Location of venous reflux in primary chronic venous disease and correlation with clinical severity: a review



by N. Labropoulos, USA

Nicos LABROPOULOS,
MD, PhD
Professor of Surgery and
Radiology
Director, Vascular Laboratory
Department of Surgery
Stony Brook University Medical
Center, Stony Brook
New York, USA

In the last 20 years, a number of articles have reported a correlation between venous reflux location and clinical severity in patients with chronic venous disease (CVD). Work from epidemiological, cross-sectional, and prospective cohort studies has identified important issues regarding this association. Overall, there is a connection between reflux location and severity of CVD, but the strength of this association has not been determined, as many other factors play an important role. Some pertinent factors include amount of reflux, efficiency of the calf-muscle pump, duration of CVD, lifestyle, obesity, physical activity, and biological responses of tissues in the affected areas. Furthermore, there is no clear distinction between symptoms arising from CVD and those arising from other causes that may coexist with or be separate from CVD. The nature of what the patient feels has not been studied in depth, because of the complexity of a patient’s neuropsychological reflections on limb symptoms and venous function. Reflecting the complexity of the correlation between CVD severity and reflux location, owing to factors such as those mentioned above, are the following examples: a patient with CVD class 1 who has local pain and tingling over the reticular veins, and a patient with CVD class 2 who is asymptomatic and has great saphenous vein (GSV) reflux from groin to ankle. Today, research on this important issue should focus more on deriving more precise correlations, taking into account contributing factors.

Medicographia. 2016;38:148-154 (see French abstract on page 154)

Chronic venous disease (CVD) is prevalent in adults and has a significant socioeconomic impact.1-4 There is a strong genetic predisposition and several risk factors associated with its development.5-8 The clinical presentation varies as patients with CVD may have no complaints or they may seek treatment for signs or symptoms, or both. Signs and symptoms develop from the increased ambulatory venous pressure, which is a result of obstruction reflux, or they develop from a combination of the two.9 Reflux in the lower extremity veins is the most common pathology in patients with CVD.10-13 The saphenous veins and their tributaries have the highest prevalence of reflux.14-16 The relationship between reflux location and clinical severity has been investigated in several studies. The results have been variable as there are many other factors that influence the severity of the disease, as shown in Table I. For example, let us examine three examples of patients with great saphenous vein (GSV) reflux from the saphenofemoral junction (SFJ) to upper calf, with the reflux extending through an upper calf medial tributary to the medial malleolus. In the first example with this pattern of reflux, let’s consider a 52-year-old female patient, for whom the disease has been apparent for 7 years without any other comorbidity. She presented with some feelings of heaviness and mild aches that are mostly felt at the end of the day. In the second example, the patient has the same age, sex, and duration of disease, but she has a fixed ankle joint. She presented with aches, a burning sensation, and skin damage (CEAP [Clinical-Etiology-Anatomy-Pathophysiology] clinical class C4b). In the third example, the patient has the same characteristics as the first patient, but the disease has been present for over 20 years. She has a small ulcer in the medial malleolus and extensive skin discoloration. As seen from these examples, reflux by itself often is not the only determinant for the development of CVD signs and symptoms. Furthermore, there are other factors that influence the duration and velocity of reflux, as seen in Table II. In the above patient examples, the first patient had a reflux duration varying from 2.2 seconds to 3.8 seconds with a GSV diameter ranging from 3.8 mm to 7.9 mm. The second patient had a similar reflux range, but the GSV diameter ranged from 4.3 mm to 9.2 mm. The third patient had a reflux duration from 3.4 seconds to >8 seconds and a GSV diameter ranging from 4.8 mm to 13.5 mm. Unfortunately, in published papers, although some of these variables are mentioned, data are not provided, and the comparison among patients is clearly unequal and inappropriate. Even more fascinating is the fact that patients with class C1 disease may have more symptoms or symptoms of higher intensity than those with class C2 or more advanced CVD. The reason for this is unknown. This article focuses on patients with primary CVD; thus, patients with previous thrombosis, malformations, and venous obstruction have been excluded from the analysis.

