Digital ulcers in systemic sclerosis are strongly associated with digital arterial disease: a finger-by-finger analysis of Finger Brachial Pressure Index Measurements.

OBJECTIVES: The digital ulcers of systemic sclerosis are disabling and frequent· Their pathogenesis involves a capillary microangiopathy and a digital arterial disease that few studies were able to quantify up to now. A multicentre observational study about the predictive value of capillaroscopy in systemic sclerosis offered us the opportunity to evaluate further the complementary information provided by both capillary and arterial evaluations. METHODS: During the SCLEROCAP study, five out of the nine centers performed a systematic evaluation of the finger brachial pressure index (FBPI) in the last four fingers of both hands at baseline, using the same laser-doppler device. In the present work, FBPI measurements were compared between fingers with vs without digital ulcers or scars, before and after adjusting for the capillaroscopic pattern and systemic factors. RESULTS: FBPI measurements were performed in 2537 fingers from 326 patients. Active ulcers or scars were found in 10·8% of those fingers, more often on the right hand, and in the second and third fingers. FBPI was lower than 0·70 in 26% of all fingers and in 57·5% of those with ulcers. A strong association was found between a low FBPI and the presence of digital ulcers, even after adjusting for capillaroscopic pattern, ulcer location and the patient himself. CONCLUSION: These results confirm the importance of digital arterial disease in the pathogenesis of digital ulcers of systemic sclerosis, which is independent from the microangiopathy. FBPI measurements complement the information provided by capillaroscopy and might have an important predictive value for subsequent digital ulcers.

Correlation of nailfold capillaroscopy findings with history of digital ulcer on same finger: Results of SCLEROCAP study.

Systemic sclerosis may be complicated by digital ulcers. Nailfold capillaroscopy on one finger might reflect an increased risk of digital ulcer (DU). In the present study we studied the correlations between a history of ulcer and capillary findings on the finger. METHOD: This study is part of Sclerocap, a multicenter study aiming at validating prospectively the prognostic value of Maricq's and Cutolo's capillaroscopic classifications during a three-year longitudinal follow-up. A history of past or present digital ulcer was recorded at inclusion and nailfold capillaroscopy was performed. Elementary findings as well as Cutolo and Maricq's classifications were assessed. RESULTS: 387 patients were included in Sclerocap (327 females, 60 males) and 3096 fingers were examined by capillaroscopy at inclusion: 316 fingers (10%) belonging to 113 patients had a history of DU. Late Cutolo's stage was statistically correlated with a history of DU, both by univariate: OR 2.08 [1.09-3.96] and multivariate analysis: OR 1.97 [1.06-3.63]. Among the elemental abnormalities, only edema and decreased capillary density were correlated with a history of DU by multivariate analysis: respectively OR 1.92 [1.17-3.16] and 0.65 [0.49-0.85]. CONCLUSION: This cross-sectional study in a large cohort of patients with systemic sclerosis shows a correlation between a history of digital ulcer and edema, a decrease in capillary density and the late stage in Cutolo's classification. The extent of capillary abnormalities on one finger is associated with a history of local digital ulcer. Capillaroscopy might be used to predict the risk of DU but these results need first to be confirmed by prospective studies.

Optimizing finger systolic blood pressure measurements with laser Doppler: Validation of the second phalanx site.

OBJECTIVE: Finger systolic blood pressure measurement (FSBP) has been shown helpful in the detection of distal arterial insufficiency in upper limbs. This work assesses the possibility to measure FSBP on the 2nd phalanx instead of the first one in order to improve its sensitivity and to verify this would not alter the repeatability of the measurement. METHODS: In this multicenter study, FSBP was measured twice in all fingers but the thumbs in consecutive systemic sclerosis patients on the first phalanx and the second phalanx in alternate order using laser-Doppler flowmetry. RESULTS: Thirty-seven patients were enrolled. The repeatability of FSBP was excellent and similar on the first and 2nd phalanxes with coefficients of variation respectively of 7.1% and 7.6%. While the correlation between the FSBP at the two sites was fair (Pearson coefficient 0.69; p < 0.001). The agreement was poor, with a mean difference of 14 mm Hg between the two sites. Significantly higher differences were found in fingers with digital ulcers. The ROC curves showed a better prediction of the 2nd phalanx measurements. CONCLUSION: FSBP has an excellent repeatability whatever the site of phalanx. However, measurements performed on the 2nd phalanx have a better sensitivity for the prediction of digital ulcers.

Fluorescence angiography compared to toe blood pressure in the evaluation of severe limb ischemia.

