Servier – Phlebolymphology

I. UIP Consensus, UIP Fellowships

Angelo Scuderi, Brazil


The President of the Union Internationale de Phlébologie (UIP) summarized the 60-year history of the UIP, which evolved from national associations to supranational phlebological societies, to become an international learning society. It now represents 61 societies from 57 countries over five continents. In the last 5 years, more than 20 new societies have joined the UIP, and this year 10 new candidate countries wish to join the society.

Guidelines and consensus documents are a very important focus of a President’s term and cover a variety of subjects, led by prestigious experts:

• Update on venous malformations (B.B. Lee)
• Phlebology training curriculum (K. Parsi)
• Invasive treatment of deep venous thrombosis (F. Lurie)
• Update on diagnosis and treatment of primary lymphedema (B.B. Lee)
• Venous edema (A. Scuderi, Thernard A.C.)
• Duplex ultrasound investigation of the veins in chronic venous disease, part I and II (A. Cavezzi)
• Duplex ultrasound investigation after treatment of varicose veins (M. Meissner)
• Superficial thrombophlebitis (E. Kalodiki)
• Compression therapy (H. Partsh)
• Venous symptoms in C0 and C1 patients (J.P. Benigni)
• Corona phlebectatica (P.L. Antignani)
• Endovenous thermal ablation for varicose vein disease (S. Schuller)
• Prevention and treatment of venous thromboembolism (A. Nicolaides)
• Venous hemodynamics (B.B. lee)
• Sclerotherapy (P. Coleridge-Smith)
• Venous ulcer (G. Mosti)
• Redefining venous disease (A. Caggiati)

The dissemination of UIP messages is furthered by the excellent Internal Angiology journal and electronically via www.uip-phlebology.org

Pier Luigi Antignani, Italy


Corona phlebectatica is characterized by a fan-shaped pattern of numerous bluish, intradermal veins with a diameter less than 3 mm on the medial and/or lateral aspects of the ankle and foot in the inframalleolar area. The new recommendations recognize two grades of severity: grade 1 for insipient corona with more than five clusters of bluish intradermal veins in the retromalleolar area; and grade 2 for definite corona with tortuous bluish intradermal veins with a diameter less than 3 mm in the submalleolar area, extending to over half the length of the foot or more.

Corona phlebectatica is a strong clinical predictor of chronic venous disease (CVD) and subsequent occurrence of skin changes, and has prognostic value for the progression of CVD. It is also a highly significant clinical sign for chronic venous insufficiency. The author stressed that corona phlebectatica should be evaluated in every patient with CVD, and should be considered for inclusion in existing or future classifications/scoring systems of CVD.

Jean-François Uhl, France


The correlation between venous symptoms and the presence of telangiectases or reticular veins (C1) is very controversial. Even though the inflammatory reaction and subsequent interaction with venous nociceptors can explain the venous pain, other symptoms, such as a feeling of swelling and cramps, do not appear to be related to the nociception. A scoring system that could incorporate more specificity may help in distinguishing vein symptoms from other conditions. Furthermore, static foot disorders can be present in more than 30% of C0s and C1s patients. In fact, postural changes and impairment of the foot and calf pumps may lead to an increase in the pain. Current treatment of these specific patients may include compression, venoactive drugs, and reduction of risk factors. Meanwhile, future research should include epidemiological studies on venous pain in C0s and C1s patients, look at the possible relationship between female hormones and symptomatic telangiectases, and evaluate the potential relationship between venous pain, static foot disorders, and postural changes.

Sanja Schuller-Petrovic, Austria


The recommendations on the use of endovenous thermal ablation for varicose vein disease (ETAV) were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts’ opinion. Most of the evidence accumulated so far relates to endovenous laser ablation and radiofrequency segmental ablation. As a result, 26 recommendations were presented concerning the qualification of ETAV providers, pretreatment and post-treatment evaluation and documentation, indications and contraindications, anesthesia to be delivered, vein cannulation and catheter introduction, infiltration of tumescent solution, treatment records, post-treatment advice, and complications.

