Mycophenolate therapy in Autoimmune Pancreatitis

Abstract

Autoimmune pancreatitis (AIP) is an uncommon cause of chronic pancreatitis with an estimated prevalence rate of 0.82/100,000 in Japan [1][2][3]. Exact incidence and prevalence in the United States is unknown. AIP is generally divided into two types: Type 1 (Lymphoplasmacytic sclerosing pancreatitis/IgG4 related) and Type 2 (Idiopathic ductcentric pancreatitis) [4,5]. Systemic glucocorticoids remain the mainstay of treatment for AIP. However, more than 50% of patients with AIP treated with steroids experience relapse with the steroid taper [6]. Remission maintenance in many patients requires chronic steroid use, which poses risk of adverse effects [7]. In order to minimize risk of chronic steroid use, drugs such as azathioprine (AZA), 6-mercaptopurine (6-MP) and rituximab (RTX) have been used in AIP [7]. Thiopurine Methyl Transferase (TPMT) activity is reduced in about 11% of general population, who therefore may not tolerate AZA or 6-MP [8]. Also, AZA is associated with drug-induced pancreatitis, which may mimic AIP flare and cause therapeutic confusion. Disadvantages of RTX include its requirement for intravenous infusion and its expense. Hence there is a need for alternative cheaper, effective and safer oral steroid-sparing agents for AIP. Mycophenolate mofetil (MMF), a powerful inhibitor of lymphocyte proliferation, is a commonly used immunosuppressive agent by rheumatologists. It is available in generic form and also the safety profile is known over few decades. It may be better tolerated than AZA or 6-MP in some patients. However data regarding efficacy and safety of MMF in AIP are lacking. As of 4-2016, less than 15 such cases have been reported in Englishlanguage literature [9][10][11][12]. AIP patients were identified by Rheumatology and Gastroenterology providers at the University of Minnesota (UMN), a tertiary referral center for patients with pancreatic diseases. On the basis of previous case series [13], UMN providers have used mycophenolate for AIP treatment in recent years. Here we present one center's experience with mycophenolate mofetil in 4 patients with AIP.Patient A is a 23-year-old female with history of celiac disease, type 1 diabetes mellitus, and chronic urticaria who presented with recurrent abdominal pain. Her abdominal pain was initially thought to be due to sphincter of Oddi dysfunction, but failed to respond to biliary and pancreatic sphincterotomies by endoscopic retrograde cholangio-pancreatography (ERCP). She was started on prednisone 40mg daily for chronic urticaria of unclear etiology (skin biopsy was non-specific) and the prednisone was quickly tapered off. Surprisingly, her abdominal pain improved dramatically. However, she was not a candidate for long-term prednisone therapy because of underlying type 1 diabetes mellitus and anxiety. MMF (750 mg twice daily) was started for her urticaria. However both urticarial rash and abdominal pain improved. When MMF dose was tapered down, her abdominal pain worsened. EUS showed hyper-echoic foci and lobularity in the pancreas. Ampullary ...