Relationship Between Clozapine-Induced Inflammation and Eosinophilia: A Retrospective Cohort Study

Eosinophilia has not been highlighted in clozapine-induced adverse inflammatory events, as it is often asymptomatic and self-limiting, while drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome occurs rarely. This study aimed to reveal the temporal relationships between eosinophilia and other inflammatory events during clozapine initiation.

The temporal relationships between eosinophilia and other inflammatory events were evaluated among 241 patients with schizophrenia treated with clozapine for the first time at 7 hospitals. Risk factors for eosinophilia were investigated among preceding inflammatory events and other clinical characteristics. Furthermore, patients with eosinophilia were stratified by the severity of adverse inflammatory events and their clinical characteristics were compared.

Of the 54 patients who experienced inflammatory adverse events, 27 (50%) developed eosinophilia. In all but 1 patient, clinical symptoms of inflammatory adverse events preceded eosinophilia. In contrast, of the 187 patients without inflammatory events, 21 (11%) developed eosinophilia. Multivariate analysis revealed that more severe preceding inflammatory adverse events were associated with a greater risk of eosinophilia. The median time to the first detection of eosinophilia and peak eosinophil count occurred significantly earlier in patients with severe adverse events than in asymptomatic patients.

In most cases, eosinophilia developed after the onset of inflammatory symptoms. Preceding inflammation was associated with the development of clozapine-induced eosinophilia. Eosinophilia may not be suitable as an early detection marker of severe inflammatory adverse effects. These findings enhanced our understanding of the involvement of eosinophilia in clozapine-induced inflammatory events.