European guidelines for sclerotherapy in chronic venous disorders.

AIM: Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy. METHODS: This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7-10 May 2012 in Mainz. The conference was organized by the German Society of Phlebology. These guidelines review the present state of knowledge as reflected in published medical literature. The regulatory situation of sclerosant drugs differs from country to country but this has not been considered in this document. The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines. RESULTS: This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, polidocanol and sodium tetradecyl sulphate. Other sclerosants are not discussed in detail. The guideline gives recommendations concerning indications, contraindications, side-effects, concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy of varicose veins and venous malformations.

Treatment of chronic venous disease with flavonoids: recommendations for treatment and further studies.

OBJECTIVES: A variety of studies have suggested that flavonoids are effective for the treatment of CVD. However, many questions remain about their mechanism of action and when, how, and for what signs and symptoms they should be used. METHOD: A panel of experts in CVD met in Budapest, Hungary in December 2011 to discuss the current state of knowledge of CVD and the role of flavonoids in its treatment. The discussion was based on a literature search in the current databases. The goals of this paper are recommendations for further studies on the use of flavonoids in the treatment of CVD. RESULTS: There is good evidence to recommend the use of flavonoids in the treatment of CVD. However, because of the poor quality of some older clinical trials, inadequate reporting, and insufficient information, much work is still needed to firmly establish their clinical efficacy and to determine when and how they should be employed. In particular, long-term randomized, placebo-controlled, double-blind studies are needed to establish the efficacy and safety of flavonoids. Additional studies are also needed to establish their mechanism of action, pharmacokinetics, toxicity, and cost-effectiveness. CONCLUSIONS: Aside from good evidence for the use of flavonoids in CVD further studies are indicated to establish long term treatment in this indication.

Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions.

AIM: The aim of this article was first to review the complex pathophysiological mechanisms responsible for symptoms and signs of primary chronic venous disease (CVD) that allow the identification of targets for pharmacological treatment. The results of CVD treatment with venoactive drugs (VADs) were emphasised and presented in the form of recommendations. The last section raises key questions to be answered to improve protocols for good clinical trials and to draw up future guidelines on these agents. METHODS: The literature has been reviewed here using PubMed and Embase. RESULTS: Venous hypertension appears to underlie all clinical manifestations of primary CVD. Inflammation is key in wall remodelling, valve failure and subsequent venous hypertension. Changes in the haemodynamics of veins are transmitted to the microcirculation, resulting in capillary alteration leading to oedema, skin changes and eventually venous ulceration. Venous symptoms may be the result of interplays between pro-inflammatory mediators and nerve fibres located in the venous wall. Therefore, venous inflammation constitutes a promising therapeutic target for pharmacological intervention, and some available VADs could attenuate various elements of venous inflammation. Based on recent studies, reviews and guidelines, tentative recommendations for the use of VADs were proposed and strong recommendations were given to two of them (micronised purified flavonoid fraction and oxerutins). CONCLUSION: VADs should be accorded a better role in the management of CVD. However, larger and more definitive clinical trials are needed to improve the existing recommendations.

[Chronic venous insufficiency in postthrombotic syndrome and varicose veins]. / Chronische venöse Insuffizienz bei postthrombotischem Syndrom und Varikose.

Venous disorders have a high prevalence and require approximately 1% of health budgets of industrialized countries. The postthrombotic syndrome (PTS) is defined by subjective symptoms and morphologic trophical skin changes following deep venous thrombosis. Prevention of venous thromboembolism in risk situations, easy availability of diagnostic tools (D-dimers, colour-coded duplex sonography) and early detection of deep venous thrombosis, as well as immediate therapeutic anticoagulation along with leg compression during the acute phase and over a two year period of time significantly reduce the incidence of PTS. Chronic venous insufficiency (CVI) includes trophical skin and soft tissue pathologies of the lower leg due to venous hypertension in the distal venous system of the lower extremity. Roughly, two main causes can be distinguished. (A) Deep venous insufficiency (A1 in postthrombotic syndrome; A2 in primary deep venous insufficiency) and (B) superficial venous reflux, usually varicose veins. Compression therapy, surgical ablation of superficial venous reflux, and tangential ablation with split skin graft (shave treatment) of refractory venous ulcers are the mainstays in the treatment of CVI.

