| Description: |
Objective: Fatal Familial Insomnia (FFI) is an intractable and rare inherited prion disease characterized by sleep disturbances, rapidly progressive dementia, and dysautonomic symptoms. We aimed to estimate the prevalence of “pruritus” as a symptom onset of the disease. Materials and Method: Data from FFI cases visited at the Istituto Besta and referred to the period 2018-2024 were retrieved. A literature search was conducted on February 19th 2025 via PubMed, utilizing the search string: “(FFI OR fatal familial insomnia) AND (case report OR case series OR case history OR registry)”. Results: Pruritus has been reported at onset in 3 patients: in 2 cases it occurred with insomnia, myoclonus, and cognitive decline, while in one case it was isolated. The symptom was experienced by 3 females belonging to 2 different families. In all situations, pruritus started from the head, becoming then widespread and presenting, in one case, a migrant distribution. Due to the enrollment in a clinical trial (NCT04846335, Sponsor Negri Institute, Collaborator Telethon), all cases experienced a long-term administration of Doxycycline. In two cases, pruritus occurred in association with neuropathic pain) and with the M/M genotype at codon 129 in the PRNP gene. From Pubmed, 241 results were retrieved including 180 cases, 8 of them experiencing pruritus. In particular, 3 out of 23 cases were reported in a German cohort (1). Discussion: Pruritus occurs rarely in FFI, however, since this symptom may characterize the prodromal phase, it is of particular interest. Three main hypotheses have been proposed to explain its origin: it may be caused by a deposition of the abnormal prion protein 1.in the skin, 2.in the peripheral nerves/dorsal root ganglia, 3.in the central pathways. Finally, considering the long-term assumption of Doxycycline, a “toxic / skin sensitization” pathogenesis may also be hypothesized. The “central hypothesis” is the most probable, supported by brain imaging findings. However, pathological prion protein has been ... |