Artificial intelligence-enabled penicillin allergy delabelling: an implementation study.

Inaccurate penicillin allergy labels may be delabelled following evaluation. The intervention in this study was an email-based notification system regarding the appropriateness for penicillin allergy evaluation, with a view to delabelling, as identified by a deep learning artificial intelligence algorithm. Of the intervention group (n = 59), three (5.1%) individuals had their penicillin allergies delabelled, which was significantly more than the control group (0%, P = 0.002). Further research to optimise such approaches is required.

The role of major and minor determinants in penicillin allergy testing: Time to revisit an old friend?

Background: Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated in vivo after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic. Objective: We aimed to evaluate the performance and utility of PPL and MDM in penicillin allergy testing. Methods: A retrospective audit over a 5-year period was undertaken for those with penicillin testing in a tertiary immunology unit. Results: In all, 214 patients were identified. Of those patients, 151 (70.6%) were female and the average age was 58 years. Unspecified penicillin was the most common index drug (n = 127 [59.3%]), followed by amoxicillin (n =3 [24.8%]) and amoxicillin-clavulanic acid (n = 21 [9.7%]). The result of skin testing was positive in 23 patients (10.7%); skin prick testing was positive in 10 patients (4.7%), and intradermal testing (IDT) was positive in 13 patients (6.1%), the majority of whom had identified amoxicillin or amoxicillin-clavulanic acid as the index drug (n = 22 [95.7%]). The result of testing to PPL and/or MDM was positive with IDT only (n=5 [23.8%]). PPL and MDM positivity coexisted with a positive reaction to amoxicillin IDT in 2 patients, 1 of whom passed an amoxicillin challenge. Additionally, 2 positive tests to PPL were present with a negative result for MDM; of these 2 positive results, 1 was positive to amoxicillin IDT. In only 1 case were the results of testing for MDM and PPL both positive, with negative results to all native ß-lactams tested; the patient tolerated an amoxicillin challenge. Overall, the negative predictive value for both skin prick testing and IDT was 89.5%. Conclusion: Benzyl penicillin and amoxicillin alone may be sufficient for in vivo testing in suspected individuals with penicillin allergy.

Myopericarditis following both BNT162b2 and NVX-CoV2373.

BACKGROUND: Myopericarditis is a well reported complication associated with SARS-Cov-2 (COVID-19) infection and vaccinations; particularly with mRNA vaccines (BNT162b2 and mRNA-1273), and in the young male population. The risk-to-benefit ratio in sequential vaccination dosing in young males is further clouded in the era of the omicron variant with its reported enhanced immune escape. STUDY DESIGN: A case series of two cases of post vaccination myopericarditis following the NVX-CoV2373 after also developing myopericarditis with BNT162b2. CONCLUSION: To our knowledge, we are the first to describe post vaccination myopericarditis following NVX-CoV2373 after also developing myopericarditis with BNT162b2. The similarities in presentation between the reactions of both platforms would suggest a similar pathogenesis, although the exact mechanism remains unknown. Further studies are necessary to identify these mechanisms, as well as to identify biomarkers that may identify vulnerable populations. On-going vigilance is necessary to identify those who may be at an increased risk of post-COVID vaccine myopericarditis.

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

AstraZeneca ChAdOx1-S COVID-19 vaccine can be safely administered in patients with EDTA allergy.

BACKGROUND: Immediate hypersensitivity reactions to COVID-19 vaccines have been postulated to be linked to their excipients, such as polyethylene glycol (PEG) in Pfizer Comirnaty, or polysorbate 80 and ethylenediaminetetracetic acid (EDTA) in AstraZeneca ChAdOx1-S [recombinant] (Vaxzevria). These excipients are found in a range of other products, including injectable and oral medications as well as intravenous radiocontrast media (RCM) and various cosmetic products. Patients with proven excipient allergy may be advised to avoid a COVID-19 vaccine containing that excipient and/or potentially cross-reactive excipients. This may result in individual patients not receiving vaccines, especially if an alternate option is not available, and on a broader level contribute to vaccine hesitancy. We present two cases of previously confirmed EDTA anaphylaxis with positive intradermal testing, who had negative Vaxzevria vaccine in-vivo testing and subsequently tolerated the vaccine. CASE 1: A patient with history of anaphylaxis to RCM and local anaesthetics (LA) had positive intradermal test (IDT) to EDTA nine years earlier. Skin testing to Vaxzeria vaccine (up to 1:10 IDT), Comirnaty vaccine (up to 1:10 IDT) and EDTA 0.3 mg/mL IDT were negative. However, following EDTA 3 mg/ml IDT, he developed immediate generalised urticaria without anaphylaxis. Basophil activation testing was negative to disodium EDTA, Vaxzevria and Cominarty vaccines. Given the negative in-vitro and in-vivo testing to Vaxzevria vaccine, he proceeded to Vaxzevria immunisation and tolerated both doses. CASE 2: A patient with history of anaphylaxis to RCM had positive skin testing to EDTA and RCM containing EDTA six years earlier. Following referral to COVID19 vaccine clinic, Vaxzevria vaccine (1:10 IDT) and Cominarty vaccine (1:10 IDT) were negative whilst EDTA was positive at 0.3 mg/mL IDT. He subsequently tolerated both Vaxzevria vaccinations. CONCLUSION: Excipient allergy does not necessarily preclude a patient from receiving a vaccine containing that excipient. Allergy testing can help identify excipient-allergic patients who may still tolerate vaccination, which is important in situations where COVID-19 vaccination options are limited.

Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in patients with PEG allergy.

BACKGROUND: The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause. OBJECTIVE: Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy. METHODS: Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.

Rituximab hypersensitivity reactions and tolerance of ofatumumab therapy.

B-cell depleting agents play a key role in a variety of disease entities. Rituximab, a murine-human chimeric anti-CD20 monoclonal antibody, as one of these major agents, has been associated with hypersensitivity reactions, which not only include the classic hypersensitivity ranging from immediate (type 1) to delayed (type IV), but also infusion-related reactions (IRRs). Whilst these typical hypersensitivity reactions occur in the setting of prior exposure, IRRs may occur in first exposure. Factors to consider include chimeric composition of agent, for example, rituximab with murine component, which may be responsible for such hypersensitivity reactions. In these individuals, alternate anti-CD20, such as oftatumumab, a fully human monoclonal antibody may be used. We report three cases of rituximab hypersensitivity in patients with auto-immune disease, and in whom ofatumumab therapy was given and subsequently tolerated.