View source for Venous ulcer

{{Short description|Skin sore sustained by a vasculatory disease}}
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{{Infobox medical condition (new)
| name          = Venous ulcer
| synonyms      = Venous insufficiency ulceration, stasis ulcer, stasis dermatitis, varicose ulcer, ulcus cruris, crural ulceration
| image         = Venous ulcer dorsal leg.jpg
| caption       = Venous ulcer on the back of the right leg
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'''Venous ulcer''' is defined by the [[American Venous Forum]] as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing."<ref>{{cite journal | vauthors = O'Donnell TF, Passman MA, Marston WA, Ennis WJ, Dalsing M, Kistner RL, Lurie F, Henke PK, Gloviczki ML, Eklöf BG, Stoughton J, Raju S, Shortell CK, Raffetto JD, Partsch H, Pounds LC, Cummings ME, Gillespie DL, McLafferty RB, Murad MH, Wakefield TW, Gloviczki P | title = Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery ® and the American Venous Forum | journal = Journal of Vascular Surgery | volume = 60 | issue = 2 Suppl | pages = 3S–59S | date = August 2014 | pmid = 24974070 | doi = 10.1016/j.jvs.2014.04.049 | doi-access = free }}</ref> Venous ulcers are [[wounds]] that are thought to occur due to improper functioning of [[venous valve]]s, usually of the legs (hence '''leg ulcers''').<ref name="Andrews">{{cite book | vauthors = James WD, Berger TG, Elston DM |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |oclc= 968428064 }}</ref>{{rp|846}}  They are an important cause of [[chronic wound]]s, affecting 1% of the population.<ref name="pmid16023934">{{cite journal | vauthors = Lal BK | title = Venous ulcers of the lower extremity: Definition, epidemiology, and economic and social burdens | journal = Seminars in Vascular Surgery | volume = 28 | issue = 1 | pages = 3–5 | date = March 2015 | pmid = 26358303 | doi = 10.1053/j.semvascsurg.2015.05.002 }}</ref> Venous ulcers develop mostly along the medial distal leg, and can be painful with negative effects on quality of life.<ref name="pmid28960514">{{cite journal | vauthors = Phillips P, Lumley E, Duncan R, Aber A, Woods HB, Jones GL, Michaels J | title = A systematic review of qualitative research into people's experiences of living with venous leg ulcers | journal = Journal of Advanced Nursing | volume = 74 | issue = 3 | pages = 550–563 | date = March 2018 | pmid = 28960514 | doi = 10.1111/jan.13465 | s2cid = 206018724 | url = http://eprints.whiterose.ac.uk/120327/5/WR_SR_QR_VLU%20%283%29.pdf }}</ref>
Exercise, together with [[compression stocking]]s, increases healing.<ref name=Jull2018>{{cite journal | vauthors = Jull A, Slark J, Parsons J | title = Prescribed Exercise With Compression vs Compression Alone in Treating Patients With Venous Leg Ulcers: A Systematic Review and Meta-analysis | journal = JAMA Dermatology | volume = 154 | issue = 11 | pages = 1304–1311 | date = November 2018 | pmid = 30285080 | pmc = 6248128 | doi = 10.1001/jamadermatol.2018.3281 }}</ref> The NICE guideline recommends that everyone with a venous leg ulcer, even if healed, should be referred to a vascular specialist for venous duplex ultrasound and assessment for endovenous surgery.<ref>{{cite web |url=http://www.nice.org.uk/guidance/cg168/chapter/1-Recommendations |title=Varicose veins in the legs: The diagnosis and management of varicose veins. 1.2 Referral to a vascular service |author=NICE |access-date=June 15, 2019 |date=July 23, 2013 |publisher=[[National Institute for Health and Care Excellence]]}}</ref>
==Signs and symptoms==
Signs and symptoms of venous ulcers include:{{citation needed|date=October 2021}}
* Moderate pain, which improves on elevation (unlike [[Arterial insufficiency ulcer|arterial ulcers]] which worsen with elevation)
* Irregular, sloping edges
* Associated oedema, due to increased hydrostatic pressure, which contributes to 'atrophie blanche'
* 'Atrophie blanche', localised loss of skin pigmentation due to death of erythrocytes and scarring
* [[Lipodermatosclerosis]], a hardening of the skin which can lead to an "inverted champagne bottle" appearance to the leg
* Associated superficial [[varicose veins]] or "[[ankle flare]]", a collection of small, dark, engorged superficial veins<ref>{{Cite book | vauthors = Hugo F, Norris-Cervetto E, Warbrick-Smith J |title=Oxford cases in medicine and surgery |isbn=978-0198716228|edition= Second|location=Oxford | publisher = Oxford University Press |oclc=923846134|year = 2015}}</ref>
<gallery mode="packed" widths="360px" heights="220">
File:Úlceras antes da cirurgia.JPG|Venous ulcer before surgery
File:WIRA-Wiki-GH-012-de-Ulkus-Verlauf-unter-wIRA.png|Healing process of a chronic venous stasis ulcer of the lower leg