Exercise-induced vasculitis.

BACKGROUND: Usually misdiagnosed and ignored in the literature, exercise-induced vasculitis (EIV) is not uncommon, occurring mostly in long-distance runners and in females after long walks, especially in hot weather. OBSERVATIONS: I report 23 otherwise healthy patients (22 females, 1 male) who developed EIV after walking or hiking in hot weather. Erythematous, urticarial or purpuric plaques arose on the lower legs, not involving skin compressed by socks. Symptoms included itch, pain, and burning sensation. Lesions resolved after some days. Relapses were frequent at further muscular exercise, and could be prevented in some cases by compression hosiery, manual lymphatic drainage, intake of oedema protective agents, or steroids (local or systemic). INVESTIGATIONS: Histopathology demonstrated leucocytoclastic vasculitis in five biopsies, and urticarial vasculitis in one. Extensive blood investigations have been performed in six patients and were negative. No clear relation with chronic venous disease (duplex or Doppler) had been established in 12 patients. CONCLUSIONS: I suggest denominating this condition exercise-induced vasculitis. This clinical entity is well defined, but poorly recognized. The presentation of 23 original cases demonstrates its reality.

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

[What are the epidemiological data on the consequences of smoking-related increased risk in pregnant women? Dermatological consequences]. / Quelles sont les données épidémiologiques concernant les conséquences de l'excès de risque lié au tabagisme chez les femmes enceintes? Conséquences dermatologiques.

Smoking has numerous effects on skin. Some of them are well established, others are more debatable. Smoking is a cofactor of skin aging after chronic sun exposure, as demonstrated by recent histological, biochemical and cutaneous relief studies. Smoking is a well established risk factor of cutaneous, mucous membrane cancers, and some gynecologic cancers as well, in some cases increased by pregnancy. However, published studies have included small numbers of subjects. Some skin affections are worsened by smoking, and others might be improved. However scientific data on smoking and skin or pregnancy are both scarce.

Venous leg ulcer: a meta-analysis of adjunctive therapy with micronized purified flavonoid fraction.

OBJECTIVE: To assess the effect of oral treatment with micronized purified flavonoid fraction (MPFF) on leg ulcer healing. DESIGN: Meta-analysis of randomised prospective studies using MPFF in addition to conventional treatment. MATERIALS AND METHODS: Five prospective, randomised, controlled studies in which 723 patients with venous ulcers were treated between 1996 and 2001 were identified. Conventional treatment (compression and local care) in addition to MPFF was compared to conventional treatment plus placebo in two studies (N = 309), or with conventional treatment alone in three studies (N = 414). The primary end point was complete ulcer healing at 6 months. RESULTS: At 6 months, the chance of healing ulcer was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone (RRR: 32%; CI, 3-70%). This difference was present from month 2 (RRR: 44%; CI, 7-94%), and was associated with a shorter time to healing (16 versus 21 weeks; P = 0.0034). The main benefit of MPFF was present in the subgroup of ulcers between 5 and 10 cm2 in area (RRR: 40%; CI, 6-87%), and those present for 6-12 months duration (RRR: 44%; CI, 6-97%). CONCLUSION: These results confirm that venous ulcer healing is accelerated by MPFF treatment. MPFF might be a useful adjunct to conventional therapy in large and long standing ulcers.

The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.

BACKGROUND: The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur. CONCLUSION: This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.

Compression therapy.

Compression therapy, either active or passive, is the cornerstone of treatment for all venous and lymphatic disorders. Its major limitations are poor patient compliance, difficulty to apply in the elderly, and insufficient knowledge and skill in the majority of physicians. New modalities, such as four-layer bandage, tubular gradient compression, or new textile technologies, may secure a better application in difficult cases such as leg ulcers.

