COVID-19 mRNA vaccine allergy.

PURPOSE OF REVIEW: A known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine is the only contraindication to coronavirus disease 2019 (COVID-19) mRNA vaccination. It is important for pediatricians to understand the likelihood of an allergic reaction to COVID-19 mRNA vaccines, including its excipients. RECENT FINDINGS: Episodes concerning for anaphylaxis were immediately reported following early administration of COVID-19 mRNA vaccines to adults. Although allergic type symptoms were reported equally in recipients of placebos and test vaccines in phase 3 clinical trials, post-authorization prospective studies state that 0.2-2% of vaccine recipients have experienced allergic reactions. Subsequent allergy testing of affected individuals has focused largely on evaluation of allergic sensitization to a novel vaccine excipient, polyethylene glycol (PEG). PEG is a polymer incorporated in numerous pharmaceutical products because of its favorable, inert properties. The results of allergy testing in adults to date indicate that IgE mediated anaphylaxis to PEG allergy is rarely identified after COVID-19 mRNA vaccine reactions. Numerous individuals with presumed anaphylaxis have tolerated a second vaccine after evaluation and testing by an allergist, suggesting either misdiagnosis or a novel immune mechanism. SUMMARY: Confirmed anaphylactic reactions to COVID-19 mRNA vaccines are rare, likely due to a lack of preexisting IgE against the vaccine components, including PEG.

Evaluation of pediatric patients with suspected polyethylene glycol and polysorbate allergy before mRNA SARS-CoV2 vaccination.

mRNA vaccines, particularly, have been associated with an increased risk of allergic reactions and rarely anaphylaxis. Although rare, vaccine reactions can cause significant anxiety and fear in the population, leading to indecision and vaccine refusal. This study aimed to retrospectively evaluate the role of polyethylene glycol (PEG) sensitivity in vaccination decision-making in pediatric patients at high risk of allergy or with suspected allergic reactions to the first dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine. Seventeen enrolled patients were found to have decreased readiness to receive the Coronavirus Disease 2019 (COVID-19) vaccine after developing hypersensitivity to multiple and/or injectable drugs. Skin testing was performed. A basophil activation test with PEG-2000 and 4000 was performed on three patients who were ineligible for skin prick tests. Nine patients with negative tests received the vaccine without complications. One patient had urticarial angioedema despite negative tests. Three patients with positive tests did not agree to desensitization with the mRNA vaccine, and one of them was vaccinated with the inactivated COVID-19 vaccine. Four patients recurred despite negative tests. The general recommendation for patients describing severe reactions to drugs, foods, and allergens, such as toxins that do not contain the adjuvants of the SARS-CoV-2 vaccines, is to be routinely vaccinated with safety precautions. Excipients such as PEG and polysorbate-80 used in COVID-19 vaccines could be potential allergens, but this hypothesis is unclear. The predictive values of these adjuvants for skin testing and in vitro testing are controversial. Further research is needed on the hypersensitivity reactions of adjuvants, the predictive values of skin tests, and etiopathogenesis.

[Allergy to Pfizer-BioNTech® vaccine demonstrated by skin testing]. / Alergia a la vacuna Pfizer-BioNTech® demostrada mediante pruebas cutáneas.

BACKGROUND: The Pfizer-BioNTech® BNT162b2 vaccine, provides 95% effectiveness from the second dose onwards. The reported rate of anaphylaxis to COVID-19 vaccines is 4.7 cases/million doses administered. CASE REPORT: 30-year-old female, health professional, history of allergic rhinitis, asthma, reaction to eye cosmetics and adhesive tape: erythema, edema, and local pruritus. Immediately after application of the first dose of Pfizer-BioNTech vaccine, she presented grade III anaphylaxis. The patient was stratified, phenotyped and skin tests with PEG 3350 were positive. A recommendation was issued not to reapply vaccine containing polyethylene glycol and alternatives were offered. CONCLUSIONS: An adequate risk stratification should be performed before applying mRNA-based COVID-19 vaccines for the first time in at-risk groups. In case of anaphylaxis at the first dose, phenotyping and further study with PEG skin tests should be performed and vaccination alternatives should be offered.

INTRODUCCIÓN: La vacuna Pfizer-BioNTech® BNT162b2 proporciona efectividad del 95% a partir de la segunda dosis. La tasa de anafilaxia reportada de vacunas para COVID-19 es de 4.7 casos por millón de dosis administradas. REPORTE DEL CASO: Paciente femenina de 30 años, profesional de la salud, con antecedentes de rinitis alérgica, asma, reacción a productos cosméticos en los párpados y al pegamento de la cinta adhesiva (eritema, edema y prurito local). Posterior a la aplicación de la primera dosis de la vacuna Pfizer-BioNTechÒ tuvo un evento de anafilaxia grado III. Se estratificó, fenotipificó y efectuaron pruebas cutáneas con PEG-3350, que resultaron positivas. Se sugirió no aplicar la aplicar vacuna de refuerzo que contuviera polietilenglicol y se ofrecieron alternativas de tratamiento. CONCLUSIONES: Es importante efectuar la adecuada estratificación de riesgo antes de aplicar las vacunas para COVID-19 basadas en ARNm por primera vez. En caso de anafilaxia es necesario fenotipificar y ampliar el estudio con pruebas cutáneas con PEG, además de otorgar alternativas de vacunación.

