Are You Confident of the Diagnosis?

  • What you should be alert for in the history

Leg ulcers are skin lesions with full-thickness loss of epidermis and dermis on the lower extremities. Among a wide variety of etiologies for chronic leg ulcers, four common types are venous stasis ulcers, arterial ulcers, diabetic neuropathic ulcers, and pressure ulcers. By definition, chronic leg ulcers last greater than 6 weeks. Acute ulcers such as traumatic wounds undergo normal healing in healthy patients without the need for further treatment. As a result, only chronic leg ulcers will be discussed here.

  • Characteristic findings on physical examination

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Patients with venous leg ulcers commonly complain of swelling and aching of the legs that is worse at the end of the day and improves with leg elevation. The medial lower leg is the most common site. The borders of venous ulcers are typically saucer-shaped, initially with a shallow wound base. The surrounding skin often exhibits pitting edema, induration, hemosiderosis, varicosities, lipodermatosclerosis, atrophie blanche, and/or stasis dermatitis (Figure 1).

Figure 1.

Venous leg ulcer

Patients with arterial ulcers often have a history of peripheral vascular disease, atherosclerosis, and/or smoking. They have signs and symptoms that include rest pain, cool extremities, skin pallor, weak pulses, and claudication. Elevation of the legs frequently results in exacerbation of the pain and skin pallor.

Arterial ulcers typically have a punched-out appearance and often occur distally.

Diabetic foot ulcers are another major type of lower extremity wound. Diabetics with Charcot arthropathy, or musculoskeletal abnormalities of the foot due to diabetic neuropathic changes, can develop a thickened callus on the plantar surface where repeated pressure occurs during ambulation. Ultimately the skin breaks down, leading to ulcer formation.

Diabetics with an insensate foot have lost one form of the body’s protective mechanism against trauma. Thus, the development of sensory neuropathy over time increases their chances of developing a wound on the plantar foot.

Diabetic foot ulcers often have a callused border with sloping edges and a deep base that may go down to muscle and bone. They are commonly located on the first metatarsal joint or the heel of the foot (Figure 2).

Figure 2.

Diabetic heel ulcer

Pressure ulcers occur most commonly in individuals who have decreased mobility including the elderly, bedbound patients, paraplegics, and incontinence moistening the skin as well as those with poor healing due to malnutrition.

Pressure ulcers are confined to locations where impaired blood supply and tissue malnutrition occur as a result of prolonged pressure, friction, or shear. Skin overlying bony prominences such as the maleoli, hips or sacrum is especially vulnerable. Pressure ulcer development begins with nonblanching erythema of intact skin and can progress to full-thickness skin loss with extensive destruction of underlying tissues.

  • Expected results of diagnostic studies

Venous leg ulcers: The history and physical exam are often sufficient to make a diagnosis for ulcers of venous etiology. However, confirmation with a venous reflux study to evaluate the presence of reflux in the superficial, deep or perforating veins in the leg is helpful especially if there is a localized lesion which might be amenable to surgery.

Arterial ulcers: Assessment with ankle-brachial index (ABI), digital brachial index and Doppler ultrasound for distal pulses can confirm a compromised blood supply to the limb. The ABI in affected legs is usually less than 0.8 and digital pressures are lower than 50 mmHg.

Diabetic foot ulcers: The Weinstein 10g monofilament test can be used to assess the presence of sensory neuropathy. An MRI is often recommended when there are signs and symptoms of infection to rule out osteomyelitis, since amputation is a significant complication of diabetic foot ulcers.

  • Diagnosis confirmation

The differential diagnosis for leg ulcers also includes less common conditions, such as Marjolin’s ulcer, pyoderma gangrenosum, ulcerative cutaneous vasculitis and ulcerative necrobiosis lipoidica, which are discussed in the last section on “Unusual clinical scenarios to consider in patient management.”

Who is at Risk for Developing this Disease?

Risk factors for venous stasis leg ulcers include obesity, prolonged standing, and a genetic predisposition. Patients with a history of idiopathic deep venous thromboses or pulmonary embolus, especially at a young age, frequently have an underlying genetic thrombophilia. These inherited defects are best remembered by the mnemonic STALL Coagulation and include protein S deficiency, proThrombin mutation, Antithrombin III deficiency, Lupus anticoagulant antibodies, factor V Leiden mutation, and protein C deficiency, in addition to hyperhomocysteinemia.

The risk for lower extremity arterial ulcers is increased in smokers, diabetics, obese and elderly patients, and individuals with hypertension, hypercholesterolemia, homocystinemia, and evidence of arterial disease at other sites. Lower extremity arterial disease increases with age and is higher among men. There is significant overlap between individuals with coronary artery disease and lower extremity arterial disease. In the young adult population, arterial ulcers are typically due to premature atherosclerosis or thromboangiitis obliterans.

