Raynaud's Phenomenon Group Research Articles

Is there any Sympathetic Skin Response Abnormality in Raynaud Phenomenon?

ObjectivesThis study aimed to evaluate sympathetic skin response (SSR) among patients with Raynaud phenomenon (RP). SSR is a technique for assessment of the damage of peripheral neuropathies and the disorders of the sympathetic system.MethodsBetween January 2015 and December 2018, approximately 20 patients with RP and 20 healthy subjects (control group) were recruited from patients referred to the outpatient clinics of Shiraz University of Medical Sciences, Shiraz, Iran. All participants were clinically examined and the SSR was evaluated using a standard protocol. SSR is abnormal when the latency is prolonged and/or the amplitude is reduced.ResultsThe RP group consisted of 19 women (95%) and one male (5%); three patients (15%) had primary Raynaud’s phenomenon (PRP) and 17 patients (85%) had secondary Raynaud’s phenomenon. The control group consisted of 16 women (80%) and four males (20%). The mean age of the RP group and control subjects was 43.1 ± 9 and 36.7 ± 8.6 years, respectively. The SSR to the electrical stimulus was absent in three patients with PRP. The total median nerve mean latencies in the upper limb were 1.90 ± 0.57 and 1.19 ± 0.52 seconds for the RP group and control groups, respectively (P <0.001). These findings revealed significantly prolonged SSR latencies in the RP group, while the mean amplitude showed no significant differences in both groups (P = 0.756).ConclusionAbsence or prolonged latency of SSR was associated with the disorders of the unmyelinated axons in the sympathetic system. The findings of the present study suggested the disorders of unmyelinated axons in Raynaud’s phenomenon.

Pain Intensity, Pressure Pain Hypersensitivity, Central Sensitization, and Pain Catastrophizing Related to Vascular Alterations in Raynaud's Phenomenon: A Preliminary Case-Control Study.

To evaluate pain intensity, widespread pressure pain, central sensitization (CS), and catastrophizing between subjects with primary and secondary Raynaud's phenomenon (RP) and healthy controls and to compare the relationships between vascular impairment and pain perception. A preliminary case-control study was performed with a total sample of 57 participants (37 with RP). Sociodemographic data, clinical/vascular data, and pain variables (pain intensity, pressure pain sensitivity, pain magnitude and threshold, CS, and catastrophizing) were registered. Results were analyzed by analysis of covariance and Pearson correlation. Participants with RP had a lower basal temperature (more vasoconstriction) in their hands (P ≤ 0.012), higher pain intensity (P ≤ 0.001), higher electrical pain magnitude (P < 0.001), and lower pressure pain (P ≤ 0.05) and electrical pain (P < 0.001) thresholds in comparison with healthy controls. Secondary RP participants showed a significantly higher level of CS compared with controls and primary RP participants (P = 0.001). Catastrophizing was higher in the primary and secondary RP (P ≤ 0.001) groups than in controls. No correlations were observed between severity of vasoconstriction and pain variables. RP participants showed bilateral hypersensitivity to pressure pain. However, the severity of vascular alterations seems not to be related to central pain experiences. Additional mechanisms such as catastrophizing may influence pain in RP; nevertheless, central sensitization only appears to be involved in the secondary form of RP.

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.

The role of endothelial microparticles in autoimmune disease patients with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a microvascular disorder characterized by episodic peripheral vasospasm and ischemia and is commonly found in patients with autoimmune diseases (AID). The vasomotor homoeostasis and endothelial cells damage are involved in RP. Endothelial microparticles (EMPs) may act as a biomarker for endothelial damage. The aim of this study is to investigate the correlation between the levels of microparticles (MPs) and microvasculopathy in AID with RP. Thirty-seven patients with AID and RP (RP group) and 27 patients with AID but without RP (non-RP group) were enrolled. The microvasculopathy score of RP was graded by nailfold capillary microscopy. The plasma levels of MPs were measured by flow cytometry utilizing specific labels for endothelial MPs (CD105 and CD144) and annexin V staining for phosphatidylserine bearing-MPs (annexin V+MPs). The levels of circulating EMPs (CD105+p=0.005, CD144+p=0.004), and the annexin V+MPs (p<0.001) were significantly elevated in the RP group compared with the non-RP group. Moreover, the high microvasculopathy scores were closely related with annexinV+MPs levels in the RP group (p=0.041). Levels of circulating EMPs and annexin V+ MPs are elevated in AID patients withRP indicate the endothelial damage and endothelial dysfunctions. In addition, levelsof annexin V+MPs canpredict the severity of microvasculopathy in AIDwith RP.

