Guðmundur Daníelsson and Bo Eklöf

A 59-year-old female secretary was referred for evaluation and treatment of a nonhealing painful ulcer on the medial aspect of her right lower leg. The ulcer had been recurrent almost every year for the past 9 years, often healing during the winter season. She had since early childhood been overweight (currently 87 kg, 170 cm, body mass index 30) and had difficulty in using compression stocking. She was otherwise healthy. She had two children, the first child born when she was 32 year of age and her second child 2years later. After the birth ofher secondchild she began tonotice varicoseveins onthelowerlegonbothsidesandsheoftenfelttirednessandheavinessintheleginthe afternoon. There was no history of deep venous thrombosis. She had been on birth controlpillsfor10yearsandwascurrentlyonhormonereplacementtherapybecauseof severepostmenopausalsymptoms.Shehadbeentreatedatalocaldermatologicalclinic for the past 2 years and was now being evaluated by a vascular surgeon. Clinical evaluation showed that she had 5 × 5 cm well-granulated ulceration above the right median malleolus which was surrounded by brownish leathery skin. She had slight swelling of the right leg with large varicosities below the knee. The left leg had large varicosities below the knee but no swelling or skin changes. Doppler examination revealed clear reflux in the groin that could be followed over both great saphenous veins (GSV) down the thigh. A possible minimal reflux was also noted in the popliteal fossa on the right side, although it was difficult to confirm this when the Doppler examination was repeated. Foot arteries were palpable on the dorsum of the foot on both sides.

Question 1

What should be the next step in this patient evaluation?

A.  Measurement of ankle-brachial index.

B.  Duplex ultrasound scanning of the venous system.

C.  Plethysmography.

G. Daníelsson ( )

Department of Vascular Surgery, The National University Hospital of Iceland, Fossvogi, 108 Reykjavík, Iceland

D.  Ascending phlebography. E.  Biopsy of the ulcer.

Doppler measurement revealed a normal ankle/brachial index with systolic blood pressure 130 in both legs and right arm. Duplex ultrasound scanning of the venous system performed with the patient in 60° reversed-Trendelenburg position, using pneumatic cuff with automatic inflation/release on the lower leg to evaluate the reflux, showed bilateral reflux in the GSV, from the common femoral vein down to below knee, as well as two incompetent perforator veins on the medial aspect of the right calf with a diameter of 4 mm. The diameter of the GSV at the groin was 12 mm on the right side and 9 mm on the left side. The reflux time exceeded 4 s in both GSV, with peak reverse flow velocity more than 30 cm/s. Reflux less than 0.5 s was noted in the lesser saphenous vein on right side. No reflux was present in the deep veins except for minimal reflux in the common femoral vein with reflux duration of approximately 1 s on the right side. There were no signs of post-throm- botic changes.

Question 2

How should this patient be classified?

A.  Leg ulcer B.  Varicose ulcer

C.  C 6, S, Ep, As, p, d, Pr

D.  C2, 3, 4b, 5, 6, S, Ep, As, p, d, Pr2, 3, 11, 18

The patient was classified according to the CEAP (clinical, (a)etiological, anatomical, pathophysiological) classification based on history and results of duplex ultrasound.

Question 3

Which of the following is not regarded as a risk factor for venous ulcer?

A.  Diabetes

B.  Essential hypertension C.  Smoking

D.  Overweight

E.  Resistance to activated protein C

Question 4

What would be appropriate management for the right leg in this patient?

A.  Conservative treatment with below-knee compression bandage, rest and leg elevation B.  High ligation and stripping of GSV to below knee, with local extirpation of varicose veins C.  High ligation of GSV with extirpation of varicose veins

GSV it is worthwhile to continue with duplex ultrasound scanning as deep venous incompetence and post-thrombotic changes can otherwise be overlooked. This is especially important when reflux is noted at the back of the knee where it is difficult with certainty to differentiate between deep venous reflux in the popliteal vein and reflux in the lesser saphenous vein. Although the history (no claudication or rest pain, no diabetes) and the location of the ulcer (medial aspect of lower leg) strongly suggest a venous ulcer, sometimes an arterial component is also present that might reduce the ability of the ulcer to heal. Palpable pulse on the dorsum of the foot (dorsalis pedis) or behind the medial malleolus (posterior tibial artery), as was evident in this case, almost rules out an arterial component. Although plethysmography can estimate the overall venous function it is not mandatory as a first line of investigation. Obtaining an ascending phlebography is also not necessary as it does not add any information that duplex ultrasound scanning does not provide and it is also an invasive method with the risk of complications. Non-healing ulcer with unusual appearance should be considered for other etiology and investigated with biopsy in the early stage of evaluation. [Q1: A, B]

