Varicose veins are a common pathology that affects 25-33% of the adult population. It is estimated that 1% of adults will suffer from a venous ulcer at some point in their life, thus making it a significant healthcare problem. An ulcer is a full-thickness break in the skin which fails to heal. Varicose veins are said to be the most important factor in the development of a venous ulcer, its significance attributed to the disabling effect venous ulcers have on the quality of life of those affected. Patients with a venous ulcer are said to have an impaired quality of life compared to those with congestive heart failure and chronic lung disease. The etiology of venous ulcers is reported to be multifactorial, with the underlying cause being chronic venous hypertension. It is suggested that persistent hypertension causes tissue inflammation and therefore microcirculatory disturbance. This then leads to changes in the nutrition of the skin and subcutaneous tissue causing lipodermatosclerosis and atrophie blanche. The final result of these tissue changes is an ulcer. Varicose veins are dilated, tortuous veins that are >3mm in diameter. They can be a cause of considerable morbidity but conversely can be a chance finding with no symptoms. The benefit of treatment is often a relief in symptoms rather than improvement in appearance. Symptoms include leg fatigue, aching, pain, ankle swelling, restless legs, and night cramps. These are often worse in warm weather or after long periods of standing. More severe symptoms are said to be a good indication for referral to a vascular specialist for further investigation into treatment options. Treatment can include a range of methods from simple leg elevation and compression to more invasive techniques such as surgery or thermal ablation. The aim of treatment is to stop the reflux through the saphenofemoral junction and therefore have a beneficial effect on the skin changes and reduce the chance of developing a venous ulcer.
Understanding Varicose Veins
When left untreated, chronic venous insufficiency can progress to the more severe cases of deep vein thrombosis and varicose veins. A venous ulcer is a further progression of chronic venous insufficiency where there is a loss of considerable vein function. The skin becomes significantly affected with increased levels of hemosiderin, an iron storage complex, and above normal levels of skin and fatty tissues due to minor hemorrhages and other skin changes. Approximately 10-15% of people with varicose vein will go on to develop a venous ulcer, further reinforcing the idea that varicose veins are a major predisposing factor to venous ulcers. This provides evidence for the importance of researching the relationship between varicose veins and venous ulcers in order to advance current treatment for venous ulcers.
Causes of Varicose Veins
There is no single nor simple answer to the cause of varicose veins. It has been suggested that the primary cause of varicose veins is the failure of the one-way, pocket-valve in the veins. The valve will deteriorate, be damaged or be congenitally deficient. When the valve fails, blood will collect in the lower portion on the leg. This will lead to increased pressure on the vein and cause it to become distended. This theory would explain primary varicose veins and also how varicose veins can occur after damage to the deep veins in the leg. This cause of varicose veins is difficult to correlate to patients and is not fully understood. The valve reflux theory is summarised with the equation e2 > es = φ. e = valve competence, es = elastic tissue and fibres in the vein, φ = pressure of blood in the vein. It has also been described that the increased pressure on the vein from a number of systems can be transmitted to the leg veins. This pressure transmitted from the abdominal and pelvic diaphragms can be attributed to chronic cough, constipation, and obesity. Another theory of the cause of varicose veins attributes it to a venous wall weakness. This theory has a number of associations to pregnancy. Hormones that are released in pregnancy and also the increase in blood volume may cause relaxation of the vein walls. This will reduce the absorptive capacity of the wall resulting in increased tension in the wall. This can cause dilatation of the vein and be a cause of varicose veins or a contribution to existing varicosities. The increased blood volume can also attribute to the formation of varicose veins.
Symptoms of Varicose Veins
In many western countries, these mild symptoms may be inadvertently made worse with the treatment of trunk varicose veins with compression, stockings, and bandaging in preparation for avulsion when often all that is really needed is definitive endovenous ablation.
Symptoms such as dull aching with or without associated cramps, ankle swelling, and a heavy tired or restless feeling in the legs are often throughout the world put down to wear and tear or simply old age. While these symptoms may not be dramatic, it has been shown in a few small trials that in some patients they respond well to a well-conducted elimination of truncal reflux with an improvement in quality of life and the patient’s own global assessment of the symptoms.
The subject is poorly understood and somewhat neglected by traditional vascular practitioners who have often underestimated the effect of venous disease on the quality of people’s lives. This historical neglect of symptoms and their response to treatment has often led to less aggressive treatment of varicose veins and of venous disease as a whole than is often seen for arterial conditions, despite the fact that varicose veins and their complications are a lot more common.
