P-175 YI Fatal Outcome Following First Infliximab Infusion in a Child with Ulcerative Colitis and Primary Sclerosing Cholangitis

Abstract

BACKGROUND: Infliximab is used for a variety of autoimmune conditions, including Crohn's disease and Ulcerative Colitis. Established severe side effects include: infusion reactions, hematologic abnormalities, infections, hepatotoxicity, as well as slight increases in the risk of malignancy and lymphoma. Neurologic complications are rare and include worsening of demyelinating diseases, and neuropathies, often commencing months following treatment.to date. METHODS: We report the case of a 7 year old boy who was diagnosed with ulcerative colitis and primary sclerosing cholangitis at 6 and half years of age, who continued to have mild disease, manifested primarily by ongoing hematochezia and anemia despite Balsalazide and 6-Mercaptopurine therapy. His course to this point was unremarkable and his disease severity was mild with a Pediatric Ulcerative Colitis Score of 30. He was admitted for blood transfusion and underwent endoscopy and colonoscopy. He then received his first infusion of Infliximab. Other than mild sinus arrhythmia, he tolerated this well. There were no other notable events surrounding the infusion, he was interacting appropriately with normal vital signs and was discharged home. RESULTS: Within 6 hours of his infusion, he awoke from sleep from a severe headache and developed acute nausea and emesis. Half an hour later, he was slumped to one side and parents brought to a local emergency room. Upon arrival, he was completely unresponsive and emergently intubated. Given slight hypotension, he was suspected to have an anaphylactic reaction and received intravenous fluids, packed red blood cells and Epinephrine. Once transferred to our pediatric center, CT image of his brain revealed multifocal bilateral hypodense lesions with surrounding edema involving multiple lobes, the pons, and brainstem. Left sided lesions were largest and consistent with parenchymal hemorrhage. He was started on hypertonic saline and mannitol and external ventricular drains were promptly inserted, but his initial intracranial pressures were low. MRI imaging confirmed bilateral multi-territory infarcts that appeared to be arterial in nature without evidence of arterial clots, or venous infarcts. A workup for infectious encephalitis was negative, as was investigation for underlying anatomic anomalies of his vasculature. His presentation was not in keeping with an underlying vasculitis. An echocardiogram showed a dilated left ventricle, but did not show evidence of an arterial-septal defect, intracardiac thrombi or other abnormality. CONCLUSIONS: Our patient met criteria for brain death within 5 days following his single dose of Infliximab. Family refused an autopsy. We report a case of acute hemorrhagic stroke and ultimately fatal outcome following an initial infusion of Infliximab. Although the etiology of this event remains unclear, the close temporal relation to the Infliximab infusion cannot be ignored. To our knowledge, such a life threatening reaction within hours of Infliximab infusion has not been reported.