Long-term management of patients with anaphylaxis

INTRODUCTION — The medical management of anaphylaxis has traditionally focused on recognition and treatment of the acute event. Equally important, however, is the long-term care of a patient who has experienced anaphylaxis and the implementation of measures to prevent and treat recurrences in community settings [1,2].

This topic will discuss the proactive, long-term management of patients after diagnosis and treatment of their acute anaphylaxis episode and confirmation of the cause(s). The diagnosis and treatment of acute anaphylaxis episode and an approach to identifying causes for anaphylaxis are discussed separately. (See "Anaphylaxis: Emergency treatment" and "Anaphylaxis: Confirming the diagnosis and determining the cause(s)".)

ONGOING EDUCATION FOR PATIENTS — Patients (and, for children, their families and caregivers) must be able to recognize the signs and symptoms of an anaphylaxis recurrence in the community and initiate treatment in a prompt and effective manner. Education about the recognition and management of anaphylaxis is an ongoing, long-term process that should be continued at follow-up visits with an allergy specialist at least annually while the patient remains at risk.

Important teaching points — Important teaching points, which should be reviewed on a regular basis, include the following (table 1) [2]:

●Epinephrine (adrenaline) is the first-line and most appropriate treatment for anaphylaxis; it should be given by intramuscular injection into the upper outer thigh muscle as soon as possible after symptoms of anaphylaxis are present (or if there is any doubt as to whether epinephrine is indicated) [2-7]. If a patient at risk for anaphylaxis had an epinephrine autoinjector prescribed but did not fill the prescription, did not have the autoinjector available at the time of the episode, or had it available but failed to use it, these issues should be discussed in-depth during the follow-up visit [6].

●H1 antihistamines and asthma inhalers (eg, albuterol) alone are not adequate treatment and are often ineffective for anaphylaxis. H1 antihistamines relieve itch and hives but take approximately 30 minutes to have an effect; they are ineffective against symptoms of anaphylaxis. Similarly, asthma inhalers provide temporary relief from wheezing and coughing but do not prevent or relieve upper airway obstruction, hypotension, or shock and are therefore not lifesaving [1-5,7,8].

●The severity of previous episodes of anaphylaxis does not always predict the severity of future episodes, which may be more severe, less severe, or similar to previous episodes [1,9]. However, in patients who experience recurrent anaphylaxis, the severity as well as the sequence of symptoms of subsequent episodes are most often the same as previous episodes [10].

●Anaphylaxis is underrecognized and undertreated, even by health care professionals [11,12]. Some patients do not have ready access to emergency medical services, and some emergency medical services teams are still not equipped with epinephrine or permitted to inject it. Therefore, people at risk for anaphylaxis (and, for children, their families or caregivers) must have an epinephrine autoinjector available at all times so that effective treatment can be initiated without delay.

PREPARING THE PATIENT TO TREAT POSSIBLE RECURRENCES — Patients who have experienced anaphylaxis should be equipped to treat possible recurrences in the community by carrying self-injectable epinephrine, having an anaphylaxis emergency action plan, and wearing medical identification.

Self-injectable epinephrine — Any patient who has experienced anaphylaxis should be supplied with one or more epinephrine autoinjectors and trained in why, when, and how to inject epinephrine [1-7,13]. For children who have experienced anaphylaxis, families and caregivers should be trained. Issues with regard to prescribing epinephrine autoinjectors correctly are reviewed in detail separately. (See "Prescribing epinephrine for anaphylaxis self-treatment".)

Patient educational materials include autoinjector trainers and printed handouts (see "Patient education: Using an epinephrine autoinjector (Beyond the Basics)"). Most autoinjector manufacturers provide trainer devices and website videos for training purposes.

Important issues with regard to epinephrine injection include need for prompt administration [14], need for a second dose [15], inability of children to access their epinephrine autoinjectors in school [16], lack of availability and/or high cost of autoinjectors in many countries [17], and need for training and regular coaching in correct and safe use of autoinjectors [18].

Important issues for discussion — There are some important reasons why a patient (or, for children, their families and caregivers) may fail to administer epinephrine when it is appropriate to do so. Providers should address these issues directly with patients as appropriate.