Diabetics have a 15% to 25% lifetime risk of developing a foot ulcer. Diabetic foot ulcers have a high recurrence rate, frequently lead to amputation, and are associated with a high mortality. The Charcot neuropathic foot of diabetes is characterized by joint deformities that also predisposes the patient to secondary ulceration. Infection is a frequent complication of diabetic foot ulcers. Lower extremity amputation is 28 times greater in diabetics compared to non-diabetics. Furthermore, the mortality rate is 20-50% at three years following the amputation.

Pressure ulcers occur most often in patients who are immobile, paralyzed, elderly or malnourished. The Braden Scale is a scoring system used to predict the risk of developing a pressure sore. It is divided into six risk categories: sensory perception, moisture, activity, mobility, nutrition, and friction and shear.

The best possible interpretation is a score of 23, and the worst is a 6. The Braden Scale has been correlated with levels of risk based on the percentage of patients expected to develop ulcers: 15 to 18, at risk; 13 to 14, moderate risk; 10 to 12, high risk; and 9 or below, very high risk. The recurrence rates of pressure ulcers may be as high as 90%.

What is the Cause of the Disease?

Venous insufficiency is responsible for approximately 75% of lower extremity ulcerations. Risk factors can increase pressure and reverse flow in the leg veins, causing structural changes in the valve leaflets and vein walls. This leads to physical distortion and distention as well as transduction in endothelial cells which promote inflammatory and a prothrombotic phenotype.

Venous leg ulcers are the most severe manifestation of chronic venous incompetence, producing venous hypertension and turbulent flow related to reflux through incompetent valves in the lower extremities. Approximately 80% of the adult population have some degree of venous disease, manifested by telangiectases, varicose veins, edema, stasis dermatitis, lipodermatosclerosis and ulcerations.

Arterial ulcers result from inadequate blood supply to the skin. Arterial insufficiency can be due to atherosclerotic or thromboembolic disease that causes skin infarction and ulcer formation. In the young adult population, arterial ulcers are typically due to premature atherosclerosis involving the peripheral circulation. Ulceration is believed to result from progressive occlusion leading to cellular ischemia and necrosis.

Minor trauma can also produce a nonhealing wound due to the inability of damaged vessels to meet the oxygen demands associated with tissue repair. External occlusive pressures on bony prominences such as the heel or lateral foot can further compromise blood supply to these locations, leading to the formation of arterial ulcers.

Multiple overlapping factors can lead to a diabetic foot ulcer. Metabolic abnormalities from diabetes cause vascular and neuropathic changes. Diabetes causes ischemia from microvascular and macrovascular disease with reduced distribution of blood to skin surfaces in need of healing.

Peripheral sensory neuropathy results in loss of protective sensation that increases the risk of acute trauma or repetitive injury to an existing ulceration. Motor neuropathy affects the muscles required for normal foot movement, altering the distribution of forces during walking and causing reactive thickening of skin, or callus, at sites of abnormal load. Ischemic tissue necrosis beneath the callus leads to breakdown of skin and subcutaneous tissue, resulting in a neuropathic ulcer with a punched-out appearance.

Pressure ulcers are caused by prolonged pressure, friction, or shear of the skin surface leading to impaired blood supply and tissue malnutrition. Tissue compression exceeding the capillary filling pressure of 32 mmHg that lasts longer than 2 hours can cause local ischemia and necrosis.

The most widely accepted classification system for pressure ulcers is described by the National Pressure Ulcer Advisory Panel. This four-stage classification is designed only to describe the depth of a visible ulcer at the time of examination.

Stage I represents intact skin with signs of impending ulceration: blanching and/or nonblanching erythema, warmth, and induration. It is especially important to recognize and effectively treat Stage I disease because lesions can resolve with proper care in 5-10 days.

Stage II ulcers present as a shallow ulcer with pigmentation changes. They are usually reversible if treated appropriately.

A Stage III ulcer represents the typical pressure ulcer that appears as a necrotic, foul-smelling crater. It has full-thickness skin loss with extension through subcutaneous tissue, but not underlying fascia.

Stage IV ulcers represent full-thickness skin and subcutaneous tissue loss, with ulcer penetration into the deep fascia, resulting in involvement of muscle, bone, tendon, or joint capsule.

Systemic Implications and Complications

Chronic wounds contain persistent microbial populations which may function as benign colonizers or pathogenic impediments to wound healing. Bacterial populations in wounds are usually polymicrobial and include both aerobic and anaerobic organisms such as Staphylococcus, Pseudomonas, Streptococcus, Escherichia, and Bacteroides.