File:Venous ulcer Wound healed in one month - Varicose Vein.jpg|Healing venous ulcer after one month
</gallery>
[[File:Chronic venous insufficiency & Venous ulcer.jpg|thumb|Chronic venous insufficiency & Venous ulcer]]
==Pathophysiology==
The exact cause of venous ulcers is not certain, but a common denominator is generally [[venous stasis]], which may be caused by [[chronic venous insufficiency]],<ref>{{cite web|url=https://my.clevelandclinic.org/health/diseases/16872-chronic-venous-insufficiency-cvi|title=Chronic Venous Insufficiency (CVI)|website=Cleveland Clinic}} Last reviewed by a Cleveland Clinic medical professional on 05/14/2019.</ref> and/or [[congestive heart failure]].<ref name="ZhuHu2017">{{cite journal | vauthors = Zhu R, Hu Y, Tang L | title = Reduced cardiac function and risk of venous thromboembolism in Asian countries | journal = Thrombosis Journal | volume = 15 | issue = 1 | pages = 12 | year = 2017 | pmid = 28450810 | pmc = 5404284 | doi = 10.1186/s12959-017-0135-3 | doi-access = free }}</ref> Venous stasis causes the [[pressure]] in veins to increase.<ref name="pmid15223495"/><ref name="pmid15147994">{{cite journal | vauthors = Mustoe T | title = Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy | journal = American Journal of Surgery | volume = 187 | issue = 5A | pages = 65S–70S | date = May 2004 | pmid = 15147994 | doi = 10.1016/S0002-9610(03)00306-4 }}</ref><ref name="pmid15818347">{{cite journal | vauthors = Moreo K | title = Understanding and overcoming the challenges of effective case management for patients with chronic wounds | journal = The Case Manager | volume = 16 | issue = 2 | pages = 62–3, 67 | year = 2005 | pmid = 15818347 | doi = 10.1016/j.casemgr.2005.01.014 }}</ref><ref name="pmid16171604">{{cite journal | vauthors = Stanley AC, Lounsbury KM, Corrow K, Callas PW, Zhar R, Howe AK, Ricci MA | title = Pressure elevation slows the fibroblast response to wound healing | journal = Journal of Vascular Surgery | volume = 42 | issue = 3 | pages = 546–551 | date = September 2005 | pmid = 16171604 | doi = 10.1016/j.jvs.2005.04.047 | doi-access = free }}</ref> The body needs the pressure [[gradient]] between [[arteries]] and [[vein]]s 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, and blood is not pumped as effectively into or out of the area.<ref name="pmid15223495"/><ref name="pmid15147994"/><ref name="pmid15818347"/><ref name="pmid16171604"/>
Venous [[hypertension]] may also stretch veins and allow [[blood protein]]s to leak into the [[extravascular space]], isolating [[extracellular matrix]] (ECM) molecules and [[growth factor]]s, preventing them from helping to heal the wound.<ref name="pmid15223495"/><ref name="pmid16171604"/>  Leakage of [[fibrinogen]] from veins as well as deficiencies in [[fibrinolysis]] may also cause [[fibrin]] to build up around the vessels, preventing [[oxygen]] and [[nutrient]]s from reaching [[cell (biology)|cells]].<ref name="pmid15223495"/>  Venous insufficiency may also cause [[white blood cell]]s (leukocytes) to accumulate in small [[blood vessel]]s, releasing inflammatory factors and [[reactive oxygen species]] (ROS, [[free radical]]s) and further contributing to chronic wound formation.<ref name="pmid15223495"/><ref name="pmid16171604"/> Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to [[ischemia]].<ref name="Clark2005">{{cite web |url=http://www.emedicine.com/neuro/topic602.htm |title=eMedicine - Reperfusion Injury in Stroke : Article by Wayne M Clark, MD |access-date=2007-08-05 }}</ref>  This blockage of blood vessels by leukocytes may be responsible for the "[[no reflow phenomenon]]", in which ischemic tissue is never fully reperfused.<ref name="Clark2005"/>  Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to [[reperfusion injury]].<ref name="pmid15147994"/>  Other [[comorbidity|comorbidities]] may also be the root cause of venous ulcers.<ref name="pmid15818347"/>
It is in the [[Crus (lower leg)|crus]] that the classic venous stasis ulcer occurs.  Venous stasis results from damage to the vein valvular system in the lower extremity and in extreme cases allows the pressure in the veins to be higher than the pressure in the arteries.  This pressure results in transudation of inflammatory mediators into the subcutaneous tissues of the lower extremity and subsequent breakdown of the tissue including the skin.{{citation needed|date=February 2021}}
Wounds of the distal lower extremities arising from causes not directly related to venous insufficiency (e.g., scratch, bite, burn, or surgical incision) may ultimately fail to heal if underlying (often undiagnosed) venous disease is not properly addressed.{{citation needed|date=January 2019}}
