Accidental allergic reactions to immediate-type food allergens in Japanese children: A single-center study.

BACKGROUND: Few studies have assessed the nature of accidental allergic reactions (AAR). We assessed the prevalence and risk factors for AAR in Japanese children. METHODS: This study included children with immediate-type hen's egg (HE), cow's milk (CM), wheat, or peanut allergy who developed allergic reactions within at least 2 years and were followed up regularly at a single national allergy center in Japan. From January to December 2020, low-dose reactivity was defined as allergic reactions to ≤250, ≤102, ≤53, or ≤ 133 mg of HE, CM, wheat, or peanut protein, respectively. The annualized AAR rate showed the number of reactions per patient per year (95% confidence interval). AAR risk factors were analyzed using multiple logistic regression. RESULTS: Of the 1096 participants, 609, 457, 138, and 90 had HE, CM, wheat, and peanut allergies, respectively. The median (interquartile range) age was 5.0 (2.3-8.6) years, 39% had completely eliminated allergenic food, and 24% had low-dose reactivity. The annualized AAR rate was 0.130 (0.109-0.153) in all sub-cohorts. Moderate and severe symptoms occurred in 50% and 0.7%, respectively, of children who experienced AAR. Multiple logistic regression revealed that low-dose reactivity was a significant risk factor for AAR in the overall and CM cohorts, respectively (p < .001 and p = .036). CONCLUSION: In this single-center study in Japan, the annualized AAR rate was relatively low during the COVID-19 pandemic; however, half of the participants with AAR had moderate to severe symptoms. Especially in the case of low-dose reactivity, children would require careful AAR risk management.

Perioperative Cefazolin for Total Joint Arthroplasty Patients Who Have a Penicillin Allergy: Is It Safe?

BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.

Impact of asthma on severe food-induced allergic reactions: a systematic review and meta-analysis.

Summary: Background. Food allergy can range from mild to severe, life-threatening reactions with various symptoms and organ involvement. The impact of asthma on severe food-induced allergic reactions is not completely understood. In the hypothesis that asthma increases the risk of severe food-induced allergic reactions, the aim of this study is to compare the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Methods. We performed a systematic research on electronic databases, including PubMed, Scopus, and Web of Science. Observational studies, studies reporting medical characteristics of patients diagnosed with food allergy, and studies reporting medical history of patients with allergic reactions were included. The primary outcome was the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. The protocol of this review was registered in PROSPERO (CRD42023448293). Results. Eight studies with a total of 90,367 patients met the inclusion criteria and were included, with a total population of 28,166 of patients with food allergy. The incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma was increased (OR = 1.28; 95% CI 1.03-1.59; p = 0.03; I2 = 59%). Conclusions. Individuals with both food allergy and asthma are at high risk of severe, potentially fatal allergic reactions. Healthcare professionals should prioritize prevention and management strategies for these subjects.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis.

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.

COVID-19 Vaccines Are Safely Tolerated in Adolescents with Cutaneous Mastocytosis.

INTRODUCTION: The management of the COVID-19 vaccine in children with mastocytosis is unclear due to a lack of data. In the current study, we aimed to evaluate the adverse reactions following COVID-19 vaccination in adolescents with cutaneous mastocytosis (CM). METHODS: This study included 27 paediatric patients who were diagnosed with CM and were followed up in the paediatric allergy department of a tertiary care children's hospital. RESULTS: The median (IQR) age of the patients at the time of COVID-19 vaccination was 180 (156-203) months. Forty-four per cent of patients were vaccinated with the COVID-19 vaccine. Among all participants, the vaccination rate was found to be higher in older children, those who had been diagnosed with MPCM, and those who had not been infected with COVID-19 (p = 0.019, p = 0.009, p = 0.002, respectively). A total of 23 doses of the COVID-19 vaccine, including two doses of Sinovac/CoronaVac and 21 doses of Pfizer/BioNTech, were administered to 12 paediatric patients with CM. One of the patients had a history of intense itch, erythematous urticarial plaques, and had an exacerbation of existing skin lesions within 24-48 h after both doses of Pfizer/BioNTech vaccination. CONCLUSION: The COVID-19 vaccination of patients with CM in this series seems to be safe, and the rate of adverse events was comparable to that in the general population. These results found in adolescents with CM are in line with the existing evidence that CM does not preclude vaccination in children.

Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA-B*1502 genotyping in Taiwan, 2000-2017: A nationwide longitudinal study.

