Dramatic deterioration or new‐onset dipeptidyl peptidase‐4 inhibitor‐associated bullous pemphigoid after COVID‐19 vaccination: A possible manifestation of immune reconstitution inflammatory syndrome

Abstract

BackgroundMany reports have described the development of bullous pemphigoid (BP) following COVID‐19 vaccination. In dipeptidyl peptidase‐4 inhibitor‐associated BP (DPP‐4i‐BP), cessation of DPP‐4i appears to have a paradoxical effect on the clinical course of the BP. Interestingly, similar paradoxical reactions have been shown to develop after antibody‐based therapies that inhibit pro‐inflammatory cytokine signalling. These heterogenous outcomes could be explained by assuming that DPP‐4i‐BP is a manifestation of immune reconstitution inflammatory syndrome (IRIS). Onset of IRIS could be triggered by a variety of stimuli, including initiation of immune checkpoint blockade and vaccination.ObjectivesTo examine whether the onset of postvaccine BP, although rarely reported, is preferentially observed in DPP‐4i‐BP and whether severe outcomes of IRIS can be predicted by specific cytokine profiles.MethodsThis single‐centre retrospective study was based on the medical records of 63 consecutive outpatients with BP.ResultsExacerbation or new onset BP following COVID‐19 vaccination was observed in 6 of 11 patients with BP who were receiving DPP‐4i. One patient who developed dramatic exacerbation of DPP‐4i‐BP and cytomegalovirus (CMV) disease following COVID‐19 vaccination showed high concentrations of granulocyte‐colony‐stimulating factor and interleukin‐10 after vaccination, both of which have been associated with CMV‐IRIS in other settings.ConclusionsCOVID‐19 vaccine‐induced BP was more frequently associated with DPP‐4i‐BP than with ‘classic’ BP. COVID‐19 vaccination may trigger the shift to infectious IRIS. When infectious IRIS is suspected from the cytokine profile after COVID‐19 vaccination, thorough clinical evaluation for reactivation of CMV should be performed immediately with prompt initiation of anti‐CMV medication if necessary.