Offering pearls from the literature as well as her clinical experience, this author discusses the impact of infection, reviews common diabetic dermatopathology and notes other pertinent diagnostic keys.
Beginning with the initial patient presentation, there are a number of keys to manage chronic diabetic foot ulcerations. The first of these is the ability to make a definitive diagnosis.
When a patient reports to the office with a concern about pre-ulcerative or ulcerative conditions, it is critical to determine the etiology of the condition and make an accurate diagnosis. To some, this may sound overly basic but it is not uncommon for a patient to report being treated for a prolonged period of time and never getting any better.
Often when patients are asked if they received a diagnosis, they say the doctor told them they had an ulcer and that was the extent of the diagnosis. When asked about the plan for home care, patients often say they only got instructions to put antibiotic ointment and a bandage over the ulcer. Other patients will ask rhetorically, “What home care?”
About 2.5 percent of patients with diabetes develop foot ulcers each year and foot ulcers are the most common cause of hospitalization for the patient with diabetes.1 Furthermore, 15 percent of diabetic foot ulcers result in amputation of the foot or leg.2
Given these statistics, clinicians need to strive for an accurate, timely diagnosis, determining specific wound measurements and quickly beginning an aggressive wound management program. This typically includes the benefit of baseline radiographs and ancillary imaging when indicated. At the beginning of wound care planning, one should consider offloading the limb, systemic conditions such as enhanced glycemic control, dietary adjustments and neurovascular testing among other factors.
When there is no suspicion of infection, the need for blood work becomes debatable. Baseline serologic testing may include complete blood cell count (CBC), C-reactive protein (CRP) and a complete metabolic profile as these patients often do not present regularly (if ever) for care by an internist. When treating a wound over time, there may come a point where the wound progress stalls or one suspects infection. At this point, it may be regrettable that one did not perform baseline serologic screening as neutropenia and hematologic imbalances can influence a patient’s ability to mount a sufficient immune response to infection. This is particularly true in the patient with diabetes.
The history of the condition will often shed light on the etiology. For instance, certain chief complaints often correlate with the etiology of the ulcerative condition.
One must differentiate acute wounds from chronic wounds as they have a different prognostic potential. An acute wound caused by trauma breaks down intact skin. These wounds should have a predictable timetable to healing that correlates with the nature and extent of the injury. Acute injuries as a result of surgery, trivial trauma (abrasions, contusions) or otherwise (gunshot wounds or burns) often have a clinical course in healing that is predictable once the wound has become fully apparent.
In contrast, chronic wounds often result from systemic etiologies such as peripheral vascular disease (PVD), impaired venous return (chronic venous stasis and venous hypertension), diabetes, autoimmune disease, obesity, poor nutrition and illicit drug use, just to name a few key conditions. Documented cases of spider bites or other wounds that involve venom retention and tissue necrosis are particularly troublesome and can complicate the health of patients with diabetes suffering from neuropathy as they often lack sufficient protective sensation to feel the bite or sting of the insect. These conditions result in wounds that are slow to heal and the clinical course of healing is often unpredictable.
Mechanical wounds, which are often associated with peripheral neuropathy and foot deformity, can be either acute or chronic depending on the time to discovery and how promptly the patient reported the wound to a physician. In either case, acute or chronic, wounds that have exposed subcutaneous tissues are at higher risk for bacterial colonization and infection in contrast to the more superficial wounds. Be certain to categorize the etiology of the wound and consistently document that with each successive note.
Bacterial colonization or infection can slow if not halt wound healing, especially in the patient with diabetes. If malodor or discoloration of the wound and surrounding skin are present, be suspicious that bacteria or fungal elements may be working against healing the wound bed. A biopsy of the tissue is the best way to determine whether there is bacteria or fungus affecting the wound. A tissue culture will allow differentiation between colonization and infection as the microbiology lab can quantify organisms within tissues. From an academic standpoint, researchers suspect the density of microorganisms is the critical factor in determining whether a wound is likely to heal.3-7
Since it is common to find that bacterial colonization and infection are polymicrobial, one can argue that the specific pathogens are of primary importance when wound healing appears to be blunted.8-13
While it is intuitive that the specific organism and the numbers of those organisms that are present in a wound are important to determine when attempting to optimize wound healing, there are other researchers who put more credence in the type of material one places over the wound bed.14-20
In fact, there has been a study to explore the potential benefits of using a topical bacteriophage solution to aid in reducing bacterial load and enhancing the wound healing process.21 This study used an animal model and based upon histologic findings, researchers demonstrated that topically applied bacteriophage treatment effectively decreased bacterial colony counts and improved wound healing. The study notes the treatment was the most effective in Staphylococcus aureus and Pseudomonas aeruginosa infections but the results were not as promising with the organism Acinetobacter baumannii.
These results suggest that topically administered bacteriophage treatment may be effective in resolving chronic infections, especially when one applies them in conjunction with wound debridement. From these findings, I extrapolated that this treatment can be effective and safe when treating chronic infections in diabetic populations.