The old concept that the majority of venous ulcers are due to previous deep venous thrombosis1,2 hasbeenalteredduringthelast20yearswhenduplexultrasoundstudieshave shown the importance of primary reflux in all venous segments.3–7 Superficial venous incompetence is often noted to be the sole pathology in patients presenting with nonhealing venous ulcer.8 Formerly the venous ulcer was often judged as being related to a post-thrombotic condition without any objective diagnosis. Because of the benign course of varicose veins in the majority of patients with superficial venous incompetence, the need for thorough evaluation is often neglected. Formerly used classifications of chronic venous disease used the term varicose ulcer if varicose veins were present, or post-throm- botic ulcer if they were less evident or if there was a previous history of deep venous thrombosis. The importance of classification, based on findings from duplex ultrasound scanning, has become more evident during the last decades as treatment and prognosis is largely dependent on the background history and the results of clinical investigation. CEAP (clinical, (a)etiological, anatomical, pathophysiological) classification has gained more acceptance as the “gold standard” for classifying all aspects of venous pathology such as clinical class, etiological background, anatomical distribution and pathophysiological findings (Table 50.1). There is a clear correlation between the CEAP clinical class and the venous function as measured by plethysmography (foot volumetry), indicating that the clinical classification has a realistic meaning concerning the functional evaluation of venous disease. The duration of reflux in venous segments, on the other hand, does not correlate with clinical class, but the peak reverse flow velocity is significantly higher in patients with skin changes/ulcer (C4–C6).9 The basic part of CEAP indicates the highest clinical class (C6, active venous ulcer) and the anatomical distribution in superficial, perforator or deep system (As, p, d) with reflux (Pr). S is added behind clinical class to indicate that the patient is symptomatic. The basic classification is sufficient for most clinical doctors. [Q2: C, D] The detailed version of CEAP is used when more information is needed as in longitudinal studies comparing treatment alternatives (Table 50.2). For more detailed information regarding the disease and its effect on daily life it is possible to use a venous severity scoring system.11 Venous severity scoring is used as a complement to the

Table 50.1  CEAP classification

Clinical classification

C0: no visible or palpable signs of venous disease C1: telangiectases 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

Etiological classification

Ec: Congenital

Ep: Primary

Es: Secondary (post-thrombotic) En: No venous etiology identified

Anatomic classification

As: Superficial veins Ap: Perforator veins Ad: Deep veins

An: No venous location identified

Pathophysiological classification

Pr: Reflux Po: Obstruction

Pr,o: Reflux and obstruction

Pn: No venous pathophysiology identifiable

CEAP classification (Fig. 50.1). Some medical conditions are clearly a risk factor for venous ulcer while others are less important. Venous ulcers are overrepresented in patients with diabetes although it is not clear if it is the venous pathology or if it is the diabetic microangiopathy that is the reason for this. Neither essential hypertension nor smoking is a proven risk factor for venous ulcer. The prevalence of varicose veins is increased in overweight individuals but the role of obesity is less clear when it comes to the risk of developing skin changes or ulcer. The apparent association between overweight and varicose veins in women suggests that it is a risk factor even in the more severe form of chronic venous disease.12–14 In a consecutive series of 272 patients with chronic venous disease investigated with duplex ultrasound scanning, 58% of patients with healed or open ulcer (C5–C6) had body mass index >30 kg/m2 (obese) as compared to 15% of those with varicose veins but without skin changes or ulcer.15 [Q3: A, B, C] Most thrombophilic conditions are risk factors for deep venous thrombosis and venous ulceration, as is resistance to activated protein C.16 The prevalence of thrombophilia is high in patients with

524 G. Danielsson and B. Eklöf

Table 50.2  Advanced CEAP

Same as basic CEAP with the addition that any of 18 named venous segments can be utilized as locators for venous pathology.