OBJECTIVE: The HLA-B*1502 allele is strongly associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA-B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA-B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score-based stabilized weighting (PSSW) ensured well-balanced covariates. The difference in 3-month SCAR and SJS/TEN rates between phase 2 (2011-2017) and phase 1 (2000-2009) was examined using a one-sample Z-test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA-B*1502 genotyping. RESULTS: CBZ prescriptions reduced from 7% (2000-2003) to 6% (2004-2010) and 4% (2011-2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3-month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = -.38, p = .0342) and nonusers (r = -.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates. SIGNIFICANCE: Recognizing HLA-B*1502 allele and avoiding CBZ therapy in HLA-B*1502-positive patients is critical for preventing CBZ-induced severe adverse events.

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.

Update on Gadolinium Based Contrast Agent Safety, From the AJR Special Series on Contrast Media.

Since its introduction 35 years ago, gadolinium-enhanced MRI has fundamentally changed medical practice. While extraordinarily safe, gadolinium-based contrast agents (GBCAs) may have side effects. Four distinct safety considerations include: acute allergic-like reactions, nephrogenic systemic fibrosis (NSF), gadolinium deposition, and symptoms associated with gadolinium exposure. Acute reactions after GBCA administration are uncommon-far less than with iodinated contrast agents-and, while rare, serious reactions can occur. NSF is a rare, but serious, scleroderma-like condition occurring in patients with kidney failure after exposure to American College of Radiology (ACR) Group 1 GBCAs. Group 2 and 3 GBCAs are considered lower risk, and, through their use, NSF has largely been eliminated. Unrelated to NSF, retention of trace amounts of gadolinium in the brain and other organs has been recognized for over a decade. Deposition occurs with all agents, although linear agents appear to deposit more than macrocyclic agents. Importantly, to date, no data demonstrate any adverse biologic or clinical effects from gadolinium deposition, even with normal kidney function. This article summarizes the latest safety evidence of commercially available GBCAs with a focus on new agents, discusses updates to the ACR NSF GBCA safety classification, and describes approaches for strengthening the evidence needed for regulatory decisions.

Comparison of Two-Bag Versus Three-Bag N-Acetylcysteine Regimens for Pediatric Acetaminophen Toxicity.

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.

Type I Kounis syndrome induced by COVID-19 vaccination in China: a case report.

BACKGROUND: Kounis syndrome is a rare clinical condition characterized by the occurrence of an acute coronary event induced by an acute allergic episode. The ongoing pandemic of coronavirus disease 2019 (COVID-19) has contributed to an increase in the incidence of allergic reactions to a certain extent, thereby increasing the incidence of Kounis syndrome. Timely diagnosis and effective management of this disease are important in clinical practice. CASE PRESENTATION: We report a 43-year-old woman who developed generalized pruritus, breathlessness, paroxysmal precordial crushing pain, and dyspnea after receiving the third dose of the COVID-19 vaccine. After anti-allergic treatment and therapy for acute myocardial ischemia, her symptoms resolved with improvement in cardiac function and resolution of ST-segment changes. The prognosis was satisfactory, and the final diagnosis was type I Kounis syndrome. CONCLUSION: This patient with type I Kounis syndrome rapidly developed acute coronary syndrome (ACS) after an acute allergic reaction to the COVID-19 vaccine. ​Timely diagnosis of acute allergic reaction and ACS, and targeted treatment based on the relevant guidelines are the key to successful treatment of the syndrome.​.

Exposure to household dust, allergens, and endotoxin and allergy-related outcomes alternation in the general U.S. population.

It has been widely reported that the general population was at an increased risk of allergy diseases, which probably be related with household allergens exposure. However, the difference of local and systemic allergic reactions exposure to allergens has not been reported in the general population previously. The data of 1094 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 data bank were analyzed. Dust, allergens (Bia g 1, Bia g 2, Can f 1, Feld 1, Derp 1, Mus m 1, Rat n 1, Alternaria alternate, and Aspergillus fumigatus), and endotoxin, were measured to estimate sensitizing source exposure. And allergy-related outcomes indicators including hay fever, sneezing, allergic rhinitis (AR), immunoglobulin E (IgE), and allergic sensitization, were evaluzted to estimate local and systemic allergic reactions. Multiple linear regression and logistic regression models were used to examine the associations of sensitizer and allergy-related outcomes. The mean or median concentration of dust and endotoxin were 0.66 g and 12.98 EU/mg dust. The Derp 1, Mus m 1, Rat n 1, Alternaria alternate, and Aspergillus fumigatus were the main allergens in the dust, with the concentrations of 30.66 ng/g dust, 30.73 ng/g dust, 5.94 ng/g dust, 5.20 ng/g dust, and 207.68 µg/g dust, respectively. The prevalence of AR was 34.2% among the general population. After controlling for sociodemographic factors, we found that the allergens, such as Can f 1 and Feld 1, were positively associated with AR. The prevalence of allergic sensitization was about 20%. Dust and endotoxin were found positively associated with allergic sensitization, while Bia g 2, Rat n 1, Alternaria alternate, and Aspergillus fumigatus were inversely associated with that. Dust and endotoxin probably be associated with higher risk of local allergic reactions, while some allergens, such as Bia g 2, Rat n 1, Alternaria alternate, and Aspergillus fumigatus probably be associated with lower risk of systemic allergic reactions.

