TOPIC 11. VARICOSE VEINS, POSTTROMBOTOC SYNDROM.
VARICOSE VEINS
Epidemiology of Chronic Peripheral Venous Disease
The term chronic venous disease, or more specifically of interest here, chronic peripheral venous disease (CPVD) has been used more generally to refer to either visible and/or functional abnormalities in the peripheral venous system. The most widely used classifi cation of such abnormalities is the CEAP (Clinical, Etiological, Anatomic, Pathophysiologic), which includes both anatomic (superfi cial, deep, or perforating veins) and pathophysiologic (reflux, obstruction, both) categories.
The CEAP classification was created by an international committee of clinical experts, and reflects the clinical situation in patients typically referred to a vascular specialist for clinically significant venous disease. In contrast to the clinical situation, population studies of CPVD typically have focused on broader categories determined by visual inspection only. The three major categories of interest have been varicose veins (VV), chronic venous insufficiency (CVI), and venous ulcers. However, there has not been a standard definition of these categories. VV has been defined bothincluding and excluding telangiectasias (spider veins), and at differing levels of visible disease severity. CVI typically has been defined by skin changes and/or edema in the distal leg. Venous ulcers, both active and healed, have been defined by visual inspection and subjective inference as to etiologic origin.
Two studies have now reported results on defined free-living populations with simultaneous assessment of both visible abnormalities and functional impairment by Duplex ultrasound.
The Duplex examination for the San Diego Population Study (SDPS) determined both obstruction and reflux, whereas the
Although these discrepancies occurred in a minority of cases, they were frequent enough to lead us to separately classify visible and functional CPVD in each limb evaluated in the SDPS. Specially, we classified each limb into four visible categories: normal, telangectasias/spider veins (TSV), VV, and trophic changes (TCS), the latter category being one or more of hyperpigmentation, lipodermatosclerosis, or active or healed ulcer. The presence/absence of edema was not by itself a criterion for TCS. For functional disease, we determined the presence of obstruction and reflux separately for the superficial, perforating, and deep systems. The presence of either reflux or obstruction in superficial or deep veins was categorized as functional disease, and because of small numbers, abnormalities of the perforating veins were considered as deep disease. Three functional categories were defined: normal, superficial functional disease (SFD), and deep functional disease (DFD). Here, the term “functional” is essentially interchangeable with “anatomic.” Also, in this population study obstruction was uncommon, and virtually all legs with obstruction also had reflux, such that SFD and DFD essentially refer to reflux.
In addition to separately assessing edema, we asked about a history of superficial venous thrombosis (SVT) and deep venous thrombosis (DVT), with or without pulmonary embolism.
AGE AND CVPD
Using mutually exclusive categories for both visible and functional CVPD, we found a graded relationship with increasing age for VV, with those aged 70–79 years having nearly twice the prevalence of those aged 40–49 years. TSV also increased with age, but this difference was obscured by the mutually exclusive categories with increasing numbers of participants with TSV also having VV or TCS at older ages. TCS showed the most dramatic age-related increase, with the oldest age group having more than four times the prevalence of the youngest.
These findings for visible disease are consistent with most previous population studies, which generally have found a linear increase in TSV or VV with age (reviewed in Reference 4). Earlier studies typically defined CVI only by venous (assumed) ulcers, and reported exponential increases in CVI with age, findings similar to the dramatic age increase we reported for the broader TCS category.
For functional CVPD, SFD was more than twice as common and DFD was 64% more common in the oldest age group. SFD showed both a higher prevalence and a steeper age gradient than did DFD.
The only other population data on functional disease were from the
Edema was strongly age-related as expected, but history of SVT and DVT were somewhat less so, perhaps reflecting selective recall bias in older participants.
Nonetheless, our data for DVT overall are quite similar to the lifetime prevalence in a large population-based study.
GENDER AND CPVD
For visible disease, we found nearly twice as much VV in women as in men, but TCS were 50% more common in men. These findings for VV are consistent with earlier studies, but earlier studies also have suggested a small excess of CVI in women, in contrast to our findings for the broader category of TCS. However, more concordant with our findings, the
Edema was about 50% more common in men than women, consistent with a 50% greater history of DVT in men. The
ETHNICITY AND CPVD
The SDPS reported data for four ethnicities, nonHispanic White, Hispanic, African-American, and Asian. Non-Hispanic Whites showed the highest prevalence of CPVD, with only 14.3% with a normal examination. Non-Hispanic Whites had the highest rates of TSV, TCS, and DFD, and the second highest rates (after Hispanics) of VV and SFD. African-Americans and Asians had a somewhat lower prevalence of CPVD. Consistent with the visible and functional findings, Non-Hispanic Whites also had the highest rates of edema and DVT by history, and Hispanics the highest rate of SVT by history.
Several previous studies have suggested a higher prevalence in developed than developing countries, although these studies are not entirely consistent. The SDPS is the first population study to evaluate multiple ethnic groups who were residents of the same geographical area.
RISK FACTORS FOR CPVD
Age was positively consistently related to all levels of visible and functional disease in both sexes. In comparison with non Hispanic whites (NHW), African-American Asian had less TSV and VV in both sexes, less TCS in men, and less DFD in women. Our results thus confirm that older age and NHW ethnicity are risk factors for CPVD.
Family history of venous disease based on subject recall was a risk factor for all levels of visible and functional disease. Although this finding could be biased, it is consistent with many other studies, although not all.
Ankle motility was a risk factor for visible disease SFD in women and for TSV in men. It was protective for women with DFD and men with SFD. The association of increasing laxity in connective tissue with venous disease corroborated previous research.
The protective associations could reflect increased ankle motility leading to decreased venous pressure by increasing pumping action.
Lower limb injury was a risk factor in women for DFD. Coughlin et al., in a case-control study, found serious lower limb trauma to be a risk factor for CVI.
CVD-related factors, such as angina, PTCA, hypertension, and diastolic pressure were associated with less TSV, SFD, and DFD for men and women and less VV for men. Although some studies have found a relationship between atherosclerosis and venous disease, others have not.
The reason for any protective effect of cardiovascular disease and hypertension on CPVD is not readily apparent, although venous vasoconstriction and microthrombosis could conceivably be involved.
Hours spent walking or standing was positively associated with VV, TCS, and SFD in men and women. Fowkes et al. found that walking was a risk factor for women with venous insufficiency when age-adjusted, but less so when multiply adjusted. They found walking to be related to lessened risk of venous insufficiency in men. Our data indicate that standing was a strong risk factor for venous disease in women. This is concordant with a number of studies, and contrasts with some other studies.
Weight, height, waist, and BMI, defined as weight in kg divided by height squared in meters squared, were positively associated with TCS, and DFD in men and VV, TCS, and SFD in women. Weight, waist circumference, the waist/hip ratio, and body mass index are all measures of adiposity.
A number of studies have found an association of obesity with venous disease. Gourgou et al. found a relationship in both men and women with VV. Our finding of increased waist circumference in men with TCS was consistent with findings that both obesity and male gender were associated with CVI and with the finding that weight was an independent risk factor for CVI in multivariate analysis In contrast, Coughlin et al. and Fowkes et al. both found that obesity was not a factor in venous insufficiency among women. Fowkes et al. extended this finding to men as well. Other studies also have found no association between obesity and venous disease.
However, the
During exercise the venomuscular pump is activated, which leads to a transient decrease in venous pressure, which should be protective for venous disease. This is consistent with our results in men.
HRT duration or parity was positively associated with all levels of visible and functional disease in women. Gourgou et al. found increasing VV prevalence with increasing numbers of births. Coughlin et al. found that multiparity was associated with varicose veins in pregnant women.
Some studies have found that the changes are effected with only one pregnancy. The increase of CPVD with HRT duration may indicate yet another underexamined systemic effect of HRT.
Our data indicate that age and family history were the strongest risk factors for CPVD, and neither is subject to intervention. Other significant findings on inherent factors included associations with connective tissue laxity and height. CVD-related factors were associated with lower rates of venous disease. Among volitional factors important findings were a relationship of CPVD with central adiposity, positional factors such as hours spent standing or sitting, exercise, and selected hormonal factors in women. In contrast with prior studies, we found no relationship with dietary fiber intake. In women but not men we confirmed the importance of a previous lower limb injury for DFD.
VENOUS ANATOMY, PHYSIOLOGY, AND PATHOPHYSIOLOGY
ANATOMY
The venous system in the lower extremities can be divided, for purposes of understanding, into three systems: the deep system, which parallels the tibia and femur; the superficial venous system, which resides in the superficial tissue compartment between the deep muscular fascia and the skin; and the perforating or connecting veins, which join the superficial to the deep systems. It is because these latter veins penetrate anatomic barriers, they are called perforating veins.
Although the superficial veins are the targets of most therapy, the principal return of blood flowfrom the lower extremities is through the deep veins. In the calf, these deep veins are paired and named for their accompanying arteries.
Therefore, the anterior tibial, posterior tibial, and peroneal arteries are accompanied by their paired veins, which are interconnected. These crural veins join and form the popliteal vein. Occasionally the popliteal veins as well as more proximal deep veins are also paired like the calf veins.
As the popliteal vein ascends, it becomes the femoral vein. Formerly, this was called the superficial femoral vein, but that term has been abandoned. Near the groin the femoral vein is joined by the deep femoral vein, and the two become the common femoral vein, which ascends to become the external iliac vein proximal to the inguinal ligament.
Ultrasound imaging has shown that the superficial compartment of the lower extremities consists of two compartments, one enclosing all the structures between the muscular fascia and the skin, and the other, within the superficial compartment enclosing the saphenous vein and bounded by the muscular fascia inferiorly and the superficial fascia superiorly, is termed the saphenous compartment (see Figure 1). The importance of this anatomic structure is underscored by its being targeted during percutaneous placement of endovenous catheters and the instillation of tumescent anesthesia.
Fig. 1 This diagram of the Saphenous Compartment shows its relationships with the Superficial and Deep compartments as well as the Saphenous Vein (SV) and Nerve and their relationships to the Medial, Anterior, and Lateral
Accessory Saphenous Veins (ASV).
The main superficial veins are the great saphenous vein and the small saphenous vein. These receive many interconnecting tributaries, and these tributaries may be referred to as communicating veins. They are correctly called tributaries rather than branches of the main superficial veins. The great saphenous vein has its origin on the dorsum of the foot.
It ascends anterior to the medial malleolus of the ankle and further on the anteromedial aspect of the tibia. At the knee, the great saphenous vein is found in the medial aspect of the popliteal space. It then ascends through the anteromedial thigh to join the common femoral vein, just below the inguinal ligament. Throughout its course, it lies within the saphenous compartment. The small saphenous vein originates laterally from the dorsal venous arch of the foot and travels subcutaneously behind the lateral malleolus at the ankle. As it ascends in the calf, it enters the deep fascia and ascends between the heads of the gastrocnemius muscle to join the popliteal vein behind the knee (see Figure 2). In fact, there are many variations of the small saphenous vein as it connects both to the popliteal vein and to cranial extensions of the saphenous vein, as well as connections to the posteromedial circumfl ex vein (vein of Giacomini).
Fig.2. This diagrammatic representation of the Great Saphenous
Vein emphasizes it relationship to perforating veins and the Posterior Arch
Vein.
The third system of veins is called the perforating vein system. As indicated earlier, they connect the superficial and deep systems of veins. There is a fundamental fact, which confuses understanding of perforating veins. This relates to flow direction. Some perforating veins produce normal flow from the superficial to the deep circulation, others conduct abnormal outflow from the deep circulation to the superficial circulation. This is termed perforating vein reflux. Any of these perforating veins may demonstrate bidirectional flow (see Table 1).
Table 1. Summary of Important Changes in
Nomenclature of Lower Extremity Veins
In the leg, the principal clinically important perforating veins are on the medial aspect of the ankle and leg, and are found anatomically at approximately
Fig.3. Deep connections of the main thigh and leg perforating
veins are shown in this diagram of the deep veins of the lower extremity.
