The limited role for excipient skin testing after COVID-19 vaccine reactions

Published: June 21, 2021

The impact of the Coronavirus Disease-2019 (COVID-19) pandemic has been far-reaching, and vaccines represent our most important tool for protection. The two COVID-19 mRNA vaccines by Pfizer and Moderna have been associated with more allergic reactions than the Janssen vaccine, but the rate of anaphylaxis remains very low; as of November 2021, the Centers for Disease Control and Prevention reports 2-5 people per million vaccinated experience anaphylaxis. Additionally, up to 2% of individuals report allergic symptoms after vaccination. Patients and physicians alike require guidance for management of allergic symptoms after vaccination. The Pfizer and Moderna COVID-19 mRNA vaccines both contain the excipient polyethylene glycol (PEG), and the Janssen vaccine contains polysorbate-80. Both of these excipients are present in other medications and are rare causes of allergic reactions including anaphylaxis with skin testing protocols which were previously published.1

In the study by Wolfson et al. published in The Journal of Allergy and Clinical Immunology: In Practice, 80 consecutive patients were referred to the allergy clinic between January and March 2021 after first dose mRNA COVID-19 vaccine allergic reactions. In-person skin-testing visits occurred after initial allergy/immunology telemedicine visits with clinical discussion and risk stratification. All patients with objective symptoms of allergy or anaphylaxis within 4 hours of vaccination were recommended to undergo excipient skin testing; for patients with subjective symptoms within 4 hours or delayed symptoms, shared decision-making was used prior to proceeding to skin testing. Skin tests at Massachusetts General Hospital were done to PEG (using Miralax and methylprednisolone acetate) for all patients, and to polysorbate-80 (using triamcinolone acetonide) in the case of a positive PEG skin test result. At Brigham and Women’s Hospital, all patients underwent skin testing to PEG (using Miralax and methylprednisolone acetate) and polysorbate-80 (using Refresh Tears). Subsequently, concern arose that Refresh Tears caused irritant reactions further confirmed after skin tests were performed on 25 controls. At the time, there was no access to the COVID-19 vaccines themselves for skin testing. All patients received their COVID-19 vaccines within one medical system, and electronic surveys were used to report symptoms for 3 days following vaccination. If individuals did not complete all 3 days or if allergic symptoms were reported, patients were contacted for clarification regarding their symptoms.

Of the 80 patients who underwent excipient skin testing, 70 (88%) received a second dose of the same mRNA COVID-19 vaccine and 52 (74%) tolerated the second dose vaccine without a reaction, irrespective of skin test results. Among the 8 (12%) patients who reported a history of an immediate allergic reaction and a positive skin test: 4 (67%) tolerated the vaccine; 2 (33%) had mild allergic reactions; 2 (25%) after shared decision-making, opted to not receive the second mRNA COVID-19 vaccine dose (1 patient opted to instead receive the Janssen vaccine). There were 13 (25%) patients who were skin test negative but reacted to the second dose of the vaccine, most had mild reactions, but 4 (31%) patients were seen in the Emergency Department and 2 (15%) received epinephrine. Polysorbate-80 skin testing using Refresh Tears caused irritant reactions and Refresh Tears should not be used for this purpose. Overall, excipient skin testing did not add value to the clinical risk assessment in those reporting first dose mRNA COVID-19 vaccine reactions and should only be considered in specific cases, e.g. patients with convincing history of anaphylaxis to mRNA COVID-19 vaccine or recently to oral PEG-containing medications.  The clinical history remains the most important aspect in the allergist evaluation; using shared decision-making, most individuals with reactions to the first dose of an mRNA COVID-19 vaccine can proceed safely with second dose.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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