Primary Biliary Cholangitis-Associated Granulomatous Interstitial Lung Disease: Pulmonary Epithelial-Interface Injury Supporting the Concept of Generalized Autoimmune Epithelitis.

Abstract

Primary biliary cholangitis (PBC) can be accompanied by interstitial lung disease (ILD) manifesting as granulomatous interstitial lung disease, but the mechanism of granuloma formation remains unclear. We report a case of PBC-ILD coexisting with anti-synthetase syndrome (ASS) in a 49-year-old woman who presented with persistent cough, facial rash, and arthritis. Laboratory tests demonstrated cholestatic enzyme elevation, anti-mitochondrial M2 positivity, and anti-aminoacyl-tRNA synthetase antibody positivity, with elevated KL-6 and SP-D levels. High-resolution CT revealed lower-lobe-predominant ground-glass opacities. Bronchoalveolar lavage fluid showed lymphocytosis with high CD4/CD8 ratio. Liver biopsy confirmed PBC. Surgical lung biopsies revealed epithelial-interface injury and focal apoptosis of bronchiolar and alveolar epithelium accompanied by CD4-dominant T-cell infiltration and non-caseating granulomas (NCGs). Segment 2 showed cellular NSIP pattern and segment 9 showed fibrotic NSIP pattern. NCGs were more prominent in the cellular NSIP areas and decreased in the fibrotic NSIP areas. These findings suggest a possible pathological continuum from active inflammation by epithelial-interface injury to fibrotic remodeling. These observations may highlight the potential relevance of generalized autoimmune epithelitis in the pathogenesis of PBC-ILD.