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].
Long-term risk reduction includes the following elements [1]:
●Ongoing education about recognition and prompt treatment of future anaphylactic episodes.
●Optimal management of relevant comorbidities (eg, asthma or cardiovascular disease) and assessment or reassessment of the benefits and risks of concurrent medications (eg, beta-blockers or angiotensin-converting enzyme [ACE] inhibitors).
●Strict avoidance of specific relevant allergens.
●Specific interventions to reduce or prevent anaphylaxis recurrences from some allergens (examples include venom immunotherapy for those with anaphylaxis from stinging insects such as bees, yellow jackets, wasps, and hornets, and desensitization for those with anaphylaxis from some medications).
This topic will discuss the proactive, long-term management of patients after diagnosis and treatment of their acute anaphylactic episode and confirmation of the cause(s). The diagnosis and treatment of an acute anaphylactic 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 and best treatment for anaphylaxis and should be injected as soon as possible after the reaction begins [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 [7].
●H1 antihistamines and asthma inhalers (eg, albuterol) alone are not adequate treatment for anaphylaxis. H1 antihistamines relieve itch and hives, and asthma inhalers relieve wheezing and coughing, but these medicines do not prevent or relieve upper airway obstruction, hypotension, or shock and are therefore not lifesaving [1-6,8].
●The severity of previous anaphylactic episodes does not reliably predict the severity of future episodes, which may be more severe, less severe, or similar to previous episodes [1,9].
●Anaphylaxis is under-recognized and undertreated, even by health care professionals [10,11]. 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 [1-7,12]. 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 website videos.
Important issues with regard to epinephrine injection include need for prompt administration [13], need for a second dose [14], inability of children to access their epinephrine autoinjectors in school [15], lack of availability and/or high cost of autoinjectors in some countries [16], and need for training and regular coaching in correct and safe use of autoinjectors [17].
Prescriptions for epinephrine autoinjectors should be renewed prior to the expiration date. However, they maintain the vast majority of their potency even up to four years past their expiration date [18], and expired devices should be used if they are the only ones available.
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. 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, never receiving a prescription for an epinephrine autoinjector, and/or not having the epinephrine autoinjector available when the medical emergency occurred [19].
In another study of children who had experienced anaphylactic episodes, 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]. Thus, 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 room, 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.
Anaphylaxis emergency action plan — Any individual who has experienced 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, Spanish). These plans are appropriate for patients with anaphylaxis from any cause.
Formal evaluation of the clinical efficacy and cost-effectiveness of anaphylaxis emergency action plans is needed [21].
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 [21].
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].
MANAGEMENT OF COMORBIDITIES — Persistent asthma, especially if symptoms are poorly controlled, is an important risk factor for severe or fatal anaphylaxis [22]. Optimal asthma management is therefore critically important in those patients with asthma who are also at risk of anaphylaxis. Cardiovascular disease is an important risk factor for deaths from anaphylaxis in middle-aged and older patients [23,24], and 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".)
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 anaphylactic episodes:
●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 [3,25]. (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 [25,26]. Angiotensin II receptor blockers might be less likely to have this effect, although this has not been conclusively documented [27].
●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 (for example, diphenhydramine), which are widely used for the treatment of insomnia and allergic diseases [2,4,6,8].
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. The discussions should be documented in the patient's medical record. Substitution of medications may be necessary in some patients.
EFFECTIVE AVOIDANCE OF SPECIFIC RELEVANT ALLERGENS AND COFACTORS — 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 [1-3].
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 [28,29]. This is easier said than done [30]. Difficulties arise because of hidden, substituted, and cross-reacting foods, as well as foods that are contaminated with allergen because of cross-contact. In addition to avoiding the actual food in question, some extremely allergic patients need to avoid foods labeled with "may contain…" or similar less precise warnings.
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 [31,32]. Adolescents and young adults at risk for food-induced anaphylaxis are particularly prone to risk-taking behaviors [33]. (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 may be impossible for beekeepers, park rangers, gardeners, and others with occupational exposure [3,34]. (See "Stinging insects: Avoidance".)
●Medications – Patients with a history of anaphylaxis to a medication or biologic agent should have this documented in the allergies section of their medical record and should 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 [3,6,35-37].
