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Volume 20, Issue 1
  • ISSN: 1574-8863
  • E-ISSN: 2212-3911

Abstract

Introduction

Myasthenia gravis (MG) is an autoimmune disorder of post-synaptic neuromuscular junction characterised by fatigable muscle weakness and is treated with prednisolone with or without other immunosuppressants, including azathioprine (AZA). Veno-occlusive hepatotoxicity of AZA is a rare complication in MG.

Case Report

We report a 35-year-old man with MG, was treated with pyridostigmine, prednisolone, and AZA for 5 years. He presented with abdominal pain and increased fatiguability for 7 days. His serum bilirubin and liver enzymes were elevated, and ultrasound revealed a dilated hepatic vein and portal vein suggestive of veno-occlusive liver disease. The clinical symptoms, liver functions, and ultrasound of the hepatobiliary system normalized after withdrawal of AZA.

Conclusion

A possibility of AZA veno-occlusive hepatoxicity should be considered in a MG patient if presented with abdominal pain, elevated bilirubin and transaminases, and ultrasound showing dilatation of hepatic veins. Physicians should be aware of this complication because this toxicity is reversible following dose reduction or withdrawal of AZA.

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2025-04-24

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References

  1. CaiX.J. LiZ.W. XiJ.Y. SongH.Z. LiuJ. ZhuW.H. GuoY. JiaoZ. Myasthenia gravis and specific immunotherapy: Monoclonal antibodies.Ann. N. Y. Acad. Sci.201914521183310.1111/nyas.1419531393614
     [Google Scholar]
  2. DeenenJ.C.W. HorlingsC.G.C. VerschuurenJ.J.G.M. VerbeekA.L.M. van EngelenB.G.M. The epidemiology of neuromuscular disorders: A comprehensive overview of the literature.j. Neuromuscul. Dis.201521738510.3233/JND‑14004528198707
     [Google Scholar]
  3. WalkerMB Treatment of myasthenia gravis with physostigmine.Lancet193422357791200110.1016/S0140‑6736(00)94294‑6
     [Google Scholar]
  4. TindallR.S.A. PhillipsJ.T. RollinsJ.A. WellsL. HallK. A clinical therapeutic trial of cyclosporine in myasthenia gravis.Ann. N. Y. Acad. Sci.1993681153955110.1111/j.1749‑6632.1993.tb22937.x8357194
     [Google Scholar]
  5. TindallR.S.A. RollinsJ.A. PhillipsJ.T. GreenleeR.G. WellsL. BelendiukG. Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis.N. Engl. J. Med.19873161271972410.1056/NEJM1987031931612053547126
     [Google Scholar]
  6. LindbergC. AndersenO. LefvertA.K. Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study.Acta Neurol. Scand.199897637037310.1111/j.1600‑0404.1998.tb05968.x9669469
     [Google Scholar]
  7. PalaceJ. Newsom-DavisJ. LeckyB. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis.Neurology19985061778178310.1212/WNL.50.6.17789633727
     [Google Scholar]
  8. MeriggioliM.N. CiafaloniE. Al-HaykK.A. RowinJ. Tucker-LipscombB. MasseyJ.M. SandersD.B. Mycophenolate mofetil for myasthenia gravis.Neurology200361101438144010.1212/01.WNL.0000094122.88929.0B14638974
     [Google Scholar]
  9. NaganeY. UtsugisawaK. ObaraD. KondohR. TerayamaY. Efficacy of low-dose FK506 in the treatment of Myasthenia gravis--a randomized pilot study.Eur. Neurol.200553314615010.1159/00008583315900097
     [Google Scholar]
  10. SandersD.B. HartI.K. MantegazzaR. ShuklaS.S. SiddiqiZ.A. De BaetsM.H.V. MelmsA. NicolleM.W. SolomonsN. RichmanD.P. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis.Neurology200871640040610.1212/01.wnl.0000312374.95186.cc18434638
     [Google Scholar]
  11. HeckmannJ.M. RawootA. BatemanK. RenisonR. BadriM. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis.BMC Neurol.20111119710.1186/1471‑2377‑11‑9721819556
     [Google Scholar]
  12. HowardJ.F.Jr BarohnR.J. CutterG.R. FreimerM. JuelV.C. MozaffarT. MellionM.L. BenatarM.G. FarrugiaM.E. WangJ.J. MalhotraS.S. KisselJ.T. A randomized, double‐blind, placebo‐controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.Muscle Nerve2013481768410.1002/mus.2383923512355
     [Google Scholar]
  13. PasnoorM. HeJ. HerbelinL. BurnsT.M. NationsS. BrilV. WangA.K. ElsheikhB.H. KisselJ.T. SapersteinD. ShaibaniJ.A. JacksonC. SwensonA. HowardJ.F.Jr GoyalN. DavidW. WicklundM. PulleyM. BeckerM. MozaffarT. BenatarM. PazcuzziR. SimpsonE. RosenfeldJ. DimachkieM.M. StatlandJ.M. BarohnR.J. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis.Neurology2016871576410.1212/WNL.000000000000279527306628
