Therapeutics in chronic pruritus of unknown origin

Chronic pruritus of unknown origin (CPUO) is a common condition that is underrecognized and underdiagnosed. Patients suffer from 6 or more weeks of pruritus with no identified cause, or with multiple potential causes, of which the primary cause cannot be determined. Despite being a common condition and prevalent in nearly 30% of the elderly in certain populations, most patients suffer from CPUO for years from inadequate treatments for itch and are made to undergo extensive diagnostics. There is no FDA-approved treatment for CPUO, and providers are often tasked to treat CPUO patients with limited knowledge and guidance on CPUO and its treatments. However, recent breakthroughs in antipruritic therapeutics have led to an increase in therapies available for CPUO patients. These include a variety of both pharmacological and nonpharmacological interventions, as well as topical and systemic therapies. Newer therapies such as biologics and Janus kinase inhibitors are currently under investigation due to their therapeutic effects in other pruritic diseases and are promising for treating CPUO. Here, we review the various therapeutic options that are currently available or are on the horizon, with a special emphasis on the therapies antipruritic mechanism, available clinical evidence of efficacy and safety, and the appropriate contexts for their application. By doing so, we hope to educate clinicians on the known treatments for pruritus and their applicability to CPUO to guide optimal management of this highly prevalent disease.