Primary Raynaud's Phenomenon Group Research Articles

Capillaroscopic differences between primary Raynaud phenomenon and healthy controls indicate potential microangiopathic involvement in benign vasospasms.

For primary Raynaud phenomenon (PRP), an otherwise unexplained vasospastic disposition is assumed. To test the hypothesis of an additional involvement of distinct ultrastructural microvascular alterations, we compared the nailfold capillary pattern of patients with PRP and healthy controls. A total of 120 patients with PRP (with a median duration of vasospastic symptoms of 60 [IQR: 3-120] months) were compared against 125 controls. In both groups, nailfold capillaroscopy was performed to record the presence of dilatations, capillary edema, tortuous capillaries, ramifications, hemorrhages, and reduced capillary density and to determine a semiquantitative rating score. Further, the capacity of finger skin rewarming was investigated by performing infrared thermography in combination with cold provocation. Unspecific morphologic alterations were found in both, PRP, such as controls, whereby the risk for PRP was four times as high in the presence of capillary dilations (CI: 2.3-7.6) and five times as high if capillary density was reduced (CI: 1.9-13.5). Capillary density correlated with thermoregulatory capacity in both hands in the PRP group, but not in controls. In addition, a negative correlation between the microangiopathy score and the percentage degree of rewarming in both hands was found for patients with PRP only. We found specific differences within the microvascular architecture between patients with PRP and controls. As a conclusion, PRP may not be an entirely benign vasospastic phenomenon, but might be associated with subtle microcirculatory vasculopathy. In addition, we suggest that the implementation of a scoring system might serve as guidance in the diagnostic process at least of patients with long-standing PRP.

Microcirculation disorders of the oral cavity in patients with primary Raynaud phenomenon.

INTRODUCTION Raynaud phenomenon is a medical condition in which the spasm of the arteries causes episodes of reduced blood flow. Potential disorders in the microcirculation of the oral mucosa may promote the occurrence of lesions. OBJECTIVES The aim of the study was to investigate the association of the frequency of oral cavity lesions with oral microcirculatory dysfunction in patients with primary Raynaud phenomenon (PRP) in comparison with healthy control group. PATIENTS AND METHODS Measurements of oral capillary flow were performed using laser doppler flowmetry (LDF) in 61 patients with PRP. In a group of 31 of 61 patients (group 1), the measurements were made during a Raynaud phenomenon (RP) attack. The RP attack was caused by stress initiated by the examination or the first visit itself. The RP attack was not deliberately caused by a cold test, vibration40w56 or any stress test. After 10 to 14 days, the measurements were repeated in all 61 patients and in the control group, and a dental examination was performed. Follow‑up visits were conducted every 3 months for a period of 12 months to monitor oral mucosa. RESULTS Differences in LDF were found between various anatomical points in both the PRP and control groups. On the first visit, the LDF flow in group 1 was significantly lower at all examined points in comparison with those in the control group. On the second visit, differences were observed in the LDF of the teeth and oral mucosa temperature in all patients with PRP in comparison with controls. Oral cavity lesions reported in the past and at follow‑up were significantly more common in patients with PRP. CONCLUSIONS Patients with PRP have dysfunction in the microcirculation of the oral mucosa and they more often have lesions in the oral cavity.

Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and Possible Clinical Associations: Results of a Multicenter International Study.

To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

Decreased interleukin-20 level in patients with systemic sclerosis: are they related with angiogenesis?