Conversely, when they are dysfunctional, they allow muscular compartment pressure to be transmitted directly to unsupported cutaneous and subcutaneous veins and venules.
VENOUS PHYSIOLOGY
It is estimated that 60 to 75% of the blood in the body is to be found in the veins. Of this total volume, about 80% is contained in the veins that are less than 200 μm in diameter. It is important to understand this reservoir function as it is related to the major components. The splanchnic venous circulation and the veins of the skin are richly supplied by the sympathetic nervous system fibers, but muscular veins have little or none of these. The veins in skeletal muscle, on the other hand, are responsive to catecholamines.
Although arterial pressures are generated by muscular contractions of the heart, pressures in the venous system largely are determined by gravity. In the horizontal position, pressures in the veins of the lower extremity are similar to the pressures in the abdomen, chest, and extended arm. However, with the assumption of the upright position, there are dramatic changes in venous pressure. The only point in which the pressure remains constant is the hydrostatic indifferent point just below the diaphragm. All pressures distal to this point are increased due to the weight of the blood column from the right atrium. When assuming the upright position, there is an accumulation of approximately 500 ml of blood in the lower extremities, largely due to reflux through the valveless vena cava and iliac veins. There is some loss of fluid into the tissues, and this is collected by the lymphatic system and returned to the venous system.
Venous valves play an important role in transporting blood from the lower extremities to the heart. In order for valve closure to occur, there must be a reversal of the normal transvalvular pressure gradient. A pressure and generated velocity flow exceeding 30 cm/second leads to valve closure. Direct observation of human venous valves has been made possible by specialized ultrasound techniques.
Venous flow is not in a steady state but is normally pulsatile, and venous valves undergo regular opening and closing cycles. Even when fully opened, the cross-sectional area between the leaflets is 35% smaller than that of the vein distal to the valve. Flow through the valve separates into a proximally directed jet and vortical flow into the sinus pocket proximal to the valve cusp. The vortical flow prevents stasis and ensures that all surfaces of the valve are exposed to sheer stress. Valve closure develops when the vortical flow pressure exceeds the proximally directed jet flow.
The role of venous valves in an individual quietly standing is not well understood. Pressures in the superficial and deep veins are essentially the same during quiet standing, but as Arnoldi has found, the pressure in the deep veins is
Normally functioning perforating vein valves protect the skin and subcutaneous tissues from the effects of muscular contraction pressure. This muscular contraction pressure may exceed 100 to 130 mmHg.
Intuitively, the role of venous valves during muscular exercise is obvious, since their major purpose is to promote antegrade flow from superficial to deep. Volume and pressure changes in veins within the calf occur with muscular activity. In the resting position, with the foot fl at on the floor, there is no flow. However, in the heel strike position, the venous plexus under the heel and plantar surface of the foot (Bejar’s plexus) is emptied proximally. Blood flows from the foot and ankle into the deep veins of the calf. Then, calf contraction transports this blood into the deep veins of the thigh, and henceforth, blood flow proceeds to the pelvic veins, vena cava, and ultimately to the heart all due to the influence of lower extremity muscular contraction.
PATHOPHYSIOLOGY
Abnormal functioning of the veins of the lower extremities is recognized clinically as venous dysfunction or, more commonly, venous insufficiency. Cutaneous telangiectases and subcutaneous varicose veins usually are grouped together under the title Primary Venous Insufficiency, and limbs with skin changes of hyperpigmentation, edema, and healed or open venous ulceration are termed Chronic Venous Insufficiency (CVI).
Primary Venous Insufficiency
Explanations of venous pathophysiology as published in reviews, texts, and monographs are now for the most part out of date. The new science as we now know it is incorporated in the following summary.
A dysfunctional venous system follows injury to vein walls and venous valves. This injury is largely due to inflammation, an acquired phenomenon. Factors, which are not acquired, also enter into such injury. These include heredity, obesity, female gender, pregnancy, and a standing occupation in women. Vein wall injury allows the vein to elongate and dilate thus producing the visual manifestations of varicose veins. An increase in vein diameter is one cause of valve dysfunction that results in reflux. The effect of persistent reflux through axial veins is a chronic increase in distal venous pressure. This venous pressure increases as one proceeds from the inguinal ligament past the knee to the ankle.
Prolonged venous hypertension initiates a cascade of pathologic events. These manifest themselves clinically as lower extremity edema, pain, itching, skin discoloration, and ulceration.
The earliest signs of venous insufficiency often are elongated and dilated veins in the epidermis and dermis, called telangiectasias. Slightly deeper and under the skin are fl at, blue-green veins of the reticular (network) system. These may become dilated and elongated as well (see Figure 4).
And finally, still deeper but still superficial to the superficial fascia are the varicose veins themselves. All of these abnormal veins and venules have one thing in common: they are elongated, tortuous, and have dysfunctional venous valves.
This implies a common cause, which is inflammation.
Fig. 4. This cross-sectional view of the subcutaneous venous circulation shows how venous hypertension is transmitted to the unsupported veins of the dermis and subcutaneous tissues from axial veins (GSV) and the deep veins
of the muscular compartments.
Chronic Venous Insufficiency
Skin changes of hyperpigmentation, scarring from previous ulceration, and active ulcerations are grouped together under the term chronic venous insufficiency (CVI). Numerous theories have been postulated regarding the cause of chronic venous insufficiency and the cause of venous ulceration.
All the theories proposed in the past century have been disproved. An example is the theory of venous stasis, first proposed in a manuscript by John Homans of Harvard in 1916.
It was a treatise on diagnosis and management of patients with chronic venous insufficiency, and in it, Dr. Homans coined the term “post-phlebitic syndrome” to describe the skin changes of CVI. He stated that, “Over-stretching of the vein walls and destruction of the valves . . . interferes with the nutrition of the skin . . . there-fore, skin which is bathed under pressure with stagnant venous blood will form permanent open sores or ulcers.”
That statement, like many others that describe venous conditions and their treatments, is steeped in dogma and is short of observational fact. The erroneous term stasis ulcer honors that misconception, as do the terms venous stasis disease and stasis dermatitis.
Alfred Blalock, who later initiated cardiac surgery, disproved the stasis theory by studying oxygen content from varicose veins and normal veins.
He pointed out that the oxygen content of the femoral vein in patients with severe chronic venous insufficiency was greater than the oxygen content of the contralateral nonaffected limb. Because oxygen content was higher, some investigators felt that arteriovenous fi stulas caused venous stasis and varicose veins.
That explanation, though disproved, has some basis in fact since the entire thermal regulatory apparatus in limbs depends on the opening and closing of arteriovenous shunts. These shunts are important as they explain some terrible accidents that happen during sclerotherapy when sclerosant entering a vein is shunted into the arterial system and distributed in its normal territory.
Microsphere investigations have failed to show any shunting and the theory of arteriovenous communications has died despite the fact that these shunts actually exist and do open under the influence of venous hypertension.
Hypoxia and its part in causation of chronic venous insufficiency was investigated throughout the last 25 years of the twentieth century. English investigators thought that a fi brincuff, observed histologically, blocked transport of oxygen and was responsible for skin changes of CVI at the ankles and distally.
That theory has been abandoned even though a true periarteriolar cuff is easily identified histologically.
The two elements that make up all the manifestations of lower extremity venous insufficiency are failure of the vein valves and vein walls and skin changes at the ankles, both of which are related to venous hypertension.
Failure of Vein Walls and Valves
Our work suggests that venous hypertension causes a shear stress dependent leukocyte-endothelial interaction, which has all the manifestations of chronic inflammation.
These are leukocyte rolling, firm adhesion to endothelium, and subsequent migration of the cells through the endothelial barrier into parenchyma of valves and vein walls.
There, macrophages elaborate matrix metalloproteases, which destroy elastin and possibly collagen as well. Vein walls become stretched and elongated. Vein valves become perforated, torn, and even scarred to the point of near total absence. These changes are seen both macroscopically and angioscopically.
Similar changes have been produced in the experimental animal by constructing an arteriovenous fistula to mimic the venous hypertension of venous dysfunction in humans.
Skin Changes
The second manifestation of chronic venous insufficiency is expressed in the skin where leukocytes also are implicated in the observed changes. There is evidence that leukocyte activation in the skin, perhaps related to venous hypertension, plays a major role in the pathophysiology of CVI. Thomas, working with Dormandy, reported that 25% fewer white cells and platelets left the dependent foot of the patients with venous hypertension. When the foot was elevated there was a significant washout of white cells but not platelets, suggesting platelet consumption within the microcirculation of the dependent foot. They concluded that the decrease in white cell exodus was due to leukocyte trapping in the venous microcirculation secondary to venous hypertension. They further speculated that trapped leukocytes may become activated, resulting in release of toxic metabolites causing damage to the microcirculation and overlying skin. Apparently, the primary injury in the skin is extravasation of macromolecules and red blood cells into the dermal interstitium. Red blood cell degradation products and interstitial protein extravasations are potent chemoattractants and represent the initial chronic inflammatory signal responsible for leukocyte recruitment.
The important observations of Dormandy’s group were historically the first to implicate abnormal leukocyte activity in the pathophysiology of CVI.
The importance of leukocytes in the development of dermal skin alterations was further emphasized by Coleridge Smith and his team. They obtained punch biopsies from patients with primary varicose veins, lipodermatosclerosis, and patients with lipodermatosclerosis and healed ulcers. They counted the mediaumber of white blood cells per high power field in each group but there was no attempt to identify the types of leukocytes. In patients with primary varicose veins, lipodermatosclerosis, and healed ulceration there was a median of 6, 45, and 217 WBCs per mm2, respectively. This demonstrated a correlation between clinical disease severity and the number of leukocytes in the dermis of patients with CVI.
The types of leukocytes involved in dermal venous stasis skin changes remain controversial. T-lymphocytes, macrophages, and mast cells have been observed on immunohistochemical and electron microscopic examinations.
The variation in types of leukocytes observed may reflect the types of patients investigated. The
SYMPTOMS OF PRIMARY VENOUS INSUFFICIENCY
It is well known that the presence and severity of symptoms do not correlate with the size or severity of the varicose veins present. Symptoms usually attributable to varicose veins include feelings of heaviness, tiredness, aching, burning, throbbing, itching, and cramping in the legs (see Table 2). These symptoms are generally worse with prolonged sitting or standing and are improved with leg elevation or walking. A premenstrual exacerbation of symptoms is also common. Generally, patients find relief with the use of compression in the form of either support hose or an elastic bandage. Weight loss or the commencement of a regular program of lower extremity exercise may also lead to a diminution in the severity of varicose vein symptoms. Clearly, these symptoms are not specific, as they may also be indicative of a variety of rheumatologic or orthopedic problems. However, their relationship to lower extremity movement and compression is usually helpful in establishing a venous origin for the symptoms. Significant symptoms suggestive of venous disease should prompt further evaluation for valvular insufficiency and calf muscle pump dysfunction. If a venous etiology is suspected but all examinations are negative, repeat examination during a symptomatic period is warranted and often fruitful.
The recent development of an extremely painful area on the lower leg at the ankle associated with an overlying area of erythema and warmth may be indicative of lipodermatosclerosis, which may be associated with insufficiency of an underlying perforator vein, and examination for this lesion should be performed. Lipodermatosclerosis may precede ulceration and has been shown to be improved by stiff compression and certain pharmacologic interventions. Patients with a history of iliofemoral thrombophlebitis who describe “bursting” pain with walking may be suffering from venous claudication. In these patients an evaluation for persistent hemodynamically significant obstruction, possibly treatable with angioplasty and stenting, may be in order.
