Quandaries in prescribing an emergency action plan and self-injectable epinephrine for first-aid management of anaphylaxis in the community

Article Outline

• Abstract
• Scope of the problem
• First quandary for the physician: Which patients require prescription of self-injectable epinephrine?
• Second quandary for the physician: Instructions to the patient for use of self-injectable epinephrine
• Other considerations
• Conclusions
• Acknowledgment
• References
• Copyright

Anaphylaxis often occurs in the community in the absence of a health care professional. Prompt administration of self-injectable epinephrine as first-aid treatment in the context of a personalized emergency action plan is the key to survival. There is little argument that physicians should prescribe self-injectable epinephrine for individuals who have already experienced anaphylaxis involving respiratory distress or shock triggered by allergens that might be encountered in the community. A quandary faced by physicians is that additional individuals with identified allergy who have no recognized prior history of anaphylaxis or who have a history of mild symptoms after exposure to a known trigger might also be at risk for subsequent life-threatening anaphylaxis and might also warrant prescription of self-injectable epinephrine. Prescribing for the latter individuals requires considerable clinical judgment and has led to controversy regarding possible overprescription or underprescription of self-injectable epinephrine. A second quandary for physicians occurs with regard to the advice they should give to at-risk individuals about actual use of their self-injectable epinephrine. It is difficult for health care professionals, let alone persons with no health care training, to predict whether anaphylaxis symptoms will occur in an at-risk individual after exposure to a known trigger. Moreover, at the onset of an acute allergic reaction, it is difficult to predict the symptoms that will ultimately develop. We examine these 2 common quandaries and provide examples of clinical scenarios and potential pitfalls in the management of persons identified as being at risk for anaphylaxis in the community. Additional studies of the recognition and treatment of anaphylaxis in the community are needed to develop comprehensive, evidence-based recommendations for its management in this setting.

Key words: Anaphylaxis, self-injectable epinephrine, adrenaline, allergic reaction, food allergy, insect sting allergy

The updated practice parameter on anaphylaxis, which appears as a supplement to this issue of the Journal, states that patients who have had anaphylaxis from exposures that may be encountered in non-medical settings should carry self-injectable epinephrine for use if anaphylaxis develops and emphasizes the need for prompt self-injection of epinephrine if acute anaphylaxis is suspected.¹ In a previous evidenced-based approach to the use of epinephrine autoinjectors in a community setting, prescriptions for self-injectable epinephrine were suggested for individuals who experienced a systemic reaction to a trigger that might be encountered in the community if the patient had also experienced a severe reaction (respiratory difficulty or hypotension) or if they were at high risk, as defined by any of the following: asthma, reactions to trace amount of allergen, at risk for repeated exposure with lack of access to emergency care, or comorbidity increasing the risk of a severe reaction.² An American Academy of Allergy, Asthma and Immunology Board of Directors Position Statement regarding treatment of anaphylaxis in schools indicated that for patients “who have had an anaphylactic reaction … epinephrine be given at the start of any reaction occurring in conjunction with exposure to a known or suspected allergen” and further suggests that physicians can instruct patients who previously experienced severe anaphylaxis, including cardiovascular collapse, after a specific trigger to self-inject epinephrine even before symptoms arise if re-exposure to that trigger occurs.³

Although these recommendations appear to be straightforward, in many situations their application to individual patients requires clinical judgment. The first quandary for the physician is to determine which patients who have not actually experienced anaphylaxis as such might also be at risk of anaphylaxis and might also benefit from prescription of self-injectable epinephrine in the context of an emergency action plan. The second quandary concerns interpretation of the words “when acute anaphylaxis is suspected” and provision of clear and unambiguous recommendations to patients regarding the circumstances that warrant use of their self-injectable epinephrine. This is no easy task, considering the fact that anaphylaxis is not defined by any specific symptom or sign and that recognition of anaphylaxis in the community and assessment of its severity is usually being undertaken by persons without medical training, either the individual himself or herself or, for a child, a caregiver. These 2 quandaries regarding self-injectable epinephrine for anaphylaxis occurring in the community are the subject of this perspective.

Back to Article Outline

Scope of the problem 

Data on the epidemiology of anaphylaxis in the general population are sparse and influenced by definitions, coding issues, and misclassification errors. A population-based study of anaphylaxis from any cause in Olmsted County, Minnesota, using data collected in the mid-1980s (possibly before the increase in allergic disease), calculated an annual occurrence rate of 30 per 100,000 person-years⁴ and raised the concern that anaphylaxis is frequently not recognized by patients and physicians. This estimate does not account for persons at risk who might warrant a prescription of self-injectable epinephrine but have not experienced a reaction; this group could exceed 3% to 4% (300-400 per 100,000 person-years), even with conservative estimates.⁵ In other recent studies of cases of anaphylaxis caused by a variety of triggers occurring in the community, presenting to an emergency department, or both, occurrence rates range from about 8 to 11 per 100,000 person-years⁶, ⁷, ⁸ to as high as 590 per 100,000 persons,⁹ and almost certainly reflect underestimates.⁷, ¹⁰

