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.

Video-capillaroscopy, a promising tool for the clinical evaluation of patients with chronic venous insufficiency.

Background: The cutaneous microangiopathy plays a key role in the development of the skin clinical lesions of venous insufficiency. Capillaroscopy allows a non-invasive observation of the superficial skin capillaries of the lower leg, which have previously been shown to be altered in patients with advanced venous disease. As it is now available in a friendly, easy to handle way through modern video devices, we report our findings in a short series of patients with C3-C5 chronic venous disorders using this technique. Methods: A total of 21 patients with venous insufficiency (C3-C5 on at least one leg) underwent a capillaroscopic examination of both legs and pictures recorded from the sites of the most severe venous skin lesions. This was performed with a CapXview handheld video-capillaroscope (×100 magnification), allowing easy manual measurement of maximum capillary bulk diameter and capillary density. Results: Dramatic changes in capillary density, size, and shape were easily observed at the site of the venous skin lesions. A significant negative linear relationship was found between capillary density and the "C" classes (r = -0.45; P < 0.001). A significant negative correlation was also found between capillary density and bulk diameter (r = -0.52; P < 0.001). The area under the ROC curve for the mathematical prediction of venous skin changes by capillary density was 0.842, which shows the strength of the link between the microvascular and the clinical status. Conclusion: Video-capillaroscopy allows a direct observation of the cutaneous venous microangiopathy and provides the possibility to measure capillary density which allows its quantification. This simple to use technique shows the potential for a more precise follow-up and treatment evaluation of the cutaneous consequences of venous disease, which remains to be further investigated.

Patient Education in Spa Resorts: Experience from a French National Program for Patients with Chronic Venous Insufficiency.

The prognosis of chronic venous insufficiency (CVI) is greatly depending upon the ability of the patients to optimize their health-related behaviors (mainly compliance to compression stockings, physical activity and diet). As this is usually challenging for the patients, we developed a therapeutic education program (TEP) aiming at helping them to achieve these optimizations. We report here the preliminary results obtained with this program. This structured TEP was developed by a working group of 15 health professionals to be used during the regular French spa 3-week treatment course for CVI patients. The program included three interactive workshops aiming at improving the patients' knowledge, skills and motivation, two educational consultations allowing to set and follow-up their personal action plans and a built-in evaluation. It was implemented in spa resorts specialized in CVI. Among the first 150 patients (116 women and 34 men, mean age 69 years old (SD 8 years), 49% had post-thrombotic disease. Compliance to the education workshops was 98%. After a 3-month follow-up, 83% of the patients fully achieved at least one behavioral objective. Quality of life, as assessed by the CIVIQ 2 auto-questionnaire, improved at 3 months (p = 0.0024) and 9 months (p = 0.018). These results demonstrate the feasibility of a TEP for CVI patients and its ability to improve their health-related behaviors, opening the way for the development of similar programs for other chronic diseases in the setting of spa resorts.

Risks and contraindications of medical compression treatment - A critical reappraisal. An international consensus statement.

OBJECTIVES: Medical compression therapy is used for non-invasive treatment of venous and lymphatic diseases. Medical compression therapy-associated adverse events and contraindications have been reported, although some contraindications are theoretically based. This consensus statement provides recommendations on medical compression therapy risks and contraindications. METHODS: A systematic literature search of medical compression therapy publications reporting adverse events up until November 2017 was performed. A consensus panel comprising 15 international experts critically reviewed the publications and formulated the recommendations. RESULTS: Sixty-two publications reporting medical compression therapy adverse events were identified. The consensus panel issued 21 recommendations on medical compression therapy contraindications and adverse event risk mitigation, in addition to reviewing medical compression therapy use in borderline indications. The most frequently reported non-severe medical compression therapy-associated adverse events included skin irritation, discomfort and pain. Very rare but severe adverse events, including soft tissue and nerve injury, were also identified. CONCLUSION: This consensus statement summarises published medical compression therapy-associated adverse events and contraindications, and provides guidance on medical compression therapy. Severe medical compression therapy-associated adverse events are very rarely encountered if compression is used correctly and contraindications are considered.

The 2020 update of the CEAP classification system and reporting standards.

The CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification is an internationally accepted standard for describing patients with chronic venous disorders and it has been used for reporting clinical research findings in scientific journals. Developed in 1993, updated in 1996, and revised in 2004, CEAP is a classification system based on clinical manifestations of chronic venous disorders, on current understanding of the etiology, the involved anatomy, and the underlying venous pathology. As the evidence related to these aspects of venous disorders, and specifically of chronic venous diseases (CVD, C2-C6) continue to develop, the CEAP classification needs periodic analysis and revisions. In May of 2017, the American Venous Forum created a CEAP Task Force and charged it to critically analyze the current classification system and recommend revisions, where needed. Guided by four basic principles (preservation of the reproducibility of CEAP, compatibility with prior versions, evidence-based, and practical for clinical use), the Task Force has adopted the revised Delphi process and made several changes. These changes include adding Corona phlebectatica as the C4c clinical subclass, introducing the modifier "r" for recurrent varicose veins and recurrent venous ulcers, and replacing numeric descriptions of the venous segments by their common abbreviations. This report describes all these revisions and the rationale for making these changes.

Quantification of early cutaneous manifestations of chronic venous insufficiency by automated analysis of photographic images: Feasibility and technical considerations.

We postulate that blue telangiectasia and brownish pigmentation at ankle level, early markers of chronic venous insufficiency, can be quantified for longitudinal studies of chronic venous disease in Caucasian people. Objectives and methods To describe a photographic technique specially developed for this purpose. The pictures were acquired using a dedicated photo stand to position the foot in a reproducible way, with a normalized lighting and acquisition protocol. The image analysis was performed with a tool developed using algorithms optimized to detect and quantify blue telangiectasia and brownish pigmentation and their relative surface in the region of interest. To test the short-term reproducibility of the measures. Results The quantification of the blue telangiectasia and of the brownish pigmentation using an automated digital photo analysis is feasible. The short-term reproducibility is good for blue telangiectasia quantification. It is a less accurate for the brownish pigmentation. Conclusion The blue telangiectasia of the corona phlebectatica and the ankle flare can be assessed using a clinimetric approach based on the automated digital photo analysis.

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.

Impact of an educational program on the quality of life of patients with lymphedema: A preliminary evaluation.

OBJECTIVE: We report on the preliminary evaluation of a well-designed program, Living with Lymphedema. This longitudinal cohort study assessed patients' quality of life using questionnaires. Our main objective was to evaluate the satisfaction of the patients and their adherence to the program. This was done using a specific questionnaire of satisfaction as well as by noting patients' adherence to the program (number of patients attending all three consultations). The secondary objective was to assess the effect of the program on the patient's quality of life. The assessment criteria were the evolution of the Medical Outcomes Study 36-Item Short Form Health Survey and EuroQol questionnaire scores between the first (C1) and third (C3) consultations. METHODS: The Living with Lymphedema program targeted all patients with lymphedema in the Grenoble (France) conurbation and within the GRANTED health care network that includes vascular medicine specialists, primary care physicians, physical therapists, and dietitians in the Alpine region of France. All studied patients were ambulatory patients. The GRANTED network took care only of the educational aspect of the disease. All patients with primary or secondary lymphedema were offered the Living with Lymphedema program, whatever their age and the location of the lymphedema (upper or lower limbs). The collection of patient data conformed to the ethical and administrative regulations of the regional health authority. Grenoble Institutional Review Board (CPP Sud-Est V; No. 5891) approval for the study was specifically obtained for this evaluation on December 24, 2012. The program was built around one-to-one consultations, group workshops, and more specialized appointments. It was complementary to the routine medical care received by the patient (not evaluated in this study). It proposed three individual "educational" consultations, seven group workshops, and two specialized consultations with a dietitian. All the consultations or workshops were led by certified professionals trained in therapeutic education. RESULTS: The cohort was the 34 patients included in the program. We found a significant improvement in the physical dimension of the Medical Outcomes Study 36-Item Short Form Health Survey score (P = .01) between C1 and C3 but not for the psychic dimension. Visual analog scale scores of the ability to cope with the lymphedema showed a statistically significant improvement between C1 and C3 (P = .05). No difference was observed in adherence to compression therapy. CONCLUSIONS: This therapeutic educational program showed a significant improvement in several criteria of quality of life and in the autonomy of patients with lymphedema.

Controlling the digital ulcerative disease in systemic sclerosis is associated with improved hand function.

OBJECTIVES: Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan. METHODS: ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. RESULTS: Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046). CONCLUSIONS: In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.

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.

Ischemic digital ulcers affect hand disability and pain in systemic sclerosis.

