Venous ulcer

Venous ulcers are wounds that are thought to occur due to improper functioning of valves in the veins usually of the legs. They are the major cause of chronic wounds, occurring in 70% to 90% of chronic wound cases.^[1]

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Pathophysiology

The exact etiology of venous ulcers is not certain, but they are thought to arise when venous valves that exist to prevent backflow of blood do not function properly, causing the pressure in veins to increase.^[2][3][4][5] The body needs the pressure gradient between arteries and veins in order for the heart to pump blood forward through arteries and into veins. When venous hypertension exists, arteries no longer have significantly higher pressure than veins, blood is not pumped as effectively into or out of the area,^[2][3][4][5] and it pools.

Venous hypertension may also stretch veins and allow blood proteins to leak into the extravascular space, isolating extracellular matrix (ECM) molecules and growth factors, preventing them from helping to heal the wound.^[2][5] Leakage of fibrinogen from veins as well as deficiencies in fibrinolysis may also cause fibrin to build up around the vessels, preventing oxygen and nutrients from reaching cells.^[2] Venous insufficiency may also cause white blood cells (leukocytes) to accumulate in small blood vessels, releasing inflammatory factors and reactive oxygen species (ROS, free radicals) and further contributing to chronic wound formation.^[2][5] Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to ischemia.^[6] This blockage of blood vessels by leukocytes may be responsible for the "no reflow phenomenon," in which ischemic tissue is never fully reperfused.^[6] Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to reperfusion injury.^[3] Other comorbidities may also be the root cause of venous ulcers.^[4]

Treatment

Venous ulcers are costly to treat, and there is a significant chance that they will recur after healing;^[1][2] one study found that up to 48% of venous ulcers had recurred by the fifth year after healing.^[2]

A review by Clinical Evidence concluded that several beneficial treatments exist.^[7]

Bisgaard regimen

Most venous ulcers respond to a regimen called Bisgaard regimen for treating ulcers.^{[citation needed]} Best remembered as a mnemonic 4E's - education, elevation, elastic compression and evaluation.

Compression therapy

Non-elastic, ambulatory, below knee (BK) compression aggressively counters the impact of reflux on venous pump failure.^[8] Compression therapy is used for venous leg ulcers and can decrease blood vessel diameter and pressure, which increases their effectiveness, preventing blood from flowing backwards.^[2] Compression is also used ^[2][9] to increase release of inflammatory cytokines, lower the amount of fluid leaking from capillaries and therefore prevent swelling, and prevent clotting by decreasing activation of thrombin and increasing that of plasmin.^[1]

Compression is applied using elastic bandages or boots specifically designed for the purpose.^[2] It is not clear whether non-elastic systems are better than a multilayer elastic system.^[7] Patients should wear as much compression as is comfortable. ^[10] The type of dressing applied beneath the compression does not seem to matter, and hydrocolloid is not better than simple low adherent dressings.^[11][12]

Pentoxifylline

A meta-analysis of randomized controlled trials by the Cochrane Collaboration found that "Pentoxifylline is an effective adjunct to compression bandaging for treating venous ulcers and may be effective in the absence of compression".^[13]

Artificial skin

Artificial skin, made of collagen and cultured skin cells, is also used to cover venous ulcers and excrete growth factors to help them heal.^[14] A meta-analysis of randomized controlled trials by the Cochrane Collaboration concluded "Bilayer artificial skin, used in conjunction with compression bandaging, increases the chance of healing a venous ulcer compared with compression and a simple dressing".^[15]

Surgical correction of superficial venous reflux

A randomized controlled trial found that surgery "reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer free time".^[16]

References

1. ^ ^{a b c} Snyder RJ (2005). "Treatment of nonhealing ulcers with allografts". Clin. Dermatol. 23 (4): 388-95. doi:10.1016/j.clindermatol.2004.07.020. PMID 16023934.
2. ^ ^{a b c d e f g h i j} Brem H, Kirsner RS, Falanga V (2004). "Protocol for the successful treatment of venous ulcers". Am. J. Surg. 188 (1A Suppl): 1-8. doi:10.1016/S0002-9610(03)00284-8. PMID 15223495.
3. ^ ^{a b c} Mustoe T (2004). "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy". Am. J. Surg. 187 (5A): 65S-70S. doi:10.1016/S0002-9610(03)00306-4. PMID 15147994.
4. ^ ^{a b c} Moreo K (2005). "Understanding and overcoming the challenges of effective case management for patients with chronic wounds". The Case manager 16 (2): 62-3, 67. doi:10.1016/j.casemgr.2005.01.014. PMID 15818347.
5. ^ ^{a b c d} Stanley AC, Lounsbury KM, Corrow K, et al (2005). "Pressure elevation slows the fibroblast response to wound healing". J. Vasc. Surg. 42 (3): 546-51. doi:10.1016/j.jvs.2005.04.047. PMID 16171604.
6. ^ ^{a b} eMedicine - Reperfusion Injury in Stroke : Article by Wayne M Clark, MD. Retrieved on 2007-08-05.
7. ^ ^{a b} Nelson EA, Cullum N, Jones J (2006). "Venous leg ulcers". Clinical evidence (15): 2607-26. PMID 16973096.
8. ^ B. McDonagh, S. Sorenson, A. Cohen, T. Eaton, D.E. Huntley, M. Schul, C. Martin, C. Gray, P. Putterman, T. King, J.L. Harry, R.C. Guptan. Venous Stasis Ulcer. Retrieved on 2007-08-05.
9. ^ Taylor JE, Laity PR, Hicks J, et al (2005). "Extent of iron pick-up in deforoxamine-coupled polyurethane materials for therapy of chronic wounds". Biomaterials 26 (30): 6024-33. doi:10.1016/j.biomaterials.2005.03.015. PMID 15885771.
10. ^ Nelson EA, Harper DR, Prescott RJ, Gibson B, Brown D, Ruckley CV (2006). "Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression". J. Vasc. Surg. 44 (4): 803-8. doi:10.1016/j.jvs.2006.05.051. PMID 17012004.
11. ^ Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA (2006). "Dressings for healing venous leg ulcers". Cochrane database of systematic reviews (Online) 3: CD001103. doi:10.1002/14651858.CD001103.pub2. PMID 16855958.
12. ^ Palfreyman S, Nelson EA, Michaels JA (2007). "Dressings for venous leg ulcers: systematic review and meta-analysis". BMJ 335 (7613): 244. doi:10.1136/bmj.39248.634977.AE. PMID 17631512.
13. ^ Jull A, Arroll B, Parag V, Waters J (2007). "Pentoxifylline for treating venous leg ulcers". Cochrane database of systematic reviews (Online) (3): CD001733. doi:10.1002/14651858.CD001733.pub2. PMID 17636683.
14. ^ Mustoe T. 2005. Dermal ulcer healing: Advances in understanding. Presented at meeting: Tissue repair and ulcer/wound healing: molecular mechanisms, therapeutic targets and future directions. Paris, France, March 17-18, 2005. Available.
15. ^ Jones JE, Nelson EA (2007). "Skin grafting for venous leg ulcers". Cochrane database of systematic reviews (Online) (2): CD001737. doi:10.1002/14651858.CD001737.pub3. PMID 17443510.
16. ^ Gohel MS, Barwell JR, Taylor M, et al (2007). "Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial". BMJ 335 (7610): 83. doi:10.1136/bmj.39216.542442.BE. PMID 17545185.