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.

Níveis séricos elevados de homocisteína em pacientes pediátricos com fenômeno de Raynaud primário

Raynaud's phenomenon (RP) is a paroxysmal and recurrent acral ischemia resulting from an abnormal arterial vasospastic response to cold or emotional stress. Homocysteine, a sulphured amino acid, has been linked to cardiovascular and neurodegenerative diseases, diabetes, thrombosis, and bone fragility. Homocysteine has been also linked to the pathogenesis of RP, as increased serum homocysteine (S-homocysteine) levels were observed in patients with RP. As all publications concerning S-homocysteine in RP involved only adult patients, our aim was to evaluate S-homocysteine in children and adolescents with RP. Nineteen patients (two boys and 17 girls; mean age 16.1 ± 2.2 SD) with primary RP were enrolled. The controls were 51 children and adolescents (21 boys and 30 girls; mean age 15.1 ± 1.8 SD). The S-homocysteine level was significantly higher in the RP group in comparison with controls (11.2 ± 2.4 vs. 8.0 ± 2.0 µmol/L; P = 0.00001). S-homocysteine levels in RP were not age-dependent. Paediatric patients with RP have increased S-homocysteine levels, suggesting that homocysteine plays an important role in the development of vascular dysfunction, even at an early age.

Prevalence of paraneoplastic rheumatic syndromes and their antibody profile among patients with solid tumours

The aims of this study were to assess the prevalence of paraneoplastic rheumatic syndromes in a cohort of patients with newly diagnosed solid tumours and to describe their autoimmune profile, comparing it to the controls. Screening questionnaires (3,770) were distributed, and during a three-step study, 94 patients were confirmed to have both paraneoplastic syndrome and oncology diagnoses. Three control groups-patients with undifferentiated arthritis, Raynaud's phenomenon for non-malignant causes and solid tumours only-were designed to compare with the paraneoplastic cases and their immunology profile. The prevalence of paraneoplastic rheumatic syndromes was 2.65% (95% CI 0.21-3.20). The group of patients with arthritis and the group of patients with Raynaud's syndrome were found to prevail among other clinical presentations of paraneoplastic rheumatic syndromes. Both paraneoplastic syndromes were linked to malignancies of the urogenital system. Antinuclear antibodies were found to be similarly frequent in the paraneoplastic arthritis, paraneoplastic Raynaud's phenomenon and the solid tumour groups. No differences were observed when comparing paraneoplastic arthritis and undifferentiated arthritis, except that the patients with paraneoplastic arthritis were older. Comparing paraneoplastic Raynaud's to Raynaud's phenomenon, male preponderance in the paraneoplastic Raynaud's phenomenon group was observed, and the patients were obviously older. Paraneoplastic rheumatic syndromes are rare and more often occur in older patients. Among them, paraneoplastic arthritis and Raynaud's syndrome were the most frequent. The immunology profile does not help in discriminating between arthritis and paraneoplastic arthritis patients and is of limited use in Raynaud's differential diagnosis.

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.

