Neuromyelitis optica spectrum disorder (NMOSD), previously neuromyelitis optica, is an autoimmune, inflammatory CNS syndrome that can present in a variety of manifestations. It is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG); however, its presence is not required for the diagnosis. In this report, a rare case of NMOSD is presented in a patient with systemic lupus erythematosus (SLE). The patient is a 21-year-old female with SLE who presented with intractable nausea, vomiting and hiccups. She underwent a thorough gastrointestinal workup that was non-revealing. A CNS workup was initiated ultimately revealing the diagnosis of NMOSD. Her symptoms resolved after initiating high-dose intravenous steroids and she was subsequently started on rituximab. In patients presenting with area postrema syndrome, in the setting of an established autoimmune disorder, clinicians should have a high clinical suspicion of NMOSD. An MRI of the brain and checking for serum AQP-4 IgG are important in making the diagnosis.