Allergic reactions and anaphylaxis are potentially life-threatening processes that present with a variety of clinical symptoms. Emergency clinicians must be able to recognize these presentations and make prompt clinical decisions regarding management of a patient’s airway, treatment options, and disposition of a patient who improves after initial presentation. Furthermore, emergency clinicians may be faced with patients who have atypical presentations or require special consideration, such as high-risk patients with comorbid conditions and patients who do not respond to first-line treatments. An increasing number of patients in the United States carry allergy diagnoses, and it is expected that this subset of the population will continue to seek care in the emergency department. This review assesses the research and evidence on the diagnosis, etiology, and treatment of anaphylaxis, as well as the utilization of epinephrine, both in and out of the hospital setting.
A 55-year-old man with no significant medical history presents to the ED after breaking out in an “itchy” rash on day 3 of using an antibiotic for a sinus infection, but he can't recall the name of the medication. He has no other recent exposures or food allergies. His girlfriend once had a similar reaction to a medication, and just prior to arrival she gave the patient her epinephrine auto-injector to use. The patient reports abdominal cramping and wheezing, and he states that he feels a tingling in his lips, although there is no lip swelling, and he is breathing without difficulty. He notes that the rash seems to be spreading to different parts of his body, and resolves in one place only to reappear somewhere else. He denies any history of allergy to medications in the past, and says he has taken many different types of antibiotics without untoward effects. His vital signs are: temperature, 37°C; blood pressure, 130/80 mm Hg; heart rate, 90 beats/min; and respiratory rate, 12 breaths/min. The patient also took diphenhydramine 25 mg by mouth 30 minutes prior to arrival in the ED, and he notes that the rash and itching seem to be improving, although he has residual abdominal cramping and mild wheezing. The patient wants to go home, and you wonder if that’s a good idea.
A 40-year-old woman with a history of hypertension who takes 100 mg a day of metoprolol is brought to the ED by EMS after experiencing a sensation of throat tightening and dizziness about 10 minutes into her normal indoor exercise routine on a treadmill. She has no other medical problems and no significant family history. In an effort to eat more healthfully, she has been consciously increasing her intake of green vegetables lately, and consumed 16 ounces of a juice comprised of celery and kale 1 hour prior to exercise. She denies chest pain or pressure, and the initial ECG from EMS shows sinus tachycardia at 120 beats/min, without any other concerning changes for acute coronary syndromes. En route to the ED, she developed a diffuse, pruritic rash and received diphenhydramine and methylprednisolone from EMS, but does not appear better. Her vital signs are: temperature, 37.2°C; blood pressure, 90/60 mm Hg; heart rate, 120 beats/min; and respiratory rate, 16 breaths/min. Her physical examination is remarkable for a diffuse rash, expiratory wheezing, and uvula and posterior oropharyngeal mucosal swelling. Although she adamantly denies any food and drug allergies and has not had exposure to any new medications, you proceed to treat her for an anaphylactic reaction and administer 0.5 mg of a 1:1000 solution of intramuscular epinephrine to the anterolateral thigh. However, soon after the administration of epinephrine, you note that she is no better, and, in fact, her heart rate has now increased to 140 beats/min, and her blood pressure has dropped to 80/50 mm Hg. Your nurse and medical student look a bit concerned, and your student asks why this is happening when epinephrine is the first-line drug for anaphylaxis. The medical student wonders out loud whether there is anything else you might give this patient to help her, and whether you could be missing a cardiac event...
Allergic reactions occur when hypersensitivity to a foreign protein or antigen that normally would not be deleterious is acquired. On the spectrum of allergic responses, anaphylaxis is a profound reaction. Historically, anaphylaxis has lacked a standard, universally accepted definition, which has hampered the ability to consistently diagnose it. The National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network consensus defines anaphylaxis clinically as a continuum of a constellation of acute symptoms affecting multiple systems in the body after exposure to an allergen. Anaphylaxis is probable when any of the following criteria are met: (1) the presence of skin signs or symptoms together with respiratory involvement or signs of organ dysfunction or hypotension; (2) the involvement of at least 2 organs or systems after recent exposure to an allergen; or (3) signs of organ dysfunction or hypotension after exposure to a known allergen.1 The areas of organ dysfunction are skin and mucosal tissue, as well as respiratory, neurologic, and vascular systems.