In recent population-based surveys of peanut, tree nut, and seafood allergy in the United States, considering only individuals who reported respiratory or multiple organ system reactions and making a generous assumption that 25% might have both seafood and peanut-nut allergy, about 1.5% of the general population could be at risk for anaphylaxis to these foods.¹¹, ¹² Among children, real-time reporting from the Canadian Pediatric Surveillance Program indicated that food allergy is a primary trigger of anaphylaxis in children (81% of reactions), and only 32% of episodes of anaphylaxis were treated with epinephrine.¹³ From 1995 through 2000 in the general population of the province of Manitoba, Canada, 950 of 100,000 persons (nearly 1% of the population) had self-injectable epinephrine dispensed¹⁴ in response to physicians' decision making regarding risk of recurrent anaphylaxis in the community. This rate of dispensing might seem high; however, only a small fraction (10% to 32%) of those who experience anaphylaxis are typically prescribed self-injectable epinephrine.¹¹, ¹², ¹⁵ One might extrapolate from these various studies that conservative prescription of self-injectable epinephrine for at least 1% of the general population or possibly to approximately 3% to 4% who could be at risk might carry an enormous cost to the health care system, although it would undoubtedly save additional lives.

Concern has been raised that the risks of poor outcomes and the need for self-injectable epinephrine are overestimated, at least in regard to food allergy in young children. Macdougall et al¹⁶ reviewed death certificates and surveillance reports in the United Kingdom and Ireland that identified 0.006 deaths and 0.19 severe reactions per 100,000 children up to 15 years of age. Extrapolation for a food allergy rate of 5% would indicate a risk of death for a child with food allergy to be 1 in 800,000. Although these data were presented as in some sense reassuring, the age group identified and the definitions of severity (cardiopulmonary arrest, inotropic support, fluid bolus, >1 dose of epinephrine or bronchodilator) likely underestimated the number of affected children with significant morbidity. Kemp¹⁷ made suggestions in regard to prescription of self-injectable epinephrine and included the observations by Macdougall et al¹⁶ to suggest young children were not at high risk, and he additionally suggested that prescriptions were appropriate for risk factors such as asthma, prior reactions involving the respiratory tract, peanut-tree nut allergy, reactions to trace exposures, and a strong positive allergy skin test response. Another concern that might be raised about lowering the threshold for prescribing self-injectable epinephrine to include persons who are not obvious candidates is that such persons might unnecessarily experience an adverse effect on quality of life if they view the prescription as the physicians' confirmation of a potentially deadly malady.¹⁸, ¹⁹

Back to Article Outline

First quandary for the physician: Which patients require prescription of self-injectable epinephrine? 

Recognizing that a person has experienced anaphylaxis from a trigger encountered in the community is the first step toward a decision to prescribe self-injectable epinephrine. However, there is as yet no universal consensus definition or diagnostic description of anaphylaxis, as stated in the National Institutes of Health report in this issue of the Journal.²⁰ The text of the practice parameter in this issue of the Journal¹ describes anaphylaxis as an acute life-threatening reaction with varied clinical presentations, in which respiratory compromise and cardiovascular collapse cause the most concern. Where does the risk assessment for prescription of self-injectable epinephrine fit in regard to this definition? It is straightforward to suggest that persons with a previous episode of anaphylaxis characterized by respiratory or cardiovascular compromise to a trigger that might be encountered outside the hospital should carry self-injectable epinephrine, but only about 70% of individuals with anaphylaxis have respiratory symptoms, and even fewer, only about 10%, experience cardiovascular symptoms.⁶, ¹³ In addition, physicians cannot assume that patients and caregivers necessarily recognize and report all symptoms because even trained health care professionals underrecognize anaphylaxis.⁴, ¹⁰

Up to 10% of individuals with anaphylaxis have no obvious skin manifestations (eg, urticaria, angioedema, flushing, and itching); nevertheless, urticaria and angioedema are the most common manifestations of anaphylaxis,¹³, ²¹, ²² and they might also be the first symptoms in what ultimately progresses to a severe reaction. In isolation, acute urticaria and angioedema might not warrant a diagnosis of anaphylaxis (a point of potential controversy). For example, it is the authors' impression that physicians are likely to prescribe self-injectable epinephrine to a child who experienced generalized acute urticaria after an insect sting, as per published consensus and evidence,²³, ²⁴ but are less likely to do so if the trigger had been a food. Persons older than 16 years with a generalized cutaneous reaction to insect stings are considered to be at increased risk for anaphylaxis from subsequent stings and are candidates for venom immunotherapy. Children with generalized symptoms limited to the skin after insect sting have a lower risk of anaphylaxis (approximately 10%), however, and although immunotherapy is not necessarily recommended for these children, prescription of self-injectable epinephrine is recommended.²³

