Prevention and treatment of venous ulcers in primary chronic venous insufficiency

Abstract

Primary chronic venous disease (PCVD) is a progressive degenerative condition that usually results in vein wall weakness, producing valvular incompetence. The disease most frequently occurs in the superficial veins and presents as asymptomatic cosmetic varicose veins. PCVD may also advance to symptomatic stages with pain, edema, skin changes, or venous ulcerations. Primary venous reflux can also develop in the deep and perforating veins. PCVD may also include a symptomatic obstructive element when a nonthrombotic iliac vein lesion (NIVL) is present. PCVD is defined by the basic CEAP classification as: C2-6 Ep As,d,p Po,r.1Eklöf B. Rutherford R.B. Bergan J.J. Carpentier P.H. Gloviczki P. Kistner R.L. et al.American Venous Forum International Ad Hoc Committee for Revision of the CEAP ClassificationRevision of the CEAP classification for chronic venous disorders: consensus statement.J Vasc Surg. 2004; 40: 1248-1252Abstract Full Text Full Text PDF PubMed Scopus (1431) Google Scholar The letter p (primary) refers to nonthrombotic, noncongenital etiology. The pathology is mainly related to deep and/or superficial valve incompetence creating an axial reflux projecting into the ulcer area.2Bergan J.J. Schmid-Schonbein G.W. Coleridge-Smith P.D. Nicolaides A.N. Boisseau M.R. Eklof B. Chronic venous disease.N Engl J Med. 2006; 355: 488-498Crossref PubMed Scopus (692) Google Scholar Symptomatic NIVL has previously been described as May-Thurner syndrome, Cockett's, or “iliac vein compression” syndrome.3May R. Thurner J. The cause of the predominantly sinistral occurrence of thrombosis of the pelvic veins.Angiology. 1957; 8: 419-427Crossref PubMed Scopus (493) Google Scholar, 4Cockett F.B. The iliac compression syndrome alias “iliofemoral thrombosis” or “white leg.”.Proc R Soc Med. 1966; 59: 360-361PubMed Google Scholar The existence of marked iliac vein compressions (more than 50% obstruction) with or without intraluminal lesions has been shown to be more pathogenic than previously thought. In the past, these lesions have been considered a common finding of little clinical importance.5Raju S. Neglén P. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in pathogenicity.J Vasc Surg. 2006; 44 (discussion 144): 136-143Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar Primary venous insufficiency should be differentiated from secondary postthrombotic venous insufficiency because the two conditions differ in pathophysiology, management, and prognosis. “Hydrostatic” leg ulcers without venous reflux and/or obstruction (eg, in morbidly obese patients [C5-6 Es An Pn]) are excluded in this discussion.6Bjellerup M. Determining venous incompetence: a report from a specialised leg ulcer clinic.J Wound Care. 2006; 15 (433-6): 429-430PubMed Google Scholar As early as 1948, the Swedish surgeon Gunnar Bauer found a group of patients with venous leg ulceration who had no history of previous deep venous thrombosis (DVT) but a family history of varicose veins. Descending transfemoral venography showed a patent, uniformly wide, deep vein with plentiful valve stations identified, which allowed the contrast to descend into the calf veins.7Bauer G. The etiology of leg ulcers and their treatment by resection of the popliteal vein.J Int Chir. 1948; 8 (937-7)Google Scholar No postthrombotic changes, such as irregular lumen, collaterals, or poorly identified valve stations, were noted. Bauer's interpretation was that there was a loss of elasticity in the vein wall leading to dilatation and subsequent incompetence of the valve. He termed this condition idiopathic deep vein incompetence; this condition today is defined as primary valvular incompetence. Hach et al have later suggested an additional hypothesis (ie, the deep veins will dilate secondary to massive superficial reflux because of “overloading”).8Hach-Wunderle V. Hach W. Invasive therapeutic options in truncal varicosity of the great saphenous vein.Vasa. 2006; 35: 157-166Crossref PubMed Scopus (16) Google Scholar Treatment of the