     [Google Scholar]
  14. FarmakidisC. PasnoorM. DimachkieM.M. BarohnR.J. Treatment of myasthenia gravis.Neurol. Clin.201836231133710.1016/j.ncl.2018.01.01129655452
     [Google Scholar]
  15. MatellG. Immunosuppressive drugs: Azathioprine in the treatment of myasthenia gravis.Ann. N. Y. Acad. Sci.1987505158859410.1111/j.1749‑6632.1987.tb51327.x3479940
     [Google Scholar]
  16. AbramskyO. Tarrab-HazdaiR. AharonovA. FuchsS. Immunosuppression of experimental autoimmune myasthenia gravis by hydrocortisone and azathioprine.J. Immunol.1976117122522810.4049/jimmunol.117.1.225932425
     [Google Scholar]
  17. SheikoM.A. SundaramS.S. CapocelliK.E. PanZ. McCoyA.M. MackC.L. Outcomes in pediatric autoimmune hepatitis and significance of azathioprine metabolites.J. Pediatr. Gastroenterol. Nutr.2017651808510.1097/MPG.000000000000156328272159
     [Google Scholar]
  18. WeeJ.S. MarinakiA. SmithC.H. Life threatening myelotoxicity secondary to azathioprine in a patient with atopic eczema and normal thiopurine methyltransferase activity.BMJ2011342mar25 1d141710.1136/bmj.d141721441287
     [Google Scholar]
  19. JoshiR. SinghS. Plica neuropathica (Plica polonica) following Azathioprine-induced pancytopenia.Int. J. Trichology20102211011210.4103/0974‑7753.7752321712900
     [Google Scholar]
  20. BroekmanM.M.T.J. CoenenM.J.H. van MarrewijkC.J. WantenG.J.A. WongD.R. VerbeekA.L.M. KlungelO.H. HooymansP.M. GuchelaarH.J. SchefferH. DerijksL.J.J. de JongD.J. More dose-dependent side effects with mercaptopurine over azathioprine in ibd treatment due to relatively higher dosing.Inflamm. Bowel Dis.201723101873188110.1097/MIB.000000000000116328644183
     [Google Scholar]
  21. WeinshilboumR.M. SladekS.L. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity.Am. J. Hum. Genet.19803256516627191632
     [Google Scholar]
  22. NielsenO.H. VainerB. Rask-MadsenJ. The treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine.Aliment. Pharmacol. Ther.200115111699170810.1046/j.1365‑2036.2001.01102.x11683683
     [Google Scholar]
  23. Anthony SawayP. HeckL.W. BonnerJ.R. KirklinJ.K. Azathioprine hypersensitivity.Am. J. Med.198884596096410.1016/0002‑9343(88)90079‑43284343
     [Google Scholar]
  24. FuggleN.R. BragoliW. MahtoA. GloverM. MartinezA.E. KinslerV.A. The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring.J. Am. Acad. Dermatol.201572110811410.1016/j.jaad.2014.08.04825440430
     [Google Scholar]
  25. Van GeenenE.J.M. De BoerN.K.H. StassenP. LinskensR.K. BrunoM.J. MulderC.J.J. StegemanC.A. Van BodegravenA.A. Azathioprine or mercaptopurine‐induced acute pancreatitis is not a disease‐specific phenomenon.Aliment. Pharmacol. Ther.201031121322132910.1111/j.1365‑2036.2010.04287.x20222913
     [Google Scholar]
  26. GuptaP. ShaffraliF. An unusual side effect of azathioprine.Clin. Exp. Dermatol.201540892993010.1111/ced.1263925810100
     [Google Scholar]
  27. ChenS.C. CummingsO.W. HartleyM.P. FilomenaC.A. ChoW.K. Hepatocellular carcinoma occurring in a patient with Crohn’s disease treated with both azathioprine and infliximab.Dig. Dis. Sci.200651595295510.1007/s10620‑005‑9009‑916670938
     [Google Scholar]
  28. BrinkertF. ArrenbergP. KrechT. GrabhornE. LohseA. SchrammC. Two cases of hepatosplenic T-cell lymphoma in adolescents treated for autoimmune hepatitis.Pediatrics20161383e2015424510.1542/peds.2015‑424527516526
     [Google Scholar]
  29. GisbertJ.P. González-LamaY. MatéJ. Thiopurine-induced liver injury in patients with inflammatory bowel disease: A systematic review.Am. J. Gastroenterol.200710271518152710.1111/j.1572‑0241.2007.01187.x17391318
     [Google Scholar]
  30. ReadA. WiesnerR.H. LaBrecqueD.R. TifftJ.G. MullenK.D. SheerR.L. PetrelliM. RicanatiE.S. McCulloughA.J. Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy.Ann. Intern. Med.1986104565165510.7326/0003‑4819‑104‑5‑6513008617
     [Google Scholar]
  31. KatzkaD.A. SaulS.H. JorkaskyD. SigalH. ReynoldsJ.C. SolowayR.D. Azathioprine and hepatic venocclusive disease in renal transplant patients.Gastroenterology198690244645410.1016/0016‑5085(86)90947‑93510146
     [Google Scholar]
  32. ZafraniE.S. von PinaudeauY. DhumeauxD. Drug-induced vascular lesions of the liver.Arch. Intern. Med.1983143349550210.1001/archinte.1983.003500301090186338851
     [Google Scholar]