The nature and extent of diabetic dermopathy oftentimes interferes with the wound healing process. Unfortunately, while diabetic dermopathy is often obvious clinically, it is not often diagnosed, much less treated.
Think about the last time a diabetic ulceration gave you a problem. Do you recall just how thick the skin was? Did it seem like the center of the ulcer was improving but that the edges of the wound became thick, keratotic and kept developing a macerated base? Have you ever noticed the center of an ulcer that seemed to fill in but the edges of the wound stayed so stiff that the margins never would epithelialize toward the center?
What is missing in this scenario is the identification and treatment of an associated dermopathy. While the easiest way to a diagnosis is biopsy of the skin, in the case of diabetic dermopathy, a simple pinprick test can be revealing. There are a few types of dermopathy associated with the population of patients with diabetes and those entities can often thwart wound healing progress.
Dermatopathology associated with ulcerations in patients with diabetes. Chronic skin conditions can be present as a primary etiology of ulceration or as a secondary complicating condition interfering with the wound healing process. Diabetic dermopathy, necrobiosis lipoidica diabeticorum and diabetic thick skin are categories of dermatopathology that physicians commonly encounter yet they often go undiagnosed.
Diabetic dermopathy. One can suspect diabetic dermopathy when the history includes the development of darkening spots throughout the pretibial portion of the limb. The pattern of distribution is asymmetric and typically bilateral. These areas of skin appear atrophic and heal by way of scarring.22 Under the microscope, you will see edema of the papillary dermis, thickened superficial blood vessels, extravasation of erythrocytes and a mild lymphocytic infiltrate. Whenever red blood cells extravasate into layers of the skin, the iron in the hemosiderin essentially causes a tattooing of the skin and dark patches develop.23-25
Necrobiosis lipoidica diabeticorum. This is a degenerative disease of collagen of the skin and subcutaneous tissue in which an atrophic epidermis and granulomatous dermis develop. If patients are exposed to trauma, trivial or otherwise, an ulceration can develop. In some patients, the lesions become vesicular and rupture the skin, often causing ulcerations in the most vulnerable portion of the lower extremity, the pretibial region. As many as one-third of these lesions may go on to ulcerate.26,27 What causes this condition? It is not perfectly understood but the theory is that microangiopathy causes degradation of dermal collagen. Some authors have suggested that it may be an immune modulated dysfunction that causes the condition.26,27
Chronic inflammation of the lower extremity from exposure to cytokines may be responsible for the degradation of collagen.28,29 This condition reportedly affects 0.3 to 0.7 percent of patients with diabetes, and affects women more often. At their earliest onset, necrobiosis lipoidica diabeticorum lesions look well-circumscribed with erythematous plaques that have a concave and waxy telangiectatic centroid.26,30
Early on, these areas appear vasculitic. Microscopic examination will confirm these areas of vasculitis to be the result of neutrophil infiltration. Over time, lesions progress from granulomatous to sclerotic and most often present in the pretibial regions. When this occurs in regions other than the lower extremity, there is less of an association with diabetes.23,31-32
Diabetic thick skin. When it comes to skin changes that include thickening of the dermis, clinicians can divide this into three main categories: scleroderma-like (commonly in the hand and often accompanied by stiff joints); measurable skin thickness that is clinically insignificant; and scleredema diabeticorum. Thickening of the dorsum of the hands may occur in a third of patients with diabetes.23
The pathogenesis of diabetic thick skin has not been clearly defined. One theory suggests that polyol accumulation results in the hydration of collagen and subsequently leads to thickened skin.25,33 Another viable theory is that there is a non-enzymatic glycosylation of collagen.27,34 While there are suggested therapies for simple diabetic thick skin, there is no specifically indicated treatment. However, it is intuitive that tight glycemic control could be beneficial and the literature has supported this.35
Neurotrophic ulceration. One may suspect diabetic neuropathy when the patient reports the history in a particular way. Consider some of the following examples you may hear from patients.
• “I just began noticing drainage on my socks and had been wondering where it was coming from.”
• “I could tell that my foot was changing shape and it got a lot fatter and more red looking than the other foot.”
• “I have always had this callus but it never hurt. Now it has gotten dark brown and is draining.”
• “It looks like it should hurt but I do not feel it.”
• “My pet began licking my foot and has been doing that more and more often.”
Often when patients describe purely visual clues in the history of a wound rather than tactile information such as pain, this validates the finding of loss of protective sensation. Regarding neuropathic diabetic foot ulcers, researchers have developed a standard protocol.36 The stepwise approach in this protocol includes a seven-step process beginning with wound measurement; enhanced glycemic control; surgical debridement of necrotic, keratotic and infected tissue; systemic antibiotics when deep infection, drainage or cellulitis are present; offloading of the limb; maintaining a moist wound bed; and treatment with growth factors and cellular therapy if the wound is not healing (not producing a new epithelial layer) after two weeks of care.
