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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." Venous ulcers are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs (hence leg ulcers). They are an important cause of chronic wounds, affecting 1% of the population. Venous ulcers develop mostly along the medial distal leg, and can be painful with negative effects on quality of life. Exercise, together with
compression stocking Compression stockings (Flight Socks, Support Bandage) 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 ...
s, increases healing. 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.


Signs and symptoms

Signs and symptoms of venous ulcers include: * Moderate pain, which improves on elevation (unlike 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 "flare" is a spreading area of redness or flush. It is the second reaction in the triple response to injury and is due to dilatation of the arteriole. When this flare occurs around the ankle, it is called an ankle flare. The condition is also ...
", a collection of small, dark, engorged superficial veins 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


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, and/or
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
. Venous stasis causes the
pressure Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country a ...
in veins to increase. The body needs the pressure gradient between arteries and veins in order for the
heart The heart is a muscular organ found in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon diox ...
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. Venous hypertension may also stretch veins and allow blood proteins to leak into the extravascular space, isolating
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...
(ECM) molecules and growth factors, preventing them from helping to heal the wound. Leakage of fibrinogen from veins as well as deficiencies in fibrinolysis may also cause fibrin to build up around the vessels, preventing
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as we ...
and
nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s from reaching cells. Venous insufficiency may also cause
white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s (leukocytes) to accumulate in small
blood vessel Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...
s, releasing inflammatory factors and reactive oxygen species (ROS, free radicals) and further contributing to chronic wound formation. Buildup of white blood cells in small blood vessels may also plug the vessels, further contributing to ischemia. This blockage of blood vessels by leukocytes may be responsible for the "
no reflow phenomenon No reflow phenomenon is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed. The underlying mechanism is related to arterial microvasculature damage. It is primarily seen during percutane ...
", in which ischemic tissue is never fully reperfused. Allowing blood to flow back into the limb, for example by elevating it, is necessary but also contributes to reperfusion injury. Other comorbidities may also be the root cause of venous ulcers. 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. 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.


Diagnosis


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.


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 Arterial insufficiency ulcers (also known as ischemic ulcers, or ischemic wounds) are mostly located on the lateral surface of the ankle or the distal digits. They are commonly caused by peripheral artery disease (PAD). Characteristics The 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.


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 Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agains ...
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);
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
s such as
squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
(
Marjolin's ulcer Marjolin's ulcer refers to an aggressive ulcerating squamous cell carcinoma presenting in an area of previously traumatized, chronically inflamed, or scarred skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed ...
) or myelodysplastic syndrome;
neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
(e.g., diabetic peripheral neuropathy); or atypical infections such as nocardiosis, sporotrichosis, or
mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...
l infections.


Prevention

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


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. Most venous ulcers respond to patient education, elevation of foot, elastic compression, and evaluation (known as the Bisgaard regimen). Exercise together with
compression stocking Compression stockings (Flight Socks, Support Bandage) 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 ...
increases healing. There is no evidence that antibiotics, whether administered intravenously or by mouth, are useful. Silver products are also not typically useful, while there is some evidence of benefit from cadexomer iodine creams. There is a lack of quality evidence regarding the use of medical grade honey for venous leg ulcers. 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 Spruce resin salve is a traditional wound treatment method that has gained new popularity again after clinical studies in the 21st century. The pure coniferous resin from Norway spruce is antimicrobial against a wide range of bacteria and fungi a ...
. These products are considered as Medical Devices in EU and the products have to be CE marked. 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. It is uncertain whether therapeutic ultrasound improve the healing of venous ulcer.


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. Compression is also used to decrease release of inflammatory
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
s, 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. Compression is applied using elastic bandages or boots specifically designed for the purpose. A 2021
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
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. 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. It is not clear whether non-elastic systems are better than a multilayer elastic system. Patients should wear as much compression as is comfortable. 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. 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. Intermittent pneumatic compression devices may be used, but it is not clear that they are superior to simple compression dressings. It is not clear if interventions that are aimed to help people adhere to compression therapy are effective. More research is needed in this field.


Medications

Pentoxifylline Pentoxifylline, also known as oxpentifylline, is a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease. It is generic and sold under many brand names worldwide.Drugs.codrugs.com international listings ...
is a useful add on treatment to compression stockings and may also help by itself. It works by reducing platelet aggregation and thrombus formation. Gastrointestinal disturbances were reported as a potential adverse effect. 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. Further research is necessary to determine potential adverse effects, the effectiveness, and the dosing protocol for sulodexide treatment. 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. Oral
zinc supplements Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic ta ...
have not been proven to be effective in aiding the healing of venous ulcers, however more research is necessary to confirm these results. Treatments aimed at decreasing protease activity to promote healing in chronic wounds have been suggested, however, the benefit remains uncertain. There is also lack of evidence on effectiveness on testing for elevated proteases in venous ulcers and treating them with protease modulating treatment. There is low certainty evidence that protease modulating matrix treatment is helpful in the healing of venous ulcer. Flavonoids may be useful for treating venous ulcers but the evidence needs to be interpreted cautiously.


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


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. Artificial skin, made of collagen and
cultured Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tylor ...
skin cells, is also used to cover venous ulcers and excrete growth factors to help them heal. A
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
found that bilayer artificial skin with compression bandaging is useful in the healing of venous ulcers when compared to simple dressings.


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". Local anaesthetic endovenous surgery using the thermoablation (endovenous laser ablation or radiofrequency), perforator closure (TRLOP) and
foam sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations (vascular malformations) and also malformations of the lymphatic system. A medicine is injected into the vessels, wh ...
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. No studies are found on the effect of endovenous thermal ablation on ulcer healing, recurrence, and quality of life. The use of subfascial endoscopic perforator surgery is uncertain in the healing of venous ulcer.


Dressings

It is not certain which dressings and topical agents are most effective for healing venous leg ulcers. Silver-containing dressings may increase the probability of healing for venous leg ulcers. A clinical trial was successfully performed with a mixture of 60% sugar or glucose powder and 40% vaseline. A 2013
Cochrane Cochrane may refer to: Places Australia *Cochrane railway station, Sydney, a railway station on the closed Ropes Creek railway line Canada * Cochrane, Alberta * Cochrane Lake, Alberta * Cochrane District, Ontario ** Cochrane, Ontario, a town wit ...
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
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. However, there is some evidence that ibuprofen dressings may offer pain relief to people with venous leg ulcers.


Prognosis

Venous ulcers are costly to treat, and there is a significant chance that they will recur after healing; one study found that up to 48% of venous ulcers had recurred by the fifth year after healing. However treatment with local anaesthetic endovenous techniques suggests a reduction of this high recurrence rate is possible. 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. Some topical drugs used to treat venous ulcer may cause
venous eczema Stasis dermatitis refers to the skin changes that occur in the leg as a result of "stasis" or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins. Insuffic ...
.


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. Research from the
University of Surrey The University of Surrey is a public research university in Guildford, Surrey, England. The university received its royal charter in 1966, along with a number of other institutions following recommendations in the Robbins Report. The institut ...
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.


References


External links

{{Authority control Vascular diseases Vascular-related cutaneous conditions