The issue of assessing future risk of anaphylaxis is particularly confusing for food allergy and has led to various papers.²¹, ²⁵, ²⁶, ²⁷ In regard to peanut allergy, among children who have a positive skin test response to peanut and have avoided the food, perhaps by self-selection on the basis of prior mild reactions, about half will react on challenges, indicating a clear potential risk and need for food challenge to determine clinical allergy in this situation.²⁵ Vander Leek et al²⁶ showed that among 24 young children with peanut allergy whose first reaction was isolated to the skin after ingestion or skin contact, 18 (75%) experienced symptoms beyond the skin in a subsequent reaction. Indeed, severity of a previous reaction is a poor guide to symptoms during a future reaction: only 22% of patients with fatal food-induced anaphylaxis had a previous severe reaction, and only 18% with fatal venom-induced anaphylaxis had a previous severe reaction.²¹ In young children with peanut- or tree nut–related anaphylaxis, episodes might worsen progressively with time, and this could relate to the fact that increased numbers of such children develop asthma as they get older.²⁷ Indeed, comorbidities also influence the decision to prescribe self-injectable epinephrine. Most important among comorbidities is asthma, which has been associated with severe and fatal anaphylaxis.²⁸, ²⁹, ³⁰ However, even in persons without a previous diagnosis of asthma, the studies on peanut allergy could be interpreted as supporting the argument to prescribe self-injectable epinephrine for most persons with a clinical history of symptoms after eating peanut and evidence of sensitization to peanut.

There are certain clinical situations in which prescription of self-injectable epinephrine might at first seem unwarranted but might become reasonable as the situation evolves over time. For example, atopic dermatitis–eczema is often associated with food allergy and is definitely of itself not an indication for the prescription of self-injectable epinephrine. However, after excluding a causal food from the diet of children with atopic dermatitis, anaphylactic reactions can occur on re-exposure.³¹, ³², ³³ In addition, for young children with moderate-to-severe atopic dermatitis and allergy to a food other than peanut, about 20% to 25% eventually have a reaction to peanut, a positive food challenge to peanut, or both,³², ³⁴ and this is a food allergy that might intrinsically warrant prescription of self-injectable epinephrine. Conversely, the type of food to which there is an allergy cannot provide a guarantee against a severe or fatal outcome because fatalities have been reported to foods usually not considered to cause severe reactions, such as cow's milk, soy, or fruit.³⁵, ³⁶, ³⁷

Pollen-food syndrome (oral allergy syndrome) is triggered in persons with pollen allergy when a food, most typically a raw fruit or vegetable, contacts the oropharyngeal mucosa. It involves local IgE-mediated mast cell activation. Symptoms rarely involve other target organs, and this syndrome is therefore an example of a disorder in which prescription of self-injectable epinephrine is usually optional. However, nearly 2% of patients with pollen-food syndrome might at some time experience anaphylaxis from the same triggers,³⁷, ³⁸ and in one recent series, anaphylaxis from fruits and vegetables was surprisingly common.³⁷ A survey of practicing allergists in the United States indicated that self-injectable epinephrine was prescribed for pollen-food syndrome by 3% all the time, 30% none of the time, and 67% on a case-by-case basis.³⁹

The risk of recurrence of a reaction and the potential severity of a recurrence needs to be factored into the decision to prescribe self-injectable epinephrine. In a review of 142 adult patients with a previous episode of anaphylaxis, Kemp et al⁴⁰ found that 35% had a recurrence. Of these, 44% used self-injectable epinephrine for the reaction with a good clinical response. However, 47% were not carrying epinephrine as prescribed, and one such patient required tracheostomy and ventilation for a reaction. In a study of recurrence of anaphylaxis among persons (median age, 26 years; age range, 1-82 years) presenting to a specialty medical practice in Australia, 1 of 12 patients per year had recurrence, and 1 of 50 required epinephrine or hospital treatment.⁴¹ The severity of reaction on recurrence in this group was related to the severity of the initial reaction; however, about 1 in 4 recurrences were more severe than the previous reaction, and 18 of 45 patients with a serious recurrence used self-injectable epinephrine. Cianferoni et al⁴² performed a follow-up study on children whom they had evaluated for anaphylaxis 7 years earlier. Of the original 76 children (food allergy, 56%; insect venom, 12%), 46 were contacted, and 30% had experienced recurrent anaphylaxis. Those with atopic dermatitis or positive test responses to a food at the original evaluation were about twice as likely, compared with those without, to have a recurrence. These studies show that recurrence is common, but there is no certain way to identify who is at risk for a recurrence or to predict the severity of a recurrence. Although we might rightly ask, “Who should not be prescribed self-injectable epinephrine?,” it is also important to note that there is no absolute contraindication to prescription of self-injectable epinephrine. Examples of quandaries in risk assessment are shown in Table I.

Table I. Examples of quandaries regarding whether to prescribe self-injectable epinephrine

These are illustrations and should not be construed to suggest any specific course of action, because specific situations might vary. Physicians should err on the side of caution with regard to prescribing self-injectable epinephrine for patients at risk for anaphylaxis in community settings where health care professionals are not available to assist in recognition and monitoring of signs and symptoms. Epinephrine should always be prescribed in the context of an emergency action plan, along with instructions to avoid the anaphylaxis trigger and other specific preventive measures as indicated. Patients require regular re-evaluation with regard to risk.

SIE, Self-injectable epinephrine.

Back to Article Outline

Second quandary for the physician: Instructions to the patient for use of self-injectable epinephrine 

At one extreme, a physician could advise that self-injectable epinephrine be used after possible exposure to a known allergen in the absence of symptoms, whereas at the other extreme, a physician could advise that epinephrine would not be injected unless progressive respiratory symptoms, cardiovascular symptoms, or both were developing. Neither of these extreme positions can be recommended.

