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 cm2, IQR 9.7-22.8 and 8.3-16.9; patients 6.9 and 8.0 cm2, 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.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.