Case Presentation: Valproic acid (VPA) is a widely-used medication in various neurological disorders. Although generally well-tolerated, we present a rare complication of VPA therapy inducing pancreatitis. A 49-year-old male with PMH of autism, epilepsy (on VPA), HTN and HLD presented to the ED with complaints of lethargy and pallor. He denied abdominal pain, fever, diarrhea, vomiting or appetite changes. Of note, his dose of VPA 750mg BID was increased to 1000mg BID one month earlier. On examination, BP 90/51, HR 64, T 98.2̊ F, SpO2 100% on RA; remainder of the exam was negative for any focal findings. Pertinent labs demonstrated AST 66, ALT 84, lactate 3.0, WBC 20.6, lipase 1306; alcohol, triglyceride and bilirubin levels were normal. A CT abdomen was suggestive of acute pancreatitis. He was admitted for acute pancreatitis and managed with IV fluids, pain control and broad-spectrum antibiotics; VPA was also held. The next day, VPA level resulted 60.8 mg/L; abdominal ultrasound did not demonstrate gallstones and IgG-4 was normal. He improved clinically and was eventually discharged.
Discussion: Pancreatitis is an inflammatory disorder of the pancreas usually arising from intrapancreatic activation of enzymes. VPA acts by inhibiting GABA-transaminase and inactivating sodium and calcium channels. The therapeutic serum range is 50-100 mg/L and typically dosed 500-2500 mg/day in adults. Although VPA has been associated with pancreatitis, the incidence of VPA-induced pancreatitis remains relatively rare. In a study of 34 clinical trials studying VPA in headache patients, the incidence of VPA-induced pancreatitis was 0.2%. VPA-induced pancreatitis presents similarly to other forms of pancreatitis (abdominal pain, nausea and/or vomiting) with risk factors including recent initiation of treatment (typically < 1 year) and recent dosage increase. Currently, VPA-induced pancreatitis is thought to be an idiosyncratic reaction; however it is hypothesized the pathogenesis surrounds a direct-toxicity mediated reaction leading to free radical induced cell membrane damage via depletion of superoxide dismutase, catalase and glutathione perioxidase enzymes. The diagnosis and treatment of VPA-induced pancreatitis is similar to other forms of pancreatitis. A literature review of VPA-induced pancreatitis identified mortality to be 16%.
Conclusions: Although VPA-induced pancreatitis is relatively rare, clinicians should keep it in mind when evaluating patients on VPA presenting with GI symptoms.