Case reports of immune checkpoint inhibitor (ICI) overlap syndrome of myasthenia gravis, myositis and myocarditis, are increasing in the published literature. This is a potentially fatal adverse event of ICIs and emergency physicians need to be familiar with this triad when patients present to the emergency department (ED).

We performed a retrospective chart review of the electronic medical record between September 1, 2016 to March 9, 2020. We identified patients with the overlap syndrome who presented to our ED.

Seven patients were identified. Most were female and treated with a programmed cell death-1 inhibitor. Most patients presented with abnormal vital signs and the most common symptoms were ptosis, diplopia, dyspnea and fatigue. Most required supplemental oxygen and had a prolonged length of stay. All received steroids in addition to other immunomodulators. Two patients died.

Presence of one of the diagnosis should lead to evaluation for the others. Suspicion should be raised by patients presenting with ptosis, muscular weakness, fatigue and dyspnea. Early recognition of this triad can allow for early administration of high-dose glucocorticoids (1–2 mg/kg of prednisone or equivalent), which is the mainstay of treatment. However, it is likely that patients will need further immunomodulators and therefore, will need hospitalization.

Emergency physicians should be aware of this potentially lethal triad in cancer patients receiving ICIs. The life-saving interventions in the ED include recognizing the triad, airway support, administration of high-dose glucocorticoids, and early involvement of a multidisciplinary team.