Phlebectomy. Technique, indications and complications.

Phlebectomy, first described by Aulus Cornelius Celsus (25 BC - 45 AD), was re-invented 40 years ago by Dr. Robert Müller, in Neuchâtel, Switzerland. This safe, esthetic, effective and economical operative technique has now been fully developed and adopted all over the world. Phlebectomy hooks enable venous extraction through minimal skin incisions (1-3 mm) or even needle punctures, assuring complete and definite eradication of the veins. The small size of the skin incisions usually results in little or no scarring, contrary to that found in classical venous surgery, and avoids the possible complications of sclerotherapy, such as skin necrosis or residual hyperpigmentation. Sites particularly appropriate for ambulatory phlebectomy include incompetent saphenous veins (except the sapheno-femoral and in most cases the sapheno-popliteal junctions), their major tributaries, perforating, groin pudendal veins, reticular veins (popliteal fold, lateral thigh and leg) and veins of the ankles and the dorsal venous network of the foot. Curettage of telangiectasias is a less well known indication, but it is also quite effective in removing networks of thick blue spider veins. Ambulatory phlebectomy of body areas, other than the legs, include dilated periorbital, temporal or frontal venous networks and venous dilatation of the abdomen, arms or dorsum of the hands. Long term results, if the indications and technique were correct, are excellent. Complications, in skillful hands, seldom occur. They may be classified as cutaneous, vascular, neurological or general and are usually benign.

Phlebectomy--cosmetic indications.

Ambulatory phlebectomy is a safe, aesthetic, effective and economical operative technique, which enables venous extraction with a special hook, assuring complete and definitive eradication of the veins. Minimal skin incisions (1-3 mm), or even needle punctures, usually result in little or no scarring. This aesthetic method is particularly indicated to treat unsightly varicose veins, such as reticular veins (popliteal fold, lateral thigh and leg), groin pudendal veins, veins of the ankles and the dorsal venous network of the foot. Curettage of telangiectasias is a less well-known technique, but it is also effective in removing networks of thick blue spider veins. Ambulatory phlebectomy of body areas other than the lower limbs include dilated periorbital, temporal or frontal venous networks and venous dilatation of the abdomen, upper limbs or dorsa of the hands.

Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous insufficiency.

Chronic venous insufficiency (CVI) affects a large number of people in Western countries, and is responsible for considerable inconvenience, discomfort, suffering, and costs. Micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin-Daflon 500 mg) is a potent venotropic drug used in the treatment of venous insufficiency. Pharmacological and clinical studies demonstrated the comprehensive mode of action of Daflon 500 mg: it increases venous tone, it improves lymph drainage, and it protects the microcirculation. Clinical international, prospective, multicenter, randomized, controlled studies versus placebo studies documenting the effects of Daflon 500 mg in CVI at advanced stages with edema, skin changes, and venous leg ulcer are reviewed. In edema, one of the most frequent complaints of patients, Daflon 500 mg brings about a significant reduction in leg circumference, thanks to its capacity to inhibit inflammatory reactions and to decrease capillary hyperpermeability. The rationale for the use of Daflon 500 mg for treatment of skin disorders and venous leg ulcer is its action on the microcirculation-damaging processes. Regarding skin changes, Daflon 500 mg has been shown to improve venous trophic disorders, like gravitational (stasis) dermatitis, and dermatofibrosclerosis. In venous leg ulcer, Daflon 500 mg's clinical efficacy has been demonstrated in addition to standard treatment or versus standard treatment alone. Daflon 500 mg, thanks to its comprehensive mode of action on the veins, lymphatics, and microcirculation, is the method of choice not only in the early stages of CVI treatment, but also in the severe stages of this condition, in combination with compression treatment, sclerotherapy, and surgery if appropriate.