When growth and death of microbes are kept in balance by host defenses, a wound is considered to be colonized. Wounds become clinically infected when host defenses are overwhelmed. These wounds often demonstrate increased erythema, edema, warmth, pain, drainage, malodor and wound breakdown. Wound infection may also manifest as a failure to heal.

The concern for cellulitis appears when infection has spread to the contiguous skin or soft tissue with clinical signs of erythema, induration, warmth and tenderness. Systemic signs, such as fever, chills, and leukocytosis may suggest progression to bacteremia or septicemia. Osteomyelitis is an important complication, particularly for diabetic foot ulcers, and may eventually necessitate amputation.

Work-up of a wound infection consists of obtaining curette samples and less preferably swabs of the wound slough to culture for the offending microorganism(s). Wounds can be treated topically with antimicrobial dressings that contain silver, iodine, or gentian violet; or systemically with oral antibiotics based on the sensitivities of the bacteria cultured.

Cellulitis or soft tissue infections are always treated with oral antibiotics. If osteomyelitis is suspected, an MRI with and without contrast, indium-tagged white blood cell scan, or triple phase bone scan can be performed. Patients who demonstrate image-positive osteomyelitis should be treated with 6 weeks of the appropriate oral or intravenous antibiotics. Debridement is useful in cases where there is a significant amount of necrotic tissue. If the bone infection does not resolve with prolonged antibiotic coverage, amputation of the affected limb may be required.

Treatment Options

Treatment options are summarized in the Table I.

Table I.
Medical (Topical) Wound dressings (films, hydrogels, hydrocolloids, alginates, foams, tissue-engineered skin substitutes)
Compression therapy
Medical (Systemic) Systemic antibiotics
Surgical Conservative sharp debridement
Physical Pressure dispersion or off-loading
Negative pressure wound therapy
Hyperbaric oxygen treatment

Optimal Therapeutic Approach for this Disease

Appropriate therapeutic choice depends on many factors. Different wound etiologies require different management approaches to counteract the cause of the ulcer.

The mainstay of treatment of venous ulcers is compression therapy, which counters the impact of reflux, reduces blood vessel diameter and pressure, and decreases the release of inflammatory cytokines and leakage of fluid causing edema.

Pressure dispersion is the cornerstone for management of the diabetic foot ulcer, and includes devices such as off-loading shoes and contact casting to redistribute the weight off the ulcer site.

Management of arterial ulcers involves revascularization of the affected limb.

Pressure ulcers on the legs which are typically located on the ankle can be prevented and treated with protective foam dressings.

Adjuvant therapy for leg ulcers is wide ranging. Appropriate treatment choice depends on the local condition of the wound, which may greatly impact the healing process. Various conditions include the moisture balance of the wound, the nature of the wound base, the vascular supply and the general health and underlying disease status of the patient. Local conditions can evolve during the natural course of an ulcer and/or vary significantly among different wounds.

There are several important wound management principles that can be applied to the treatment of any wound regardless of its etiology: moisture and occlusion, debridement, infection control, compression, pressure dispersion, negative pressure, and hyperbaric oxygen. These principles and related treatment modalities will be discussed in greater detail in the remainder of this section, with particular attention to their appropriate use in different types of wounds.

  • Moisture and occlusion

It is important to understand the principles of moisture and occlusion when choosing the appropriate wound dressing. Moisture in a wound prevents dehydration of delicate new epithelial cells and allows their migration and survival on the wound. While moisture is essential for proper healing, excessive wetness on the wound bed can be problematic.

Highly exudative wounds may cause maceration to the surrounding skin, resulting in tissue that appears soft, white and friable. The macerated skin has a tendency to breakdown, which can delay wound healing or make the wound deteriorate further. In addition to keeping moisture in the wound, occlusion works for other reasons as well: protection from external contamination and physical trauma, stimulation of collagen synthesis, creation of a hypoxic environment to promote angiogenesis, and pain relief.

Wound dressings constitute the most basic wound management strategy. They are used to manipulate the local environment to optimize wound healing. An important goal is balancing the moisture content at the wound base. Thus some dressings are used for absorbency of excess exudates, while others provide moisture for a dry wound base.

Since wounds evolve over time, the appropriate dressing will need to be changed to suit the particular condition of the wound. The major categories of wound dressings include: gauze, film, hydrogel, hydrocolloid, alginate, and foam. In conjunction, barrier creams, ointments, and other periwound protectants are frequently used because skin around a wound is vulnerable to damage from wound-associated inflammation, excess moisture, wound fluid proteases, dressing adhesives, and contact allergic reaction.

