Coronavirus 2 is an infectious agent primarily identified as the cause of a pandemic viral pneumonia. With the mass vaccination against this virus, one of the health issues is the safety of currently available vaccines considering their adverse reactions. This systematic review was conducted to assess and summarize all reported data on histopathologic findings associated with mucocutaneous reactions that developed after COVID-19 vaccination for a better pathophysiology interpretation and clinical management of these reactions. A systematic search was performed in PubMed, Web of Science, and Scopus databases as well as Google Scholar engine for relevant English articles published till July 1, 2022. This review includes 131 studies with a total number of 287 cases. Eruptions that underwent a biopsy were mostly described as erythematous maculopapular, papulosquamous, vasculitis-like, lichenoid, or urticarial lesions. Histopathology revealed spongiosis, interstitial, and perivascular lymphohistiocytic infiltration, erythrocyte extravasation, parakeratosis, endothelial inflammation, and the like. Findings were highly consistent with morbilliform erythema, psoriasiform dermatosis, leukocytoclastic vasculitis, and lichenoid or urticarial drug reactions. The majority of these reactions had a mild nature and were primarily observed in patients with underlying health conditions. Microscopic evaluation was also consistent with transient inflammatory changes, and features like neutrophilic infiltrates, subcorneal pustules, and vasculopathy were less frequently reported than what seen in COVID infection. Therefore, dermatologic reactions developing after vaccination in the general population should not hinder a complete vaccination.
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