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Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease: case-based review

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Abstract

In rheumatology practice, the risk of hepatotoxicity from medications, including non-steroidal anti-inflammatory drugs, notably, and methotrexate, sulfasalazine, leflunomide, and azathioprine is highly recognized by the rheumatologists. On the other hand, hepatotoxicity is neither a commonly expected nor a well-known side effect of cyclophosphamide (CYC) which is particularly used for vital organ involvements in systemic lupus erythematosus (SLE) and systemic vasculitis. Here we reported a 19-year-old case of SLE who, while on oral CYC treatment of 100 mg/day, was detected to have asymptomatic liver enzyme elevation and then developed acute hepatitis due to intravenously administered high-dose (1 g) CYC for neuro-lupus. Results of liver biopsy indicated drug-related toxicity. We discussed here with the other, although rare, cases available in the literature with an attempt to highlight the risk of hepatotoxicity and acute hepatitis due to CYC.

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References

  1. Anelli MG, Scioscia C, Grattagliano I, Lapadula G (2012) Old and new antirheumatic drugs and the risk of hepatotoxicity. Ther Drug Monit 34:622–628

    Article  CAS  PubMed  Google Scholar 

  2. Wood PR, Caplan L (2018) Drug-induced gastrointestinal and hepatic disease associated with biologics and nonbiologic disease-modifying antirheumatic drugs. Rheum Dis Clin North Am 44:29–43

    Article  PubMed  Google Scholar 

  3. Tsang-A-Sjoe MW, Bultink IE (2015) Systemic lupus erythematosus: review of synthetic drugs. Expert Opin Pharmacother 16:2793–2806

    Article  CAS  PubMed  Google Scholar 

  4. Bacon AM, Rosenberg SA (1982) Cyclophosphamide hepatotoxicity in a patient with systemic lupus erythematosus. Ann Intern Med 97:62–63

    Article  CAS  PubMed  Google Scholar 

  5. Subramaniam SR, Cader RA, Mohd R, Yen KW, Ghafor HA (2013) Low-dose cyclophosphamide-induced acute hepatotoxicity. Am J Case Rep 14:345–349

    Article  PubMed  PubMed Central  Google Scholar 

  6. Martínez-Gabarrón M, Enríquez R, Sirvent AE, García-Sepulcre M, Millán I, Amorós F (2011) Hepatotoxicity following cyclophosphamide treatment in a patient with MPO-ANCA vasculitis. Nefrologia 31:496–498

    PubMed  Google Scholar 

  7. Mok CC, Wong WM, Shek TW, Ho CT, Lau CS, Lai CL (2000) Cumulative hepatotoxicity induced by continuous low-dose cyclophosphamide therapy. Am J Gastroenterol 95:845–846

    Article  CAS  PubMed  Google Scholar 

  8. Cleland BD, Pokorny CS (1993) Cyclophosphamide related hepatotoxicity. Aust N Z J Med 23:408

    Article  CAS  PubMed  Google Scholar 

  9. Gustafsson LL, Eriksson LS, Dahl ML, Eleborg L, Ericzon BG, Nyberg A (1996) Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism: a causal relationship? J Intern Med 240:311–314

    Article  CAS  PubMed  Google Scholar 

  10. Snyder LS, Heigh RI, Anderson ML (1993) Cyclophosphamide-induced hepatotoxicity in a patient with Wegener’s granulomatosis. Mayo Clin Proc 68:1203–1204

    Article  CAS  PubMed  Google Scholar 

  11. Akay H, Akay T, Secilmis S, Kocak Z, Donderici O (2006) Hepatotoxicity after low-dose cyclophosphamide therapy. South Med J 99:1399–1400

    Article  PubMed  Google Scholar 

  12. Aithal GP (2011) Hepatotoxicity related to antirheumatic drugs. Nat Rev Rheumatol 7:139–150

    Article  CAS  PubMed  Google Scholar 

  13. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245

    Article  CAS  Google Scholar 

  14. Pinto N, Ludeman SM, Dolan ME (2009) Drug focus: pharmacogenetic studies related to cyclophosphamide-based therapy. Pharmacogenomics 10:1897–1903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jonge ME, Huitema AD, Beijnen JH, Rodenhuis S (2006) High exposures to bioactivated cyclophosphamide are related to the occurrence of venoocclusive disease of the liver following high-dose chemotherapy. Br J Cancer 94:1226–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. McDonald GB, Slattery JT, Bouvier ME, Ren S, Batchelder AL, Kalhorn TF, Schoch HG, Anasetti C, Gooley T (2003) Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood 101:2043–2048

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, 26480, Eskisehir, Turkey

    Döndü Üsküdar Cansu & Cengiz Korkmaz

  2. Division of Gastroenterology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskisehir, Turkey

    Erkin Öztaş

  3. Department of Pathology, Eskişehir Osmangazi University, Eskisehir, Turkey

    Evrim Yilmaz

Authors
  1. Döndü Üsküdar Cansu
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  2. Erkin Öztaş
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  3. Evrim Yilmaz
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  4. Cengiz Korkmaz
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In accordance with ICMJE criteria, all authors were involved in writing and drafting the article or revising it critically for important intellectual content. All authors approved the final version to be submitted for publication and agree to be accountable for all aspects of the work.

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Correspondence to Döndü Üsküdar Cansu.

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Author DUC, Author EÖ, Author EY and Author CK declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from our patient.

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Üsküdar Cansu, D., Öztaş, E., Yilmaz, E. et al. Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease: case-based review. Rheumatol Int 39, 377–385 (2019). https://doi.org/10.1007/s00296-018-4189-8

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  • DOI: https://doi.org/10.1007/s00296-018-4189-8

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