●One study surveyed a unique population of 1885 survivors of anaphylaxis in the community and asked about administration of epinephrine [19]. Users of epinephrine autoinjectors were defined as those who self-injected epinephrine or injected it into a person for whom they were responsible (eg, a child) during anaphylaxis. Users reported problems in deciding whether to use the epinephrine autoinjector, whether to go to the emergency department after using it, holding it in place, choosing the correct site on the thigh for the injection, deciding whether to repeat the dose, and disposing of the autoinjector(s) after use. Nonusers were defined as those who did not self-inject epinephrine or failed to inject it into a person for whom they were responsible (eg, a child) during anaphylaxis. Nonusers reported a variety of reasons for not injecting epinephrine, such as using an H1 antihistamine or an asthma inhaler instead and/or not having the epinephrine autoinjector available when the medical emergency occurred [19].

●In another study of children who had experienced anaphylaxis, caregivers' reasons for not using an epinephrine autoinjector included the belief that it was unnecessary (54.4 percent), uncertainty about its necessity (19.1 percent), having called an ambulance (7.8 percent), not having the device available (5.4 percent), fear of using it (2.5 percent), lack of training (2.5 percent), decision to go to the emergency department (1.5 percent), and expired device (1 percent) [20]. The use of expired autoinjectors is discussed elsewhere. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)

Educational efforts should focus on reviewing the following with patients and caregivers: the circumstances under which the autoinjector should be used, the importance of using it even if they have already called an ambulance or are headed to the emergency department, using it even if it is out of date, and having the device available at all times. Providers should repeatedly train patients and caregivers. Patients/caregivers can increase their comfort with the device by practicing with a trainer on themselves/the child and by practicing with expired live devices (once replaced) by injecting an orange. Some health care professionals have advocated for "practice" injections using nearly expired devices or a needle/syringe [21].

Anaphylaxis emergency action plan — Any individual who is at risk of anaphylaxis should have a written, personalized, and regularly updated anaphylaxis emergency action plan, developed with the assistance of their health care professional. In order to help patients recognize anaphylaxis, this form should list typical symptoms and signs that might develop suddenly during an episode. In addition, it should provide instructions for prompt epinephrine injection followed by transportation to the nearest hospital emergency department.

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 and Spanish). Other organizations across the world also provide their own plans, such as in the United Kingdom and Australia/New Zealand. These plans are appropriate for patients with anaphylaxis from any cause. (See 'Internet resources' below.)

Multiple copies of the completed form should be available at home, work, or school and when discussing the information with anyone who may be responsible for administering epinephrine to the patient at risk of anaphylaxis recurrence. In addition, the written personalized anaphylaxis emergency action plan should be reviewed and updated periodically at follow-up visits. This process often reveals areas in which the patient needs further instruction and also stimulates discussion of more complex and patient-specific issues [2].

Anaphylaxis wallet cards are also available from the AAAAI [2]. These cards contain similar information to the information on the anaphylaxis emergency action plan. Data from a randomized, controlled trial indicate that they are practical, concise anaphylaxis education mini-handouts [22].

Formal evaluation of the clinical efficacy and cost effectiveness of anaphylaxis emergency action plans is needed [22].

Medical identification — Patients should also be advised to consider medical identification jewelry listing the known causes for their anaphylaxis and their relevant comorbidities and concurrent medications. Options include medical identification bracelets and medallions. Bracelets are deemed safest for children to wear.

Detailed information about the known causes for a patient's anaphylaxis should be accurately documented in an individual's electronic and/or paper medical records and updated as needed [2].

DETECTION AND MANAGEMENT OF COMORBIDITIES — Coexistent medical conditions and medications that could impact the ability of the patient to withstand anaphylaxis or respond to epinephrine should be explored in all patients who have experienced anaphylaxis.

Comorbidities

Asthma — Persistent asthma, especially if symptoms are poorly controlled, may be an important risk factor for more severe anaphylaxis [23]. Optimal asthma management is therefore critically important in those patients with asthma who are also at risk of anaphylaxis to reduce morbidity from asthma and possibly anaphylaxis. (See "Fatal anaphylaxis", section on 'Possible risk factors'.)

