Pathogenesis

Chronic venous insufficiency, which must be semantically distinguished from venous disease or disorder, may be defined as relative impedance of venous flow back to the heart and responsible for clinical consequences. When this occurs in the lower extremities, the normal reabsorption of perivascular fluids by osmotic and pressure gradients is impaired, resulting in accumulation of perivascular and lymphatic fluid. This leads to edema and impaired oxygenation of surrounding tissue (Figs 2.1 and 2.2). This disruption of the normal vascular and lymphatic flow of the lower extremities may result in pain, cramping (especially at night), restlessness, pigmentary changes, dermatitis, and ulceration (Fig. 2.3).^1–3 The association of abnormal venous flow with various signs and symptoms has been noted for centuries: first by Hippocrates in the fourth century BC and by Wiseman in England in 1676.⁴ It has been estimated that chronic venous insufficiency will develop in almost 50% of patients with major varicose veins.^5,6

Figure 2.1 Schematic diagram showing the normal resorption of pericapillary fluid in response to precapillary and postcapillary pressure and interstitial pressure.

Figure 2.2 Flowchart showing etiology of cutaneous venous hypertension.

Figure 2.3 Flowchart showing etiology of cutaneous manifestations of venous hypertension.

Several alterations of normal venous flow cause venous hypertension. Such hypertension in the lower extremities is usually caused by a loss or disruption of the normal one-way valvular system. This may occur because of deep vein thrombosis (DVT), thrombophlebitis, or a dilation of veins from other causes.^7,8 When perforating vein valvular function becomes incompetent, there may be shunting of blood flow from the deep to the superficial venous system through the incompetent perforating veins, with resultant adverse sequelae.^9–11 The superficial veins respond by dilating to accommodate the increased blood flow, which produces superficial valvular incompetence leading to the development of varicosities.¹² In addition, with muscular movement in the lower limbs, the high venous pressure normally occurring within the calf is transmitted straight to the superficial veins and subcutaneous tissues.^13,14 Venous pressure in the cuticular venules may greatly exceed the normal 100 mmHg in the erect position.¹⁵ This causes venular dilation over the whole area, resulting in capillary dilation, increased permeability,^16–19 and increase in the subcutaneous capillary bed.^17,20 This is manifested as telangiectasia and venectasia (Fig. 2.4). Venous hypertension has also been demonstrated to destroy the venous valves that are present in the subcuticular vascular system.²¹ This destruction promotes persistent and progressive changes in the venous drainage system of the skin and subcutaneous tissues. The greater the degree of venous hypertension, the greater the risk of venous ulcer development.^22,23 Fortunately, both sclerotherapy and surgical treatment are capable of normalizing abnormal venous hypertension.

Figure 2.4 Telangiectasia in the medial ankle/pedal area in a patient with chronic venous insufficiency, referred to as corona phlebectasia.

Venous hypertension and subsequent insufficiency may also derive from venous obstruction, either at lower limb level or at iliocaval level, usually associated with reflux.²⁴

Molecular Mechanisms

The molecular mechanisms involved in leukocyte adhesion and activation in chronic venous disease (CVD) are beginning to be elucidated. Circulating leukocytes and vascular endothelial cells express membrane adhesion molecules. For example, binding of L-selectin on the leukocyte surface to E-selectin on endothelial cells may be involved in leukocyte ‘rolling’ along the endothelial surface (Fig. 2.5A). Then, when leukocytes are activated, they shed L-selectin into the plasma and express molecules of the integrin family, including CD11b, which binds firmly to intercellular adhesion molecule-1 (ICAM-1). Integrin binding can promote firm adhesion of leukocytes, the starting point for their degranulation⁸ and migration through the endothelium.

Figure 2.5 A: Leukocyte-endothelial interactions on a venous valve. ICAM-1, intercellular adhesion molecule-1. B: Summary of contrasting effects of steady, laminar shear stress (upper panel) and turbulent or reversing shear stress (lower panel) on vessel walls. NO, nitric oxide; PGI₂, prostacyclin; t-PA, tissue plasminogen activator; TGF-β, transforming growth factor beta; MCP-1, monocyte chemotactic protein-1; VCAM-1, vascular cell adhesion molecule-1; ANG II, angiotensin II; PDGF, platelet-derived growth factor.

(Modified from Traub O, Berk BC: Arterioscler Thromb Vasc Biol 18:677, 1998, with permission.)

(Modified from Takase S, Bergan JJ, Schmid-Schönbein GW: Ann Vasc Surg 14:427, 2000 and from Coleridge Smith PD, Bergan JJ: Inflammation in venous disease: In Schmid-Schönbein GW, Granger N, editors, Molecular basis for microcirculatory disorders, Paris, 2003, Springer-Verlag, pp 489–500, with permission.)

Inflammation and Skin Changes

There has also been progress in linking the chronic inflammatory state seen in CVD patients with the specific skin changes typical of the condition. In lipodermatosclerosis, the skin capillaries become elongated and tortuous, giving the appearance in histologic sections of elevated capillary density.³⁰ In advanced skin disease especially in the ulcerative stages, the capillaries may take on a glomerular appearance,³¹ and it seems clear that substantial proliferation of the capillary endothelium occurs. Several factors could contribute to endothelial proliferation, but vascular endothelial growth factor (VEGF) is an obvious candidate. VEGF is known to be involved in inflammatory and healing processes in the skin and has been shown to increase microvascular permeability both acutely and chronically.³² Plasma levels of VEGF have been shown to increase during the venous hypertension induced by 30 minutes of standing both in normal subjects and in CVD patients. Both supine and standing VEGF levels are higher in patients than in normal controls.³³ Furthermore, plasma VEGF levels are higher in CVD patients with skin changes than in CVD patients with normal skin.³⁴

Another feature of the skin changes associated with CVD is dermal tissue fibrosis. Transforming growth factor-β₁ (TGF-β₁) is a known fibrogenic cytokine. Detailed analysis of punch biopsy specimens has shown that skin from the lower calf of CVD patients had significantly elevated active TGF-β₁ levels compared with normal skin. In addition, this was true relative to skin taken from the lower thigh region of the same patients.³⁵ Immunohistochemistry and immunogold labeling showed the TGF-β₁ to be located in leukocytes, fibroblasts, and on collagen fibrils. Pappas el al³⁶ proposed that activated leukocytes migrate out of the vasculature and release TGF-β₁, which stimulates increased collagen production by dermal fibroblasts. Over an extended period, such a process could contribute to the typical dermal fibrosis seen in CVD.

Altered collagen synthesis has also been reported for dermal fibroblasts taken from apparently healthy areas of skin in patients with varicose veins.³⁷ It has been possible to correlate altered levels and distributions of growth factors, including basic fibroblast growth factor (bFGF), transforming growth factor-3 (TGF-3), and the receptor for epidermal growth factor (EGF), with different types of skin change, including venous eczema, pigmentation, lipodermatosclerosis, and ulceration.³⁸

Advanced cutaneous changes of lipodermatosclerosis appear as an erythematous, telangiectatic, edematous plaque with mottled hyperpigmentation. Histologic examination shows advanced stasis changes, including zones of ischemic necrosis in the central part of fat lobules. Septal fibrosis, fat microcysts, membranous fat necrosis, and sclerosis occur later. This advanced clinical–histologic change is termed sclerosing panniculitis.³⁹ With superficial venous insufficiency alone, changes in the histologic appearance of capillaries are moderate. The combination of deep venous insufficiency, with or without superficial venous insufficiency, produces more profound changes.^40,41

Venous hypertension is not a benign condition. The cutaneous chain of events following the onset of venous stasis is thought to occur in the following temporal order: localized edema, induration, pigmentation, dermatitis, atrophie blanche, and, in untreated cases, eventual ulceration, infection, scarring, lymphatic obstruction and sensitization to applied medications.

