Primary Biliary Cirrhosis Associated with Systemic Sclerosis: Diagnostic and Clinical Challenges

Abstract

Patients with primary biliary cirrhosis (PBC) often have concurrent limited systemic sclerosis (SSc). Conversely, up to one-fourth of SSc patients are positive for PBC-specific antimitochondrial antibodies (AMA). The mechanisms responsible for the co-occurrence of these diseases are largely unknown. Genetic, epigenetic, environmental, and infectious factors appear to be important for the pathogenesis of the disease, but the hierarchy of events are not well defined. Patients with SSc and PBC have an increased morbidity and mortality compared with the general population, but whether the presence of both diseases in an affected individual worsens the prognosis and/or outcome of either disease is not clear. Some case reports suggested that the presence of SSc in PBC patents is associated with a more favorable prognosis of the liver disease, whereas others report an increased mortality in patients with PBC and SSc compared to patients with PBC alone. This paper discusses the features of patients with PBC-associated SSc. Our aims are to clarify some of the pathogenetic, diagnostic, and clinical challenges that are currently faced in the routine management of these patients. We also intend to provide some practical hints for practitioners that will assist in the early identification of patients with PBC-associated SSc.

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

“…The known adverse effects of pirfenidone on the GI system, skin, and liver 17,18 were of interest in SSc-ILD because these organ systems are also affected in patients with SSc 1,24,25 . Although GI AE were common, this was not unexpected because of the high frequency of such events observed in clinical trials of pirfenidone in patients with IPF, although patients with moderate to severe gastroesophageal reflux disease (UCLA GIT reflux subscale score > 1.0) were excluded from our study.…”

“…Pirfenidone also significantly reduces the risk of mortality in patients with IPF compared with placebo and can benefit patient outcomes including the 6-min walking distance and dyspnea 17,23 . However, pirfenidone is known to be associated with adverse events (AE) of the liver, gastrointestinal (GI) system, and skin 17,18 , which may overlap with the organ systems frequently affected in patients with SSc 1,24,25 . Therefore, in the setting of SSc-ILD, it is important to investigate the tolerability of pirfenidone before assessing its efficacy.…”

Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis

“…The most PBC-specific antinuclear antibody (ANA) patterns detected by indirect immunoflourescence (IFL) are ''nuclear-rim'' and ''multiple nuclear dots'' produced by antibodies directed against the nuclear membrane gp210 and nucleoporin 62, and the nuclear body sp100, sp140, and promyeolocytic leukaemia proteins, respectively [21][22][23][24][25]. A considerable proportion of PBC patients show both PBCspecific ANA patterns [26]. Disease-specific ANA may be present in PBC patients who are initially found to be AMA negative, as well as in asymptomatic individuals and family members of PBC patients [25].…”

“…Less common, but still observed in a considerable proportion of PBC patients, is SSc [57][58][59]. Conversely, PBC is the most common form of liver disease reported in SSc patients [26].…”

From pruritus to CREST syndrome in a middle aged woman

“…According to the literature these two pathologies seem to be closely related 9,10 , not only on their clinical manifestations, since they are both types of fibrotic disease, but also on their laboratory findings and therefore, their diagnostic approach which is based on antibodies (ANA, AMA, ACAs).…”