==Diagnosis==
[[File:Úlcera varicosa (RPS 24-08-2020) en pierna con insuficiencia venosa crónica.png|thumb|Venous ulcer (45 x 30 mm)]]
===Classification===
A clinical severity score has been developed to assess chronic venous ulcers. It is based on the CEAP (clinical, etiology, anatomy, and pathophysiology) classification system developed by an expert panel. A high score gives a poor prognosis.<ref name="pmid15622385">{{cite journal | vauthors = Eklöf B, Rutherford RB, Bergan JJ, Carpentier PH, Gloviczki P, Kistner RL, Meissner MH, Moneta GL, Myers K, Padberg FT, Perrin M, Ruckley CV, Smith PC, Wakefield TW | title = Revision of the CEAP classification for chronic venous disorders: consensus statement | journal = Journal of Vascular Surgery | volume = 40 | issue = 6 | pages = 1248–1252 | date = December 2004 | pmid = 15622385 | doi = 10.1016/j.jvs.2004.09.027 | doi-access = free }}</ref>
===Distinction from arterial ulcer===
A venous ulcer tends to occur on the medial side of the leg, typically around the [[Malleolus|medial malleolus]] in the 'gaiter area' whereas [[arterial ulcer]] tends to occur on lateral side of the leg and over bony prominences. A venous ulcer is typically shallow with irregular sloping edges whereas an arterial ulcer can be deep and has a 'punched out' appearance. Venous ulcers are typically 'wet' with a moderate to heavy exudate, whereas arterial ulcers are typically 'dry' and scabbed. The skin surrounding a venous ulcer may be edematous (swollen) and there may be evidence of varicose veins; the skin surrounding an arterial ulcer may be pale, cold, shiny and hairless. Both venous and arterial ulcers may be painful, however arterial ulcers tend to be more painful, especially with elevation of the leg, for example when in bed.{{citation needed|date=February 2021}}
===Differential diagnosis===
Leg ulcerations may result from various pathologic processes. Common causes of leg ulcerations include [[Ischemia|inadequate blood flow and oxygen delivery to tissues]] as seen in [[peripheral arterial disease]] and venous stasis ulcerations. Additional causes include neutrophilic [[skin conditions]] such as [[pyoderma gangrenosum]] or [[Sweet's syndrome]]; [[Vasculitis|vasculitic processes]] such as [[cryoglobulinemia]]; [[calciphylaxis]] (often seen in people with [[end-stage kidney disease]] but may also occur with medications such as [[warfarin]]); [[cancer]]s such as [[squamous cell carcinoma]] ([[Marjolin's ulcer]]) or [[myelodysplastic syndrome]]; [[neuropathy]] (e.g., [[Diabetic neuropathy|diabetic peripheral neuropathy]]); or atypical infections such as [[nocardiosis]], [[sporotrichosis]], or [[mycobacteria]]l infections.{{citation needed|date=February 2021}}
==Prevention==
Compression stockings appear to prevent the formation of new ulcers in people with a history of venous ulcers.<ref>{{cite journal | vauthors = de Moraes Silva MA, Nelson A, Bell-Syer SE, Jesus-Silva SG, Miranda F | title = Compression for preventing recurrence of venous ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2024 | issue = 3 | pages = CD002303 | date = March 2024 | pmid = 38451842 | pmc = 10919450 | doi = 10.1002/14651858.CD002303.pub4 | pmc-embargo-date = March 7, 2025 }}</ref>
==Treatment==
The main aim of the treatment is to create such an environment that allows skin to grow across an ulcer. In the majority of cases this requires finding and treating underlying venous reflux. The [[National Institute for Health and Care Excellence]] (NICE) recommends referral to a vascular service for anyone with a leg ulcer that has not healed within two weeks or anyone with a healed leg ulcer.<ref>{{cite web |url=http://www.nice.org.uk/guidance/cg168/chapter/1-Recommendations |title=Varicose veins in the legs: The diagnosis and management of varicose veins. 1.2 Referral to a vascular service |author=NICE |access-date=August 25, 2014 |date=July 23, 2013 |publisher=[[National Institute for Health and Care Excellence]]}}</ref>
Most venous ulcers respond to patient education, elevation of foot, elastic compression, and evaluation (known as the Bisgaard regimen).<ref>{{cite journal | vauthors = van Gent WB, Wilschut ED, Wittens C | title = Management of venous ulcer disease | journal = BMJ | volume = 341 | pages = c6045 | date = November 2010 | pmid = 21075818 | doi = 10.1136/bmj.c6045 | s2cid = 5218584 }}</ref> Exercise together with [[compression stocking]] increases healing.<ref name=Jull2018/> There is no evidence that [[antibiotic]]s, whether administered intravenously or by mouth, are useful.