In this study, we aimed to evaluate the relation between angiogenesis indicators and T helper 17 cytokine group in patients with systemic sclerosis (SSc) which is a disease characterized by impaired angiogenesis and autoimmune response. In our study, patients with SSc are compared with patients with primary Raynaud's phenomenon (RP) and healthy controls. Forty SSc patients, 18 primary RP cases, and 20 healthy controls were included in our study. The demographic and clinical features of patients with SSc were recorded. The serum levels of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, interleukin (IL)-20, IL-22, and IL-23 were assessed. In the SSc group, IL-20 level was significantly lower than in both primary RP group and controls (p values <0.001). VE-cadherin level in SSc was significantly higher than in primary RP (p = 0.016). The IL-22 and IL-23 and VEGF levels of SSc, primary RP, and control groups were similar (p values >0.05). In SSc patients, IL-23 correlated negatively with VEGF (r = -0.36, p = 0.025) and positively with VE-cadherin (r = 0.55, p < 0.001). IL-20 levels in SSc patients correlated with disease duration (r = 0.32, p = 0.044). SSc patients with limited involvement had significantly higher VE-cadherin levels than SSc patients with diffuse involvement (p = 0.044). We observed that IL-20 which is an IL-10 group angiogenesis indicator was observed to be suppressed in SSc, suggesting abnormal angiogenesis.

The combination of laser Doppler perfusion imaging and photoplethysmography is useful in the characterization of scleroderma and primary Raynaud's phenomenon

Objective: To investigate simultaneously skin perfusion and digital artery pulsatility of hands in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc).Methods: In 100 SSc patients, 92 PRP patients, and 80 healthy controls, perfusion and digital artery pulsatility of the hands were investigated by laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG), respectively.Results: Both the mean value of mean perfusion and the mean value of sphygmic wave amplitude were lower (p < 0.0001) in the PRP group than in the SSc group, and also in the SSc group compared with the healthy controls. A positive correlation (r = 0.95) was found between the mean value of mean perfusion and the mean value of sphygmic wave amplitude. A homogeneous perfusion distribution pattern was present in 95% of the healthy controls, 93% of the PRP patients, and 4% of the SSc patients. PPG shows a homogeneous pattern in 95% of the healthy controls, 93% of the PRP patients, and 28% of the SSc patients. LDPI and PPG showed a positive concordance (p < 0.05) in homogeneous pattern evaluation. In the SSc patients, no correlation (r = 0.38) was observed between the mean value of sphygmic wave amplitude and the mean value of mean perfusion of each finger.Conclusion: LDPI and PPG can provide useful information in distinguishing patients with PRP and SSc, although nailfold videocapillaroscopy (NVC) is the best method for analysing microvascular damage in rheumatic diseases.

The Different Photoplethysmographic Patterns Can Help to Distinguish Patients With Primary and Sclerodermic Raynaud Phenomenon

IntroductionThe aim of this study is to investigate pulsatility of digital arteries of hands by means of photoplethysmography (PPG) in patients with primary Raynaud phenomenon (PRP) and systemic sclerosis (SSc) and to compare the results with those obtained in healthy controls. MethodsOne hundred five patients with SSc, 96 patients with PRP and 85 healthy controls were recruited in this study. Nailfold videocapillaroscopy and PPG were performed in healthy controls and patients. In patients with SSc, the capillaroscopic pattern was classified as early, active and late group pattern. A baseline PPG was recorded simultaneously in all 10 fingers of the hands. The photoplethysmographic curves were evaluated for morphology and amplitude of sphygmic wave. ResultsIn healthy controls group, PPG shows the presence of photoplethysmographic homogeneous pattern and high mean value of sphygmic wave amplitude. In PRP group, PPG demonstrates homogeneous photoplethysmographic pattern and low mean value of sphygmic wave amplitude. Finally, in the SSc group, photoplethysmographic pattern is dyshomogeneous, and the mean value of sphygmic wave amplitude is intermediate between the other 2 groups. The PPG findings are different in the 3 capillaroscopic groups of patients with SSc and 2 subsets of disease. ConclusionPPG represents a technique noninvasive to evaluate simultaneously in all 10 fingers of hands digital arteries pulsatility. PPG improves the evaluation of vascular damage in patients with primary and sclerodermic RP.

