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Wound Facts & Prevention

About Venous Leg Ulcers

Of those patients afflicted with chronic wounds, the majority suffer from slow-healing or nonhealing lower extremity ulcers.2 Lower extremity or leg ulcers2 are the most common of the chronic wounds, with an estimated prevalence between 1% and 1.3% of the world population and 2.5 million people in the United States.11,12

It has been estimated that approximately 600,000 people seek treatment for venous leg ulcers on an annual basis in the United States. However, this number is likely to be an underestimation of the true prevalence of venous ulceration since many patients fail to seek medical care. Moreover, since older individuals are more prone to developing venous ulcers, the prevalence of these chronic wounds is expected to dramatically increase as the life expectancy of the world’s population continues to rise.2

In many cases, venous ulcers are particularly hard to heal. In addition, the recurrence rates for venous ulcers are high.13,14 As a result, these wounds are typically associated with a negative impact on quality of life, including impaired mobility, reduced self-esteem, and loss of productivity.

In a 1994 survey of patients with venous ulcers:12

  • 81% reported an adverse effect on mobility
  • 56% reported spending up to 8 hours per week on ulcer care
  • 68% reported a negative emotional impact, including fear, social isolation, anger, depression, and negative self-image
  • Of the 20% employed, leg ulceration correlated with time lost from work, job loss, and adverse effects on finances.12

In a recent (1995) study focusing on direct medical costs incurred by 78 hard-to-heal venous ulcer patients at the Cleveland Clinic Foundation, a large primary and tertiary referral center15

  • The mean total cost per patient was $9,688 ± $14,136
  • Home health care, hospitalizations, and home dressing changes accounted for 48%, 25%, and 21% of total costs
  • Patients incurred an average cost of $5,736 from day 0 to 90, $5,088 from day 91 to 180, and $5,108 from day 181 to 270, yielding a total mean patient cost per month of approximately $2,400
  • Costs incurred by patients with ulcer sizes >2.8 cm2 were nearly twice as high as those incurred by patients with ulcers < 2.8 cm2 during the first 90 days of follow-up
  • Patients with a history of venous ulcers incurred higher mean costs than those with no history of venous ulceration

Pathophysiology

Approximately 7 million people in the United States suffer from chronic venous insufficiency, which can progress to venous leg ulceration.16,17 While the specific pathophysiology leading from venous insufficiency to ulceration remains somewhat controversial, localized venous hypertension resulting from valvular incompetence (secondary to deep vein thrombosis or unknown cause) is integral to the development of tissue trauma and eventual ulceration.18,19

Normal venous circulation in the extremities is regulated by unidirectional valves that facilitate blood flow from capillary beds to the superficial system to the deep venous system (Fig 3). When primary valvular dysfunction occurs (the valves leading from the superficial to the deep venous system are not functioning properly), localized ambulatory venous hypertension in the superficial veins results.18,20


Figure 3. Incompetent valves in the development of venous insufficiency and ulceration. Normal venous circulation is illustrated on left; valvular incompetence resulting in ambulatory venous hypertension and capillary dilation is shown on right.

Wound VLU Photo


Adapted with permission from Phillips TJ, Dover JS. Leg ulcers. J Am Acad Dermatol. 1991;25:965-987.


While various hypotheses have been proposed to describe the pathophysiologic processes leading to ulceration, it is generally agreed that chronic exposure to localized venous hypertension, resulting from valvular dysfunction, leads to (Fig 4):

  • Dilation of capillaries with increased permeability and leakage of plasma and erythrocytes18
  • “Trapping” and activation of leukocytes in the microcirculation result in the release of free radicals and other toxic products (eg, tumor necrosis factor, collagenase), which promote cell death and tissue damage
  • Leakage of fibrinogen into surrounding tissues binds or “traps” growth factors/cytokines and renders them unavailable for maintenance and repair of tissue integrity21

Additionally, recent research has shown that fibroblasts from the edges of nonhealing venous ulcers are unresponsive to TGF-b1, (a key cytokine involved in extracellular matrix formation). This may contribute to the overall failure of these wounds to heal once formed.22


Figure 4. Pathogenesis of venous leg ulcers.18,19,21 Valvular dysfunction results in high pressure within the superficial venous system. Localized hypertension leads to leukocyte trapping and activation (right), resulting in surrounding tissue damage, and leakage of fibrinogen (left), which “traps” growth factors necessary for tissue repair. Untreated, these conditions lead to the development of venous ulceration.

