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Diabetes Watch

Current Concepts In Treating Venous Leg Ulcerations

July 2021

Venous leg ulcers (VLUs) typically occur due to damage to the valves inside the leg veins.1 Venous valves regulate the blood pressure inside the veins and allow the intra-venous pressure to drop or increase accordingly as you walk, sit, stand or lie down. Sustained venous hypertension occurs when the venous blood pressure inside your leg veins does not adjust as you move.2 The increase in venous blood pressure, coupled with venous insufficiency, can potentially cause ulcerations to form around the ankles. For patients with diabetes and VLUs, complications from each illness not only increase the risk of leg swelling and infection from the added stress, but these complications can also be more severe.

Understanding The Etiology, Impact And Characteristics Of VLUs

The etiology of the formation of venous leg ulcers is multi-factorial. Occurrence of ulcer formation can be a combination of genetic and environmental factors, theorized to be about a 70 to 30 ratio of environmental to genetic factors, respectively.3 We may be able to control outside environmental factors surrounding VLU formation, however the genetic component consists of certain genes that increase the propensity for easy vein distension and faultable venous valves which may break down more easily and quickly over time. This is a more difficult factor to treat/mitigate, albeit, the ability to modify or express more favorable genes is becoming easier and more readily available as knowledge evolves. These gene editing therapies are not quite as commercially available on such a small scale as to reduce instances of varicose veins or improve the competence of valves within the veins themselves.4 Because genetic components and therapy are a minor factor with marginal success thus far, behavioral changes present themselves as the best tactic to prevent VLU development.

Average VLU detriment on the world health care system today is unknown to date, but we will detail its effects on the United States health care system. Venous leg ulcers are responsible for more than half of all lower extremity ulcerations, affecting over one million Americans annually with an annual cost upward of $2.5 billion.5 Reasons for this large encumbrance on our health system include frequent mismanagement, leading to more harm than benefit to the patient from both a general health and cost/benefit perspective.

Current risk factors for the development of VLUs include, but are not limited to, obesity and varicose veins.6 Varicose veins are long, distended and tortuous leg veins that extend distally or downwards projecting from the inguinal groin region and travel down to the inside portion of the ankle or medial aspect of the leg and communicate with the foot and ankle. Additionally, a sedentary lifestyle, a history of smoking and blood pressure elevations in the venous pulmonary blood system can contribute to VLU development.6 VLUs typically manifest just proximal to the medial malleolus.7 They appear as shallow, irregularly shaped, punched out lesions with varying sizes and well-defined borders. VLUs are classically discolored or bluish with a purple tinge to them, often denoting a pooling of deoxygenated blood from the venous system.8 Along with gravity-dependent pooling, incompetent valves and the repetitive impact of smoking over time on blood vessels, venous leg ulcers typically have a high volume of proteinaceous exudate.8 That decaying, nitrogenous, protein-rich exudate produces noxious, foul smelling and appearing venous stasis leg ulcers.

One can easily determine the presence of infection clinically or by standard laboratory analysis. Incidence rate of infection in VLU is high because of the large output of protein-rich fluid, which serves as an ideal medium for bacteria to infiltrate, proliferate and subsequently seed to infection.

From our experience, if not appropriately treated, these infections can lead to significant increases in morbidity and mortality rates in the VLU patient population.

A rare but insidious outcome from a chronic VLU is malignant transformation into a form of squamous cell carcinoma.9 Although rare, transformation is plausible due to an insult to cells with high turnover (mitotic rates) surrounding venous leg ulcers, whether it be blood cells themselves or of the periwound skin. This type of transformation, or Marjolijn’s ulcer, is typically locally malignant, with no universally accepted treatment plan.10 However, the most widely recommended therapy is referral to a Mohs surgeon, a highly specialized dermatological specialist.11 The treatment plan may then vie for localized radical excision of ulcerated tissue often with one-to-two cm of margins and/or amputation to an extent, taking safety and functionality into consideration.12

What You Should Know About Optimal VLU Management

Proper management of VLUs should include a thorough evaluation of the patient’s vascular system. Untreated or undiagnosed venous disease may pose a threat to life and limb due to the development of venous thromboembolism (VTE), which can be broken down into either deep vein thrombosis (DVT) or pulmonary embolism (PE).13 Vascular surgery consultation is advisable to test the integrity of the superficial and deep venous system in the leg, foot and ankle in instances of longstanding venous disease. The vascular surgeon may monitor the integrity of valves and competency of the perforator veins which connect the superficial and deep venous networks utilizing venous duplex ultrasonography. If that does not provide definitive diagnostic information, they may choose to utilize venous plethysmography in the evaluation of a patient with a suspected venous leg ulcer. Other less commonly utilized venous imaging modalities may include selective computed tomography venography, magnetic resonance venography, contrast venography and/or intravascular ultrasound in patients with suspected venous leg ulceration if additional advanced venous diagnosis is required for thrombotic or non-thrombotic venous obstructions. The Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, revised venous clinical severity scoring (VCSS), and venous disease-specific quality of life (QOL) assessment are diagnostic criteria methods recommended by the Society for Vascular Surgery to classify the clinical characteristics of the venous ulcer.14