Labropoulos et al⁴² studied 255 limbs in 217 patients. These had superficial venous insufficiency alone, with normal perforating veins and deep veins. The color-flow duplex imaging techniques were used. The researchers concluded that aching, ankle edema and skin changes in limbs with reflux confined to the superficial venous system were associated predominantly with reflux in veins below the knee. An important finding was that ulceration occurred only when the entire great saphenous vein (GSV) was involved or when reflux was extensive in both the great and small saphenous systems.

Classification of Venous Disease

An international ad hoc committee of the American Venous Forum developed the CEAP classification for CVD in 1994. The goal was to stratify clinical levels of venous insufficiency. The four categories selected for classification were: clinical state (C), etiology (E), anatomy (A), and pathophysiology (P). The CEAP classification has been endorsed worldwide despite its acknowledged deficiencies. It has been adopted as a standard in many clinics in Europe, Asia and South America and is considered the only modern method for reporting data in the United States.^43–45

The first step in evaluating a patient with CVD is to establish his or her clinical class. The patient’s clinical class will dictate the need for further evaluation.

The CEAP classes are shown in Box 2.1. Each clinical class is further characterized by a subscript for the presence of symptoms (S, symptomatic) or their absence (A, asymptomatic). Symptoms include aching, pain, tightness, skin irritation, heaviness, and muscle cramps, as well as other complaints attributable to venous dysfunction. A basic CEAP is suggested. For the practicing physician, CEAP is an instrument for correct diagnosis, to guide the treatment and assess the prognosis. Venous disease is complex, but can be described. In modern phlebologic practice, the vast majority of patients will undergo a duplex scan of the venous system of the leg, which will provide data on E, A and P. In basic CEAP where a duplex scan is performed, E, A and P should be utilized. For the anatomical classification A in basic CEAP, the simple s = superficial, p = perforator and d = deep descriptors should be used. Multiple descriptors should be permitted for all four components in basic CEAP; for example a patient could be classified as C234s Ep Asd Pr. Use of all components of CEAP is encouraged. Definitions that apply to the CEAP classification are shown in Box 2.2.

But the CEAP is a description of the disease, not an assessment of its severity. It serves for classification, not evaluation. For this reason, several scores have been added to the CEAP, such as the VCSS (venous clinical severity score).⁴⁶ However, a physician reported outcome such as the VCSS is influenced by the ‘experimenter-expectancy effect’ and so the need for the application of patient reported outcomes (PROs) to clinical trials is now recognized.⁴⁷ Revicki summarizes: ‘… the patient’s perspective and patient-reported HRQL (health related quality of life) is the ultimate outcome for health care interventions.’⁴⁸ Basically, a PRO will increase the validity of randomized controlled trials (RCTs) especially when they cannot be double or even single blinded. The influence of the experimenter’s opinion about the efficacy of a treatment significantly changes the RCT results in many different fields of medicine.⁴⁹ An additional precaution for outcome evaluation could be the use of an external evaluation, but this would not take into account the patient’s point of view and self-appraisal.

The patient’s opinion is a point that, albeit obvious, has been too long neglected. Several Quality of Life questionnaires, generic (e.g. SF12⁵⁰) and specific (e.g. CIVIQ,⁵¹ AVVQ) already exist and have been successfully used.⁵² However, they have not take into account the only sure thing we could ever state: if the patient is not happy with the result of the treatment, it means it (you) failed. Therefore, the need to assess the patient’s own appraisal in detail, with satisfactory sensitivity and specificity, appears of utmost importance. Guex et al addressed this point and observed that CVD patients had one main concern belonging to one of the following five groups: discomfort/pain, appearance/attractiveness, risk/threat to health, restriction of movements/activities, emotional distress.⁵³ They have therefore constructed a novel PRO (the SQOR-V), specially dedicated to CVD and based on these five patient concerns.⁵⁴ Its values range from 20 to 100, 20–30 being normal, 30–50 moderate consequences of CVD and >50 being severe CVD. This questionnaire is free to use and is available in several languages, including French, English and Spanish.

Pittaluga et al have established a classification of venous refluxes based on the extent of saphenous vein reflux.⁵⁵ They noted a positive correlation between age and progression of superficial venous insufficiency.

Incidence

Varicose veins have been noted to increase in incidence with age and have been estimated to occur in 7% to 60% of the adult population in the United States.^5,15,56–60 Varicose veins occur in 8% of women aged of 20 to 29 years, increasing to 41% in the fifth decade and 72% in the seventh decade of life.^57,61,62 A similar rate of increase in the incidence of varicose veins occurs in men: 1% in the third decade, increasing to 24% in the fourth decade and 43% in the seventh decade.^57,61 The Basle study III found that the greatest correlation between age and incidence of varicose veins occurred in those with varicose veins only, rather than in those with the presence of telangiectasias (hyphenwebs) or reticular veins (Fig. 2.6).⁵ The Framingham study,⁶³ curiously, showed no difference in the incidence of varicose veins with age.

Figure 2.6 Risk of varicosity by age. Increasing age best correlated with the development of varicose or reticular veins.

(From Widmer L: Peripheral venous disorders: prevalence and socio-medical importance: observations in 4529 apparently healthy persons, Basle Study III, Bern, Switzerland, 1978, Hans Huber.)

Varicosities in childhood are rare, occurring almost exclusively in association with congenital vascular malformations (see Chapter 3). When varicosities occur, they usually appear as a subtle physical finding, such as a slight bulge over the popliteal fossa (Fig. 2.7). One estimation on the incidence of telangiectasias in children was performed by Oster and Nielsen⁶⁴ in Denmark. Of 2171 Danish schoolchildren examined, 46.2% of the girls and 35.1% of the boys had telangiectasias on the nape of the neck; 1% of these children had pronounced telangiectasias elsewhere; that is, on the shoulders, thorax, cheeks and ears. No mention was made of the occurrence of telangiectasias on the legs. An examination of 403 children in the former East Germany, aged 8–18 years, disclosed a 50% incidence of ‘very discrete’ venous abnormalities of leg veins. Of the children examined, 15% had clear symptoms (without visible varices) that could be assigned to a prospective varicose disease. Only between the ages of 17 and 18 years could reticular varicose veins be identified. In the 403 children studied by venous Doppler, 2.3% had incompetent communicating veins and 3.2% had an incompetent saphenofemoral junction.⁶⁵ An epidemiologic study of 419 Czechoslovakian children aged 8 to 13 years, with clinical examination plus digital photoplethysmography, showed clinically apparent varices in 8.7% and an impairment of venous function in 14.3% of the examined extremities.⁶⁶

Figure 2.7 Subtle, asymptomatic varicosity of the great saphenous vein at the junction in the popliteal fossa of an 11-year-old girl. There is no significant family history of varicose veins.

