Skin Care & the Wound Clinic: Employing Nutrient-Rich Skin Care for the Improvement of Stasis Ulcers & Dermatitis

It has been estimated that 1% of individuals in the Western population are living with venous (stasis) leg ulcers and approximately 2.5 million Americans are experiencing chronic venous insufficiency (CVI), which can lead to stasis ulcers and dermatitis.^1,2 In fact, close to 20% of individuals living with CVI develop stasis ulcers³ that often require long-lasting rehabilitation resulting in a significant socioeconomic impact due to work incapacity and a substantially reduced quality of life.^2–6 CVI typically affects the lower legs due to insufficient blood flow in these extremities and is frequently experienced as a dull ache or pain and swelling that decreases when the legs are elevated.^3,4,7 

Risk factors for CVI include pregnancy, obesity, age, family history, and occupations requiring excessive standing.^3,5,8 Varicose veins are associated with CVI and chronic venous disease (CVD),⁹ of which CVI is a major component. CVD often occurs because the valves in the legs that are unidirectional become dysfunctional. This causes blood to collect in the lower legs instead of returning to the heart. Venous valve dysfunction results from genetic factors, trauma, blood clotting (thrombosis), or venous inflammation (phlebitis). Other factors that may lead to venous insufficiency include immobility and ineffective calf muscle pumping.^4,10 Decreased blood circulation associated with CVI results in decreased nutrients gaining access to the skin from the blood, which can result in weakening of the skin barrier and increased vulnerability to skin irritation, stasis dermatitis, ulcers, and infection.⁹ Evidence suggests 50% of ulcers in lower extremities result from stasis dermatitis, which has an incidence of approximately 6-20% in individuals older than 65-70.^10,11

This article will discuss how beneficial wound and skin care that utilizes small nutrient molecules (< 500 Daltons in size) capable of penetrating the epidermis can increase skin health and healing for patients living with stasis ulcers and dermatitis.

Stasis Ulcer Management & Prevention In The Clinic

When a clinician has identified that a patient’s skin may be compromised as a result of CVI or other circulatory problems, it’s important to incorporate therapies that address this issue to restore and maintain skin integrity while preventing breakdown and complications. It’s vital that therapies employed in the clinic are continued through any transitions in care that may occur, especially into extended care and homecare environments where there may be less opportunity for regular rehab monitoring by licensed clinicians.¹² 

Identifying skin care regimens that address the compromised nutritional status of the skin and are transferable across various care settings will be an important component in assuring adherence to the approved therapy.¹³ Some clinics are beginning to utilize specialty skin care kits that provide hospital-grade skin care products and protocols that can be easily acquired through retailers and incorporated in home-care settings.¹³ This is one method that has allowed providers to initiate care plans in a facility setting and continue the same quality care through the transition(s) while helping to maintain the nutrient status and integrity of skin with improved adherence to products and protocols.

Decreasing Inflammation, Oxidative Stress & Fibrosis 

Venous hypertension that is linked to CVI corresponds with increased shear stress (the tangential force produced by moving blood acting on the endothelial surface of veins).  Shear stress is thought to activate leukocytes and endothelial cells to produce and release inflammatory molecules including leukotrienes, prostaglandins, bradykinin, reactive oxygen species (ROS), and cytokines.^6,14 Increased venous pressure may result in increased dermal capillary permeability, allowing fibrinogen to leak out to pericapillary tissues. Fibrinogen is consequently thought to polymerize into fibrin and form a “fibrin cuff” around capillaries, trapping activated leukocytes.^2,3,9 Many of the small molecule ingredients found in select skin care products have potent anti-inflammatory activities to help decrease skin inflammation involved with stasis dermatitis. These include the polyphenols oleuropein, resveratrol, and epigallocatechin-3-gallate (EGCG) from olives, grapes, and green tea, respectively, as well as melatonin and L-glutathione.^15–19 In addition, dipotassium glycyrrhizate from licorice and avenanthramides in oats, aloe vera, and shea butter possess anti-inflammatory activities.^20–23 

Chronic scratching of inflamed skin can often lead to thickening of the skin (lichenification) in those living with CVI.⁹ Production of excessive ROS can result in oxidative stress along with increased inflammation, and fibrosis may develop in the dermis and subcutaneous tissue.² Various ingredients in the products also counteract oxidative stress, including oleuropein, resveratrol, and EGCG, as well as melatonin and L-glutathione.^{15,17,24–26}

Reducing Risk of Stasis Ulcers & Cellulitis

Leukocyte adhesion and inflammation contribute to injury and the development of venous ulcers. The expression of inflammatory mediators and matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, has deleterious effects on the vein wall, venous valve, and endothelium, including destruction of the dermis.^6,14 In fact, increased expression and levels of MMPs have been associated with stasis ulcers and dermatitis.^6,14,27 In addition, studies have shown the expression of MMPs is altered during CVI and is associated with spongiosis and structural skin abnormalities.^14,27 Interestingly, oleuropein has been shown to down-regulate levels of MMP-2 and MMP-9 in human endothelial cells.²⁸ Resveratrol has been shown to reduce MMP-2 activity in human microvascular endothelial cells²⁹ and EGCG was found to inhibit vascular permeability in human microvascular endothelial cells via the suppression of MMP-9.³⁰ Melatonin was also found to inhibit MMP-9 expression and activity in human endothelial cells.³¹ 