<ref name=OM2014>{{cite journal | vauthors = O'Meara S, Al-Kurdi D, Ologun Y, Ovington LG, Martyn-St James M, Richardson R | title = Antibiotics and antiseptics for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD003557 | date = January 2014 | pmid = 24408354 | doi = 10.1002/14651858.CD003557.pub5 | doi-access = free | pmc = 10580125 }}</ref> Silver products are also not typically useful, while there is some evidence of benefit from [[cadexomer iodine]] creams.<ref name=OM2014/> There is a lack of quality evidence regarding the use of medical grade honey for venous leg ulcers.<ref>{{cite journal | vauthors = Jull AB, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N | title = Honey as a topical treatment for wounds | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD005083 | date = March 2015 | pmid = 25742878 | doi = 10.1002/14651858.CD005083.pub4 | pmc = 9719456 }}</ref>
The recommendations of dressings to treat venous ulcers vary between the countries. Antibiotics are often recommended to be used only if so advised by the physician due to emergence of resistance of bacteria to antibiotics. This is an issue on venous ulcers as they tend to heal slower than acute wounds for example. Natural alternatives that are suitable for the longer term use exists on the market such as honey and [[resin salve]]. These products are considered as Medical Devices in EU and the products have to be CE marked.<ref name="pmid20559190">{{cite journal | vauthors = Lohi J, Sipponen A, Jokinen JJ | title = Local dressings for pressure ulcers: what is the best tool to apply in primary and second care? | journal = Journal of Wound Care | volume = 19 | issue = 3 | pages = 123–127 | date = March 2010 | pmid = 20559190 | doi = 10.12968/jowc.2010.19.3.47282 }}</ref><ref>{{cite web | title = Regulation (Eu) 2017/745 of the European Parliament and of the Council on medical devices | date = 5 April 2017 | url = http://data.europa.eu/eli/reg/2017/745/oj | work = Official Journal of the European Union }}</ref>
[[Sugar]] has long been known for its effectiveness in [[wound]] treatment, notably through the use of [[honey]] or powdered sugar. A number of articles demonstrate the efficacy of sugar application in the treatment of ulcers of [[Diabetes|diabetic]] origin,<ref name="PMID_20920433">{{cite journal | vauthors = Biswas A, Bharara M, Hurst C, Gruessner R, Armstrong D, Rilo H | title = Use of sugar on the healing of diabetic ulcers: a review | journal = Journal of Diabetes Science and Technology | volume = 4 | issue = 5 | pages = 1139–1145 | date = September 2010 | pmid = 20920433 | pmc = 2956799 | doi = 10.1177/193229681000400512 }}</ref> as well as [[Necrosis|necrotic]] wounds.<ref>{{cite journal | vauthors = Murandu M, Webber MA, Simms MH, Dealey C | title = Use of granulated sugar therapy in the management of sloughy or necrotic wounds: a pilot study | journal = Journal of Wound Care | volume = 20 | issue = 5 | pages = 206, 208, 210 passim | date = May 2011 | pmid = 21647066 | doi = 10.12968/jowc.2011.20.5.206 }}</ref>{{Unreliable medical source|sure=y|reason=Primary source|date=June 2024}}
A study of 50 leg ulcer patients demonstrated the efficacy of a weekly treatment consisting solely of a 60% / 40% [[glucose]]/[[vaseline]] mixture applied to the wound, without [[debridement]]. Complementary compression therapy is used to reduce the effects of venous insufficiency.<ref name = "Franceschi_2017">{{Cite journal | vauthors = Franceschi C, Bricchi M, Delfrate R |date=2017-05-10 |title=Anti-infective effects of sugar-vaseline mixture on leg ulcers |url=http://www.pagepressjournals.org/index.php/vl/article/view/6652 |journal=Veins and Lymphatics |volume=6 |issue=2 |doi=10.4081/vl.2017.6652 |issn=2279-7483}}</ref>{{Unreliable medical source|sure=y|reason=Primary source|date=June 2024}}
There is uncertain evidence whether alginate dressing is effective in the healing of venous ulcer when compared to hydrocolloid dressing or plain non-adherent dressing.<ref>{{cite journal | vauthors = O'Meara S, Martyn-St James M, Adderley UJ | title = Alginate dressings for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 8 | pages = CD010182 | date = August 2015 | pmid = 26286189 | pmc = 7087437 | doi = 10.1002/14651858.CD010182.pub3 | collaboration = Cochrane Wounds Group }}</ref>
It is uncertain whether therapeutic ultrasound improve the healing of venous ulcer.<ref>{{cite journal | vauthors = Cullum N, Liu Z | title = Therapeutic ultrasound for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 5 | pages = CD001180 | date = May 2017 | pmid = 28504325 | pmc = 6481488 | doi = 10.1002/14651858.CD001180.pub4 | collaboration = Cochrane Wounds Group }}</ref>
===Compression therapy===
