Diabetic Ketoacidosis as a Delayed Immune-Related Event after Discontinuation of Nivolumab.

BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody with immune checkpoint inhibitory activity, represents a novel treatment for several cancers. Immune checkpoint inhibitors cause side effects, known as immune-related adverse events (irAEs) or delayed immune-related events (DIRE), after immunotherapy discontinuation. Type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis have been reported to develop as an irAE during the treatment with nivolumab. Here, we report on a patient who developed T1DM and diabetic ketoacidosis after discontinuation of treatment with nivolumab as a DIRE. CASE REPORT: A 59-year-old man, who received nivolumab for an alpha fetoprotein-producing gastric cancer, presented with acute fatigue 4 months after discontinuation of nivolumab. Throughout therapy with nivolumab, the patient's hemoglobin A1c (HbA1c) level was ≤ 6%. However, 1 month prior to the patient's emergency department visit, he noticed weight loss, and 3 weeks prior to that, his HbA1c was 7.1%. Urinalysis showed ketone bodies, and arterial blood gas analysis suggested metabolic acidosis with hyperglycemia (690 mg/dL), which established the diagnosis of diabetic ketoacidosis. An endogenous insulin deficiency without verifiable anti-islet autoantibodies was confirmed; the patient had a human leukocyte antigen haplotype that does not increase the risk of acute-onset T1DM. We considered that T1DM in this patient developed possibly due to nivolumab. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the need for clinicians to be vigilant of the fact that a history of anti-PD-1 monoclonal antibody therapy may increase the risk of diabetic ketoacidosis, whether treatment is ongoing or discontinued.

Urinary Retention as the Presenting Clinical Manifestation of Unstable Thoracic Spinal Fracture with Diffuse Idiopathic Skeletal Hyperostosis.

Patients with diffuse idiopathic skeletal hyperostosis (DISH) are at high risk for unstable vertebral fracture, which can be frequently missed. An 80-year-old man with pre-existing muscle lower limb weakness due to frailty was referred from another hospital, presenting with progressive urinary retention and its related symptoms, which had been treated as a urinary tract infection at previous hospital. One week prior to our visit, he had fallen. On arrival, he appeared lethargic and unable to follow commands. He denied any back pain. Computed tomography identified a T10 fracture and dislocation associated with DISH. Although immediate surgical fixation was performed, the patient did not recover from the neurological deficits. Diagnostic delay of DISH-associated vertebral fracture can occur due to both patients' and clinicians' delayed action. We believe this case report can help clinicians recognize this potentially devastating condition.