Cardiovascular disease — Cardiovascular disease may be an important risk factor for deaths from anaphylaxis in middle-aged and older patients [24,25]. These risks need to be discussed with the patient as needed and with the other health care professionals involved in the patient's care. (See "Fatal anaphylaxis", section on 'Possible risk factors'.)

Mast cell disorders — Individuals with idiopathic anaphylaxis or severe anaphylaxis, particularly in response to insect stings, should be screened for underlying mast cell disease, such as indolent systemic mastocytosis. In contrast, there is no good evidence that underlying mast cell disease is a risk factor in severe anaphylaxis due to food allergy. Note that individuals with indolent mastocytosis can have a normal serum baseline tryptase level and no cutaneous or systemic findings such as organomegaly [26]. Such patients may be identified through mutational assays using D816V allele-specific polymerase chain reaction (PCR) primers (allele-specific quantitative PCR), performed on peripheral blood. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

Hereditary alpha tryptasemia — Hereditary alpha tryptasemia (HaT) is a common, autosomal dominant genetic trait, first recognized in 2016, which affects 5 to 6 percent of White populations in the United States, and Europe. Other populations have not yet been studied. The majority of individuals with HaT appear to be asymptomatic. In symptomatic patients, the presence of HaT is associated with an increased frequency and severity of immediate hypersensitivity reactions in at least three disorders: systemic mastocytosis, Hymenoptera venom allergy (ie, allergy to the stings of bees and related insects), and idiopathic anaphylaxis. (See "Hereditary alpha-tryptasemia".)

Medications for other disorders — The long-term management of patients with anaphylaxis also involves discussion of medications taken concomitantly for other disorders. The following classes of medications potentially present problems for patients at risk for recurrence of anaphylaxis:

●Beta-adrenergic blockers administered orally or topically (eg, eye drops) may be associated with severe anaphylaxis and may also potentially make anaphylaxis more difficult to treat by causing unopposed alpha-adrenergic effects and hypertension and reduced bronchodilator response to the beta-adrenergic effects of endogenous or exogenous epinephrine [7,27]. (See "Anaphylaxis: Emergency treatment", section on 'Glucagon for patients taking beta blockers'.)

●Alpha-adrenergic blockers may decrease the effects of endogenous or exogenous epinephrine at alpha-adrenergic receptors, rendering patients less responsive to the alpha-adrenergic effects of epinephrine.

●Angiotensin-converting enzyme (ACE) inhibitors may interfere with endogenous compensatory mechanisms, resulting in more severe or prolonged symptoms [27,28]. ACE inhibitors in combination with beta blockers may increase risk synergistically. Angiotensin II receptor blockers might be less likely to have this effect, although this has not been conclusively documented [29].

●Central nervous system (CNS) active medications, such as psychotropics, anxiolytics, and insomnia remedies, may impair cognitive function and patients' ability to recognize anaphylaxis causes and symptoms. CNS-active medications include sedating, first-generation H1 antihistamines (eg, diphenhydramine), which are widely used for the treatment of insomnia and allergic diseases [2,3,5,8].

The relevant risks and benefits of medications in the above classes should be discussed with these patients and with other health care professionals involved in their care, as the benefits of ongoing prescription may outweigh the risks of anaphylaxis. These discussions should be documented in the patient's medical record. Substitution of medications may be necessary in some patients.

EFFECTIVE AVOIDANCE OF TRIGGERS — Complete avoidance of an allergen requires ongoing education about the allergen and where it is likely to be encountered. Printed information on avoidance of relevant, specific allergens should be provided and reviewed at regular intervals with those at risk and their families and caregivers [1,2,7].

Allergens — The most common allergens are mentioned here. However, the list of implicated substances continues to lengthen (table 2). The cause of a patient's anaphylaxis is determined by taking a meticulous history and confirming the suspected culprit(s) by allergen-specific skin tests and allergen-specific immunoglobulin E (IgE) levels in serum. This is reviewed in more detail elsewhere. (See "Anaphylaxis: Confirming the diagnosis and determining the cause(s)", section on 'Testing for allergen cause(s)'.)