OBJECTIVE: Ischemic digital ulcers (DU) are frequent and severe complications of systemic sclerosis (SSc). The purpose of our study was to assess the effect of DU on hand disability and pain in patients with SSc. METHODS: The Evaluation of the Impact of Recurrent Ischemic DU on Hand Disability in Patients with SSc (ECLIPSE) is a prospective, multicenter, noninterventional study with a 2-year followup. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan therapy were included between October 2009 and March 2011. This cohort is described at the time of inclusion. RESULTS: There were 190 patients (132 females) from 53 centers. Mean age ± SD was 43 ± 15 years at SSc diagnosis and 53 ± 15 years at inclusion. In 105 patients (56.2%), DU were the first non-Raynaud symptoms of SSc. The mean time interval between the occurrence of Raynaud phenomenon and the first DU episode was 6.6 ± 9.1 years. The mean numbers of active DU and fingers affected per patient for both hands were 2.3 ± 1.8 and 2.2 ± 1.6, respectively. Presence of active DU at inclusion was significantly associated with pain and impaired hand function: Visual Analog Scale for pain (0 to 10) was 6.2 ± 2.6 versus 2.5 ± 2.4 (p < 0.0001) and Cochin Hand Function Scale for hand disability (0 to 90) was 38 ± 20 versus 25 ± 19 (p < 0.0001), respectively. CONCLUSION: DU represent a major sign of SSc, often affecting multiple fingers and both hands. They are significantly associated with pain and hand disability.

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.

Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials.

INTRODUCTION: Recent controlled trials have assessed the efficacy of phosphodiesterase-5 (PDE-5) inhibitors in secondary Raynaud's phenomenon (RP). However, the conclusions are conflicting, and whether these drugs are effective remains unclear. The objective of this meta-analysis was to determine the efficacy of PDE-5 inhibitors on Raynaud's Condition Score (RCS) and frequency and duration of attacks. METHODS: A systematic review of articles was performed (sources included Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials). Only double-blind, randomised controlled trials (RCTs) were included. Studies were selected independently by two authors using predefined data fields, including study quality indicators. RESULTS: Six RCTs were included (one with sildenafil, one with modified-release sildenafil, three with tadalafil and one with vardenafil). PDE-5 inhibitors significantly decreased mean RCS by -0.46 (-0.74 to -0.17) (p=0.002), the daily frequency of ischaemic attacks by -0.49 (-0.71 to -0.28) (p<0.0001), and daily duration of RP attacks by -14.62 (-20.25 to -9.00) min (p<0.0001). CONCLUSIONS: PDE-5 inhibitors appear to have significant but moderate efficacy in secondary RP. A further large RCT is needed.

Clinical analysis of the corona phlebectatica.

BACKGROUND: The corona phlebectatica (CP) is classically described as the presence of abnormally visible cutaneous blood vessels at the ankle with four components: "venous cups," blue and red telangiectases, and capillary "stasis spots." Previous studies showed that the presence of CP is strongly related to the clinical severity of chronic venous disorders (CVD) and the presence of incompetent leg perforators. The aim of this study was to select the most informative components of the CP in the assessment of the clinical severity of CVD patients. METHODS: A multicentric series of 262 unselected patients (524 limbs) consulted for CVD were clinically evaluated using a standardized form to record the CEAP "C" items and the presence of the four CP components. Standard categorical and ordinal statistics were used to describe the external validity of the CP components as severity indexes, taking the "C" classes as reference. RESULTS: "Stasis spots" (P < .001; r = .44) and blue telangiectases (P < .01; r = .32) were linearly associated with the ascending order of "C" classes, whereas the relationship is less clear for the red telangiectases and the "venous cups." The association pattern of the four components showed that only the blue telangiectases and the "stasis spots" were consistent with each other. Blue telangiectases were found more sensitive (0.91 vs 0.75) but less specific (0.52 vs 0.80) than "stasis spots" for advanced venous insufficiency (CEAP "C4-6"). CONCLUSION: This study shows that only blue telangiectases and "stasis spots" provide valuable information in patients with CVD and deserve to be taken into account in the evaluation of such patients. Further studies are needed to show the reproducibility of this data, which we regard as essential for clinical use.

Prevalence, risk factors, and clinical correlates of ulnar artery occlusion in the general population.

