The role of dermatological manifestations in the early diagnosis of Fabry disease: a scoping review

Fabry disease (FD) is a rare X-linked lysosomal storage disorder characterized by the progressive accumulation of globotriaosylceramide in multiple organs. Despite the availability of disease-specific therapies, diagnosis is often delayed due to heterogeneous and nonspecific manifestations. This review aimed to synthesize current evidence on dermatological manifestations of FD and their potential contribution to earlier disease recognition. A scoping review was conducted following the Arksey and O'Malley framework and the PRISMA-ScR guidelines. PubMed, Scopus, and Web of Science were searched for relevant studies, and additional records were identified through snowballing of reference lists from retrieved reviews. Thirty-two records were included, comprising data on 2,209 patients, with detailed patient-level information available for 146 individuals. Dermatologists were involved in the diagnostic process in 66% of the included studies, and 69% of these reported a potential contribution of dermatological evaluation to earlier disease recognition. Angiokeratomas (88% of included studies) and hypohidrosis (50% of included studies) were the most frequently reported cutaneous manifestations. Skin biopsy or histopathological examination was reported in 59% of included studies and was the most frequently reported dermatological investigative technique. Among patients with dermatological manifestations and available diagnostic delay information, 66% had a reported diagnostic delay of 1–10 years. These findings suggest that dermatological manifestations may contribute to earlier recognition of FD. However, they should be interpreted cautiously given the descriptive nature of the available evidence, the absence of an appropriate comparator group, and the potential influence of selection and publication bias.