In addition to inflammation, edema associated with CVD may predispose individuals to cellulitis (bacterial infection of the dermis and subcutaneous fat) due to the skin becoming taut, fragile, and more easily disrupted by minor trauma.³² Cellulitis can be very challenging since several microbes, including methicillin-resistant Staphylococcus aureus (MRSA), have become resistant to antibiotics. One important reason for the antibiotic resistance of some microorganisms is related to their ability to produce biofilms.³ The microbes in biofilms frequently act together to cause chronic infections, including within ulcers.³³ Several ingredients that are included in specialized skin care kits¹³ have activities against microorganisms (including against biofilms). Resveratrol has been reported to inhibit MRSA biofilms.³⁴ EGCG was shown to have antimicrobial effects against Pseudomonas aeruginosa³⁵ and S. aureus that included activities against biofilm formation.³⁶ EGCG has been shown to disrupt the communication signaling required for Escherichia coli to form biofilms.³⁷ Oleuropein has been shown to inhibit the growth of several bacterial strains including S. aureus.³⁸ Another important natural antioxidant found in these kits, melatonin offers antimicrobial effects against MRSA and antibiotic-resistant P. aeruginosa.³⁹

Promoting Wound Healing, Strengthening Skin Barrier

CVI-related stasis ulcers and skin breakdown can easily become chronic wound and skin issues. The products included in the specialized skin care kits referenced in this article provide optimal skin nutrition to enhance wound healing and strengthen the skin barrier. Oleuropein has been shown to reduce transepidermal water loss, indicating its ability to increase skin barrier function.⁴⁰ 

Evidence also demonstrates melatonin has a stimulatory role in building and maintaining the epidermal barrier.⁴¹ Various ingredients in the skin care kits have been found to enhance wound healing, including oleuropein, which was discovered to improve wound healing in an aging model.⁴² Resveratrol has been shown to reduce the size of some ulcers.⁴³ EGCG was found to accelerate keratinocyte differentiation and wound healing,⁴⁴ and melatonin was shown to accelerate the process of wound repair in full-thickness incisional wounds.⁴⁵ In addition, L-carnosine stimulated wound healing in an incision wound model⁴⁶ and L-glutathione was shown to be beneficial for ischemic wound healing.²⁴ Moreover, Centella asiatica⁴⁷ and one of its main components — asiaticoside⁴⁸ — have important wound healing activities. Dipotassium glycyrrhizate is known to inhibit hyaluronidase and protect hyaluronic acid,⁴⁹ which plays an important role in wound healing.⁵⁰ 

Improving Compression Therapy & Rehabilitation

Dysfunctional calf muscle pumping may either exacerbate or cause venous hypertension that can lead to stasis dermatitis and slow-healing ulcers.^3,51 In fact, the calf muscle has been called the “peripheral heart” due to its function in enhancing venous return from the lower extremities.¹ Restricted movement of the ankle joint may cause reduced calf muscle contractions and calf muscle pumping. Supervised physical exercise focused on ankle joint mobility has resulted in decreased stasis ulcers and increased healing in some patients with stasis ulcers.³ Most notably, compression therapy, including the use of compression stockings, is the standard treatment for CVI and stasis ulcers that substantially increases the likelihood of rehabilitation. By opposing venous pressure, compression therapy decreases edema and promotes venous and lymphatic return.^5,52 Surprisingly, some of the benefits of compression therapy have also been linked to its ability to reduce excessive levels of MMPs, including MMP-9.⁵³ With the risk of swelling, it’s important not to occlude skin. A nonocclusive silicone/dimethicone-based product is preferred over occlusive petrolatum-based products.¹³ Application of a silicone barrier can help compression stockings move easily into place, preventing skin irritation from friction that can damage fragile skin. Also included in the kit is the Clean N Moist skin protectant spray, which is perfectly pH balanced to ensure the most fragile skin is gently cleansed without causing irritation. Individuals living with stasis ulcers and dermatitis can easily apply the products to promote stasis ulcer healing, reduce the risk of infection, and help decrease stasis dermatitis. The products within the kit contain antioxidants, vitamins, and amino acids that also strengthen the skin barrier and help prevent stasis ulcers.  Certified organic and pharmaceutical-grade ingredients ensure pesticides and contaminants are excluded from the products.

Summary

CVI, stasis ulcers, and dermatitis involve inflammation and oxidative stress. They often lead to other serious complications, including cellulitis. Understanding the impact of impaired circulation on the integrity of overlying skin can help clinicians adapt care plans to better address the various physiological manifestations of impaired circulation in the skin. When initiating a care plan in the wound clinic, it’s essential to select one that can be continued across all care settings, including at home. Appropriate selection and incorporation of products and protocols can be a determining factor in properly addressing compromised skin and preventing further complications. Utilizing specialized skin care kits can be an effective method to continue care plans across all settings while utilizing appropriate products that address the underlying issues of impaired circulation and venous insufficiency. 

D. Elizabeth McCord, senior researcher at McCord Research, Coralville, IA, is a renowned biochemist who has worked in the field of skin and wound care for more than 30 years. She has been awarded six patents and two medical devices in the field. She has more than 60 health products marketed globally. She previously commercialized wound and skin care products under the Remedy^® Olivamine^® brand. Kyle D. Hilsabeck is vice president of pharmaceutical affairs at McCord Holdings and licensed by the Iowa Board of Pharmacy. He completed bachelor’s degrees in biology and biochemistry at Wartburg College before earning his doctorate from the University of Iowa College of Pharmacy. Upon graduation, he completed a community pharmacy residency through the University of Iowa and taught courses for the University of Iowa College of Pharmacy on nutritional supplements and dermatology therapeutics. Nancy B. Ray is science officer at McCord Research. She currently writes articles and provides presentations concerning diabetes, skin care, and other health issues for McCord Research to advance skin care and wound healing awareness. She received her PhD in biochemistry and biophysics at Oregon State University and was a postdoctoral fellow at the National Institutes of Health, Harvard University, Dana-Farber Cancer Institute, and the University of Iowa. She also earned bachelor’s degrees in chemistry and microbiology from the University of Montana.