The area postrema, located on the floor of the fourth ventricle, regulates vomiting, fluid balance, osmoregulation, and immunomodulation. First documented in 1896, it has been a subject of scientific interest ever since. Area postrema syndrome (APS) is characterised by intractable nausea, vomiting, or hiccups, typically associated with neuromyelitis optica spectrum disorder (NMOSD). This paper presents a case of APS related with autoimmunity due to systemic lupus erythematosus (SLE) and not related to NMOSD. Additionally, a comprehensive review of the literature is conducted. A 27-year-old Colombian female with a five-year history of systemic lupus erythematosus (SLE) presented with vomiting, epigastric pain, dysphagia, and seizures. Initial tests suggested acute pancreatitis and a lupus flare, but imaging of the gastrointestinal tract showed no abnormalities. Brain MRI revealed a lesion in the area postrema, indicating area postrema syndrome (APS). Treatment with hydrocortisone and later high-dose methylprednisolone and cyclophosphamide led to improvement. Negative anti-aquaporin 4 antibodies ruled out neuromyelitis optica spectrum disorder (NMOSD), leading to a probable diagnosis of APS associated with SLE. Given the patient's negative AQP4-IgG results, clinical profile, and medical history, we propose APS associated with SLE, marking the first reported case in Latin America.