Non-Surgical Management of Diabetic Foot Ulcers

Special Article - Diabetic Foot Care

Foot Ankle Stud. 2018; 2(2): 1014.

Non-Surgical Management of Diabetic Foot Ulcers

Edward B Miller1* and Zvi Landau2

1Assistant Chairman, Internal Medicine "D", Kaplan Medical Center, Affiliated to the Hebrew University School of Medicine, Israel

2Chairman Emeritus, Internal Medicine "D" and Diabetic Foot Clinic, Kaplan Medical Center, Affiliated to the Hebrew University School of Medicine, Israel

*Corresponding author: Edward B Miller, Assistant Chairman, Internal Medicine "D", Kaplan Medical Center, Affiliated to the Hebrew University School of Medicine, Israel

Received: September 11, 2018; Accepted: October 16, 2018; Published: October 23, 2018


Ulcerations of the foot in diabetic patients are common, disabling and predispose to ascending infections such as gangrene and sepsis which frequently necessitate amputation of all or part of the lower extremity. Effective treatment of Diabetic Foot Ulcers (DFU) can have a major therapeutic benefit resulting in reduced morbidity, mortality and the need for surgical intervention. We review the major factors contributing to the development of these lesions and the components of an effective multidisciplinary approach to treatment with the goal of limiting major surgical intervention such as amputation when possible.

Scope of the Problem

Lower extremity ulceration in diabetic individuals is common, with a lifetime risk estimated at between 12-25% [1,2]. Presence of a DFU results in substantial patient morbidity, impairment of the quality of life, and ultimately in higher treatment costs estimated at tens-of-thousands of dollars per lesion [3,4]. Up to 85% of lower extremity amputations in diabetic individuals may be preceded by skin ulceration [5] emphasizing the need for effective preventative and therapeutic strategies in dealing with these lesions.

The etiology of DFU is usually multi-factorial with a combination of factors coalescing to result in the clinical lesion. Of the multiple etiologic factors summarized in (Table 1), the presence of neuropathy is considered the most significant [4]. Diabetes induced peripheral neuropathy results in the loss of the protective sensation of pain, while autonomic dysfunction and sympathetic denervation result in dry skin and a warm foot. Additional contributing factors may include the presence of peripheral vascular disease, callus formation, edema and deformity. These combined factors result in tissue-damaging mechanical loads applied to an insensate and poorly perfused foot which is unable to sense and prevent the impending ulceration, and impedes the tissue’s ability torepair the resulting damage and defend against subsequent infection [6,7].

There are many known physiologic factors which contribute to wound healing deficiencies in diabetic individuals.

These include decreased or impaired growth factor production, angiogenic response, macrophage function, collagen accumulation, epidermal barrier function, quality of granulation tissue, keratinocyte and fibroblast migration and proliferation, number of epidermal nerves and bone healing. The imbalance of these factors impairs the cytokine and chemokine controlled migration of epithelial progenitor cells to the affected tissue [8].

Ulcer Classification

There is no universally accepted classification of DFU although several classification schemes have been proposed.

The Wagner-Meggitt classification is the traditional method of ulcer grading with six levels of wounds classified by the depth of ulceration and the extent of gangrene. Deficiency of this system is that all infections are lumped into one category limiting its clinical relevance [9]. The commonly employed University of Texas system measures ulcer depth and presence or absence of ischemia, but does not include measures of neuropathy or ulcer area [9]. Other more recently proposed classifications include the SAD and PEDIS (perfusion, extent, depth, infection severity and sensation) grading systems which incorporate multiple factors useful in comparative research studies but are cumbersome to use in clinical practice [10,11].

For clinical simplicity and utility we prefer the Infectious Diseases Society of America (IDSA) guidelines which classify infected DFU into categories of mild, moderate or severe based on relatively easily determined clinical parameters [12]. Mild infections are those defined as having two or more clinical manifestations of inflammation - purulent discharge, erythema, pain, tenderness or induration-but these changes must be limited to the skin, and the patient must lack evidence of a local complication or systemic illness. Moderate lesions are those occurring in patients who are clinically well, but exhibit evidence of more extensive cellulitis, lymphangitic streaking, or spread of infection to deeper structures (superficial fascia, deep-tissue abscess, gangrene, muscle, tendon, joint or bone)

Severe lesions are those in which evidence of systemic toxicity or metabolic instability is present. These features may include fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis,severe hyperglycemia or azotemia.

The clinical utility of this system was recently validated in a study by Lavery and colleagues [13]. In this longitudinal study of over 1600 diabetic patients, individuals with DFU lacking infection or with only mild infection rarely required repeat hospitalizations. Only 3% of these individuals required amputations during the study period.

In contrast, patients with moderate or severe infections were far more likely (46% and 78% respectively) to require amputations during the study period.