●Food – Patients with a history of food-induced anaphylaxis should avoid the foods that cause the reaction [30,31]. This is easier said than done [32]. Difficulties arise because of hidden, substituted, and cross-reacting foods, as well as foods that are contaminated with allergen because of cross-contact, for example, on shared production lines or in catering kitchens. Food producers often use "advisory" or "precautionary" allergen statements (such as "may contain X") to communicate risk; unfortunately, such statements are currently unregulated and may not accurately communicate the true presence or absence of unintended low-level allergen contamination in food products [33].

Vigilant food avoidance measures potentially decrease quality of life for those at risk of anaphylaxis to food and their families and for children, their caregivers, teachers, childcare workers, and classmates [34,35]. Adolescents and young adults at risk for food-induced anaphylaxis are particularly prone to risk-taking behaviors [36]. (See "Food allergy: Impact on health-related quality of life".)

●Insect stings – Ideally, patients with a history of insect sting-induced anaphylaxis should avoid subsequent exposure to insects. However, this is impractical under many circumstances and may be impossible for beekeepers, park rangers, gardeners, and others with occupational exposure [7,37]. (See "Stinging insects: Avoidance".)

●Medications – Patients with a history of anaphylaxis to a medication or biologic agent should have this clearly documented in the allergies section of their medical record and must not be given that specific medication. A safe and effective non-cross-reacting drug, preferably from a different pharmacologic class, should be substituted, if available. A written list containing the name of the medication that caused the anaphylaxis and the names of related and cross-reacting drugs should be provided [5,7,38-40].

●Vaccines – Anaphylaxis to vaccines for prevention of infectious diseases is rare [41], even to vaccines introduced during the coronavirus disease 2019 (COVID-19) pandemic (see "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'Immediate-type hypersensitivity reactions'). Patients with this history may be evaluated by using skin tests to the vaccine and its components (excipients) [41]. (See "Allergic reactions to vaccines".)

●Exercise – Prevention strategies for anaphylaxis caused by exercise depend upon the avoidance of cofactors, including potential trigger foods, ethanol, or specific medications (eg, nonsteroidal antiinflammatory drugs [NSAIDs]). Where reactions are triggered by a food in combination with a cofactor, empirical advice is for the food to be avoided for approximately four hours before exercise. If no specific cofactor for exercise-induced anaphylaxis has been identified, it might be prudent for the individual to avoid ingesting anything at all within four hours of exercise. Factors amplifying exercise-induced anaphylaxis might include airborne pollen or mold allergens, high humidity, extreme heat, or extreme cold. Based on a detailed history of the patient's previous episodes, avoidance of one or more of these factors might be relevant. People with exercise-induced anaphylaxis need to be advised that they should not exercise alone. They should discontinue exercise at the earliest hint of symptom development and inject epinephrine. They should not run for help [7,42]. (See "Exercise-induced anaphylaxis: Management and prognosis".)

●Natural rubber latex (NRL) – Patients at risk for anaphylaxis from NRL should avoid exposure to NRL, which can be found in disposable gloves, condoms, infant pacifiers, toys, balloons, sports equipment, and other items. They should inform all of their health care professionals about their NRL allergy, particularly when being evaluated for potential surgery or dental work. In some of these patients, foods that cross-react with NRL (for example, kiwi, banana, avocado, tomato, and white potato) should also be avoided [7]. (See "Latex allergy: Management", section on 'Individual avoidance' and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Latex-fruit syndrome'.)

Cofactors — Many patients develop symptoms more readily in the presence of one or more additional cofactors or augmenting factors. The cofactors that are relevant for any given patient vary considerably, but may include the following:

●Exercise, physical exertion

●Stress or jet lag

●Nonsteroidal antiinflammatory drugs (NSAIDs)

●Alcoholic beverages

●Premenstrual or ovulatory phases of the menstrual cycle

●Extremes of temperature (either high heat and humidity or cold exposure)

●Seasonal pollen exposure in pollen-sensitized patients

●Infections or illness

INTERVENTIONS TO REDUCE SENSITIVITY — Specific interventions to reduce the risk of recurrent reactions are available for certain causes of anaphylaxis [37-44].