Non-elastic, ambulatory, below knee (BK) compression counters the impact of reflux on venous pump failure. [[Cold compression therapy|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.<ref name="pmid15223495"/>  Compression is also used<ref name="pmid15223495"/><ref name="pmid15885771">{{cite journal | vauthors = Taylor JE, Laity PR, Hicks J, Wong SS, Norris K, Khunkamchoo P, Johnson AF, Cameron RE | title = Extent of iron pick-up in deforoxamine-coupled polyurethane materials for therapy of chronic wounds | journal = Biomaterials | volume = 26 | issue = 30 | pages = 6024–6033 | date = October 2005 | pmid = 15885771 | doi = 10.1016/j.biomaterials.2005.03.015 }}</ref> to decrease release of inflammatory [[cytokine]]s, lower the amount of fluid leaking from [[capillary|capillaries]] and therefore prevent [[edema|swelling]], and prevent [[clotting]] by decreasing activation of [[thrombin]] and increasing that of [[plasmin]].<ref name="pmid16023934"/>  Compression is applied using elastic bandages or boots specifically designed for the purpose.<ref name="pmid15223495"/>
A 2021 [[systematic review]] found that compression dressings probably reduce pain and help ulcers to heal more quickly (usually within 12 months) and may also improve quality of life.<ref name=":1">{{cite journal | vauthors = Shi C, Dumville JC, Cullum N, Connaughton E, Norman G | title = Compression bandages or stockings versus no compression for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 7 | pages = CD013397 | date = July 2021 | pmid = 34308565 | pmc = 8407020 | doi = 10.1002/14651858.CD013397.pub2 | collaboration = Cochrane Wounds Group }}</ref><ref name="pmid16973096">{{cite journal | vauthors = Nelson EA, Cullum N, Jones J | title = Venous leg ulcers | journal = Clinical Evidence | issue = 15 | pages = 2607–2626 | date = June 2006 | pmid = 16973096 }}</ref> However, it is not clear whether or not compression bandages have any unwanted effects or if the potential health benefits of using compression outweigh its costs.<ref name=":1" /> It is not clear whether non-elastic systems are better than a multilayer elastic system.<ref name="pmid16973096"/> Patients should wear as much compression as is comfortable.<ref name="pmid17012004">{{cite journal | vauthors = Nelson EA, Harper DR, Prescott RJ, Gibson B, Brown D, Ruckley CV | title = Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression | journal = Journal of Vascular Surgery | volume = 44 | issue = 4 | pages = 803–808 | date = October 2006 | pmid = 17012004 | doi = 10.1016/j.jvs.2006.05.051 | doi-access = free }}</ref>  In treating an existing ulcer, the type of dressing applied beneath the compression does not seem to matter, and [[hydrocolloid]] is not better than simple low adherent dressings.<ref name="pmid17631512">{{cite journal | vauthors = Palfreyman S, Nelson EA, Michaels JA | title = Dressings for venous leg ulcers: systematic review and meta-analysis | journal = BMJ | volume = 335 | issue = 7613 | pages = 244 | date = August 2007 | pmid = 17631512 | pmc = 1939774 | doi = 10.1136/bmj.39248.634977.AE }}</ref> Good outcomes in ulcer treatment were shown after the application of double compression stockings, e.g. ulcer stockings. These systems contain two different stockings, one often of white colour. This one is to be put on first, is also worn overnight and exerts a basic pressure of 20 mmHg or less. Also it keeps the wound dressing in place. A second stocking, often brown, sometimes black, achieves a pressure of 20–30 mmHg and is applied over the other stocking during the daytime.<ref>{{cite journal | vauthors = Partsch H, Mortimer P | title = Compression for leg wounds | journal = The British Journal of Dermatology | volume = 173 | issue = 2 | pages = 359–369 | date = August 2015 | pmid = 26094638 | doi = 10.1111/bjd.13851 | doi-access = free }}</ref>
Intermittent pneumatic compression devices may be used, but it is not clear that they are superior to simple compression dressings.<ref name="pmid24820100">{{cite journal | vauthors = Nelson EA, Hillman A, Thomas K | title = Intermittent pneumatic compression for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD001899 | date = May 2014 | pmid = 24820100 | doi = 10.1002/14651858.CD001899.pub4 | pmc = 10788769 | arxiv = quant-ph/0403227 }}</ref>
It is not clear if interventions that are aimed to help people adhere to compression therapy are effective.<ref>{{cite journal | vauthors = Weller CD, Buchbinder R, Johnston RV | title = Interventions for helping people adhere to compression treatments for venous leg ulceration | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD008378 | date = March 2016 | issue = 3 | pmid = 26932818 | pmc = 6823259 | doi = 10.1002/14651858.CD008378.pub3 | author-link2 = Rachelle Buchbinder }}</ref> More research is needed in this field.