BACKGROUND: Occlusion of the ulnar artery is found in a substantial proportion of elderly patients. The aim of this study was to estimate the prevalence of ulnar artery occlusion in a sample of the general population of France, look for its risk factors, and evaluate its clinical correlates. METHODS: This study was an offshoot of a cross-sectional epidemiologic study in the general population of four locations in France (Tarentaise, Grenoble, Nyons, and Toulon). In phase I, random samples of 2000 individuals per location aged >or=18 years old were interviewed by phone for screening of Raynaud phenomenon. In phase II, subsamples of individuals were invited to a medical interview and physical examination where the presence of Raynaud phenomenon and occupational risk factors were recorded and a bilateral clinical Allen test was performed for the detection of ulnar artery occlusion. Phase II comprised 688 women and 335 men. RESULTS: In 36 men and seven women, at least one occluded ulnar artery was found. The estimated prevalence was 9.6% in men and 1.0% in women (P < .001). The occluded artery was more often in the dominant hand of both men (8.1% vs 2.4%; P < .001) and women (0.9% vs 0.4%; P = .34). Ulnar artery occlusion was found more often in men aged >50 years (16.4%) than in younger men (1.4%; P < .001). Besides age, male sex, and dominant side, the only independent risk factor was an occupational exposure in men to repeated palmar trauma, with a significant quantitative relationship in the frequency of the impacts (P < .001) and the duration of the exposure (P < .001). Exposures to hand-held vibrating tools and cigarette smoking did not show a significant relationship in the multivariate analysis. Most individuals with ulnar artery occlusion did not have associated complaints; however, the diagnostic criteria for Raynaud phenomenon was validated in 13 of the 36 affected men. The association remained significant after adjusting for occupational exposure to vibrating tools. One individual reported a previous episode consistent with an attack of permanent digital ischemia. CONCLUSION: This study confirms a substantial prevalence of ulnar artery occlusions in the general population, mostly in middle-aged and elderly men, which appears to be principally related to an occupational exposure to repeated occupational palmar trauma. Although there is a significant association with Raynaud phenomenon, most often the consequences of this occlusion remain subclinical.

Clinical features of scleroderma patients with or without prior or current ischemic digital ulcers: post-hoc analysis of a nationwide multicenter cohort (ItinérAIR-Sclérodermie).

OBJECTIVE: Digital ulcers are the most frequent vascular manifestations of systemic sclerosis (SSc). Clinical features of patients with prior or current digital ulcers have not been extensively described. This cross-sectional analysis of a large multicenter cohort compared the characteristics of SSc patients with prior or current digital ulcers with those never affected. METHODS: Patients with prior/current digital ulcers or never affected were identified in the cohort of SSc patients enrolled in the French ItinérAIR-Sclérodermie registry. Rodnan skin scores, pulmonary function test results, and clinical and immunological data were analyzed to identify digital ulcerassociated clinical features. RESULTS: Of 599 SSc patients, 317 had prior or current digital ulcers. These patients were more frequently male, with impaired diffusing capacity for carbon monoxide (DLCO), and higher Rodnan skin scores than patients never affected by digital ulcers. In a multivariate analysis, male gender, early onset of SSc, increased duration of SSc, high Rodnan skin score, and presence of anti-topoisomerase I antibodies (anti-topo I) were associated with prior or current digital ulcers. Comparison of patients with current digital ulcers versus patients never affected indicated that affected patients had increased duration of SSc, impaired DLCO, increased Rodnan score, and younger age at onset of SSc. CONCLUSION: Male patients with early onset SSc, more severe skin fibrosis, impaired DLCO, and anti-topo I were most likely to exhibit prior or current digital ulcers. Confirmation of these results in a prospective longitudinal study may enable identification of patients at greatest risk of developing digital ulcers, facilitating management of this disabling complication.

Correlation of biomarkers of endothelium dysfunction and matrix remodeling in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease characterized by microvascular dysfunction and excessive fibrosis. However, the relationship between these 2 features remains unclear. Endothelial dysfunction can be assessed by quantifying plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase. Matrix remodeling can be assessed by quantifying serum tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Both biomarkers are elevated in patients with SSc. Our objective was to test whether plasma ADMA is correlated with serum TIMP-1. METHODS: We enrolled 91 subjects, 39 patients with SSc, 28 patients with primary Raynaud's phenomenon (RP), and 24 healthy volunteers. Plasma ADMA concentrations were measured by liquid chromatography-tandem mass spectrometry. Serum TIMP-1 concentrations were determined by ELISA. RESULTS: Mean ADMA concentrations were higher in patients with SSc (0.68 microM +/- 0.12) than in patients with primary RP or healthy volunteers (respectively, 0.56 microM +/- 0.14 and 0.62 microM +/- 0.12; p = 0.002). Median serum TIMP-1 concentrations were increased in patients with SSc compared to primary RP and healthy volunteers [12 (9-15), 11 (8-13), and 10 (7-13) nM, respectively; p = 0.05]. In the SSc group, we observed a statistically significant correlation between plasma ADMA and serum TIMP-1 (r = 0.34, p = 0.035). CONCLUSION: These data are consistent with our hypothesis of an association of endothelial dysfunction and matrix remodeling in scleroderma spectrum disorders.