Studies of deaths caused by anaphylaxis, the worst-case scenario, might hold important lessons with regard to optimal treatment or at least indicate errors that can and should be avoided. For insect sting reactions, most of the fatalities were from a first reaction²¹; however, in contrast, most fatal food-allergic reactions occurred in persons given diagnoses of previous mild reactions and concomitant uncontrolled asthma.²⁸, ³⁰, ³⁶ In the series of fatalities reviewed by Pumphrey,²¹ the median time to cardiorespiratory arrest for venom allergy was 15 minutes (range, 4-120 minutes) and 30 minutes after food ingestion (range, 6-360 minutes). Epinephrine was given to none of 32 victims of fatal stings and to 8 of 37 with fatal food allergy before arrest. Pumphrey's conclusions regarding risks for fatality²⁸ include the following: food allergy when there is concomitant asthma, poor asthma control, poor self-treatment, and no prophylactic treatment with immunotherapy for persons with venom-induced anaphylaxis.

Sampson et al³⁰ reported on 6 children with fatal reactions to food, all of whom had asthma, previous severe reactions to foods, and delay in treatment with epinephrine. None of the children received epinephrine before the onset of severe respiratory symptoms (obvious respiratory distress, retractions, wheezing, and in some cases cyanosis), whereas 7 children with near-fatal food anaphylaxis evaluated at the same period of time received epinephrine before or within 5 minutes of severe respiratory symptoms. Reactions occurred outside of the home in 5 of the 6 who died and in the home for all 7 who survived. None of the children with fatal reactions and all but one with near-fatal reactions had recognized cutaneous symptoms. This raises the concern that absence of or failure to recognize skin symptoms and other symptoms could result in a delay in treatment and a poor outcome. Among 32 food anaphylaxis fatalities recorded in a registry maintained through the Food Allergy & Anaphylaxis Network,³⁶ the following salient features were noted: all but one of the individuals had a known allergy to the food, only 10% had self-injectable epinephrine available, peanut or tree nut caused 94% of the reactions (milk and fish caused the others), most of those who died were adolescents or young adults, and 96% had asthma. Major themes again are concurrent asthma and delay in treatment with epinephrine and, additionally, identification of particular risks for teens, who might take more risks in their diet and be reluctant to use self-injectable epinephrine.

Generalized acute urticaria is not itself a life-threatening symptom, yet in the context of a known exposure to an allergen that previously triggered anaphylaxis, the recommendation for an exposure outside of a medical setting is to inject epinephrine.³ Whether generalized acute urticaria indicates anaphylaxis is a controversial topic, and there is a notion that epinephrine might not intrinsically be indicated for this symptom. For example, Brown²² reported retrospective data from 1149 patients, primarily adults, evaluated in the emergency department with systemic allergic reactions (30% with venom allergy, 22% with iatrogenic allergy, 18% with food allergy, 5% with “other” allergy, and 25% with unidentified cause) and showed that hypotension or hypoxia was associated with a variety of individual symptoms (eg, incontinence, collapse, confusion, and, to a lesser extent, diaphoresis, cyanosis, presyncope, nausea, vomiting, abdominal pain, dizziness, dyspnea, stridor, and wheezing) but not with urticaria. However, it might be inappropriate to apply the results of this study to patients with anaphylaxis experiencing generalized acute urticaria outside of a hospital setting. The study represents a monitored evaluation of anaphylaxis and did not discuss the rates of combinations of symptoms nor differences in clinical presentations for different anaphylaxis triggers.

Physician-supervised allergen challenge and inadvertently induced anaphylaxis is not comparable with reactions to unknown degrees of exposure with unmonitored symptoms in the field. However, some lessons might be derived. In a study of 138 patients with previous sting anaphylaxis undergoing supervised stings,⁴³ 39 subjects had a reaction, and 18 had Mueller grade 1 reactions (generalized urticaria or erythema, itching, and malaise or anxiety). One of these 18 received an antihistamine for severe itching, and the remainder had spontaneous improvement. Among 718 patients undergoing graded, physician-supervised oral food challenges at Mount Sinai Hospital (unpublished data) who were selected primarily for a prechallenge estimated greater than 50% likelihood of tolerating the tested foods, 256 (36%) had reactions. Among them, 147 (57%) had isolated skin (n=109) or gastrointestinal (n=38) reactions, and only one of these patients received epinephrine on the basis of the physician's observations and clinical judgment for the treatment of severe generalized urticaria. Overall, antihistamines were administered for 93% of reactions, and epinephrine was administered for 9%. Of reactions with a respiratory component (86 reactions), 23 (27%) were treated with epinephrine (primarily those with wheezing or significant throat symptoms rather than occasional cough and rhinitis symptoms). One could surmise from these studies that there is room for judgment by trained and experienced physicians and nurses regarding injection of epinephrine when symptoms are isolated to the skin or are only mild. However, in the community, in the absence of a health care professional, a given patient or caregiver might not recognize anaphylaxis symptoms or their severity and might fail to inject the epinephrine as instructed. Recommendations for treatment in the real world (ie, out in the community where no health care professional is available) should therefore be more proactive than they are for situations supervised by trained and experienced physicians and nurses.