Table 2. Symptoms of Varicose Veins and
Telangiectasias
PHYSICAL EXAMINATION
Using no special equipment, the practitioner can obtain a degree of information regarding overall venous out flow from the leg, the sites of valvular insuffi ciency, the presence of primary versus secondary varicose veins, and the presence of DVT. The screening physical examination consists of careful observation of the legs. Any patient with the following conditions should be examined more fully: large varicose veins; bulges in the thigh, calf, or the inguinal region representative of incompetent perforating veins (IPVs) or a saphena varix; signs of superficial venous hypertension such as an accumulation of telangiectasias in the ankle region (corona phlebectatica); or any of the findings suggestive of venous dermatitis (pigmentation, induration, eczema). This includes patients with obvious cutaneous signs of venous disease such as venous ulceration, atrophie blanche, or lipodermatosclerosis. An obvious but often forgotten point is the necessity of observing the entire leg and not confining the examination simply to the area that the patient feels is abnormal.
Finally, because the veins of the leg empty into the pelvic and abdominal veins, inspection of the abdomen is very important, since dilation of veins on the abdominal wall or across the pubic region suggests an old iliofemoral thrombus. Dilated veins along the medial or posterior aspect of the proximal thigh or buttocks most often arise from varicosities involving the pudendal or other pelvic vessels, and these can be of ovarian reflux origin.
CLINICAL TESTING
Historically important tests of venous function have been part of the physical examination of venous insufficiency (see Table 3). These tests have been laid aside largely because of their lack of specificity and sensitivity. The continuouswave Doppler examination has replaced most of these tests, and confirmatory duplex testing has relegated them to an inferior role. However, the educated physician who treats venous insufficiency must have knowledge of these tests and their physiologic background, such as the Trendelenburg test or Brodie-Trendelenburg test.
Table 3. Tests of Historic Interest
Trendelenburg Test
A tourniquet may be placed around the patient’s proximal thigh while the patient is standing. The patient then assumes the supine position with the affected leg elevated 45 degrees. The tourniquet is removed, and the time required for the leg veins to empty, which is indicative of the adequacy of venous drainage, is recorded. When compared with the contralateral leg, the method just described may demonstrate a degree of venous obstructive disease. Another approach is to elevate the leg while the patient is supine and to observe the height of the heel in relation to the level of the heart that is required for the prominent veins to collapse. Unfortunately, neither procedure is sufficiently sensitive nor accurate and does not differentiate acute from chronic obstruction, thus being of minimal assistance in current medical practice.
Cough Test
One hand is placed gently over the GSV or SFJ, and the patient is asked to cough or perform a Valsalva maneuver. Simply palpating an impulse over the vein being examined may be indicative of insufficiency of the valve at the SFJ and below to the level of the palpating hand.
Percussion/Schwartz Test
One hand is placed over the SFJ or SPJ, and the other hand is used to tap very lightly on a distal segment of the GSV or SSV. The production of an impulse in this manner implies insufficiency of the valves in the segment between the two hands. Confirmation of the valvular insufficiency can be achieved by tapping proximally while palpating distally. This test can also be used to detect whether an enlarged tributary is in direct connection with the GSV or SSV by palpating over the main trunk and tapping lightly on the dilated tributary, or vice versa. The presence of a direct connection results in a palpable impulse being transmitted from the percussing to the palpating hand. As might be expected, these tests are far from infallible.
Perthes’ Test
The Perthes’ test has several uses, including distinguishing between venous valvular insufficiency in the deep, perforator, and superficial systems and screening for DVT. To localize the site of valvular disease, the physician places a tourniquet around the proximal thigh with the patient standing. When the patient walks, a decrease in the distension of varicose veins suggests a primary process without underlying deep venous disease because the calf muscle pump effectively removes blood from the leg and empties the varicose veins. Secondary varicose veins do not change caliber (if there is patency of the deep venous system) because of the inability to empty blood out of the veins as a result of impairment of the calf muscle pump. In the setting of a current DVT, they may increase in size. If there is significant chronic or acute obstructive disease in the iliofemoral segment, the patient may note pain (venous claudication) as a result of the obstruction to outflow through both the deep and superficial systems. The Perthes’ test is now of more historical than actual clinical importance.
CLASSIFYING VENOUS DISEASE
The Swedish physician and scientist Carl von Linné published a classification of plants based on the number of stamina and pistils in
Clinical Classification
C0: No visible or palpable signs of venous disease
C1: Telangiectasias or reticular veins
C2: Varicose veins
C3: Edema
C4a: Pigmentation and/or eczema
C4b: Lipodermatosclerosis and/or atrophie blanche
C5: Healed venous ulcer
C6: Active venous ulcer
S: Symptoms including ache, pain, tightness, skin irritation, heaviness,
muscle cramps, as well as other complaints attributable to venous
dysfunction
A: Asymptomatic
Etiologic Classification
Ec: Congenital
Ep: Primary
Es: Secondary (postthrombotic)
En: No venous etiology identified
Anatomic Classification
As: Superficial veins
Ap: Perforator veins
Ad: Deep veins
An: No venous location identified
Pathophysiologic Classification
Basic CEAP:
Pr: Reflux
Pr,o: Reflux and obstruction
Pn: No venous pathophysiology identifiable
Same as basic, with the addition that any of 18 named venous segments
can be utilized as locators for venous pathology:
Superficial veins:
1. Telangiectasias/reticular veins
2. Great saphenous vein (GSV) above knee
3. GSV below knee
4. Small saphenous vein
5. Nonsaphenous veins
Deep veins:
6. Inferior vena cava
7. Common iliac vein
8. Internal iliac vein
9. External iliac vein
10. Pelvic: gonadal, broad ligament veins, other
11. Common femoral vein
12. Deep femoral vein
13. Femoral vein
14. Popliteal vein
15. Crural: anterior tibial, posterior tibial, peroneal veins (all paired)
16. Muscular: gastrocnemial, soleal veins, other
Perforating veins:
17. Thigh
18. Calf
TREATMENT OF VENOUS INSUFFICIENCY
The term venous insufficiency implies that normal functioning is deranged. Terms used to describe the various manifestations of venous insufficiency lend confusion to the general topic. Some of these terms, such as telangiectasias, thread veins, and spider veins are descriptive but imply different conditions. And it is in the chronic disorders, dominated by venous reflux through failed check valves causing hyperpigmentation, ulceration, and corona phlebectatica, where disorientation reigns. Some order can come from subscribing to a unifying theory of primary venous insufficiency and of a common theory of effects of an inflammatory cascade that clarify both situations.
The manifestations of simple primary venous insufficiency appear to be different from one another. However, reticular varicosities, telangiectasias, and major varicose veins are all elongated, dilated, and are tortuous. Investigations into valve damage and venous wall abnormalities eventually may lead to an understanding of the problem, and therefore, a solution by surgery or pharmacotherapy.
Scanning electron microscopy has shown varying degrees of thinning of the varicose venous wall. These areas of thinning coincide with areas of varicose dilation and replacement of smooth muscle by collagen, which is also a characteristic of varicose veins. Our approach to this has been to assume that both the venous valve and the venous wall are affected by the elements that cause varicose veins. We and others have observed that in limbs with varicose veins, an absence of the subterminal valve at the saphenofemoral junction is common. Further, perforation, splitting, and atrophy of saphenous venous valves have been seen both by angioscopy and by direct examination of surgical specimens.
Supporting the theory of weakness of the venous wall leading to valvular insufficiency is the observation that there is an increase in the vein wall space between the valve leaflets. This is the first and most commonly observed abnormality associated with valve reflux. Realizing these facts, our investigations have led us to explore the possible role of leukocyte infiltration of venous valves and the venous wall as part of the cause of varicose veins. In our investigations of surgical specimens, leukocytes in great number have been observed in the venous valves, and wall and monoclonal antibody staining has revealed their precise identification as monocytes. Similar findings are present in the skin of patients with venous insufficiency.
SURGICAL TREATMENT
Removal of the Great Saphenous vein (GSV) from the circulation is one of two essential steps in treating lower limb varicose veins. Incompetent valves along the GSV allow blood to reflux down the vein and into its tributaries, transmitting high pressure into smaller tributaries, which become varicose as a result. Much emphasis has been placed on the correct technique of high sapheno-femoral ligation, in which meticulous attention is paid to identifying, ligating, and dividing all the tributaries of the GSV as they join the vein in the groin. It has always been a matter of surgical dogma that overlooking any of these allows continued reflux into the residual tributary and subsequent development of recurrent varicose veins.
A number of studies have confirmed that patients in whom the GSV is stripped tend to have fewer than those undergoing simple high ligation of the Sapheno-femoral junction (SFJ). Sarin et al. studied 89 limbs in 69 patients with LSV incompetence.
Legs were randomized to SFJ ligation with or without stripping, and evaluated by photoplethysmography (PPG), duplex scanning, clinical examination, and patient satisfaction. The follow-up period was 18 months. Significant differences in favor of the stripped group were found in all four parameters at final evaluation.
Asimilar study of 78 patients (110 limbs) was reported by Dwerryhouse et al. in 1999, with a longer follow-up period of five years. This demonstrated a significantly lower reoperation rate among patients undergoing GSV stripping (6%), as opposed to 20% in those undergoing high SFJ ligation alone.
Duplex scanning showed a much lower incidence of residual reflux in the remaining GSV when the proximal vein had been stripped to the knee than when it had not. However, the patient satisfaction rate was not significantly different between the two groups. Ninety percent of the stripped groups were satisfied as opposed to 87% in the nonstripped group (p = ns).A further study from Jones et al. came to similar conclusions.
One hundred patients (133 limbs) were randomized as before. After two years, 43% of those who had not had GSV stripping demonstrated recurrent varicose veins as opposed to 25% who had. There was a statistically significant difference.
NEOVASCULARIZATION
Of great importance was the fact that duplex scanning showed that neovascularization in the groin was the commonest cause of varicose recurrence. It was often seen in the ligation group that reflux through the neovascularization entered the residual saphenous vein and perpetuated the old varices while new ones developed. The authors concluded that by stripping the GSV, one was removing the run-off into which the new vessels could drain. Again, however, the satisfaction was broadly similar between the two groups: 91% in the stripped group and 87% in the unstripped.
All these authors concluded that stripping the long GSV gave better long-term results than simple high saphenous ligation. This appears to be true in terms of objective assessment of recurrence rates and in objective measurement of post-operative venous function but is not generally reflected in patient satisfaction rates, which tend to be similar which-ever procedure is performed. This led Woodyer and Dormandy to reach a contrary conclusion—that stripping the LSV was a procedure based on surgical dogma, and one that did not confer subjective benefit to the patients so treated. This leads one to conclude that a better method of evaluation of treatment results should be developed.
NONSURGICAL TREATMENT
In recent years, endovenous ablation has been found to be safe and effective in eliminating the proximal portion of the GSV from the venous circulation, with even faster recovery and better cosmetic results than stripping. The two currently available methods used to achieve ablation of the GSV are the Closure© procedure using a radiofrequency (RF) catheter and generator (VNUS Medical Technologies, Inc.,
The major difficulty with defining success as reduction or absence of refl ux is that attempts to establish whether reflux is present in a portion of a previously closed GSV may be inaccurate. Also, most recurrent patency is seen in the proximal portion of the treated GSV. Therefore, distal compression of the closed portion of the GSV to identify reflux in a proximal segment is futile. Likewise, using the Valsalva maneuver is unreliable and lacks reproducibility. Finally, the importance of distinguishing a partially patent channel with flow, from one with reflux, is academic, since the valves are just as thoroughly destroyed as the rest of the vein wall.
CHEMICAL VENOUS CLOSURE
Some phlebologists have advocated liquid sclerotherapy of the saphenous vein, but the results of such treatment have been disappointing, and published long-term results are absent. Comparisons between liquid and foam sclerotherapy have been done and the results strongly favor foam.
Ultrasound-guided sclerotherapy (USGS) with foam must be considered as a completely new treatment of varicose veins. Although it needs proper training and some skill, it is simple, affordable, and extremely efficient.
