Venous ulcer

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Venous ulcer
Other namesVenous insufficiency ulceration, stasis ulcer, stasis dermatitis, varicose ulcer, ulcus cruris, crural ulceration
Venous ulcer dorsal leg.jpg
Venous ulcer on the back of the right leg
Specialty Dermatology   OOjs UI icon edit-ltr-progressive.svg

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." [1] Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs (hence leg ulcers). [2] : 846  They are an important cause of chronic wounds, affecting 1% of the population. [3] Venous ulcers develop mostly along the medial distal leg, and can be painful with negative effects on quality of life. [4]

Contents

Exercise, together with compression stockings, increases healing. [5] 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. [6]

Signs and symptoms

Signs and symptoms of venous ulcers include:[ citation needed ]

Chronic venous insufficiency & Venous ulcer Chronic venous insufficiency & Venous ulcer.jpg
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, [8] and/or congestive heart failure. [9] Venous stasis causes the pressure in veins to increase. [10] [11] [12] [13] 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, and blood is not pumped as effectively into or out of the area. [10] [11] [12] [13]

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. [10] [13] 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. [10] 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. [10] [13] Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to ischemia. [14] This blockage of blood vessels by leukocytes may be responsible for the "no reflow phenomenon", in which ischemic tissue is never fully reperfused. [14] Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to reperfusion injury. [11] Other comorbidities may also be the root cause of venous ulcers. [12]

It is in the 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 ]

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 ]

Diagnosis

Venous ulcer (45 x 30 mm) Ulcera varicosa (RPS 24-08-2020) en pierna con insuficiencia venosa cronica.png
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. [15]

Distinction from arterial ulcer

A venous ulcer tends to occur on the medial side of the leg, typically around the 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 ]

Differential diagnosis

Leg ulcerations may result from various pathologic processes. Common causes of leg ulcerations include 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; vasculitic processes such as cryoglobulinemia; calciphylaxis (often seen in people with end-stage kidney disease but may also occur with medications such as warfarin); cancers such as squamous cell carcinoma (Marjolin's ulcer) or myelodysplastic syndrome; neuropathy (e.g., diabetic peripheral neuropathy); or atypical infections such as nocardiosis, sporotrichosis, or mycobacterial infections.[ citation needed ]

Prevention

Compression stockings appear to prevent the formation of new ulcers in people with a history of venous ulcers. [16]

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. [17]

Most venous ulcers respond to patient education, elevation of foot, elastic compression, and evaluation (known as the Bisgaard regimen). [18] Exercise together with compression stocking increases healing. [5] There is no evidence that antibiotics, whether administered intravenously or by mouth, are useful. [19] Silver products are also not typically useful, while there is some evidence of benefit from cadexomer iodine creams. [19] There is a lack of quality evidence regarding the use of medical grade honey for venous leg ulcers. [20]

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. [21] [22]

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 diabetic origin, [23] as well as necrotic wounds. [24] [ unreliable medical source ] 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. [25] [ unreliable medical source ]

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. [26]

It is uncertain whether therapeutic ultrasound improve the healing of venous ulcer. [27]

Compression therapy

Non-elastic, ambulatory, below knee (BK) compression counters the impact of reflux on venous pump failure. 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. [10] Compression is also used [10] [28] to decrease 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. [3] Compression is applied using elastic bandages or boots specifically designed for the purpose. [10]

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. [29] [30] 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. [29] It is not clear whether non-elastic systems are better than a multilayer elastic system. [30] Patients should wear as much compression as is comfortable. [31] 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. [32] 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. [33]

Intermittent pneumatic compression devices may be used, but it is not clear that they are superior to simple compression dressings. [34]

It is not clear if interventions that are aimed to help people adhere to compression therapy are effective. [35] More research is needed in this field.

Medications

Pentoxifylline is a useful add on treatment to compression stockings and may also help by itself. [36] It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect. [36]

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. [37] Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for sulodexide treatment.[ citation needed ]

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. [38]

Oral 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. [39]

Treatments aimed at decreasing protease activity to promote healing in chronic wounds have been suggested, however, the benefit remains uncertain. [40] There is also lack of evidence on effectiveness on testing for elevated proteases in venous ulcers and treating them with protease modulating treatment. [41] There is low certainty evidence that protease modulating matrix treatment is helpful in the healing of venous ulcer. [42]

Flavonoids may be useful for treating venous ulcers but the evidence needs to be interpreted cautiously. [43]

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. [44] It is uncertain whether the choice of cleaning solution or method of application makes any difference to venous leg ulcer healing. [44]  

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. [45]

