PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS: OVERLAPPING CHALLENGES IN DIAGNOSIS AND TREATMENT

Abstract

Abstract Overlap syndromes (OS) describe the simultaneous presentation of more than one immune-mediated liver disease in a singular patient, and present unique challenges both in diagnosis and treatment. Here we report a case of primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) OS, ultimately treated with Vancomycin. A 30-year-old female with known ulcerative pancolitis (UC) and alcoholic cirrhosis in the setting of AIH presented to the ED with severe abdominal pain, bloody diarrhea, and bilious emesis. Initial labs showed ESR 48 mm/hr, CRP 32.97 mg/L, fecal calprotectin 1131.2 µg/mg, AST 45 IU/L, and total protein 9.1 g/dL. Clostridium Difficile and stool studies were negative. Patient was admitted with concern for acute UC flare. CT scan showed mild worsening of intrahepatic and extrahepatic biliary ductal dilatation suspicious for PSC, and a cirrhotic liver with signs of portal hypertension and splenomegaly (Fig. 1a). Endoscopy revealed multiple non-bleeding duodenal ulcers and grade II esophageal varices. Colonoscopy found moderately active UC Mayo score 2, worsened from prior exam. MRCP was significant for cirrhotic liver morphology with nodular surface contour, and intrahepatic and extrahepatic biliary dilatation with beading and irregularity of the intrahepatic biliary tree and cystic duct, consistent with PSC (Fig. 1b). She was diagnosed with PSC-AIH OS and underwent treatment with Prednisone, Azathioprine, and Ustekinumab with minimal improvement. Only after the addition of Vancomycin was there normalization of biochemical markers and clinical status. Autoimmune liver disease is generally categorized into hepatic (AIH) or cholestatic (PSC and PBC) predominance. PSC is known to be associated with IBD, specifically UC. It is hypothesized that PSC evolves in UC patients due to uptake into the enterohepatic circulation of proinflammatory cells from the colon; these agents typically concentrate in the biliary system where they ultimately cause the biliary ductal damage frequently seen with PSC. By targeting enteric bacteria, Vancomycin decreases the absorption of these inflammatory biliary toxins. For PSC patients with UC and co-occurring AIH, the addition of Vancomycin could significantly reduce mortality and disease burden. Several case reports and one pilot study have investigated Vancomycin’s role in the treatment of PSC. However, it remains a vastly underutilized therapy, and its role specifically in PSC-AIH OS has not been previously reported. There remains an evident need for a large double blind randomized placebo-controlled clinical trial to further support the addition of Vancomycin to the standard treatment regimen for PSC, and to establish clear parameters on effective dosage and length of treatment. In the meantime, clinicians should be aware of the possible use of Vancomycin to treat patients with PSC +/- AIH and IBD. Figure 1a: CT abdomen pelvis with IV contrast highlighting stigmata of cirrhosis with portal hypertension and splenomegaly. Image also shows worsening of intrahepatic and extrahepatic biliary ductal dilatation in the setting of PSC given the patient’s underlying history of ulcerative colitis. Figure 1b: MRCP showing beading and irregularity of the intrahepatic biliary tree and cystic duct, in keeping with known history of primary sclerosing cholangitis. This image also highlights the dilation of the intrahepatic and extrahepatic biliary system.