Food oral immunotherapy: Any distinguishing factors predicting the need of anti-IgE?

Oral immunotherapy (OIT) has gained popularity recently for IgE-mediated food allergy. Omalizumab (OMZ) has been used in patients (10-20%) who have too severe/frequent allergic reactions (AR) to continue OIT, to reduce these reactions. In this study, it was aimed to compare two groups of patients who completed OIT with and without OMZ and to seek determinants predicting the need of this treatment. It was also aimed to share the clinical findings regarding the long-term use of OMZ and the withdrawal process. Forty-one patients were started OIT and 93% could be desensitized. Two groups were similar in means of demographic characteristics, and clinical and laboratory findings. The patients who needed OMZ during OIT had also lower reaction doses during oral challenge (p = 0.037). Higher AR rate in this group declined after starting OMZ (p < 0.001). The injection intervals of OMZ were gradually extended. Most patients were able to discontinue OMZ (81%). There were no severe reactions during drug withdrawal attempts. The low reaction thresholds during oral food challenge may give a clue about OMZ requirement during OIT. It may be an option to start the treatment before OIT if reaction was seen in the first few steps of the oral food challenge. For the sake of safety, extension of injection intervals should be preferred instead of abruptly stopping OMZ.

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer.

AIM: To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer. METHODS: From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer. RESULTS: We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients. CONCLUSION: Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

The value of the basophil activation test in the evaluation of patients reporting allergic reactions to the BNT162b2 mRNA COVID-19 vaccine.

BACKGROUND: mRNA-based COVID-19 vaccines have been reported to induce hypersensitivity reactions (HSR) in a small number of individuals. We aimed to evaluate the real-world incidence of the BNT162b2 mRNA COVID-19 vaccine HSR and to determine the value of the basophil activation test (BAT) in the allergological workup of patients reporting these reactions. METHODS: We prospectively enrolled patients with a clinical history indicative of HSR to the BNT162b2 mRNA COVID-19 vaccine. The allergological workup included skin testing (STs) and BAT with polyethylene glycol (PEG) and the vaccine. In those with negative allergy assessments, the administration of the second dose of the BNT162b2 mRNA COVID-19 vaccine was offered. RESULTS: Seventeen adults were included. Eleven cases (64.7%) tested negative in the allergological workup and tolerated the re-administration of the second dose of the vaccine and considered non-allergic. Six cases (35.3%) were considered allergic and classified into three groups: 2 subjects displayed positive STs and/or BAT to PEG (Group A), two individuals displayed positive BAT to the vaccine (Group B), and in 2 patients with moderate or severe reactions, the culprit was not identified, tested negative to STs and BAT to both PEG and vaccine (Group C). We further evaluated the value of BAT when the results were positive to the vaccine and negative to PEG by performing BAT in controls groups, finding positive BAT results in 50% of controls, all of them recovered from COVID-19 infection. In contrast, BAT was negative in patients who had not suffered from COVID-19 disease. CONCLUSIONS: BAT can be used as a potential diagnostic tool for confirming allergy to PEG excipient but not to the vaccine as a positive result in BAT may indicate a past COVID-19 infection instead of an allergy.

