Case Presentation: A 49-year-old female with a past medical history of metastatic melanoma to the brain treated with resection, radiation, and chemotherapy with nivolumab, ipilumab, and dabranefib presented to the emergency department with vomiting, fatigue and lethargy of a few days’ duration. She also had dysuria, abdominal pain, and staring spells prior to presentation. She was febrile and tachycardic, prompting admission for presumed sepsis due to acute cystitis. Her chemotherapy was held upon admission due to sepsis. Two nights later, a stroke code was called for confusion and speech changes. Computed tomography (CT) of her head showed stable hemorrhagic brain metastases with magnetic resonance imaging of the brain confirming these findings. The patient developed lethargy and waxing and waning orientation, as well as headache, neck pain, and an erythematous, macular rash on her arms and legs bilaterally. She was started on meningitis treatment with ceftriaxone, ampicillin, vancomycin, and acyclovir. She also developed hemodynamic instability requiring pressors. Labs revealed leukopenia. CT of the abdomen and pelvis did not reveal any acute process. Her electroencephalogram was without seizures. Further workup was pursued with a lumbar puncture showing eleven white blood cells with a lymphocytic predominance, as well as elevated glucose and protein. Her cerebrospinal fluid, blood, and urine cultures were negative, as was her meningitis and encephalitis panel. Enteric pathogen and C. difficile testing was negative. Given no evidence of a potential infectious etiology, she was started on methylprednisolone for concern of immunotherapy side effects. Her symptoms, fever, hemodynamic instability, and leukopenia resolved with steroid treatment. She was ultimately diagnosed with immune checkpoint inhibitor encephalitis due to the subacute onset of mental status changes, cerebrospinal fluid pleocytosis, and the exclusion of alternate causes. Following discharge, she continued on the steroid taper without relapse of her prior symptoms.
Discussion: Immune checkpoint inhibitors come with a variety of side effects, many of which can mimic infection. These include cytokine release syndrome, causing hypotension and an uncontrolled systemic inflammatory response syndrome, as well as rash, colitis, and pneumonitis. Immune checkpoint inhibitor encephalitis is diagnosed when patients have symptoms of encephalitis such as mental status changes, evidence of central nervous system inflammation, and no other likely cause. The prognosis is highly variable, ranging from completely resolving to lethal. Interestingly, fever and inflammatory changes in the cerebrospinal fluid are associated with a favorable prognosis. Steroids are used to treat this process.
Conclusions: Immune checkpoint inhibitors can cause many infection mimics, including non-infectious meningoencephalitis. Although in this patient’s case, the condition fully resolved, given the potentially lethal nature of the disease, prompt diagnosis and treatment is imperative.