Table I. Factors contributing to the clinical severity of chronic
venous disease.

Superficial veins

Reflux in the superficial veins is the most common pathology in patients with primary CVD. It is most often found in the saphenous veins, but reflux in nonsaphenous veins can be found in about 10% of CVD patients.

Table II. Factors affecting duration and velocity of reflux.

Saphenous veins
The vast majority of patients with CVD have reflux in the superficial veins, with the saphenous veins and their tributaries having the highest prevalence.13-16 This statement is true for all CEAP clinical classes from 2 to 6. Variable patterns of reflux have been described in the GSV and small saphenous vein (SSV). The location and extent of reflux in the saphenous veins has been associated with severity of CVD. This was first shown in 1994.14 Usually, segmental saphenous reflux is asymptomatic or is associated with mild symptoms. In most symptomatic patients, the saphenous reflux extends below the knee. Many studies, including those having patients with skin damage, have stressed the importance of distal vein reflux. This has been shown for both GSV and SSV. In fact, reflux in both veins together or separately can be responsible for venous ulceration.10,17-20 The hemodynamic importance of reflux is higher when the SFJ is involved.21 However, this is true when both the saphenous trunk and the SFJ are involved, as there are many patients with SFJ reflux where the saphenous trunk is competent.22

In order to better illustrate this subject, Figures 1 and 2 (page 150) and Figure 3 (page 151) show images based on patients from our center. We chose patients with bilateral lower extremity varicose veins in order to compare the extent of disease with the signs and symptoms of the patients. Figure 1 depicts a female patient with bilateral GSV reflux. Only the left limb is symptomatic. This is probably because the left limb has larger refluxing veins and somewhat more extensive reflux, which is also significantly more prolonged. Furthermore, the disease duration is twice as long in the left limb. The patient started developing symptoms 4 years ago, which is 11 years after the first varicose veins appeared in her calf. Figure 2 illustrates a male patient with varicose veins in both lower extremities. He has a leg ulcer in the right limb and no symptoms in the left. The right limb has longer disease duration, larger veins, and far more prolonged and extensive reflux. Both patients make a good case for the proposed association, with regard to extent of reflux and vein characteristics, as well as the CVD duration. However, this is not the case in the third patient. Figure 3 demonstrates a female patient with larger veins, more reflux, and longer CVD duration in the right limb than in the left. However, it is the left limb that is more symptomatic. In this case, this finding is most likely due to restricted mobility of the left limb that has resulted in an inefficient muscle pump; her right lower limb is used more to work around the house and support herself.

Figure 1. Female patient, aged 49 years, presenting with varicose
veins in both limbs.
The right limb is asymptomatic. She reports heaviness, a burning sensation,
and itching in the left limb. The symptoms are worse at the end of the day. She
had two normal pregnancies and has a body mass index of 27. Her mother had
varicose veins. She has no other significant medical and surgical history. The
duration of disease is about 15 years in the left limb and about 7 years in the
right. This was recognized by the appearance of varicose veins in each limb.
The varicosities in the left calf became apparent about 3 years after the second
child was born. They continue to extend toward the thigh and over the years
have become larger. She started developing noticeable symptoms 4 years ago,
and these have become worse. The reflux duration in the left limb ranges from
2.2 seconds to >5 seconds; in the right limb, it ranges from 1.4 seconds to 3.7
seconds. The diameter of the great saphenous vein (GSV) and varicosities are
larger in the left limb.
Abbreviations: Based on CEAP classification of chronic venous disease: AS,
anatomy classification (superficial veins); C2A, clinical classification (large varicose
veins, asymptomatic); C2S, clinical classification (large varicose veins, symptomatic);
EP, etiology classification (primary); PR, pathophysiology classification
(reflux).