Background: Severity of limb ischemia in peripheral arterial disease (PAD) patients is usually evaluated by clinical assessment and toe blood pressure (TBP) or transcutaneous oxygen pressures (TcPO 2). Indocyanin green angiography (IGA) is a promising tool generating a foot cartography of skin microvascular perfusion. However, there is no consensus about the fluorescence parameters that should be used to evaluate ischemia. The purpose of this cross-sectional evaluation and 3-month clinical follow-up was to determine the best fluorescence parameter for the evaluation of severe PAD, using TBP as reference. Patients and methods: IGA was realized in patients with clinical suspicion of CLI in addition to TBP and TcPO 2. Parameters from the time intensity fluorescence curve measured on the foot were compared with TBP (primary reference), and with TcPO2. Clinical outcomes (amputation, revascularization, death) were recorded at 3 months follow-up. Results: Thirty-four patients were included and IGA could be analysed in 29 of them. When all limbs were studied, no significant correlation was found between any of the measured fluorescence parameters (saturation time, ingress slope, amplitude, delay) and TBP pressure neither TCPO2. In the limbs with CLI, a significant correlation between the TBP and amplitude on the forefoot was found. According to the outcome, none of the fluorescence parameters showed a significant prognostic value in contrast to the significant results for TBP and TcPO2. Conclusions: In this study, quantitative analysis of IGA parameters did not show any prognostic value, nor was there any significant statistical association with well-established prognostic parameters such as TBP and TcPO 2 in patients with suspected CLI. A correlation was found between amplitude and TBP in patients with CLI. Topographical information such as perfusion heterogeneity was not evaluated and remains a valuable target to be investigated.

Correlation between capillaroscopic classifications and severity in systemic sclerosis: results from SCLEROCAP study at inclusion.

OBJECTIVES: We assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nailfold capillaroscopy. METHODS: SCLEROCAP is a multicenter prospective study including consecutive scleroderma patients who have a yearly routine follow-up with capillaroscopy and digital blood pressure measurement. Capillaroscopy images were read by two observers blinded from each other, then by a third one in the case of discordance. A follow-up of 3 years is planned. The present study assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nail fold capillaroscopy at enrollment in the SCLEROCAP study. Univariate and multivariate logistic regression analysis was performed for both the Maricq and Cutolo classifications. RESULTS: SCLEROCAP included 387 patients in one year. Maricq's active and Cutolo's late classifications were very similar. In multivariate analysis, the number of digital ulcers (OR for 2 ulcers or more, respectively 2.023 [1.074-3.81] and 2.596 [1.434-4.699]) and Rodnan's skin score >15 (OR respectively 32.007 [6.457-158.658] and 18.390 [5.380-62.865]) correlated with Maricq's active and Cutolo's late stages. Haemoglobin rate correlated with Cutolo's late stage (hemoglobin<100 vs. >120 g/dl: OR 0.223 [0.051-0.980]), and total lung capacity with Maricq's active one: increase in 10%: OR0.833 [0.717-0.969]. CONCLUSIONS: The correlations found between capillaroscopy and severity of SSc are promising before the ongoing prospective study definitively assesses whether capillaroscopy staging predicts complications of SSc. Only two capillaroscopic patterns seem useful: one involving many giant capillaries and haemorrhages and the other with severe capillary loss.

On-Demand Sildenafil as a Treatment for Raynaud Phenomenon: A Series of n-of-1 Trials.

Background: Treatment of Raynaud phenomenon (RP) with phosphodiesterase-5 inhibitors has shown moderate efficacy. Adverse effects decrease the risk-benefit profile of these drugs, and patients may not be willing to receive long-term treatment. On-demand single doses before or during exposure to cold may be a good alternative. Objective: To assess the efficacy and safety of on-demand sildenafil in RP. Design: Series of randomized, double-blind, n-of-1 trials. (ClinicalTrials.gov: NCT02050360). Setting: Outpatients at a French university hospital. Participants: Patients with primary or secondary RP. Intervention: Each trial consisted of a multiple crossover study in a single patient. Repeated blocks of 3 periods of on-demand treatment were evaluated: 1 week of placebo, 1 week of sildenafil at 40 mg per dose, and 1 week of sildenafil at 80 mg per dose, with a maximum of 2 doses daily. Measurements: Raynaud Condition Score (RCS) and frequency and daily duration of attacks. Skin blood flow in response to cooling also was assessed with laser speckle contrast imaging. Mixed-effects models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated efficacy. Results: 38 patients completed 2 to 5 treatment blocks. On the basis of aggregated data, the probability that sildenafil at 40 mg or 80 mg was more effective than placebo was greater than 90% for all outcomes (except for RCS with sildenafil, 80 mg). However, the aggregated effect size was not clinically relevant. Yet, substantial heterogeneity in sildenafil's efficacy was observed among participants, with clinically relevant efficacy in some patients. Limitation: The response to sildenafil was substantially heterogeneous among patients. Conclusion: Despite a high probability that sildenafil is superior to placebo, substantial heterogeneity was observed in patient response and aggregated results did not show that on-demand sildenafil has clinically relevant efficacy. In this context, the use of n-of-1 trials may be an original and relevant approach in RP. Primary Funding Source: GIRCI (Groupement Interrégional de Recherche Clinique et d'Innovation) Auvergne Rhône-Alpes (academic funding) and Pfizer.