●Vaccines – Anaphylaxis to vaccines for prevention of infectious diseases is rare [38]. Patients with this history should be evaluated by using skin tests to the vaccine and its components (excipients). If test results are negative, the vaccine can be administered in usual doses under observation. If test results are positive, it should be administered in graded doses under observation [38]. (See "Allergic reactions to vaccines".)
●Exercise – Prevention strategies for anaphylaxis caused by exercise depend upon the avoidance of cofactors, including foods, ethanol, or specific medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs]). Food cofactors should 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 [3,39]. (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 [3]. (See "Latex allergy: Management", section on 'Individual' and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Latex-fruit syndrome'.)
INTERVENTIONS TO REDUCE SENSITIVITY TO SPECIFIC ALLERGENS — Specific interventions to reduce the risk of recurrent reactions are available for certain causes of anaphylaxis [34-41].
●Food – Immunotherapy for food-induced anaphylaxis is not recommended [28,40]. Clinical trials of food-specific oral and epicutaneous (patch) immunotherapy have been completed or are ongoing in carefully selected, highly motivated, closely monitored patients who have experienced anaphylaxis from peanut, milk, or egg. Desensitization to small amounts of the food protein (temporary antigen hyporesponsiveness that depends on regular food ingestion) can often be achieved 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. Treatment-related symptoms are common, and anaphylaxis has been reported [42]. Although such treatment has not been approved for clinical use, it is under consideration by the US Food and Drug Administration (FDA) [43]. (See "Investigational therapies for food allergy: Immunotherapy and nonspecific therapies".)
●Insect stings – Anaphylaxis caused by venom from insects in the order Hymenoptera (eg, honey bees, yellow jackets, 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, it is continued indefinitely [34]. (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 should be followed by regular daily administration [35]. (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, NSAIDs, chemotherapeutics (eg, platinum salts and taxanes), and biologics [35,36]. (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 women. 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 [3,41].
●Idiopathic anaphylaxis – Idiopathic anaphylaxis is a diagnosis of exclusion that is made when no cause for the anaphylactic 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 (>11.4 ng/mL) may help to identify such patients [26,44,45]. (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 immunoglobulin E (IgE) levels in serum or less commonly, food-specific skin tests at intervals. Most children allergic to milk and egg will outgrow this allergy over time, while only a minority that are allergic to peanuts and tree nuts will do so [46]. (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 [47]. (See "Penicillin allergy: Immediate reactions".)
FUTURE LABORATORY TESTS TO PREDICT RISK OF ANAPHYLAXIS — An individual's risk of future anaphylaxis is most often estimated based upon the clinical history, skin testing, and measurement of the immunoglobulin E (IgE) level to the allergen. However, there are several laboratory tests in development that may increase the accuracy of these predictions for some types of allergens (eg, foods, venoms, latex). Component-resolved diagnostics, allergen epitope profiling, and cellular assays are each promising techniques that may help to identify patients sensitized to specific allergens who are at increased risk of anaphylaxis after exposure versus those who are sensitized to the allergens but clinically tolerant (ie, remain asymptomatic after exposure). These techniques are reviewed elsewhere. (See "Future diagnostic tools for food allergy".)
Internet resources — There are several 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)
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 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 topics (see "Patient education: Anaphylaxis (The Basics)" and "Patient education: Epinephrine autoinjectors (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
●Patients (and for children, their families and caregivers) should be taught to recognize the early symptoms of anaphylaxis and to inject epinephrine promptly. They should be counseled regularly that epinephrine injection is the first and best treatment for anaphylaxis. For patients with confirmed anaphylaxis causes, education about specific allergen avoidance is also important. This is an ongoing, long-term process that should be continued at each follow-up visit. (See 'Ongoing education for patients' above.)
●Patients should be supplied with at least one and preferably two doses of epinephrine in an autoinjector formulation and trained in when and how to use the autoinjector. (See 'Preparing the patient to treat possible recurrences' above.)
●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.)
●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.)
●Avoidance of anaphylaxis causes is easier said than done and is difficult to maintain over years or decades. However, it is of fundamental importance in prevention of recurrent anaphylactic episodes in the community. (See 'Effective avoidance of specific relevant allergens and cofactors' above.)
●Specific immunomodulation is available for patients with anaphylaxis caused by certain causes, such as stinging insect venoms and some medications. (See 'Interventions to reduce sensitivity to specific allergens' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges F Estelle R Simons, MD, FRCPC, who contributed to an earlier version of this topic review.
