Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab: A case report

Abstract

Background: Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events, the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4 (IgG4) related disease when the pancreaticobiliary system is affected. Nivolumab, an IgG4 monoclonal antibody, has been associated with cholangitis and pancreatitis, however its association with IgG4 related disease has not been reported to date.

Case summary: We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma. Patients IgG4 levels was normal on presentation. She responded to steroids but due to concerns for malignant biliary stricture, she opted for surgery, the pathology of which suggested IgG4 related disease.

Conclusion: We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.

Keywords: Biliary stricture; Case report; Cholangitis; Immunoglobulin G4 related disease; Nivolumab; Pancreatitis.

Figure 1

Cholangiogram obtained via endoscopic retrograde cholangiopancreatography demonstrating a single localized biliary stricture within the distal common bile duct with upstream dilation.

Figure 2

Hematoxylin and eosin stained. A: Low power hematoxylin and eosin (H&E) showing marked chronic mixed cell infiltrates and fibrosis within epithelial and subepithelial region; B: Medium power H&E microscopy showing venules flanked by lymphocytes consistent with lymphocytic phlebitis (arrows); C: Medium power trichrome microscopy showing Prussian blue trichome staining of fibrosis with storiform pattern; D: High power H&E microscopy showing plasma call predominant inflammatory cell infiltrates amidst biliary glands; E: High power view of same area in D, showing numerous plasma cells highlighted with dark brown signal by CD138 immunohistochemistry antibody, a plasma cell biomarker; F: High power view of same area in D, showing numerous immunoglobulin G4 (IgG4) positive plasma cells highlighted with dark brown signals by IgG4 immunohistochemistry antibody.