Byung-Boong Lee, USA


The management of primary lymphedema continues to be a challenge for patients and treating physicians worldwide. Progress in the past decades has been significant in both the diagnosis and treatment of this disabling condition. Yet, significant controversies relating to the nomenclature/definition of primary lymphedema and its contemporary management remained from the previous consensus, with many issues left open for future updating. For the 2013 consensus, 20 experts were gathered to give special consideration to the following topics:1) genetic issues; 2) molecular biology issues; 3) perspectives on edema; 4) lipedema as a differential diagnosis; 5) primary phlebolymphedema; 6) decongestive lymphatic therapy (DLT) based on compression therapy; 7) update on lymphatic microsurgery; 8) pharmacological treatment; and 9) elephantiasis management.

The author underlined that primary lymphedema can be managed adequately as a form of chronic lymphedema by a sequenced and targeted treatment and management program based around a combination of DLT with compression therapy. Treatment in the maintenance phase should include compression and self-care (self-massage, thorough personal hygiene and skin care, lymph transport promoting exercises, and pneumatic compression therapy applied at home). When conservative treatment is not effective, the management of primary lymphedema can be improved with suitable surgery, either reconstructive or ablative. Both surgical techniques are very effective for initially controlling the progression of lymphedema, but ultimately initial success cannot be maintained without additional postoperative DLT. Compliance with a long-term commitment to postoperative DLT is actually the most critical factor determining the success of any new treatment strategy, whatever the surgical procedure. The future management of primary lymphedema may be significantly enhanced with the prospect of new gene-, and perhaps, stem cell–oriented.

Gyozo Szolnoky, Hungary


Lipedema is a bilateral, symmetrical, ‘bike pant’ or column-shaped fatty swelling of the lower limbs; upper limbs are less commonly involved. It is a female disorder; males usually only develop lipedema as a result of a hormonal disturbance. The general incidence of lipedema among women is estimated to be around 11%.

The diagnosis is mostly clinical (no involvement of the foot, absent Stemmer’s sign, bilateral fat pads, filling of the retromalleolar sulci, non- or minimally-pitting edema, pinch test), but can be complemented by several noninvasive (waist-toheight ratio, vacuum suction method for capillary fragility, assessment of aortic stiffness, ultrasound, computed tomography, magnetic resonance imaging [MRI]) and minimally invasive tests (lymphoscintigraphy, MRI lymphoscintigraphy, fluorescent microlymphoscintigraphy). The condition has a high familial incidence with X-linked or more likely, autosomal dominant, inheritance with sex limitation. There are three progressive stages. Treatment is based on dietary restrictions for weight control, and decongestive lymphatic therapy followed by compression in the maintenance phase. A surgical approach (liposuction) may be considered, but must always be followed by compression.

Sandro Michelini, Italy


Primary lymphedema is an inherited condition caused by mutations in three genes VEGFR3, FXOC2 and GJC2. Diseases causing mutations in single probands affected by lymphedema have also been identified in another two genes from eight different families: HGF and MET.

To understand more clearly the role of mutations in genes VEGFR3 and FOXC2 in the manifestation of lymphedema the author designed a study with two objectives:

Define the detailed pedigree for each lymphedema family and establish the genotype for the familial mutation identified in the proband for each individual family member.

Perform lymphoscintigraphy in family members who, although characterized by the presence of the familial mutation, do not show clinically manifest signs of the disease.

Among seven families (two VEGFR3-related, one FOXC2-related) at least one subject carried the familial pathogenic allele despite clinically silent disease. In some families (VEGFR3 and FOXC2-related), lymphoscintigraphic data from individuals with clinically silent disease showed a monolateral delay in lymphatic drainage through the inguinal nodes.

In four subjects, mutant alleles of lymphangiogenic genes (VEGFR3 or FOXC2) were identified without clinical signs of lymphedema; lymphoscintigraphic data from one family revealed an insufficiency of the lymphatic system in one clinically silent subject.

