Cutaneous manifestations of Fabry disease: A systematic review

Abstract

Fabry disease (FD) is a rare X-linked lysosomal storage disorder resulting in potential debilitating accumulation of glycosphingolipids in organs such as skin, nerves, heart, kidneys, lungs, and the central nervous system. Skin is easily investigated and can guide clinicians to diagnose FD, minimizing delay of enzyme substitution therapy. This systematic review followed the PICO and PRISMA guidelines. Using Web of Science, PubMed, and Embase, a total of 968 studies were retrieved by January 1, 2024. All clinical studies describing the skin characteristics and abnormalities of FD patients were included. After inclusion of articles, the methodological quality was assessed using the QUADAS-2 critical appraisal checklist. Twenty-three studies were included. Different skin manifestations were described in FD patients. Fifteen studies described angiokeratomas, five studied telangiectasias, 13 studied sweat abnormalities (anhidrosis/hypohidrosis/hyperhidrosis), nine described lymphoedema, and two reported hair abnormalities. Sweat abnormalities were the most common skin manifestation, affecting 57.6% of patients with FD; angiokeratomas were observed in 51.5% of patients. A high prevalence (16.5%) of lymphoedema was seen in a large study (n = 5487). Skin involvement appeared age-dependent and increased with age. Quality assessment showed high or unclear risk of bias in 19/23 studies. We summarized data on skin manifestations in 10 757 FD patients. The pathogenesis of sweat abnormalities and the occurrence of cutaneous vascular lesions, such as angiokeratomas and telangiectasias, in only half of FD patients remains poorly understood. Enzyme replacement therapy generally did not reduce skin manifestations in FD patients. Direct comparisons between studies were challenging due to variations in reported outcomes.