Since as many as 15 percent of diabetic foot ulcers result in amputation of the foot or leg, protocols such as this are beneficial from a practical perspective and aid in the day-to-day management of patients with diabetic foot ulcers including neuropathic ulcers.2,37 At the time that this protocol was published, the prevalence of foot ulcers in the diabetic population was 12 percent and the five-year mortality rate of diabetes-induced limb amputations ranged between 39 and 68 percent.38
These patients remain at an increased risk for subsequent amputations and when considering the overall cost of care, the statistics published by the National Institutes of Health (NIH) indicate that hospital length of stay is approximately 60 percent longer among patients with diabetic foot ulcers in comparison to those without ulcers.40
Historically, researchers have devised wound care initiatives with the intent to improve the wound healing rate, reduce the incidence of infection and ultimately reduce the incidence of amputations resulting from ulcerations in the diabetic population specifically.40-44 Critical to the success of any wound care initiative is a decisive program for offloading the limb and detailed patient education that mandates full patient cooperation in the plan.
Traumatic ulceration. One may suspect a traumatic ulceration when patients report the history in a particular way. Here are just a couple of examples.
• “I hit my shin on the coffee table and the sore just will not get better.”
• “The dog’s chain got wrapped around my leg and as I was trying to get the chain off the dog was trying to run away.”
• “I fell and scraped my ankle on the concrete.”
An acute wound caused by trauma breaks down intact skin. These wounds should have a predictable timetable to healing that correlates with the nature or extent of the injury. Injury as a result of surgery, trivial trauma (abrasions, contusions) or otherwise (gunshot wounds or burns) often has a clinical course in healing that is predictable.
Arterial ulceration (ischemic ulceration). Suspect an arterial ulceration when the history includes the onset of pain in association with the development of a sore or ulceration in an unusual location. One may hear patient variations on the following statements.
• “I noticed pain and a sore developing on the outside of my ankle or the tips of the toes.”
• “I noticed a chunk of skin was missing from the outside of my leg” (a punched out appearance).
When considering chronic ulcerations, it is often difficult to determine exactly when to shift gears in therapy. Knowing when to say when in using simple in-office local wound care methods is important to successful patient management. After all, in-office wound care can be very time consuming. When the physician becomes overwhelmed with the time, amount of supplies and equipment that are required to handle chronic wounds, it is easy to lose sight of just how long this wound care program has been going on. After all, getting the patient into the room, documenting the subjective information and then providing the patient care (debridement, irrigation, application of dressings and detailed patient education) usually takes more time than the schedule typically allows.
The last thing to consider is the duration of the ulcer. It is common to have a patient with an ulcer returning with great frequency and the patient allowing this therapy to go on indefinitely rather than making an alternate decision that might not include limb salvage. But how long can a patient continue to care for an ulceration and have the physician document the wound as having a “very good clinical appearance and healing well”?
In 2003, Sheehan and colleagues considered this point and conducted a study to determine just how much wound healing was considered sufficient to predict successful definitive wound healing.45 The purpose was to assess the four-week healing rate as an indicator of healing within 12 weeks in foot ulcers in patients with diabetes. This study focused on 203 patients with ulcerations that had been present for 12 weeks. What they found was that when a wound’s area was reduced by greater than 53 percent at four weeks, it was not just a good indicator but a robust indicator that the wound could heal by the 12-week mark. This study supplied physicians with a very good rule of thumb when dealing with chronic wounds and enabled prognostication to include the estimated time to healing.
Shifting gears in a wound care plan typically includes ancillary imaging, tissue and/or bone biopsy. When advancing the care plan in a more aggressive direction, the use of grafting and specialized tissue membrane transplants often has a role. From a common sense perspective, there are a number of traditional rules of thumb in wound care that have truly withstood the test of time and these include topical agents geared at improving the quality of skin, reducing bacterial colonization and ridding the wound bed of fibrous ingrowths. The table at left provides a summary of some effective common agents that can be of benefit in day-to-day wound care strategies.
This article is meant to provide basic practical information regarding wound care in the patient with diabetes, which can be an arduous task. There are four fundamental concepts to bear in mind when diagnosing these ulcerations.
1. Whenever possible, make a definitive diagnosis in the very first patient encounter as this allows the patient to more fully understand the course of therapy.
2. Be sure to classify the wound type for documentation purposes as this will directly correlate with the treatment plan you select. In the event that the conservative wound care plan is not successful, then it is important to question the working diagnosis and wound classification. In fact, this may well be the time to consider a second opinion.
3. Determining whether there is an organism interfering with wound healing is important as bacterial colonization and infection commonly interfere with wound healing, and at times can be indolent with subtle outward signs of change. There are numerous methods to reduce bacterial load in a wound bed and when this is a problem, modifying the debridement method and/or the wound care plan are in order.
4. Understand the nature of the most common diabetic dermatopathology as this is often a coexisting and confounding factor when dealing with the chronic ulceration in patients with diabetes.
Dr. Judge is a Fellow of the American College of Foot and Ankle Surgeons. She is in private practice at North West Ohio Foot and Ankle Institute, serving Ohio and Michigan. Dr. Judge is an adjunct faculty member at Ohio University and the Kent State University College of Podiatric Medicine. She is also on the faculty for graduate medical education at Mercy Health Partners in Toledo, Ohio.
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