Plain dry cotton gauze has historically been one of the most popular wound dressings, yet it has several shortcomings. Dry gauze promotes desiccation of the wound and will stick to the wound base causing pain and trauma during dressing changes. Dry gauze also has a limited ability to protect against external contamination, especially when wound exudate has saturated the entire thickness of the gauze.

Films are transparent, adhesive, thin and semi-occlusive, permitting exchange of oxygen and water vapor, but not of liquid and bacterial contaminants. Films should be reserved for wounds with minimal exudate. Transparent films allow visualization of the wound so dressing changes may occur less frequently and only as needed.

Hydrogels are best suited for dry wounds or those with limited exudate. They are ideal for patients with painful wounds, since they can be applied and removed with minimal trauma to the wound. Patients often experience pain relief with hydrogel, likely because of their cooling effect. Hydrogels are water-based products available in amorphous gel and sheet forms (e.g. DuoDERM Hydroactive gel and Xcell sheet).

In contrast to the fluid-donating hydrogels, hydrocolloids maintain a moist healing environment by absorption of excess exudate forming a hydrophilic gel covering. Hydrocolloids such as DuoDERM CGF are ideal for low to moderate exudative wounds. They have a relatively long wear time and protect against shear force.

Hydrocolloids should not be used for wounds with too much exudate because the large amount of moisture will cause the dressing to separate or cause periwound maceration. In addition, hydrocolloids have a tendency to produce a brown, malodorous drainage, which can be mistaken for infection and be troubling for the patient.

Fibrous dressings, including alginates and hydrofibers, have very high absorbency and are used for wounds with heavy exudates. Alginates are derived from brown seaweed and can hold up to 20 times their weight.

Alginates require moisture to function, thus they should not be used over dry wounds. Because of a tendency to absorb fluid across the entire surface of the dressing (lateral wicking), some alginates may cause periwound maceration if they overlap with normal skin, therefore, alginates should be cut to the shape of the wound bed. Select Silver, which can be cut into strips and used to pack the tunnel in deep wounds, helps to wick the drainage out of wounds. A unique advantage of some fibrous dressings such as Aquacel Ag is that they are inherently hemostatic and can be used to control minor bleeding.

Foam dressings protect against shear force, provide thermal insulation, and offer different levels of absorption depending on their thickness. They are particularly useful to prevent and treat pressure ulcers on the ankles and heels by protecting the skin from repetitive trauma.

Tissue engineered skin substitutes are dressings comprised of living cells, such as fibroblasts and keratinocytes, in a scaffold, or natural or synthetic extracellular matrices. The goals of skin substitutes include wound coverage, complete wound closure, reduced healing time, reduced pain, reduced post-operative contracture, and improved aesthetics and functional abilities.

Dermal skin substitutes help prevent wound contraction and offer greater mechanical stability. Examples include bovine collagen and Dermagraft, a cryopreserved dermal substitute composed of fibroblasts that is indicated in the treatment of full thickness diabetic foot ulcers greater than 6 weeks duration.

Combined dermal and epidermal skin substitutes include Apligraf, an allogeneic, bilayered skin substitute containing both keratinocytes and fibroblasts in a bovine collagen I matrix. Multi-centered prospective, randomized clinical trials have demonstrated that Apligraf, in conjunction with standard compression therapy for venous leg ulcers and standard diabetic foot care for diabetic foot ulcers, is well-tolerated and more efficacious compared to standard of care.

Becaplermin is a recombinant human platelet-derived growth factor isoform BB which promotes chemotactic recruitment and proliferation of cells involved in wound repair. This topical growth factor is approved for the treatment of chronic neuropathic lower extremity diabetic ulcers.

  • Debridement

Debridement is the removal of bacterial biofilm, exudate, and nonviable, unhealthy tissue which may appear as slough or eschar, from the wound bed. There is no question that adequate debridement is necessary to improve healing because it enables normal, well-vascularized tissue to proliferate within the wound while reducing the bacterial burden and risk of wound infection. Callus, or hyperkeratosis at the rim of the wound, frequently seen in neuropathic ulcers also requires debridement.

Debridement converts chronic wounds into acute wounds which improves ulcer bed perfusion and activates the acute wound healing response. There are a wide range of removal techniques which include surgical, conservative sharp, wet-to-dry, autolytic, enzymatic, maggot, high-pressure fluid irrigation, and ultrasound mist therapy.

