Le diabète fulminant, un effet secondaire grave des anticorps anti-PD1 : à propos de quatre cas survenus en cours de traitement pour mélanome

Fulminant diabetes (FD) is a subtype of type 1 diabetes (T1D), previously reported in Japan in the early 2000s, revealed by a severe ketoacidosis with fatal outcome if untreated, due to a rapid and irreversible destruction of islet ß-cell pancreas. This type of diabetes is characterized by negative specific T1D antibody, negative C- peptide, and mildly elevated HbA1c. The emergence of cases of FD in patients on anti-PD1 (programmed cell death-1) immunotherapy and anti-CTLA4 (Cytotoxic T-Lymphocyte-Associated Protein-4) appears to mediate the PD-1 and CTLA-4 protein cellular immunity central role. However, among the reported cases, despite similar clinical presentation to Japanese patients, some had positive antibody (anti-GAD, anti-IA2), as autoimmune T1D. In patients with a presentation of T1D and positive antibodies, HLA predisposition groups are not found (HLA-DR3, -DR4). The prevalence of these forms of diabetes, based on a review of the literature, is quite low (1-3%), but must be known by practitioners because of the increase of prescription of these immunotherapeutic molecules. Clarifying the mechanisms of these diabetes, and identify people at highest risk, represent two issues of the future.