Zusammenfassung
Leberwerterhöhungen bei Patienten mit rheumatoider Arthritis (RA) können unterschiedliche Ursachen haben. Diese reichen von der Grunderkrankung über Therapiefolgen bis zur (Erst-)Manifestation einer assoziierten Autoimmunerkrankung. Wir stellen den Fall einer 19-jährigen Patientin mit seropositiver RA vor, bei der unter antirheumatischer Therapie mit Adalimumab und Leflunomid nach etwa 9 Monaten ein drastischer Anstieg der Leberenzyme sowie der Cholestaseparameter auftrat. Daraufhin wurde die spezifische Therapie ausgesetzt. Außer der Grunderkrankung und der antirheumatischen Therapie kamen auch eine stattgehabte Behandlung mit Flucloxacillin sowie eine Assoziation zu einer zeitgleich diagnostizierten Zöliakie als mögliche Ursachen der Transaminasenerhöhung in Betracht. Nach mehrfacher Leberbiopsie wurde unter Annahme einer Autoimmunhepatitis mit Prednisolon und Azathioprin behandelt. Hierunter trat eine rasche Normalisierung der Leberwerte ein.
Abstract
Elevated liver enzymes in patients with rheumatoid arthritis may have various causes. These can range from the rheumatic disease itself, the anti-rheumatic medication or be the manifestation of an associated autoimmune disease. We present the case of a 19-year-old female with known seropositive rheumatoid arthritis who developed severe liver damage after 9 months of anti-rheumatic therapy with leflunomide and adalimumab. Both drugs were stopped. In addition to the underlying disease and the specific anti-rheumatic drugs, a temporary therapy with flucloxacillin as well as an association with newly diagnosed celiac disease had to be considered as possible causes of elevated liver enzymes. Following repeated liver biopsy, autoimmune hepatitis was assumed and prednisolone and azathioprine were initiated. Elevated liver enzymes and bilirubin rapidly returned to normal values.
Literatur
Alderman CP (1996) Adverse effects of the angiotensin-converting enzyme inhibitors. Ann Pharmacother 30: 55–61
Björnsson E, Jerlstad P, Bergqvist A, Olsson R (2005) Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol 40: 1095–1101
Cannon GW, Kremer JM (2004) Leflunomide. Rheum Dis Clin North Am 30: 295–309
Davison S (2002) Coeliac disease and liver dysfunction. Arch Dis Child 87: 293–296
Dechant C, Schauenberg P, Antoni CE et al. (2004) Langzeitergebnisse einer TNF-Blockade beim Morbus Still im Erwachsenenalter. DMW 129: 1308–1312
Fairley CK, McNeil JJ, Desmond P et al. (1993) Risk factors for development of flucloxacillin associated jaundice. BMJ 306: 233–235
Gause AM, Schöning C (2007) Manifestation einer auoimmunen Lebererkrankung unter Adalimumab. Z Rheumatol (Suppl) 1: 54
Germano V, Picchianti Diamanti A, Baccano G et al. (2005) Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis. Ann Rheum Dis 64: 1519–1520
Hartleb M, Biernat L, Kochel A (2002) Drug-induced liver damage a three-year study of patients from one gastroenterological department. Med Sci Monit 8: 292–296
Iwai M, Harada Y, Ishii M et al. (2003) Autoimmune hepatitis in a patient with systemic lupus erythematosus. Clin Rheumatol 22: 234–236
Katayama Y, Kohriyama K, Kirizuka K et al. (2000) Sjögren’s syndrome complicated with autoimmune hepatitis and antiphospholipid antibody syndrome. Intern Med 39: 73–76
Koek GH, Stricker BH, Blok AP et al. (1994) Flucloxacillin-associated hepatic injury. Liver 14: 225–229
Li EK, Tam LS, Tomlinson B (2004) Leflunomide in the treatment of rheumatoid arthritis. Clin Ther 26: 447–459
Lohse AW, Hennes E (2007) Diagnostic criteria for autoimmune hepatitis. Hepatol Res (Suppl 3) 37: 509
Ludwig J, Viggiano TR, McGill DB, Oh BJ (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55: 434–438
Misdraji J, Thiim M, Graeme-Cook FM (2004) Autoimmune hepatitis with centrilobular necrosis. Am J Surg Pathol 28: 471–478
Ramos-Casals M, Brito-Zerón P, Munoz S et al. (2007) Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 86: 242–251
Rubio-Tapia A, Murray JA (2007) The liver in celiac disease. Hepatology 46: 1650–1658
Russmann S, Kaye JA, Jick SS, Jick H (2005) Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: cohort study using data from the UK General Practice Research Database. Br J Clin Pharmacol 60: 76–82
Scheinfeld N (2005) Adalimumab: a review of side effects. Expert Opin Drug Saf 4: 637–641
Sema K, Takei M, Uenogawa K et al. (2005) Felty’s syndrome with chronic hepatitis and compatible autoimmune hepatitis: a case presentation. Intern Med 44: 335–341
Tobon GJ, Canas C, Jaller JJ et al. (2007) Serious liver disease induced by infliximab. Clin Rheumatol 26: 578–581
Turner IB, Eckstein RP, Riley JW, Lunzer MR (1989) Prolonged hepatic cholestasis after flucloxacillin therapy. Med J Aust 151: 701–705
Putte LBA van de, Rau R, Breedveld FC et al. (2003) Efficacy and safety of the fully human anti-tumour necrosis factor α monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study. Ann Rheum Dis 62: 1168–1177
Wiegand J, Mössner J, Tillmann HL (2007) Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Internist (Berl) 48: 154–163
Wiegard C, Lohse AW (2005) Leber und Rheuma. Z Rheumatol 64: 26–31
Yatsuji S, Hashimoto E, Kaneda H et al. (2005) Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol 40: 1130–1138
Yeung E, Wong FS, Wanless IR et al. (2003) Ramipril-associated hepatotoxicity. Arch Pathol Lab Med 127: 1493–1497
Youssef WI, Tavill AS (2002) Connective tissue diseases and the liver. J Clin Gastroenterol 35: 345–349
Zeniya M, Watanabe F, Morizane T et al. (2005) Diagnosing clinical subsets of autoimmune liver diseases based on a multivariable model. J Gastroenterol 40: 1148–1154
Danksagung
Unser herzlicher Dank gilt Prof. Dr. med. J. Rüschoff und Dr. med. E. Alexandrakis, Institut für Pathologie, Klinikum Kassel, für die freundliche Überlassung der histologischen Bilder mit den entsprechenden Erklärungen.
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Hartmann, U., Schmitt, S. & Reuss-Borst, M. Leberwerterhöhung bei rheumatoider Arthritis. Z. Rheumatol. 67, 440–444 (2008). https://doi.org/10.1007/s00393-008-0288-3
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DOI: https://doi.org/10.1007/s00393-008-0288-3