===Medications===
[[Pentoxifylline]] is a useful add on treatment to compression stockings and may also help by itself.<ref name=Jull2012>{{cite journal | vauthors = Jull AB, Arroll B, Parag V, Waters J | title = Pentoxifylline for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD001733 | date = December 2012 | issue = 12 | pmid = 23235582 | pmc = 7061323 | doi = 10.1002/14651858.CD001733.pub3 }}</ref> It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect.<ref name=Jull2012 />
[[Sulodexide]], which reduces the formation of blood clots and reduces inflammation, may improve the healing of venous ulcers when taken in conjunction with proper local wound care.<ref>{{cite journal | vauthors = Wu B, Lu J, Yang M, Xu T | title = Sulodexide for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD010694 | date = June 2016 | volume = 2016 | pmid = 27251175 | doi = 10.1002/14651858.CD010694.pub2 | pmc = 9308373 }}</ref> Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for [[sulodexide]] treatment.{{citation needed|date=February 2021}}
An oral dose of [[aspirin]] is being investigated as a potential treatment option for people with venous ulcers. A 2016 Cochrane systematic review concluded that further research is necessary before this treatment option can be confirmed to be safe and effective.<ref>{{cite journal | vauthors = de Oliveira Carvalho PE, Magolbo NG, De Aquino RF, Weller CD | title = Oral aspirin for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 2 | pages = CD009432 | date = February 2016 | pmid = 26889740 | pmc = 8627253 | doi = 10.1002/14651858.CD009432.pub2 }}</ref>
Oral [[Zinc sulfate|zinc supplements]] have not been proven to be effective in aiding the healing of venous ulcers, however more research is necessary to confirm these results.<ref>{{cite journal | vauthors = Wilkinson EA | title = Oral zinc for arterial and venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD001273 | date = September 2014 | volume = 2014 | pmid = 25202988 | pmc = 6486207 | doi = 10.1002/14651858.CD001273.pub3 }}</ref>
Treatments aimed at decreasing protease activity to promote healing in chronic wounds have been suggested, however, the benefit remains uncertain.<ref>{{cite journal | vauthors = Westby MJ, Dumville JC, Stubbs N, Norman G, Wong JK, Cullum N, Riley RD | title = Protease activity as a prognostic factor for wound healing in venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 9 | pages = CD012841 | date = September 2018 | pmid = 30171767 | pmc = 6513613 | doi = 10.1002/14651858.CD012841.pub2 }}</ref> There is also lack of evidence on effectiveness on testing for elevated proteases in venous ulcers and treating them with protease modulating treatment.<ref>{{cite journal | vauthors = Norman G, Westby MJ, Stubbs N, Dumville JC, Cullum N | title = A 'test and treat' strategy for elevated wound protease activity for healing in venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 1 | pages = CD011753 | date = January 2016 | pmid = 26771894 | pmc = 8627254 | doi = 10.1002/14651858.CD011753.pub2 | collaboration = Cochrane Wounds Group }}</ref> There is low certainty evidence that protease modulating matrix treatment is helpful in the healing of venous ulcer.<ref>{{cite journal | vauthors = Westby MJ, Norman G, Dumville JC, Stubbs N, Cullum N | title = Protease-modulating matrix treatments for healing venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD011918 | date = December 2016 | issue = 4 | pmid = 27977053 | pmc = 6463954 | doi = 10.1002/14651858.CD011918.pub2 | collaboration = Cochrane Wounds Group }}</ref>
Flavonoids may be useful for treating venous ulcers but the evidence needs to be interpreted cautiously.<ref>{{cite journal | vauthors = Scallon C, Bell-Syer SE, Aziz Z | title = Flavonoids for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD006477 | date = May 2013 | pmid = 23728661 | doi = 10.1002/14651858.CD006477.pub2 | collaboration = Cochrane Wounds Group | doi-access = free | pmc = 11513187 }}</ref>
==== Wound Cleansing Solutions ====
There is insufficient evidence to determine if cleaning wounds is beneficial or whether wound cleaning solutions (polyhexamethylene biguanide, aqueous oxygen peroxide, etc.) are better than sterile water or saline solutions to help venous leg ulcers heal.<ref name=":02">{{cite journal | vauthors = McLain NE, Moore ZE, Avsar P | title = Wound cleansing for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 3 | pages = CD011675 | date = March 2021 | pmid = 33734426 | pmc = 8092712 | doi = 10.1002/14651858.CD011675.pub2 | collaboration = Cochrane Wounds Group }}</ref> It is uncertain whether the choice of cleaning solution or method of application makes any difference to venous leg ulcer healing.<ref name=":02" />  
