A small proportion of PSC patients had elevated serum IgG4. In these patients parameters of liver disease severity were more pronounced and time to liver transplantation was shorter, suggesting a more severe disease course. It is possible that this subset of patients behaves similarly to autoimmune pancreatitis patients with biliary strictures, and could potentially respond to corticosteroids. Testing PSC patients for IgG4 and treating those with elevated levels with corticosteroids in clinical trials should be considered.
Primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA) are chronic medical conditions in which, although the etiology is uncertain, autoimmune features predominate. These two conditions are, in fact, multisystemic diseases, with a multitude of manifestations that are not limited to their target end organ. It has been well established that patients with PBC may have musculoskeletal complaints and patients with RA may have evidence of hepatic dysfunction. Both of these conditions are fairly rare, with RA being found in approximately 1% of the population and PBC being found in approximately 20/100,000 women and 2/100,000 men.The likelihood of these uncommon conditions occurring in the same patient is very rare and unusual. We have identified a unique group of 25 patients who have met disease-defining criteria for both RA and PBC. Awareness of this combination should prompt rheumatologists to assess for PBC with antimitochondrial antibody testing in patients with abnormal liver tests and also to raise awareness that abnormal liver tests in RA patients are not always due to drugs.
Fatigue is a common symptom in primary biliary cirrhosis (PBC). In animal models of cholestasis, abnormalities in serotonin neurotransmission are observed with fatigue. The role of selective serotonin reuptake inhibitors in fatigue-related PBC, however, is unknown. A double-blind, placebo-controlled study design was conducted to determine the safety and efficacy of fluoxetine for the treatment of fatigue in PBC. Patients were randomized to fluoxetine, 20 mg daily, or matched placebo for 8 weeks' duration. Fatigue was assessed by the Fisk Fatigue Impact Scale (FFIS). The primary study endpoint was a > or =50% reduction in overall FFIS score at the end of treatment. Health-related quality of life (HRQL) was assessed as a secondary endpoint. Among 220 consecutively screened patients, only 18 (9%) eligible individuals were randomized to fluoxetine (n=10) or placebo (n=8) for 8 weeks. Baseline variables including median FFIS scores (52 vs 42; P=0.21) were similar between treatment arms (P > 0.05). After 8 weeks of therapy, no statistically significant change in median FFIS score was observed in the fluoxetine group. Median FFIS score in the placebo group was reduced (42 to 28), but not statistically significant. No difference in HRQL was observed between treatment arms after 8 weeks. Fourteen (78%) patients completed therapy, while four (22%) individuals withdrew from the trial. Three of the four patients had drug-related adverse events with fluoxetine. In this study, fluoxetine did not improve fatigue in PBC and was associated with adverse events.
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