Reproducibility of the scleroderma pattern assessed by wide-field capillaroscopy in subjects suffering from Raynaud's phenomenon.

Objectives: The aim of this work was to study inter- and intra-observer agreement for the diagnosis of scleroderma pattern by wide-field capillaroscopy. Methods: Images were taken from 50 patients known to have SSc and 50 controls consulting for RP who did not have SSc. These images were rated simultaneously by 11 experienced vascular medicine physicians as scleroderma pattern or not. Two weeks later, 7 of the 11 observers again rated the same images. Results: Inter-observer agreement was almost perfect between the 11 observers (κ 0.86 ± 0.01), and the proportion of concordant observations was 79% (70-87). When each observer was compared with the reference, agreement was also almost perfect: κ coefficient 0.92 ± 0.03 and proportion of concordant observations 79% (70-87). Intra-observer agreement was also almost perfect: median κ coefficient 0.94 (0.78-0.96) and median proportion of concordant observations 97% (89-98). Conclusion: Excellent inter- and intra-observer agreement was obtained in experienced vascular physicians for the diagnosis of capillaroscopic landscape by wide-field nailfold capillary microscopy.

Reproducibility of capillaroscopic classifications of systemic sclerosis: results from the SCLEROCAP study.

Objectives: Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc. Methods: SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement. Results: Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas. Conclusion: The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.

Is contrast enhanced ultrasonography a useful tool for the evaluation of muscular microcirculation in patients with critical limb ischaemia?

BACKGROUND: Evaluation of skin microcirculation in patients with critical limb ischemia (CLI) may be achieved by the measurement of transcutaneous oxygen pressure or skin perfusion pressure, but there is no practical method available for the evaluation of muscle microcirculation. Contrast enhanced ultrasonography (CEUS) has been used to assess muscle perfusion in patients with peripheral arterial disease. We conducted a monocentric pilot study evaluating the ability of CEUS to assess the impact of arterial revascularization on the perfusion of the calf muscle in patients with CLI. PATIENTS AND METHODS: Patients with CLI (TASC II criteria) and a possibility of proximal or medial revascularization were included. In addition to TcPO2 and toe systolic blood pressure measurements, CEUS of the calf muscle was performed just before and one month after the therapeutic procedure. Parameters derived from muscular perfusion curves were evaluated in a blinded fashion and compared with the clinical outcome. RESULTS: Thirty eight patients were included (74 % men, median age 71 years, 53 % diabetics). Thirty benefited from revascularization with a clinical success rate of 70 %. Twenty three patients could benefit from analysis before and after revascularization. No significant difference was shown in time to peak (22.3 s vs 24.0 s, P = 0.61) nor in peak intensity (2.30 dB vs 1.27 db, P = 0,26), contrasting with significant improvements of TcPO2 (43 mm Hg vs 20 mm Hg, P = 0.007) and toe systolic blood pressure (54 mm Hg vs 32 mm Hg, P = 0.002). CONCLUSIONS: The evaluation of muscular microvascular perfusion by CEUS as performed in this study is not enough sensitive to change to allow a clinically relevant evaluation of the improvement in muscle microvascular perfusion in patients with CLI benefiting from revascularization procedures.

ESVM guidelines - the diagnosis and management of Raynaud's phenomenon.

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

Treprostinil Iontophoresis Improves Digital Blood Flow during Local Cooling in Systemic Sclerosis.

INTRODUCTION: Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. METHODS: Eleven patients with limited cutaneous SSc underwent a double-blinded iontophoresis of treprostinil (2.56 × 10(-4) M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8 °C, and skin blood flow was recorded continuously using LSCI. RESULTS: During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test. CONCLUSIONS: In patients with SSc, digital treprostinil iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil iontophoresis should now be tested in larger scale studies.

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study.

OBJECTIVE: To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). METHODS: Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). RESULTS: Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). CONCLUSIONS: The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. TRIAL REGISTRATION NUMBER: NCT01295736.

