Venous Stasis Leg Ulcers: A Review

Chronic venous stasis ulcers (CVSU) of the lower extremity affect up to 5% of the population over 65 years and 1.5% of the general population. CVSU is caused by chronic venous disease produced by venous hypertension. Venous hypertension results from valvular incompetence within the deep venous system, or by the obstruction of venous outflow. Both of these mechanisms produce poor venous return. Additionally, poor mobility and decreased calf muscle pump function are thought to be contributing factors. Life-long use of compressive therapy is indicated in patients with chronic venous disease in lower extremities. It reduces ambulatory venous pressure. These include bandaging systems, garments (stockings), or devices. Keywods: venous stasis leg ulcers, Up to date, review Úlceras venosas en extremidades inferiores por estasis venoso. Revisión

in up to half of patients and the lack of evidence-based treatment results in CVSU representing a significant public health challenge. (3)

Pathophysiology Venous Hypertension
CVSU is caused by chronic venous disease produced by venous hypertension. Venous hypertension results from valvular incompetence within the deep venous system, or by the obstruction of venous outflow. Both of these mechanisms produce poor venous return.(4) Additionally, poor mobility and decreased calf muscle pump function are thought to be contributing factors. (5) Venous hypertension from the deep venous system is transferred to the superficial venous system ( fig. 1) through perforating veins, causing a chronic inflammatory process that is not well understood. White blood cells are trapped in capillaries or post-capillary venules. These white cells are then activated, releasing inflammatory mediators that result in tissue injury, inadequate healing, and, finally, necrosis. This "fibrin cuff theory" suggests that the fibrin deposited around these capillaries results in skin hypoxia.(6)   Symptoms tend to be worse at the end of the day, and can improve with leg elevation.

Ulcer Characteristics
Ulcer location is variable, but are commonly found in the "gaiter" area, particularly the medial aspect, where perforating veins from the superficial system connect to the deep system and venous pressure might be highest. ( fig. 5) Trauma may be associated with the development of the venous ulcer. At the time of presentation, the ulcer may be secondarily infected, with increased pain, exudate and malodorous.

Figure 5. Chronic Venous Stasis Ulcer with chronic lipodermatosclerosis
Up to 25% of venous ulcers are mixed venous/arterial. In these patients, cardiovascular risk factors should be assessed, along with symptoms of claudication. In areas of endemic Leishmaniasis transmission, other signs of venous stasis can help to clarify the etiology of the ulcer. (fig 6) Ankle Brachial Index (ABI) can also assist to distinguish arterial disease.

Laboratory Analysis and Imaging
Complete blood count is useful to rule out anemia, polycythemia, and leukocytosis. Diabetes, dyslipidemia, and chronic renal disease should be excluded as well. Wound culture is only required in the presence of infection or cellulitis. Ultrasound study of the lower extremity can assess for venous incompetence and exclude ongoing venous thrombus. If arterial ulcers are suspected, Ankle Brachial Pressure Index (ABPI) can be measured. If the ABPI is less than 0.6, peripheral artery disease is likely and compression devices are contraindicated.

Leg Elevation
Limited evidence exists to support the use of leg elevation as a modality to prevent ulcer recurrence, as leg elevation with compression did not improve ulcer healing. (11) One study demonstrated a reduction in venous ulcer recurrence when leg elevation daily for at least one hour for at least 6 weeks was coupled with compression. (12) Exercise Addressing calf-muscle pump failure is of significant therapeutic importance, as one study demonstrated a 60% prevalence among patients with venous ulcers.(13) Focus on calf muscle strengthening and stretching, particularly with compression, can improve pump function. (14) Progressive resistance exercise with prescribed physical activity can result in 9-45 additional venous ulcers healed per 100 patients. (15) Compression Therapy Life-long use of compressive therapy is indicated in patients with chronic venous disease in lower extremities. It reduces ambulatory venous pressure. These include bandaging systems, garments (stockings), or devices. Before applying compression, the physician must be aware of contraindications to compression, which include: (16)  peripheral arterial disease  decompensated heart failure  Ankle Brachial Pressure Index of less than 0.6

Bandages
Compression bandages are divided into elastic and inelastic. Difficulty in applying the bandages, physical impairment, excessive wound drainage, and pain can be significant barriers to their use.
The Unna boot is the most common inelastic compression bandage. The boot is impregnated with zinc-oxide, which also provides relief from venous stasis dermatitis. It has limited utility due to incapacity to absorb highly exudative ulcers, and is indicated only in ambulatory patients with small ulcers. (17) Elastic compression bandages are fitted to leg dimensions and are effective at rest and during ambulation. They require changing on an average of once per week. (18) Multiple layer systems (Fig 7) are superior to single layer for ulcer healing. (19) Stockings & Devices Compression stockings demonstrate utility for ulcer healing and prevention. (20) THey can be knee high, or thigh high, and are removed at night. One suggestion is to don them first thing in the morning before even getting out of bed, as venous pooling can begin as legs are swung to a sitting position at the bedside. They should be replaced approximately every 6 months due to normal wear. Intermittent Pneumatic Compression devices have not demonstrated effectiveness compared to other forms of compression and can be costly.

Dressings
Dressings can promote wound healing., and occupy a supporting role in compression. They come in many varieties, and are chosen based on protection, absorption, pain reduction, infection, odor control, and patient preference. Their is no robust evidence that one is superior to another when used with appropriate compression therapy. (21), (22) y (23) The presence of matrix embedded with bacteria, or biofilm, on a wound such as a venous ulcer can impede healing. Up to 60% of non-healing wounds in one study demonstrated the presence of biofilm. (24) Certain dressings appear to be more effective at disrupting biofilm, such as cadexomer iodine and time-release silver gel. (25) Pharmacologic Therapy

Pentoxifylline and Flavonoid
A hemorheologic agent that affects blood viscosity and red cell deformability, pentoxifylline has demonstrated improved venous ulcer healing, alone, or with compression therapy.(26) Micronized purified flavonoid fraction (MPFF) is a vasotonic agent that can reduce venous distension and improve lymphatic drainage. (27) However, there was no difference in venous healing when compared with placebo.(28)

Aspirin & Statins
A platelet inhibitor, and anti-inflammatory agent, aspirin, when coupled with compression therapy, promote faster healing of venous ulcers, but long term effectiveness remains unclear. (29) In one study Simvastatin demonstrated a higher rate of ulcer healing than matched placebo.(30)

Debridement
There is limited evidence for the benefit of debridement. A review of 10 RCTs showed no benefit, but did not include sharp surgical debridement. (31) Two other studies of sharp surgical debridement as an office procedure showed significant reduction in wound size compared with no sharp surgical debridement. (32) The theoretical benefits of debridement include preparation of the wound bed, removal of necrotic tissue, biofilm disruption, and the identification of the extent of the wound. Other forms of debridement such as collagenase and maggot therapy, offer no advantages over sharp surgical debridement. (33), (34) Surgery Surgery can remove the incompetent superficial vein, diverting flow to the deep system. This reverses the effect of venous hypertension on the ulcerated skin. Procedures include vein ligation, stripping, laser ablation, and foam injection. The ESCHAR study, comparing surgery/compression versus compression alone, demonstrated similar healing rates, but lower recurrence in the surgical group.