Phenotyping peripheral neuropathies with and without pruritus: a cross-sectional multicenter study

Pruritus often escapes physicians' attention in patients with peripheral neuropathy (PNP). Here we aimed to characterize neuropathic pruritus in a cohort of 191 patients with PNP (large, mixed, or small fiber) and 57 control subjects with deep phenotyping in a multicenter cross-sectional observational study at 3 German sites. All participants underwent thorough neurological examination, nerve conduction studies, quantitative sensory testing, and skin biopsies to assess intraepidermal nerve fiber density. Patients filled in a set of questionnaires assessing the characteristics of pruritus and pain, the presence of depression and anxiety, and quality of life. Based on the severity of pruritus and pain, patients were grouped into 4 groups: "pruritus," "pain," "pruritus and pain," and "no pruritus/no pain." Although 11% (21/191) of patients reported pruritus as their only symptom, further 34.6% (66/191) reported pruritus and pain. Patients with pain (with or without pruritus) were more affected by anxiety, depression, and reduced quality of life than control subjects. Patients with pruritus (with and without pain) had increases in cold detection threshold, showing Aδ-fiber dysfunction. The pruritus group had lower intraepidermal nerve fiber density at the thigh, concomitant with a more proximal distribution of symptoms compared with the other PNP groups. Stratification of patients with PNP by using cross-sectional datasets and multinominal logistic regression analysis revealed distinct patterns for the patient groups. Together, our study sheds light on the presence of neuropathic pruritus in patients with PNP and its relationship with neuropathic pain, outlines the sensory and structural abnormalities associated with neuropathic pruritus, and highlights its impact on anxiety levels.