Sclerosing agents produce a lesion of the venous wall, predominantly of the endothelium and, to a minor extent, of the media. The reaction that follows depends on the concentration of the agent and on the duration of the contact. If the venous diameter is greater than
Making the foam is easy and quick. Based on the technique initially described by Tessari, it can be prepared with two 5 cc syringes and a three-way stopcock. Only detergent sclerosing agents can be used: Sotradecol and Polidocanol at any desired concentration from 0.25% to 3%. Microbubbles of foam sclerosing agents are hyperechogenic and represent an excellent contrast medium for ultrasound techniques. They appear as a shadow within the lumen early, and like a hyperechogenic mass later with a acoustic shadow. Massaging the sclerosing agent to the desired part of the varicose network with the duplex probe or the hand is also very easily carried out. Progression from the varicose clusters to the GSV and then to the SFJ is always visible, provided a sufficient volume has been injected. Venous spasm usually is observed within minutes. The importance of the initial spasm has been emphasized in several studies and protocols.
Post-sclerotherapy compression is mandatory: on the varicose clusters for 48 hours, and then whole limb compression with 20–30 mmHg thigh-high medical elastic stockings. They must be worn during the daytime for at least 15 days. Patients must be examined both clinically and with duplex at 7 to 15 days.
The absolute risk of deep venous thrombosis is not confirmed. A few cases have been reported: most of them are gastrocnemius vein thrombosis, typically after telangiectasia and reticular vein sclerotherapy. Most frequent complications are visual disorders. These adverse reactions have been observed also with liquid sclerosing agents but their incidence is much higher with foam; they can be estimated at 0.5–1 per 100 foam sessions.
They are observed more frequently in patients suffering from migraine with visual aura. They usually reproduce this aura. The patho-physiology of this phenomenon has been questioned but has received no answer so far. The existence of a patent foramen ovale is the most likely explanation, as has been the liberation of toxic component associated with endothelial cell destruction (endothelin).
All published results demonstrate an immediate effiacy better than 80% in terms of immediate/primary venous occlusion. Repetition of injections in case of initial failure allows closure to approach 95% of efficacy with two to three sessions. Early and mid-term results demonstrate a recurrence rate of about 20%. The re-do injections remain as simple as primary injections and at least as effiient.
INVERSION STRIPPING OF THE SAPHENOUS VEIN
One of the cornerstones of surgery for varicose veins is removal of the Great Saphenous vein (GSV) from the circulation. This can be done using minimally invasive techniques described elsewhere in this volume, but specific indications for performing saphenous surgery remain. These are largely institutional and geographic but they justify the following exposition.Indications for intervention in primary venous insufficiency are listed in Table 4 Often, it is the appearance of telangiectatic blemishes or protuberant varicosities that stimulates consultation. Ultimately, this may be the only indication for intervention.
Table 4.Varicose Veins: Indications for Intervention
Characteristic symptoms include aching, pain, easy leg fatigue, and leg heaviness, all relieved by leg elevation, and worsened on the first day of a menstrual peritod. Other indications for intervention for venous varicosities include superficial thrombophlebitis in varicose clusters, external bleeding from high-pressure venous blebs, or advanced changes of chronic venous insufficiency such as severe ankle hyperpigmentation, subcutaneous lipodermatosclerosis, atrophie blanche, or frank ulceration. Symptoms are frequent throughout the CEAP Classes 1 through 6. Clinical Disability Scores parallel the clinical classification.
Objectives of treatment should be ablation of the hydrostatic forces of axial refl ux and removal of the effects of hydrodynamic forces of perforator vein reflux. The latter can be accomplished by removal of the saphenous vein in the thigh and the varicose veins without specific perforating vein interruption. In
Ligation of the saphenous vein at the saphenofemoral junction has been practiced widely in the belief that this would control gravitational reflux while preserving the vein for subsequent arterial bypass. It is true that the saphenous vein is largely preserved after proximal ligation. Unfortunately, refl ux continues and hydrodynamic forces are not controlled. Less refl ux persists when the long saphenous vein has been stripped. There is a better functional outcome after stripping and fewer junctional recurrences. Randomized trials show efficacy of stripping compared to simple proximal ligation.
Earlier comparisons of saphenous ligation versus stripping were fl awed by today’s standards. Subjective evaluation was the only means of measuring outcome for a time.
Duplex scanning came into use, verifying that stripping was superior to proximal ligation; this fact was supported by PPG. Despite those facts, it was acknowledged that the period of disability after stripping was greater than that after simple ligation. In attempts to decrease disability and improve efficacy, high tie was added to saphenous vein sclerotherapy, but foot volumetry showed that radical surgery, including stripping produced superior results.
Ultimately, attention became focused on saphenous nerve injury associated with ankle to groin stripping. It was concluded that nerve injury was reduced by groin to ankle stripping (see Figure 5). Preservation of calf veins by stripping to the knee was shown to reduce nerve injury and did not adversely affect early venous hemodynamic improvement.
Fig. 5.
This fact is contraintuitive, and the subject deserves further study.Attempts to reduce nerve injury and simultaneously clean up varicose vein surgery led to use of the hemostatic tourniquet. In a study with level 1 evidence, it was shown that use of a hemostatic cuff tourniquet during varicose vein surgery reduces perioperative blood loss, operative time, and postoperative bruising without any obvious drawbacks.
Recurrent varicose veins after surgery are acknowledged to be a major problem for patients and society. Traditionally, it was thought that the most common reason for varicose recurrence was failure to perform an adequate saphenofemoral junction dissection (see Figure 6), or to correctly identify the saphenous vein for removal.
Fig.6. In the past, a proper groin dissection consisted of laying out each of the named saphenofemoral junction tributaries and dissecting them back beyond their primary tributaries. Now, this is acknowledged by most to be the
strongest stimulus to neovascularization.
Duplex scans have clarified this situation and instead of technical error, some investigators are convinced that new vessel growth contributes to recurrent varicose veins. In particular, incomplete superficial surgery, at the saphenofemoral and saphenopopliteal junctions, is a less frequent cause of recurrent disease, and neovascular reconnection and persistent abnormal venous function are the major contributors tomdisease recurrence.
PREOPERATIVE PREPARATION
Over the years, much space has been given to clinical examination of the patient with varicose veins. Many clinical tests have been described. Most carry the names of now-dead surgeons who were interested in venous pathophysiology. This august history notwithstanding, the Trendelenburg test, the Schwartz test, the Perthes test, and the Mahorner and Ochsner modifications of the Trendelenburg test essentially are useless in preoperative evaluation of patients today.
The clinical evaluation can be improved by using hand-held Doppler devices. However, preoperative evaluation is best performed by means of duplex scanning and a focused physical examination. Our protocol for duplex mapping of incompetent superficial veins has been published. Although many cite cost considerations as a reason for omitting duplex evaluation, we believe that duplex scanning for venous insufficiency is in fact both simple and cost effective. Duplex mapping defines individual patient anatomy with considerable precision and provides valuable information that supplements the physician’s clinical impression.
Three principal goals must be kept in mind in planning treatment of varicose veins: 1) the varicosities must be permanently removed and the underlying cause of venous hypertension treated; 2) the repair must be done in as cosmetic a fashion as possible; 3) complications must be minimized.
Current practice of treating the source of venous hypertension, the saphenous vein alone either by EVLT or VNUS technology, is inadequate. The patient’s complaint, the varicose veins, must be addressed. This is as important as the physician’s knowledge that the sources of venous hypertension must be addressed.
To speak of permanent removal of varicosities implies that all potential causes of recurrence have been considered and that surgery has been planned so as to address them. There are four principal causes of recurrence of varicose veins, of which three can be dealt with at the time of the primary operation.
One cause of recurrent varicosities is failure to perform the primary operation in a correct fashion. Common errors include missing a duplicated saphenous vein and mistaking an anterolateral or accessory saphenous vein for the greater saphenous vein. Such errors can be eliminated by careful and thorough groin dissection. Accordingly, failure to do a proper groin dissection has long been held to be a second principal cause of recurrent varicose veins. It is now known, however, that such dissection causes neovascularization in the groin, leading to recurrence of varicose veins. A third cause of recurrent varicosities is failure to remove the greater saphenous vein from the circulation. As mentioned earlier, reasons often cited for this failure is the desire to preserve the saphenous vein for subsequent use as an arterial bypass. It is clear, however, that the preserved saphenous vein continues to reflux and continues to elongate and dilate its tributaries. This produces more and larger varicosities. A fourth cause of recurrent varicosities is persistence of venous hypertension through nonsaphenous sources—chiefly, perforating veins with incompetent valves. Muscular contraction generates enormous pressures that are directed against valves in perforating veins. Venous hypertension induces a leukocyte endothelial reaction, which, in turn, incites an infl ammatory response that ultimately destroys the venous valves and weakens the venous wall. The perforating veins most commonly associated with recurrent varicosities are the midthigh perforating vein, the distal thigh perforating vein, the proximal anteromedial calf perforating vein, and the lateral thigh perforating vein, which connects the profunda femoris vein to surface varicosities.
Finally, there is a fi fth cause of recurrent varicosities, which is out of control of the operating surgeon—namely, the genetic tendency to form varicosities through development of localized or generalized vein wall weakness, localized blowouts of venous walls, or stretched, elongated, and floppy venous valves.
SAPHENOUS SURGERY
For varicose vein surgery to be successful, two tasks must be accomplished. The fi rst is ablation of reflux from the deep to the superficial veins, including the saphenofemoral junction, the saphenopopliteal junction, and midthigh varices from the Hunterian perforating vein. Accomplishment of this task is guided by the careful preoperative duplex mapping of major superficial venous reflux.
The second task is removal or destruction of all varicosities present at the time of the surgical intervention. Accomplishment of this task is guided by meticulous marking of all varicose vein clusters. A number of options are available for surgical treatment of varicose veins. Regardless of the specific approach taken, the general technical objectives are the same: 1) ablation of the hydrostatic forces of axial saphenous vein refl ux (see Figure 7) and 2) removal of the hydrodynamic forces of perforator vein outflow.
Fig. 7. Inversion stripping of the saphenous vein was an important step forward in minimizing soft tissue trauma while accomplishing the principal objective of ablating hydrostatic venous hypertension by removing saphenous
reflux. Tearing of the vein during its removal fl awed its performance.
Ankle-to-groin stripping of the saphenous vein has been a dominant treatment of varicose veins over the past 100 years. One argument against routine stripping of the leg (i.e., ankle-to-knee) portion of the saphenous vein is the risk of concomitant saphenous nerve injury. Another argument is that whereas the objective of saphenous vein removal is detachment of perforating veins emanating from the saphenous vein, which are seen in the thigh, the perforating veins in the leg are actually part of the posterior arch vein system rather than the saphenous vein system. This latter argument notwithstanding, preoperative ultrasonography frequently shows that the leg portion of the saphenous vein is in fact directly connected to perforating veins. Therefore, removal of the saphenous vein from ankle to knee should be a consideration in every surgical case.
OPERATIVE TECHNIQUE
The surgical approach taken must be individually tailored to each patient and each limb. Groin-to-knee stripping of the saphenous vein should be considered in every patient requiring surgical intervention. Iearly all patients, this measure is supplemented by removal of the varicose vein clusters via stab avulsion or some form of sclerotherapy.
Preoperative marking, if correctly performed, will have documented the extent of varicose vein clusters and identified the clinical points where control of varices is required. Incisions can then be planned. As a rule, incisions in the groin and at the ankle should be transverse and should be placed within skin lines. In the groin, an oblique variation of the transverse incision may be appropriate. This incision should be placed high enough to permit identification of the saphenofemoral junction.
Generally, throughout the leg and the thigh, the best cosmetic results are obtained with vertical incisions. Transverse incisions are used only in the region of the knee, and oblique incisions are appropriate over the patella when the incisions are placed in skin lines.
