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

Vaccination seems the most effective public health tools to contrast the spreading of Coronavirus disease- 19 (COVID- 19) pandemic. Mucous- cutaneous adverse reactions have been rarely observed. Among hypersensitivity reactions, immediate reactions (anaphylaxis, urticaria- angioedema syndrome) were more frequently observed than delayed reactions. In this study 5574 healthcare professional received the first dose of Pfizer- BioNTech vaccine. Six subjects (0.11%) without previous drug hypersensitivity or polyethylene glycol reactions developed mucous- cutaneous adverse reactions. These patients underwent an allergologic workup with Pfizer- BioNTech vaccine as suggested by EAACI and German allergy centres. 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. It is impossible to draw conclusions about the utility of immediate readings of SPT and IDT to investigate anaphylaxis to Pfizer- BioNTech vaccine, but for purely cutaneous reactions, they have not shown positive results in six patients and IDT has a high risk of positive delayed reactions due to cellular immune protection.