Conservative sharp debridement is the most rapid and precise method and is performed using a curette, scalpel, forceps or scissors. Sharp debridement can be used in venous, diabetic, and pressure ulcers, but caution should be exercised with arterial ulcers because ischemic tissue tends to desiccate after debridement, potentially causing ulcer enlargement.

Autolytic debridement is a gentle process that involves rehydrating the slough and necrotic tissue in a wound to aid separation from healthy tissue. Moisture-donating dressings or the application of ointments or creams under occlusion provide a moist environment for autolytic debridement to occur.

Enzymatic debridement uses ointments containing enzymes that break down the collagen and fibrin in wound exudates and necrotic tissue. It may also take several weeks. Examples include urea and collagenase (Santyl). Care should be taken to avoid application on the normal skin surrounding a wound.

  • Infection control

Oral antibiotics are selected based on the sensitivities of cultured microorganisms from the wound. Commonly prescribed oral antibiotics include amoxicillin for Gram-positive bacteria, trimethoprim-sulfamethoxazole for MRSA, fluoroquinones for Pseudomonas, and metronidazole for anaerobic organisms. Anaerobic bacteria are typically difficult to culture, but exude a distinctive foul odor from the wound. Corynebacterium and coagulase-negative Staphylococcus are normal skin flora and do not need to be treated.

Patients who have systemic signs of infection require hospital admission, blood cultures and intravenous antibiotics.

Topical cleansers decrease the bacterial burden in chronic wounds. Antiseptics are chemical agents that are broadly toxic to microbes. Commonly used topical antiseptic solutions that should not be used on chronic wounds include hydrogen peroxide and povidone-iodine, as they are also toxic to human tissue and prevent re-epithelialization of the wound. Rather, gentle soap and water is sufficient to clean wounds.

Other antiseptic preparations may be beneficial in appropriate situations. For example, a modified Dakin’s solution at a concentration of 0.025% sodium hypochlorite elicits antimicrobial effects without harming human tissue. Antiseptic dressings are also available and include Mesalt and Xeroform. Mesalt is a hypertonic sodium chloride-impregnated gauze that is highly absorbent and discourages bacterial growth as well as inhibits overexuberant granulation tissue formation. Xeroform is impregnated with 3% bismuth tribromophenate in petrolatum. It is less adherent than plain gauze.

Topical dressings that contain ionic silver are believed to be effective against bacteria in wound biofilms. Silver ions have efficacy against Gram-negative bacteria and antibiotic resistant organisms like MRSA and vancomycin-resistant Enterococcus (VRE). Disadvantages of silver products include potential irritation or discoloration of the surrounding tissues (argyria).

Cadexomer iodine is the active ingredient in Iodosorb gel and Iodoflex. The brown paste-like compound turns white corresponding with loss of bactericidal activity after extended use, indicating the need for a new application.

Other topical antimicrobial compounds utilized in wound care include mupirocin ointment which is particularly effective against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), metronidazole gel, cream or lotion, which provides good anaerobic coverage, and silver sulfadiazine 1% cream commonly used on burn wounds. Neomycin and bacitracin are typically infrequently used because of their potential to induce contact sensitivity.

  • Compression therapy

Compression therapy is considered first-line treatment for venous leg ulcers, and is also used for other wounds associated with the presence of edema and inflammation. Compression reduces edema and stasis by decreasing distention in superficial veins and assisting the calf muscle pump in venous return. It also stimulates healthier granulation tissue.

The use of compression is not without risk in patients with arterial disease, which may result in ischemia due to impaired blood supply. As a result, arterial insufficiency must first be ruled out by obtaining vascular studies for arterial-brachial index (ABI) or great toe pressure. A normal ABI is in the range of 0.8 to 1.2, and an acceptable great toe pressure is above 50 mmHg.

If a patient feels significant pain or discomfort while under compression, we instruct the patient to cut off the bandage at home. Uncompensated congestive heart failure is also a relative contraindication to compression therapy since the intervention mobilizes fluid from the legs and increases the intravascular volume.

Various forms of compression exist, ranging from multi-layered bandages to stockings. The optimal pressure to overcome venous hypertension and prevent capillary exudation is generally thought to be an external pressure of 35 to 40 mmHg at the ankle.

The Unna boot is a commonly used compression bandage, consisting of a zinc oxide-impregnated gauze wrap applied over the skin from the base of the toes to the popliteal flexure, covered with a layer of soft cotton, and wrapped with an elastic bandage that supplies compression. The zinc oxide protects the periwound skin and is thought to also enhance wound re-epithelialization and decrease inflammation.

Compression boots are typically left in place for a week, though they may need to be changed more frequently if the wound is especially exudative. Proper application of an Unna boot to supply the appropriate degree of pressure requires training and experience.

