A57 VALPROATE INDUCED DRESS SYNDROME CAUSING MIXED LIVER INJURY. (26th February 2020)

• Record Type: Journal Article
• Authors: Schneider, R; Verstegen, R; Hulst, J; Ito, S; Ng, V
• Is Part Of: Journal of the Canadian Association of Gastroenterology. Volume 3:Supplement 1(2020)
• Page Start: 67
• Page End: 68
• Publication Date: 2020-02-26
• Subjects: Gastroenterology -- Periodicals; 616.33005
• DOI: 10.1093/jcag/gwz047.056
• Languages: English
• ISSNs: 2515-2084

Abstract

Abstract: Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome occurs with 1 in every 1, 000 to 10, 000 drug exposures and has a mortality rate of up to 10%. It is one mechanism by which medications can induce liver injury with elevated liver enzymes seen in the majority of cases. In children, aromatic anticonvulsants are the drugs most commonly associated with DRESS syndrome. Valproate, a non-aromatic anti-epileptic, is not known to have a heightened risk of hypersensitivity syndromes and is often the anti-epileptic of choice in patients who develop hypersensitivity syndromes from other anti-epileptics. Valproate hepatotoxicity is normally caused by its inhibition of fatty acid transport and mitochondrial β-oxidation; vanishing bile duct syndrome is also reported. Aims: We present a case, to the best of our knowledge the first in paediatrics, in which valproate causes DRESS syndrome and a secondary, predominantly cholestatic, liver injury. Methods: Literature review and case report. Results: A previously healthy 14-year-old girl was diagnosed with new-onset seizures and started on valproate. Three weeks later, she developed a pruritic exanthem. Despite discontinuing her valproate, the rash persisted and she developed fever and jaundice. She was admitted to the ICU at the Hospital for Sick Children with a diagnosis of DRESS syndrome (RegiSCAR DRESS score 7) for treatment with IV steroids. At admission, she had a skin eruption, fever, leukocytosis (22.86 x10 9 /L), eosinophilia (1.03x10 9 /L), atypical lymphocytes (1.62 x10 9 /L), lymphadenopathy, and internal organ involvement (BiliC 138, GGT 501, INR 1.3, ALT 543, AST 370, Crt 109). Of note, her EBV PCR was positive. By discharge, her rash improved and kidney function normalized. Her cholestasis persisted, despite improvement in her transaminases and eosinophilia (BiliC 163, INR 1.0, GGT 338, ALT 506, AST 220, Eos 0.98x10 9 /L). She was discharged home on an oral steroid wean, ursodeoxycholic acid, levocarnitine, and levetiracetam. Upon reaching a daily dose of 20mg of prednisone, her rash and pruritus worsened, she had lost 7kg, and she was readmitted for IV steroids. Her rash improved within 4 days and she was discharged on a slower steroid taper, with the addition of cholestyramine and insulin for steroid induced diabetes. At present (2 ½ months after diagnosis), she continues her oral steroids and has persistent liver injury and pruritus. Conclusions: We report the first paediatric case of valproate induced DRESS syndrome causing a significant cholestatic presentation with otherwise preserved liver synthetic function. The prolonged cholestasis and pruritus may be a result of the natural course of DRESS syndrome, EBV reactivation/infection, or polypharmacy. Early recognition of DRESS syndrome as a mechanism of valproate induced liver injury in children is essential for earlier diagnosis and initiation of targeted therapy. Funding Agencies: None