Systemic sclerosis and primary biliary cholangitis: An overlapping entity?

Abstract

Systemic sclerosis (SSc) is a complex autoimmune disease that may lead to skin and internal organ fibrosis. Based on skin involvement, two subsets of the disease are recognized (limited cutaneous SSc and diffuse cutaneous SSc). The new 2013 American College of Rheumatology/European League against Rheumatism classification criteria allow to identify SSc patients at the early stage of the disease that allows new research avenues. The aetiology of the disease is still unknown, but it has an important autoimmune basis and its association with other autoimmune diseases has been reproducibly reported. Among them, primary biliary cholangitis is considered the most common liver disease in SSc. The aim of this review is to provide an overview on recent findings about SSc associated to primary biliary cholangitis. Although the aetiology of the two diseases is still unknown, data suggest that these two disorders share the expression of fibrogenic cytokines, involved both in generation and function of T lymphocytes subpopulation (Th17 cells) and regulatory T lymphocytes. In addition, the relationships between SSc and primary biliary cholangitis may be closer as suggested by the presence of primary biliary cholangitis-specific antibodies in SSc patients and vice versa. Recent findings confirm a prevalence of overt primary biliary cholangitis in about 2% of SSc population, in particular in patients with limited cutaneous SSc and positive anticentromere antibodies. The prevalence increases if also patients with only primary biliary cholangitis-specific antibodies are considered. Data regarding SSc prevalence in primary biliary cholangitis patients have also been recently clarified. Altogether, stimulating results are moving the field forward regarding the relationships of these two autoimmune and fibrotic disorders that may belong to an overlapping entity.

Evaluation of GLOBE and UK-PBC Scores and Long- Term Outcomes in Primary Biliary Cholangitis Complicated with CREST Syndrome

“…Limited ndings have been reported regarding the etiology of combined PBC-SSc, including a higher expression level of T-cell receptor beta chain variable region 3 on CD8 + T cells and a higher prevalence of human leukocyte antigen (HLA)-DR9 expression in patients with combined PBC-SSc than in patients with either disorder alone (13,34) . Both disorders are autoimmune brotic diseases characterized by increased levels of the pro brotic cytokines TGF-β and IL-6, which have recently been suggested to be involved in the production and function of Th17 cells and regulatory T cells (Tregs), which play a role in acquired immunity (35)(36)(37)(38)(39) . Aberrant numbers and functions of natural killer (NK) cells have been reported in several different autoimmune disorders.…”

“…Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease characterized by portal in ammation, immune-mediated destruction of the intrahepatic bile ducts, and the presence of highly speci c anti-mitochondrial antibodies (AMAs) in the serum (1) . Patients with PBC occasionally suffer complications from other autoimmune diseases (2)(3)(4)(5) , such as Sjögren's syndrome, rheumatoid arthritis, Hashimoto's thyroiditis or scleroderma caused by either systemic sclerosis (SSc) or limited cutaneous SSc (lcSSc), which was previously called CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasias) syndrome. LcSSc is accompanied by CREST symptoms, although CREST cases that involve all of these symptoms are rare, with a high prevalence of Raynaud's phenomenon, sclerodactyly and telangiectasia and a lower prevalence of calcinosis and esophageal dysmotility (6) .…”

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes

“…14 Studies estimated the prevalence of PBC in SSc around 2%-3%, higher than in general population, but the prevalence of PBC-specific autoantibodies is even higher. [15][16][17][18] PBC seems more frequent in lcSSc than in dcSSc 19 and therefore associated with a higher frequency of limited skin involvement. 20 Previous studies suggest that the presence of PBC may identify a group of SSc patients with a milder systemic disease.…”

“…20 Previous studies suggest that the presence of PBC may identify a group of SSc patients with a milder systemic disease. 15,21 Although, the phenotype of PBC in patients with SSc still remains debated, some studies reported a less aggressive course of the liver disease and the patients mortality rather linked to SSc complications than to liver progression. [22][23][24] Given these data, the aim of this study was to describe clinical characteristics of two populations: PBC-SSc patients and of SSc patients with PBC-specific antibodies (first group) compared to a control SSc population free from HBI (second group), in order to evaluate not only cross-sectional data but also to determine the outcomes of such patients affected by two fibrotic conditions.…”

“…20 Previous studies suggest that the presence of PBC may identify a group of SSc patients with a milder systemic disease. 15,21 Although, the phenotype of PBC in patients with SSc still remains debated, some studies reported a less aggressive course of the liver disease and the patients mortality rather linked to SSc complications than to liver progression. 22–24…”