Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome

Abstract

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…Cold acra have been found in FS similar to Raynaud's phenomenon (CREST) or even Raynaud's disease, yet less pronounced [98]. The role of endothelial dysfunction in primary and secondary Raynaud's phenomenon has been demonstrated with evidence from various modalities including autonomic nervous stress tests like the cold pressor test [121][122][123][124][125]. It may be regarded a heterogeneous syndrome involving endothelial dysfunction as a key player but not every form entails a propensity for atherosclerosis.…”

Impairment of microcirculation and vascular responsiveness in adolescents with primary Raynaud phenomenon

“…Previous studies in the adult primary RP population showed that the initial neurogenic vasodilator response to heating was not affected by the disease [ 27 , 38 ]. Few capillary microscopy studies have investigated the vasculature in RP children, but none of them described functional investigations of responsiveness to heat [ 39 , 40 ].…”

“…The loss of CGRP- and VIP-containing nerves in the cutaneous microvasculature [ 17 , 18 ] and abnormal response of cold-sensitive nerves were described in primary adult RP patients [ 50 ]. A recent study found a strong relationship between microangiopathy and higher serum endothelin-1 and E-selectin levels in children with RP [ 40 ], although previous data had not confirmed the diagnostic value of endothelin concentration [ 51 ]. It is well-established that peptide mediators play a role in neurovascular responses, but there is limited data about neuropeptide concentration changes in primary RP [ 12 ].…”

Contactless Monitoring of Microcirculation Reaction on Local Temperature Changes

“…It is manifested by the increased reactivity of microvessels in response to cold stress. However, preclinical assessment of vascular reactivity is possible only with the help of the nailfold capillaroscopy [6]. Diseases such as type 2 diabetes mellitus (DM) or Raynaud's disease cause a disturbance of blood microcirculation or local neural activity, which leads to impaired thermoregulation and thermal sensation, both locally (mainly in the limbs) and generally, thus increasing the risk of heat exhaustion or heat stroke [7].…”