Peripheral vasoconstriction induced by ß-adrenoceptor blockers: a systematic review and a network meta-analysis.

AIM: Peripheral vasoconstriction has long been described as a vascular adverse effect of ß-adrenoceptor blockers. Whether ß-adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to ß1 -adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta-analysis in order to assess the comparative risk of peripheral vasoconstriction of different ß-adrenoceptor blockers. METHOD: We searched for randomized controlled trials (RCTs) including ß-adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of ß-adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the ß-adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374). RESULTS: Among 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with ß-adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not. CONCLUSION: Our results suggest that ß-adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to ß1 -adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra-indications of use of ß-adrenoceptor blockers and suggest that ß-adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.

Drug-induced Raynaud's phenomenon: beyond ß-adrenoceptor blockers.

AIM: Drug-induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or ß-adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug-induced RP. METHODS: A systematic review of English and French language articles was performed through Medline (1946-2015) and Embase (1974-2015). Further relevant papers were identified from the reference lists of retrieved articles. RESULTS: We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by ß-adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism. CONCLUSION: Drug-induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered.

Paroxysmal finger haematoma--a benign acrosyndrome occurring in middle-aged women.

BACKGROUND: Paroxysmal finger haematoma (PFH) is an under-recognised vascular acrosyndrome with no epidemiological description to date. The aim of this work was to evaluate the prevalence, risk factors and clinical correlates of PFH in a population-based sample of subjects and to describe their semiological characteristics. PATIENTS AND METHODS: This cross-sectional study of random samples of the general population in three geographic areas of France involved 802 subjects, 548 women and 254 men, aged 18 to 84 years. The diagnosis of PFH was made from a report by the subject of a history of recurrent haematoma in the fingers with a sudden, painful and unexpected occurrence. Diagnosis of associated conditions and evaluation of lifestyle variables were obtained through standardised medical interview and examination. RESULTS: A history of PFH was detected in 71 subjects, with a prevalence of 1.2% in men and 12.4% in women; there was no significant regional variation. Onset before 40 years of age was rare. Besides female sex and age, no socio-economical nor lifestyle risk factors were detected. PFH was associated with Raynaud phenomenon and a history of chilblains, but no link with any health threatening disease was found. In addition to the sudden onset of pain and hematoma, the main clinical features were a frequent digital swelling during the painful attack, and their predominant location on the volar side of the first and second phalanges of the third or second fingers of the dominant hand. CONCLUSIONS: PFH is a benign phenomenon, frequently found in middle-aged women, to be classified among the vascular acrosyndromes. Patients seeking medical evaluation for this disorder should be reassured.

A multicenter randomized controlled trial evaluating balneotherapy in patients with advanced chronic venous insufficiency.

BACKGROUND: Apart from compression therapy, physical therapy has scarcely been evaluated in the treatment of chronic venous disorders (CVDs). Spa treatment is a popular way to administer physical therapy for CVDs in France, but its efficacy has not yet been assessed in a large trial. The objective was to assess the efficacy of spa therapy for patients with advanced CVD (CEAP clinical classes C4-C5). METHODS: This was a single-blind (treatment concealed to the investigators) randomized, multicenter, controlled trial (French spa resorts). Inclusion criteria were primary or post-thrombotic CVD with skin changes but no active ulcer (C4a, C4b, or C5). The treated group had the usual 3-week spa treatment course soon after randomization; the control group had spa treatment after the 1-year comparison period. All patients continued their usual medical care including wearing compression stockings. Treatment consisted of four balneotherapy sessions per day for 6 days a week. Follow-up was performed at 6, 12 and 18 months by independent blinded investigators. The main outcome criterion was the incidence of leg ulcers at 12 months. Secondary criteria were a modified version of the Venous Clinical Severity Score, a visual analog scale for leg symptoms, and the Chronic Venous Insufficiency Questionnaire 2 and EuroQol 5D quality-of-life autoquestionnaires. RESULTS: Four hundred twenty-five subjects were enrolled: 214 in the treatment group (Spa) and 211 in the control group (Ctr); they were similar at baseline regarding their demographic characteristics, the severity of the CVD, and the outcome variables. At 1 year, the incidence of leg ulcers was not statistically different (Spa: +9.3%; 95% confidence interval [CI], +5.6 - +14.3; Ctr: +6.1%; 95% CI, +3.2 - +10.4), whereas the Venous Clinical Severity Score improved significantly in the treatment group (Spa: -1.2; 95% CI, -1.6 - -0.8; Ctr: -0.6; 95% CI, -1.0 - -0.2; P = .04). A significant difference favoring spa treatment was found regarding symptoms after 1 year (Spa: -0.03; 95% CI, -0.57 - +0.51; Ctr: +0.87; 95% CI,+0.46 - +1.26; P = .009). EuroQol 5D improved in the treatment group (Spa: +0.01; 95% CI, -0.02 - +0.04) while it worsened (Ctr: -0.07; 95% CI, -0.10 - -0.04) in the control group (P < .001). A similar pattern was found for the Chronic Venous Insufficiency Questionnaire 2 scale (Spa: -2.0; 95% CI, -4.4 - +0.4; Ctr: +2.4; 95% CI, +0.2 - +4.7; P = .008). The control patients showed similar improvements in clinical severity, symptoms, and quality of life after their own spa treatment (day 547). CONCLUSIONS: In this study, the incidence of leg ulcers was not reduced after a 3-week spa therapy course. Nevertheless, our study demonstrates that spa therapy provides a significant and substantial improvement in clinical status, symptoms, and quality of life of patients with advanced venous insufficiency for at least 1 year.