●Food – Immunotherapy for individuals at risk of food-induced anaphylaxis is becoming increasingly available in many countries [45,46], and a treatment for peanut allergy has been approved by the US Food and Drug Administration (FDA), although uptake has been limited [47]. Immunotherapy is typically performed through oral exposure ("oral immunotherapy"), although the sublingual and epicutaneous (skin patch) routes have also been evaluated; the latter has been shown to be efficacious as well, but an approved product is not yet available. Desensitization (temporary antigen hyporesponsiveness that depends on regular food ingestion) is successful in approximately 60 percent of individuals but is often lost after a period of avoidance. Permanent immunologic tolerance (the ability to ingest food without symptoms despite prolonged periods of avoidance or irregular intake) has been difficult to demonstrate, but several studies have shown that this can now be achieved in approximately 30 percent of subjects with longer durations of treatment (three to five years) prior to avoidance [48]. Treatment-related symptoms are common, as is anaphylaxis [49,50]. Alternative approaches are undergoing clinical trials, including vaccines for food allergy and also the use of monoclonal antibodies such as anti-IgE therapies, both of which also have shown promising results in preliminary studies [51,52]. (See "Oral immunotherapy for food allergy" and "Experimental therapies for food allergy: Immunotherapy and nonspecific therapies".)

●Insect stings – Anaphylaxis caused by venom from insects in the order Hymenoptera (eg, honey bees, yellowjackets, yellow hornets, white-faced hornets, paper wasps, and fire ants) can be almost entirely prevented by use of allergen-specific immunotherapy, as demonstrated in randomized, placebo-controlled trials. This therapy is initiated by an allergy/immunology specialist. A five-year treatment period provides long-lasting protection for most patients, although, in some high-risk patients (such as those with underlying systemic mastocytosis), it is continued indefinitely [37]. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Indications and patient selection' and "Stings of imported fire ants: Clinical manifestations, diagnosis, and treatment", section on 'Venom immunotherapy'.)

●Medications needed daily – Anaphylaxis may be caused by a medication that is essential for the patient and is needed on a daily basis and for which there is no effective and safe substitute available (eg, aspirin for the patient with atherosclerotic heart disease). Successful desensitization must be followed by regular daily administration; otherwise, the desensitization effect is lost [38]. (See "NSAIDs (including aspirin): Allergic and pseudoallergic reactions" and "Diagnostic challenge and desensitization protocols for NSAID reactions" and "Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization".)

●Medications needed temporarily – Desensitization can be performed successfully to prevent anaphylaxis caused by a drug that is needed temporarily as a single dose or an uninterrupted course of multiple doses and for which there is no effective and safe substitute available. Examples include antimicrobials, especially beta-lactam antibiotics, antifungals, antivirals, nonsteroidal antiinflammatory drugs (NSAIDs), chemotherapeutics (eg, platinum salts and taxanes), and biologics [38,39]. It is important to counsel the individual that the desensitization effect only persists for as long as the treatment is taken. Even just a break of a few days is sufficient to cause the patient to be reactive, and, if the medication is subsequently needed again, then the patient must undergo further desensitization. (See "Rapid drug desensitization for immediate hypersensitivity reactions" and "Penicillin allergy: Immediate reactions" and "Infusion reactions to systemic chemotherapy".)

●Human seminal fluid – Uncommonly, seminal fluid can cause anaphylaxis in females. Symptoms typically begin during or shortly after sexual intercourse. Reactions to seminal fluid can be prevented by use of condoms. Desensitization strategies have been described [7,44]. (See "Allergic reactions to seminal plasma".)

●Idiopathic anaphylaxis – Idiopathic anaphylaxis is a diagnosis of exclusion that is made when no cause for the anaphylaxis episode can be identified. Some patients with this diagnosis actually have a mast cell disorder. Therefore, in addition to a meticulous history and physical examination for skin lesions of cutaneous mastocytosis, an elevated baseline serum tryptase level may help to identify such patients [28,53,54]. Omalizumab, a monoclonal antibody to IgE, may also provide some protection. (See "Idiopathic anaphylaxis" and "Mast cell disorders: An overview".)