Artificial skin, made of collagen and cultured skin cells, is also used to cover venous ulcers and excrete growth factors to help them heal. [46] A systematic review found that bilayer artificial skin with compression bandaging is useful in the healing of venous ulcers when compared to simple dressings. [45]

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". [47]

Local anaesthetic endovenous surgery using the 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. [48]

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. [49] The use of subfascial endoscopic perforator surgery is uncertain in the healing of venous ulcer. [50]

Dressings

It is not certain which dressings and topical agents are most effective for healing venous leg ulcers. [51] [52] Silver-containing dressings may increase the probability of healing for venous leg ulcers. [51]

A 2013 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 trials are needed to help answer this research question. [53] However, there is some evidence that ibuprofen dressings may offer pain relief to people with venous leg ulcers. [54]

Prognosis

Venous ulcers are costly to treat, and there is a significant chance that they will recur after healing; [3] [10] one study found that up to 48% of venous ulcers had recurred by the fifth year after healing. [10] However treatment with local anaesthetic endovenous techniques suggests a reduction of this high recurrence rate is possible. [48]

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 ]

Some topical drugs used to treat venous ulcer may cause venous eczema. [55]

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. [56]

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. [57]

Related Research Articles

<span class="mw-page-title-main">Varicose veins</span> Medical condition in which superficial veins become large and twisted

Varicose veins, also known as varicoses, are a medical condition in which superficial veins become enlarged and twisted. Although usually just a cosmetic ailment, in some cases they cause fatigue, pain, itching, and nighttime leg cramps. These veins typically develop in the legs, just under the skin. Their complications can include bleeding, skin ulcers, and superficial thrombophlebitis. Varices in the scrotum are known as a varicocele, while those around the anus are known as hemorrhoids. The physical, social, and psychological effects of varicose veins can lower their bearers' quality of life.

<span class="mw-page-title-main">Ulcer (dermatology)</span> Type of cutaneous condition

An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin of the lower extremities and in the gastrointestinal tract. An ulcer that appears on the skin is often visible as an inflamed tissue with an area of reddened skin. A skin ulcer is often visible in the event of exposure to heat or cold, irritation, or a problem with blood circulation.

<span class="mw-page-title-main">Wound</span> Acute injury from laceration, puncture, blunt force, or compression

A wound is any disruption of or damage to living tissue, such as skin, mucous membranes, or organs. Wounds can either be the sudden result of direct trauma, or can develop slowly over time due to underlying disease processes such as diabetes mellitus, venous/arterial insufficiency, or immunologic disease. Wounds can vary greatly in their appearance depending on wound location, injury mechanism, depth of injury, timing of onset, and wound sterility, among other factors. Treatment strategies for wounds will vary based on the classification of the wound, therefore it is essential that wounds be thoroughly evaluated by a healthcare professional for proper management. In normal physiology, all wounds will undergo a series of steps collectively known as the wound healing process, which include hemostasis, inflammation, proliferation, and tissue remodeling. Age, tissue oxygenation, stress, underlying medical conditions, and certain medications are just a few of the many factors known to affect the rate of wound healing.

<span class="mw-page-title-main">Macular edema</span> Medical condition

Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell (edema). The swelling may distort a person's central vision, because the macula holds tightly packed cones that provide sharp, clear, central vision to enable a person to see detail, form, and color that is directly in the centre of the field of view.

<span class="mw-page-title-main">Peripheral neuropathy</span> Nervous system disease affecting nerves beyond the brain and spinal cord

Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropathies affecting motor, sensory, or autonomic nerve fibers result in different symptoms. More than one type of fiber may be affected simultaneously. Peripheral neuropathy may be acute or chronic, and may be reversible or permanent.

<span class="mw-page-title-main">Pressure ulcer</span> Skin damage resulting from long-term pressure

Pressure ulcers, also known as pressure sores, bed sores or pressure injuries, are localised damage to the skin and/or underlying tissue that usually occur over a bony prominence as a result of usually long-term pressure, or pressure in combination with shear or friction. The most common sites are the skin overlying the sacrum, coccyx, heels, and hips, though other sites can be affected, such as the elbows, knees, ankles, back of shoulders, or the back of the cranium.

<span class="mw-page-title-main">Electrotherapy</span> Use of electricity for medical purposes, and to stimulate Muscle for more strength.

Electrotherapy is the use of electrical energy as a medical treatment. In medicine, the term electrotherapy can apply to a variety of treatments, including the use of electrical devices such as deep brain stimulators for neurological disease. The term has also been applied specifically to the use of electric current to speed wound healing. The use of EMS is also very wide for managing muscular pain. Additionally, the term "electrotherapy" or "electromagnetic therapy" has also been applied to a range of alternative medical devices and treatments. Evidence supporting the effectiveness of electrotherapy is limited.

