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A Case in Which HLA-DR4 is Involved in the Development of Complex Immune-Related Endocrinological Adverse Events
Yonekazu Kidawara1, Manabu Kadoya1, Miki Kakutani-Hatayama1
1Department of Diabetes, Endocrinology and Clinical Immunology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo, Japan.
Immune checkpoint inhibitors (ICIs) have become a focal point in cancer immunotherapy, though their utilization is also linked to the occurrence of diverse immune-related adverse events (irAEs). Herein, we present details of a 42-year-old woman diagnosed with a malignant vaginal melanoma who underwent ICI therapy with the combination of nivolumab and ipilimumab. Approximately two months after initiating therapy, the patient manifested destructive thyroiditis and fulminant type 1 diabetes mellitus, thus necessitating intensive insulin therapy. Following the onset of adrenocorticotropic hormone deficiency, frequent hypoglycemic episodes prompted the initiation of replacement therapy with hydrocortisone. Human leukocyte antigen (HLA)-DNA typing revealed the presence of HLA-DRB104 : 05 and DQB104 : 01. HLA-DR4 has been suggested to be associated with the development of multiple endocrine irAEs. This is the first reported case of three endocrine irAEs occurring within a short period, in which the presence of HLA-DR4 may have contributed to the pathogenesis.
Immune checkpoint inhibitors (ICIs) have become a focal point in cancer immunotherapy, though their utilization is also linked to the occurrence of diverse immune-related adverse events (irAEs). Herein, we present details of a 42-year-old woman diagnosed with a malignant vaginal melanoma who underwent ICI therapy with the combination of nivolumab and ipilimumab. Approximately two months after initiating therapy, the patient manifested destructive thyroiditis and fulminant type 1 diabetes mellitus, thus necessitating intensive insulin therapy. Following the onset of adrenocorticotropic hormone deficiency, frequent hypoglycemic episodes prompted the initiation of replacement therapy with hydrocortisone. Human leukocyte antigen (HLA)-DNA typing revealed the presence of HLA-DRB104 : 05 and DQB104 : 01. HLA-DR4 has been suggested to be associated with the development of multiple endocrine irAEs. This is the first reported case of three endocrine irAEs occurring within a short period, in which the presence of HLA-DR4 may have contributed to the pathogenesis.