In vivo study of skin mechanical properties in Raynaud's phenomenon

Raynaud's phenomenon (RP) is usually the first symptom in patients with systemic sclerosis (SS) and may precede skin changes by several months or years. Non-invasive measurements of skin elasticity are very sensitive and appropriate for objective and quantitative evaluation of sclerodermatous skin. The aim of this study was to investigate and compare the mechanical properties of the skin in patients with primary, secondary, and suspected secondary RP. A total of 63 patients were studied. They were classified as having scleroderma-type nailfold capillary abnormalities--17 with indurative phase of scleroderma (group 1), nine with edematous phase of scleroderma (group 2), 18 with suspected secondary RP (group 3) and as having RP-type nailfold capillary abnormalities, 19 with primary RP (group 4). Thirty-nine sex- and age-matched healthy individuals with normal nailfold capillaroscopy pattern were also studied as controls. Mechanical properties of the skin were evaluated using a non-invasive suction device (Cutometer) equipped with a 2 mm probe. Measurements were performed over five anatomic regions: cheeks, volar forearms, wrists, hands, and proximal phalanx of the fingers. The skin mechanical parameters analyzed were distensibility (Uf), elasticity (Ua/Uf) and viscoelasticity (Uv/Ue). Most demonstrative changes were observed over volar forearms. Patients included in groups 1-3 were characterized by significantly lower Uf and higher Uv/Ue compared with patient group 4 and controls. Patient groups 1 and 2 showed significantly lower Ua/Uf, as well. There were no significant differences in skin mechanical parameters between patient group 4 and control group. Mechanical properties of the skin in patients with suspected secondary RP significantly differ from these in patients with primary RP and resemble those in patients with edematous phase of scleroderma. Our findings suggest that the non-invasive measurements of skin elasticity could be helpful in identifying patients with RP at risk of developing SS.

Local hyperhemia to heating is impaired in secondary Raynaud's phenomenon

Accurate and sensitive measurement techniques are a key issue in the quantification of the microvascular and endothelial dysfunction in systemic sclerosis (SSc). Thermal hyperhemia comprises two separate mechanisms: an initial peak that is axon reflex mediated; and a sustained plateau phase that is nitric oxide dependent. The main objective of our study was to test whether thermal hyperhemia in patients with SSc differed from that in patients with primary Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 patients suffering from SSc, 20 patients with primary RP and 20 healthy volunteers. All subjects were in a fasting state. Post-occlusive hyperhemia, 0.4 mg sublingual nitroglycerin challenge and thermal hyperhemia were performed using laser Doppler flowmetry on the distal pad of the third left finger. In a second study, thermal hyperhemia was performed in 10 patients with rheumatoid arthritis and 10 patients with primary RP. The thermal hyperhemia was dramatically altered in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy volunteers and 18 patients with primary RP exhibited the classic response, including an initial peak within the first 10 minutes followed by a nadir and a second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to 51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively (p = 0.01), while the 44°C thermal peak was 43.1 (21.3 to 62.1), 42.6 (31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal hyperhemia was more sensitive and specific than post-occlusive hyperhemia for differentiating SSc from primary RP. In patients with rheumatoid arthritis, thermal hyperhemia was also altered in terms of amplitude. Thermal hyperhemia is dramatically altered in patients with secondary RP in comparison with subjects with primary RP. Further studies are required to determine the mechanisms of this altered response, and whether it may provide additional information in a clinical setting.

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.

Elevated Homocysteine Levels in Patients with Raynaud’s Phenomenon Secondary to Systemic Lupus Erythematosus

The objective of this study was to analyse the association between serum homocysteine (Hcy) levels and the presence of Raynaud's phenomenon (RP) in a cohort of systemic lupus erythematosus (SLE) patients. We enrolled premenopausal, disease-inactive SLE patients ( n = 34) with RP (group I, n = 11) or without RP (group II, n = 23), and age-matched healthy premenopausal women as controls (group III, n = 20). Fasting Hcy levels were determined for all these subjects. The results reveal that group I patients exhibited significantly greater serum Hcy levels (11.68+/-2.98 mmol/l) than group II patients (8.29+/-2.89 mmol/l) ( P = 0.003), and group III healthy subjects (8.00+/-1.50 mmol/l) ( P = 0.001); however, in this regard there was no significant difference between group II and group III patients ( P = 0.927). In conclusion, elevated serum Hcy levels were noted for this cohort of SLE patients with RP compared to those not evidencing RP and healthy controls. Although the pathogenesis of RP still remains obscure, this study suggests that Hcy may play a role in the aetiopathogenesis of SLE patients with RP.