A major cause of discomfort and occasional permanent skin pigmentation is subcutaneous extravasation of blood during and after saphenous vein stripping. Such extravasation can be minimized by applying a hemostatic tourniquet after Esmarch exsanguination of the limb. The pressure in the hemostatic tourniquet should be between 250 and
The practice of identifying and carefully dividing each of the tributaries to the saphenofemoral junction has been dominant over the past 50 years. The rationale for this practice has been that it would be inadvisable to leave behind a network of interanastomosing inguinal tributaries. Accordingly, special efforts have been made to draw each of the saphenous tributaries into the groin incision so that when they are placed on traction, their primary and even secondary tributaries can be controlled. The importance of these efforts has been underscored by descriptions of residual inguinal networks as an important cause of varicose vein recurrence. Currently, however, this central practice of varicose vein surgery is under challenge, on the grounds that groin dissection can lead to neovascularization and hence to recurrence of varicosities.
Preoperative duplex studies have already demonstrated incompetent valves in the saphenous system, and a disposable plastic stripper can be introduced from above downward; alternatively, a metal stripper can be employed. Both of these devices can be used to strip the saphenous vein from groin to knee via the inversion technique. This approach should reduce soft tissue trauma in the thigh.
In the groin, the stripper is inserted proximally into the upper end of the divided internal saphenous vein and passed down the main channel through incompetent valves until it can be felt lying distally approximately
Stripping of the saphenous vein has been shown to produce profound distal venous hypertension. This occurs in virtually every operation, even when the limb is elevated. Therefore, after the stripper is placed, one should consider performing the stab avulsion portion of the procedure before the actual stripping maneuver.
Incisions to remove varicose clusters vary according to the size of the vein, the thickness of the vein wall, and the degree to which the vein is adhering to the perivenous tissues. In general, vertical incisions 1 to
Phlebectomy techniques for varicose clusters have been markedly refined by experienced workers in
Once the stab avulsion portion of the procedure is complete, the previously placed stripper is pulled distally to remove the saphenous vein. Although plastic disposable vein strippers and their metallic equivalents were designed to be used with various-sized olives to remove the saphenous vein, in fact, a more efficient technique is simply to tie the vein to the stripper below its tip so that the vessel can then be inverted into itself and removed distally. To decrease oozing into the tract created by stripping, a
Fig. 8 . Adding a hemostatic pack to inversion stripping corrected the principal fl aw in inversion stripping, the tearing of the saphenous vein. The pack acted as an obturator, which insured total vein removal. In most instances, the
pack entered the vein as it was being removed, thus minimizing the soft tissue trauma.
POST-THROMBOTIC SYNDROME
Postthrombotic syndrome (PTS) is a frequent sequel to deep venous thrombosis (DVT). Awareness of this long-term debilitating complication is low among treating physicians whose main focus is the acute embolic complications of DVT. PTS may take years and even decades to fully evolve when the patient is no longer in the care of the original treating physician. Recurrent DVT that may occur years later after the initial event is a known risk factor for the development of PTS. Serial follow up of patients after onset of DVT has provided important new perspectives on many aspects of PTS. After a bout of DVT, only a third of the patients are asymptomatic long term; but the other two thirds have PTS, half of them severe. The direct and indirect costs of this disease that affects all adult age groups is estimated to be enormous, arousing the interest of public health planners.
CLINICAL FEATURES
Major symptoms are limb pain, swelling, and stasis skin changes including ulceration. Recurrent thrombophlebitis and recurrent cellulitis, the latter related to underlying tissue edema, are less well known and less frequent features. Symptoms are present in varying combinations and severity in individual patients. Pain is an important but variable component of the symptom complex. Limb swelling may be described by the patient as severe because it is painful even though only mild pitting is evident on examination. Some patients may not even be aware of limb edema evident to the examiner because it is pain free. Pain is absent in about 20% of patients. In about 10% of patients, pain may be the only symptom without other signs; a diagnosis of PTS may altogether be missed, because the limb looks normal. Severity of pain present may be exaggerated or understated by the patient due to individual variations in pain tolerance and other socioeconomic factors such as work situation; daily or frequent use of nonsteroidal or narcotic dependency for pain relief may not be readily disclosed unless specifically quetioned. Other essential elements of history may not be readily forthcoming as well. For example, previous DVT or severe trauma to the limb may not be volunteered because the remote event years ago had been forgotten or not considered relevant to current complaints. Because of these variables, a detailed comprehensive history-taking with leading questions is essential for proper assessment; clinical features detected on examination should be recorded and graded for severity during initial and follow-up visits for proper assessment of outcome. All components of relevant history and physical examination preloaded on a handheld device is a useful guide to those who see these patients only infrequently. The CEAP classification and Venous Severity Scoring endorsed by the vascular societies can serve as readily usable templates for this purpose. In our own system, we have made some additional enhancements that we find useful. Pain is measured on a visual analogue scale, a simple reliable measure of pain that can be used for outcome assessment as well. Limb swelling is variable throughout the day; limb measurement of swelling should be carried out at the same time of the day to be valid for follow-up assessment. Quality of life (QOL) measurements provide a view of outcome from the patient’s perspective. The degree of disability and social constraint imposed by this disease can be surprising. Many QOL forms (e.g., CIVIQ) are brief enough for routine use.
DIFFERENTIAL DIAGNOSIS
A clinical diagnosis of chronic venous insufficiency is readily apparent from history and physical examination in most cases but other rarer causes with somewhat similar clinical features have to be borne in mind: Periarteritis nodosa, ruptured Baker’s cyst, rheumatoid arthritis, gout, Marjolin’s ulcer, arterio-venous malformations of the calf muscles, adverse drug reactions with limb pain and swelling, acanthoma nigricans, pyoderma, and numerous other dermatological and systemic conditions. As venous insufficiency is common, particularly among the elderly, mixed pathologies that aggravate venous symptoms do occur. Combined arterial/venous insufficiency is not uncommon in the elderly; attention to the arterial component first is usually recommended. Differentiating primary from PTS may not be easy and mixed presentations occur as the following discussion on pathology indicates. Differentiation cannot be made on clinical grounds alone as history and physical findings may be similar including the appearance and size of ulcers. About 30% of DVT are estimated to be silent. In others DVT following trauma or surgery is simply missed as symptoms are submerged by expected postoperative pain—a common occurrence following orthopedic procedures on the hip or knee or for treatment of fractures. Patients with deep valvular insuffi ciency whether primary or post-thrombotic not infrequently present with new onset of acute calf pain and increased swelling in the context of ongoing chronic symptoms. In some, new or recurrent thrombosis is found. In others, no new thrombus is found; the symptoms are presumably due to decompensation of the calf pump from minor injury, low grade cellulitis or other obscure insult that disturbs the equilibrium of the calf pump. A diagnosis of PTS vs primary venous insufficiency is academic from the surgical viewpoint as the approach is the same regardless. But a diagnosis of PTS may have implications for long-term anticoagulation. In many cases, further investigations may provide helpful clarification.
PATHOLOGY
Our current view of PTS pathology is strongly influenced by the work of Strandness and colleagues. Before then, post-thrombotic clinical syndrome had been viewed as primarily related to the development of reflux. In a remarkable series of landmark papers, these authors showed that the dominant pathology was a combination of obstruction and reflux even though isolated obstruction and reflux occurred in some. The location and progression of post-thrombotic reflux followed by serial duplex were unexpected and intriguing. Reflux occurred not only in segments involved by thrombus but also in segments remote from them. Reflux occurred and progressed over time not only in deep venous segments distal to the thrombotic segment but also in segments proximal; in the distal segments, dilatation of the valve station due to cephalad obstruction was not found to be the cause of reflux. The fact that reflux occurs and progresses over time in superfi cial as well as deep valves proximal to the obstructed segment suggests a different (maybe cytokines), as yet poorly understood, mechanism.
Some patients present with femoral valve reflux and thrombosis in the distal femoral popliteal segment or even the calf. This clinical profile could be due to reflux stasis–induced distal thrombosis. Repair of the valve reflux can abate recurrent thrombosis. Similar type of clinical presentation also can result from evolution of de novo reflux above the thrombotic segment as described by Strandness and colleagues. Perivenous and mural fi brosis is a feature of these valves with constriction and foreshortening of the valve station (see Figure 9). The valve cusps themselves are redundant and reflexive apparently as a result of the fibrotic wall changes. The fi brotic valve station is somewhat smaller than the classic primary valve, but the cusps themselves appear normal but redundant and can be repaired like the primary valve using direct repair techniques. A plausible explanation for these features and perhaps for the remote reflux described by Strandness’s group is that perivenous and mural fi brosis may extend beyond the thrombosed segment to involve adjacent segments of preserving valve cusps, but inducing secondary reflux from valve station restriction.
Valves may also escape destruction because the thrombus in the resident segment lyses, but not without inducing fi brotic changes as described.
Fig.
INVESTIGATIONS
A comprehensive set of investigations are necessary for proper management of patients, particularly if invasive or other surgical intervention is contemplated. The aim is to clarify the pathology, identify the sites and nature of pathology, and grade its severity.
Duplex
Duplex is the initial and in many centers the only technique used. It has many deficiencies when used alone in assessment. As a qualitative tool, it can detect local reflux but cannot grade it nor can it adequately provide a measure of the overall severity of refl ux in the limb when multiple segments are involved. Valve closure time (VCT) has received much attention as a quantitative tool in this regard. Though it can identify reflux in a particular segment, VCT has poor correlation with the severity of reflux present. Trivial reflux may be associated with prolonged VCT and conversely high grade reflux may have only slightly prolonged VCT. Peak reflux velocity has a better correlation, but not to a degree that is clinically useable. At present relatively crude indices such as multisegment score (number of refl uxive segments) or the presence of axial reflux are the best measures available. Iliac vein outflow obstruction, an important contributor to PTS, is frequently impervious to duplex.
Venography
Unlike duplex, ascending venography provides a more composite view of venous pathology below the inguinal ligament. Post-thrombotic changes, segmental occlusions, and collateral patterns are readily apparent. The profunda femoris vein is the major natural collateral pathway in femoral stenoses and occlusions. This has an embryologic basis as the profunda femoris is the early axial vein receding to the mature pattern later in embryologic development. A putative profunda-popliteal connection apparently exists as a high resistance embryologic residue; profunda collateral flow can be observed as early as a few hours after onset of acute DVT in venograms. In chronic femoral vein occlusions, the profunda enlarges to the same caliber as the normal femoral vein (see Figure 11). This pattern of complete axial transformation of the profunda femoris vein occurs in about 15% of postthrombotic limbs. Reflux may result from enlargement of the profunda valve station and may be severe with symptoms. Lesser degrees of profunda enlargement can be found in other cases where the femoral vein is not totally occluded but is stenotic.
Because the direction of collateral flow in the profunda is the same as natural fl ow direction in the vessel, it is very efficient. Once fully developed, the profunda fully compensates for the loss of femoral flow with few residual clinical symptoms from outfl ow obstruction. In iliac vein occlusions, collateral flow is mainly through tributaries of the iliac vein itself, requiring reversal of normal flow direction. Collateral flow seems to be less efficient and residual outflow obstruction is present iearly half the cases with iliac occlusions.
These differential patterns of collateral development and function have clinical import. In patients with symptoms of outflow obstruction, iliac vein pathology is likely to be the culprit even if associated femoral vein occlusion is more readily seen on ascending venography. Ascending venography is inadequate for assessment of the iliac vein and the vena cava due to contrast dilution; stenotic lesions may easily be missed.
Fig. 11. Axial transformation of profunda femoral vein through a
large profunda-popliteal connection. The femoral vein is largely occluded
with the distal end seen as a stump.
Transfemoral venography is the procedure of choice for pelvic venous assessment. Exercise femoral venous pressures can be concurrently measured, hich can be helpful in grading severity of outflow obstruction. Descending venography can also be performed at the same time to define the architecture of femoral valves. Descending venography is no longer used for grading reflux due to lack of specificity.
A common pattern in severely post-thrombotic limbs is where the entire outflow appears to occur through the superficial veins with nonvisualization of deep veins giving the appearance of wiped-out deep system. This is invariably an artifact of technique. In most such cases a patent but post-thrombotic deep system with numerous collateral elements can be demonstrated on descending venography (see Figure 12). Presumably, there is a positive gradient across superficial to deep venous connections in these cases that contrast flow preferentially is restricted to the superficial system. The collateral contribution of the superficial system in such cases is negligible. Since the deep system is patent, reconstructive procedures can be planned despite the spurious appearance on ascending venography.