Chronic venous insufficiency, in general, irrespective of the cause, is a condition that generally bothers those affected only with old age. It can also sometimes be seen in the population who have no varicose veins at all. Varicose veins, however, are a lot more likely to cause signs and symptoms of disease than a skin change from causes of C1 or C2. These symptoms cover a broad and diverse spectrum and are generally attributed to the positive pressure defects of reflux and obstruction.
Diagnosis of Varicose Veins
If the patient has advanced chronic venous insufficiency with or without skin changes and/or ulceration, further, more advanced studies and consultations with specialists may be required. An examination known as photoplethysmography utilizes a light probe to gauge vein function. This test helps in more accurately determining the cause of skin changes and ulceration and can provide an indication of the potential for ulcer healing, as this is affected by the possibility of any intervention improving underlying vein function. Deep vein problems, including obstruction, are best assessed using a venous CT scan or MRI. Finally, referral to a specialist such as a vascular surgeon or dermatologist may be required when the diagnosis is difficult or when the patient is considering varicose vein treatment options.
Diagnosis of varicose vein disease is largely based upon the patient’s symptoms and physical examination by a healthcare professional. Ultrasonography is also utilized to help confirm the diagnosis if a significant amount of vein disease is suspected. Duplex ultrasound is the gold standard. This is an easy, painless process that uses sound waves to examine the venous system and requires no special preparation. During the examination, the patient is asked to stand so that veins can be evaluated under conditions that simulate the hydrostatic load within the veins when the patient is up. This is important because the severity of varicose veins and the likelihood of treatment benefit are both determined to a significant extent by the effect of gravity on vein function.
Venous Ulcers and their Relationship with Varicose Veins
Similar to varicose veins, venous ulcers usually affect the lower extremities around the calf and the inner aspect of the ankle. Also like varicose veins, ulcers are more common in females. An understanding of the etiology of venous ulcers is essential in order to prevent recurrence. It is widely accepted that venous ulcers occur as a result of venous hypertension. It is thought that the hemostatic mechanism in the skin is disrupted by an increase in venous pressure. This results in red blood cells and other hemostatic products leaving the microvasculature and entering the dermal tissue. This in turn leads to pigmentation of the skin and dermatitis. Continuing hypertension will cause fibrosis around the capillary bed and inflammatory disruption of the capillary walls. This process will cause a reduced healing response to localized injury and is therefore thought to be the cause of how an ulcer forms, albeit from an injury of minimal significance. It is because of this mechanism that the location of the ulcer can be easily identified as a venous ulcer. More recently, it is thought that increased capillary permeability caused by high concentrations of white cell-mediated growth factors including VEGF are the primary cause of ulcer formation. High concentrations of these agents are known to occur in areas of skin that have supported ulcer formation.
What are Venous Ulcers?
Venous ulceration is a significant and increasingly prevalent medical problem which affects approximately 1-2% of the population at some time in their lives. Venous ulcers are caused by the sustained damage to the skin as a result of prolonged venous hypertension. This is usually due to incompetent valves within the deep venous system or the superficial system, but can be as a result of a combination of both. Chronic sustained venous hypertension leads to a process known as lipodermatosclerosis in which there is inflammation in the skin and subcutaneous tissues. This leads to fibrosis and the development of an ‘atrophie blanche’ appearance to the skin. Any subsequent minor trauma to the area can lead to skin breakdown and the formation of an ulcer. Ulceration is a huge burden on patients and healthcare systems; they cause pain, loss of mobility and have a significant impact on quality of life. It is estimated that they cost the NHS £400 million per year. Venous ulcers characteristically occur in the gaiter area (the area of leg from the knee to the ankle which is covered by socks) and are shallow with irregular margins. They often have a ruddy coloured base and produce little or no exudate. A significant proportion of ulcers become chronic and because of the relationship between duration of ulcer and probability of healing, many will remain unhealed for long periods. Healed ulcers have a high chance of recurrence with 70% of ulcers recurring within 5 years.
How Varicose Veins Contribute to Venous Ulcers
Turning to specific points mentioned in the CEAP classification, clinical grade C4 patients (i.e., those with significant skin changes without ulceration) have a 10% chance of developing a venous ulcer within one year. Those with an ulcer have a 15% chance of recurrence within three months and a 40-50% chance within one year, even with proper treatment of the underlying venous hypertension. A systematic review argues that the ideal treatment for patients with varicose veins and an ulcer is surgery. This may also be an effective measure to prevent ulceration in those with C4 disease.
