The spectrum of valproic acid-associated pancreatitis

Our goal was to characterize valproic acid-associated pancreatitis in children.

The charts of all patients with pancreatitis (diagnosed by using strict criteria) associated with valproic acid during a 10-year period were reviewed. Clinical and laboratory results were abstracted.

Twenty-two patients with valproic acid-associated pancreatitis were seen during the study period. Symptoms were similar to those of patients with pancreatitis from other etiologies and included abdominal pain/tenderness (83%), vomiting/retching (74%), abdominal distention (30%), and fever/chills (26%). Valproic acid levels were in the therapeutic range in all but 1 patient. The mean duration of therapy before the onset of pancreatitis was 32 months. The serum lipase level was >3 times the reference value in all patients, but the serum amylase level was not significantly elevated in 31% of the patients tested. Imaging studies altered clinical management in only 1 patient. The length of stay was generally brief (mean: 8 days). Two patients died. Of the 5 patients who were rechallenged, 4 had relapses.

Valproic acid-associated pancreatitis does not depend on valproic acid serum level and may occur any time after the onset of therapy. The serum lipase level is more sensitive than the serum amylase level and should be obtained when pancreatitis is suspected. Early imaging studies did not change clinical management. Rechallenge with valproic acid is dangerous and should be avoided.