The tensile strength of a newly healed wound is low. As a result, it is important to continue compression, frequently at a lower pressure with stockings, for an additional 6 weeks. In addition, long term use of compression stockings will help to prevent recurrence or new ulcers from forming. Patients with venous disease require long term compression even after the ulcer is healed. We usually recommend below the knee stockings of 30 mmHg pressure or above.

  • Pressure dispersion

Offloading, or pressure dispersion, works by spreading the pressure forces over a wide area in order to reduce pressure over the at-risk or previously ulcerated area. Offloading devices are important in the prevention and treatment of diabetic foot ulcers.

Common methods to offload the foot include the following: bedrest, wheelchair, crutch-assisted gait, total contact casts, removable cast walkers, half-shoes, therapeutic shoes, custom splints, felted foam or heel lift devices, wheelchair cushions, and specialty beds including air loss beds and alternating pressure beds.

Although theoretically effective and frequently prescribed, crutches, wheelchairs and bed rest rarely work in practice for diabetic patients. Crutches often cause additional pressure to be applied to the contralateral limb, thus putting it at risk for ulceration. Wheelchairs are effective pressure reduction devices, but for many diabetic foot ulcer (DFU) patients, their homes are not designed to accommodate the bulkiness of wheelchairs. Compliance with bed rest is often difficult.

The gold standard for achieving pressure redistribution for diabetic foot ulcers is by total contact casting. The total contact cast (TCC) employs a well-molded, minimally padded cast that maintains contact with the entire plantar aspect of the foot and lower leg. The intimate fit of the cast material to the plantar surface of the foot increases the plantar weight bearing surface area to help distribute the plantar pressure from one or two distance areas to the plantar foot as a whole.

TCC is quite effective in treating the majority of non-infected, non-ischemic plantar DFUs, with healing rates ranging in the 75% success rate over the course of 5 to 7 weeks.

  • Negative pressure

Negative pressure wound therapy (NPWT), or vacuum-assisted closure (VAC), devices consist of a fenestrated evacuation tube embedded in a foam dressing and covered with an airtight film dressing. The tube is attached to a vacuum source. Sub-atmospheric pressure of -125 mmHg (with a range of -50 to -200 mmHg depending on the nature of the wound) is applied in a continuous or intermittent manner. A canister is attached to the vacuum pump to collect the excess wound fluid.

NPWT dressings hasten wound healing by maintaining a moist environment, removing wound exudates, reducing bacterial loads, increasing local blood flow and granulation tissue formation, and applying mechanical pressure to promote wound closure. Another potential mechanism is that “microstrain,” or cell stretching, stimulates cell division and proliferation in the presence of soluble mitogens, whereas retracted cells remain quiescent.

The United States Food and Drug Administration (FDA) most recently expanded the approved indications for NPWT devices, which now include chronic, acute, traumatic, sub-acute, and dehisced wounds, flaps and grafts, pressure ulcers, venous ulcers, and diabetic ulcers.

NPWT dressings are not appropriate for ischemic wounds because they may cause necrosis of the wound edges. They are also contraindicated for wounds associated with untreated osteomyelitis, fistulas to body cavities or organs, malignancy, and exposed arteries or veins within the ulcer bed. Wounds must be thoroughly debrided of all necrotic tissue before beginning therapy. The foam component of the dressing should be changed every other day.

  • Hyperbaric oxygen therapy

Hyperbaric oxygen therapy (HBOT) is used as an adjunct to standard wound care. HBOT, which involves breathing 100% oxygen at supra-atmospheric pressures between 1.5 to 3ATMs while inside a compression chamber, is based on the rationale that tissue hypoxia contributes to the failure of many chronic wounds to heal. HBOT increases arterial oxygen pressure which increases oxygen delivery to tissues as well as resulting in vasoconstriction and aiding in the reduction of edema.

Hyperoxygenated plasma enhances angiogenesis and ultimately collagen formation to aid in wound healing. HBOT has also been found to be effective against anaerobic bacteria, which survive better in the body’s deeper tissues. Increased tissue oxygenation also enhances leukocytes in their ability to fight infection. Hyperbaric oxygen treatments are administered 1 to 2 times daily and last 60 to 90 minutes.

Medicare reportedly reimburses HBOT as adjunctive therapy for diabetic wounds of the lower extremities if certain conditions are met, including a deep diabetic ulcer with associated abscess, osteomyelitis or joint sepsis, and unresponsive to standard wound therapy for at least 30 consecutive days. Medicare will not continue to cover costs if there are no measurable signs of healing within any 30 day period of treatment.

