{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T16:06:49Z","timestamp":1760890009256},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8\u2009years and on leflunomide for 6\u2009years 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\u2009\u03bcg\/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found.<\/jats:p>\n<jats:p>For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4\u2009units of fresh-frozen plasma were given. Steroid therapy was administered for 5\u2009days, 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\u2009weeks, 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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13256-020-2349-4","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T01:02:38Z","timestamp":1580864558000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report"],"prefix":"10.1186","volume":"14","author":[{"given":"Rainer Ullrich","family":"Pliquett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"L\u00fcbbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Girndt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"issue":"7","key":"2349_CR1","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1002\/1529-0131(199907)42:7<1322::AID-ANR4>3.0.CO;2-P","volume":"42","author":"ME Weinblatt","year":"1999","unstructured":"Weinblatt ME, Kremer JM, Coblyn JS, Maier AL, Helfgott SM, Morrell M, Byrne VM, Kaymakcian MV, Strand V. 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A written consent for publication was obtained from the patient presented in this case report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}