Only a few studies report experiences of patients with anaphylaxis outside of a medical setting. Grabentsein and Smith⁴⁴ reported on 34 adults with anaphylaxis (insect, 28; food, 6) prescribed self-injectable epinephrine and followed prospectively. Recurrence (a total of 82 episodes) developed in 33 patients. In 42 of these episodes antihistamines alone were used, 10 were treated with self-injectable epinephrine, and 30 were treated with both, without poor outcomes. However, as mentioned previously, Kemp et al⁴⁰ reported that among 47% of their patients with anaphylaxis who did not carry self-injectable epinephrine, one required tracheostomy for a reaction. Gold and Sainsbury⁴⁵ surveyed families of children to whom self-injectable epinephrine was prescribed for a previous reaction with respiratory or cardiovascular involvement. Sixty-eight of 86 families (42 with sting and 24 with food allergy) were contacted a mean of 20 months after initial prescription. Recurrence was reported for 54% (121 reactions among 37 children), with 45 of them (12 with insect, 22 with food, and 11 with idiopathic triggers) demonstrating respiratory or cardiovascular symptoms. Epinephrine was used in 15 (12%) of the reactions, but it was used before respiratory or cardiovascular symptom onset in just 2 of the 15 episodes. For the 13 who received self-injectable epinephrine with respiratory or cardiovascular symptoms, 9 were for insect sting, 2 for food, and 2 for idiopathic triggers. For 32 episodes of reactions with respiratory or cardiovascular symptoms without use of self-injectable epinephrine, 15 eventually received epinephrine from a medical caregiver, but only 2 of the 13 who used self-injectable epinephrine received more epinephrine (P < .05). The hospitalization rate was lower (15% vs 47%, P < .05) for those who received the self-injectable epinephrine, which was more likely given for insect sting rather than food triggers. The majority of reactions did not involve the respiratory or cardiovascular systems and were untreated or treated with an antihistamine. Taken together, these studies support the notion that isolated skin reactions need not always be considered an indication for administration of self-injectable epinephrine. Nevertheless, our recommendation is to err on the side of caution when developing an emergency action plan for an individual to use out in the community in the absence of a health care professional; that is, we advise patients-caregivers to inject epinephrine promptly when symptoms occur after known exposure to a trigger that previously caused a significant reaction. For patients with idiopathic anaphylaxis, in whom exposure is an irrelevant issue, a symptom-based approach is required. Table II illustrates examples of quandaries regarding the instructions for actual use of self-injectable epinephrine.

Table II. Examples of quandaries regarding instructions for use of self-injectable epinephrine when no health care professional is available

These are illustrations and should not be construed to suggest any specific course of action, because specific situations might vary. Physicians should instruct patients at risk for anaphylaxis in the community to err on the side of caution and, if in doubt as to whether they are reacting or if the reaction is going to be severe, to implement their emergency action plan and use their self-injectable epinephrine promptly rather than wait too long.

SIE, Self-injectable epinephrine; MDI, metered-dose inhaler.

Back to Article Outline

Other considerations 

For a physician evaluating an individual patient, risk factors, such as prior allergic reaction history, comorbid medical conditions (eg, asthma and use of medications, such as nonselective β-blockers), and specific allergies (eg, to peanut, tree nut, seafood, or insect venom that are more likely to be associated with severe reactions compared with milder reactions), are summarized in Table III. These factors will affect decisions for prescribing self-injectable epinephrine and defining the indication for its administration. Of course, preparation for first-aid treatment of anaphylaxis is not characterized solely by prescription of self-injectable epinephrine. Comprehensive management should include development of a personalized emergency action plan that lists potential anaphylaxis symptoms and gives instructions for the indications for self-injectable epinephrine, the technique of using epinephrine autoinjectors, and the necessity of taking the patient to an emergency department after an epinephrine injection. The emergency action plan and coaching with regard to use of self-injectable epinephrine should be reviewed with the patient on a regular basis. Additional important considerations include confirmation-reconfirmation of the trigger factor, instructions with regard to trigger avoidance, medical identification jewelry, and specific recommendations for prevention of anaphylaxis (eg, allergen-specific immunotherapy for venom anaphylaxis and fasting for 4-6 hours before exercise and avoidance of specific food or other cotriggers for exercise-induced anaphylaxis). For patients with food allergy, the Food Allergy & Anaphylaxis Network (www.foodallergy.org) is an important resource. Omission of these strategies might contribute to poor outcomes.²¹, ³⁰, ³⁶

Table III. Examples of factors that influence the physician's decision to prescribe self-injectable epinephrine and to instruct patients to use it promptly when anaphylaxis occurs in the community

Reaction history

•previous life-threatening reaction∗

•reaction to trace allergen exposure

•repeat exposures likely

•specific triggers associated with severe reaction (eg, insect venom, peanut, tree nut, seafood)

•idiopathic anaphylaxis

Comorbidities

•asthma

•use of nonselective β-blockers

Persons in whom it is difficult for a caregiver to recognize anaphylaxis symptoms-severity

•those supervised by caregivers without any health care training or experience

•dysfunctional family

•infants or young children

•skin disease (eg, eczema) or color that makes it difficult to detect erythema

•those unable to recognize or describe their symptoms accurately (eg, infants, children, persons with learning disabilities or language barriers)

Persons with barriers to recognizing-treating their own symptoms

•those in age groups at increased risk of fatality (eg, teenagers, young adults, elderly)

•those with learning disabilities

•those who have previously had trouble recognizing or assessing their own symptoms

•those who abuse alcohol or drugs

Persons with barriers to prompt treatment by professionals

•those living alone

•those living in a remote area

•those lacking reliable transportation

•those lacking a telephone

Competent patients and caregivers who are not health care professionals might fail to recognize anaphylaxis, and even if they do recognize it, might fail to inject epinephrine promptly. Therefore they should be instructed to err on the side of caution.

