Thakkar Hemang H, Mathew Nissy V, Reddy Etikala P, Cheetiyar Anusha L, Kommalapati Varun, Mathew Aksa, Rajendiran Abirami, Riyaz Raina, Joseph Nixon, Obadi Abdullah H, Vahora Nazmi, Alamgir Mariam, Ali Hossam T
Internal Medicine, Gujarat Medical Education and Research Society (GMERS) Medical College and Hospital, Sola, Ahmedabad, IND.
Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, GBR.
Cureus. 2025 Apr 10;17(4):e82008. doi: 10.7759/cureus.82008. eCollection 2025 Apr.
Primary biliary cholangitis (PBC) is an autoimmune liver disease of a chronic nature that can lead to liver cirrhosis, predominantly in females. PBC frequently coexists with other autoimmune diseases, such as systemic sclerosis (SSc), rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Despite variations in the literature, most studies have reported that a few PBC patients have SSc, especially the limited cutaneous subtype. Pathology of SSc includes microvascular affection and widespread fibrotic changes along with the autoimmune process. This narrative review aims to provide a comprehensive overview of the existing literature up to December 2024 regarding PBC, SSc, and overlap syndrome with emphasis on diagnostic points. Clinical manifestations can be significantly overlapping for both conditions. Thus, laboratory and histopathological investigations are necessary. The antibody profile is a cornerstone in such autoimmune diseases. While the antimitochondrial antibody (AMA) is considered specific for PBC, the presence of anticentromere antibody (ACA) highly suggests the concomitant presence of SSc. Several common pathologic mechanisms and triggers have been suggested for both diseases, and genes like HLA-DRB1, DQA1, STAT4, and IRF5 are shared between the two conditions. It is noteworthy that the prognosis and outcome of PBC cases are affected by the presence of SSc; for instance, the high liver-related PBC mortality decreases with the presence of SSc, although overlapping cases are at high risk of non-liver-related mortality. The overlapping cases comprise a clinical challenge for diagnosis and tailored management, although some promising medications are being investigated for both conditions, possibly due to common pathogenic mechanisms. Herein, we comprehensively review the available literature on PBC-SSc overlapping syndrome in terms of epidemiology, underlying pathophysiology, and clinical aspects.
原发性胆汁性胆管炎（PBC）是一种慢性自身免疫性肝病，主要发生于女性，可导致肝硬化。PBC常与其他自身免疫性疾病共存，如系统性硬化症（SSc）、类风湿关节炎、系统性红斑狼疮和干燥综合征。尽管文献报道存在差异，但大多数研究报告称，少数PBC患者患有SSc，尤其是局限性皮肤亚型。SSc的病理包括微血管病变和广泛的纤维化改变以及自身免疫过程。本叙述性综述旨在全面概述截至2024年12月关于PBC、SSc及重叠综合征的现有文献，重点关注诊断要点。两种疾病的临床表现可能有显著重叠。因此，实验室和组织病理学检查是必要的。抗体谱是此类自身免疫性疾病的基石。抗线粒体抗体（AMA）被认为是PBC的特异性抗体，而抗着丝点抗体（ACA）的存在高度提示同时存在SSc。两种疾病都提出了几种常见的病理机制和触发因素，并且HLA - DRB1、DQA1、STAT4和IRF5等基因在两种疾病中都有共享。值得注意的是，PBC病例的预后和结局受SSc的影响；例如，尽管重叠病例有非肝脏相关死亡的高风险，但随着SSc的存在，与肝脏相关的PBC高死亡率会降低。重叠病例对诊断和个性化管理构成临床挑战，尽管针对这两种疾病正在研究一些有前景的药物，这可能是由于共同的致病机制。在此，我们从流行病学、潜在病理生理学和临床方面全面综述了关于PBC - SSc重叠综合征的现有文献。