Nerve conduction velocities in the lower extremity in patients with Raynaud's phenomenon and clinical applications

The purpose of the study is to study the nerve conductivity of the tibial motor, peroneal motor, peroneal sensory, and sural nerves in patients with primary and secondary Raynaud's phenomenon (RP). Twenty each: primary RP, secondary RP, and normal controls. Electromyography using distal latency (DL) and nerve conduction velocity (NCV) as dependent variables. Peroneal nerve DLs were slower and NCVs were weaker for the secondary RP group compared to the primary RP group and controls. Tibial motor nerve DLs from slowest to fastest were: primary RP, secondary RP, and controls. NCV strength order was: secondary RP weakest, primary RP, and controls. Patients with secondary RP generally had the slowest DLs and the weakest NCVs, with differences most pronounced in the motor nerves. With the exception of the tibial motor nerve, patients with primary RP had similar NCVs to the control group. Neural mobilization techniques can be applied to assist with patient symptoms.

Laser Doppler-recorded venoarteriolar reflex in Raynaud's phenomenon

The aim of the study was to assess whether Laser Doppler-recorded venoarteriolar reflex (VAR) response to hand lowering can contribute to differentiate primary from secondary Raynaud's phenomena. Materials and methods Skin fingerpulp perfusion (PU) of each hand of 60 persons was investigated: 15 healthy controls; 15 primary Raynaud's phenomenon (RP) patients; 15 patients with Raynaud's phenomenon secondary to systemic sclerosis (SSc); 15 patients with Raynaud's phenomenon secondary to vibration exposure. Blood perfusion was monitored by Laser Doppler flowmetry (LDF) as initial values and at a temperature of 32 °C with hands on the sternum (PUh) and in dependency (PUd). VAR indices were analyzed: delta VAR (ΔVAR) calculated as (PUd−PUh); percent change of perfusion—{(ΔVAR/PUh)×100}; and vasoconstriction response—(PUd/PUh). Results Initial mean superficial skin temperatures and perfusions in Raynaud's phenomenon groups were significantly lower compared to healthy controls but with wide overlap of the values in individual cases. Venoarteriolar indices were significantly different between secondary Raynaud's phenomenon groups and healthy controls and between secondary and primary Raynaud's phenomenon groups. Percent changes were significantly higher in control and primary RP groups compared to secondary RP groups. Vasoconstriction indices between primary and secondary RP patients ( p<0.0001) and between controls and secondary RP patients ( p<0.0001) also differed. A loss of venoarteriolar reflex (ΔPU≥0) was established in 10.0% of primary, 53.3% of sclerodermic, and 36.7% of vibration-induced Raynaud's phenomenon patients. The significantly higher prevalence rate of impaired venoarteriolar reflex in secondary Raynaud's phenomenon patients proves local vasomotor dysfunction and reflects either postganglionar sympathetic insufficiency with vascular tone failure or altered smooth muscle cells' responses. Conclusions Laser Doppler flowmetry is a valuable noninvasive method for investigation of the very early skin venoarteriolar dysfunctions, for evaluation of focal autonomic dysregulation and skin vasomotor abnormalities in RP patients. Laser Doppler-recorded venoarteriolar reflex testing is a simple procedure and an adequate additional diagnostic tool, which contributes to diagnose RP and differentiate primary from secondary RP.

Digital iontophoresis of vasoactive substances as measured by laser Doppler imaging--a non-invasive technique by which to measure microvascular dysfunction in Raynaud's phenomenon.