These data suggest that additional genes may be involved in cases of incomplete penetrance of lymphedema, which may be VEGFR3-related or due to variable expressivity of VEGFR3, or FOXC2-related. These “additional genes” could be identified by the use of next generation technologies for the analysis of subjects belonging to large families.

Nonsense or missence mutations are detectable in cases of both familial and sporadic lymphedema. Among probands with lymphedema and wild type VEGFR3, FOXC2, GJC2, HGF, and MET genes, it is plausible that others genes are responsible (Mendelian Disease), and the molecular analysis of large pedigrees is recommended. A conspicuous number of subjects (in particular in “sporadic cases”) are affected by a complex genetic disorder (non-Mendelian disease), where a major causative gene is not identifiable, but a complex pattern of inheritance (in which the person is at increased risk for developing the condition) could be involved.

Further reading:
Northup KA, Witte MH, Witte CL Syndromic classification of hereditary lymphedema. Lymphology. 2003;36:162-189.

Ferrell RE, Kimak MA, Lawrence EC, Finegold DN. Candidate gene analysis in primary lymphedema. Lymphat Res Biol. 2008;6:69-76.

Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nature Rev. 2007;8:464-478.

Byung-Boong Lee, USA


The diagnosis of venous malformations for therapeutic decisions can be made with non- to minimally-invasive investigation alone. The full integration of open surgical and endovascular therapies by a multidisciplinary team will be the main strategy for the contemporary management of venous malformations. A team approach using new treatment strategies can improve long-term treatment outcomes and reduce the morbidity and recurrence/persistence rate compared with more conventional approaches.

Byung Boong Lee, USA


Venous hemodynamic issues, concepts, and measurements in the study of lower limb venous disease have remained unchanged for a long time because of their complexity. However, the improvements in diagnostic technologies (ultrasound) that have taken place in the last decades have increased our knowledge in this area.

The aim of this document is to provide guidelines on venous hemodynamic measurements in the investigation of lower limb venous disease according to the best currently available scientific evidence. This will provide clinicians and researchers involved in the diagnosis and management of lower limb venous disease with a clear and concise account of the hemodynamic evidence for various concepts in the management of venous disorders. The information will either back up previous recommendations or show that they are unfounded.

Where scientific evidence was lacking or weak, a consensus of opinion among the expert members of the panel was reached to support the recommendations. The chairmen of the document (B.B. Lee, A. Nicolaides, and M. Meissner), with the editorial secretary (E. Kalodiki), led a group of more than 50 prestigious authors to summarize this knowledge in 13 review chapters.

Philip Coleridge-Smith, UK


Foam sclerotherapy is a safe and effective treatment for venous disorders when carried out by trained physicians following the recommendations of this consensus.

The consensus provides a tool for decision making in foam sclerotherapy that could help in all aspects of treatment, and provides general recommendations to physicians practicing this technique:

• Suitability of patients for treatment
• Clinical findings with an indication for foam sclerotherapy
• Duplex ultrasound investigation
• Relative and absolute contraindications
• Equipment and methodology
• Follow-up standardization

UIP award presentations

David Connor, Australia


This study is designed to improve knowledge of sclerosant agents at sites distant from the endothelium of the target vein, as sclerosants can produce microparticles when interacting with cellular membranes, which promote angiogenesis and procoagulant activity.

The study will determine the in vitro effect of sclerosants on endothelial cells at sites 5, 15, 30, and 45 cm distant from the target in both superficial and deep veins. While this has been previously studied in other cells (eg, platelets), this is the first time such a study has been performed in endothelial cells.

