Reactivation of the scar resulting from intracutaneous injection of Bacillus Calmette-Guérin (BCG) is a common specific reaction in Kawasaki’s Disease. It has also sporadically been associated with viral infections, Multisystem Inflammatory Syndrome in Children, influenza vaccination and mRNA COVID-19 vaccination. Since the start of the COVID-19 vaccination campaign in January 2021, the Netherlands Pharmacovigilance Centre Lareb has received 22 case reports of BCG reactivation after vaccination with a COVID-19 vaccine. In 20 case reports it concerned mRNA COVID-19 vaccines Moderna (14) and Pfizer (6). In 2 case reports the viral vector COVID-19 vaccine AstraZeneca was administered. Erythema and pain were the most frequently reported symptoms and the size of the inflammation was between 1.5 to 5 cm. BCG reactivation occurred with a median time to onset of 2 days after the second or booster COVID-19 vaccination, whereas the median time to onset was 7 days after the first COVID-19 vaccination. None of the BCG reactivations were treated. The exact mechanism of the occurrence of this specific reaction remains unknown, however involvement of heat shock protein 65 is suggested. BCG reactivation is a non-serious, self-limiting reaction that can occur after vaccination with both mRNA and viral vector COVID-19 vaccines.

Aim To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitors (non-TNFis) compared to certolizumab pegol (CZP) Material and methods A retrospective comparative study was conducted in the EudraVigilance (EV) database. EV is a pharmacovigilance database, which can be used for detecting safety signals and generating hypotheses on possible relations between drugs and adverse events. A supposedly safe biologic (CZP) was considered as the reference group. Pregnancy-reports of non-TNFis and CZP were extracted. Odds ratios (ORs) for CMs were calculated for each non-TNFi, versus CZP (quantitative assessment). Then, CM patterns were compared to CZP in consultation with a clinical geneticist (qualitative assessment). Results ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Although qualitative analyses did not show any specific patterns for belimumab but three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus null in CZP and other investigated non-TNFis). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out. Conclusion No special safety signal was identified regarding the occurrence of CMs after exposure to non-TNFis, except for vedolizumab. Based on available information, no firm conclusions can be made regarding observed CCAs in the vedolizumab group (it warrants further research)