Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

A survey study on antibiotic prescription practices for acute asthma exacerbations: An European academy of allergy and clinical immunology task force report.

INTRODUCTION: Guidelines recommend treating asthma exacerbations (AAEs) with bronchodilators combined with inhaled and/or systemic corticosteroids. Indications for antibiotic prescriptions for AAEs are usually not incorporated although the literature shows antibiotics are frequently prescribed. AIM: To investigate the antibiotic prescription rates in AAEs and explore the possible determining factors of those practices. METHODS: A digital survey was created to determine the antibiotic prescription rates in AAEs and the influencing factors for the prescription practices. The survey was distributed among European academy of allergy and clinical immunology (EAACI) members by mass emailing and through regional/national societies in the Netherlands, Italy, Greece, and Poland. Furthermore, we retrieved local antibiotic prescription rates. RESULTS: In total, 252 participants completed the survey. Respondents stated that there is a lack of guidelines to prescribe antibiotics in AAEs. The median antibiotic prescription rate in this study was 19% [IQR: 0%-40%] and was significantly different between 4 professions: paediatrics 0% [IQR: 0%-37%], pulmonologists 25% [IQR: 10%-50%], general practitioners 25% [IQR: 0%-50%], and allergologists 17% [IQR: 0%-33%]) (p = 0.046). Additional diagnostic tests were performed in 71.4% of patients before prescription and the most common antibiotic classes prescribed were macrolides (46.0%) and penicillin (42.9%). Important clinical factors for health care providers to prescribe antibiotics were colorised/purulent sputum, abnormal lung sounds during auscultation, fever, and presence of comorbidities. CONCLUSION: In 19% of patients with AAEs, antibiotics were prescribed in various classes with a broad range among different subspecialities. This study stresses the urgency to compose evidence-based guidelines to aim for more rational antibiotic prescriptions for AAE.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

EAACI/ENDA position paper on drug provocation testing.

In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low-risk patients. The task force suggests a strict definition of such low-risk patients in children and adults. Based on experience and evidence from studies of allergy to beta-lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non-steroidal anti-inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources.

A practical guide to address reactions to vaccines in children.

Currently available vaccines are safe, but, potentially, any vaccine can cause an allergic reaction and, albeit very rare, anaphylaxis can occur. Although its rarity, the precise diagnostic management of a suspected anaphylaxis postvaccination is of paramount importance due to the risk of a potentially serious reaction after re-exposure, while a misdiagnosis might lead to an increase in the number of children that interrupt vaccinations resulting in an unjustifiably individual and collective risk of loss of protection against immune preventable diseases. In the light that most cases of suspected allergy to a vaccine are not effectively confirmed in up to 85% of the cases referred for an allergy evaluation, patients can continue the vaccination schedule with the same formulation and tolerance of the booster doses. The patient assessment has to be done by an expert in the vaccine field, usually an allergist or an immunologist depending on the country, to select subjects at risk of allergic reactions and to perform the correct procedures for vaccine hypersensitivity diagnosis and management, in order to guarantee safe immunization practices. The aim of this review is to provide a practical guidance for the safe management of allergic children undergoing immunization procedures. The guide is referred both to the evaluation of children who have previously experienced a suspected allergic reaction to a specific vaccine and their management in case of further booster doses, and to children allergic to a component of the vaccine to be administered.

Allergic Reactions to COVID-19 Vaccines: Risk Factors, Frequency, Mechanisms and Management.

Conventional vaccines have been widely studied, along with their risk of causing allergic reactions. These generally consist of mild local reactions and only rarely severe anaphylaxis. Although all the current COVID-19 vaccines marketed in Europe have been shown to be safe overall in the general population, early post-marketing evidence has shown that mRNA-based vaccines using novel platforms (i.e., lipid nanoparticles) were associated with an increased risk of severe allergic reactions as compared to conventional vaccines. In this paper we performed an updated literature review on frequency, risk factors, and underlying mechanisms of COVID-19 vaccine-related allergies by searching MEDLINE and Google Scholar databases. We also conducted a qualitative search on VigiBase and EudraVigilance databases to identify reports of "Hypersensitivity" and "Anaphylactic reaction" potentially related to COVID-19 vaccines (Comirnaty, Spikevax, Vaxzevria and COVID-19 Janssen Vaccine), and in EudraVigilance to estimate the reporting rates of "Anaphylactic reaction" and "Anaphylactic shock" after COVID-19 vaccination in the European population. We also summarized the scientific societies' and regulatory agencies' recommendations for prevention and management of COVID-19 vaccine-related allergic reactions, especially in those with a history of allergy.