The benefits of HBOT remain controversial. HBOT is associated with several potential adverse events, including reversible myopia, otic, sinus or pulmonary barotrauma, neurological oxygen toxicity, and claustrophobia. Absolute contraindications to HBOT include untreated pneumothorax, restrictive airway disease, and concomitant chemotherapy.

Patient Management

Wound healing is a dynamic process and close patient follow-up is important. After the initial assessment, including diagnostic work-up, measurement of wound size, and selection of treatment modalities, the patient will need to be re-evaluated at regular intervals due to the evolving nature of wounds.

Local wound care choices for topical dressings, antimicrobial agents, and debridement will depend on the degree of dryness of moisture in the wound, signs and symptoms of infection, and amount of slough and callus around the wound.

Once a wound has completely healed, compression stockings are recommended to prevent edema from accumulating in the legs, which would predispose them to new or recurrent ulcers, as well as to protect the healed legs from physical trauma since scar tissue is weaker than normal skin.

Underlying causes need to be addressed. For example, patients with venous or arterial ulcers may require intervention by a vascular surgeon for radioablation or surgery of the veins or bypass surgery for arterial insufficiency. Diabetics need to see their primary care physician for frequent monitoring and control of their blood glucose levels. Prevention of trauma and repetitive pressure to bony prominences is key in the management of pressure ulcers.

Unusual Clinical Scenarios to Consider in Patient Management

  • Marjolin’s ulcer

Marjolin’s ulcer is an aggressive squamous cell carcinoma that can occur in previously traumatized or chronically inflamed skin in a leg ulcer. It spreads locally and is associated with a poor prognosis. The malignant change of the wound happens slowly, usually over 10 to 25 years. The wound edges may appear heaped up or rolled.

Wedge biopsy is the preferred method of diagnosis and must be done from both the center and margin of the lesion. The histopathology is that of a well-differentiated squamous cell carcinoma. Treatment usually consists of wide local excision or Mohs micrographic surgery.

  • Pyoderma gangrenosum

Pyoderma gangrenosum is primarily a sterile inflammatory neutrophilic dermatosis. It starts as a pustule and rapidly grows with development of tissue necrosis, resulting in painful recurrent ulcerations with undermined violaceous borders. Pyoderma gangrenosum disproportionately affects the pretibial area in women. The etiology is unknown, but 50% of Pyoderma gangrenosums are associated with other disease such as ulcerative colitis, Crohn’s disease, hepatitis C, seronegative polyarticular arthritis, spondylitis, IgA paraproteinemia, leukemia and lymphoma.

Treatment involves high dose steroids to prevent further progression of the ulcer and to rapidly stop the inflammatory process. Second line therapy which can also be combined with the steroid, includes cyclosporine, dapsone, azathioprine, and TNF-alpha blockers. Use local wound care with the appropriate dressing and compression. It is important to have continued follow-up by a physician as recurrence or development of new ulcers is common.

  • Cutaneous vasculitis

Cutaneous vasculitis comprises a group of diseases that combine segmental inflammation with necrosis of the blood vessel walls. The vascular damage is caused by an immunologic and/or inflammatory mechanism. Classification is traditionally based on the size of the vessels involved. The skin lesions of vasculitis are polymorphous. Palpable purpura is characterized by the classic lesions. They most often appear in the lower extremities or dependent areas such as the buttocks and back.

Small and medium vessel vasculitides include cryoglobulinemia, hypersensitivity vasculitis and polyarteritis nodosa. Vasculitis is associated with connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematous and Sjögren’s syndrome, as well as malignancies. Severe systemic infections including gonococcal, meningococcal and staphylococcal infections and drugs can also precipitate the acute onset of vasculitis.

A biopsy is done for diagnostic purposes and laboratory studies including CBC with differential, platelet count, chemistry, serum protein, electropheresis, hepatitis B and C, cryoglobulins, ANA, rheumatoid factor, and ANCA.

Treatment consists of removal of the antigen, management of the underlying comorbidity, and immunosuppressive agents for control of the cutaneous vasculitic lesions. Severe ulcerating disease will require high-dose steroids, and the addition of a steroid-sparing agent while the corticosteroid is being tapered.

Prednisolone is a standard therapy with normal dosage between 40 and 60 mg daily. Cyclosporine, IVIG, methotrexate, and azathioprine have been shown to be effective steroid-sparing agents. Ulcers also need to be managed locally by selecting the appropriate dressings and/or other modality based on previously described wound management principles.

  • Necrobiosis lipoidica

Necrobiosis lipoidica is characterized by erythematous plaques and nodules on the bilateral anterior shins that evolve into flattened brown plaques with a yellow atrophic center and prominent telangiectases. The most serious complication is the development of ulcerations due to atrophy.