Current well-established treatment for VLUs centers around compression therapies and elevation, which remain the gold standard.15 Compression therapies are often utilized alongside pneumatic compression pumps, with multiple chambers to apply compression in a segmented fashion. These therapies work by increasing pressure around the areas of collected fluid in the lower extremity to overcome the incompetent non-functional valves. Traditional clinical practice treats the ulcer by making it wet if it’s dry, and conversely makes it dry if it’s wet. In addition, providers usually employ dressing changes that provide compression and absorption. The former assists with blood flow while the latter treats the large amount of exudate associated with VLUs.

Novel therapies for VLUs include sclerosing agents such as hypertonic saline, sodium tetradecyl sulfate, 1.0% sotradecol and chromated glycerin, with percutaneous variations of sclerotherapies utilizing an injectable foam form called terminal interruption of the reflux source(TIRS).16-18 TIRS therapy is aimed at temporarily reducing the venous hypertension at the local level, which promotes healing. TIRS therapy utilizes 1% sotradecol foam injected into a venous branch in close proximity to the ulcer bed under ultrasound guidance. Likely, more than one outflow source may be localized, however all targeted veins must have documentation of reflux and have continuity with the primary source.

Among other novel therapies is endovenous laser ablation (EVLA) of perforator veins, utilizing a diode laser with a wavelength of 1470 nm in order to prevent reflux of venous blood backwards through the deep to the superficial system to attenuate the massive fluid reflux of venous leg ulcers. The American Society of Vascular Surgery concluded that EVLA is a safe, effective and less traumatic method of ablating deficient perforated veins performed on an outpatient basis.19 This allows us to consider the EVLA technique as a successful method of eliminating reflux in perforated veins, rapid treatment of chronic venous ulcer (CVU), and a possible replacement for traditional surgical treatment.

Maintenance care of VLUs should involve exudative fluid absorbent dressings with multilayer segmental compression to force the fluid past these incompetent, non-functional venous valves only if there is no infection present. Clinical practice guidelines (CPGs) for vascular surgery recommends VLUs receive thorough debridement at their initial evaluation to remove obvious necrotic tissue, excessive bacterial burden and cellular burden of dead and senescent cells.20 These CPGs suggest additional maintenance debridement to maintain the appearance and readiness of the wound bed for healing. They also add that the health care provider may choose from a number of debridement methods including sharp, enzymatic, mechanical, biological or autolytic.21 More than one debridement method may be appropriate based on the characteristics of the wound.

However, compression therapies are not advisable in instances of infection to prevent further deep seeding of the infection in other parts of the body. Any or all instances of infection must be completely and totally resolved before compressive therapies may be initiated. A treating physician may also need additional input from an infectious disease physician to guide or target therapies towards a specific offending pathogen. The primary care physician may also wish to order fluid maintenance medications, such as diuretics, in order to remove some of the overall body fluid. Compression therapy is key to maintaining a healing state for venous ulcers and keeping legs healthy, in conjunction with patient maintenance of an active lifestyle by walking or doing calf pumps and toe-up exercises. It’s also a good idea to collaborate with physical and occupational therapists who can teach patients and caregivers the best ways to apply compression and techniques to stay active.22

Patients with venous disease should learn how to inspect their feet and legs for any changes, just as we educate patients with diabetes to do. They should avoid sitting or standing for extended periods of time. Smoking cessation is paramount because nicotine has direct adverse effects on oxygenation. Patients should strive to maintain a healthy weight, limit salt intake and stay hydrated.23 It’s also wise to help patients take accountability for their own care. When devising a care plan, help them set reasonable care goals based on their lifestyle choices, such as determining when they will elevate their legs, do exercises or start a smoking cessation plan.

In Conclusion

VLUs are a complex pathology with several treatment guidelines across specialties, which if not properly treated can lead to a myriad of poor outcomes for patients. A multidisciplinary approach is often the safest and most effective means for resolution of VLUs. Following resolution of VLU’s continued compression devices such as compression hose or socks are typically necessary to prevent re-occurrence as well after resolution of the VLU routine surveillance is recommended to monitor for any lingering physiologic effects. 

Dr. Love is a Diplomate of the American Board of Podiatric Medicine and a Fellow of the Academy of Physicians In Wound Healing. She is an Assistant Professor in the Department of Medicine at Temple University School of Podiatric Medicine in Philadelphia.

