Pruritus of unknown origin and elevated total serum bile acid levels in patients without clinically apparent liver disease

Background and Aim:  Generalized pruritus of unknown origin (PUO) is a highly distressing condition that is unrelated to any underlying dermatologic or systemic disorder (e.g. cholestasis). Little is known about the potential contribution of elevated total serum bile acid (TSBA) levels to PUO. Our aim in the present study was to investigate the role of elevated TSBA levels in patients with PUO and the efficacy of ursodeoxycholic acid (UDCA) and cholestyramine therapy. Methods:  Retrospective study comprising 117 patients with chronic pruritic conditions (PUO, atopic disease, asteatotic eczema, latent cholestasis, etc.); 99 patients with available TSBA levels were included and compared with healthy controls. Results:  Elevated TSBA levels were detected more frequently in patients with chronic pruritic diseases than in the control population (28.28% vs 6%; P < 0.001) with significantly higher pathological absolute levels (mean 17.45 ± 34.46 µmol/L vs 6.02 ± 4.73 µmol/L; P = 0.001). Patients with PUO (n = 18) showed the second-highest prevalence of pathological bile acid level elevation (83.3%; control population 6%; P < 0.001), after patients with subclinical cholestasis and presented with particularly high TSBA serum values (mean 37.79 ± 53.38 µmol/L; P < 0.001). Cholestyramine (n = 9) and UDCA (n = 8) therapy were both effective in lowering TSBA levels and lead to substantial improvement of pruritus in patients with elevated TSBA levels. Conclusions:  Total serum bile acid levels are elevated in a high proportion of patients with PUO. These results provide evidence of a potential involvement of subclinical cholestasis in the pathogenesis of PUO. We suggest that evaluation of TSBA levels should be included in the diagnostic work-up of patients with chronic unexplained pruritus.