Safety of an inactivated COVID-19 vaccine in patients with - wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Inactivated vaccines against coronavirus disease-2019 (COVID-19) offer an effective public health intervention to mitigate this devastating pandemic. However, little is known about their safety in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). METHODS: We recruited 72 WDEIA patients and 730 healthy matched controls who received an inactivated COVID-19 vaccine. Participants were monitored for 4 weeks after each immunization for adverse reactions and completed questionnaires regarding local and systemic reactions at 7 and 28 days after each vaccination. For those who had received the COVID-19 vaccine prior to enrollment, adverse event data were obtained retrospectively. RESULTS: Local and systemic adverse events occurred at similar rates in the WDEIA group and the control group. In both groups, injection-site pain and fatigue were the most common local and systemic reactions, respectively. Compared with healthy controls, more allergic events were reported in the WDEIA group (after dose 1, 0.5% vs. 4.2%, p=0.019; after dose 2, 0% vs. 1.4%, p=0.089). Allergic reactions mainly manifested as rash, urticaria, and edema, which were mild and controllable. No serious allergic events were reported. CONCLUSIONS: The adverse event profile of inactivated COVID-19 vaccine did not differ between WDEIA patients and healthy controls. The risk of allergic reactions in patients with WDEIA seems higher, but no anaphylaxis was reported, and the allergic reactions were controllable. Inactivated COVID-19 vaccines appear to be well-tolerated in WDEIA patients, but patients with potential allergy risks should be cautious.

Severity grading system for acute allergic reactions: A multidisciplinary Delphi study.

BACKGROUND: There is no widely adopted severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions, thus limiting the ability to optimize and standardize management practices and advance research. OBJECTIVE: The aim of this study was to develop a severity grading system for acute allergic reactions for use in clinical care and research. METHODS: From May to September 2020, we convened a 21-member multidisciplinary panel of allergy and emergency care experts; 9 members formed a writing group to critically appraise and assess the strengths and limitations of prior severity grading systems and develop the structure and content for an optimal severity grading system. The entire study panel then revised the grading system and sought consensus by utilizing Delphi methodology. RESULTS: The writing group recommended that an optimal grading system encompass the severity of acute allergic reactions on a continuum from mild allergic reactions to anaphylactic shock. Additionally, the severity grading system must be able to discriminate between clinically important differences in reaction severity to be relevant in research while also being intuitive and straightforward to apply in clinical care. Consensus was reached for all elements of the proposed severity grading system. CONCLUSION: We developed a consensus severity grading system for acute allergic reactions, including anaphylactic and nonanaphylactic reactions. Successful international validation, refinement, dissemination, and application of the grading system will improve communication among providers and patients about the severity of allergic reactions and will help advance future research.

Lactic acid suppresses MRGPRX2 mediated mast cell responses.

MAS related G-protein coupled receptor X2 (MRGPRX2) is a G-protein coupled receptor (GPCR) expressed in human mast cells that has been implicated to play an important role in causing pseudo-allergic reactions as well as exacerbating inflammation during asthma and other allergic diseases. Lactic acid, a byproduct of glucose metabolism, is abundantly present in inflamed tissues and has been shown to regulate functions of several immune cells. Because the endogenous ligands for MRGPRX2 (substance P and LL-37) are elevated during pathologic conditions, such as cancer and asthma, and given that lactic acid levels are also enhanced in these patients, we explored the role of lactic acid in regulating mast cells response via MRGPRX2 and MrgprB2, the mouse orthologue of the human receptor. We found that lactic acid suppressed both the early (Ca2+ mobilization and degranulation) and late (chemokine/cytokine release) phases of mast cell activation; this data was confirmed in LAD2, human skin and mouse peritoneal mast cells. In LAD2 cells, the reduction in degranulation and chemokine/cytokine production mediated by lactic acid was dependent on pH. In agreement with our in vitro studies, lactic acid also reduced passive systemic anaphylaxis to compound 48/80 (a known MRGPRX2/MrgprB2 ligand) and skin inflammation in a mouse model of rosacea that is dependent on MrgprB2 expression on skin mast cells. Our data thus suggest that lactic acid may serve to inhibit mast cell-mediated inflammation during asthma and reduce immune response during cancer by affecting mast cell activation through MRGPRX2.

ARIA-EAACI statement on severe allergic reactions to COVID-19 vaccines - An EAACI-ARIA Position Paper.

Further to the approval of the Coronavirus disease 2019 (COVID-19) vaccine BNT162b2, several severe anaphylaxis cases occured within the first few days of public vaccination. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and there are raising concerns that severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerge. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal, all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as this could have a significant impact on reaching the goal of population immunity. Healthcare practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognize and treat anaphylaxis properly with the ability to administer adrenaline. Further to vaccine administration, a mandatory observation period of at least 15 minutes should be followed for all individuals. The current data have not shown any higher risk for patients suffering from allergic rhinitis or asthma, and this message should be clearly stated by physicians to enable our patients to trust the vaccine. More than 30% of the population suffers from allergic diseases and the benefit of the vaccination clearly outweighs the risk of severe COVID-19 development.