Tacrolimus as a Reasonable Alternative in a Patient with Steroid-Dependent and Thiopurine-Refractory Autoimmune Pancreatitis with IgG4-Associated Cholangitis

Abstract

Background: More recently, autoimmune pancreatitis (AIP) in association with IgG4-positive cholangitis (IAC) has been recognised as a new and challenging entity. Currently, initiation of high dose steroids (e. g., prednisolone 0.5 − 1 mg/kg/day) followed by a steroid dose taper in combination with purine antagonists (e. g., azathioprine or 6-mercaptopurine) after resolution has been recommended as standard therapy.

Case Report: A 68-year-old male patient was referred to our institution in February 2012 for therapy evaluation of a steroid-dependent course of autoimmune pancreatitis type 1 with IgG4-associated cholangitis. Since the first diagnosis in March 2011, the patient was treated with high-dose steroids with good response. Whenever steroids were tapered down to a daily dose < 20 mg, cholestatic liver enzymes increased dramatically despite concurrent immunosuppressive therapy primarily with azathioprine and 6-MP thereafter. Therefore, we restarted steroid therapy (1 mg/kg/day) in combination with tacrolimus achieving a target level of 5 − 7 ng/mL. During the down-tapering phase, follow-up examinations presented a patient in good general condition without jaundice. Moreover, liver and pancreatic enzymes and also immunoglobulins returned to normal values without any evidence of relapse up today (66 weeks).

Conclusion: In this case, the combination of steroids with tacrolimus seems to be a reasonable alternative in a patient with steroid-dependent and thiopurine-refractory autoimmune pancreatitis with IgG4-associated cholangitis. To date, this is the first description of such a therapeutic approach for this entity.

Zusammenfassung

Hintergrund: Im Laufe der vergangenen Jahre ist die Autoimmunpankreatitis in Assoziation mit der IgG-4-positiven Cholangitis als neues und herausforderndes Krankheitsbild begriffen worden. Zum aktuellen Zeitpunkt besteht die Standardtherapie aus einem Steroidstoß (z. B. Prednisolon 0,5–1 mg/kg/Tag) gefolgt von einer Steroiddosisreduktion in Kombination mit Purin-Antagonisten (z. B. Azathioprin oder 6-Mercaptopurin).

Fall: Ein 68-jähriger Patient wurde im Februar 2012 zur Therapieevaluation einer steroidabhängigen Autoimmunpankreatitis Typ 1 mit IgG-4-assoziierter Cholangitis zu uns überwiesen. Nach Erstdiagnosestellung im März 2011 wurde der Patient mit hoch dosierten Steroiden behandelt und zeigte ein gutes Therapieansprechen. Immer wenn die Steroide unter eine tägliche Dosis von 20 mg reduziert wurden, kam es zu einem dramatischen Anstieg der Cholestaseparameter trotz begleitender immunsuppressiver Therapie zunächst mit Azathioprin und danach mit 6-Mercaptopurin. Deshalb begannen wir eine Steroidtherapie (1 mg/kg/Tag) nun in Kombination mit Tacrolimus mit einem Zielspiegel von 5–7 ng/ml. Während der Phase der Steroiddosisreduktion zeigte sich der Patient in den Kontrolluntersuchungen in gutem Allgemeinzustand ohne Ikterus. Ebenso kam es zu einer Normalisierung von Leber- und Pankreasenzymen sowie Immunglobulinen ohne Hinweise für ein Rezidiv bis heute (66 Wochen).

Schlussfolgerung: In unserem Fall war eine Kombination von Steroiden mit Tacrolimus eine Therapiealternative bei einem Patienten mit Steroid-abhängiger und Thiopurin-refraktärer Autoimmunpankreatitis mit IgG-4-assoziierter Cholangitis. Bis dato ist dies die erste Beschreibung eines solchen Therapieverfahrens für diese Entität.

Schlüsselwörter

Autoimmunhepatitis - Autoimmunpankreatitis - IgG4-Cholangitis

Key words

autoimmune hepatitis - autoimmune pancreatitis - IgG4-associated cholangitis

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