Christopher Lattimer, UK


The effects of graduated elastic compression (GEC) in veins of the calf are to reduce venous volume and reflux, and to assist venous return. The aim of this study is to assess the effects of GEC in healthy subjects. The study will be prospective, performed in 20 consecutive right legs, with three groups of subjects: those with no compression, those with class 1 compression, and those with class 2 stockings. Venous outflow parameters (venous volume, incremental pressure causing the maximum increase in volume [IPMIV], outflow at 1 sec, and time taken to empty 90% of venous volume [VET90) will be assessed using air plethysmography (APG). Preliminary results show a dose-response improvement in parameters of venous outflow, suggesting that stocking performance is quantifiable and that APG could be an adequate tool to customize stockings for patients.

Markus Fokou, Cameroon


There is a lack of evidence on the incidence and prevalence of chronic venous disorders (CVDs) in tropical regions around the world, where more than 700 million people live. There is only one study in a black population, but this was performed in the USA (San Diego) and does not provide any valid data on sub- Saharan countries.

The current study will examine 400 patients over a 24 month period to determine, using clinical examination (CEAP), quality of life, and Doppler ultrasound, the epidemiological characteristics of CVDs in sub-Saharan populations.

Gyozo Szolnoky, Hungary


Several other factors in addition to venous congestion play a role in ulcer formation. The aim of the study was to clarify the role of the immune response in venous ulcers. The authors used measures of several humoral and cellular parameters to determine the characteristics of ulcers from patients with normal control, and to differentiate between ulcers with a capacity for healing and those without this capacity. Cellular immune activity was determined by measuring Candida albicans killing activity, and humoral immunity response by measuring xIL-A, IL-6, CXCL8 (IL-8), IL-10, TNF, Tyro3, and Avl.

The study was performed in 69 patients with venous leg ulcers and 42 age- and sex-matched controls. The authors found that patients with leg ulcers have lower Candida killing activity and a “silencing” counteraction against the active innate immune response.

Venous education around the world

This session was particularly interesting for physicians specializing in patients with chronic venous disease (CVD). Physicians intending to start a practice in phlebology require a high-quality basic education in this field, and those who are already working must keep their knowledge and skills up to date. One of the goals of E. Rabe’s (Germany) presentation was to demonstrate the need for a well-organized education system in the world, in view of the fact that about 30% of the population has pronounced forms of CVD. He also stated that despite the huge incidence of CVD, phlebology is not recognized as a specialty in all parts of the world. The way to change the situation is to accept phlebology as a multidisciplinary specialty. It is also mandatory to maintain a worldwide cooperation between vascular societies when establishing phlebology training, educational programs and certification.

The experience of the Australasian College of Phlebology was presented by K. Parsi from Australia. This College has created a training program with three tiers. Physicians wanting to confine their treatment to sclerotherapy attend a 1-year course. Those wanting to perform more advanced procedures such as laser or radiofrequency ablation, require a 2-year training program. For physicians interested in managing all types of venous pathology, a 4-year training is mandatory. The system uses online training models to cover the whole curriculum. After every level, physicians perform written and clinical exams – the higher the tier, the more in-depth and difficult the tests become.

S. Zimmet (USA) described venous education in the USA. He underlined that in an ideal world, a venous specialist would be able to manage all patients with all the acceptable tools. However, currently no single specialty provides a comprehensive curriculum covering all aspects of venous diseases. The American Board of Venous and Lymphatic Disorders has composed an exam test with 200 items across six categories. This exam is not yet mandatory, but can help an examinee improve his/her knowledge base.

B. Eklöf described the situation in Europe where two countries, France and Germany, have a well-developed system of postgraduate training in phlebology as a sub-specialty. However, these are the only countries in Europe with such a program and certification process. This was confirmed by M. Kurtoglu (Turkey) who has analysed the issues surrounding venous education in other European countries. The main problem, in his opinion, is the absence of standardized training models in phlebology.

Current efforts to create a standardized education in Europe were presented by M. Neumann (The Netherlands), one of the founders of the European College of Phlebology. The aim of this organization is to cooperate with scientific societies and authorities to create a Europe-wide system of venous education and certification.

Take-home message: Phlebology is a multidisciplinary specialty. A unified system of phlebology training is required worldwide.