superficial reflux in these patients may correct the deep venous reflux. This normalization of venous flow is frequently seen with segmental primary deep incompetence, but rarely with axial deep reflux.9Adam D.J. Bello M. Hartshorne T. London N.J. Role of superficial venous surgery in patients with combined superficial and segmental deep venous reflux.Eur J Vasc Endovasc Surg. 2003; 25: 469-472Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 10MacKenzie R.K. Allan P.L. Ruckley C.V. Bradbury A.W. The effect of long saphenous vein stripping on deep venous reflux.Eur J Vasc Endovasc Surg. 2004; 28: 104-107Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 11Makarova N.P. Lurie F. Hmelniker S.M. Does surgical correction of the superficial femoral vein valve change the course of varicose disease?.J Vasc Surg. 2001; 33: 361-368Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 12Sharp M.A. Nawabi D.H. Walton J. Hands L. Popliteal venous reflux is not abolished by superficial venous ligation.Phebology. 2003; 18: 143-145Crossref Scopus (6) Google Scholar Mapping of reflux by duplex ultrasound scanning in limbs with primary or secondary reflux and leg ulceration has shown that superficial reflux is present in approximately 80% of limbs, and in half of these limbs it is combined with deep venous reflux.13Grabs A.J. Wakely M.C. Nyamekye I. Ghauri A.S. Poskitt K.R. Colour duplex ultrasonography in the rational management of chronic venous leg ulcers.Br J Surg. 1996; 83: 1380-1382Crossref PubMed Scopus (57) Google Scholar, 14Hanrahan L.M. Araki C.T. Rodriguez A.A. Kechejian G.J. LaMorte W.W. Menzoian J.O. Distribution of valvular incompetence in patients with venous stasis ulceration.J Vasc Surg. 1991; 13 (discussion 811-2): 805-811Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar, 15Labropoulos N. Giannoukas A.D. Nicolaides A.N. Ramaswami G. Leon M. Burke P. New insights into the pathophysiologic condition of venous ulceration with color-flow duplex imaging: implications for treatment?.J Vasc Surg. 1995; 22: 45-50Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar The prevalence of significant NIVL in these patients is not known. Current evidence suggests that multiple factors may lead to intrinsic structural and biochemical abnormalities of the vein wall in PCVD resulting in remodeling of the venous wall and valvular incompetence in PCVD (see Critical Issue 2). This process appears to be multicentric; thus, primary valve incompetence develops simultaneously in discontinuous vein segments. Valves may not fail in a progressive descending or ascending uninterrupted order as previously thought.16Lim C.S. Davies A.H. Pathogenesis of primary varicose veins.Br J Surg. 2009; 96: 1231-1242Crossref PubMed Scopus (187) Google Scholar PCVD is widespread in the population and is far more prevalent than secondary (postthrombotic) disease. It is responsible for the development of chronic venous insufficiency (C3-C6) in 20% of the older population. A meta-analysis comprising 390 ulcer patients with PCVD having duplex ultrasound scanning revealed superficial incompetence alone and combination of deep and superficial reflux in 44% and 43% of ulcerated limbs, respectively.17Perrin M. Rationale for surgery in the treatment of venous ulcer of the leg.Phlebolymphology. 2004; 45: 276-280Google Scholar, 18Labropoulos N. Hemodynamic changes according to the CEAP classification.Phlebolymphology. 2003; 40: 103-106Google Scholar The clinical expression of PCVD is indistinguishable from that of postthrombotic disease in its late stages, but the medical and surgical treatment considerations are distinctly different. We have identified four critical issues concerning primary chronic venous disease, which are central in the endeavor to decrease the prevalence of venous leg ulcers by 50% at 10 years. Studies on how to identify patients with PCVD that will progress to ulceration do not exist. It has been shown to be important to correct the underlying pathology in patients with established venous ulcer disease to prevent recurrence.19Gohel M.S. Barwell J.R. Taylor M. Chant T. Foy C. Earnshaw J.J. et al.Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial.BMJ. 2007; 335: 83-88Crossref PubMed Scopus (304) Google Scholar However, there is no standard for evaluation of reflux/obstruction and changes of the microcirculation in CVD by Intersocietal Commission for Accreditation of Vascular Laboratories (ICAVL) in the United States. Standardization is vital to move forward because of its importance to direct treatment in clinical practice as well as to perform research. There is also a lack of basic information on ambulatory venous pressure and hemodynamic changes in the microcirculation.20Pascarella L. Schonbein G.W. Bergan J.J. Microcirculation and venous ulcers: a review.Ann Vasc Surg. 2005; 19: 921-927Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar Many laboratories have developed protocols for evaluating reflux and obstruction in the lower limbs, but there is no standardization of method and interpretation. Duplex ultrasound scanning (DUS) is the most common and available test, and, therefore, central in evaluation of CVD, regardless of etiology, in clinical practice. Standardizing the method of scanning and the interpretation of the results would quickly have a major impact on CVD treatment. Primary care physicians would learn when to consult a vascular specialist for assessment and possible intervention. Since DUS of the ilio-caval vein segment is frequently difficult to perform, additional imaging studies may be needed to detect iliofemoral venous outflow obstruction as per institutional preference (eg, transfemoral contrast venography, magnetic resonance venography, computed tomography venography, or intravascular ultrasonography [IVUS]). There are no standard methods of quantification of hemodynamically significant venous outflow obstruction.21Neglén P. Raju S. Proximal lower extremity chronic venous outflow obstruction: recognition and treatment.Semin Vasc Surg. 2002; 15: 57-64Abstract Full Text PDF PubMed Scopus (50) Google Scholar Methods of measuring outflow resistance also need to be developed. There are no known hemodynamic methods to identify which patient with PCVD and limbs with C-class 2 to 4 will progress to develop leg ulcers. To achieve this goal, other hemodynamic tests in addition to ultrasound scanning should be utilized. Duplex ultrasound scanning parameters of interest would be the anatomic extent and distribution of reflux and obstruction (such as the system proposed by Hach),22Hach W. (Diagnosis and surgical methods in primary varicose veins).Langenbecks Arch Chir. 1988; ([in German]): 145-151PubMed Google Scholar and quantification of reflux by peak volume reflux, peak reflux, etc.23Neglén P. Egger 3rd, J.F. Olivier J. Raju S. Hemodynamic and clinical impact of ultrasound-derived venous reflux parameters.J Vasc Surg. 2004; 40: 303-310Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Hemodynamic tests, such as plethysmography (air plethysmography, foot volumetry, or strain-gauge)24Nicolaides A.N. Allegra C. Bergan J. Bradbury A. Cairols M. Carpentier P. et al.Management of chronic venous disorders of the lower limbs: guidelines according to scientific evidence.Int Angiol. 2008; 27: 1-59PubMed Google Scholar and laser Doppler measurements, such as veno-arterial response (VAR) and vasomotor activity (VA),25Shami S.K. Scurr J.H. Smith P.D. The veno-arteriolar reflex in chronic venous insufficiency.Vasa. 1993; 22: 227-231PubMed Google Scholar, 26Chittenden S.J. Shami S.K. Cheatle T.R. Scurr J.H. Coleridge Smith P.D. Vasomotion in the leg skin of patients with chronic venous insufficiency.Vasa. 1992; 21: 138-142PubMed Google Scholar need further evaluation. When these hemodynamic tests are used, the patients need to be followed with clinical severity scores (venous clinical severity, segmental disease, and disability scores or others), which are more sensitive than C-classification to detect symptomatic progression. It is necessary to develop first a protocol for CVD investigation for clinical practice, and then introduce a more sophisticated protocol for longitudinal research of CVD.