Contemporary issues in anaphylaxis and the evolution of epinephrine autoinjectors: What will the future bring?

BACKGROUND: Food allergy and anaphylaxis appear to be increasing in the United States, especially in young children, and preparedness is paramount to successful emergency management in the community. Although the treatment of choice for anaphylaxis is epinephrine delivered by autoinjection, some devices are challenged by less user-friendly designs or pose the risk of injury, especially in young patients. Human factors engineering has played a larger role in the development of more recent epinephrine autoinjector technologies and will continue to play a role in the evolution and future design of epinephrine autoinjectors. OBJECTIVE: To discuss contemporary issues related to the identification and management of anaphylaxis, current and future epinephrine autoinjector design, and unmet needs for the treatment of special populations, namely, young children weighing less than 15 kg. METHODS: The literature was reviewed and select articles retrieved to support expert clinical opinions on the need for improved recognition of anaphylaxis, epinephrine autoinjector design, and unmet needs in special populations. RESULTS: Anaphylaxis may be underrecognized and poorly defined in infant- and toddler-aged children, current devices may not be adequate to safely treat these patients (ie, inappropriate needle length), and health care professionals may not be aware of these issues. CONCLUSION: As epinephrine autoinjector technology continues to evolve, device characteristics that promote safe, user-friendly experiences and give clinicians and their patients confidence to successfully treat anaphylaxis during an emergency, without injury, will be favored.

An analysis of anaphylaxis cases at a single pediatric emergency department during a 1-year period.

BACKGROUND: Case series of anaphylaxis can vary regarding causes, treatments, and follow-up of patients. Unfortunately, case series that are specific to the pediatric population are few. OBJECTIVE: To describe confirmed cases of pediatric anaphylaxis in patients presenting to a pediatric hospital emergency department (ED). METHODS: We identified all ED visits with the International Classification of Diseases, Ninth Revision (ICD-9) codes 995.XX (allergic reactions) and 989.5 (sting or venom reaction) for 1 calendar year (January 1, 2014, through December 31, 2014). Cases were reviewed by an allergist and an emergency medicine physician to identify true anaphylaxis cases using National Institute of Health/National Institute of Allergy and Infectious Diseases criteria. Any questionable or debatable cases were evaluated and adjudicated by a second allergist. RESULTS: We identified 927 unique ED visits. Of these visits, 40 were determined to definitively meet anaphylaxis criteria. Median age of the patients was 6.5 years. A total of 70% of patients were male, and 80% were African American. Causes included foods (65%), venom or insect sting (12.5%), and medications (5%), and 17.5% were idiopathic. All patients had multiorgan involvement, with 98% having skin involvement, 78% having lower respiratory tract symptoms, and 40% having gastrointestinal symptoms. There were no deaths. Only 33% of patients received epinephrine at some point in their care. Only 12 patients were referred to an allergist, and only 4 of these were actually seen by an allergist. CONCLUSION: At our center, foods are the most common trigger for pediatric anaphylaxis. Patients continue to be undertreated, and referral to an allergist from the ED is rare.

Nonallergic Rhinitis: Treatment.

Chronic nonallergic rhinitis (NAR) is a syndrome rather than a specific disease. A lack of understanding of the pathogenesis of this condition has led to imprecise terminology with several alternate names for the condition, including vasomotor rhinitis, nonallergic rhinopathy, and idiopathic rhinitis. The therapy for NAR is best based on the underlying pathology, which typically exists in a form whereby an abnormality of the autonomic nervous system is dominant or a form in which inflammation seems to be the cause of symptoms. In general the most effective therapy is the combination of an intranasal antihistamine and an intranasal corticosteroid.

Anaphylaxis: underdiagnosed, underreported, and undertreated.

Diagnostic criteria and administrative codes for anaphylaxis have evolved in recent years, partly reflecting the challenges in recognizing anaphylaxis and understanding its symptoms. Before the diagnostic criteria were disseminated by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network, several studies showed that a substantial proportion of anaphylaxis cases presenting to the emergency department (ED) were not recognized as such. Furthermore, epinephrine, the first-line treatment, was used in fewer than half of cases, especially if anaphylaxis was not diagnosed at the time. Although management practices may have improved since that time, anaphylaxis continues to be underrecognized and undertreated in the US. Of particular concern are findings that the majority of patients who visited the ED for an acute allergic reaction or anaphylaxis were not given a prescription for an epinephrine autoinjector, educated about avoiding the offending allergen, or advised to consult with an allergist. Improvements in the recognition and management of anaphylaxis have the potential to reduce the substantial burden that it currently places on the health care system. The articles in this supplement cover a wide range of issues surrounding anaphylaxis and seek to disseminate information helpful to health care professionals in general and primary care providers in particular.