  33. LorenzoniPaulo José CláudiaSuemi Kamoi Kay ZanlorenziMarcelo Farago DucciRenata Dal-Prá WerneckLineu Cesar ScolaRosana Herminia Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms.J Neurol Sci202041211673410.1016/j.jns.2020.116734
     [Google Scholar]
  34. AnsariA. HassanC. DuleyJ. MarinakiA. Shobowale-BakreE.M. SeedP. MeenanJ. YimA. SandersonJ. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease.Aliment. Pharmacol. Ther.200216101743175010.1046/j.1365‑2036.2002.01353.x12269967
     [Google Scholar]
  35. BouhnikY LémannM MaryJY Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurineLancet19963478996215910.1016/S0140‑6736(96)90402‑X
     [Google Scholar]
  36. CaprilliR. CarratùR. BabbiniM. A double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis.Am. J. Dig. Dis.197520211512010.1007/BF01072336235835
     [Google Scholar]
  37. BastidaG NosP AguasM Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease.Aliment Pharmacol Ther20052297758210.1111/j.1365‑2036.2005.02636.x
     [Google Scholar]
  38. RomagnuoloJ. SadowskiD.C. LalorE. JewellL. ThomsonA.B.R. Cholestatic hepatocellular injury with azathioprine: A case report and review of the mechanisms of hepatotoxicity.Can. J. Gastroenterol.199812747948310.1155/1998/2947529812167
     [Google Scholar]
  39. GrossR. ScapaE. Hepatotoxicity of 6-mercaptopurine in Crohn’s disease.Am. J. Gastroenterol.19928712188518861449165
     [Google Scholar]
  40. de BoerN.K. MulderC.J. van BodegravenA.A. Myelotoxicity and hepatotoxicity during azathioprine therapy.Neth. J. Med.2005631144444616397313
     [Google Scholar]
  41. RussmannS. ZimmermannA. KrähenbühlS. KernB. ReichenJ. Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis.Eur. J. Gastroenterol. Hepatol.200113328729010.1097/00042737‑200103000‑0001311293451
     [Google Scholar]
  42. HoltmannM. SchreinerO. KöhlerH. DenzerU. NeurathM. GalleP.R. HöhlerT. Veno-occlusive disease (VOD) in Crohn’s disease (CD) treated with azathioprine.Dig. Dis. Sci.20034881503150510.1023/A:102475552142312924643
     [Google Scholar]
  43. WanlessI.R. GodwinT.A. AllenF. FederA. Nodular regenerative hyperplasia of the liver in hematologic disorders: A possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis.Medicine198059536737910.1097/00005792‑198009000‑000047432153
     [Google Scholar]
  44. SeidererJ. ZechC.J. DieboldJ. SchoenbergS.O. BrandS. TillackC. GökeB. OchsenkühnT. Nodular regenerative hyperplasia: A reversible entity associated with azathioprine therapy.Eur. J. Gastroenterol. Hepatol.200618555355510.1097/00042737‑200605000‑0001816607155
     [Google Scholar]
  45. de BoerN.K.H. ReinischW. TemlA. van BodegravenA.A. SchwabM. LukasM. OchsenkühnT. PetritschW. KnoflachP. AlmerS. van der MerweS.W. HerrlingerK.R. SeidererJ. VogelsangH. MulderC.J.J. 6-Thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party.Digestion2006731253110.1159/00009166216493198
     [Google Scholar]
  46. HohlfeldR. MichelsM. HeiningerK. BesingerU. ToykaK.V. Azathioprine toxicity during long-term immunosuppression of generalized myasthenia gravis.Neurology198838225826110.1212/WNL.38.2.2583340289
     [Google Scholar]
  47. BoothRA AnsariMT LoitE Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: A systematic review.Ann Intern Med2011154128142310.7326/0003‑4819‑154‑12‑201106210‑00009
     [Google Scholar]
  48. ArberN. ZajicekG. NordenbergJ. SidiY. Azathioprine treatment increases hepatocyte turnover.Gastroenterology199110141083108610.1016/0016‑5085(91)90737‑61889701
     [Google Scholar]
  49. SamarasenaJ. BorgaonkarM. Development of hepatocellular carcinoma in a patient with Crohn’s disease treated with azathioprine.Dig. Dis. Sci.200752102748275010.1007/s10620‑006‑9613‑317404860
     [Google Scholar]
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Azathioprine-induced Veno-occlusive Hepatotoxicity in a Patient with Myasthenia Gravis
Curr Drug Saf 20, 68 (2025); https://doi.org/10.2174/0115748863272041231116104839
/content/journals/cds/10.2174/0115748863272041231116104839
/content/journals/cds/10.2174/0115748863272041231116104839
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  • Article Type:     Case Report
Keyword(s): AChR; Azathioprine; dilatation of hepatic veins; hepatotoxicity; MuSK; myasthenia gravis; vena-occlusive

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