The most recent and complete studies of 518 children aged 10 to 20 years, using photoplethysmography in addition to venous Doppler, are the Bochum I, II, and III studies. This continuing investigation initially demonstrated a 10.2% incidence of reticular varicose veins without other venous abnormalities in children who were 10 to 12 years of age.⁶⁷ When these children were examined 4 years later, the incidence of reticular veins was 30.3%; 2% of the children had developed varicose veins and 4% had developed incompetent communicating veins. When they were examined another 4 years later, the frequency of saphenous refluxes and large varices was still increasing (19.8% saphenous refluxes, 3.3% truncal varices, 5% tributary varices, and 5.2% incompetent perforators). The incidence of reticular veins increased to 35.5%, and the incidence of telangiectasia increased to 12.9%.⁶⁸ Therefore, venous disease can be demonstrated in a small number of children, its progression can be documented, and saphenous reflux is a risk factor for the development of truncal varices.

Symptoms

Varicose veins may be symptomatic in addition to being large and unsightly (Box 2.3). A study of 4280 town and country inhabitants of Tübingen, Germany, found symptoms in 98% of patients with clinically relevant venous alterations.⁶⁹ One American health survey found that nearly 50% of those with varicose veins were bothered by their symptoms once in a while, and 18% noted frequent to continuous symptoms.⁷⁰ Galen⁷¹ described the symptoms of varicose veins as ‘a heavy and depressing pain’. Pain is related most likely to pressure on the dense network of somatic nerve fibers present in the subcutaneous tissues adjacent to the affected nerve. Alternatively (or in addition), pain may occur from the dilated vein compressing adjacent nerves or from lactic acid accumulation that results from retrograde, circular, or slower venous blood flow clearance. Symptoms may precede the clinical appearance of the varicosity and are proportional to the presence of intermittent edema. At this point, discomfort usually occurs during warm temperatures when the patient is standing for prolonged periods.⁷² These patients may respond to systemic hydroxyrutosides, which decrease inflammation of the vein wall.^73–75 Paroven – a mixture that mainly consists of mono-, di-, tri-, and tetra-O-β-hydroxyethyl rutosides containing at least 45% troxerutin (Zyma, United Kingdom) – 250 mg three or four times a day has been reported to help.⁷⁶ Reduction in venous hypertension or excision of the involved segment usually causes prompt relief of pain.⁴

Almost all patients with postthrombotic obstruction complain of ‘bursting’ calf pain that is exacerbated by exercise.⁷⁷ Venous claudication is an appropriate term to use in this situation to emphasize the relationship of exercise to pain. Pain during exercise may be due to nociceptor stimulation of the distended vein wall.⁷⁸ Alternatively, exercise pain may be due to an accumulation of tissue metabolites or an increase in interstitial pressure. Patients with acute DVT have an increased intramuscular pressure that is proportional to the degree of thrombosis.^79,80

Kistner⁸¹ has found that perforator incompetence leads to indurated skin with ulceration, whereas incompetence of the tibial, popliteal, or femoral system produces aching and swelling in the leg. There are patients who have a significant amount of valvular incompetence without symptoms. Clinical symptoms vary based on the effectiveness of the calf muscle pump to compensate for venous hypertension. Young, thin, and more athletic patients have fewer symptoms than older and obese patients.

Varicose vein pain is described usually as a dull aching of the legs, particularly after prolonged standing or during certain times of the menstrual cycle (especially during menses).⁸² A small number of women also experience painful varicose veins after sexual intercourse.⁸³ It is proposed that the increase in venous pressure with distension of the varicose vein contributes to heaviness and tightness of the lower legs.^4,84 The Basel study III found a similar range of complaints in both men and women (Fig. 2.8) and an increased incidence of complaints among women and older patients.⁵ Many patients in the Basel study III had complaints without evidence of peripheral vascular disease. Strandness and Thiele⁴ suggest that symptoms specifically caused by varicose veins improve with aging as the level of activity declines.

Figure 2.8 Type of complaint according to sex. Except for an increase in the complaint of ankle swelling, men with varices have complaints similar to those of women.

(From Widmer L: Peripheral venous disorders: prevalence and socio-medical importance: observations in 4529 apparently healthy persons, Basle Study III, Bern, Switzerland, 1978, Hans Huber.)

Symptoms in varicose veins are often disproportionate to the amount of actual pathologic change. Patients with small, early-stage varices may complain more than those with large, longstanding varicosities.^85–89 A survey of 350 patients who presented for sclerotherapy treatment of veins that were less than 1 mm in diameter noted that 53% of these patients complained of swelling, burning, throbbing and cramping of the legs, in addition to a ‘tired feeling’.⁹⁰ A retrospective analysis of 401 patients who sought treatment solely for telangiectasia showed 69% with various symptoms, including pain, cramping, burning, throbbing and heaviness.⁹¹ These symptoms are so insidious that most patients fail to realize how good their legs can feel until after treatment of these blood vessels by either compression sclerotherapy or by wearing lightweight (20 mmHg) graduated compression stockings.⁵⁹ Patients with nonsaphenous reflux had twice the incidence of painful legs (43%) than did patients with saphenous reflux (22%).⁹²

The increased incidence of symptomatic varicose veins in women may have a hormonal etiology. It has been estimated that 27.7% of women with varicose veins have premenstrual pain in their varices.⁹³ Varicose veins during pregnancy appear to be more symptomatic than those unassociated with pregnancy. In a study of 150 pregnant women with varicose veins, 125 noted pain and 26 were unable to stand for more than 1 to 2 hours because of the pain.⁹⁴

Warm weather tends to increase the severity of pain, as does continual standing. Cooling the legs with water immersion or compresses, or raising the legs, relieves the symptoms.

The differential diagnosis of leg pain is extensive and not necessarily attributable to a patient’s varicosities (Box 2.4). Symptoms derived from varicose veins can usually be distinguished from arterial symptoms. Pain associated with arterial diseases often disappears at rest and is exacerbated with walking. Pain associated with varicosities is dull, vague and localized on the medial side of the legs. It is usually relieved with walking. In addition to the dull aching, varicose veins associated with venous hypertension may produce cramping or painful spasms of the legs and an increase in leg fatigue and restless legs, especially at night. Unfortunately, a patient’s perception and reporting of pain are subjective in nature and difficult to document. Browse et al⁹⁵ advocate the use of compression hosiery as a diagnostic test to determine if the pain is of venous origin. The authors have found that if a patient’s symptoms are alleviated with 20 mmHg graduated compression stockings, sclerotherapy treatment also alleviates the symptoms.

In a study that compared groups matched by age as well as gender, it was found that subjects with venous disease were markedly symptomatic compared with control individuals. Symptoms specific to venous disease were found to correlate with the presence of both small vein and large vein disease. Vein size did not predict the presence or severity of symptoms.⁹⁶ A study of 1366 people in Edinburgh, Scotland, found that women were more likely than men to report a wide range of lower limb symptoms.⁹⁷ In men, only itching was significantly related to the presence of varicose veins. In women, there was a significant relation between varicose veins and heaviness or tension, aching and itching.

Using the Aberdeen varicose vein questionnaire, a prospective cohort of 137 patients was studied and the results compared with the well-accepted short form (SF-536). The two questionnaires correlated highly. Both showed the patients having worse health preoperatively than postoperatively. After surgery, all domains of health were improved and reached significance, chiefly in mental health. The conclusion of the authors of this study was that persons with varicose veins have a reduced quality of life (QOL) compared with the general population and that this discrepancy is significantly improved at 6 weeks after surgery.⁹⁸

Two recent QOL studies were conducted on people with varicose veins. An analysis of 5688 consecutive outpatients in Belgium, Canada, France, and Italy found that the QOL in patients with varicose veins is associated with concomitant venous disease, rather than the presence of varicose veins per se.⁹⁹ Sixty-five percent of patients with varicose veins also have concomitant venous diseases such as edema, skin changes or ulcers. A study of 2404 employees of the University of California, San Diego Medical Center, also found an adverse effect on QOL in patients with CVD.¹⁰⁰ The effect of venous disease is more on the functional scale (what a person can do) and does not seem to affect the well-being aspects (how a person feels). Thus, venous disease is more than simply a cosmetic problem to most patients.