===Skin grafts and artificial skin===
Two layers of skin created from animal sources as a [[skin graft]] has been found to be useful in venous leg ulcers.<ref name="Jones">{{cite journal | vauthors = Jones JE, Nelson EA, Al-Hity A | title = Skin grafting for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD001737 | date = January 2013 | pmid = 23440784 | pmc = 7061325 | doi = 10.1002/14651858.CD001737.pub4 }}</ref>
[[Artificial skin]], made of collagen and [[cell culture|cultured]] skin cells, is also used to cover venous ulcers and excrete [[growth factor]]s to help them heal.<ref name="Mustoe2005">{{cite conference | vauthors = Mustoe T |title=Dermal ulcer healing: Advances in understanding |conference=Tissue repair and ulcer/wound healing: molecular mechanisms, therapeutic targets and future directions |location=Paris, France |date=March 17–18, 2005}}</ref> A [[systematic review]] found that bilayer artificial skin with compression bandaging is useful in the healing of venous ulcers when compared to simple dressings.<ref name="Jones" />
===Surgery===
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".<ref name="pmid17545185">{{cite journal | vauthors = Gohel MS, Barwell JR, Taylor M, Chant T, Foy C, Earnshaw JJ, Heather BP, Mitchell DC, Whyman MR, Poskitt KR | title = Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial | journal = BMJ | volume = 335 | issue = 7610 | pages = 83 | date = July 2007 | pmid = 17545185 | pmc = 1914523 | doi = 10.1136/bmj.39216.542442.BE }}</ref>
Local anaesthetic endovenous surgery using the [[Ablation|thermoablation]] (endovenous laser ablation or radiofrequency), perforator closure (TRLOP) and [[foam sclerotherapy]] showed an 85% success rate of healing, with no recurrence of healed ulcers at an average of 3.1 years, and a clinical improvement in 98% in a selected group of venous leg ulcers.<ref name="Thomas CA, Holdstock JM, Harrison CC, Price BA, Whiteley MS 132–9">{{cite journal | vauthors = Thomas CA, Holdstock JM, Harrison CC, Price BA, Whiteley MS | title = Healing rates following venous surgery for chronic venous leg ulcers in an independent specialist vein unit | journal = Phlebology | volume = 28 | issue = 3 | pages = 132–139 | date = April 2013 | pmid = 22833505 | doi = 10.1258/phleb.2012.011097 | s2cid = 9186619 }}</ref>
Endovenous ablation, in combination with compression, on superficial venous incompetence has been shown (high quality evidence) to  improve leg ulcer healing when compared to compression alone.<ref>{{cite journal | vauthors = Cai PL, Hitchman LH, Mohamed AH, Smith GE, Chetter I, Carradice D | title = Endovenous ablation for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 7 | pages = CD009494 | date = July 2023 | pmid = 37497816 | pmc = 10373122 | doi = 10.1002/14651858.CD009494.pub3 }}</ref> The use of subfascial endoscopic perforator surgery is uncertain in the healing of venous ulcer.<ref>{{cite journal | vauthors = Lin ZC, Loveland PM, Johnston RV, Bruce M, Weller CD | title = Subfascial endoscopic perforator surgery (SEPS) for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 3 | pages = CD012164 | date = March 2019 | pmid = 30827037 | pmc = 6397791 | doi = 10.1002/14651858.CD012164.pub2 | collaboration = Cochrane Wounds Group }}</ref>
=== Dressings ===
It is not certain which dressings and topical agents are most effective for healing venous leg ulcers.<ref name=":0" /><ref>{{cite journal | vauthors = Ribeiro CT, Dias FA, Fregonezi GA | title = Hydrogel dressings for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 8 | pages = CD010738 | date = August 2022 | pmid = 35930364 | pmc = 9354941 | doi = 10.1002/14651858.CD010738.pub2 | collaboration = Cochrane Wounds Group }}</ref> Silver-containing dressings may increase the probability of healing for venous leg ulcers.<ref name=":0">{{cite journal | vauthors = Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC | title = Dressings and topical agents for treating venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 6 | pages = CD012583 | date = June 2018 | pmid = 29906322 | pmc = 6513558 | doi = 10.1002/14651858.CD012583.pub2 }}</ref>