Figure 2. Male patient, aged 58 years, presenting with a right leg
ulcer, aching on standing, edema, and skin damage extending
from the medial malleolus to mid-calf.
The left limb has varicose veins and is asymptomatic. He has had varicose veins
in the right limb for over 25 years. The veins have been large for a long time,
but he started developing skin discoloration about 7 years ago, and the ulcer
began developing in the last 2 months. The ulcer measures 2.2 cm x 1.8 cm.
He has thus far undergone no procedure for venous disease. He had an uneventful
appendectomy and tonsillectomy. His body mass index is 31, and he
is on two medications for hypertension, which is under control. His mother and
his sister had varicose veins. The duplex ultrasound exam showed reflux in the
small saphenous vein (SSV) and its thigh extension, in a short great saphenous
vein (GSV) segment at the knee, and in calf tributaries draining into the ulcer
area. The reflux duration ranges from 2.8 seconds to >10 seconds.
Abbreviations: Based on CEAP classification of chronic venous disease: AS,
anatomy classification (superficial veins); AS+P, anatomy classification (superficial +
perforating veins); C1-6S, clinical classification (small and large varicose veins;
edema; skin changes without ulceration, with healed ulceration, and with active
ulceration; symptomatic); C2A, clinical classification (large varicose veins, asymptomatic);
EP, etiology classification (primary); PR, pathophysiology classification (reflux).

In patients with saphenous vein incompetence, the presence and severity of CVD symptoms appear to correlate with the location and extent of reflux. However, this is not always the case, and more importantly, the strength of this association is undetermined.

Nonsaphenous veins
Reflux in nonsaphenous veins is found in about 10% of CVD patients, and this prevalence increases to 20% in patients who present with recurrent varicose veins.23-26 Most of these patients are females with two or more pregnancies. CVD signs and symptoms of class C1 to class C3 disease are found in about 90% of these patients, but 10% present with skin damage. Common locations of reflux in these veins are the perineum, vulva, inner thigh, buttock, posterolateral thigh, lower posterior thigh, popliteal fossa, knee, and lateral to posterior calf. Reflux can be found in these veins only or in combination with the saphenous and the pelvic veins. There is high association with reflux in the pelvic veins. The extent and location of nonsaphenous vein reflux is associated with the presence and severity of symptoms. However, such reflux is underdiagnosed and, therefore, underreported. Two clinical cases with nonsaphenous vein reflux from our center are depicted in Figure 4 and Figure 5 (page 152). The first patient, in Figure 4, is a 37-year-old female with four children. She has right lower limb pain and a sense of heaviness in the vulvar area and along the varicose veins that extend from her pelvis to the medial malleolus. At the end of the day, she feels a burning sensation, and the pain and heaviness are worse. In the left limb that was asymptomatic, she has small varicosities and reticular veins in the lateral and posterolateral thigh. The saphenous veins are normal in both extremities. In this case, the symptoms have a good association with the location and extent of venous reflux. The second patient, in Figure 5, has varicose veins in both limbs, without symptoms. The right limb has reflux in the accessory saphenous vein and in a thigh tributary. The left limb has reflux in the vein of the popliteal fossa and no saphenous reflux. Many patients with varicose veins may have no symptoms. This patient came to our clinic seeking treatment for cosmesis.

Figure 3. Female patient, aged 61 years, with bilateral varicose veins.
She has three children, and her mother had varicose veins. She has some aching
and itching in the right limb, whereas she has more pain, swelling, heaviness,
and some skin discoloration in the left limb. She has undergone no procedures
for the veins and no other procedures. She takes aspirin and medication for
hyperlipidemia. Her body mass index is 26.4, and she has no other complaints.
Duplex ultrasound demonstrated great saphenous vein (GSV) reflux in the right
limb from the saphenofemoral junction (SFJ) to the calf and in a few of its tributaries.
The duration of disease is >20 years; the vein diameters range from 3.2
mm to 8.4 mm, and the reflux duration range is from 2.2 seconds to 4.7 seconds.
The left limb has segmental GSV reflux, and one tributary is incompetent. The
disease duration in this limb is about 10 years. The vein diameters range from
2.3 mm to 4.9 mm, and the reflux duration range is from 1.3 seconds to 2.7
seconds. She has restricted mobility in the left limb due to degenerative knee
disease.
Abbreviations: Based on CEAP classification of chronic venous disease: As,
anatomy classification (superficial veins); C1-2s, clinical classification (small and
large varicose veins, symptomatic); C1-4S, clinical classification (small and large
varicose veins, edema, skin changes without ulceration; symptomatic); EP, etiology
classification (primary); PR, pathophysiology (reflux).

