A prospective study of small fiber neuropathy in AL amyloidosis

The peripheral nervous system (PNS) is commonly affected in immunoglobulin light chain amyloid protein (AL) amyloidosis. PNS involvement and particularly small fiber neuropathy (SFN) is often clinically underestimated, requiring a standardized approach for comprehensive assessment. We prospectively evaluated the prevalence and clinical significance of SFN in 81 patients with newly diagnosed AL amyloidosis using clinical examination, nerve conduction studies (NCSs), quantitative sensory testing (QST) examination and distal-leg skin biopsy. Neuropathy was detected in 89% of patients and SFN in 65%. Combined small and large fiber neuropathy was seen in 48.1%, pure large fiber neuropathy in 20% and pure SNF in 10%. Older age was a significant risk factor for SFN (OR 1.06, 95% CI 1.01-1.12, <i>p</i> = .014); patients with SFN were also more likely to have soft tissue involvement (OR 7.1, 95% CI 1.5-33.4, <i>p</i> = .013). After a median follow-up of 37.5 months, SFN was associated with poorer overall survival (OS) and it emerged as an independent prognostic factor for early mortality (<12 months) in multivariate analysis (HR 4.3 95% CI 1.23-15.04, <i>p</i> = .023). Our study demonstrates the high prevalence and clinical significance of SFN as an adverse factor for survival and indicates the need for multiparametric neurological evaluation in patients with AL amyloidosis at diagnosis.