It is now generally accepted that venous ulcers occur solely as a result of sustained venous hypertension and/or ambulatory venous hypertension. Likewise, an extensive review on the pathophysiology of venous ulcers explains that these ulcers result from minor trauma, often going unnoticed by the patient, to an area of already discolored skin. This triggers an inflammatory response involving cytokines, venous wall remodeling, and a breakdown in the balance between the hemostatic and fibrinolytic systems to favor fibrin formation. Fibrin cuffing around the microvasculature traps red cells resulting in hemosiderin deposition and white cell diapedesis. This in turn leads to lipodermatosclerosis and ultimately an ulcer. The healing time of the ulcer is dependent on how successfully the underlying venous hypertension is treated.
Venous ulcers develop as a result of sustained venous hypertension, flow reversal, and persistent white cell activation. The tissue fluid arising from these processes may cause an eczematous rash or lipodermatosclerosis before ulceration. It is thought that the high pressure around the ankle in cases of varicose veins causes the ulceration to occur around this site. Other factors that increase the risk of ulceration in varicose vein patients include obesity, previous deep vein thrombosis, and occupations requiring prolonged standing. It is apparent that varicose veins are the most common cause of venous ulcers and the CEAP classification provides a detailed account of the relationship between varicose veins and ulceration.
Identifying Venous Ulcers Associated with Varicose Veins
Both clinical and non-invasive studies confirm that most venous ulcers occur in the presence of calf muscle pump failure and/or previous deep vein thrombosis. The ambulatory venous pressure is raised in the majority of patients and there is often a history of ankle edema and skin changes. An APTT below the reference range is an independent risk factor for ulceration. It is hypothesized that in the presence of an abnormal coagulation system, fibrin is deposited within the microvasculature causing inflammation and ultimately resulting in tissue damage. The significance of varicose veins differs as an independent study has shown no correlation between superficial venous reflux and ulceration. This study concluded that superficial venous surgery was ineffective for the healing and prevention of venous ulcers. However, EVLT and stripping of trunkal varices is associated with a reduction of ulcer recurrence. This suggests that it is reflux and obstruction in the truncal system that is relevant to chronic venous insufficiency and ulceration.
An ulcer is defined as an area of tissue erosion that results in damage to the skin or underlying tissue. In the case of venous ulcers, the erosion is a result of extravasation of blood components into the tissue due to venous hypertension. This results in hemosiderin deposition, atrophie blanche, fibrin cuffing, and epidermal maceration.
Treatment and Prevention of Venous Ulcers
A person with a venous leg ulcer is cared for by doctors, nurses, and therapists. It is important that the underlying vein problem is treated to get the leg ulcer to heal. In many cases, when the ulcer is a certain age and in many simple cases, this will mean the use of compression bandaging to treat the underlying vein problem. In more complex cases, it may be necessary to refer a patient to a vascular surgeon. There are an increasing number of vascular surgeons who have an interest in treating patients with leg ulcers, and certain centers now have rapid access leg ulcer services. Once the ulcer is healed, it is important that efforts are made to prevent the ulcer from recurring. This usually means the use of compression stockings or support. In patients who have had more severe ulceration or whose ulcer has taken a long time to heal, it may be necessary to continue with nursing input in the form of maintenance bandaging to prevent ulcer recurrence.
Managing Varicose Veins to Prevent Venous Ulcers
High ligation and stripping is an older method of treatment that is still effective today. The process involves tying off the greater saphenous vein at the junction with the common femoral vein and removing the vein through a small incision in the groin. Although this was once seen as the gold standard, there is now more evidence to support the effectiveness of the minimally invasive treatments. As there can be complications such as DVT, it is not recommended for the elderly and those with comorbidities.
Endothermal ablation and foam sclerotherapy are minimally invasive procedures that have a very high success rate in the ablation of superficial reflux in varicose veins. The meta-analysis of the 2014 NICE varicose vein guidelines found that endothermal ablation had a 93% occlusion rate of the treated veins at 1 year, and foam sclerotherapy had a 90% occlusion rate at 1 year. However, it is thought that these rates are actually higher, as technological and procedural advances have been made since the studies were evaluated. These treatments only require a short time to recover, and even patients with venous ulcers can still be treated, significantly reducing symptoms and healing ulcers.