Wound VLU Photo


Adapted with permission from Phillips TJ, Dover JS. Leg ulcers. J Am Acad Dermatol. 1991;25:965-987.


Clinical Features and Diagnosis

Successful management of venous leg ulcers is dependent on the proper diagnosis of this condition.18 Importantly, venous ulcers must be differentiated from ulcers due to arterial insufficiency, as the treatment regimens for these conditions are vastly different.

Clinical features of venous ulcers include redness, leg swelling and edema, pruritus, scaling, discharge, and lipodermatosclerosis (fibrosis of the dermis and subcutaneous tissues).12 These ulcers generally develop on the medial aspect of the leg and possess irregular borders. Pain is often present, in some cases severe, and can be complicated by bacterial infection.

Following careful assessment of general health, patient history, and physical examination,16 measurement of systolic blood pressure in the ankle is the most sensitive method for differentiating between venous and arterial insufficiency.13 Using a Doppler flowmeter, systolic blood pressure is measured in the ankle and compared with that in the arm to obtain the ankle/brachial index (ABI). An ABI less than 0.7 is indicative of moderate to severe arterial insufficiency.

Doppler ultrasonography is a simple and relatively inexpensive method to confirm venous reflux but cannot differentiate between superficial and deep venous insufficiency. Alternatively, photoplethysmography (PPG), which takes advantage of the light-absorbing property of hemoglobin, can be used to distinguish between superficial and deep vein incompetence by measuring the extent of light absorption.13 Duplex Doppler ultrasonography, a combination of ultrasonic scanning and pulsed Doppler flow examination, enables anatomical and functional assessment of the venous system but may not be widely available.13,18

Clinical Management

At the present time, treatment regimens for chronic venous insufficiency are mostly palliative with the goal of healing existing ulcers and minimizing their recurrence.13,17,4 In fact, clinicians easily exhaust their current supply of treatments for hard-to-heal ulcers.

Conservative protocols are aimed at combining local wound care to cleanse, protect, and aid healing of the ulcer, with ambulatory support to control the underlying condition.19 Following cleansing and debriding, wound dressings promote healing by maintaining a moist wound environment and protecting the wound against contaminants.13 Among the several types of wound dressings available (films, hydrogels, hydrocolloids, alginates, foam dressings, bilaminar synthetic dressings), proper selection of dressing should be based on clinical assessment of the wound. To control the underlying condition, compression therapy (eg, bandage wraps, Unna’s boot, elastic stockings, mechanical devices) remains the cornerstone of most treatment protocols. These agents provide necessary support to the leg by decreasing superficial venous pressure and improving venous return. Ideally, compression should be accompanied by complete bed rest and leg elevation to relieve edema; however, this is not always practical.13

While some systemic drug treatments (eg, zinc, fibrinolytic agents, pentoxifylline) have demonstrated minimal success in promoting healing of venous ulcers in small studies, their effectiveness in treating venous ulcers remains controversial.13

If conservative therapy with leg compression is unsuccessful, surgical intervention may be warranted. Surgical intervention for venous ulceration consists of either treating the ulcer via skin grafting or addressing the cause of the venous hypertension via invasive procedures.11,18 Grafting (eg, pinch, split-thickness) may be considered to promote healing in patients with nonhealing ulcers.17 A major disadvantage of this technique is creation of a donor site, which may be slow to heal and generate significant pain.13 Surgical invasive procedures, such as subfascial perforator ligation and superficial vein stripping, are aimed at correcting or bypassing the source of venous insufficiency and can produce long-term improvement in patients with incompetent valves of superficial and perforating veins.17,18

It should be noted that patient compliance and education is essential to the successful treatment of venous leg ulcers. After healing of a venous ulcer is achieved, it is imperative that each patient receive sufficient follow-up care. The patient should be instructed on proper skin care and the importance of leg elevation and avoidance of prolonged standing. The permanent use of compression stockings must also be emphasized to the patient in order to minimize recurrence.18 Patients must be educated on the value of proper nutrition (adequate protein, vitamin A, vitamin C, zinc) and on lifestyle changes (eg, exercise, weight loss). Lastly, long-term favorable results are dependent on continued patient follow-up by qualified personnel to ensure patient compliance.

