Wounds that fail to proceed through the normal phases of healing in an orderly and timely manner are classified as chronic wounds.1 Chronic nonhealing wounds affect a significant part of the patient population, impairing quality of life while also increasing patient morbidity and mortality. In the United States, chronic wounds affect more than 6 million people. This number is expected to increase secondary to the aging patient population, which has a high prevalence of comorbidities such as diabetes mellitus, neuropathy, and peripheral arterial disease that make patients prone to chronic wounds.2

The health care expenditure for treatment of chronic wounds has been recognized as a public health issue. More than $25 billion is spent each year on the evaluation and treatment of chronic wounds.3 The negative effect of chronic wounds on quality of life is similar to that of renal and heart disease, and diabetic foot ulcers are associated with a mortality rate comparable to that of the pooled mortality rate for cancer.2,4 As such, it is crucial for health care providers to recognize the etiology of chronic wounds and develop a comprehensive treatment plan.

Among the most frequently encountered chronic wounds that present in the office setting are diabetic foot ulcers (Figure), venous ulcers, arterial ulcers, and pressure ulcers. The respective underlying etiologies of diabetes mellitus with peripheral neuropathy, venous insufficiency, peripheral arterial disease, and immobility are common among the chronic wound patient population. Other frequently observed etiologies of chronic wounds include traumatic, neuropathic, lymphatic, infectious, surgical, radiation-induced wounds, and thermal burns.5


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Figure. Example of a diabetic foot wound exhibiting dry gangrene. Credit: Sproles et al.

Pathophysiology of Chronic Wounds

Although the etiology of chronic wounds may vary and is often multifactorial, these ulcers share common pathophysiologic features.1 The process of wound healing occurs in 3 phases: inflammation, proliferation, and remodeling. When a skin injury occurs, platelets are activated at the site and promote clot formation to stop blood loss. The inflammatory phase initiates when platelets release factors that attract immune cells from the circulation into the wound. Neutrophils within the wound produce high levels of reactive oxygen species, proteases, and proinflammatory cytokines that sanitize the wound. At the end of this process, neutrophils undergo apoptosis and become phagocytosed by macrophages within the wound. These macrophages then undergo phagocytosis to engulf bacteria and debris to cleanse the wound. This allows for wound sterilization and entry into the proliferative phase, at which time tissue regrowth occurs.6

Key Points

Chronic wounds affect more than 6 million people in the US and more than $25 billion is spent each year on the evaluation and treatment of chronic wounds
When managing chronic wounds, the treatment plan should first address any underlying disease processes that resulted in the wound or stalled wound healing
The TIME wound management guidelines should be considered to overcome important barriers to wound healing
Hyperbaric oxygen therapy is a noninvasive procedure with few side effects and contraindications that has been used for chronic wound treatment for more than 2 decades

In the proliferative phase, wound cells rapidly multiply and migrate to regenerate the lost tissue within the wound. Endothelial cells and fibroblasts are involved in this process by forming granulation tissue. This granulation tissue is a highly vascularized extra-cellular matrix that allows keratinocytes to migrate to close the wound. Subsequently, the wound enters the remodeling phase of wound healing during which the granulation tissue matures and increases in mechanical strength. Wound healing is complete when a collagen-rich scar is left following apoptosis of myofibroblasts and vascular cells.1,6

Chronic wounds that remain in the inflammatory stage and do not readily progress to the proliferative and remodeling stages are unable to regenerate tissue. Proinflammatory cytokines, proteases, reactive oxygen species, senescent cells, and deficiency of stem cells are characteristics that can be affiliated with chronic wounds. These factors result in prolonged or excessive inflammation of the wound, persistent infections, formation of drug-resistant microbial biofilms, and inability of dermal and epidermal cells to repair.1 As such, it has been suggested that targeting and correcting cellular and molecular causes of prolonged inflammation in chronic wounds may promote healing.6

Treatment of Chronic Wounds

When managing chronic wounds, the treatment plan should first address any underlying disease process that resulted in the wound or stalled wound healing. In the setting of vascular wounds, this could entail collaboration with vascular surgery or vein clinics for interventional procedures. Referral to a lymphedema specialist should also be considered in cases of nonhealing lymphedema wounds. Clinicians should ensure that patients with foot ulcers from uncontrolled diabetes are receiving treatment and management of their blood glucose levels.1 Consultation with other disciplines such as infectious disease, dermatology, rheumatology, podiatry, or even behavioral medicine should also be considered based upon presentation of the wound and the index of suspicion for the underlying etiology.

Reduce Modifiable Risk Factors

Modifiable risk factors that contribute to stalled wound healing should also be considered when treating patients with chronic wounds. These risk factors commonly include nicotine dependence, alcohol use, and obesity. Nicotine functions as a vasoconstrictor, reducing the nutritional blood flow to the wound and resulting in tissue ischemia with impaired healing of the injured tissue. Excess alcohol consumption can contribute to an impaired immune system, thus increasing susceptibility to wound infection. Furthermore, increased pressure in the portal vein from alcoholic liver cirrhosis predisposes patients to lower extremity swelling with concurrent lower extremity wounds. A primary concern of obesity interfering with wound healing is hypovascularity of subcutaneous adipose tissue resulting in relative hypoperfusion and ischemia. Obesity is also associated with stress, anxiety, and depression, all of which can result in an impaired immune response. As such, smoking cessation, discontinuation of alcohol use, and weight loss should be included in the treatment regimen for patients with chronic wounds.7

Nutritional Support

Patients with chronic wounds should also receive adequate nutritional supplementation. Wound healing is dependent upon nutrition and requires the presence of proteins, polyunsaturated fatty acids, carbohydrates, and micronutrients (vitamins, zinc, and magnesium) within the diet.8 Of these, protein could perhaps be considered the most important macronutrient as the exudate from wounds is a proteinaceous fluid. Chronic wounds with a high exudate loss can result in a deficit of as much as 100 grams of protein in a day. This is an important consideration as protein deficiency contributes to poor wound healing by prolonging the inflammatory process, impairing collagen synthesis, and increasing the risk for wound dehiscence.9 To counter this protein loss, dietary protein shakes or protein bars can be added to the patient’s diet. Protein supplementation via parenteral nutrition should be used in patients who are unable to tolerate oral intake.