A comprehensive review of systemic sclerosis-primary biliary cholangitis overlap: emerging evidence for a distinct clinical subtype.

Abstract

Purpose of review: To synthesize current knowledge on the genetic, immunopathogenic, and clinical presentations of systemic sclerosis (SSc) and primary biliary cholangitis (PBC) with a focus on their co-occurrence as a clinically relevant overlap syndrome. This narrative review summarizes preclinical and clinical studies addressing SSc-PBC overlap.

Recent findings: Genomic studies highlight shared susceptibility loci between SSc and PBC. Furthermore, SSc-PBC overlap patient sera reveals anticentromere antibodies which cross-react with an antigenic motif on pyruvate dehydrogenase-E2 (structural core of pyruvate dehydrogenase complex catalyzing formation of acetyl coA), the most common target of antimitochondrial antibodies in PBC. Similar profibrotic cytokines and T regulatory cell profiles are identified in sera and skin and liver biopsies of patients with SSc and PBC respectively. Analysis of clinical phenotypes reveals that SSc-PBC overlap patients have reduced incidence of pulmonary fibrosis and pulmonary arterial hypertension compared to SSc alone, and less severe hepatic involvement compared to PBC alone.

Summary: SSc-PBC overlap remains an understudied disease process. This review summarizes current knowledge and outlines future directions to guide research and improve care for patients with this distinct clinical overlap.