A 2013 [[Cochrane (organisation)|Cochrane]] [[systematic review]] aimed to determine the effectiveness of foam dressings for helping to heal venous leg ulcers. The authors concluded that is uncertain whether or not foam dressings are more effective than other dressing types and that more [[randomized controlled trial]]s are needed to help answer this research question.<ref>{{cite journal | vauthors = O'Meara S, Martyn-St James M | title = Foam dressings for venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD009907 | date = May 2013 | pmid = 23728697 | doi = 10.1002/14651858.cd009907.pub2 | doi-access = free | pmc = 11531896 }}</ref> However, there is some evidence that ibuprofen dressings may offer pain relief to people with venous leg ulcers.<ref>{{cite journal | vauthors = Briggs M, Nelson EA, Martyn-St James M | title = Topical agents or dressings for pain in venous leg ulcers | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD001177 | date = November 2012 | issue = 11 | pmid = 23152206 | pmc = 7054838 | doi = 10.1002/14651858.CD001177.pub3 | collaboration = Cochrane Wounds Group }}</ref>
==Prognosis==
Venous ulcers are costly to treat, and there is a significant chance that they will recur after [[healing]];<ref name="pmid16023934"/><ref name="pmid15223495">{{cite journal | vauthors = Brem H, Kirsner RS, Falanga V | title = Protocol for the successful treatment of venous ulcers | journal = American Journal of Surgery | volume = 188 | issue = 1A Suppl | pages = 1–8 | date = July 2004 | pmid = 15223495 | doi = 10.1016/S0002-9610(03)00284-8 | doi-access = free }}</ref> one study found that up to 48% of venous ulcers had recurred by the fifth year after healing.<ref name="pmid15223495"/> However treatment with local anaesthetic endovenous techniques suggests a reduction of this high recurrence rate is possible.<ref name="Thomas CA, Holdstock JM, Harrison CC, Price BA, Whiteley MS 132–9"/>
Without proper care, the ulcer may get infected leading to [[cellulitis]] or [[gangrene]] and eventually may need amputation of the part of limb in future.{{citation needed|date=October 2021}}
Some topical drugs used to treat venous ulcer may cause [[venous eczema]].<ref>{{cite book |title=Roxburgh's Common Skin Diseases |edition= 17th |isbn=978-0-340-76232-5 |page=127| vauthors = Marks R |date= 2003-04-30 |publisher= CRC Press }}</ref>
==Research==
The current 'best' practice in the UK is to treat the underlying venous reflux once an ulcer has healed. It is questionable as to whether endovenous treatment should be offered before ulcer healing, as current evidence would not support this approach as standard care. The EVRA (Early Venous Reflux Ablation) ulcer trial, a randomised clinical trial funded by the [[National Institute for Health and Care Research]] (NIHR) to compare early versus delayed endovenous treatment of superficial venous reflux in patients with chronic venous ulceration, opened for recruitment in October 2013. The study hopes to show an increase in healing rates from 60% to 75% at 24 weeks.<ref name="ICL">{{cite web |url=http://www.imperial.ac.uk/department-surgery-cancer/research/surgery/clinical-trials/evra/ |title=EVRA (Early Venous Reflux Ablation) Ulcer Trial |vauthors =Davies A, Heatley F|publisher= Faculty of Medicine Imperial College London }}</ref>
Research from the [[University of Surrey]] and funded by the Leg Ulcer Charity looked at the psychological impact of having a leg ulcer, on the relatives and friends of the affected person, and the influence of treatment.<ref>{{cite web |url=http://www.legulcercharity.org/research.html |title=Impact of Leg Ulcers on Relatives and Carers of Affected Patients - A PhD Study funded by The Leg Ulcer Charity | vauthors = Tollow P |access-date=August 25, 2014 |date=April 2014 |publisher=The Leg Ulcer Charity |archive-date=August 26, 2014 |archive-url=https://web.archive.org/web/20140826114451/http://www.legulcercharity.org/research.html |url-status=dead }}</ref>
== References ==
{{Reflist}}
== External links ==
{{Medical resources
|  DiseasesDB      = 29114
|  ICD10           = {{ICD10|I|83|0|i|80}}, {{ICD10|I|83|2|i|80}}, {{ICD10|L|97|}}
|  ICD9            = {{ICD9|454.0}}
|  ICDO            =
|  OMIM            =
|  MedlinePlus     = 000834
|  eMedicineSubj   =
|  eMedicineTopic  =
|  MeshID          = D014647
}}
{{Vascular diseases}}
{{Authority control}}
[[Category:Vascular diseases]]
[[Category:Vascular-related cutaneous conditions]]