It is clear that individuals and caregivers are often reluctant to use self-injectable epinephrine despite instruction to do so. This probably occurs for a variety of reasons, including failure to recognize the allergic reaction, spontaneous recovery from a previous episode, incorrectly thinking the episode is mild, reliance on oral H₁-antihistamines or asthma relief inhalers, fear of needles and injections, lack of availability of an epinephrine autoinjector, and concern about epinephrine's adverse effects.⁴⁶ The physician should review these issues as part of anticipatory guidance. Serious side effects of self-injectable epinephrine (in contrast to pallor, tremor, anxiety, and palpitations, which are common anticipated pharmacologic effects) should not be a concern for otherwise healthy persons. This contrasts with poor outcomes when epinephrine has been administered intravenously in large doses, overdoses, or inappropriately high concentrations.²¹, ⁴⁶, ⁴⁷

Several other treatments, although not primary therapies for the first-aid treatment of anaphylaxis, warrant consideration as part of the care plan. Patients should be instructed about the secondary role of H₁-antihistamines in symptom relief. Although useful adjunctive therapy for pruritus and other skin symptoms, when administered orally they do not even begin to act for an hour or so. In short, they do not replace epinephrine in the first-line treatment of anaphylaxis.⁴⁸, ⁴⁹ Inhaled β₂-adrenergic agonists, such as albuterol, cannot replace epinephrine as primary therapy but are usually carried by asthmatic patients and might be a useful adjunct for these patients if lower respiratory tract symptoms occur during anaphylaxis.²⁸ Because of the fact that the upright posture might result in insufficient venous return, loss of filling to the heart, and circulatory collapse during anaphylactic shock, another important adjunct in first-aid treatment of a severe reaction is to position the individual supine with raised legs.⁵⁰

Outcome studies of emergency care plans for anaphylaxis are few. Ewan and Clark⁵¹ report on the outcome of a management plan for persons with peanut and tree nut allergy. Reactions were initially graded as mild, moderate, or severe on the basis of symptoms of worst reaction and additional information, such as underlying asthma and triggering dose. The mild categories included various degrees of skin involvement and gastrointestinal or rhinoconjunctival symptoms. Trigger avoidance instructions were detailed, and 567 patients were followed prospectively (median, 21 months; 13% had been categorized as severe reactions). Subsequent reactions occurred in 88, and only 0.5% were severe. None of the mild reactions (62 of the total) were treated with self-injectable epinephrine. On the basis of experiences with personal care plans for food allergy in schoolchildren, Moneret-Vautrin et al⁵² suggested plans be individualized for previous severe reactions, peanut allergy, idiopathic anaphylaxis, reactions after small exposures, “moderate allergy” to foods, asthmatic children, and multiple food allergies. Continued efforts to educate persons in the community about anaphylaxis (parents, child care and school personnel, food manufacturers, and hospitality industry workers) are important and will help to hold back the potential tide of poor outcomes from anaphylaxis.

Back to Article Outline

Conclusions 

It is clear that an individual experiencing respiratory or cardiovascular symptoms after exposure to a known allergen in the community should receive self-injectable epinephrine immediately. Others who might be at risk for anaphylaxis should also have self-injectable epinephrine prescribed for use in the community. Individuals in the community who are experiencing an acute systemic allergic reaction and assessing their own symptoms (and, for children, caregivers without health care training) should be instructed to err on the side of caution and inject epinephrine promptly, even when few or mild symptoms occur after exposure to the individual's known anaphylaxis trigger. Self-injectable epinephrine should always be prescribed in the context of an individualized emergency action plan, along with appropriate allergen-specific risk-reduction measures. More outcome studies are needed to create comprehensive evidence-based guidelines for first-aid self-management of anaphylaxis in the community.

Back to Article Outline

Acknowledgment 

Data on food challenges were reported from studies conducted in the General Clinical Research Unit of Mount Sinai Hospital (National Institutes of Health grant RR 00071).