While the etiology of necrobiosis lipoidica is unclear, approximately 75% of patients have diabetes. Women are more frequently affected than men. There are no evidence-based guidelines for the treatment of necrobiosis lipoidica.

First-line therapy usually consists of topical, intralesional, and systemic corticosteroids, although this may promote further atrophy. Pentoxyphylline, aspirin and dipyridamole are also used with variable results and thought to increase arterial flow. Ulcers are treated with the appropriate wound dressing, compression, and antimicrobial agent if needed. Maintenance treatment after wound closure consists of compression stockings to control edema and protect from trauma.

What is the Evidence?

Alavi, A, Sibbald, RG, Phillips, TJ, Miller, OF, Margolis, DJ, Marston, W, Woo, K, Romanelli, M, Kirsner, RS. “What’s new: Management of venous leg ulcers: Treating venous leg ulcers”. J Am Acad Dermatol.. vol. 74. 2016 Apr. pp. 643-64. (A recent comprehensive review of management of venous leg ulcers.)

Fonder, MA, Lazarus, GS, Cowan, DA, Aronson-Cook, B, Kohli, AR, Mamelak, AJ. “Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings”. J Am Acad Dermatol. vol. 2. 2008. pp. 185-206. (This CME article describes the pertinent aspects of a history and physical examination of a patient who presents with a nonhealing wound, and provides a brief overview of common ulcers, different wound dressings, and adjuncts to wound care.)

Bryant, R, Nix, D. Acute and Chronic Wounds Current Management Concepts. 2007. (This textbook provides clinicians with a strong knowledge base for understanding the complete spectrum of wound care, including the structure and function of the skin, general principles of wound management and recent advances in disease etiology, diagnosis and treatment.)

Krasner, D, Sibbald, G, Rodeheaver, GT. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals. 2007. (This textbook is written for the clinician and takes a multidisciplinary approach to nonhealing wounds. It is written by experts from every subspecialty of wound care.)

Han, A, Lazarus, GS, Maibach, H., Gorouhi, F.. “Chronic Wounds”. Evidence-Based Dermatology. 2011. (This book chapter thoroughly analyzes the data in the published literature regarding the best diagnostic and treatment options for different types of chronic wounds.)

Hermans, MH, Bolton, LL. “The influence of dressings on the costs of wound treatment”. Dermatol Nurs. vol. 8. 1996. pp. 93-4. (This article demonstrates that advanced wound dressings are more cost-effective than inexpensive gauze dressings. It calculates the cost of treatment to include all aspects influencing wound care including the actual materials, labor, and nonmedical costs to society.)

Singer, AJ, Clark, RA. “Cutaneous wound healing”. N Engl J Med. vol. 341. 1999. pp. 738-46. (This review discusses the biology of normal wound healing and its overlapping processes of inflammation, epithelialization, formation of granulation tissue, and neovascularization. It touches on abnormal healing and fetal wound healing, as well as advanced therapies using growth factors and skin substitutes.)

Grey, JE, Harding, KG, Enoch, S. “Venous and arterial leg ulcers”. BMJ. vol. 332. 2006. pp. 347-50. (This concise article describes the practical ABCs of venous and arterial leg ulcers. It has information on risk factors, physical findings, and management.)

Gottrup, F, Karlsmark, T. “Leg ulcers: uncommon presentations”. Clin Dermatol. vol. 23. 2005. pp. 601-11. (This article has information on uncommon leg ulcers, including pyoderma gangrenosum, cutaneous vasculitis, ulcerative necrobiosis lipoidica, malignancy and those found in the tropics. Uncommon presentations account for 1%-2% of patients suffering from leg ulcers.)

Ovington, LG. “Advances in wound dressings”. Clin Dermatol. vol. 25. 2007. pp. 33-8. (This article describes recent advances in dressings technology and a new proliferation of topical dressings that do more to help heal the wound. These dressings may contain materials that either deliver active ingredients or interact directly with cells or specific chemicals in the local wound environment.)

Han, A, Zenilman, JM, Melendez, JH, Shirtliff, ME, Agostino, A, James, G. “The importance of a multifaceted approach to characterizing the microbial flora of chronic wounds”. Wound Repair Regen.. vol. 19. 2011 Sep. pp. 532-41. (This article describes cutting-edge research on the microbial biofilm in chronic wounds, which provides a mechanism for antibiotic resistance and delayed wound healing. Advanced techniques such as metagenomic analysis, epifluorescence imaging, fluorescent in-situ hybridization and quorum sensing analysis are used to study and characterize biofilm composition, structure and behavior in chronic wounds.)