges and universities (see "Food allergy in college and university students: Overview and management")