Several authors beginning with Rokitanski have documented the development of a dense perivenous sheath in postthrombotic iliac veins. This prevents or retards the development of collaterals. Surgical attempts have been made to remove the sheath for improving flow. The venographic appearance in such cases is one of diffuse stenosis without collaterals. Iliac vein pathology is easily missed in such cases, especially with ascending venography. With transfemoral venography, the diffuse lesion can be quite evident or subtle requiring measurements of vein diameter, which is seldom practiced. Because of this and other factors cited earlier, the sensitivity of venography in iliac vein pathology is only in the order of 60%.
Fig. 12. Ascending venogram opacifies only superficial network
(right). The deep system appears wiped out. This is often a technical artifact
ample deep venous elements are demonstrated on descending
venography (left).
Intravascular Ultrasound (IVUS)
Intravascular ultrasound is superior to venography in the assessment of post-thrombotic iliac vein and the inferior vena cava. Perivenous and mural fibrosis, stenoses and trabeculae are readily seen. It is invaluable in iliac vein stent placement.
Lymphangiography
About 30% of patients with deep venous insufficiency have lymphographic abnormalities such as pooling and delayed or absent lymphatic transport. Most are thought to be secondary to venous pathology from lymphatic exhaustion or damage. Some may be reversible with correction of venous pathology. Lymphographic information has prognostic value in resolution of leg swelling and affected patients may be adequately forewarned before interventions.
Airplethysmography (APG)
Measurement of ejection fraction and residual volume have been suggested as indirect indices of outflow obstruction. In our own and others’ experience, specifi city and sensitivity have been inconsistent. VFI appears to be a useful measure of reflux.
Ambulatory Venous Pressure Measurement
Ambulatory venous pressure measurement provides a global index of venous function in the limb encompassing multiple components. Post-exercise pressure (% drop) has an inconsistent relationship to the severity of outflow obstruction presumably because of the variability of calf pump efficiency. The recovery time or venous filling time (VFT) has been useful in assessing severity of postthrombotic pathology and reflux. A postoperative VFT of >5 seconds bodes well for a good surgical outcome; a VFT of <5 seconds the opposite. The mean improvement in VFT after successful repairs with good clinical outcome is generally in the order of about 6 ± 4 (SD) seconds. After successful valve repair, postoperative VFT does not reach normal levels in many patients. VFT is influenced not only by reflux but a multiplicity of other factors. Compliance of the conduit below the valve profoundly affects VFT even more than reflux at the valve. Failure to normalize or substantially improve VFT is probably related to the poor venous compliance in post-thrombotic extremities.
Measurement of Outflow Obstruction
Reduced or absent phasicity on duplex examination is often indicative of outflow obstruction at the iliac vein level, the information being qualitative. There are no reliable methods of functionally quantifying and grading outflow obstruction at the present time. Plethysmographic outflow fraction measurement such as with strain gauge technique and APG yield unacceptably high false positives due to compliance changes in the post-thrombotic calf; a reduced outflow fraction (<50%) results from subpar emptying of the venous pool from poor compliance as often as from outflow obstruction per se. And poor compliance may be present without obstruction. A reduced outflow fraction is indicative of post-thrombotic changes, not necessarily obstruction.
Pressure-based tests to detect and grade severity of obstruction such as arm/foot venous pressure differential with reactive hyperemia, exercise femoral venous pressures measurement, and intraoperative femoral vein pressure measurement with papavarine are positive only in about a third of cases. Assessment of outflow obstruction currently rests entirely on morphologic methodology (IVUS) restricted to the iliac vein segment.
TREATMENT
Compression Therapy
Compression therapy is the oldest and until recently the only therapeutic option available to treat PTS. It has been reported anecdotally to be ineffective in PTS but no systematic study has been undertaken. Compression therapy remains the initial approach in chronic venous disease including PTS. Some patients do fail compression therapy despite faithful compliance. Noncompliance, however, is the major cause of compression failure and recurrent symptoms. Noncompliance is high even in cold climates as documented in several community surveys. Longerm supervision or monitoring by health care workers has been advocated to improve compliance. However, noncompliance is high even under supervision. The reasons for noncompliance are many—tightness or fi t (cutting off circulation), warm weather, lack of efficacy, contact dermatitis, recurrent cost and inability to apply stockings due to frailty or arthritis are among the many reasons/excuses cited by patients. But the main underlying reason, often unstated, appears to be the restrictions and negatives of compression regimens in today’s image–conscious world with expectations of an unrestricted lifestyle. Thus compression is a quality of life issue from the patient’s viewpoint. Demands for compliance are unlikely to succeed after previous entreaties have failed and may not be appropriate when therapeutic alternatives have become available. Compression should be viewed not as an end itself, but complementary to the extent patients are willing to use them. Compression should be considered a failure regardless of the cause including noncompliance if symptom relief is not obtained after trial over a reasonable period of time, say three to six months depending on the clinical and socioeconomic situation of the patient. Worsening of symptoms or onset of complications such as recurrent infections during the trial period are also considered failures. Some patients are not candidates for compression therapy at all due to comorbidities (e.g., arthritis, frailty, or arterial compromise) or special work situations. Nonresponders should be offered alternatives, not life-longunna boot regimens as was the case before by necessity, and continues to be so in many parts of the world due to a conservative philosophy of health care delivery.
Saphenous Vein Ablation
There has been traditional advice against saphenous ablation in the presence of deep venous obstruction (secondary varices) to preserve its collateral contribution. The collateral contribution of saphenous vein in the presence of deep venous obstruction is insignificant. Stripping of a refluxive saphenous vein in PTS cases can provide significant symptom benefit by eliminating the reflux component without jeopardizing the limb. Stripping can be easily combined with valve reconstruction in the femoral area. The newer minimally invasive techniques of saphenous ablation are suitable alternatives as well and are easily combined with iliac vein stent placement when indicated
Valvuloplasty
In PTS patients, direct femoral or popliteal valve repair can be performed if the basic valve architecture is preserved. Eriksson stressed the importance of profunda valve repair in post-thrombotic cases due to the frequent presence of collateral reflux. We prefer an external or transmural technique without a venotomy for these cases as they are faster and hence multiple repairs (i.e., femoral and profunda) can be performed in a single sitting; and repairs can be carried out even in constricted or small valve stations. The internal technique is disadvantaged in comparison.
Trancommissural technique, which closes the wide valve angle present at the commissure and simultaneously tightens the lax valve cusps by transmural sutures that can be placed blindly in a reliable fashion. The first step in the procedure is to carry out an adventitial dissection to peel away the fibrous sheath surrounding the valve station. Valve attachment lines should become visible after the dissection. They should be defined in their entirety, which is necessary for placement of transcommissural sutures. Though the sutures are placed blindly, adherence to the technique as described in the original publication will result in technical success of >95%.
Absent or interrupted valve attachment lines invariably indicate cusp dissolution or damage beyond direct repair. In such cases one should proceed forthwith with axillary vein transfer without wasting time on performing a venotomy in a futile search for repairable valve cusps.
Axillary Vein Transfer
Axillary vein transfer is the mainstay of repair in PTS cases when direct valve repair is not feasible due to damage to the valve cusps. Seemingly a simple technique, it is in fact, quite demanding, requiring precise execution. Proctored learning is recommended to achieve consistently good results. The transferred valve should match the size of the native valve station being reconstructed. In most cases, the axillary vein is the preferred donor site to obtain a good size match. In a minority, the proximal brachial vein may also be suitable in size. We approach the axillary-brachial veins through a transverse incision in the armpit along the skin crease; exposure of 5 to
In trabeculated post-thrombotic veins, modifications of the basic technique are necessary. The trabeculae at the site of proximal and distal suture lines are excised (see Figure 13, 14, 15) to create a single lumen at the site for anastamoses.
Fig. 13.
Fig. 14.
Fig. 15.
In a subset of PTS patients both the femoral and profunda femoral veins are severely post-thrombotic with destroyed valve structures. The femoral confluence can be repaired with individual axillary vein transfers or by en bloc transfer of basilic-brachial confluence provided valves are present and size match requirements are satisfied (see Figure 16).
Fig.16.
LYMPHEDEMA
Background
Lymphedema is an abnormal collection of protein-rich fluid in the interstitium due to a defect in the lymphatic drainage network. Lymphedema most commonly affects the extremities, but it can involve the face, genitalia, or trunk. Numerous causes, both primary and secondary iature, have been identified for this condition.
The primary causes are due to abnormalities in the lymphatic system that are present at birth, although not always clinically evident until later in life. The 3 primary categories of lymphedema (due to genetic factors) are congenital lymphedema (Milroy disease), lymphedema praecox (Meige disease), and lymphedema tarda. Primary lymphedema can also be associated with various cutaneous syndromes.
Secondary lymphedema is due to an acquired obstruction or infiltration of the lymphatic system. Secondary lymphedema has a number of causes, which include malignancy, infection, obesity, trauma, congestive heart failure, portal hypertension, and therapeutic intervention. Despite the fact that the underlying etiologies of secondary lymphedema vary, clinical progression is similar and difficult to control.
Lymphedema is a progressive, deforming condition that is both physically and psychologically debilitating.
Angiosarcoma arising in an area of long-standing lymphedema is termed Stewart-Treves syndrome. Most cases of Stewart-Treves syndrome occur in the arm after surgery for breast cancer; however, sometimes angiosarcomas can arise in a chronically lymphedematous leg.
Lymphedema is a notoriously debilitating progressive condition with no known cure. The unfortunate patient faces a lifelong struggle of medical, and sometimes surgical, treatment fraught with potentially lethal complications.
The underlying problem is lymphatic dysfunction, resulting in an abnormal accumulation of interstitial fluid containing high molecular weight proteins. This condition underscores the tremendous importance of a normally functioning lymphatic system, which returns proteins, lipids, and accompanying water from the interstitium to the venous circulatioear the subclavian vein–internal jugular vein junction, bilaterally. The normal and abnormal flow of interstitial fluid through the lymphatic system are demonstrated below.
Fig. 17. The body quadrants of superficial lymph drainage
Fig. 18. (1) Normal lymphatic flow in (a) deep systems and (b) superficial systems. Note the small collateral vessels interconnecting the 2 systems. (2) Lymphedema develops from obstruction, dilation of valves, valvular insufficiency, and subsequent reversal of lymphatic flow.
Pathophysiology
The normal function of the lymphatics is to return proteins, lipids, and water from the interstitium to the intravascular space; 40-50% of serum proteins are transported by this route each day. High hydrostatic pressures in arterial capillaries force proteinaceous fluid into the interstitium, resulting in increased interstitial oncotic pressure that draws in additional water.
Interstitial fluid normally contributes to the nourishment of tissues. About 90% of the fluid returns to the circulation via entry into venous capillaries. The remaining 10% is composed of high molecular weight proteins and their oncotically associated water, which are too large to readily pass through venous capillary walls. This leads to flow into the lymphatic capillaries where pressures are typically subatmospheric and can accommodate the large size of the proteins and their accompanying water. The proteins then travel as lymph through numerous filtering lymph nodes on their way to join the venous circulation.
In a diseased state, the lymphatic transport capacity is reduced. This causes the normal volume of interstitial fluid formation to exceed the rate of lymphatic return, resulting in the stagnation of high molecular weight proteins in the interstitium. It usually occurs after flow has been reduced by 80% or more. The result, as compared to other forms of edema that have much lower concentrations of protein, is high-protein edema, or lymphedema, with protein concentrations of 1.0-5.5 g/mL. This high oncotic pressure in the interstitium favors the accumulation of additional water.
Accumulation of interstitial fluid leads to massive dilatation of the remaining outflow tracts and valvular incompetence that causes reversal of flow from subcutaneous tissues into the dermal plexus. The lymphatic walls undergo fibrosis, and fibrinoid thrombi accumulate within the lumen, obliterating much of the remaining lymph channels. Spontaneous lymphovenous shunts may form. Lymph nodes harden and shrink, losing their normal architecture.