Back to Article Outline

References 

1. Lieberman P, Kemp SF, John Oppenheimer J, Lang DM, Bernstein IL, Nicklas RA, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115:S483–S524
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (682 KB)
   • CrossRef
2. McLean-Tooke APC, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence?. BMJ. 2003;327:1332–1335
   • View In Article
   • CrossRef
3. American Academy of Allergy Asthma and Immunology Board of Directors . Anaphylaxis in schools and other child-care settings. J Allergy Clin Immunol. 1998;102:173–176
   • View In Article
   • Full Text
   • Full-Text PDF (86 KB)
   • CrossRef
4. Yocum MW, Butterfield JH, Klein JS, Volcheck GW, Schroeder DR, Silverstein MD. Epidemiology of anaphylaxis in Olmsted County: a population-based study. J Allergy Clin Immunol. 1999;104:452–456
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (107 KB)
   • CrossRef
5. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States. An investigation into its epidemiology. Arch Intern Med. 2001;161:15–21
   • View In Article
   • MEDLINE
   • CrossRef
6. Peng MM, Jick H. A population-based study of the incidence, cause, and severity of anaphylaxis in the United Kingdom. Arch Intern Med. 2004;164:317–319
   • View In Article
   • MEDLINE
   • CrossRef
7. Bohlke K, Davis RL, DeStefano F, Marcy SM, Braun MM, Thompson RS. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. J Allergy Clin Immunol. 2004;113:536–542
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (127 KB)
   • CrossRef
8. Helbling A, Hurni T, Mueller UR, Pichler WJ. Incidence of anaphylaxis with circulatory symptoms: a study over a 3-year period comprising 940,000 inhabitants of the Swiss Canton Bern. Clin Exp Allergy. 2004;34:285–290
   • View In Article
   • MEDLINE
   • CrossRef
9. Boros CA, Kay D, Gold MS. Parent reported allergy and anaphylaxis in 4173 South Australian children. J Paediatr Child Health. 2000;36:36–40
   • View In Article
   • MEDLINE
   • CrossRef
10. Klein JS, Yocum MW. Underreporting of anaphylaxis in a community emergency room. J Allergy Clin Immunol. 1995;95:637–638
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (178 KB)
    • CrossRef
11. Sicherer SH, Muñoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol. 2003;112:1203–1207
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (76 KB)
    • CrossRef
12. Sicherer SH, Muñoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol. 2004;114:159–165
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (254 KB)
    • CrossRef
13. Simons FER, Chad ZH, Gold M. Anaphylaxis in children: real-time reporting from a national network. Allergy Clin Immunol Int–J World Allergy Org. 2004;(Suppl):242–244
    • View In Article
14. Simons FER, Peterson S, Black CD. Epinephrine dispensing patterns for an out of-hospital population: a novel approach to studying the epidemiology of anaphylaxis. J Allergy Clin Immunol. 2002;110:647–651
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (499 KB)
    • CrossRef
15. Clark S, Bock SA, Gaeta TJ, Brenner BE, Cydulka RK, Camargo CA. Multicenter study of emergency department visits for food allergies. J Allergy Clin Immunol. 2004;113:347–352
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (88 KB)
    • CrossRef
16. Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child. 2002;86:236–239
    • View In Article
    • CrossRef
17. Kemp AS. EpiPen epidemic: suggestions for rational prescribing in childhood food allergy. J Paediatr Child Health. 2003;39:372–375
    • View In Article
    • MEDLINE
    • CrossRef
18. Oude Elberink JNG, de Monchy JGR, Golden DB, Brouwer JLP, Guyatt GH, Dubois AEJ. Development and validation of a health related quality-of-life questionnaire in patients with yellow jacket allergy. J Allergy Clin Immunol. 2002;109:162–170
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (79 KB)
    • CrossRef
19. Hu W, Kemp A, Kerridge I. Making clinical decisions when the stakes are high and the evidence unclear. BMJ. 2004;329:852–854
    • View In Article
    • CrossRef
20. Sampson HA, Muñoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA. Symposium on the Definition and Management of Anaphylaxis: summary report. J Allergy Clin Immunol. 2005;115:584–591
    • View In Article
    • Full Text
    • Full-Text PDF (133 KB)
    • CrossRef
21. Pumphrey RSH. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30:1144–1150
    • View In Article
    • MEDLINE
    • CrossRef
22. Brown SGA. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114:371–376
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (144 KB)
    • CrossRef
23. Moffitt JE, Golden DBK, Reisman RE, Lee R, Nicklas R, Freeman T, et al. Stinging insect hypersensitivity: a practice parameter update. J Allergy Clin Immunol. 2004;114:869–886
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (729 KB)
    • CrossRef
24. Portnoy JM. Stinging insect hypersensitivity: a practice parameter. J Allergy Clin Immunol. 1999;103:963–980
    • View In Article
    • Full Text
    • Full-Text PDF (155 KB)
    • CrossRef
25. Kagan R, Hayami D, Joseph L, St Pierre Y, Clarke AE. The predictive value of a positive prick skin test to peanut in atopic, peanut-naive children. Ann Allergy Asthma Immunol. 2003;90:640–645
    • View In Article
