Dramatic Effect of Rituximab in Immunoglobulin G4-Related Primary Sclerosing Cholangitis

Abstract

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by fibrotic obliteration of the biliary ductal system. PSC is presumed to be an autoimmune disorder but there is no specific pharmacological therapy. Ursodiol (UDCA) often improves alkaline phosphatase levels but it has not shown an effect on the natural history of PSC. An IgG4 variant of PSC has been identified which seems to respond to corticosteroids, in contrast to classic PSC, but little is known about the therapeutic options for IgG4 PSC. We report a patient who only responded to high doses of steroids, but upon infusions of rituximab exhibited a dramatic and sustained response. A 68-year-old female developed obstructive jaundice with MRCP revealing a stricture in the CBD. Suspecting cholangiocarcinoma, she had an exploratory laparotomy and resection of the bile duct stricture. Pathology of the resected bile duct showed no malignancy but abundant plasma cells; this led to stain for IgG4, which was markedly positive. She thus began prednisone (40 mg/d) which resolved the cholestasis and improved liver chemistries. However repeated attempts to taper steroids were followed by biochemical relapse. Repeat MRCP revealed no obstructive lesions, and she was forced to resume and remain on high-dose prednisone. Mycophenolate was tried as a potential steroid-sparing agent, resulting in some decline in liver enzymes, but ultimately had to be discontinued due to severe facial rash. UDCA administration had no significant effect. Due to the lack of response and considering the IgG4 plasma cells observed on the resected bile duct specimen, the decision was made to try plasma cell suppressive therapy. At the peak of the patient's liver enzymes, rituximab infusions were started biweekly (Figure 1). By September 2015, after only 5 infusions, the patient had near complete resolution of liver chemistries. Prednisone was gradually tapered off, and the patient's symptoms and liver enzymes remained within normal limits to this date.Figure 1The IgG4 variant of PSC is uncommon (5% or less of PSC) but a few reports suggest it responds to high-dose steroids. For patients with incomplete remission, steroid dependency, or steroid intolerance, there are no other options. Our patient demonstrates that in cases of histology-verified IgG4 PSC, the use of rituximab, a monoclonal antibody directed against B-lymphocytes, could be considered capable of inducing a sustained steroid-free remission.