Signs

In addition to the direct symptoms of varicose and telangiectatic veins, varicose veins may be a cutaneous marker for venous insufficiency, where they occur in more than 50% of patients (Box 2.5).^101–104 Certainly, deep venous insufficiency as a result of valvular incompetence is the major etiologic factor for the cutaneous manifestations of chronic venous insufficiency. In fact, when descending venography was used to examine patients with chronic venous insufficiency, reflux occurred in the superficial system alone in only 2% of the 644 examined limbs. Eighteen percent of the limbs had combined deep and superficial reflux.¹⁰⁵ Studies using ascending venography have shown that more than 20% of patients with chronic venous insufficiency have isolated perforator incompetence as the only demonstrable abnormality.¹⁰⁶ However, a significant group of patients has superficial venous insufficiency alone (13–38%) or in combination with deep venous insufficiency (28–78%).^{104,107–112} In addition, Walsh et al¹¹³ found that treating the incompetent superficial venous system with ligation and stripping the GSV to the knee with stab avulsion of distal varices restored competency to the femoral vein. Therefore, identification of patients with superficial venous insufficiency is important because they may respond to sclerotherapy or surgical treatment of the superficial venous system alone.

It has been estimated that between 17% and 50% of the population with varicose veins have cutaneous findings.^2,114 Approximately 70% of limbs with chronic venous insufficiency have clinical findings.¹⁰⁸ There is a strong association between the severity of clinical signs (described later in this chapter) and superficial venous incompetence.¹⁰⁸ Almost all patients with cutaneous abnormalities have incompetence of perforator veins and all patients with either active or healed venous ulcerations have evidence of perforator incompetence.¹¹⁴ The cutaneous manifestation appears as edema, hyperpigmentation, dermatitis or ulceration. More than a million Americans suffer from skin ulcers caused by abnormal circulation that results from varicose veins, and nearly 100,000 Americans are totally disabled by this condition.⁵⁷ Thus, varicose and telangiectatic leg veins are not merely of cosmetic concern but represent a widespread and potentially serious medical problem.

Pigmentation

Pigmentation (Fig. 2.9) is a sign of venous stasis disease. The elongated, distended vascular system underlying areas of stasis is more susceptible to trauma than are normal vessels. Even minor blunt injuries may cause rupture of the vascular wall with extravasation of erythrocytes into the cutis.^12,18,119 Histologically, cutaneous hyperpigmentation represents increased melanin early on and extravasated erythrocytes and hemosiderin-laden macrophages interspersed between dilated and tortuous capillaries in later stages and in inflammatory stages.^12,125,126 Erythrocytes appear either intact or to have become fragmented during their passage (Fig. 2.10). Extravasation appears to be due to increased intravascular pressure and not chemotaxis, as occurs with white blood cells.¹²⁵

Figure 2.9 Hyperpigmentation around dilated telangiectasias and venules in a 70-year-old man. There had been no history of cutaneous trauma.

Figure 2.10 Two deformed erythrocytes wind through an intercellular space (E) into the pericapillary tissue. (Osmium-cacodylate ×18,100.)

(From Wenner A et al: Exp Cell Biol 48:1, 1980.)

Extravasated erythrocytes may be found in the deep dermis around adnexal structures (Fig 2.11). When present clinically, they are a reliable guide to the existence of microangiopathy. A more acute ‘eruptive’ cutaneous pigmentation has also been noted as a ‘blow-out’ of erythrocytes into the dermis as a result of tremendous back pressure within the cutaneous microvasculature.¹²⁷ This phenomenon has been ascribed as the cause of lichen aureus (Fig. 2.12).¹²⁸ The only treatment for this condition is correction of the underlying venous hypertension (sclerotherapy and/or surgery), including graduated compression stockings and leg elevation. Fortunately, when venous hypertension is treated, dark pigmentation gradually fades. After correction of the etiology for the venous hypertension, a Q-switched laser specific for hemosiderin can then be used to remove or minimize the pigmentation (see Chapter 8). In addition, a noncoherent intense pulsed light source has also been demonstrated to lighten pigmentation in one case report.¹²⁹

Figure 2.11 Skin biopsy specimen taken from the medial malleolar area of a 38-year-old man with ankle-pedal telangiectasias and venulectases with associated hyperpigmentation. Note hemosiderin-laden macrophages interspersed among eccrine glands in the deep dermis. (Hematoxylin–eosin; A, ×50; B, ×200.)

Figure 2.12 A 52-year-old woman with a 1 to 2 year onset of cutaneous hyperpigmentation of the anterior tibial and medial malleolar areas. Venous Doppler examination was diagnostic for an incompetent communicating vein.

Venous (stasis) dermatitis

The next dermatologic manifestation to occur in the chain of events following venous hypertension–stasis is ‘stasis’ dermatitis. This dermatitis has been given many names, including stasis eczema, varicose eczema, stasis syndrome, hypostatic eczema, congestive eczema and dermatitis hypostatica. Because there may not be a true ‘stasis’ in the lower leg with venous insufficiency, but rather venous hypertension, this condition is best referred to as ‘venous’ dermatitis. Venous dermatitis occurs more frequently in women, obese people, middle-aged men and women and those with a history of DVT and thrombophlebitis.³ Edema, which causes the change from the normal cutaneous venous circulation to a high pressure system with increased vascular permeability, is the precursor of this dermatitis.^128–132

A random sample of 476 people over the age of 65 years in Sheffield, England, found an incidence of venous dermatitis of 21% in men and 25% in women.¹³³ In Denmark, the incidence in a random sample of people in homes for the aged (55–106 years old; mean age, 80 years) was 6.9%.¹³⁴ The authors speculated that the difference was due to better nutrition in the Danish population. A similar incidence of venous dermatitis (5.9%) was found in a randomized examination of noninstitutionalized volunteers aged 50 to 91 years (average age, 74 years) in Boston, Massachusetts.¹³⁵ Interestingly, a survey of dermatologic patients in the Filipino population aged 60 years and over disclosed a 12% incidence of venous dermatitis, with 49% of all patients having varicosities.⁶² This is contrary to the popular belief (see Chapter 3) that there is a lower incidence of venous disease in non-Western races.

The dermatitis usually begins in the medial paramalleolar region. This region is particularly vulnerable because the vascular supply, skin nutrition and subcutaneous tissue are less abundant here than in other areas of the lower extremity.¹³⁶ Venous dermatitis appears clinically as a sharply marginated, erythematous, crusted plaque (Fig. 2.13). With time and cutaneous trauma resulting from pruritus, overlying lichenification may occur,³ as well as exudation, depending on the extent of the inflammation and associated edema. However, an indolent venous flow may make the skin assume a much paler color with less moisture.¹³⁷ The color of the lesion darkens as a result of an increase in melanocytic postinflammatory hyperpigmentation and dermal hemosiderin (Fig. 2.14).^2,138 The dermatitis may also be complicated by a generalized systemic hypersensitivity or ‘ID’ reaction.²

Figure 2.13 Early venous eczema appearing as a nummular eczema overlying prominent dilated venules and reticular veins in a 58-year-old woman.