Direct Versus Indirect Query Performance of ICD-9/-10 Coding to Identify Anaphylaxis.

BACKGROUND: Anaphylaxis is an often under =diagnosed, severe allergic event for which epidemiological data are sporadic. Researchers have leveraged administrative and claims data algorithms to study large databases of anaphylactic events; however, little longitudinal data analysis is available after transition to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM). OBJECTIVE: Study longitudinal trends in anaphylaxis incidence using direct and indirect query methods. METHODS: Emergency department (ED) and inpatient data were analyzed from a large state health care administration database from 2011 to 2020. Incidence was calculated using direct queries of anaphylaxis ICD-9-CM and ICD-10-CM codes and indirect queries using a symptom-based ICD-9-CM algorithm and forward mapped ICD-10-CM version to identify undiagnosed anaphylaxis episodes and to assess algorithm performance at the population level. RESULTS: An average of 2.4 million inpatient and 7.5 million ED observations/y were analyzed. Using the direct query method, annual ED anaphylaxis cases increased steadily from 1,454 (2011) to 4,029 (2019) then declined to 3,341 in 2020 during the coronavirus disease 2019 (COVID-19) pandemic. In contrast, inpatient cases remained relatively steady, with a slight decline after 2015 during the ICD version transition, until a significant drop occurred in 2020. Using the indirect queries, anaphylaxis cases increased markedly after the ICD transition year, especially involving drug-related anaphylaxis. CONCLUSIONS: Nontypical drug associations with anaphylaxis episodes using the ICD-10-CM version of the algorithm suggest poor performance with drug-related codes. Further, the increased granularity of ICD-10-CM identified potential limitations of a previously validated symptom-based ICD-9-CM algorithm used to detect undiagnosed cases.

Anaphylaxis in elderly people.

PURPOSE OF REVIEW: Anaphylaxis is common in old-age adults but is insufficiently understood by physicians, and may be underdiagnosed. This review discusses the specificities of anaphylaxis in this age group and stresses the importance of adrenaline in its management. RECENT FINDINGS: Data from the European Anaphylaxis Registry on elderly patients is a major finding. Other findings include the prevention of possible anaphylactic reactions in coronavirus disease 2019 vaccination as well as some new epidemiologic data. SUMMARY: The most common risk factors are hymenoptera venom and food and drug allergy. Cardiovascular symptoms are the most important ones to reverse in old-age adults, especially due to the multiple comorbidities. Anaphylaxis in old-age adults has a more severe outcome than in younger ones. Polypharmacy is a specific factor to be considered. The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) algorithm is applicable in all clinical emergencies for immediate assessment and treatment, and should be considered for all patients. Adrenaline is the mainstay of the management of the condition. There are no absolute contraindications to the prescription of self-injectable adrenaline in elderly individuals at risk of anaphylaxis.

Acute At-Home Management of Anaphylaxis: 911: What Is the Emergency?

The appropriate at-home management of anaphylaxis begins with patient education on recognition and treatment, especially when and how to use epinephrine. Delayed administration of epinephrine as well as having severe symptoms and needing multiple doses of epinephrine to treat symptoms are risk factors for biphasic anaphylaxis. The successful implementation of at-home management of anaphylaxis requires appropriate patient selection and an algorithmic approach that recommends activation of emergency medical services (EMS) when the patient does not adequately respond to at-home administration of epinephrine or there are extenuating patient-related circumstances. Fortunately, approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine, the standard prescription used for epinephrine autoinjectors; fatal anaphylaxis is very rare, as low as 0.002 deaths/million person-years; and biphasic reactions are uncommon (∼5%), and only extremely rarely lethal. Thus, most common concerns leading to recommended EMS activation and emergency department visits after epinephrine administration are generally unsubstantiated. Furthermore, emergency department visits do not always lead to better treatment and drive health care costs higher. Open communications with patients and families regarding risks and benefits of at-home management and observation versus EMS activation and emergency department evaluation after epinephrine administration for anaphylaxis are essential. However, we believe the data indicate that it is time to reconsider the often used and taught approach that recommends EMS activation whenever epinephrine is used.

Hypersensitivity to polyethylene glycol (PEG).