In the interstitium, protein and fluid accumulation initiates a marked inflammatory reaction. Macrophage activity is increased, resulting in destruction of elastic fibers and production of fibrosclerotic tissue. Fibroblasts migrate into the interstitium and deposit collagen. The result of this inflammatory reaction is a change from the initial pitting edema to the brawny nonpitting edema characteristic of lymphedema. Consequently, local immunologic surveillance is suppressed, and chronic infections, as well as malignant degeneration to lymphangiosarcoma, may occur.
The overlying skin becomes thickened and displays the typical peau d’orange (orange skin) appearance of congested dermal lymphatics. The epidermis forms thick scaly deposits of keratinized debris and may display a warty verrucosis. Cracks and furrows often develop and accommodate debris and bacteria, leading to lymphorrhea, the leakage of lymph onto the surface of the skin.
Frequency
A common cause of lymphedema reported in the
Among the primary causes of lymphedema, lymphedema praecox is the most commonly reported.
International
Worldwide, the most common cause of lymphedema is filariasis infection. More than 100 million people are affected in endemic areas worldwide
Mortality/Morbidity
The outcome for persons with lymphedema depends on its chronicity, the complications that result, and the underlying disease state that caused the lymphedema.
The development of angiosarcoma (ie, Stewart-Treves syndrome) in the setting of lymphedema is the most serious complication of secondary lymphedema. The mean survival rate, after treatment, is approximately 24 months. The 5-year survival rate is 10%.
Other complications that increase morbidity are the development of recurrent cellulitis, bacterial or fungal infections, and lymphangioadenitis.
Sex
Primary lymphedema is most common in females. Lymphedema praecox is the most common form and affects
Age
Secondary lymphedema can affect persons of any age group, and its onset is determined by the primary cause. Hereditary (primary) lymphedema can be divided into 3 groups based on the age of onset of clinical lymphedema, as follows.
– Milroy disease is the familial form of lymphedema that usually manifests from birth to age 1 year.
– Lymphedema praecox (ie, Meige disease) occurs from age 1-35 years. It most commonly occurs around menarche.
– Lymphedema tarda manifests after age 35 years
CLINICAL
History
Patients often report that chronic swelling of an extremity preceded lymphedema. Eighty percent of patients present with lower extremity involvement, although the upper extremities, face, genitalia, and trunk can also be involved. The history confirms involvement of a distal extremity initially, with proximal involvement following. Patients with lymphedema often report painless swelling and leg heaviness.
Fevers, chills, and generalized weakness may be reported. Patients may have a history of recurrent episodes of cellulitis, lymphangitis, fissuring, ulcerations, and/or verrucous changes. Patients have a higher prevalence of bacterial and fungal infections.
In primary lymphedema, patients have a congenital defect in the lymphatic system; therefore, the history of onset is more typical of the specific type.
Also more common is for primary lymphedema to be associated with other anomalies and genetic disorders, such as yellow nail syndrome, Turner syndrome, Noonan syndrome, xanthomatosis,2 hemangiomas, neurofibromatosis type 1, distichiasis lymphedema,3,4 Klinefelter syndrome, congenital absence of nails, trisomy 21, trisomy 13, and trisomy 18.
A rare inherited disorder, distichiasis-lymphedema syndrome, is characterized by the presence of extra eyelashes (distichiasis) and swelling of the arms and legs (lymphedema). Swelling of the legs, especially below the knees, and eye irritation are common in people with this disorder. Spinal cysts (epidural) with or without other abnormalities of the spinal column can accompany distichiasis lymphedema. Distichiasis-lymphedema syndrome is inherited as an autosomal dominant genetic trait due to a mutation of the FOX2 gene.
In secondary lymphedema, the associated history should be more evident, based on the primary etiology.
If due to filariasis, the history should include travel or habitation in an endemic area.
Other patients should have a clear history of a neoplasm obstructing the lymphatic system, recurrent episodes of lymphangitis and/or cellulitis, obesity, trauma, or lymphedema resulting after surgery and/or radiation therapy.
A recent history of varicose vein surgery also is reported.
In 2009, Lu et al noted 24 cases of localized lymphedema presenting as solitary large polyps, solid or papillomatous plaques, pedunculated edematous lesions, or tumors that imitated sarcoma. Lesions most commonly occurred on the vulva.
Physical
The earliest symptom of lymphedema is nontender pitting edema of the affected area, most commonly the distal extremities. The face, trunk, and genitalia also may be involved. Radial enlargement of the area occurs over time, which progresses to a nonpitting edema resulting from the development of fibrosis in the subcutaneous fat.
The distal extremities are involved initially, followed by proximal advancement.
Patients have erythema of the affected area and thickening of the skin, which appears as peau d’orange skin and woody edema.
With long-term involvement, ENV develops, which is an area of cobble-stoned, hyperkeratotic, papillomatous plaques most commonly seen on the shins. The plaques of ENV can be covered with a loosely adherent crust, can be weepy or oozing a clear or yellow fluid, and/or can have a foul-smelling odor. The changes of ENV have been described as cobblestone, pebbly, hyperkeratotic, papillomatous, and verrucous.
Fissuring, ulcerations, skin breakdown, and lymphorrhea can also be seen. Lymphorrhea involves the weeping or oozing of clear, yellow, or straw-colored fluids. Superinfection is common and can manifest as impetigo with yellow crusts.
Four cases of cutaneous verruciform xanthomas in association with lymphedema have been cited in the literature. More recent reports have suggested that verruciform xanthomas may be a rare reactive phenomenon found in persons with common cutaneous conditions. Because verruciform xanthoma is considered by some authorities to be a reactive condition, the link between these 2 entities remains unclear at this time.
A positive Stemmer sign (inability to pinch the dorsal aspect of skin between the first and second toes) may be elicited upon examination.
Other associated physical findings specific for the cause of secondary lymphedema and genetic disorders involving lymphedema may be noted upon examination.
Causes
Both primary and secondary lymphedema can have many causes.
Primary lymphedema
Primary lymphedema is divided into 3 main types, which are distinguished by their age of onset. All are caused by a congenital abnormality in the lymphatic system, although these defects may not always be clinically evident until later in life. Additionally, primary lymphedema also can be associated with other cutaneous and genetic disorders not among the 3 main age-based categories.
Congenital lymphedema, also known as Milroy disease, is an autosomal dominant familial disorder of the lymphatic system that manifests at birth to age 1 year. It is often due to anaplastic lymphatic channels. The lower extremity edema is most commonly bilateral, pitting, and nonpainful. This condition may be linked to a mutation that inactivates VEGFR3. It has been associated with cellulitis, prominent veins, intestinal lymphangiectasias, upturned toenails, and hydrocele.
Lymphedema praecox, also known as Meige disease, is the most common form of primary lymphedema. Seventy percent of cases are unilateral, with lower extremity swelling being more common. This type of primary edema is most often due to hypoplastic lymphatic channels. This condition most often manifests clinically around menarche, suggesting that estrogen may play a role in its pathogenesis.
Lymphedema tarda manifests later in life, usually in persons older than 35 years. It is thought to be due to a defect in the lymphatic valves, resulting in incompetent valve function. Whether this defect is congenital or acquired is difficult to determine.
As mentioned, primary lymphedema is also seen in association with other cutaneous and genetic disorders.
Lymphedema-distichiasis syndrome is a form of hereditary early- and late-onset lymphedema associated with distichiasis (double row of eyelashes). Affected persons usually manifest bilateral lower extremity lymphedema by age 8-30 years. Lymphatic vessels are usually larger in affected areas. It is a hereditary condition with an autosomal dominant pattern with variable penetrance. It reportedly is associated with a mutation in FOXC2 transcription factor.5 Other associated anomalies may include vertebral abnormalities, spinal arachnoid cysts, hemangiomas, cleft palate, ptosis, short stature, webbed neck, strabismus, thoracic duct abnormalities, and microphthalmia.
Primary lymphedema has also been associated with yellow nail syndrome. This entity may be associated with recurrent pleural effusions and bronchiectasis.
Other genetic syndromes and cutaneous conditions associated with primary lymphedema are Turner syndrome, Noonan syndrome, Klinefelter syndrome, neurofibromatosis type 1, hemangiomas, xanthomatosis, and congenital absence of nails. One reported case described lymphedema in association with CHARGE (coloboma, heart anomalies, choanal atresia, somatic and mental retardation, genitourinary anomalies, ear abnormalities) syndrome.
Secondary lymphedema
Secondary Lymphedema is caused by an acquired defect in the lymphatic system and is commonly associated with obesity, infection, neoplasm, trauma, or therapeutic modalities.
The most common cause of secondary lymphedema worldwide is filariasis. This is due to a mosquito-borne nematode infection with the parasite Wucheria bancrofti. It commonly occurs in developing countries around the world. This infection results in permanent lymphedema of the limb.
In the developed world, the most common cause of secondary lymphedema is malignancy and treatment.
– It can result from obstruction from metastatic cancer or primary lymphoma or can be secondary to radical lymph node dissection and excision. Although lymphatics are thought to regenerate after transection via surgery, when combined with radiotherapy to the area, the risk of lymphedema increases because of scarring and fibrosis of the tissue.
– The most commonly affected area is the axillary region after mastectomy and radical dissection for breast cancer. Lymphedema can also be seen after regional dissection of pelvic, para-aortic, and neck lymph nodes.
– Other associated neoplastic diseases are Hodgkin lymphoma, metastatic prostate cancer, cervical cancer, breast cancer, and melanoma.
Morbid obesity frequently causes impairment of lymphatic return and commonly results in lymphedema, as shown in the image below.
Fig. 19. Morbidly obese patient with lymphedema.
– Lymphedema is also associated with trauma, varicose vein surgery, congestive heart failure, portal hypertension, and extrinsic pressure, as shown in the image below.
Fig. 20. Lymphedema in a patient with hypertension, diabetes, and impaired cardiac function
– Recurrent episodes of cellulitis or streptococcal lymphangitis have been linked to the development of lymphedema.
Laboratory Studies
Analysis of blood, urine, or tissue is not needed to make the diagnosis of lymphedema. Such tests, however, help to define the underlying causes of lower extremity edema when the etiology is unclear.
– Liver function, BUN/creatinine levels, and urinalysis results should be checked if a renal or hepatic etiology is suspected.
– Specific markers should be checked if a neoplasm is suspected.
– CBC count with differential should be checked if an infectious etiology is being considered.
Imaging Studies
Imaging is not necessary to make the diagnosis, but it can be used to confirm it, to assess the extent of involvement, and to determine therapeutic intervention.
– Lymphangiography is an invasive technique that can be used to evaluate the lymphatic system and its patency. Although it was once thought to be the first-line imaging modality for lymphedema, it is now rarely used because of the potential adverse effects.
– Lymphoscintigraphy is the new criterion standard to assess the lymphatic system. It allows for detailed visualization of the lymphatic channels with minimal risk. The anatomy and the obstructed areas of lymphatic flow can be assessed.
– Ultrasonography can be used to evaluate the lymphatic and venous systems. Volumetric and structural changes are identified within the lymphatic system. Venous abnormalities such as deep vein thrombosis can be excluded based on ultrasonography findings.
– MRI and CT scanning can also be used to evaluate lymphedema. These radiologic tests can be helpful in confirming the diagnosis and monitoring the effects of treatment. They are also recommended when malignancy is suspected.
Other Tests
A biopsy should be performed if the diagnosis is not clinically apparent, if areas of chronic lymphedema look suspicious, or if areas of chronic ulceration exist.
Histologic Findings
Histologic findings include hyperkeratosis with areas of parakeratosis, acanthosis, and diffuse dermal edema with dilated lymphatic spaces. In chronic lymphedema, marked fibrosis and scattered foci of inflammatory infiltrate can be seen.