Perforator veins

The role of reflux in the perforator veins is not clear. The number of incompetent perforator veins and their diameter is higher in patients with skin damage. Patients with ulceration have often been associated with having perforator veins in the ulcer area, but never in isolation.10,17,18 It has also been shown that in patients with primary venous disease, the perforator veins develop reflux through the connections with incompetent superficial veins.27 It is possible that perforator veins may worsen the local hemodynamics and may contribute to the development of symptoms. Some evidence exists for their impact on healing of the ulcer after being treated.28 However, this information comes from poorly designed retrospective studies, and it is far from robust.28 Further work is needed to elucidate the role of perforator veins in development of CVD signs and symptoms.

Deep veins

The deep veins are most often involved in the development of CVD signs and symptoms in post-thrombotic limbs. Primary reflux in deep veins alone is rare. Segmental reflux has been found in deep veins in the presence of saphenous reflux involving the junctions. Such deep venous reflux is correct- ed after the treatment of the superficial veins.29-31 In a recent Cochrane review, four studies performed deep vein reconstruction to alleviate CVD signs and symptoms; however, in all four interventions, superficial veins were done as well.32 Therefore, as these patients also had superficial vein disease, the symptoms cannot be attributed to deep vein reflux alone. Absence of venous valves, known as avalvulia, is an autosomal- dominant anomaly that leads to severe venous reflux. Patients with this condition develop severe orthostatic edema in the lower extremities and present with large varicose veins and skin damage.33 In a review paper on deep vein anomalies, only four reports were found, and each had few cases.34 In the last 25 years, I have examined two such patients— one 12-year-old female and one 17-year-old male. Both presented with pitting edema, significant pain on prolonged standing, and ulceration. This is a very rare anomaly, and the extent of the disease correlates with the severity of the presentation.

Figure 4. Female patient, aged 37 years, with bilateral varicose veins.
She has four children and had uncomplicated pregnancies. Both her parents
had varicose veins. She has no medical issues and has had no previous surgery.
She has symptoms in the right limb only, which become worse at the end
of the day. She feels pain and heaviness in the vulvar area and along the varicose
veins. She has a cluster of varicosities in the vulvar area that extend to the
medial malleolus by wrapping around the limb. The veins appeared 8 years ago
after the second pregnancy and over time became larger. She started developing
symptoms after the third pregnancy 5 years ago. The vein diameters range
from 3.1 mm to 6.3 mm, and the reflux duration ranges from 2.3 seconds to
>10 seconds. In the left limb, she has reticular and small varicose veins that
bother her for esthetic reasons. The diameters range from 1.7 mm to 3.4 mm,
and the reflux duration ranges from 0.9 seconds to 2.2 seconds.
Abbreviations: Based on CEAP classification of chronic venous disease: As,
anatomy classification (superficial veins); C1A, clinical classification (small varicose
veins, asymptomatic); C1-3s, clinical classification (small and large varicose
veins, edema; symptomatic); EP, etiology classification (primary); PR, pathophysiology
(reflux).

Figure 5. Female patient, aged 42 years, with bilateral asymptomatic
varicose veins.
She has one child and no other medical or surgical history. No one in her family
had varicose veins. She came to our center to have the veins treated for cosmetic
reasons. The right limb had reflux in the anterior accessory saphenous
vein and a tributary. In the left limb, reflux was found in the vein of the popliteal
fossa, extending down the calf without involvement of the saphenous veins.
The veins in both limbs are from 1.4 seconds to 3.2 seconds.
Abbreviations: Based on CEAP classification of chronic venous disease: AS,
anatomy classification (superficial veins); C1-2A, clinical classification (small and
large varicose veins; asymptomatic); EP, etiology classification (primary); PR,
pathophysiology (reflux).