Figure 2.14 Typical appearance of venous dermatitis. The affected area is erythematous, sharply marginated, and scaly with hyperpigmentation and excoriations.

Venous dermatitis may manifest as a solitary lesion in 7% of patients and may mimic neoplasms including squamous cell carcinoma and basal cell carcinoma.¹³⁹ Early recognition of the solitary venous dermatitis lesion should lead to appropriate treatment of venous hypertension, which may prevent further morbidity.

Recently, an association of venous dermatitis with amlodipine (a long-acting calcium channel blocker used in the treatment of hypertension, chronic stable angina and vasospastic angina) has been reported.¹⁴⁰ It is thought that amlodipine use may predispose those with venous insufficiency to leg edema and venous hypertension. Therefore, it is prudent to question patients with new onset stasis dermatitis about medication use.

Histologic examination (Fig. 2.15) of the dermis demonstrates a diffuse homogenization of collagen, fragmentation or absence of elastic fibers, thickening and partial occlusion of arterioles, and atrophic changes of appendages.^12,141 There may also be an associated acanthosis and hyperkeratosis of the epidermis, which rarely results in pseudoepitheliomatous hyperplasia.³ The lymphatic vessels are usually thickened and fibrotic, and there may be an associated dermal inflammatory infiltrate.³ Because these changes are those of a nonspecific dermatitis, the histologic diagnosis of venous dermatitis can be certain only with clinical correlation.

Figure 2.15 Histologic examination of a patient with longstanding venous hypertension and overlying venous dermatitis. (See text for description.) (Hematoxylin–eosin; A, ×50; B, ×200.)

Other conditions can give the appearance of venous dermatitis and should be ruled out; three cases of myelogenous leukemia cutis have been reported which appeared to be venous dermatitis.^142–144 Skin biopsy made the correct diagnosis in these cases.

Atrophie blanche

Atrophie blanche is the descriptive name given to the appearance of porcelain-white scars seen on the lower extremities as a result of infarctive lesions of the skin (Fig. 2.16). This condition was attributed originally to syphilis or tuberculosis in 1929.¹⁴⁵ The white plaques are bordered by hyperpigmentation and telangiectasias. Histologically, meandering capillaries are detected at the border of lesions, with their apex oriented towards the avascular center.¹⁴⁶

Figure 2.16 Middle-aged woman with venous insufficiency and atrophie blanche of the medial malleolar area.

(Courtesy Kim Butterwick, MD)

The process usually occurs in middle-aged women with associated varicose veins and signs of venous insufficiency. However, this descriptive term represents the sequelae of many disease processes including venous dermatitis, arteriosclerosis, dysproteinemia, diabetes mellitus, hypertension, systemic lupus erythematosus, scleroderma, juvenile rheumatoid arthritis and idiopathic segmental hyalinizing vasculitis. Therefore, this physical condition is best thought of as an intermediate stage between venous dermatitis and varicose ulceration; the term atrophie blanche is best reserved for the idiopathic vasculitic condition.

Patients with atrophie blanche have been compared with patients having severe venous insufficiency but without atrophie blanche. In turn, these have been compared with 10 healthy controls. Laser Doppler perfusion imaging was used, as were transcutaneous oxygen tension measurements. The overall results showed that resting blood perfusion was greater in atrophie blanche areas than in healthy controls, and the venoarterial response was significantly increased in these atrophie blanche areas. In contrast, there was a decrease in transcutaneous oxygen pressure values in areas of atrophie blanche lesions and in the skin of patients with chronic venous insufficiency without atrophie blanche. The authors of this study concluded that basic resting flow in atrophie blanche is higher compared to that in normal skin and in patients with chronic venous incompetence, but there is also marked decrease in flow in response to venous occlusion in these affected areas.¹⁴⁷ In addition to treating venous hypertension, treatment with antifibrinolytics (i.e. aspirin, dipyridamole); anti-inflammatory agents (i.e. as dapsone) and pentoxifylline have demonstrated to be helpful especially in patients with idiopathic forms.¹⁴⁸

Ulceration

Cutaneous ulceration represents the end-stage manifestation of venous stasis disease. This relationship has been noted for millennia. Hippocrates was the first to record the association.¹⁴⁹ More than 300 years ago, Wiseman¹⁵⁰ noted that valvular incompetence caused by venous thrombosis could result in a circulatory defect leading to ulceration of the skin.

The prevalence of varicose or post-thrombophlebotic ulcers has been estimated to be as high as 1% of the United States population and 2% of the Swedish population (Fig. 2.17).^3,151–153 Although venous ulcers may have an onset in early adulthood, they increase in frequency with age and peak at approximately 70 years.^152–155 The ratio of females to males is approximately 3 : 1 after the age of 40, with an equal incidence before 40 years of age.¹⁵⁴

Figure 2.17 Chronic venous insufficiency with cutaneous ulceration in a 68-year-old man before treatment.

Seventy-two different causes of leg ulcers have been recognized and grouped into three categories.¹⁵⁵ Between 75% and 90% are of venous etiology,^3,156,157 40% to 60% of which are associated with varicose veins,^157–159 and 35% to 90% are associated with a history of DVT.^3,157–161 Nonvenous causes of leg ulceration include arterial disease (8%) and ulcers caused by trauma or those that have bacteriologic, mycotic, hematologic, neoplastic, neurologic or systemic origins (2%).¹⁵⁶

The cost of treating leg ulcers in the United States was estimated in 1991 to be between $775 million and $1 billion, based on the annual cost of ulcer care in Sweden.¹⁶² In addition to this cost, there is an estimated loss of 2 million working days annually in the United States because of leg ulcers.¹⁶³ Therefore, optimizing treatment, or better yet, prevention, is important. Curiously, despite its importance, very little government funding is allocated towards ulcer treatment. Patients diagnosed with leg ulcers in the United States spend, on average, 12.1 days in hospital.¹⁶⁴ Because leg ulcers frequently take much longer to heal with bed rest and ancillary care, this form of therapy is impractical and not properly reimbursable.

Color duplex investigation of limbs with reflux and ulceration has shown that distal venous reflux has an important influence over skin changes and ulceration, and reflux in the superficial veins appears to be more harmful than that confined to the deep veins even when such deep venous reflux extends through the length of the limb.¹⁶⁵ Reflux in the local area near the ulcer also influences ulceration. Local reflux may be influenced by perforating vein incompetence and outward flow. Isolated perforating vein outward flow without accompanying superficial reflux or deep reflux is seen in 4% to 6% of limbs with ulceration.¹⁶⁶ There is much controversy about the role of surgery in treating such reflux. However, most of the available data suggest that ablation of superficial venous reflux and ablation of outward flow through perforating veins is an appropriate method for the management of patients with primary venous leg ulceration.¹⁶⁷

Between 20% and 25% of ulcerations have superficial venous insufficiency, either alone with perforating vein incompetence or as a significant component combined with deep venous insufficiency.^{94,98,99,168,169} In one practice of more than 20,000 lifetime patients, it was estimated that nearly 15% of patients with major varicose veins developed ulcerations.⁶ Although ulcerations are more common in patients with DVT, 13% of all venous ulcerations are observed in limbs with superficial venous insufficiency alone.

