Assessment of Patients With Anaphylaxis
Information about patient risk factors, triggers and mechanisms, and clinical diagnosis is updated in this section, which includes case series from five continents focusing on anaphylaxis in community settings, emergency departments (EDs), and hospitals.
Patient Risk Factors
Patient risk factors, including age or physiologic state-related vulnerability, concomitant diseases, concurrent medications, and co-factors, are similar worldwide.
Vulnerable patients include infants, teenagers, pregnant women, and the elderly. Although anaphylaxis can be difficult to diagnose in infants, case series of patients with anaphylaxis, published from different countries, include infants, one as young as 2 weeks of age. Adolescents and young adults are vulnerable to anaphylaxis because of risk-taking behaviors as they transition between parental control and autonomous decision-making. Some are not even aware of their life-threatening allergies and have never been instructed in allergen avoidance or the need for carrying an epinephrine auto-injector for self-administration; others are aware, but ignore the risks. Anaphylaxis during labor and delivery can lead to fatality or permanent disability from hypoxic-ischemic encephalopathy in mothers and especially in neonates. The most common triggers are intra-partum injection of penicillin, natural rubber latex, and other agents encountered in medical or perioperative settings. In patients with anaphylaxis who are more than 50 years old, typical triggers are stinging insect venoms, medications, and 'unknown'.
In young patients studied prospectively, asthma, especially when severe or uncontrolled, is strongly associated with anaphylaxis; additionally, during a food-induced anaphylactic episode, a history of asthma is predictive of dyspnea, wheezing, and respiratory arrest. A history of chronic/relapsing gastrointestinal symptoms is reported to be predictive of abdominal pain, vomiting, hypotension, bradycardia, and cardiac arrest. In patients with anaphylaxis due to insect venom, risk factors for increased severity include older age, pre-existing cardiovascular disease or mast cell disorder, elevated serum baseline total tryptase concentrations, concomitant treatment with a beta-adrenergic blocker and/or angiotensin-converting enzyme(ACE) inhibitor, a previous severe reaction, and the type of stinging insect (honey bees present the highest risk). Mast cell disorders are associated with an increased risk of severe or fatal anaphylaxis; of 137 consecutive patients with systemic mastocytosis, despite taking prophylactic medications, 12% had one or more life-threatening events. After Hymenoptera stings, two patients suffered from severe recurrent hypotensive episodes and required repeated resuscitation and hospitalization, and two other patients (one ofwhomlater died) were disabled by cerebral hypoxia.
Co-factors that amplify anaphylaxis have been described in nearly 20% of young patients in a prospective registry study. They include exercise, fever, acute infection such as an upper respiratory tract infection, premenstrual status, and emotional stress. Interestingly, these co-factors are also reported to amplify some of the acute allergic reactions to food that occur during prospective studies of oral food immunotherapy.
Triggers and Mechanisms
In contrast to older patients, foods are consistently reported to be the most common trigger of anaphylaxis in children and teenagers. In infants, sensitization to one or more foods is common and is not necessarily accompanied by any symptoms; however, in one population- based sample, more than 10% of 1-year-olds had oral challenge-proven clinical reactivity to uncooked egg, peanut, or sesame.
Patients can react clinically to a specific allergen in different ways, possibly reflecting the allergen components to which they are sensitized. As an example, in different countries, patients with elevated serum IgE levels to peanut have predominant IgE antibodies directed to different allergen components, associated with different symptom patterns. In the US, IgE antibodies directed to r Ara h 1, 2 and 3 are associated with severe earlyonset symptoms. In Spain, IgE antibodies directed to r Ara h 9 are associated with later onset of milder clinical reactivity to peanut and other plant-derived proteins such as peach. In Sweden, IgE antibodies directed to r Ara h 8, the Bet v 1 homolog, are also associated with later onset and milder clinical reactivity to peanut and other plant-derived proteins such as hazelnut.
Stinging insect venom-induced anaphylaxis has been extensively studied in Europe, North America, and Australia, where flying Hymenoptera insects are well documented anaphylaxis triggers. In North America, stings from nonflying imported fire ants (Solenopsis species) are also typical triggers, and in Australia, stings from jumper ants (Myrmecia species) are also typical triggers.
In a review of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity that included noncross- reactive NSAID (single NSAID) anaphylaxis, the authors focused on stepwise investigation, emphasizing the importance of the history and the pros and cons of skin tests, specific IgE levels, and challenge/provocation tests.
In a survey of anaphylaxis during anesthesia, of 2516 patients, 72% had an IgE-mediated reaction. In adults, this commonly involved neuromuscular blocking agents (58%), latex (20%), or antibiotics (13%); in children, it commonly involved latex (42%), neuromuscular blocking agents (32%), or antibiotics (9%).
A comprehensive review of subcutaneous immunotherapy (SCIT) with allergens includes new information about risk factors that increase the possibility of anaphylaxis during SCIT, and how to reduce this risk. In one US study, systemic reactions were reported in 4% of 28 000 SCIT injections; 22% of the 773 patients had previously reacted to SCIT.
Human IgG-mediated anaphylaxis remains an enigma. To facilitate its identification, decreased blood neutrophil Fc gamma RIII expression without increased IL-4 R alpha expression has been proposed as a marker.
Clinical Diagnosis
A poster and pocket card that capture the key messages in the Guidelines about prompt clinical diagnosis and initial treatment of anaphylaxis have been translated into ten different languages (Fig. 1). The clinical criteria for the diagnosis of anaphylaxis that emphasize sudden onset of multisystem symptoms have been validated in a retrospective cohort study of ED patients, in whom they had excellent sensitivity [96.7%, 95% confidence interval (CI) 88.8–99.9] and good specificity (82.4%, 95% CI 75.5–87.6). Additionally, use of these criteria in epidemiologic studies has significantly improved identification of patients with anaphylaxis.
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Figure 1.
Anaphylaxis diagnosis and treatment. Clinical criteria for the diagnosis of anaphylaxis and initial treatment of anaphylaxis, as illustrated in the poster and the pocket card based on the 2011 WAO Anaphylaxis Guidelines. The first part of this figure summarizes a validated approach to the clinical diagnosis of anaphylaxis, which is highly likely when any one of the three criteria is fulfilled. The second part of the figure summarizes the basic initial treatment which is relatively inexpensive to implement and should be possible even in a low resource environment. Note that steps 4, 5, and 6 should be performed promptly and simultaneously as soon as anaphylaxis is diagnosed. If precious minutes are lost early in the diagnosis and treatment of an anaphylactic episode, subsequent management can become more difficult. Guidelines are not a substitute for appropriate preparation, good clinical judgment, and strong clinical skills (adapted from [1]). WAO, World Allergy Organization.
Post mortem diagnosis of anaphylaxis can be difficult when little or no history is available, macroscopic signs are absent, and blood or other biologic fluids are unavailable or unsuitable for study. Identification of tissue mast cells, for example, in the laryngeal wall, by staining for immunohistochemical markers such as CD117, has been proposed for use in this setting.
Serum total tryptase measurements are not helpful for confirmation of the diagnosis of anaphylaxis at the time of the episode because the assay takes several hours to perform; however, they can be useful later, more so for confirmation of the clinical diagnosis of venom or medication-induced anaphylaxis than for confirmation of food-induced anaphylaxis. Serial monitoring of tryptase levels at the time of presentation, 1–2h later, and at resolution is reported to improve the sensitivity of the test.