Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report
Abstract Background Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. Case presentation A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Medical Case Reports |
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| Online Access: | https://doi.org/10.1186/s13256-020-2349-4 |
| _version_ | 1819159691558649856 |
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| author | Rainer Ullrich Pliquett Christoph Lübbert Christoph Schäfer Matthias Girndt |
| author_facet | Rainer Ullrich Pliquett Christoph Lübbert Christoph Schäfer Matthias Girndt |
| author_sort | Rainer Ullrich Pliquett |
| collection | DOAJ |
| description | Abstract Background Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. Case presentation A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 μg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found. For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered. Conclusions Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity. |
| first_indexed | 2024-12-22T16:44:35Z |
| format | Article |
| id | doaj.art-f0062e4cb8ab4779bf3a121a725486f6 |
| institution | Directory Open Access Journal |
| issn | 1752-1947 |
| language | English |
| last_indexed | 2024-12-22T16:44:35Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Medical Case Reports |
| spelling | doaj.art-f0062e4cb8ab4779bf3a121a725486f62022-12-21T18:19:46ZengBMCJournal of Medical Case Reports1752-19472020-02-011411510.1186/s13256-020-2349-4Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case reportRainer Ullrich Pliquett0Christoph Lübbert1Christoph Schäfer2Matthias Girndt3Department of Internal Medicine 2, Halle University Hospital, Martin-Luther University Halle-WittenbergDivision of Infectious Diseases and Tropical Medicine, Department of Gastroenterology and Rheumatology, Leipzig University HospitalDepartment of Internal Medicine 2, Halle University Hospital, Martin-Luther University Halle-WittenbergDepartment of Internal Medicine 2, Halle University Hospital, Martin-Luther University Halle-WittenbergAbstract Background Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy. Case presentation A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 μg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found. For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered. Conclusions Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity.https://doi.org/10.1186/s13256-020-2349-4Thrombotic microangiopathyLiver toxicityleflunomideMethotrexateCase report |
| spellingShingle | Rainer Ullrich Pliquett Christoph Lübbert Christoph Schäfer Matthias Girndt Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report Journal of Medical Case Reports Thrombotic microangiopathy Liver toxicity leflunomide Methotrexate Case report |
| title | Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report |
| title_full | Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report |
| title_fullStr | Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report |
| title_full_unstemmed | Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report |
| title_short | Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report |
| title_sort | thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate a case report |
| topic | Thrombotic microangiopathy Liver toxicity leflunomide Methotrexate Case report |
| url | https://doi.org/10.1186/s13256-020-2349-4 |
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