<span class="mw-page-title-main">Telangiectasia</span> Small dilated blood vessels

Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on the body, but are commonly seen on the face around the nose, cheeks and chin. Dilated blood vessels can also develop on the legs, although when they occur on the legs, they often have underlying venous reflux or "hidden varicose veins". When found on the legs, they are found specifically on the upper thigh, below the knee joint and around the ankles.

<span class="mw-page-title-main">Dressing (medicine)</span> Sterile pad or compress applied to wounds

A dressing or compress is piece of material such as a pad applied to a wound to promote healing and protect the wound from further harm. A dressing is designed to be in direct contact with the wound, as distinguished from a bandage, which is most often used to hold a dressing in place. Modern dressings are sterile.

<span class="mw-page-title-main">Maggot therapy</span> Wound care by maggot therapy

Maggot therapy is a type of biotherapy involving the introduction of live, disinfected maggots into non-healing skin and soft-tissue wounds of a human or other animal for the purpose of cleaning out the necrotic (dead) tissue within a wound (debridement), and disinfection.

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. To overcome that stage and jump-start the healing process, a number of factors need to be addressed such as bacterial burden, necrotic tissue, and moisture balance of the whole wound. In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and degradation plays too large a role.

<span class="mw-page-title-main">Diosmin</span> Chemical compound

Diosmin, a flavone glycoside of diosmetin, is manufactured from citrus fruit peels as a phlebotonic non-prescription dietary supplement used to aid treatment of hemorrhoids or chronic venous diseases, mainly of the legs.

<span class="mw-page-title-main">Vascular disease</span> Medical condition

Vascular disease is a class of diseases of the vessels of the circulatory system in the body, including blood vessels – the arteries and veins, and the lymphatic vessels. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood and lymph vessels can cause a range of health problems that can sometimes become severe, and fatal. Coronary heart disease for example, is the leading cause of death for men and women in the United States.

<span class="mw-page-title-main">Negative-pressure wound therapy</span> Therapeutic technique

Negative-pressure wound therapy (NPWT), also known as a vacuum assisted closure (VAC), is a therapeutic technique using a suction pump, tubing, and a dressing to remove excess exudate and promote healing in acute or chronic wounds and second- and third-degree burns. The therapy involves the controlled application of sub-atmospheric pressure to the local wound environment using a sealed wound dressing connected to a vacuum pump. The use of this technique in wound management started in the 1990s and this technique is often recommended for treatment of a range of wounds including dehisced surgical wounds, closed surgical wounds, open abdominal wounds, open fractures, pressure injuries or pressure ulcers, diabetic foot ulcers, venous insufficiency ulcers, some types of skin grafts, burns, sternal wounds. It may also be considered after a clean surgery in a person who is obese.

A hydrocolloid dressing is an opaque or transparent dressing for wounds. A hydrocolloid dressing is biodegradable, breathable, and depending on the dressing selected, may adhere to the skin, so no separate taping is needed.

<span class="mw-page-title-main">Compression stockings</span> Compression garment

Compression stockings are a specialized hosiery designed to help prevent the occurrence of, and guard against further progression of, venous disorders such as edema, phlebitis and thrombosis. Compression stockings are elastic compression garments worn around the leg, compressing the limb. This reduces the diameter of distended veins and increases venous blood flow velocity and valve effectiveness. Compression therapy helps decrease venous pressure, prevents venous stasis and impairments of venous walls, and relieves heavy and aching legs.

<span class="mw-page-title-main">Extracorporeal shockwave therapy</span> Ultrasonic, non-invasive, outpatient treatment

Extracorporeal shockwave therapy (ESWT) is a treatment using powerful acoustic pulses which is mostly used to treat kidney stones and in physical therapy and orthopedics.

<span class="mw-page-title-main">Chronic venous insufficiency</span> Pooling of blood in the veins

Chronic venous insufficiency (CVI) is a medical condition in which blood pools in the veins, straining the walls of the vein. The most common cause of CVI is superficial venous reflux which is a treatable condition. As functional venous valves are required to provide for efficient blood return from the lower extremities, this condition typically affects the legs. If the impaired vein function causes significant symptoms, such as swelling and ulcer formation, it is referred to as chronic venous disease. It is sometimes called chronic peripheral venous insufficiency and should not be confused with post-thrombotic syndrome in which the deep veins have been damaged by previous deep vein thrombosis.

