Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis

Background and purpose This study was undertaken to assess skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a treatable disease. Methods In this single center retrospective study, skin Congo red staining and intraepidermal nerve fiber density (IENFD) were evaluated in symptomatic ATTRv-PN patients and asymptomatic TTR gene mutation carriers between 2012 and 2019. Non-ATTRv subjects with suspected small fiber neuropathy who underwent skin biopsy during the same timespan were used as controls. Results One hundred eighty-three symptomatic ATTRv-PN patients, 36 asymptomatic carriers, and 537 non-ATTRv patients were included. Skin biopsy demonstrated amyloid depositions in 80% of the 183 symptomatic cases. Skin amyloid deposits were found in 75% of early stage ATTRv-PN patients, and in 14% of asymptomatic carriers. All 183 symptomatic and 34 of 36 asymptomatic patients displayed decreased ankle IENFD with a proximal-distal gradient distribution, and reduced IEFND correlated with disease severity and duration. Conclusions Our study demonstrates skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased IENFD a marker of disease progression. These results are of major importance for the early identification of ATTRv-PN patients in need of disease-modifying treatments.

Automated summary

This study aimed to assess the role of skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The results showed that skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased intraepidermal nerve fiber density (IENFD) is a marker of disease progression.