Cutaneous ulceration usually occurs 10 to 35 years (mean, 24 years) after the onset of varicose veins¹⁷⁰ and is commonly assumed to be specifically associated with incompetent calf perforating veins (see Chapter 9).^15,171–173 Dodd and Cockett¹⁵ surgically explored 135 limbs with ankle ulceration and found that the most severe lesions were always associated with an incompetent perforating vein. Lawrence et al¹⁷² studied patients with varicosities, both with and without associated ulceration, using Doppler ultrasound. They found sustained retrograde flow in incompetent veins in eight of nine ulcer patients but found it in only one of seven patients with varicose veins without ulceration. However, a recent study using duplex sonography showed no direct correlation between incompetent perforators and venous ulceration. Plethysmographic examination indicated that venous hypertension in superficial veins was the more important factor.¹⁷⁴ One study of 213 consecutive patients with venous ulceration demonstrated that 90% of patients had sustained ulcer healing (with a mean follow-up period of 3.4 years) when treated with saphenous ligation alone, without perforating vein treatment, even when incompetence of the perforating veins had been demonstrated.¹⁷⁵ Thus, any operative procedure on varicose ulcers must correct the underlying abnormal communicating superficial or perforating veins. Interestingly, no evidence or history of DVT was reported in up to 24% of patients with chronic venous leg ulcers;^159,176 therefore, the etiology may be multifactorial, with the majority of patients having a similar initiating event: superficial venous hypertension. This may arise from incompetent perforating veins alone, associated with an abnormal deep venous system, or with an incompetent superficial venous system.^177,178

Stasis ulcerations, unlike most other causes of cutaneous ulcerations, appear in the gaiter area.^159,179 The ulcers appear cyanotic, edematous, and friable. The base is usually covered with thick granulation tissue that rarely penetrates the deep fascia. The skin edges are painless, thickened and bleed easily. Adjacent skin is edematous and inflamed, with associated dilated venules, eczematous changes and pigmentation.^161,180 Calcification of the subcutaneous tissue, often not even adjacent to the ulceration, occurs in a significant number of patients,^130,181,182 up to 25% in one study (Fig. 2.18).¹⁸³ The calcium, acting as a foreign body, may perpetuate the ulceration or actually may be an essential cause of the lesion. Calcification is probably caused by venous insufficiency and represents the last stage of the inflammatory response. It almost always precedes the ulceration.¹³⁰

Figure 2.18 A sixty-five-year-old woman with varicose veins, stasis dermatitis, and medial malleolar ulcerations bilaterally. A, Right leg; B, left leg; C, close-up view of left medial calf demonstrating extensive subcutaneous calcium deposits.

In contrast to venous stasis ulceration, ischemic ulcers occur most commonly on the anterior and/or lateral leg and ankle. However, lateral ankle ulcerations may arise from incompetent small saphenous veins.¹⁸⁴ The base of an ischemic ulcer is often obscured by a pale yellow, purulent exudate. Often the borders are poorly epithelialized, with a ‘punched-out’ appearance, and are necrotic with islands of gangrenous skin. Deep fascia and tendon may be exposed at the base, with little or no spontaneous granulation tissue.

Leg ulcers can also have multiple causes. Two case reports of mixed skin ulcers misdiagnosed as pyoderma gangrenosum and rheumatoid ulcer successfully treated with ultrasound-guided injection of polidocanol microfoam has recently been reported.¹⁸⁵

Malignant degeneration

A potentially fatal, but fortunately rare, secondary change in venous ulcers is malignant degeneration (Fig. 2.19). There have been more than 100 case reports of malignant degeneration of a stasis ulcer in the world literature.^{173,186–194}

Figure 2.19 Basal cell carcinoma (keratinizing type) arising in an ulcer in the setting of chronic venous insufficiency in a 77-year-old woman. The ulceration had been present for at least 6 years. An incompetent perforating vein was found at the base of the ulceration.

The most common cancers reported are carcinomas (squamous and basal cell) and sarcomas (fibrosarcoma, osteosarcoma and angiosarcoma). Even malignant melanoma has been reported to occur in chronic venous ulceration.¹⁹⁵ The incidence of malignant degeneration of venous stasis ulcerations is 0.4% to 1%.^{193,196–198} The average duration of the ulcer before tumor growth is 21 years, with a reported span of 10 to 40 years.¹⁹⁸ The onset of malignant change usually appears as a rapid growth of exuberant cauliflower-like masses, an increase in pain, or, in a smaller number of cases, a rapid extension of the ulcer crater.¹⁹⁸ An increase in induration of the ulcer borders and surrounding tissue and a failure of the ulcer to respond to prolonged conservative treatment are also suspect.¹⁹⁹ Transition into a malignant growth is thought to be stimulated by many factors, including chronic dermatitis, irritation and infection.^199,200 Implanted epithelial cells may produce a chronic foreign-body reaction with subsequent neoplasia.²⁰¹ Chronic scarring from the sequelae of ulceration mentioned above may obliterate lymphatic channels, leading to decreased immune surveillance of the scar by immunologically competent cells. This relatively localized immune deficiency provides less protection against cellular mutation, which allows cellular progression into neoplasia.²⁰² Therefore it seems prudent to perform a biopsy of the base and border areas of ulcers with these characteristics or of ulcers that persist for more than 4 months. This is particularly important when surgically correcting the ulceration with a skin graft. One patient developed a squamous cell carcinoma following split skin grafting and, in spite of amputation and radiotherapy, died from multiple metastasis.¹⁷³

Although the appearance of malignant degeneration in a nonhealing leg ulcer is often characteristic, basal cell carcinoma in the ulcer may either appear as exuberant and translucent ‘granulation tissue’ or may have no clinical features to suggest malignancy.^188,191,203

A study of squamous cell carcinomas complicating chronic venous leg ulcer has revealed some interesting facts. The mean age at cancer diagnosis was 78.5 years; the median survival was 1 year. Of these tumors, 11 were well differentiated, 10 moderately differentiated, and 4 were poorly differentiated. All patients with poorly differentiated tumors died within 1 year. Metastases were certain in 8 cases.²⁰⁴ The disease was lethal in 10 cases, which included all of the poorly differentiated tumors. This suggests that when squamous cell carcinoma in chronic leg ulcers is found, a thorough investigation must include the degree of differentiation and a definition of extent of spread. Aggressive treatment is indicated because poorly differentiated tumors and some moderately differentiated tumors are fatal.

Secondary complications of venous hypertension–stasis

In addition to the varicose ulcers and dermatologic abnormalities already discussed, external hemorrhage, superficial thrombophlebitis and DVT are the three most severe and acute complications of varicose veins.

Hemorrhage

Hemorrhage from varicose veins may not be a rare event. Tretbar²⁰⁵ reported treating 12 patients in 3 years for 18 episodes of hemorrhagic varicose veins. All but two of his patients had had varicose veins for more than 20 years. The bleeding area typically consisted of a mat of ‘blue blebs’, each of 1 to 2 mm in diameter, on the medial ankle. Doppler examination usually disclosed an underlying incompetent communicating vein. None of Tretbar’s patients developed serious sequelae from the bleeding episodes and all were treated successfully with compression sclerotherapy of the affected veins. However, bleeding can be profuse and, if unnoticed or improperly treated, can be fatal.^15,206–208 A report on the mortality of varicose veins from Australia between 1997 and 2000 disclosed 51 deaths where varicose veins were indicated to be the primary cause of death.²⁰⁹ In one-third of these cases, hemorrhage was the cause.

