Skin tests in urticaria/angioedema and flushing to Pfizer‐BioNTech SARS‐CoV‐2 vaccine: Limits of intradermal testing

To the Editor, Vaccination seems the most effective public health tools to contrast the spreading of Coronavirus disease19 (COVID19) pandemic. To date, the European Medicines Agency (EMA) authorized three antiSARSCoV2 vaccines. The PfizerBioNTech and the Moderna vaccines contain messenger RNA (mRNA) encapsulated in lipid nanoparticles, which encodes the SARSCoV2 viral spike (S) protein, inducing both antibody and cellmediated responses. The AstraZeneca vaccine is based on a viral vector that uses a modified version of the chimpanzee adenovirus to provide instructions for synthesizing SARSCoV2 protein S. The vaccine series consists of two doses administered intramuscularly (PfizerBioNTech: 21 days apart; Moderna: 28 days apart; AstraZeneca: 28– 84 days apart). During clinical approval studies and early postmarketing phases, mucouscutaneous adverse reactions have been rarely observed. Among hypersensitivity reactions, immediate reactions (anaphylaxis, urticariaangioedema syndrome) were more frequently observed than delayed reactions (maculopapular eruptions).1,2 The antiSARSCoV2 vaccines contain excipients with known sensitizing potential: PfizerBioNTech vaccine contains polyethylene glycol2000, Moderna vaccine polyethylene glycol2000 and tromethamine and AstraZeneca vaccine polysorbate 80.3 Considering this, before receiving antiSARSCoV2 vaccination, an adequate medical history is mandatory to detect possible risk factors and, consequently, to minimize the incidence of adverse reactions. Furthermore, it is recommended to administer the vaccine by trained healthcare personnel in adequate medical settings in presence of emergency drugs and an observation period.3,4 In General Hospital of Perugia and in Local Health Unit 1, Umbria Region, Italy, 5574 healthcare professional received the first dose of PfizerBioNTech vaccine. Six subjects (0.11%) without previous drug hypersensitivity or polyethylene glycol reactions developed mucouscutaneous adverse reactions, summarized in Table 1. These patients underwent an allergologic workup with PfizerBioNTech vaccine as suggested by EAACI4 and German allergy centres.5 In absence of standardized methodology for this vaccine testing, we referred to Italian6 and EAACI recommendations.7 Unusable vaccine residues, regain from the vaccine campaign, were used under sterile conditions within 6 hours from reconstitution and according to the storage conditions. Skin prick test (SPT) with neat vaccine (reading: 20 min) and intradermal test (IDT) vaccine dilution 1/100 (readings: 20 min, 24 h) were performed. SPT resulted always negative, but IDT induced, 12 hours after, an erythematosus, oedematous and infiltrated asymptomatic reaction in all patients. A 1/1000 dilution test induced the same reaction in all patients (Figure 1A). We followed the patients daily until resolution, and the IDT reactions persisted for 2 days. All patients then received the second dose of vaccine without relapses. In order to verify these reactions, IDT with 1/1000 and 1/100 PfizerBioNTech vaccine dilution was performed in six healthcare