    • Abstract
    • Full-Text PDF (225 KB)
    • CrossRef
26. Vander Leek TK, Liu AH, Stefanski K, Blacker B, Bock SA. The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J Pediatr. 2000;137:749–755
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (119 KB)
    • CrossRef
27. Sicherer SH, Furlong TJ, Muñoz-Furlong A, Burks AW, Sampson HA. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol. 2001;108:128–132
    • View In Article
    • Abstract
    • Full-Text PDF (146 KB)
    • CrossRef
28. Pumphrey R. Anaphylaxis: can we tell who is at risk of a fatal reaction?. Curr Opin Allergy Clin Immunol. 2004;4:285–290
    • View In Article
    • MEDLINE
    • CrossRef
29. Pumphrey RS. Fatal anaphylaxis in the UK, 1992-2001. Novartis Found Symp. 2004;257:116–128
    • View In Article
    • MEDLINE
30. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380–384
    • View In Article
    • MEDLINE
    • CrossRef
31. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child. 1984;59:983–986
    • View In Article
    • CrossRef
32. Sampson HA, McCaskill CC. Food hypersensitivity and atopic dermatitis: evaluation of 113 patients. J Pediatr. 1985;107:669–675
    • View In Article
    • Abstract
    • Full-Text PDF (650 KB)
    • CrossRef
33. Barbi E, Gerarduzzi T, Longo G, Ventura A. Fatal allergy as a possible consequence of long-term elimination diet. Allergy. 2004;59:668–669
    • View In Article
    • MEDLINE
    • CrossRef
34. Burks AW, James JM, Hiegel A, Wilson G, Wheeler JG, Jones SM, et al. Atopic dermatitis and food hypersensitivity reactions. J Pediatr. 1998;132:132–136
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (289 KB)
    • CrossRef
35. Foucard T, Malmheden YI. A study on severe food reactions in Sweden—is soy protein an underestimated cause of food anaphylaxis?. Allergy. 1999;54:261–265
    • View In Article
    • MEDLINE
    • CrossRef
36. Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107:191–193
    • View In Article
    • Abstract
    • Full-Text PDF (57 KB)
    • CrossRef
37. Pastorello EA, Rivolta F, Bianchi M, Mauro M, Pravettoni V. Incidence of anaphylaxis in the emergency department of a general hospital in Milan. J Chromatogr B. 2001;756:11–17
    • View In Article
38. Ortolani C, Pastorello EA, Farioli L, Ispano M, Pravettoni V, Berti C, et al. IgE- mediated allergy from vegetable allergens. Ann Allergy. 1993;71:470–476
    • View In Article
    • MEDLINE
39. Ma S, Sicherer SH, Nowak-Wegrzyn A. A survey on the management of pollen-food allergy syndrome in allergy practices. J Allergy Clin Immunol. 2003;112:784–788
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (246 KB)
    • CrossRef
40. Kemp SF, Lockey RF, Wolf BL, Lieberman P. Anaphylaxis. A review of 266 cases. Arch Intern Med. 1995;155:1749–1754
    • View In Article
    • MEDLINE
41. Mullins RJ. Anaphylaxis: risk factors for recurrence. Clin Exp Allergy. 2003;33:1033–1040
    • View In Article
    • MEDLINE
    • CrossRef
42. Cianferoni A, Novembre E, Pucci N, Lombardi E, Bernardini R, Vierucci A. Anaphylaxis: a 7-year follow-up survey of 46 children. Ann Allergy Asthma Immunol. 2004;92:464–468
    • View In Article
    • Abstract
    • Full-Text PDF (314 KB)
    • CrossRef
43. van der Linden PW, Struyvenberg A, Kraaijenhagen RJ, Hack CE, van der Zwan JK. Anaphylactic shock after insect-sting challenge in 138 persons with a previous insect-sting reaction. Ann Intern Med. 1993;118:161–168
    • View In Article
    • MEDLINE
44. Grabenstein JD, Smith LJ. Incidence of anaphylactic self-treatment in an outpatient population. Ann Allergy. 1989;63:184–188
    • View In Article
    • MEDLINE
45. Gold MS, Sainsbury R. First aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (EpiPen). J Allergy Clin Immunol. 2000;106:171–176
    • View In Article
    • Abstract
    • Full-Text PDF (64 KB)
    • CrossRef
46. Simons FER, Gu X, Silver NA, Simons KJ. EpiPen Jr versus EpiPen in young children weighing 15-30 kg at risk for anaphylaxis. J Allergy Clin Immunol. 2002;109:171–175
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (84 KB)
    • CrossRef
47. Davis CO, Wax PM. Prehospital epinephrine overdose in a child resulting in ventricular dysrhythmias and myocardial ischemia. Pediatr Emerg Care. 1999;15:116–118
    • View In Article
    • MEDLINE
    • CrossRef
48. Simons FER. Advances in H₁-antihistamines. N Engl J Med. 2004;351:2203–2217
    • View In Article
    • CrossRef
49. Simons FER. First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin Immunol. 2004;113:837–844
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (280 KB)
    • CrossRef
50. Pumphrey RSH. Fatal posture in anaphylactic shock. J Allergy Clin Immunol. 2003;112:451–452
    • View In Article
    • Full Text
    • Full-Text PDF (197 KB)
51. Ewan PW, Clark AT. Long-term prospective observational study of patients with peanut and nut allergy after participation in a management plan. Lancet. 2001;357:111–115
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (410 KB)
    • CrossRef
52. Moneret-Vautrin DA, Kanny G, Morisset M, Flabbee J, Guenard L, Beaudouin E, et al. Food anaphylaxis in schools: evaluation of the management plan and the efficiency of the emergency kit. Allergy. 2001;56:1071–1076
    • View In Article
    • MEDLINE
    • CrossRef