Superficial veins:

 1. Telangiectases/reticular veins

 2. Great saphenous vein above knee

 3. Great saphenous vein below knee

 4. Small saphenous vein

 5. Non-saphenous 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

17.Perforating veins, thigh

18.Perforating veins, calf

venous ulceration despite no history or duplex ultrasound findings of deep venous thrombosis.17

Surgical treatment is mandatory in cases of isolated superficial incompetence as the likelihood of ulcer recurrence otherwise will remain high. Conservative treatment alone with below-knee compression had not been successful in keeping the ulcer healed, but it is important to continue with compression therapy while the ulcer is open and for some time after operation. Four-layer bandage is effective in healing venous ulcer.18 High ligation with stripping of the GSV down to below the knee, with local extirpation of varicose veins, is the method of choice. It decreases the risk of ulcer recurrence and has a low incidence of nerve damage to the saphenous nerve. Stripping of the vein from the groin to the ankle increases the risk of damage to the saphenous nerve (5% versus 29%), although the recurrence rate is still the same.19 Just doing high ligation without stripping the vein is less feasible as the recurrence rate is significantly higher.20 Other promising methods for ablation of the refluxing GSV have emerged recently and might become the methods of choice in the future. As the diameter of the GSV was less than 15 mm it was possible to use the radiofrequency closure method to obliterate the vein. The main advantage of using less invasive methods is increased patient satisfaction, as the recovery time after operation has been reported to be shorter. Follow-up time up to 5 years with the radiofrequency method indicates that the method is durable. The long-term results after ablation of GSV using laser technique or foam sclerotherapy are still unknown. [Q4: B, D]

Fig. 50.1  Venous severity scoring is used as a complement to the CEAP classification

The varicose veins on the lower leg are dealt with by using multiple stab incisions and bringing them out using hooks. The cosmetic results are better and the risk of nerve damage is less. Care should be taken not to operate close to the ulcer area as healing problems and infection are more common if the incisions are made in damaged skin.

Even though the role of surgery in venous ulcer disease has been unclear,21 a recently reported randomized controlled study comparing surgery with compression therapy, to compression therapy alone, could clearly show a significantly lower recurrence rate in the surgically treated group.22 Altogether 500 patients with open or recently healed ulcer (6 months) were included in the study. The healing rate was similar during the study period, but 12-month ulcer recurrence rates were significantly reduced in the surgically treated group or 12%, compared to the compression-only group where the ulcer recurrence rate was 28%.

The pathophysiology behind venous ulcer is mainly reflux as opposed to obstruction or occlusion. In a study on a consecutive series of 98 legs with an open venous ulcer, 85% of the extremities had some form of superficial venous incompetence that might be treated with a simple operation on the superficial venous system. Axial reflux in the superficial (great saphenous vein) or the deep veins (femoral down to popliteal level) was present in 79% of the legs.23 Incompetent perforator veins and their role in chronic venous disease have been debated for years.24 Incompetent perforator veins have been implicated as an important factor in the formation and recurrence of venous ulcers. This view is mainly based on clinical reports of excellent ulcer healing following the interruption of incompetent perforators. There is substantial evidence that subfascial endoscopic perforator surgery (SEPS) is effective in interrupting perforator veins, and it can be done without major wound complications that were often seen after the open subfascial Linton procedure.25–28 Also, the ulcer healing rate after venous procedures that included SEPS has been satisfying.25,26 Patients undergoing surgery for incompetent perforator veins almost always have surgery simultaneously on the superficial venous system and therefore it is difficult to judge the actual contribution of the incompetent perforator to the venous dysfunction. There is also evidence that reflux-eliminating surgery on one part of the venous system can abolish reflux in another part.29–31 Operations on superficial veins have been shown to eliminate concomitant reflux in perforators.32 Disregarding the incompetent perforator veins in patients with superficial venous incompetence seems therefore to be appropriate. The low incidence of isolated perforator incompetence in patients with active venous ulcer does indicate that they are less important than previously thought.8 The main indication (although not proven yet) for treating them is in patients with primary venous incompetence with recurrent ulceration despite optimal treatment of the superficial venous incompetence. The method of choice for treatment is then SEPS, mainly because of the low risk of wound complication. The use of sclerotherapy for the purpose of obliterating perforators is still under evaluation although the technique seems to be promising. [Q5: A, C]

The indication for treating varicose veins in legs without skin changes or ulcer is less clear. The decision of recommending treatment for asymptomatic legs with varicose veins has to be judged individually; often it is the patient´s preference that will decide. The cosmetic results of sclerotherapy on local varicose veins are poor if the refluxing GSV is left in place. The risk of future problems with skin changes or ulcer is increased when axial reflux is present in the GSV, as was the case with this patient, and that might be a sufficient reason to recommend even surgery for the asymptomatic left leg. A simultaneous operation on both legs in an otherwise healthy person does not seem to add any risk to the