Pharmacological management is another method of treatment, with the most promising being venous-specific drug therapy. There is limited evidence for the effectiveness of a drug called Sulodexide, which is a compound of heparin and dermatan sulfate. However, the earlier ESCHAR trial showed good results, and it is still used in many countries today. Horse chestnut seed extract is another drug that is used and is thought to be an effective treatment, although it is not available on prescription and must be purchased by the patient. This is the same case for other drugs and supplements, so patients should be advised on the evidence and cost of each treatment before they decide to purchase them.
A Cochrane review in 2016 concluded that there was not enough evidence to assess the effectiveness of compression bandaging compared with no treatment or other dressing treatments for a venous ulcer. This may be due to the complex nature of venous ulcers and the lack of standardization of bandaging or assessment of healing. Therefore, further research would be needed to come to a more accurate conclusion on this topic. Although there is no clear evidence for the best method of bandaging, using compression wrapping on its own over a dressing and below knee compression stockings is still an effective way of abolishing edema from the leg.
There is no doubt that the primary goal in the management of varicose veins is to prevent the development of a venous ulcer. In addition, reducing symptoms for the patient is also important, so treatment is aimed at correcting the venous hypertension brought about by venous reflux. Graduated compression therapy, in the form of correctly applied below knee compression stockings with a pressure of 30-40mmHg, is something the patient should be encouraged to wear for the rest of their life. Compliance with wearing stockings can often be a problem for patients, and it is worth educating them about the fact that they are the most effective method in reducing symptoms and preventing ulceration.
Treatment Options for Venous Ulcers
Treatment choices for treating venous ulcers While moist wound healing has become commonly accepted as the primary treatment in the management of patients with venous ulcers, a wide variety of adjunctive therapies are used. These are supposed to correct the rate or effectiveness of ulcer healing. Compressive therapy is recognized as the primary adjunct in venous ulcer treatment. It is effective in reducing swelling and controlling the underlying pathology in venous ulceration when used efficiently. This can be done using bandaging techniques and is followed by the use of hosiery. Unna’s boot is considered to be effective in promoting wound healing, again through edema control. However, some patients find this unpleasant and it may not be tolerated if ulcer pain is high. Foam dressings useful in promoting healing in wounds with high amounts of exudate. This can be considered an effective method, but not a cost-effective one when compared with other types of treatment. Electro-mechanical therapy is slightly promising in terms of wound healing but is also not cost-effective. Recent emphasis has been placed on specific dressings and their role in healing. Alginate and hydrocolloid dressings are effective in terms of debriding the wound and absorbing excess exudate. Again, it may not be a cost-effective approach in comparison with uncomplicated compression. Honey has been found to have several beneficial properties when added to the wound. It has antibacterial properties and creates a moist wound healing environment that is conducive to recovery. However, it does not appear to have more benefit than certain dressings and is unlikely to be a preferred choice in terms of cost. Psychological support can be a significant factor in promoting patient adherence to treatment regimens, but there is currently no research suggesting that this directly affects ulcer healing.
Lifestyle Changes to Support Healing and Prevention
Recommencement of compression and the management of edema. Venous ulcers often occur in the presence of longstanding venous disease which has been marginally compensated by various self-management strategies. Healing of the ulcer usually necessitates treatment of the underlying reflux and venous hypertension, which are frequently invisible but are best assessed by Doppler ultrasound and are an important target for ablative or surgical treatment. Healing of the ulcer with compression can cause discomfort where there is arterial insufficiency, but in general, if the arterial circulation is adequate, healing will be enhanced by the use of compression of adequate pressure and type. Treatment may cause increased ankle swelling, and patients need to understand the difference between dependent and generalized edema and the fact that a major increase in swelling may reflect cardiac failure or renal dysfunction. Associated with this, there needs to be a clear explanation of the duration and expected milestones of treatment and readiness to accommodate review and changes to the treatment plan.
A comprehensive approach to ulcer management includes consideration of venous and other comorbid conditions, regular attention to the ulcer itself, and general medical care. Healing and recurrence are influenced by the combined effects of these strategies. Compression, the most effective approach to healing, often requires substantial adaptation to individual patient needs and may need to be combined with other methods to enhance adherence and to address specific barriers to healing. The need for long-term treatment to prevent recurrence often necessitates considerable innovation and persistence on the part of both patients and healthcare providers and a readiness to reconsider goals and strategies in the light of progress and problems.