In recent years, several advances offer particular promise in the treatment of venous ulcers. Topical application of various growth factors (eg, platelet-derived growth factor [PDGF], combination of platelet-derived wound-healing factors [PDWHF]) has been shown to accelerate healing of chronic nonhealing ulcers.23,24,25 Cultured epidermal (keratinocyte) autografts (patients’ own skin) and allografts (derived from neonatal foreskin) provide wound coverage and have also been used to promote wound healing of chronic ulcers.26 In an effort to provide both epidermal and dermal components, biosynthetic replacements have been developed that consist of human fibroblasts and keratinocytes seeded onto artificial matrix materials (eg, polyglycolic matrix).

Apligraf® provides both epidermal and dermal components and is approved for the treatment of diabetic foot ulcers and venous leg ulcers.

References:
2. Kane DP, Management Publications Inc; 1997:1-4. 11. Wittens CHA, Pierik RGJM, van Urk H. The surgical treatment of incompetent perforating veins. Eur J Vasc Endovasc Surg. 1995.
4. Krasner D. Wound healing and wound management. In: Krasner D, Kane D, eds. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals. 2nd ed. Wayne, Pa: Health M:19-23.
11. Wittens CHA, Pierik RGJM, van Urk H. The surgical treatment of incompetent perforating veins. Eur J Vasc Endovasc Surg. 1995;9:19-23.
12. Phillips T, Stanton B, Provan A, et al. A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol. 1994;31:49-53.
13. Phillips TJ, Dover JS. Leg ulcers. J Am Acad Dermatol. 1991;25:965-987.
14. Monk BE, Sarkany I. Outcome of treatment of venous stasis ulcers. Clin Exp Dermatol. 1982;7:397-400.
15. Olin JW, Beusterien K, Childs MB, et al. Costs in the management of venous stasis ulcers: implications for health care providers and payers. 1998; in press.
16. Capeheart JK. Chronic venous insufficiency: a focus on prevention of venous ulceration. J Wound Ostomy Continence Nurs. 1996;23:227-234.
17. Fitzpatrick JE. Stasis ulcers: update on a common geriatric problem. Geriatrics. October 1989;44:19-31.
18. Angle N, Bergan JJ. Chronic venous ulcer. BMJ. 1997;314:1019-1023.
19. Burton CS. Venous ulcers. Am J Surg. 1994;167(suppl):37S-40S.
20. Payne SPK, London NJM, Newland CJ, et al. Ambulatory venous pressure: correlation with skin condition and role in identifying surgically correctible disease. Eur J Vasc Endovasc Surg. 1996;11:195-200.
21. Falanga V, Eaglstein WH. The "trap" hypothesis of venous ulceration. Lancet. 1993;341:1006-1008.
22. Hasan A, Murata H, Falabella A, et al. Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-b 1. J Dermatol Sci. 1997;16:59-66.
23. Knighton DR, Fiegel VD. Growth factors and comprehensive surgical care of diabetic wounds. Curr Opin Gen Surg. 1993:32-39.
24. Mustoe TA, Cutler NR, Allman RM, et al. A phase II study to evaluate recombinant platelet-derived growth factor-BB in the treatment of stage 3 and 4 pressure ulcers. Arch Surg. 1994;129:213-219.
25. Ganio C, Tenewitz FE, Wilson RC, et al. The treatment of chronic nonhealing wounds using autologous platelet-derived growth factors. J Foot Ankle Surg. 1993;32:263-268.
26. Phillips TJ, Kehinde O, Green H, et al. Treatment of skin ulcers with cultured epidermal allografts. J Am Acad Dermatol. 1989;21:191-199.