Medical Care
The goal of therapy is to restore function, to reduce physical and psychologic suffering, and to prevent the development of infection.
- The first-line treatment is complex physical therapy. This therapy is aimed at improving lymphedema with manual lymphatic drainage, massage, and exercise. It advocates the use of compression stockings (at a minimum of
40 mm Hg), multilayer bandaging, or pneumatic pumps. Leg elevation is essential. Appropriate skin care and debridement is also stressed to prevent recurrent cellulitis or lymphangitis. - In secondary lymphedema, the underlying etiology (ie, neoplasm, infection) should also be properly treated to relieve the lymphatic obstruction and to improve lymphedema.
- In cases of recurrent cellulitis or lymphangitis, long-term antibiotic therapy with agents such as penicillins or cephalosporins is sometimes used.
- Filariasis has been treated with diethylcarbamazine and albendazole.
- In cases associated with obesity, weight loss is strongly recommended.
- A few pharmacological therapies have been found to be effective in the treatment of lymphedema.
- The benzopyrones (including coumarin and flavonoids) are a group of drugs that have been found to be successful in treating lymphedema when combined with complex physical therapy. They aid in decreasing excess edematous fluid, softening the limb, decreasing skin temperature, and decreasing the number of secondary infections. The benzopyrones successfully increase the number of macrophages, leading to proteolysis and protein reabsorption. Of note, however, is that hepatotoxicity has been associated with coumarin therapy.
- Case reports have suggested effective treatment of chronic lymphedematous changes (eg, elephantiasis nostra verrucosa [ENV]) with oral and topical retinoids. These therapies are thought to help normalize keratinization and decrease inflammatory and fibrotic changes.
- Topical emollients and keratolytics, such as ammonium lactate, urea, and salicylic acid, have been recommended to improve secondary epidermal changes.
- Diuretics are not effective in treating lymphedema.
Surgical treatment is palliative, not curative, and it does not obviate the need for continued medical therapy. Moreover, it is rarely indicated as the primary treatment modality. Rather, reserve surgical treatment for those who do not improve with conservative measures or in cases where the extremity is so large that it impairs daily activities and prevents successful conservative management.
Medication
Retinoids
These therapies are thought to help normalize keratinization and decrease inflammatory and fibrotic changes.
Acitretin (Soriatane)
Metabolite of etretinate and related to both retinoic acid and retinol (vitamin A). Mechanism of action unknown; however, thought to exert therapeutic effect by modulating keratinocyte differentiation, keratinocyte hyperproliferation, and tissue infiltration by inflammatory cells.
Tazarotene, topical (Tazorac)
Topical gel 0.1%. Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties. Ensure skin is dry before applying gel
Anthelmintics
Filaria can cause lymphedema by obstruction.
Albendazole (Albenza, Valbazen)
A benzimidazole carbamate drug that inhibits tubulin polymerization, resulting in degeneration of cytoplasmic microtubules. Decreases ATP production in worm, causing energy depletion, immobilization, and, finally, death. Converted in the liver to its primary metabolite, albendazole sulfoxide. Less than 1% of the primary metabolite excreted in urine. Plasma level is noted to rise significantly (as much as 5-fold) when ingested after high-fat meal. Experience with patients <6 y limited. To avoid inflammatory response in CNS, patient must also be started on anticonvulsants and high-dose glucocorticoids.
Emollients/keratolytics
Ammonium lactate lotion (AmLactin, AmLactin XL, Lac-Hydrin)
Alpha-hydroxy acid; normal constituent of tissues and blood. Believed to act as humectant when applied to skin. This may influence hydration of the stratum corneum. In addition, when applied to skin, may act to decrease corneocyte cohesion. The mechanism by which this is accomplished is not yet known. Used to decrease scaling and pruritus. Found in a variety of topical emollient lotions. Ammonium lactate 5% lotion is available over the counter, and lactic acid 12% cream and lotion are available by prescription.
Urea, topical (Carmol, Keralac, Ureacin)
Promotes hydration and removal of excess keratin in conditions of hyperkeratosis
Indications
Surgical treatment is palliative, not curative, and it does not obviate the need for continued medical therapy. Moreover, it is rarely indicated as the primary treatment modality. Rather, reserve surgical treatment for those who do not improve with conservative measures or in cases where the extremity is so large that it impairs daily activities and prevents successful conservative management.
Relevant Anatomy
Before embarking on the treatment of lymphedema, a thorough knowledge of the relevant anatomy is essential. Blind-ended lymphatic capillaries arise within the interstitial spaces of the dermal papillae. These unvalved superficial dermal lymphatics drain into interconnected subdermal channels, which parallel the superficial venous system. These subsequently drain into the deeper, epifascial system of valved trunks lined with smooth muscle cells and located just above the deep fascia of the extremity. This system is responsible for the drainage of lymph from the skin and subcutaneous tissues. Valves provide for unidirectional flow towards regional lymph nodes and eventually the venous circulation in the neck. Flow is achieved by variations of tissue pressure through skeletal muscle contractions, pulsatile blood flow, and contractions of the spiral smooth muscle fibers surrounding larger lymphatic channels.
A deeper valved subfascial system of lymphatics is responsible for the drainage of lymph from the fascia, muscles, joints, ligaments, periosteum, and bone. This subfascial system parallels the deep venous system of the extremity. The epifascial and subfascial systems normally function independently, although valved connections do exist in the popliteal, inguinal, antecubital, and axillary regions where lymph nodes form interconnected chains. These connections probably do not function under normal conditions; however, in lymphedema, some reversed flow through perforators from the epifascial to the subfascial system may occur as a mechanism of decompression of the epifascial system. In lymphedema, the derangement is almost always exclusive to the epifascial lymphatic system, with the subfascial system being uninvolved. This is the basis for the surgical approaches to lymphedema, which focus on the epifascial system.
Contraindications
Contraindications to intermittent pneumatic pump compression therapy include congestive heart failure, deep vein thrombosis, and active infection.
Surgical Therapy
Surgical treatment is palliative, not curative, and it does not obviate the need for continued medical therapy. Moreover, it is rarely indicated as the primary treatment modality. Rather, reserve surgical treatment for those who do not improve with conservative measures or in cases where the extremity is so large that it impairs daily activities and prevents successful conservative management. The goals of surgical therapy are volume reduction to improve function, facilitation of conservative therapy, and prevention of complications. A myriad of surgical procedures have been advocated, reflecting a lack of clear superiority of one procedure over the others. In general, surgical procedures are classified as physiologic or excisional.
Physiologic procedures attempt to improve lymphatic drainage. Multiple techniques have been described, including omental transposition, buried dermal flaps, enteromesenteric bridging, lymphangioplasty, and microvascular lympholymphatic or lymphovenous anastomoses.8 None of these techniques has clearly documented favorable long-term results. Further evaluation is necessary. Moreover, many of these physiologic techniques also include an excisional component, making it difficult to distinguish between the 2 approaches.
Excisional techniques remove the affected tissues, thus reducing the lymphedema load. Some authors advocate suction-assisted removal of subcutaneous tissues, but this technique is difficult because of the extensive subcutaneous fibrosis that is present. Additionally, this approach does not reduce the skin envelope, and the lymphedema often rapidly recurs. Suction-assisted removal of subcutaneous tissue followed by excision of the excess skin envelope has no clear advantage over direct excisional techniques alone.
The Charles procedure is another quite radical excisional technique. This procedure involves the total excision of all skin and subcutaneous tissue from the affected extremity. The underlying fascia is then grafted, using the skin that has been excised. This technique is extreme and is reserved for only the most severe cases. Complications include ulceration, hyperkeratosis, keloid formation, hyperpigmentation, weeping dermatitis, and severe cosmetic deformity.
Van der Walt et al developed a modified Charles procedure in which negative-pressure dressing was employed following debulking surgery, with skin grafting delayed for 5-7 days.9 In a report on 8 patients suffering from severe primary lymphedema who underwent the procedure, the authors reported that the patients experienced no major complications. Minor complications, including operative blood loss and, in 3 patients, the need for additional grafting, did occur.
Staged excision has become the option of choice for many authors. This procedure involves removing only a portion of skin and subcutaneous tissue, followed by primary closure. After approximately 3 months, the procedure is repeated on a different area of the extremity. This procedure is safe, reliable, and demonstrates the most consistent improvement with the lowest incidence of complications.
Preoperative Details
Prior to surgery, appropriate documentation is necessary to evaluate the outcome of treatment. This includes photographic documentation as well as extremity measurements. Ideally, these measurements are of limb volume by water displacement, although some rely on circumferential measurements alone. Obtain measurements and photographs at the same time of day each time, document affected extremities and contralateral extremities, and preferably conduct documentation in the morning after extremity elevation in bed overnight.
Institute strict elevation and pneumatic compression, if available, 24-72 hours prior to surgery. This allows maximum excision to be performed. The extremity must also be free of infection at the time of surgery, and a single dose of preoperative intravenous antibiotic is administered.
Intraoperative Details
After the establishment of appropriate anesthesia, the operative field is sterilized and draped according to surgeon preference.
A pneumatic tourniquet is placed at the root of the extremity and insufflated after the extremity has been exsanguinated.
A longitudinal incision is made along the entire extremity, and skin flaps, 1.0-
Subcutaneous tissue is then excised, taking care not to injure peripheral sensory nerves.
Some authors also excise a strip of deep fascia, but this should not be performed around joints because it may cause instability.
Once the subcutaneous excision is complete, redundant skin is resected. Often, a strip that is 5-
The wound is closed over suction drains.
Postoperative Details
Postoperatively, the extremity is immobilized in a splint and elevated while the patient is placed on strict bed rest.
Antibiotics may be continued until drain removal, according to surgeon preference.
Drains are typically removed at 5-7 days postoperatively, as dictated by a decrease in drain output.
Sutures are removed at 10-14 days and replaced by Steri-Strips.
Measure the patient for a new compression garment when the new dimensions of the extremity have stabilized.
After approximately 10 days, the patient may gradually begin dependency on the extremity with compression bandages or an elastic garment in place.
Follow-up
Once discharged from the hospital, the patient should be seen regularly in the outpatient clinic.
Patients must wear compression garments for 4-6 weeks continuously, and dependency on the involved extremity may be gradually increased at the discretion of the treating physician.
Once healed to physician satisfaction, the patient may return to a normal routine of elevation at night and compression garment therapy during the day.
Follow-up visits should include documentation of circumferential measurement or water displacement of the affected and contralateral extremities as well as photographic documentation.
When staging procedures, allow approximately 3 months between procedures to allow complete healing of the initial operative site.
Complications
Patients with chronic lymphedema for 10 years have a 10% risk of developing lymphangiosarcoma, the most dreaded complication of this disease. Patients with this tumor commonly present with a reddish purple discoloration or nodule that tends to form satellite lesions. It may be confused with Kaposi sarcoma or traumatic ecchymosis. This tumor is highly aggressive, requires radical amputation of the involved extremity, and has a very poor prognosis. The 5-year survival rate is less than 10%, and the average survival following diagnosis is 19 months. This malignant degeneration is most commonly observed in patients with postmastectomy lymphedema (Stewart-Treves syndrome), where incidence is estimated to be 0.5%.
Other complications of lymphedema include recurrent bouts of cellulitis and/or lymphangitis, deep venous thrombosis, severe functional impairment, cosmetic embarrassment, and necessary amputation. Complications following surgery are common and include partial wound separation, seroma, hematoma, skin necrosis, and exacerbation of foot or hand edema.
Outcome and Prognosis
At present, no cure for lymphedema exists. Surgery is palliative at best, and it may be a part of the lifelong therapy patients must endure to manage this disease.
Future and Controversies
A myriad of surgical procedures have been advocated, reflecting a lack of clear superiority of one procedure over the others. Multiple physiological and excisional techniques have been described. None of the physiological techniques has clearly documented favorable long-term results; further evaluation is necessary. Moreover, many of the physiologic techniques also include an excisional component, making it difficult to distinguish between the 2 approaches.