Combined patterns of reflux

Patients with complex patterns of reflux are more likely to be symptomatic. Reflux in superficial, perforator, and deep veins is reported to be more common in patients with skin damage.11,13,15,35-40 These studies reported the combined patterns of reflux by including post-thrombotic limbs, so the effect of primary venous reflux is not clear. The addition of deep vein reflux in the absence of previous thrombosis needs to be studied separately. Furthermore, as stated above, deep vein reflux in the absence of previous thrombosis is not as prolonged as in patients that have had a previous thrombosis. The presence of such deep vein reflux may reflect a more advanced superficial vein disease and should be evaluated in future prospective studies. Figure 6 demonstrates bilateral varicose veins and swelling. Both limbs look similar and have an almost identical pattern of reflux, with >15 years of CVD duration. The common femoral veins have reflux at the SFJ in both limbs and the GSV from this level to the upper calf, with varicosities extending to the lower calf. A dilated and incompetent perforator vein has reflux at the medial mid-calf in both legs. Which limb is worse? Do both feel the same? The patient has aches and a sense of heaviness in both limbs, but it is worse in the right limb. No obstruction was found in the iliac veins and inferior vena cava. The patient has no other medical problems. So, what determines the difference in symptom intensity? Even more interesting is what we see in the next patient, in Figure 7. This patient has skin damage and more extensive GSV reflux from the SFJ to the ankle. He has two perforator veins at the mid- and lower calf that are incompetent. The veins are larger in diameter and duration of reflux is longer than that in the previous patient, and CVD has been present for more than 20 years. So, the clinical class of this patient’s disease correlates better with the extent of reflux than in the patient shown in Figure 6; however, this patient is asymptomatic.

Figure 6. Which limb is worse? Female patient with symptomatic
bilateral varicose veins with similar reflux distribution, vein diameters,
and reflux and chronic venous disease duration.

Figure 7. Male patient with
extensive great saphenous
vein (GSV) reflux from the
saphenofemoral junction
(SFJ) to the ankle with multiple
tributaries and two incompetent
perforator veins
in the calf. He has segmental
common femoral vein
(CFV) reflux from the SFJ
and segmental posterior
tibial vein (PTV) reflux from
the perforator veins. No
proximal obstruction was
found. Despite the extent
of reflux and the extensive
skin damage, he remains
asymptomatic.

Patients with deep vein reflux in ovarian and pelvic veins may present with abdominal and pelvic symptoms and often with symptoms in the lower extremities. Pelvic reflux is often seen to extend to the lower extremities, with a variable presentation ranging from asymptomatic to limb ulceration. Although studies have been published indicating these patterns of reflux, there are no data on clinical correlation in the lower limbs. One study on patients with nonsaphenous vein reflux indicated that about 10% had skin damage, but even in that study a correlation with pelvic reflux was not investigated.23

Current insights

In most patients, the distribution and extent of primary reflux correlates with the presence and intensity of the symptoms. Overall, the strength of this correlation has not been determined. Significant insights have come from the Bonn Vein study, both on such correlation and on CVD progression. It is worth mentioning the neuropsychological reflections that may associate limb symptoms with venous reflux, as recently reported.41 This matter is far too complex for our current understanding and deserves in-depth research.

The factors affecting CVD clinical presentation, shown in Tables I and II, further indicate the complexity of such correlations. Several other issues contributing to the complexity have been raised, such as lifestyle and the difficulty in separating other types of symptoms, eg, musculoskeletal or neurological symptoms, from those arising from CVD.42,43 It is naive to associate venous reflux location alone with the severity of CVD without taking into account all other factors discussed. Clearly, more work is needed in multiple directions in order to better understand the relationship between symptom presence and intensity in patients with CVD.

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Keywords: CEAP classification; chronic venous disease; clinical severity; venous reflux