Coronavirus disease 2019 messenger RNA vaccine skin tests and serum histamine levels in allergic reactions.

We thank de Chaisemartin et al for their correspondence in regard to our manuscript, “Coronavirus disease 2019 vaccine hypersensitivity evaluated with vaccine and excipient allergy skin testing.” De Chaisemartin et al elucidate their findings of transient elevation of serum histamine levels in 1 of 5 patients with anaphylaxis after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine. Conversely, 4 of 5 patients had normal serum histamine and tryptase levels within 2 hours of anaphylaxis.

De Chaisemartin et al reflect that their findings of transient or lack of elevated serum histamine levels after COVID-19 mRNA anaphylaxis parallel with our findings of negative excipient skin test results (polyethylene glycol [PEG], polysorbate 20 and 80) and limited positive intradermal skin test results with the vaccine. Our 4 of 39 patients with positive intradermal skin testing results to the vaccine tolerated their ensuing dose of COVID-19 mRNA vaccine. The common thread in our findings and those of de Chaisemartin et al is the suggestion that antihistamine premedication may prevent some allergic reactions. Most patients will tolerate subsequent vaccination with the mRNA COVID-19 vaccine with or without premedication.1, 2, 3, 4, 5, 6, 7 In the report of de Chaisemartin et al, 3 of 5 patients tolerated their consequent COVID-19 mRNA vaccine. Furthermore, 1 patient already received their second dose to which anaphylaxis had occurred. In addition, 1 patient passed away from unrelated cause before the receipt of vaccine dose 2. In our case series, 95% (n = 37) tolerated their succeeding COVID-19 vaccine without serious allergic reaction. Moreover, 92% (n = 36) received 2 doses of their COVID-19 vaccines. Of the patients who tolerated their subsequent mRNA vaccines, 62% received premedication, which could include H1 and H2 antihistamines and leukotriene inhibitors.

A potential explanation of transiently elevated serum histamine levels in the patient described by de Chaisemartin et al could be basophil activation. Warren et al revealed that 11 patients with anaphylactic reactions to the COVID-19 mRNA vaccine had negative skin test results to the vaccine and excipients. Nevertheless, most had positive basophil activation test results to PEG. All had positive basophil activation test results to the mRNA vaccine. Notably, PEG immunoglobulin G was found despite undetectable PEG immunoglobulin E in the tested patients with allergic reactions.

In summary, de Chaisemartin et al raise an interesting point on possible transient elevation of serum histamine levels. Further research is necessary to characterize skin tests with the specific vaccines and biomarkers such as serum histamine levels to evaluate which endotypes of post–COVID-19 mRNA vaccine allergic reactions may benefit from premedication or desensitization to COVID-19 mRNA vaccines.