Recognition and first-line treatment of anaphylaxis.

The International Classification of Diseases (ICD)-9 included a code only for anaphylactic shock. The improved ICD-10 coding defines the different symptoms and types of anaphylaxis and includes coding for anaphylaxis without shock. This new coding is consistent with the efforts of the National Institute of Allergy and Infectious Diseases (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN), who convened a panel to formulate a definition of and the diagnostic criteria for anaphylaxis. Anaphylaxis is a serious reaction that has a rapid onset and may cause death. It is a systemic immunoglobulin E-mediated reaction resulting from the sudden release of multiple mediators from mast cells and basophils. Foods are the most common triggers for anaphylactic reactions, followed by drugs, insect stings, and idiopathic anaphylaxis (anaphylaxis of unknown cause). If the NIAID/FAAN criteria are met and anaphylaxis is diagnosed, epinephrine administration is mandatory. Delays in epinephrine administration have been associated with fatalities. Patients should have ready access to >1 epinephrine autoinjector in the outpatient setting. An individualized emergency action plan should be developed for each patient at risk for anaphylaxis.

Hazards of unintentional injection of epinephrine from autoinjectors: a systematic review.

OBJECTIVES: To ascertain the rate of occurrence of unintentional injections from epinephrine autoinjectors used in the first aid treatment of anaphylaxis and to provide information about the resulting needle stick injuries. DATA SOURCES: A systematic review was performed. The MEDLINE, Scirus, CINAHL, ISI Web of Science, and Google Scholar databases were searched by title and abstract to identify reports of unintentional injections from epinephrine autoinjectors published in peer-reviewed journals. STUDY SELECTION: Publications were selected for inclusion based on predefined strict criteria. RESULTS: In 26 reports published during the past 20 years, we identified 69 people with an unintentional injection of epinephrine from an autoinjector. More than 68% of them were reported in the past 6.3 years, 58% were female, 42% were injured in the home, and 91% sustained injury to a finger or thumb. More than 65% of the 69 individuals were evaluated in an emergency department; 13% of the 69 were not treated or were treated only with observation. Warming of the injured part was used in 25%, nitroglycerin paste application in 9%, local injections of phentolamine and/or lidocaine in 22%, and other treatments in 20%; treatment, or lack thereof, was not described in 12%. No permanent sequelae were reported. CONCLUSIONS: The true rate of occurrence of unintentional injection of epinephrine from autoinjectors is unknown but is increasing. People at risk for anaphylaxis need regular coaching in how to use epinephrine autoinjectors correctly and safely. Improved autoinjector design will address the safety concerns identified in this review.

Office-based management of allergic rhinitis in adults.

Allergic rhinitis (AR), the most common form of rhinitis, affects 10% to 30% of adults. However, the prevalence of AR actually may be underestimated. Rhinitis is caused by allergic, nonallergic, infectious, hormonal, occupational, and other factors. Proper management of AR requires that the correct diagnosis be made; the clinical history and physical examination are key. Controlled studies support the utility of several available treatments that produce fewer symptoms, improve quality of life, and prevent comorbidities.

Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.

There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.

There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

Azelastine nasal spray: a review of pharmacology and clinical efficacy in allergic and nonallergic rhinitis.

Azelastine hydrochloride is a pharmacologically distinct H1-receptor antagonist with a broad spectrum of antiallergic and anti-inflammatory activity. Azelastine has established antiallergic and anti-inflammatory effects that are unrelated to H1-receptor antagonism, including inhibitory effects on the synthesis of leukotrienes, kinins, and cytokines; the generation of superoxide free radicals; and the expression of the intercellular adhesion molecule 1. Azelastine is available in the United States as a nasal spray formulation (Astelin) and is approved for treatment of seasonal allergic rhinitis and nonallergic vasomotor rhinitis. In U.S. clinical trials, azelastine nasal spray was effective in treating all of the symptoms of the allergic rhinitis symptom complex including ocular symptoms, and in double-blind clinical trials in nonallergic vasomotor rhinitis, azelastine nasal spray was effective in treating the total vasomotor rhinitis symptom complex including individual symptoms of nasal congestion and postnasal drip. This article reviews the pharmacologic profile and clinical efficacy and safety of azelastine nasal spray.