Severe cholestatic hepatitis induced by pyritinol
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《英国医生杂志》
1 Institute of Molecular Medicine, Clinical Immunology Unit and Department of Medicine 2, Faculty of Medicine of Lisbon, Hospital of Santa Maria, Av Prof Egas Moniz, 1649-028 Lisbon, Portugal
Correspondence to: V Maria vascomaria@fm.ul.pt
Introduction
Although pyritinol has been used in Europe for more than 20 years, only a few cases of drug induced hepatitis have been published.2 5-7 Interestingly, the doctors who referred the patients to our unit did not consider pyritinol to be a likely cause of hepatitis, so it is possible that this non-dose dependent drug hepatotoxicity may have been substantially under-reported during these years.
These six cases fulfil the usual criteria for diagnosis of drug induced liver injury, namely a temporal relation and the exclusion of alternative causes. Moreover, when we used a semiquantitative diagnostic scale, the results showed high levels of probability for drug induced liver injury.8 In four patients, immunological investigation showed a marked drug specific in vitro lymphocyte proliferative response, and CD4+ T lymphocytes were identified as the predominant drug specific lymphocytes. What is more striking is that the degree of T lymphocyte reactivity to the drug is much higher than the one usually observed in drug hypersensitivity hepatitis.3 Noteworthy, in addition to its putative effect on the memory and intellectual concentration, pyritinol has been shown to have favourable effects on rheumatoid arthritis1 similar to the ones described for penicillamine, which is also a drug with an active sulfhydryl group.2 Interestingly, penicillamine is typically responsible for several adverse reactions of immunological nature, such as immune complex nephropathy, autoimmune-like skin disorders, leucopoenia, and thrombocytopoenia.2
Clinically, the most striking feature in these patients was the severe and prolonged nature of the cholestasis that required admission to hospital in four previously healthy young individuals. The seriousness of this adverse reaction contrasts with the relatively small clinical importance of the problem that led to its prescription. Therefore, the cases reported here justify a reassessment of the risk and benefit of pyritinol.
Severe cholestatic hepatitis may develop in subjects taking pyritinol for minor complaints
Contributors: VM helped in the collection and analysis of clinical data, the performance of immunological studies, the design of the protocol, and the writing of the manuscript. AA helped in the laboratory immunological studies and in writing the manuscript. AL helped in the laboratory immunological studies. AS helped in the design and performance of flow cytometric studies, the analysis of data, and the writing of the mauscript. RV helped to supervise the clinical and laboratory work, plan the study, and write the manuscript. VM will act as guarantor for the article
Funding: The study was in part supported by EU "concerted action" funding: Eurohepatox (European Union BIOMED project PL9 50658).
Competing interests: None declared.
References
Lemmel EM. Comparison of pyritinol and auranofin in the treatment of rheumatoid arthritis. Br J Rheumatol 1993;32: 375-82.
Jaffe IA. Adverse effects profile of sulfhydryl compounds in man. Am J Med 1986;80: 471-6.
Maria VA, Victorino RM. Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury. Gut 1997;41: 534-40.
Cavaleiro R, Sousa AE, Loureiro A, Victorino RM. Marked immunosuppressive effects of HIV-2 envelope protein in spite of the lower HIV-2 pathogenicity. AIDS 2000;14: 2679-86.
Macedo G, Sarmento JA, Allegro S. Acute hepatitis due to pyritinol. Gastroenterol Clin Biol 1992;16: 186-7.
Straumann A, Bauer M, Pichler WJ, Pirovino M. Acute pancreatitis due to pyritinol: an immune-mediated phenomenon. Gastroenterology 1998;115: 452-4.
Imoto S, H Matsumoto, Fujii M. Drug-related hepatitis. Ann Intern Med 1979;91: 129.
Maria VA, Victorino RM. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997;26: 664-9.(Vasco Maria, assistant pr)
Correspondence to: V Maria vascomaria@fm.ul.pt
Introduction
Although pyritinol has been used in Europe for more than 20 years, only a few cases of drug induced hepatitis have been published.2 5-7 Interestingly, the doctors who referred the patients to our unit did not consider pyritinol to be a likely cause of hepatitis, so it is possible that this non-dose dependent drug hepatotoxicity may have been substantially under-reported during these years.
These six cases fulfil the usual criteria for diagnosis of drug induced liver injury, namely a temporal relation and the exclusion of alternative causes. Moreover, when we used a semiquantitative diagnostic scale, the results showed high levels of probability for drug induced liver injury.8 In four patients, immunological investigation showed a marked drug specific in vitro lymphocyte proliferative response, and CD4+ T lymphocytes were identified as the predominant drug specific lymphocytes. What is more striking is that the degree of T lymphocyte reactivity to the drug is much higher than the one usually observed in drug hypersensitivity hepatitis.3 Noteworthy, in addition to its putative effect on the memory and intellectual concentration, pyritinol has been shown to have favourable effects on rheumatoid arthritis1 similar to the ones described for penicillamine, which is also a drug with an active sulfhydryl group.2 Interestingly, penicillamine is typically responsible for several adverse reactions of immunological nature, such as immune complex nephropathy, autoimmune-like skin disorders, leucopoenia, and thrombocytopoenia.2
Clinically, the most striking feature in these patients was the severe and prolonged nature of the cholestasis that required admission to hospital in four previously healthy young individuals. The seriousness of this adverse reaction contrasts with the relatively small clinical importance of the problem that led to its prescription. Therefore, the cases reported here justify a reassessment of the risk and benefit of pyritinol.
Severe cholestatic hepatitis may develop in subjects taking pyritinol for minor complaints
Contributors: VM helped in the collection and analysis of clinical data, the performance of immunological studies, the design of the protocol, and the writing of the manuscript. AA helped in the laboratory immunological studies and in writing the manuscript. AL helped in the laboratory immunological studies. AS helped in the design and performance of flow cytometric studies, the analysis of data, and the writing of the mauscript. RV helped to supervise the clinical and laboratory work, plan the study, and write the manuscript. VM will act as guarantor for the article
Funding: The study was in part supported by EU "concerted action" funding: Eurohepatox (European Union BIOMED project PL9 50658).
Competing interests: None declared.
References
Lemmel EM. Comparison of pyritinol and auranofin in the treatment of rheumatoid arthritis. Br J Rheumatol 1993;32: 375-82.
Jaffe IA. Adverse effects profile of sulfhydryl compounds in man. Am J Med 1986;80: 471-6.
Maria VA, Victorino RM. Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury. Gut 1997;41: 534-40.
Cavaleiro R, Sousa AE, Loureiro A, Victorino RM. Marked immunosuppressive effects of HIV-2 envelope protein in spite of the lower HIV-2 pathogenicity. AIDS 2000;14: 2679-86.
Macedo G, Sarmento JA, Allegro S. Acute hepatitis due to pyritinol. Gastroenterol Clin Biol 1992;16: 186-7.
Straumann A, Bauer M, Pichler WJ, Pirovino M. Acute pancreatitis due to pyritinol: an immune-mediated phenomenon. Gastroenterology 1998;115: 452-4.
Imoto S, H Matsumoto, Fujii M. Drug-related hepatitis. Ann Intern Med 1979;91: 129.
Maria VA, Victorino RM. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997;26: 664-9.(Vasco Maria, assistant pr)