Case report: A case of fulminant type 1 diabetes mellitus after COVID-19 vaccination during treatment of advanced gastric cancer: pitfall in managing immune-related adverse events

Abstract

The occurrence of fulminant type 1 diabetes mellitus as an adverse event during cancer immunotherapy has been previously reported. However, little is known about the causal relationship between the coronavirus disease 2019 (COVID-19) vaccination and fulminant type 1 diabetes mellitus. A 60-year-old man with advanced gastric cancer, receiving S-1 + oxaliplatin and nivolumab therapy, followed by nab-paclitaxel + ramucirumab as a second-line treatment, with steroid supplementation for complications of hypopituitarism-induced hypoadrenocorticism, was administered a COVID-19 vaccine after three cycles of nab-paclitaxel + ramucirumab. Two days later, he developed severe malaise and anorexia, which required emergency admission to our hospital for suspected adrenal insufficiency. Despite increasing steroids, his general condition changed suddenly after 12 hours leading to his death. Histopathological analysis of autopsy samples revealed loss of the islets of Langerhans, indicating fulminant type 1 diabetes mellitus. We failed to recognize the onset of fulminant type 1 diabetes mellitus because its symptoms were similar to those of adrenal insufficiency. The number of reports on the onset of fulminant type 1 diabetes mellitus after COVID-19 vaccination has been increasing, and in this case, the onset occurred on the second day after COVID-19 vaccination, suggesting an association between vaccination and fulminant type 1 diabetes mellitus. Clinicians should be aware of the risk of fulminant type 1 diabetes mellitus, although rare, after COVID-19 vaccination.

Keywords: Autopsy; COVID-19 vaccination; Fulminant type 1 diabetes mellitus; gastric cancer; immune-related adverse event; nivolumab.

Figure 1

Clinical course of the patient. ACTH, adrenocorticotropic hormone; SOX, S-1 + oxaliplatin; CAPOX, capecitabine + oxaliplatin; HbA1c, hemoglobin A1c; AE, adverse event; irAE, immune-related AE.

Figure 2

Pathological findings at autopsy. (A) Anterior pituitary gland. Histopathological findings showing focal lymphocytic infiltration comprising CD3⁺ T cells, suggesting cellular damage to the anterior pituitary gland. The number of infiltrating cells was 1, 0 and 1 per three high power fields (HPFs) for CD4⁺ T-cells and 62, 44, and 57 three HPFs for CD8⁺ T-cells. In addition, the negative periodic acid-Schiff (PAS) staining and negative T-Pit expression suggested that the number of ACTH-producing cells was reduced. (B) Pancreas. The pancreas showing marked interstitial fibrosis and moderate CD3⁺ T-cell infiltration (CD4<CD8), suggesting cellular damage to the pancreas. The number of infiltrating cells was 28, 14, and 13 per three HPFs for CD4⁺ T-cells and 107, 52 and 71 per three HPFs for CD8⁺ T-cells. Moreover, there were no synaptophysin- and insulin-positive cells, and the islets of Langerhans were completely absent. ACTH, adrenocorticotropic hormone; HE, hematoxylin and eosin staining.