To test the hypothesis that microvascular vasodilation is impaired in patients with systemic sclerosis (SSc) compared with patients with primary Raynaud's phenomenon (PRP) and healthy controls, using the technique of laser Doppler imaging to quantify blood flow responses to iontophoresis of vasoactive agents. Microvascular blood flow was measured by laser Doppler imaging before, during and after 120 s iontophoresis (30 microA) of 1% acetylcholine chloride (ACh, endothelium-dependent) and 1% sodium nitroprusside (NaNP, endothelium-independent). Two adjacent fingers of the left hand were studied, and the procedure then repeated on the right. Ten patients with limited cutaneous SSc (LCSSc), 10 patients with PRP and 11 healthy control subjects were studied. Vasodilation in response to both ACh and NaNP iontophoresis, as measured by 'area under the blood flow.time curve' (AUC), normalized for baseline flux, was similar in the control and PRP groups, but was diminished in the LCSSc group compared with both control and PRP groups (ACh results: control vs LCSSc P = 0.028, PRP vs LCSSc P = 0.005; NaNP results: control vs LCSSc P = 0.004, PRP vs LCSSc P = 0.005). There were no differences between groups in baseline flux values nor in voltages required to drive the 30 microA current. Both endothelium-dependent and endothelium-independent vasodilation are impaired in patients with LCSSc. Vasodilatory responses in patients with PRP are similar to those in controls. If reproducibility is confirmed to be satisfactory, then these techniques could be used to examine disease progression over time and responsiveness to vasoactive treatment, thus facilitating clinical trials.

Characteristic of microcirculatory changes in patients with primary Raynod's phenomenon by videocapillaroscopy

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Raynaud&#x0027;s phenomenon: Infrared functional imaging applied to diagnosis and drug effects.

A non-invasive, innovative approach to the study of Raynaud&#x0027;s Phenomenon is proposed. A group of patients, with respect of a control group, underwent a simultaneous assessment of thermal properties of all ten fingers using infrared functional imaging (IRFI). The assessment highlighted a quite different behaviour between patients with Primary- (PRP) and those with scleroderma - Raynaud&#x0027;s Phenomenon (SSc) and, compared with other existing techniques, seems to be an objective and effective tool to discriminate between PRP and RP secondary to SSc. 18 healthy volunteers (Norm), 20 Primary Raynaud&#x0027;s Phenomenon (PRP) and 20 Secondary Scleroderma (SSc) patients were studied subsequently to clinical evaluation and nail fold capillaroscopy. High-resolution infrared imaging of finger re-warming processes, immediately after a 2 min cold stress, allowed to identify objective parameters. Temperature integral Q (the temperature evaluation of the area under the time-temperature curve along the re-warming period) provided particularly effective figures in describing thermal properties of the fingers. Grand average Q values were (383.4 &#x2213; 12.5) &#x00B0;C×min, (502.9 &#x00B1; 88.1) &#x00B0;C×min and (1022.0 &#x00B1; 110.2) &#x00B0;C×min for the PRP, SSc and Normal groups, respectively. Separate evaluation of the temperature integral for each finger leads to very similar results for the fingers of all the PRP patients; a different thermoregulatory response was observed in SSc patients. The sensitivity of the method in order to distinguish healthy from ill fingers was 100&#x0025;. The specificity in distinguishing SSc from PRP was 95&#x0025;. In addition, IRFI parameters provided a better understanding of the impaired control of the finger&#x0027;s temperature in PRP and SSc with respect to the Normal group. This pilot study also applied IRFI for the measurement of drug effects in patients with Raynaud&#x0027;s Phenomenon. Sixteen out of twenty SSc patients were tested in a single 1-hour session of N-acetylcysteine infusion. IRFI clearly documented a significant increase of face and hands temperature during the drug administration. The grand average value of the finger&#x0027;s temperature after the 1 hour NAC administration was (29.6 &#x00B1; 3.7) &#x00B0;C, while its value before was (27.9 &#x00B1; 3.7) &#x00B0;C (p&#x003C;0.001). N-acetylcysteine seems to act as a vasodilator in patients with Raynaud&#x0027;s phenomenon secondary to systemic sclerosis (scleroderma).

Non-invasive assessment of vascular reactivity in forearm skin of patients with primary Raynaud's phenomenon and systemic sclerosis.

