Tumor Necrosis Factor α (TNFα) Inhibitor Class Induced Acute Pancreatitis

Abstract

Introduction: We present a case of a 27-year-old female with ulcerative colitis (UC) proven by colonoscopy. Initially diagnosed with proctitis, the patient’s UC progressed to pancolitis within 2 years while receiving mesalamine per mouth and per rectum at maximum dose and eventually corticosteroids. Other causes of colitis were excluded by subsequent colonoscopy and stool testing. In light of pancolitis, infliximab (Remicade®) therapy was initiated. Following the second dose of infliximab (5 mg/kg), patient developed severe abdominal pain. Work-up revealed a lipase of 5000 U/L, normal liver function tests (LFTs), and edematous pancreatitis based on CT abdomen with IV contrast which excluded a biliary pancreatitis etiology. The patient denied any alcohol intake and tested negative for autoimmune pancreatitis based on normal IgG4 level (21 mg/dL). Triglyceride level was normal (66 mg/dL). She had no family history of pancreatitis. Infliximab was discontinued due to concern of drug-induced acute pancreatitis. The pancreatitis resolved with supportive care during a 3-day hospital admission. Afterwards the patient was started on 6-mercaptopurine (6-MP) in addition to mesalamine and corticosteroids. An interval MRI abdomen revealed resolution of pancreatitis with normal pancreatic parenchymal volume and signal intensity, normal pancreatic duct, absence of gallstones, but persistence of colitis. Despite 6-MP metabolites at maximum target range, UC symptoms worsened over the next 4 months, for which the patient was deemed to be a nonresponder to immunomodulators. 6-MP was discontinued and adalimumab (Humira®) was initiated. Following the second dose of adalimumab 40 mg, UC symptoms remained unchanged but she developed abdominal pain which radiated to her back and worsened by any oral intake. The patient presented the following day to the emergency room and was diagnosed with acute pancreatitis based on a lipase of 1500 U/L and typical abdominal pain. Biliary pancreatitis was excluded by normal LFTs and abdominal ultrasound showing a common bile duct of 2 mm without signs of cholelithiasis or biliary sludge. Alcohol and tobacco use was denied. The pain resolved after 2 days with supportive care. CT abdomen with IV contrast 7 days later showed resolution of acute pancreatitis. To our knowledge, this is the first described case of drug-induced acute pancreatitis due to a TNFα inhibitor class effect. We thoroughly excluded biliary, autoimmune, obstructive, triglyceride, and hypercalcemia-induced acute pancreatitis. Infliximab has proven to be beneficial for treatment of acute pancreatitis in rat models. Human studies are pending. Our case raises concerns for the use of infliximab in acute pancreatitis in humans.