Axon reflex-mediated vasodilation is reduced in proportion to disease severity in TTR-FAP.

Objective: To evaluate the area of the vascular flare in familial amyloid polyneuropathy (FAP).

Methods: Healthy controls and patients with genetically confirmed FAP were prospectively examined, on the upper and lower limbs, for thermal sensitivity (Medoc TSA-II thermal analyzer) and for axon reflex-mediated flare. The latter was induced by iontophoresis of histamine on the forearm and leg on 2 different visits. We used laser Doppler imaging (LDI) to measure the flare area (LDIflare).

Results: Six patients had FAP of variable severity; 1 had generalized analgesia secondary to leprosy (used as a positive control). The median Neurological Impairment Score-Lower Limbs (NIS-LLs) was 6 (0-27). The warmth detection thresholds in the feet were higher in patients (median 43°, interquartile range 39.0°-47.6°) compared with controls (37.4°, 35.3°-39.2°), indicating small fiber impairment. On the leg, LDIflare was smaller in the patients on 2 consecutive visits (controls: median 13.0 and 13.3 cm, IQR 9.7-22.8 and 8.3-16.9; patients 6.9 and 8.0 cm, 2.6-10.8 and 6.4-12.1; = 0.011). LDIflare on the leg was correlated with NIS-LL (Spearman rank correlation 0.73, = 0.09 on the first visit; Spearman rank correlation 0.85, = 0.03 on the second visit).

Conclusions: Our study underscores that histamine-induced axon reflex-mediated vascular flare on the leg is reduced in proportion to disease severity in patients with FAP.