We have non-invasively assessed neurovascular control mechanisms in forearm skin of 10 healthy control subjects, eight patients with primary Raynaud's phenomenon (PRP) and 10 patients with systemic sclerosis (SSc) by iontophoresing acetylcholine (endothelial dependent), sodium nitroprusside (endothelial independent) and adrenaline, and measuring subsequent blood flow responses by dual-channel laser Doppler. Because basal forearm blood flow is low, adrenaline response was assessed by attenuation of reperfusion hyperaemia following 60 s of upper arm occlusion. Reperfusion hyperaemia prior to adrenaline iontophoresis differed significantly between groups (F2.21 = 4.3, P = 0.03), being lowest in the SSc and highest in the PRP group. However, the degree of attenuation of this hyperaemia by adrenaline did not differ between groups and all groups demonstrated similar vasodilatory responses to acetylcholine and to sodium nitroprusside. These findings may reflect that abnormalities in vascular tone in patients with Raynaud's phenomenon are local to the digits, or that vasoactive agents not examined in this study play a key role.

Effect of Magnesium Sulfate Infusion on Circulating Levels of Noradrenaline and Neuropeptide-Y-Like Immunoreactivity in Patients with Primary Raynaud's Phenomenon

The effect of a short-term magnesium sulfate (MgSO4) infusion on venous plasma concentration of noradrenaline (NA) and neuropeptide-Y-like immunoreactivity (NPY-LI) was investigated in 12 women with primary Raynaud's phenomenon (PRP) and in 12 healthy matched controls. The Raynaud's patients did not demonstrate any significant changes in mean basal plasma NA concentration (0.29 +/- 0.15 vs 0.37 +/- 0.09 ng/mL, ns) after MgSO4 infusion. However, in the controls there was more than twice the amount of circulating noradrenaline (cNA) (0.21 +/- 0.14 vs 0.54 +/- 0.22 ng/mL, P < 0.001) after MgSO4 infusion, compared with the preinfusion value. Measurements during the cold pressor test prior to the MgSO4 infusion showed a significant increase of cNA in both the PRP group and the control group (from 0.29 +/- 0.15 to 0.33 +/- 0.16 ng/mL, P < 0.05, and from 0.21 +/- 0.14 to 0.29 +/- 0.16 ng/mL, P < 0.005, respectively). After MgSO4 infusion the levels of cNA during the cold pressor test increased significantly only in the PRP group (from 0.37 +/- 0.09 to 0.41 +/- 0.11 ng/mL, P < 0.05). Circulating NPY-LI concentrations increased significantly during MgSO4 infusion in the Raynaud's patients as well as in the controls from 105 +/- 21 to 127 +/- 23 pmol/L, P < 0.05, and from 107 +/- 17 to 132 +/- 27 pmol/L, P < 0.01, respectively. There were no detectable changes during the cold pressor tests in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cold pressor test on circulating atrial natriuretic peptide 99-126 (ANP) in patients with Raynaud's phenomenon and influence of treatment with magnesium sulphate and nifedipine.

The effect of a standardized cold pressure test (CPT) on the venous concentration of immunoreactive atrial natriuretic peptide (irANP) was studied in 12 females with primary Raynaud's phenomenon (PRP) and 12 female age-matched controls. The test was performed at the end of three stages. During the first stage no medication was given. During the second stage a magnesium infusion was given. After fourteen days of medication with a calcium antagonist (Nifedipine) the third stage of the study was performed. The venous irANP increased significantly (P < 0.05) 10 min after the start of the CPT both in the PRP group and in the control group (136 +/- 39 to 159 +/- 54 and 153 +/- 45 to 179 +/- 40 pg ml-1, given as mean and SD). Baseline irANP did not change in the PRP group after treatment with magnesium or nifedipine. In the control group nifedipine treatment significantly (P < 0.01) lowered venous irANP compared to the no treatment or magnesium sulphate infusion stages (128 +/- 31 vs. 153 +/- 45 and 160 +/- 41 pg ml-1). After the CPT in both PRP group and control group the venous irANP did not increase either during magnesium sulphate infusion or nifedipine treatment. In conclusion the study has demonstrated that a standardized CPT results in a delayed increase in irANP in venous plasma and that magnesium sulphate infusion and nifedipine treatment prevent this increase. Furthermore, our data do not suggest a role for irANP in the symptomatology of primary Raynaud's phenomenon.