MONITORING — The long-term monitoring of a patient with a history of anaphylaxis due to a known cause includes following the status of the individual's sensitization to the allergen over time.

●Food allergy – For patients with food-induced anaphylaxis, appropriate monitoring involves obtaining detailed historical information about inadvertent exposures and reactions, as well as measurements of food-specific IgE levels in serum or, less commonly, food-specific skin tests at appropriate intervals, depending on their age and thus likelihood of natural resolution or outgrowth: Most children allergic to cow's milk and hen's egg will outgrow this allergy over time, while only a minority that are allergic to peanuts and tree nuts will do so [55]. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

●Drug allergies – For patients with drug-induced anaphylaxis, monitoring of sensitization status is also important, as sensitization may resolve with sufficient time. As an example, only a small percentage of patients labeled as penicillin allergic are actually allergic. Skin testing and challenge consistently demonstrate that the vast majority can safely receive penicillin [56], although, increasingly, approaches to delabeling no longer recommend skin testing prior to oral challenge in low-risk individuals [57,58]. (See "Penicillin allergy: Immediate reactions".)

INTERNET RESOURCES — There are a number of internet resources available for patients that consistently provide accurate information, including the following:

●Food Allergy Research & Education (FARE)

●American Academy of Allergy, Asthma & Immunology (AAAAI)

●American College of Allergy, Asthma & Immunology (ACAAI)

●National Institute of Allergy and Infectious Diseases (NIAID)

●Canadian Society of Allergy and Clinical Immunology (CSACI)

●British Society for Allergy & Clinical Immunology (BSACI)

●European Academy of Allergy and Clinical Immunology (EAACI)

●Australasian Society of Clinical Immunology and Allergy (ASCIA)

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: Anaphylaxis".)

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

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

●Basics topics (see "Patient education: Anaphylaxis (The Basics)" and "Patient education: How to use an epinephrine autoinjector (The Basics)")

●Beyond the Basics topics (see "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Anaphylaxis treatment and prevention of recurrences (Beyond the Basics)" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Ongoing education – Patients (and, for children, their families and caregivers) should be taught to recognize the early symptoms of anaphylaxis and to inject epinephrine promptly (table 1). They should be counseled regularly that epinephrine injection is the only appropriate emergency treatment for anaphylaxis. For patients with confirmed anaphylaxis, evaluation to determine the responsible trigger and education about specific allergen avoidance are essential. This is an ongoing, long-term process that should be continued at each follow-up visit. (See 'Ongoing education for patients' above.)

●Training in use of an epinephrine autoinjector – Patients should be supplied with at least one and preferably two doses of epinephrine autoinjector devices and trained in when and how to use the autoinjector (See 'Preparing the patient to treat possible recurrences' above.)

●Anaphylaxis action plan – A personalized anaphylaxis emergency action plan is a written, one-page document that lists the signs and symptoms of anaphylaxis and outlines treatment appropriate for that individual. It can be used to convey information between clinician and patient, as well as between patient and family, caregivers, teachers, or other people who may be involved in emergency treatment of recurrent episodes. (See 'Anaphylaxis emergency action plan' above.)

●Review of medications for other disorders – All prescription and nonprescription medications taken by the patient for any reason should be monitored. Certain medications may interfere with early recognition of symptoms, increase the severity of symptoms, or impact the treatment of anaphylaxis. In some clinical situations, it is possible to substitute medications with a more favorable benefit:risk ratio. (See 'Medications for other disorders' above.)

●Education about allergen avoidance – Avoidance of triggers for anaphylaxis is easier said than done and is difficult to maintain over years or decades. However, it is of fundamental importance in prevention of subsequent anaphylaxis in the community. (See 'Effective avoidance of triggers' above.)

●Interventions to reduce sensitivity to specific allergens – Specific immunomodulation is available for patients with anaphylaxis caused by certain causes, such as stinging insect venoms, certain foods, and some medications. (See 'Interventions to reduce sensitivity' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges F Estelle R Simons, MD, FRCPC, who contributed to earlier versions of this topic review.