<span class="mw-page-title-main">Diabetic foot ulcer</span> Medical condition

Diabetic foot ulcer is a breakdown of the skin and sometimes deeper tissues of the foot that leads to sore formation. It may occur due to a variety of mechanisms. It is thought to occur due to abnormal pressure or mechanical stress chronically applied to the foot, usually with concomitant predisposing conditions such as peripheral sensory neuropathy, peripheral motor neuropathy, autonomic neuropathy or peripheral arterial disease. It is a major complication of diabetes mellitus, and it is a type of diabetic foot disease. Secondary complications to the ulcer, such as infection of the skin or subcutaneous tissue, bone infection, gangrene or sepsis are possible, often leading to amputation.

CHIVA method is a type of surgery used to treat varicose veins that occur as a result of long term venous insufficiency. The term is a French acronym for Conservatrice Hémodynamique de l'Insuffisance Veineuse en Ambulatoire.

References

  1. ↑ O'Donnell TF, Passman MA, Marston WA, Ennis WJ, Dalsing M, Kistner RL, et al. (August 2014). "Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery ® and the American Venous Forum". Journal of Vascular Surgery. 60 (2 Suppl): 3S–59S. doi: 10.1016/j.jvs.2014.04.049 . PMID   24974070.
  2. ↑ James WD, Berger TG, Elston DM (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN   978-0-7216-2921-6. OCLC   968428064.
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  4. ↑ Phillips P, Lumley E, Duncan R, Aber A, Woods HB, Jones GL, et al. (March 2018). "A systematic review of qualitative research into people's experiences of living with venous leg ulcers" (PDF). Journal of Advanced Nursing. 74 (3): 550–563. doi:10.1111/jan.13465. PMID   28960514. S2CID   206018724.
  5. 1 2 Jull A, Slark J, Parsons J (November 2018). "Prescribed Exercise With Compression vs Compression Alone in Treating Patients With Venous Leg Ulcers: A Systematic Review and Meta-analysis". JAMA Dermatology. 154 (11): 1304–1311. doi:10.1001/jamadermatol.2018.3281. PMC   6248128 . PMID   30285080.
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  11. 1 2 3 Mustoe T (May 2004). "Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy". American Journal of Surgery. 187 (5A): 65S–70S. doi:10.1016/S0002-9610(03)00306-4. PMID   15147994.
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  13. 1 2 3 4 Stanley AC, Lounsbury KM, Corrow K, Callas PW, Zhar R, Howe AK, et al. (September 2005). "Pressure elevation slows the fibroblast response to wound healing". Journal of Vascular Surgery. 42 (3): 546–551. doi: 10.1016/j.jvs.2005.04.047 . PMID   16171604.
  14. 1 2 "eMedicine - Reperfusion Injury in Stroke : Article by Wayne M Clark, MD" . Retrieved 2007-08-05.
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  16. ↑ de Moraes Silva MA, Nelson A, Bell-Syer SE, Jesus-Silva SG, Miranda F (March 2024). "Compression for preventing recurrence of venous ulcers". The Cochrane Database of Systematic Reviews. 2024 (3): CD002303. doi:10.1002/14651858.CD002303.pub4. PMC  10919450. PMID   38451842.
  17. ↑ NICE (July 23, 2013). "Varicose veins in the legs: The diagnosis and management of varicose veins. 1.2 Referral to a vascular service". National Institute for Health and Care Excellence . Retrieved August 25, 2014.
  18. ↑ van Gent WB, Wilschut ED, Wittens C (November 2010). "Management of venous ulcer disease". BMJ. 341: c6045. doi:10.1136/bmj.c6045. PMID   21075818. S2CID   5218584.
  19. 1 2 O'Meara S, Al-Kurdi D, Ologun Y, Ovington LG, Martyn-St James M, Richardson R (January 2014). "Antibiotics and antiseptics for venous leg ulcers". The Cochrane Database of Systematic Reviews. 1 (1): CD003557. doi: 10.1002/14651858.CD003557.pub5 . PMC   10580125 . PMID   24408354.
  20. ↑ Jull AB, Cullum N, Dumville JC, Westby MJ, Deshpande S, Walker N (March 2015). "Honey as a topical treatment for wounds". The Cochrane Database of Systematic Reviews. 3 (3): CD005083. doi:10.1002/14651858.CD005083.pub4. PMC   9719456 . PMID   25742878.