Anaphylaxis is caused by an immediate hypersensitivity response mediated by immunoglobulin-E (IgE) that releases inflammatory mediators from mast cells in tissues and from basophils into circulation. This IgE-mediated response follows a previous exposure to an allergen and sensitization to it, and it results in a rapid, potentially life-threatening reaction.
An anaphylactoid reaction is an immediate systemic reaction that, similar to an anaphylactic reaction, also releases inflammatory mediators via the stimulation of mast cells and basophils. However, unlike anaphylaxis, it is not IgE-mediated and, because the formation of IgE is not a prerequisite, an anaphylactoid reaction may occur on the initial exposure to an allergen. Clinically, anaphylactoid reactions are often indistinguishable from anaphylaxis. For this reason, the World Allergy Organization has suggested abandoning use of this terminology and referring to anaphylactic and anaphylactoid reactions as IgE-mediated anaphylaxis and nonallergic anaphylaxis, respectively.2 Some triggers of anaphylaxis include radiocontrast dye, ethanol, N-acetylcysteine, and opioids.3
Angioedema is localized, nonpitting edema of the subcutaneous and submucosal tissues, resulting from mast cell mediators or bradykinin. It may be the result of a hereditary or acquired defect modulating bradykinin-related peptides and complement activation, as a result of a C1-esterase inhibitor deficiency. Furthermore, it may occur secondary to drugs, especially angiotensin-converting enzyme (ACE) inhibitors, or via an allergic/IgE-related mechanism.
The emergency clinician must confidently identify anaphylaxis and allergic reactions, and implement definitive and rapid interventions. Delays in treatment and inadequate treatment may have dire consequences. This issue of Emergency Medicine Practice presents a review of the current evidence that guides the evaluation and treatment of anaphylaxis and allergy, and focuses on the clinical scenarios that are most often seen in common practice.
A literature search was performed using PubMed and Ovid MEDLINE® with the search terms anaphylaxis, allergy, and hypersensitivity. The search focused on English-language articles limited to humans that included systematic reviews, clinical trials, multicenter studies, or meta-analyses. References pertinent to emergency treatment were selected, and used for additional manual literature searches. Due to the plethora of literature on allergy and anaphylaxis, the search focused on literature from 1986 to 2014, including clinical diagnosis in the emergency setting and on prehospital and hospital diagnosis and treatment. In addition, a search of the National Guideline Clearinghouse (www.guideline.gov), using these refined search terms, produced guidelines and practice parameters from 2010 and 2011. A review of the Cochrane Database of Systematic Reviews yielded approximately 13 reviews on the general category of allergy and anaphylaxis. Several of these were specific to emergency management and covered the following topics: H1 antihistamines in anaphylaxis, glucocorticoids and heliox use in allergy and asthma, epinephrine auto-injectors, and an emergency action plan for people at risk of anaphylaxis. Overall, approximately 550 articles were reviewed, and 104 of these are included here for reference.
Due to the ethical challenges of randomized placebo-controlled trials of treatment for anaphylaxis, most studies are retrospective or based on clinical observations. Although a preponderance of the literature is from the field of allergy and immunology, a smaller number of references were found in the emergency medicine and pediatric emergency care literature.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.
Elizabeth Singer, MD, MPH, FACEP; David Zodda, MD;
August 1, 2015
August 31, 2018
Upon completion of this article, participants should be able to:
Date of Original Release: August 1, 2015. Date of most recent review: July 10, 2015. Termination date: August 1, 2018.
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