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.

Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases.

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.

Immunization practices and risk of anaphylaxis: a current update, comprehensive of COVID-19 vaccination data.

PURPOSE OF REVIEW: This review aims to provide an updated report in regards to the correlation between vaccines and anaphylaxis and the related risk in the population. RECENT FINDINGS: Initial reports showed higher incidence of anaphylaxis following messenger RNA COVID-19 vaccines compared with 'routine' vaccinations, likely influenced by the great attention paid to these 'new' vaccines. However, anaphylaxis has still to be considered quite rare and its incidence will be systematically reconsidered in the light of additional data collected. SUMMARY: Adverse reactions to vaccines are commonly reported but most of them are nonspecific mild events, whereas vaccine-related anaphylaxis is considered a rare event, with an incidence rate equal to 1.3 cases per million vaccine doses administered. As anaphylaxis reports usually start to be reported to passive pharmacovigilance during postmarketing surveillance, the first data are used to be influenced by under- and over-reporting and lack of denominators and following studies are needed to confirm the causal relationship. This might create an initial overcautiously approach to new immunization practices but, being anaphylaxis a potential life-threatening event, every suspected contraindication has to be deepened to maximize effectiveness and safety profile and constantly redefined not to exclude an overestimated population group who could receive the vaccine uneventfully.

A compendium answering 150 questions on COVID-19 and SARS-CoV-2.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Safety of uSCIT-MPL-4: prevalence and risk factors of systemic reactions in real life.

Aim: We assessed the safety of allergoid adjuvanted by monophosphoryl lipid A (uSCIT-MPL-4) in a real-life setting. Materials & methods: Patients treated with uSCIT-MPL-4 were followed-up for 1 year. Systemic reactions (SRs) were registered and the association with potential risk factors was evaluated. Results: 2929 patients were included. Grade 0, 1, 2, 3 and 4 SR reactions were observed respectively in 3.3, 1.5, 0.31, 0.07 and 0.07% of patients. A significant association was detected between Grade ≥1 SRs and: female gender, number of administrations, previous local reactions. Conclusion: uSCIT-MPL-4 is safe. Local reactions should be accurately assessed as they may represent a risk factor for Grade ≥1 SRs, together with gender and number of doses/year.

Anxiety and Depression Effects During Drug Provocation Test.

BACKGROUND: Drug provocation test (DPT) represents the gold standard for the diagnosis of drug allergy. A DPT can be performed in a single-blind placebo-controlled manner. In anxiety and depressive disorders, patients need to be evaluated to understand the nature of placebo reactions. OBJECTIVE: The aim of this study was to evaluate the psychological profile of patients with reactions to placebo during a DPT. METHODS: We consecutively enrolled patients with suspected drug allergy undergoing a DPT preceded by the administration of the placebo. All patients underwent the Hospital Anxiety and Depression Scale (HADS), a questionnaire aimed to identify anxiety and depression, before the challenge test. RESULTS: A total of 196 patients were enrolled into this study: 8 (4%) patients resulted positive to the DPT, 60 (30.6%) demonstrated anxiety or depression based on the HADS, and 54 had at least 1 placebo reaction during drug provocation. There were statically significant correlations between the positivity of the HADS and the finding of a placebo reaction (Fisher's exact test: P < .001), and between the latter and a history of severe reactions to drug (Fisher's exact test: P < .001). CONCLUSIONS: There is a significant and strong correlation between the loss of psychic equilibrium and the development of a placebo reaction during a DPT. We suggest the use the HADS or other validated questionnaire in clinical practice before a DPT to evaluate the possible psychiatric components.