Dr. Kalabanka is a first-year resident at Catholic Health System-Sisters of Charity Hospital in Buffalo, N.Y.

Mr. Niewrzol is the Clinical Research Coordinator at Temple University School of Podiatric Medicine in Philadelphia.

1. Vasudevan B. Venous leg ulcers: pathophysiology and classification. Indian Dermatol Online J. 2014;5(3):366-370.

2. Raffetto JD, Ligi D, Maniscalco R, Khalil RA, Mannello F. Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J Clin Med. 2020;10(1):29.

3. Stana J, Maver U, Potocnik U. Genetic biases related to chronic venous ulceration. J Wound Care. 2019;28(2):59-65.

4. Shadrina AS, Sharapov SZ, Shashkova TI, Tsepilov YA. Varicose veins of lower extremities: Insights from the first large-scale genetic study. PLoS Genetics. 2019;15(4):e1008110- e1008110.

5. Nussbaum SR, Carter MJ, Fife CE, et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value Health. 2018;21(1):27- 32.

6. Barber GA, Weller CD, Gibson SJ. Effects and associations of nutrition in patients with venous leg ulcers: a systematic review. J Adv Nursing. 2018;74(4):774-787.

7. Gordon P, Widener JM, Heffline M. Venous leg ulcers: impact and dysfunction of the venous system. J Vasc Nurs. 2015;33(2):54-59.

8. Takahashi PY, Cha SS, Kiemele LJ. Six-month mortality risks in long-term care residents with chronic ulcers. Int Wound J. 2008;5(5):625-631.

9. Sîrbi AG, Florea M, Pătraşcu V, et al. Squamous cell carcinoma developed on chronic venous leg ulcer. Rom J Morphol Embryol. 2015;56(1):309-313.

10. Eliassen A, Vandy F, McHugh J, Henke PK. Marjolin’s ulcer in a patient with chronic venous stasis. Ann Vasc Surg. 2013;27(8):1182. e5-8.

11. Prickett KA, Ramsey ML. Mohs micrographic surgery. StatPearls. StatPearls Publishing. 2021.

12. Tchanque-Fossuo Cn, Millsop JW, Johnson MA, Dahle SE, Isseroff RR. Ulcerated basal cell carcinomas masquerading as venous leg ulcers. Adv Skin Wound Care. 2018;31(3):130- 134.

13. Franks PJ, Barker J, Collier M, et al. Management of patients with venous leg ulcers: challenges and current best practice. J Wound Care. 2016;25 Suppl 6:S1-s67.

14. Lurie F, Passman M, Meisner M, et al. The 2020 update of the CEAP classification system and reporting standards. J Vasc Surg Venous Lymphat Disord. 2020;8(3):342-352.

15. Nair B. Compression therapy for venous leg ulcers. Indian Dermatol Online J. 2014;5(3):378- 382.

16. Bianchi C, Cazzell S, Vayser D, Reyzelman AM, Dosluoglu H, Tovmassian G. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/ chorion membrane (EpiFix®) allograft for the treatment of venous leg ulcers. Int Wound J. 2018;15(1):114-122.

17. Granick MS, Baetz NW, Labroo P, Milner S, Li WW, Sopko NA. In vivo expansion and regeneration of full-thickness functional skin with an autologous homologous skin construct: Clinical proof of concept for chronic wound healing. Int Wound J. 2019;16(3):841-846.

18. Armstrong DG, Orgill DP, Galiano RD, Glat PM, Carter MJ, Zelen CM. Open-label venous leg ulcer pilot study using a novel autolologous homologous skin construct. Plastic Recon Surg Global Open. 2020;8(7):e2972-e2972.

19. Teo TK, Tay KH, Lin SE, et al. Endovenous laser therapy in the treatment of lower-limb venous ulcers. J Vasc Interv Radiol. 2010;21(5):657-62.

20. Tan MKH, Luo R, Onida S, Maccatrozzo S, Davies AH. Venous Leg Ulcer Clinical Practice Guidelines: What is AGREEd? Eur J Vasc Endovasc Surg. 2019;57(1):121-129.

21. Gethin G, Cowman S, Kolbach DN. Debridement for venous leg ulcers. Cochrane Database System Rev. 2015;2015(9):CD008599- CD008599. doi:10.1002/14651858. CD008599.pub2

22. Yim E, Kirsner RS, Gailey RS, Mandel DW, Chen SC, Tomic-Canic M. Effect of physical therapy on wound healing and quality of life in patients with venous leg ulcers: a systematic review. JAMA Dermatol. 2015;151(3):320-327.

23. McDaniel JC, Browning KK. Smoking, chronic wound healing, and implications for evidence-based practice. J Wound Ostomy Continence Nurs. 2014;41(5):415.

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