A rare long-term side effect of COVID-19 vaccines: Symmetrical drug-related intertriginous and flexural exanthema-like reaction SDRIFE and potential immunogens for delayed type hypersensitivity reactions

Background: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is an important clinical entity that is rare and may develop with a Type IV delayed type hypersensitivity immune response to drug antigens. The incidence and characteristics of SDRIFE attributed to COronaVIrus Disease of 2019 (COVID-19) vaccines remain unclear, this issue requires further elucidation.

Objective: We aim to investigate the vaccine-related-SDRIFE and potential immunogens of COVID-19 vaccines through a literature review accompanied by a real case.

Methods: A new vaccine related-SDRIFE case report and a literature review regarding COVID Vaccine related SDRIFE. In the years following the COVID vaccinations, all SDRIFE cases published between 2000 and 2024 were retrieved.

Results: The new case of vaccine-related SDRIFE developed following the COVID-19 Pfizer-BioNTech vaccine and was tolerated without any issues with the CoronaVac vaccine (Sinovac Biotech.,China) after negative skin tests. A literature search has revealed fifteen different types of SDRIFE cases related to COVID-19 vaccines since 2020. Diagnostic skin testing with vaccine or any potentially immunogen parts of vaccine were performed in six patients. All tests were negative except for one late intradermal test positivity.

Conclusion: This mini review showed that SDRIFE due to COVID vaccines is a rare, but a significant adverse event that has a potential to impair patient compliance with subsequent vaccines. Identification and avoidance of potential allergens through standardized skin tests and diagnostic immunological work-up will contribute to vaccine compliance and better management of hypersensitivity reactions.