Abstract
Introduction
Anticonvulsant hypersensitivity syndrome is a severe idiosyncratic reaction to antiepileptic drugs. We report a case of a woman with lamotrigine-associated hepatitis who recovered spontaneously with supportive treatment.
Case Report
A 43-year-old woman was being treated with oxcarbazepine for depression and was started on lamotrigine 2 weeks prior to her presentation. The patient then developed nausea and a generalized pruritic macular rash, and was found to have elevated liver enzymes, which peaked at AST, 6079 IU/L; ALT, 6900 IU/L; total bilirubin, 3.9 mg/dL(66.7 μmol/L); alkaline phosphatase, 149 IU/L; international normalized ration (INR), 1.9. The patient showed no signs of encephalopathy and her clinical examination was essentially normal except for very mild jaundice and a diffuse erythematous pruritic macular rash. The patient was hydrated and managed with supportive care. On the third day of hospitalization, her liver enzymes had improved substantially and she was discharged. At follow-up 1 month later the patient’s liver enzymes were within the normal range.
Discussion
We hypothesize that lamotrigine was directly responsible for the patient’s rash and liver impairment given the time sequence of drug introduction and resolution of symptoms and liver enzyme abnormality once the drug was withdrawn. The patient suffered severe transaminitis when lamotrigine was added to oxcarbazepine, which resolved after termination of the medication and supportive management. We recommend monitoring the hepatic function in patients who have just been initiated on lamotrigine, especially if they develop jaundice.
Keywords: Lamotrigine, hepatitis, adverse drug reaction, drug hypersensitivity
Full Text
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Footnotes
There was no outside funding of any kind used for this study.
References
- 1.Shear NH, Spielberg SP. Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk. J Clin Invest. 1988;82(6):1826–1832. doi: 10.1172/JCI113798. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Sullivan JR, Shear NH. The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol. 2001;137(3):357–364. [PubMed] [Google Scholar]
- 3.Mecarelli O, Pulitano P, Mingoia M, Ferretti G, Rossi M, Berloco PB, et al. Acute hepatitis associated with lamotrigine and managed with the molecular adsorbents recirculating system (Mars) Epilepsia. 2005;46(10):1687–1689. doi: 10.1111/j.1528-1167.2005.00269.x. [DOI] [PubMed] [Google Scholar]
- 4.Overstreet K, Costanza C, Behling C, Hassanin T, Masliah E. Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review. Dig Dis Sci. 2002;47(9):1921–1925. doi: 10.1023/A:1019627618972. [DOI] [PubMed] [Google Scholar]
- 5.Fayad M, Choueiri R, Mikati M. Potential hepatotoxicity of lamotrigine. Pediatr Neurol. 2000;22(1):49–52. doi: 10.1016/S0887-8994(99)00106-X. [DOI] [PubMed] [Google Scholar]
- 6.Arnon R, DeVivo D, Defelice AR, Kazlow PG. Acute hepatic failure in a child treated with lamotrigine. Pediatr Neurol. 1998;18(3):251–252. doi: 10.1016/S0887-8994(97)00196-3. [DOI] [PubMed] [Google Scholar]
- 7.Makin AJ, Fitt S, Williams R, Duncan JS. Fulminant hepatic failure induced by lamotrigine. BMJ. 1995;29(7000):292–292. doi: 10.1136/bmj.311.7000.292b. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Schaub JE, Williamson PJ, Barnes EW, Trewby PN. Multisystem adverse reaction to lamotrigine. Lancet. 1994;13(8920):481–481. doi: 10.1016/S0140-6736(94)91818-X. [DOI] [PubMed] [Google Scholar]
- 9.Brodie MJ. Lamotrigine. Lancet. 1992;339:1397–1400. doi: 10.1016/0140-6736(92)91207-O. [DOI] [PubMed] [Google Scholar]
- 10.Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression Lamictal 602 Study Group. J Clin Psychiatry. 1999;60:79–88. doi: 10.4088/jcp.v60n0203. [DOI] [PubMed] [Google Scholar]
- 11.Calabrese JR, Bowden CL, Sachs G, Yatham LN, Behnke K, Mehtonen OP. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64:1013–1024. doi: 10.4088/JCP.v64n0906. [DOI] [PubMed] [Google Scholar]
- 12.Calabrese JR, Sullivan JR, Bowden CL, Suppes T, Goldberg JF, Sachs GS, et al. Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry. 2002;63(11):101–129. doi: 10.4088/jcp.v63n1110. [DOI] [PubMed] [Google Scholar]
- 13.Guberman AH, Besag FM, Brodie MJ, Dooley JM, Duchowny MS, Pellock JM, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia. 1999;40(7):985–991. doi: 10.1111/j.1528-1157.1999.tb00807.x. [DOI] [PubMed] [Google Scholar]
- 14.Faught E, Morris G, Jacobson M, French J, Harden C, Montouris G, et al. Adding lamotrigine to valproate: incidence of rash and other adverse effects: Postmarketing Antiepileptic Drug Survey (PADS) Group. Epilepsia. 1999;40(8):1135–1140. doi: 10.1111/j.1528-1157.1999.tb00831.x. [DOI] [PubMed] [Google Scholar]
- 15.Schlienger RG, Knowles SR, Shear NH. Lamotrigine-associated anticonvulsant hypersensitivity syndrome. Neurology. 1998;51(4):1172–1175. doi: 10.1212/wnl.51.4.1172. [DOI] [PubMed] [Google Scholar]
- 16.Kearney TE. Carbamazepine and oxcarbazepine. In: Olson KR, editor. Poisoning and Drug Overdose. 5th ed. International: McGraw-Hill Lange; 2007. pp. 148–150. [Google Scholar]
- 17.Bosdure E, Cano A, Roquelaure B, Reynaud R, Boyer M, Viard L, et al. Oxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure. Arch Pediatr. 2004;11(9):1073–1077. doi: 10.1016/j.arcped.2004.05.018. [DOI] [PubMed] [Google Scholar]
- 18.May TW, Rambeck B, Jurgens U. Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Ther Drug Monit. 1999;21(2):175–181. doi: 10.1097/00007691-199904000-00007. [DOI] [PubMed] [Google Scholar]
- 19.Guenault N, Odou P, Robert H. Increase in dihydroxycarbamazepine serum levels in patients co-medicated with oxcarbazepine and lamotrigine. Eur J Clin Pharmacol. 2003;59(10):781–782. doi: 10.1007/s00228-003-0686-z. [DOI] [PubMed] [Google Scholar]
- 20.Schaub N, Bircher AJ. Severe hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro. Allergy. 2000;55(2):191–193. doi: 10.1034/j.1398-9995.2000.00467.x. [DOI] [PubMed] [Google Scholar]
- 21.Chang CC, Shiah IS, Yeh CB, Wang TS, Chang HA. Lamotrigine-associated anticonvulsant hypersensitivity syndrome in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(4):741–744. doi: 10.1016/j.pnpbp.2005.11.033. [DOI] [PubMed] [Google Scholar]