Hemorrhage is usually spontaneous but may also occur when the skin overlying a varicose vein becomes traumatized or eroded. Most cases described in the literature occur in patients with ulcers overlying varices, but profuse bleeding may also occur from varicosities 1 to 2 mm in diameter (Fig. 2.20). Twenty-three fatal cases of hemorrhage were reported in England and Wales in 1971.²⁰⁶ The patients most at risk are solitary elderly patients with longstanding varicose veins. These patients usually live alone and are unable to apply pressure to the bleeding varix or to get help because of physical disabilities. Rarely, patients may have no history of longstanding varices or overlying ulcers. Hemorrhage in this setting is usually attributable to the rapid development of venous hypertension that occurs from DVT.²¹⁰

Figure 2.20 Venulectasia in a 90-year-old man that bled profusely while the patient was standing. Sclerotherapy caused rapid healing.

If the varicose vein is under high pressure from venous insufficiency, as it usually is, the acute hemorrhage may appear to be arterial in origin. This may result in the inappropriate application of a tourniquet, which only increases venous hypertension. If properly recognized, bleeding of venous origin is easily controlled by raising the affected area above the level of the heart and applying localized pressure to the bleeding vein. Leg elevation stops hemorrhage within seconds to minutes. Sclerotherapy or ligation of the affected vein is curative but may not prevent further episodes of hemorrhage from other varices.

Direct pressure over the area of hemorrhage stops the bleeding, and maintaining that pressure for 5 to 7 days allows complete healing of the epidermis over the area of the hemorrhage.²¹¹ It has been found that a suture of the area of hemorrhage, usually done in a hospital emergency department, causes venous ulceration. Direct suture, therefore, should be avoided.

Injection of potentially hemorrhagic veins is mandatory (Fig. 2.21). In these cases, usual aesthetic concerns do not apply and it is logical to inject the fragile venules at the very beginning of the treatment, prior to the necessary reduction of venous hypertension. Sclerosing injections of bleeding veins provide an elegant solution to the problem; provided the sclerosing agent induces a spasm (polidocanol, sodium tetradecyl sulfate), it stops the hemorrhage and usually prevents a recurrence. The leg should be elevated during injection, and higher than usual concentrations of sclerosing solution are often required. Foamed sclerosant may also help stop the bleeding more quickly.

Figure 2.21 Injection of potentially hemorrhagic veins is mandatory.

Since the responsibility for skin abrasion and subsequent hemorrhage lies mostly with patients themselves, advice should include careful nail trimming and filing, and nocturnal wear of socks (and maybe even gloves as well). Avoiding scratching of the skin is also a prerequisite as fewer complications are caused by corticosteroid creams than by ulcers and hemorrhages caused by scraping.

The ‘shear off’ phenomenon can explain ‘spontaneous’ acute pains of the calf, known in the French literature as ‘whip pains of the calf’. During a quick movement of the lower limb, inertia of muscle and fat tissues creates a relative displacement of the different anatomical layers (Fig. 2.22) responsible for wrench of communicating or perforating veins, resulting in pain, hematoma and ecchymosis. This atraumatic lesion is more common on varicose veins because of the venous wall remodeling and dysplasia, and because of venous hypertension. Duplex ultrasound shows edema and a small hematoma, and usually no sign of superficial thrombophlebitis. Local compression and massage with nonsteroidal anti-inflammatory cream is the sole treatment.

Figure 2.22 During a quick movement of the lower limb, inertia of muscle and fat tissues create a relative displacement of the different anatomic layers.

Superficial thrombophlebitis

Superficial thrombophlebitis (ST) is a painful condition that fortunately seldom results in serious embolic complications. In the absence of malignancy, thrombophlebitis of the leg is almost invariably associated with varicose veins.^4,212–214 Patients with varicose vein ST are younger and have a decreased incidence of coexistent DVT (9.75% versus 43.75%).²¹³ The condition results from the development of a clot in a varicose vein caused by one or more of the following factors: trauma to the varicosity, stasis of blood flow or occlusion of blood flow. Fifty percent of cases may occur spontaneously.^212,215 An evaluation of 51 consecutive patients with venous thrombosis and varicose veins found 8% with an underlying malignancy, 7% with an antiphospholipid syndrome and a total of 26% with other systemic illnesses.²¹⁶ Therefore it is recommended that a search for an underlying cause be made.

The great saphenous system is the usual site of ascending ST. Clinically, one notes a painful, tender, hot erythematous swelling along the course of the vein, with a variable amount of perivascular edema. The pain associated with ST is often severe, probably resulting from inflammation of the dense network of somatic nerve fibers in the associated subcutaneous tissue.⁴

Incidence of ST, irrespective of the presence of varicose veins, increases with advancing age and inactivity, and with bed rest as the result of surgery, childbirth or cardiac disease.^217,218 In patients in whom the incidence of varicose veins is not stated, ST has been estimated to occur in 0.7% of women in their fourth decade of life, increasing to 2.6% of women in the seventh decade.⁵⁷ In men, the incidence of ST has been estimated to be 0.4% in the fourth decade, increasing to 1.7% in the seventh decade.⁵⁷ The actual number of patients with ST in the United States was estimated in 1973 to be 123,000 yearly. The incidence of ST is substantially higher when related to the presence of varicose veins.⁴ A review of the lifetime work of one physician with more than 20,000 patients notes an incidence of ST in as many as 20% of patients with prominent major varicosities.⁶ Older papers have estimated a 50% lifetime incidence of thrombophlebitis in patients with varicose veins.²¹⁹ Fegan⁸³ estimates that ST occurs in approximately 4% of those with varicose veins.

Although the condition is usually treated as a benign complication of varicose veins, the development of DVT, venous hypertension and pulmonary emboli may occur in a significant percentage of patients.^{212,215,220–224} A review of 340 cases of ST in a university hospital disclosed a 10% incidence of pulmonary emboli with five deaths,²¹⁵ and this risk has been confirmed by others.²²⁵ The development of pulmonary emboli may also be related in some cases to a coexistent DVT.^4,226,227 One study of 44 consecutive patients with ST found coexistent DVT in 23%. All of these cases were occult clinically, with the site of the ST not predictive of DVT.²¹⁴ Thus, noninvasive deep venous studies are recommended for all patients with ST.

Pulmonary emboli and DVT, by definition, were supposed not to complicate ST unless the thrombus progressed into the deep venous system, but it has been observed that DVT can occur in other venous networks. This may happen because of either progression into a perforating vein or ascending involvement of the common femoral vein at the saphenofemoral junction (Fig. 2.23) or simply due to the presence of a hypercoagulable state.²²⁸ When either of these events occurs, superficial or deep venous hypertension develops as a result of valvular destruction.²¹⁸ Propagation of the thrombotic process into the deep system has been reported to occur in 6%²²⁹ to 32%²²⁰ of all cases of ST. In an 11-year retrospective series, 17% of 133 patients were noted to have extension of the clot into the deep system.²³⁰ Surgical exploration of the saphenofemoral junction, followed by ligation, thrombectomy and limited vein stripping, has been advocated, particularly if clinical signs of thrombophlebitis reach the midthigh. We recommend full anticoagulation. Surgical removal of the thrombosed vein segments and associated varicosities shortens the convalescence and mitigates recurrences.^229,231,232 Unfortunately, this latter form of treatment usually results in extensive scarring. Finally, because DVT may manifest partly in the appearance of ST, patients should be examined carefully.

