Duration Of Raynaud's Phenomenon Research Articles

Structural abnormalities associated with glaucoma using swept-source optical coherence tomography in patients with systemic sclerosis.

Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

A Randomized Controlled Trial of Acupressure for the Treatment of Raynaud's Phenomenon: The difficulty of conducting a trial in Raynaud's phenomenon.

To examine the effect of acupressure on Raynaud's phenomenon (RP) in a randomized controlled clinical trial (RCT) and to evaluate the difficulties of conducting a RP RCT. A pilot single center RCT of acupressure vs. targeted patient education was conducted for the treatment of RP. Patients with either primary (N = 15) or secondary (N = 8) RP were randomized in an 8-week study. The primary endpoints included a decrease in the frequency and duration of RP. Secondary endpoints included several serum biomarkers including endothelial dysfunction, Raynaud's attack symptoms, Raynaud's Condition Score, and patient and physician global assessments of RP. Primary data analysis was conducted using the last observation carried forward and t-tests or a Wilcoxon rank test was used to compare the two groups. 23 patients were randomized and 7 discontinued prematurely. 78% of patients were female, 96% were Caucasian, and the mean age was 49.8 (SD=16) years. No statistically significant differences were detected between the acupressure vs. education groups in primary and secondary outcomes (p> 0.05). Frequency of attacks decreased by 6.7 attacks (SD=8.8) in the acupressure group vs. 7.2 (SD=12.8) in the education group (p=0.96), and the duration of attacks decreased by 11.4 (SD=19.9) minutes in the acupressure group vs. an increase of 0.8 minutes (SD=11.2) in the education group (p=0.14). There were no adverse events noted in the RCT. This pilot study does not support efficacy of acupressure for RP.

Efficacy of cilostazol for the treatment of Raynaud's phenomenon in systemic sclerosis patients.

Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study. Cilostazol was administered at the dose of 100mg twice a day, for 12months. Evaluations included: daily RP attack diary documenting the frequency and duration of RP episodes, Health Assessment Questionnaire-Disability Index, scleroderma visual analogue scales (VAS), flow-mediated dilation and immunological status, including endothelin 1 and interleukin 6 plasma levels. Thirteen patients completed the study. RP duration and daily number episodes recorded over a 3-week period significantly decreased after cilostazol treatment (p=0.0049 and p=0.0067, respectively). VAS score indicated a significant amelioration of the patients' perception of RP (p=0.0117), and both baseline and post-ischemic brachial artery diameters were significantly increased after cilostazol treatment, as compared with basal values (p=0.0119 and p=0.0076, respectively). None of the patients developed digital ulcers during the study. A significant clinical improvement of RP was recorded in SSc patients undergoing cilostazol treatment. Study results indicate a potential role of cilostazol as oral maintenance therapy in SSc patients with RP.

SAT0300 Microcirculation and Macrovascular Disease in Systemic Sclerosis – A Nailfold Capillary Study

BackgroundEmerging evidence demonstrate that patients with systemic sclerosis (SSc) suffer from both micro- and macrovascular disease. Structural changes in nailfold capillaries, a marker of microvascular involvement, has been associated with...

AB0610 Difference in Skin Elasticity between Diffuse and Limited Systemic Sclerosis

BackgroundSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by vascular damage and severe fibroproliferative phenotype, which affects skin and internal organs. To date, the modified Rodnan Skin Score (mRSS)...

Predictive value of naitfold capillaroscopy in patients with Raynaud’s phenomenon

The objective of this study was to evaluate the long-term follow-up of patients with Raynaud's phenomenon (RP) and pathological nailfold capillaroscopy (NC) in order to analyse the predictive value of specific features of capillaroscopy for the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was performed in 1024 consecutive patients because of RP. We analysed the follow-up and pathological features of NC in all patients who had neither clinical nor serological signs of a CTD at the time of NC. Of 308 patients with neither serological findings nor clinical signs of CTD but with RP and pathological features in NC suspicious for CTD, follow-up data were available for 133 patients. An additional NaF test had been performed in 51 (38.4%) patients. After a mean follow-up of 6.5 years (range: 1-15 years), 109 patients had developed a CTD and 24 patients did not show any clinical signs or serological markers for a CTD after a mean follow-up of 8.5 years (range: 2-15 years). There were no differences in age, duration of RP or of follow-up in patients who developed a CTD compared to patients who did not. Significantly more giant capillaries (p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had been observed in patients who had developed a CTD during the follow-up of 6.5 years. The presence of giant capillaries, avascular fields and irregular architecture of nailfold capillaries is predictive for the development of a CTD in patients with RP.

Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.

Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenetic role. Recently, we graded scleroderma microangiopathy by nailfold videocapillaroscopy (NVC) into three NVC patterns (early, active and late). The aim of the present study was to confirm, in a larger number of SSc patients, the presence of three patterns of microvascular damage, and to detect any possible relationship between these patterns and both specific serum autoantibodies and the subsets of cutaneous involvement. Two hundred and forty-one consecutive patients (227 women and 14 men) affected by SSc were recruited. One hundred and forty-eight patients were affected by limited cutaneous SSc (lSSc) and 93 patients by diffuse cutaneous SSc (dSSc). The ages at onset of Raynaud's phenomenon (RP) and SSc, the durations of RP and SSc, ANA and antitopoisomerase I (anti-Scl70) and anticentromere (ACA) antibodies were investigated in all patients. The SSc patients were subdivided on the basis of the NVC pattern into three groups. A statistically significant correlation was found between the NVC patterns and the durations of both RP and SSc (P<0.001). Enlarged and giant capillaries, together with haemorrhages, constituted the earliest NVC finding in SSc (early NVC pattern). These abnormalities were mostly expressed in the active NVC pattern. Loss of capillaries, ramified capillaries and vascular architectural disorganization were increased in the late NVC pattern. Age and the duration of both RP and SSc were lower in 24 patients complaining of RP alone. Anti-Scl70 antibodies were statistically less frequent in the early vs both the active and the late NVC pattern, whereas no significant correlation was found between the presence of anti-Scl70 antibodies and the duration of either RP or SSc. ACA positivity was more frequent in patients with longer RP duration. Patients with lSSc had shorter SSc duration and showed the early or active NVC pattern more frequently. Conversely, patients with dSSc showed longer disease duration and mostly showed the late NVC pattern. NVC is an appropriate tool for differential diagnosis between primary and secondary RP through the clear recognition of the early NVC scleroderma pattern. This study confirms, in a large number of SSc patients, the existence of three distinct NVC patterns that might reflect the evolution of SSc microangiopathy. The presence of anti-Scl70 antibodies seems be related to earlier expression of the active and late NVC patterns of SSc microvascular damage. The presence of ACA seems to be related to delayed expression of the late NVC pattern.

Lack of seasonal variation in flow-mediated dilatation of the brachial artery in women with primary Raynaud's phenomenon and healthy controls.

The aim of this study was to examine endothelium function and seasonal variations of endothelium function in women with primary Raynaud's phenomenon (RP) and healthy controls. After a fast of at least 8 hours we studied 21 patients with primary RP (mean age 31.1 years, mean duration of RP 9.1 years) and 22 controls (mean age 27.8 years) by use of high resolution brachial artery sonography in winter (December/January 2000) and summer (July/August 2001). To exclude circadian variations all examinations were performed in the late afternoon only. All subjects were non-smokers. Confounding factors like serum glucose, HbAlc, and lipid concentrations were analyzed immediately before the investigations. Nicotine contamination was randomly analyzed in hair samples in 8 subjects of each study group. Flow mediated dilatation (FMD%) and nitroglycerin induced dilatation (NID%) were calculated by putting the basal vessel diameter as 100%. Basal, flow-mediated, and nitroglycerin-induced absolute diameters of the brachial artery did not differ significantly between the study groups (p = 0.85). The test conditions (basal, postocclusive, nitroglycerin-induced) always let to the same vessel response in winter and summer (p = 0.61) and there was no significant influence between these test conditions and the study groups (p = 0.07). Compared to patients FMD% was slightly reduced in controls in summer (p = 0.09). Analysis of variance excluded a significant relation between study group and season (p = 0.43). For NID% too, no statistically significant differences were found. We were not able to show impaired or seasonally variant flow-mediated or nitroglycerin-induced dilatation of the brachial artery in patients with primary RP. Our results argue against the presence of a more generalized endothelium dysfunction detectable with high resolution ultrasound of the brachial artery in patients with primary RP.

Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon.

To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients. Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data. Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18-82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 +/- 2.33 (mean +/- SD) daily RP attacks (range 0.8-14.6), with a duration of 82.1 +/- 91.6 minutes/attack. RCS for RP activity (possible range 0-10) was 4.30 +/- 1.92. HAQ scores (0-3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33-0.76). Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2).