Effect of Diabetic Control on Ulcer Healing

Improving diabetic control (along with smoking sensation) has clearly been shown to decrease the likelihood of developing DFU [14]. The prospective effect on ulcer healing is less clear. Studies commonly employ the glycosylated hemoglobin level (HgbA1C) as an indicator of glycemic control. In a meta-analysis of over 500 patients, Margolis and associates found that individuals with a lower HgbA1C at the start of management did not have an improved chance of ulcer healing [15]. However, Marston, in a study involving 245 patients treated with a bioengineered human dermal substitute, found an increased rate of ulcer healing in those individuals in which hemoglobin A1C levels decreased during the 12 week study period versus those in which levels increased during the same time [16].

The lack of improvement shown in most studies may be due to the short timeframe involved in ulcer treatment programs (typically several weeks). If present, improvement in ulcer healing due to improved glycemic control in the short run would most likely be related to impaired leukocyte function in chronic hyperglycemia [17]. While further studies may help clarify this discrepancy, we continue to believe that good overall medical practice demands effective glucose control in all patients with or without active DFU.

Principles of Ulcer Treatment

Predicting which ulcers will heal and which will resist therapy is difficult as many factors may contribute to wound healing. In general, wounds that are small (≤ 2 cm 2), have been present for ≤ 2 months, are relatively shallow and which are non-infected have the highest chance of healing [18].

The major principles of ulcer management can be summarized as follows

5.1. Treat any clinically evident infection

5.2. Relieve ischemia if present

5.3. Reduce mechanical pressure on the ulcer (offloading)

5.4. Perform ulcer debridement

We will examine each of these principles in turn.

Treatment of infection

Infection is typically the end result of the presence of an open skin lesion coupled with an impaired tissue defense system. The development of infection in the setting of DFU is what ultimately endangers the limb and the individual. Infections may be superficial and local, soft tissue and spreading (cellulitis), or involve deep tissues such as bone (osteomyelitis). All skin and ulcer surfaces are typically covered with bacteria, hence a routine surface culture is not sufficient for determining the presence of active infection, and the prescription of antibiotics based only on these cultures is not considered beneficial [19].

The decision to initiate antibiotic therapy should however be based on clinical grounds, with subsequent culture results guiding the ultimate choice of antibiotics. The typical signs of local infection or cellulitis-erythema, warmth, tenderness and/or purulent discharge-may be difficult to differentiate from chronic ischemic or neuropathic skin changes if present. Systemic signs such as fever or leukocytosis are infrequently present but usually indicate a more serious infectious process [20].

Infections in diabetic patients tend to be polymicrobial including gram positive, gram negative, aerobic and anaerobic species [21]. If osteomyelitis is present Staphylococcus aureus is the most likely pathogen [22], but deep (bone) cultures should still be obtained if possible. In practice, deep cultures are difficult to obtain and are often contaminated by surrounding soft tissue organisms. Treatment with broad spectrum antibiotics is therefore often empiric [22].

The presence of large quantities of colonizing bacteria or an untreated active infection can significantly impede ulcer healing [23-25]. However, it is important to note that studies have failed to demonstrate that administration of routine antibiotic treatment in the absence of a clinically active infection is effective either in advancing ulcer healing or in preventing future infections [19,26]. Given the worldwide risk of breeding resistant organisms (in large part due to overuse of antibiotics), increased cost and risk of side effects, antibiotic therapy should be reserved only for those individuals with clinically evident infections.

Relieve ischemia

A strong consistent relationship between hyperglycemia and the incidence and progression of micro vascular (diabetic retinopathy, loss of vision, and nephropathy) and macro vascular (amputation and cardiovascular disease mortality) complications in people with both Types I and II diabetes has long been noted [27]. The presence of diabetes increases the incidence of limb ischemia approximately 2-4 foldand the likelihood of lower extremity amputation by up to 20 times [28-29]. A 1% increase in Hemoglobin A1C levels increases the likelihood of peripheral arterial occlusive disease by up to 26% further emphasizing the need for primary prevention [30].

The therapy of micro vascular disease is largely preventative through good glycemic control, smoking cessation, control of hyperlipidemia and regulation of blood pressure [31]. Macro vascular disease is remediable by invasive therapies such as angioplasty or surgery and should be excluded in all patients with DFU. Findings on physical exam may be limited due to overlying edema, infection or ischemia necessitating the reliance on non-invasive vascular testing in many cases [32]. Subsequent confirmation by additional imaging studies (angiography, magnetic resonance angiography) may be required in some individuals.

Treatment is often complicated by the tendency in these patients to develop multilevel distal lesions within heavily calcified vessels. These factors as well as the frequently unsatisfactory results of non-invasive revascularization (angioplasty and the like) have long favored direct surgical intervention in diabetic patients [7]. Whereas the surgical approach to the treatment of large vessel disease is beyond the scope of this chapter, interested readers may review the consensus recommendations recently published by Norgen and colleagues [33].

Citation: Miller EB and Landau Z. Non-Surgical Management of Diabetic Foot Ulcers. Foot Ankle Stud. 2018; 2(2): 1014.