[When the etiology remains unclear: status quo of chronic pruritus of unknown origin]

Chronic pruritus of unknown origin (CPUO) is diagnosed when no underlying cause for the itching can be identified. Although the exact pathophysiology remains largely unclear, neuroimmune mechanisms are believed to play an important role. Clinically, CPUO typically begins on normal appearing skin, but secondary scratch excoriations may develop over time. Itching is usually moderate to severe, occurs daily, and is associated with substantial disease burden and impairment of quality of life. Since CPUO is a diagnosis of exclusion, a comprehensive diagnostic evaluation is necessary to rule out potential causes of chronic itching. This includes a comprehensive general and itch-specific medical history, a complete dermatological examination, a core laboratory workup, and individually tailored complementary diagnostic procedures. Currently, there is no approved treatment for CPUO. According to German directives, antihistamines can be prescribed for severe, persistent itching; however, their effectiveness is limited. The German guideline recommends the use of antihistamines and gabapentinoids as first-line therapies, while paroxetine, mirtazapine, phototherapy, and opioid receptor modulators constitute alternative 2nd to 5th line options. Biologics, particularly dupilumab and nemolizumab, are currently being investigated in clinical trials and may expand the therapeutic options for this indication in the future.