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  23. ↑ Biswas A, Bharara M, Hurst C, Gruessner R, Armstrong D, Rilo H (September 2010). "Use of sugar on the healing of diabetic ulcers: a review". Journal of Diabetes Science and Technology. 4 (5): 1139–1145. doi:10.1177/193229681000400512. PMC   2956799 . PMID   20920433.
  24. ↑ Murandu M, Webber MA, Simms MH, Dealey C (May 2011). "Use of granulated sugar therapy in the management of sloughy or necrotic wounds: a pilot study". Journal of Wound Care. 20 (5): 206, 208, 210 passim. doi:10.12968/jowc.2011.20.5.206. PMID   21647066.
  25. ↑ Franceschi C, Bricchi M, Delfrate R (2017-05-10). "Anti-infective effects of sugar-vaseline mixture on leg ulcers". Veins and Lymphatics. 6 (2). doi:10.4081/vl.2017.6652. ISSN   2279-7483.
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  29. 1 2 Shi C, Dumville JC, Cullum N, Connaughton E, Norman G, et al. (Cochrane Wounds Group) (July 2021). "Compression bandages or stockings versus no compression for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 2021 (7): CD013397. doi:10.1002/14651858.CD013397.pub2. PMC   8407020 . PMID   34308565.
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  36. 1 2 Jull AB, Arroll B, Parag V, Waters J (December 2012). "Pentoxifylline for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 12 (12): CD001733. doi:10.1002/14651858.CD001733.pub3. PMC   7061323 . PMID   23235582.
  37. ↑ Wu B, Lu J, Yang M, Xu T (June 2016). "Sulodexide for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 2016 (6): CD010694. doi:10.1002/14651858.CD010694.pub2. PMC   9308373 . PMID   27251175.
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  41. ↑ Norman G, Westby MJ, Stubbs N, Dumville JC, Cullum N, et al. (Cochrane Wounds Group) (January 2016). "A 'test and treat' strategy for elevated wound protease activity for healing in venous leg ulcers". The Cochrane Database of Systematic Reviews. 2016 (1): CD011753. doi:10.1002/14651858.CD011753.pub2. PMC   8627254 . PMID   26771894.
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  45. 1 2 Jones JE, Nelson EA, Al-Hity A (January 2013). "Skin grafting for venous leg ulcers". The Cochrane Database of Systematic Reviews. 1 (1): CD001737. doi:10.1002/14651858.CD001737.pub4. PMC   7061325 . PMID   23440784.
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  47. ↑ Gohel MS, Barwell JR, Taylor M, Chant T, Foy C, Earnshaw JJ, et al. (July 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. PMC   1914523 . PMID   17545185.
  48. 1 2 Thomas CA, Holdstock JM, Harrison CC, Price BA, Whiteley MS (April 2013). "Healing rates following venous surgery for chronic venous leg ulcers in an independent specialist vein unit". Phlebology. 28 (3): 132–139. doi:10.1258/phleb.2012.011097. PMID   22833505. S2CID   9186619.
  49. ↑ Cai PL, Hitchman LH, Mohamed AH, Smith GE, Chetter I, Carradice D (July 2023). "Endovenous ablation for venous leg ulcers". The Cochrane Database of Systematic Reviews. 2023 (7): CD009494. doi:10.1002/14651858.CD009494.pub3. PMC   10373122 . PMID   37497816.
  50. ↑ Lin ZC, Loveland PM, Johnston RV, Bruce M, Weller CD, et al. (Cochrane Wounds Group) (March 2019). "Subfascial endoscopic perforator surgery (SEPS) for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 2019 (3): CD012164. doi:10.1002/14651858.CD012164.pub2. PMC   6397791 . PMID   30827037.
  51. 1 2 Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC (June 2018). "Dressings and topical agents for treating venous leg ulcers". The Cochrane Database of Systematic Reviews. 2018 (6): CD012583. doi:10.1002/14651858.CD012583.pub2. PMC   6513558 . PMID   29906322.
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  53. ↑ O'Meara S, Martyn-St James M (May 2013). "Foam dressings for venous leg ulcers". The Cochrane Database of Systematic Reviews (5): CD009907. doi: 10.1002/14651858.cd009907.pub2 . PMID   23728697.
  54. ↑ Briggs M, Nelson EA, Martyn-St James M, et al. (Cochrane Wounds Group) (November 2012). "Topical agents or dressings for pain in venous leg ulcers". The Cochrane Database of Systematic Reviews. 11 (11): CD001177. doi:10.1002/14651858.CD001177.pub3. PMC   7054838 . PMID   23152206.
  55. ↑ Marks R (2003-04-30). Roxburgh's Common Skin Diseases (17th ed.). CRC Press. p. 127. ISBN   978-0-340-76232-5.
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