Lower serum magnesium level after exposure to cold in women with primary Raynaud's phenomenon

Serum levels of magnesium (s-Mg), calcium (s-Ca), potassium (s-K) and sodium (s-Na) were measured in 80 women with primary Raynaud's phenomenon (RP) and in 24 age-matched female controls recruited from a population survey. The blood samples were taken after a 40-min standardized whole body cooling test. The mean s-Mg level in the group with RP was significantly lower than in the controls (0.81 +/- 0.05 vs. 0.86 +/- 0.07 mmol l-1, P less than 0.05). One year later, 66 members of the RP group and 22 members of the control group were investigated further, but without any exposure to cold. No differences in mean s-Mg values were found between the groups. The mean s-Mg level was significantly higher in the blood samples taken later without cold exposure than at the initial examinations after exposure to cold in the RP group, but not in the controls. The s-Mg level was lower after exposure to cold in 82% of the women with RP, compared to 45% of the controls (P less than 0.001). No differences in the other electrolytes were found. It is concluded that exposure to cold under standardized conditions may decrease the s-Mg level in women with primary RP. Further studies of the role of magnesium in patients with RP are required.

Pregnancy outcomes in women with primary raynaud's phenomenon

Pregnancy outcomes were assessed in 67 women who had well-defined primary Raynaud's phenomenon and in 30 controls, each of whom had been pregnant at least once. Twenty-seven patients had onset of Raynaud's phenomenon prior to any pregnancy, and 37 patients had onset of Raynaud's phenomenon after their last pregnancy. The frequency of miscarriage, stillbirth, and small full-term infants was similar in all 3 study groups. Among the 4 Raynaud's phenomenon patients who had second-trimester miscarriages, 2 of 3 who were tested had moderately positive levels of IgG or IgM anticardiolipin antibody. Premature births were significantly more common in pregnancies that occurred after the onset of Raynaud's phenomenon (24%) than in pregnancies that occurred prior to the onset of Raynaud's phenomenon or in pregnancies among control subjects (9% and 1%, respectively). In addition, the mean weight of the full-term babies of women in both Raynaud's phenomenon groups was significantly less than that of babies born to controls. There were no neonatal deaths or other serious adverse outcomes. These findings may represent yet another manifestation of systemic vasospasm in patients with primary Raynaud's phenomenon.

Quantitative evaluation of Raynaud's phenomenon: Measurement of the finger skin temperature

Raynaud's phenomenon is an important sign which is occasionally associated with certain connective tissue disorders. This study was designed to establish a quantitative evaluation for Raynaud's phenomenon by means of recording changes in the skin temperature.Raynaud's phenomenon was induced by immersing both hands in the ice-water in a temperature-monitored room. Thereafter, the finger skin temperature was measured with the thermocupler thermometer for 30 minutes together with the observation of the skin color.Basal skin temperature (the skin temperature before the immersion) was significantly lower in Raynaud's phenomenon group (28.6±4.2°C, m±S.D.) than in the control group (33.9±1.3°C) (p<0.005).Basal skin temperature recovery time (the time taken to return to the basal skin temperature after the immersion) was significantly delayed in Raynaud's phenomenon group (29.3±2.9min.) than in the control group (15.5±6.6min.) (p<0.005).The rate of rise in the skin temperature was significantly lower in Raynaud's phenomenon group (0.34±0.18°C per min.) than in the control, group (1.25±0.39°C per min.) (p<0.005). Both groups could be separated by the borderline at 0.60°C per min.Changes in the skin color after the immersion in the ice-water were variable without consistent tendency in Raynaud's phenomenon group, whereas there was no particular change in the skin color in the control group.Oral administration of prostaglandin E1 (OP-1206 α-CD) improved the rate of rise in the skin temperature in 6 of 11 subjects in Raynaud's phenomenon group.The foregoing results suggest that the measurement of the skin temperature, especially the rate of rise in the skin temperature, is a useful method in the quantitative evaluation for Raynaud's phenomenon.