Figure 2.23 Diagrammatic representation of three methods of propagation of superficial thrombophlebitis. A, Thrombophlebitis limited to the superficial system with blockage by the perforating vein valves and at the saphenofemoral junction. B, Extension of the thrombus into the deep system through destruction and incompetence of perforating veins. C, Direct extension of the thrombus into the femoral vein at the saphenofemoral junction.

(Redrawn from Totten HP: Angiology 16:37, 1965.)

Surgical treatment of ST has been dominant when the ST has affected the GSV and ascended towards the saphenofemoral junction. It is thought that the incidence of DVT is three times that of normal individuals, and, in the past, with ascending thrombophlebitis of the GSV, an operation under local anesthesia to ligate and divide the vein was recommended.²³³ However, gradually, anticoagulant treatment has dominated clinical practice. The advantage, of course, is that the ST is treated simultaneously by the anticoagulation, compression and rest. Nonsteroidal anti-inflammatory medications have been advocated but may have potentially severe side effects. Since ST is associated with a higher risk of DVT, and since ST of the GSV when ascending to the junction leads to progression of the clot into the femoral vein, the use of low molecular weight heparins must be considered – prophylactically for 2 weeks when the clot does not threaten the deep system, but therapeutic, like for a DVT, when it does.²³⁴ External elastic compression is recommended by most authorities on this subject.²²⁸

Deep venous thrombosis

Varicose veins, by virtue of their low blood flow, are considered a high risk factor for DVT.⁴ Without other predisposing factors, patients with varicose veins have an incidence of DVT ninefold that of the normal population.²³⁵ Platelet aggregation is thought to occur behind valve cusps, especially when the valves are incompetent in varicose veins.^236,237 Thrombosis on the valve cusps then triggers the coagulation cascade and results in clot propagation.

Stasis of blood flow may cause activation of factors XII, XI, and IX, which initiates thrombin activity to propagate thrombus formation through fibrin formation and platelet aggregation.²³⁸ Stasis may also result in a significant amount of endothelial sloughing, with exposure of subendothelial collagen and subsequent activation of platelets.²³⁹ An additional reason for the propensity for DVT in patients with chronic venous insufficiency (which is commonly associated with the presence of varicose veins) may be related to a faulty fibrinolytic system, correlated with pericapillary deposition of fibrin.²⁴⁰ This hypothesis has been questioned because up to 70% of patients with idiopathic DVT have a decreased tissue plasminogen activator that probably reflects endothelial dysfunction and a decreased clearance of clotting factors.^240–243

An increased incidence of DVT is also found in the postoperative period.^244–248 This may be related to the increased incidence of thrombophlebitis in varicose veins in the postoperative period, with an incidence estimated at 6% versus the normal 0.5% to 0.7% incidence.²⁴⁹ This is of particular significance in patients less than 60 years of age. With fibrinogen scanning, DVT occurs in 56% of patients over 60 with varicose veins versus 41% in patients over 60 without varicose veins. This can be compared with 56% in patients younger than 60 years with varicose veins versus 19% in patients less than 60 without varicose veins.²⁵⁰ Therefore, all patients with varicose veins who are about to undergo surgery, or who are bedridden or pregnant, should receive thrombosis prophylaxis, such as wearing a graduated support stocking, to prevent this potentially fatal, albeit rare, complication of varicose veins.

In summary, varicose veins are associated with a number of serious medical problems and are not just of cosmetic concern. Basle study III⁵ found that the incidence of the major complications of varicose veins – chronic venous insufficiency, phlebitis and pulmonary embolism – increases with the severity of the varicosity (Fig. 2.24). Even patients with minor telangiectasias and reticular veins in combination demonstrated a significant increase of these serious medical complications when compared with patients without these types of veins.

Figure 2.24 Complications according to the type of varicose vein. N represents the number of persons in the defined group.

(Redrawn from Widmer L: Peripheral venous disorders: prevalence and socio-medical importance: observations in 4529 apparently healthy persons, Basle Study III, Bern, Switzerland, 1978, Hans Huber.)

Classification

A classification of varicose veins should be based on anatomic or subsequent therapeutic considerations. The first anatomic classification was proposed by Heyerdale and Stalker²⁵¹ in 1941 (Table 2.1). This classification is useful in determining when surgical ligation of the GSV is advantageous before performing sclerotherapy. The list of advantages presented by Heyerdale and Stalker still holds true today (Box 2.7). The Basle study⁵ classified varicose veins into three groups:

Table 2.1 Classification of varicosities of the lower extremities

Duffy²⁵² proposed a more complete classification of ‘unwanted leg veins’. Since one purpose of a classification is to provide a mechanism for evaluating pathophysiology and treatment, a modification of the Duffy classification appears useful. It provides comprehensive clinical and therapeutic criteria in an effort to optimize treatment (Box 2.8 and Figs 2.25 to 2.30).

Figure 2.25 Duffy type 1 (telangiectasia) on the inner thigh of a 58-year-old woman.

Figure 2.26 Duffy type 1A (telangiectatic matting) 6 weeks after sclerotherapy treatment on the lateral calf. Note associated reticular veins, postsclerotherapy hyperpigmentation and bruising.

Figure 2.27 Duffy type 1B (communicating telangiectasia) in a 20-year-old woman.

Figure 2.28 Duffy type 2 (mixed telangiectasia and varicose veins with no direct communication with the saphenous system) in a 54-year-old woman. There was no evidence (venous Doppler) of incompetence of the saphenofemoral or saphenopopliteal junctions or of perforating veins.

Figure 2.29 Duffy type 3 (nonsaphenous varicose (reticular) veins) located over the proximal anterolateral thigh of a 24-year-old woman.

Figure 2.30 Duffy type 4 (saphenous varicose veins). Varicose great saphenous vein with incompetent valvular function throughout its length and a grossly incompetent saphenofemoral junction in a 32-year-old man.

Varicose veins can be classified into four developmental stages. The first stage appears as a somewhat dilated blue vein in association with normal great and small saphenous veins. This stage usually occurs in teenagers with a family history of varicose veins. It is asymptomatic.

The second stage appears as a palpable, bulging, moderately dilated vein, usually in association with a larger saphenous vein. Venous Doppler examination is normal; Duplex scanning may show a dilated but competent saphenofemoral and/or saphenopopliteal junction. These veins may be symptomatic after prolonged immobilization or standing.

The third stage represents established varicose vein disease. The great and/or small saphenous veins are dilated over all or part of their length. There are associated varicose veins over the thigh and lower leg, with accompanying venules and spider veins. The varicose veins themselves may or may not be incompetent, but gross incompetence is present at the saphenofemoral and/or saphenopopliteal junctions.

The final, or fourth, stage consists of complications arising from chronic venous insufficiency and varicose veins. Perforating vein incompetence is present along with cutaneous manifestations of venous stasis disease, including ulcerations.

The development of varicose vein disease is generally progressive. Six different patterns of GSV varicosity have been described.¹¹⁴ These relate to the duration of varicose vein disease (Fig. 2.31). Certain patients may experience spontaneous stabilization of the disease in the early stages. Treatment of early-stage disease may prevent the progression and cause regression of the disease process. A complete understanding of the anatomy and pathophysiology of the venous system with regard to varicose veins allows the development of a rational treatment plan.

Figure 2.31 Patterns of great saphenous vein incompetence in 296 limbs with primary varicose veins.

(Modified from Almgren B, Eriksson I: Acta Chir Scand 156:69, 1990. © British Journal of Surgery Society Ltd. Reproduced with permission. Permission is granted by John Wiley & Sons Ltd on behalf of the BJSS Ltd.)