Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.
The U.S. Food and Drug Administration (FDA) has recently issued an Emergency Use Authorization (EUA) for 2 highly effective coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. This has brought hope to millions of Americans in the midst of an ongoing global pandemic. The FDA EUA guidance for both vaccines is to not administer the vaccine to individuals with a known history of a severe allergic reaction (eg, anaphylaxis) to any component of the COVID-19 vaccine. The Centers for Disease Control and Prevention (CDC) additionally advises individuals with a history of an immediate allergic reaction to a vaccine or injectable or any history of anaphylaxis be observed for 30 minutes after COVID-19 vaccination. All other individuals should be observed for 15 minutes after COVID-19 vaccination. Staff at vaccine clinics must be able to identify and manage anaphylaxis. Post–FDA EUA, despite very strong safety signals in both phase 3 trials, reports of possible allergic reactions have raised public concern. To provide reassurance and support during widespread global vaccination, allergists must offer clear guidance to individuals based on the best information available, but also in accordance with the broader recommendations of regulatory agencies. This review summarizes vaccine allergy epidemiology and proposes drug and vaccine allergy expert opinion informed risk stratification for Allergy specialist use in conjunction with guidance of public health and regulatory authorities. The risk stratification schema guide care for (1) individuals with different allergy histories to safely receive their first mRNA COVID-19 vaccine and (2) individuals who develop a reaction to their first dose of mRNA COVID-19 vaccine.
BACKGROUND
Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.
METHODS
In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms.
RESULTS
A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.
CONCLUSIONS
In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
38.3%) were tested on days 9 to 14. Of the 134 student contacts tested on day 3, 14 (10.4%) were positive for SARS-CoV-2 infection. Of the 839 student contacts tested on days 9 to 14, 40 (4.8%) were positive for SARS-CoV-2 infection. Of the 388 student contacts in high school who were tested, 32 (8.2%) were positive for SARS-CoV-2 infection on days 9 to 14 compared with 8 (1.8%) of 451 student contacts in elementar y and middle school who tested positive (P < .001; Table ).Among 799 student contacts of confirmed COVID-19 cases with a negative test result on days 9 to 14, only 1 student became symptomatic after returning to school and had a positive SARS-CoV-2 test result on day 14 after an initial negative test result on day 9. The virus from this student was genetically distinct from the virus isolated from the confirmed COVID-19 case to which the student had been exposed (GenBank confirmed case: MW307809; GenBank 9-day student contact: MW308137). Loss of instruction decreased by 3649 days with the 9-day testing protocol (8097 days missed) compared with a theoretical 14-day quarantine without testing (11 746 days missed).Discussion | In this study of a 9-day testing protocol for student contacts of confirmed COVID-19 cases in 1 Florida county, a reduction in loss of instructional time was found that was less than what would have occurred with a 14-day quarantine. There was no evidence that an earlier return to school with a negative test result was linked with subsequent symptomatic illness. Had students returned to school before day 14 without testing on day 9 or thereafter, 8.2% of high school contacts would have returned to school with SARS-CoV-2 infection. These findings should be considered when evaluating the December 2020 CDC recommendation for a 10-day quarantine without testing or a 7-day quarantine with testing. 5 Limitations of this study include (1) contact testing ranging from days 9 to 14; (2) lack of testing for students who quarantined for 14 days; and (3) use of symptomatic illness alone for follow-up of negative test results.
Despite its relatively common occurrence and life‐threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic‐mediated angioedema from bradykinin‐mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin‐mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM).
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