The need for mass population vaccination against Covid-19 poses a public health problem. Allergic symptoms occurring after the 1st dose of the vaccine may result in resignation from the administration of the 2nd dose. However, the majority of patients with mild and/or non-immediate symptoms may be safely vaccinated. The only absolute contraindication to administration of the vaccine is an anaphylactic reaction to any of its ingredients. Polyethylene glycol (PEG), widely used as an excipient in various vaccines, is considered the primary cause of allergic reactions associated with administration of Comirnaty (Pfizer/BioNTech) and Covid-19 Vaccine (Moderna) vaccines. However, hypersensitivity to PEG reported to date seems very rare, considering its widespread use in multiple everyday products, including medicines and cosmetics. In the paper, current literature data describing mechanisms of hypersensitivity reactions to PEG, their clinical symptoms and diagnostic capabilities are presented. Undoubtedly, the issue of hypersensitivity to PEG warrants further research, while patients with the diagnosis require individual diagnostic and therapeutic approach.

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

The Revenge of Unintended Consequences of Anaphylaxis-Risk Overdiagnosis: How Far We Have Come and How Far We Have to Go.

Overdiagnosis of anaphylaxis risk is an underappreciated aspect of anaphylaxis prevention. Whereas the benefits of anaphylaxis-risk prevention are well known, potential harms resulting from preemptive approaches to mitigate anaphylaxis-risk are not insignificant. Still, great progress has been made in recent years to avoid the unintended consequences of anaphylaxis-risk overdiagnosis. Reflection on recent advances in the use of diagnostic testing, as well as the application of diagnostic labels, provides an important perspective to understand how far the specialty of allergy and immunology has come in improving the lives of patients and families. Examples of recent paradigm shifts in anaphylaxis-risk management include approaches to peanut allergy prevention without screening, deferral of corticosteroids to prevent biphasic anaphylaxis reactions, reevaluation of reflex use of emergency medical services for resolved community anaphylaxis, and an approach to penicillin allergy delabeling with direct oral challenge. Routine medical practices to decrease anaphylaxis risk can have lifelong impacts for patients-beyond just preventing anaphylaxis. As our understanding of these trade-offs evolves, it becomes necessary to weigh both the benefits and the harms of past management approaches. Because medicine remains a science of uncertainty and an art of probability, a critical approach to risk mitigation remains necessary to find the often-elusive balance in anaphylaxis prevention.

Efficacy of a rational algorithm to assess allergy risk in patients receiving the BNT162b2 vaccine.

Among 6146 hospital employees, 118 subjects with severe allergic background were identified through a screening questionnaire and stratified into 3 groups (Low-risk (LR), Intermediate (IR) and High-risk (HR) group), based on their allergic anamnesis. Data reports on hypersensitivity reactions (HypR) have been collected in both allergic and non-allergic subjects. Seventeen patients (14%) in the allergic population had a HypR after the first, the second or both doses. Skin manifestations were the most frequent ones. Allergic events were more frequent in HR (35%) than IR (10%; p = 0.005) or LR (0%; p = 0.074) subjects. No patient had anaphylaxis. All patients completed the vaccination schedule. 13 HypR occurred in patients without severe allergic background (13/6028, 0,2%) including one (1/6148, 0.016% of total population) WAO grade-4 anaphylaxis. Our data suggest that BNT162b2 mRNA Covid-19 vaccine is relatively safe also in patients with severe allergic background; however, some precautions are required for high-risk patients.

Allergic reactions and adverse events associated with administration of mRNA-based vaccines. A health-care system experience.

Background: Adverse reactions, including anaphylaxis, to messenger RNA coronavirus disease 2019 (COVID-19) vaccines rarely occur. Because of the need to administer a timely second dose in subjects who reported a reaction to their first dose, a panel of health-care professionals developed a safe triage of the employees and health care providers (EHCP) at a large health-care system to consider administration of future dosing. Methods: There were 28,544 EHCPs who received their first dose of COVID-19 vaccines between December 15, 2020, and March 8, 2021. The EHCPs self-reported adverse reactions to a centralized COVID-19 command center (CCC). The CCC screened and collected information on the quality of reaction, symptoms, and timing of the onset of the reaction. Results: Of 1253 calls to the CCC, 113 were identified as requiring consideration by a panel of three (American Board of Allergy and Immunology) ABAI-certified allergists for future dosing or formal in-person assessment. Of the 113 EHCPs, 94 (83.2%) were recommended to get their second dose. Eighty of 94 received their second planned dose without a severe or immediate reaction. Of the 14 of 113 identified as needing further evaluation, 6 were evaluated by a physician and subsequently received their second dose without a serious adverse reaction. Eight of 14 did not receive their second dose. Only 5 of the 113 EHCPs reported reactions (4.4%) were recommended to not take the second dose: 3 (2.6%) because of symptoms consistent with anaphylaxis, and 2 because of neurologic complications (seizure, stroke). Conclusion: The panel demonstrated that, by consideration of reaction history alone, the ECHPs could be appropriately triaged to receive scheduled second dosing of COVID-19 vaccines without delays for in-person evaluation and allergy testing.