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(2), IQR 9.7–22.8 and 8.3–16.9; patients 6.9 and 8.0 cm(2), 2.6–10.8 and 6.4–12.1; p = 0.011). LDIflare on the leg was correlated with NIS-LL (Spearman rank correlation 0.73, p = 0.09 on the first visit; Spearman rank correlation 0.85, p = 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.