[Pharmacology of Raynaud's phenomenon]. / Pharmacologie du phénomène de Raynaud.

Raynaud's phenomenon (RP) is characterised by transient ischaemia in the extremities in response to cold or emotions. It can be primary (idiopathic) or secondary to an underlying disease. The pathophysiology of RP is multifactorial and complex. Microvascular impairment is a hallmark of the disease. The objective of this work is to review the different pharmacological treatments currently used in the management of RP, from their mechanism of action to the available evidence regarding their efficacy. We also propose to discuss potential pharmacological targets such as the potentiation of the nitric oxide pathway, or the inhibition of the RhoA-Rho kinase pathway. The last part of this review deals with drug-induced RP. Among various medications, beta-blockers, interferons, tyrosine-kinase inhibitors or cytotoxic agents such as bleomycin are involved.

Performance of an adjustable compression wrap in occupational leg swelling.

BACKGROUND: Edema in some subjects worsens over time and wraps help to reduce the leg volume. MATERIAL AND METHODS: An adjustable compression wrap was tried on volunteers for 5 h and volumes measured in each limb before and after wrapping using a 3D surface scanner (HandySCAN 3D®) to estimate the volume of the leg. The contralateral leg was used as control. RESULTS: We observed a significant decrease in volume in the wrap legs and an increase in the control legs (p < .001), both in the lower part of leg (p = .001) and in the upper part (p = .001). CONCLUSIONS: Using the Readywrap® for 5 hours significantly reduces the leg volume. This study enables Readywrap to be studied in a population that is easy to observe in the context of a research program. The Handyscan3D® was shown accurate and reproducible to assess leg volume in future studies.

Very long-term risk of moderate-to-severe postthrombotic syndrome after deep vein thrombosis.

BACKGROUND: Postthrombotic syndrome (PTS) refers to manifestations of chronic venous insufficiency after a deep vein thrombosis (DVT). The risk of developing moderate-to-severe PTS in the very long term is largely unknown and particularly in case of distal DVT. Furthermore, the impact of DVT vs other causes of chronic venous insufficiency on long-term manifestations of PTS is also unknown. OBJECTIVES: To assess the very long-term risk of moderate-to-severe PTS after DVT and the role that DVT plays in PTS symptoms. METHODS: Patients with lower-limb DVT enrolled in the multicenter Optimisation de l'interrogatoire dans l'evaluation du risque thromboembolique veineux (OPTIMEV) study underwent a very long-term telephone follow-up. We assessed i) the proportion of moderate-to-severe PTS (assessed with the patient-reported Villalta score) according to DVT extent and ii) the population attributable fraction that DVT plays in patients' moderate-to-severe PTS manifestations. RESULTS: Fourteen years after DVT, moderate-to-severe PTS developed in 35 of 185 patients with distal DVT (18.9%; 95% CI, 13.5%-25.3%), 11 of 47 patients with popliteal DVT (23.4%; 95% CI, 12.3%-38.0%), and 27 of 74 patients with iliofemoral DVT (36.5%; 95% CI, 25.6%-48.5%). The population attributable fraction of DVT in moderate-to-severe symptoms of PTS was 25.7% (-18.1% to 53.3%) in patients with distal DVT, 27.3% (-63.7% to 67.7%) in patients with popliteal DVT, and 43.1% (+0.7%-67.4%) in patients with iliofemoral DVT. CONCLUSION: In the very long term after DVT, a quarter of patients have moderate-to-severe PTS manifestations. However, the impact of the DVT on these manifestations appears nonpredominant and varies according to DVT extent. Distal DVT does not significantly increase the risk of developing moderate-to-severe PTS.