WHS (Wound Healing Society) guidelines update: Diabetic foot ulcer treatment guidelines

1 BACKGROUND

Globally, it is estimated that at least 536.6 million people are diagnosed with diabetes globally, and it is projected that by 2045, the amount of people with diabetes will increase by 49.6% to a total of 783.2 million individuals.¹ Diabetic foot ulcers (DFUs) are a growing health problem. DFUs are a leading cause of infection, amputation, and hospitalisation in patients with diabetes mellitus.

Guidelines for the treatment of DFUs were published by the Wound Healing Society (WHS) in 2006 and 2016. However, in the past few years new evidence has emerged that has improved our understanding of previous recommendations. The objectives of the WHS DFU guidelines are to systematically evaluate the medical literature to assist clinicians in making health care decisions, identify areas that need additional research, and to clarify controversial diagnosis and treatment strategies. An advisory panel comprised of academicians, clinicians, and researchers was chosen to update the 2016 guidelines.

2 METHODS

In 2006 and 2016, we published guidelines to improve the information for clinicians with our goal to improve patient care. Even in the absence of high-quality human data, the WHS developed guidelines using a different approach to evidence citations and past approaches to evidence-based guidelines. There is a growing number of randomised clinical trials (RCTs), meta-analysis, and society directed practice guidelines that evaluate diagnoses, treatments, and prevention strategies for patients with DFUs. There is better evidence to support recommendations. The strength of evidence supporting a guideline is listed as Level I, Level II, or Level III.

3 DATA SOURCES AND SEARCHES

Since the 2006 and 2016 guidelines, we sought to capture the highest quality of literature available regarding DFU diagnosis using a key word search of PubMed, Embase, and Cochrane Library databases. Similarly, the citations of relevant articles were examined by hand. Key terms were generated from the existing guidelines. In this search as opposed to the previous data collection prior to 2006, we used human and disease specific data and limited to meta-analyses, systematic reviews, RCTs, retrospective series reviews, clinical case series, and expert panel recommendations published between January 2006 and present. References prior to 2016 supporting the previous guideline recommendations are not included. Therefore, in some cases no additional updated references were included and the support for the guideline recommendation is based on evidence presented in the 2006 guideline. It was further limited to English publications. Any relevant additional references found after the formal search were also included. The findings of these articles have been divided into one or more of the appropriate categories as performed in the original guideline. Each of the separate guidelines has undergone a Delphi consensus among the panel members.

4 GUIDELINES FOR THE DIAGNOSIS OF LOWER EXTREMITY DIABETIC ULCERS

Preamble: Globally, 9–26 million people develop diabetic foot ulcers annually. The lifetime risk of developing a DFU is thought to be high (19%–34%), and once a patient has had a DFU, ulcer recurrence is 30%–60% a year [1]. Foot ulcers may be caused by various conditions, including neuropathy, ischemia, venous hypertension, limited joint mobility, trauma, and biomechanical pressure. Patients with diabetes develop foot ulcers secondary to neuropathy with or without biomechanical abnormalities, and peripheral arterial disease, or both.

Guideline #1.1: In patients with diabetic foot ulcers, peripheral arterial disease (PAD) should be evaluated with clinical examination and advanced vascular testing. A high index of suspicion for ischemia complicating a DFU is necessary since PAD is quite common. In patients with diabetes with an ankle-brachial index (ABI) between 0.9 and 1.3, a triphasic Doppler-derived waveform, a toe-brachial index (TBI) of >0.75, or a transcutaneous oxygen pressure of >25 mmHg may help to suggest an adequate arterial flow to heal. (Level I – unchanged).

Principle: Diabetic ulcers can result from or be complicated by arterial insufficiency. Although clinical history and physical examination can be very suggestive of an ischemic component in patients with DFUs, when significant PAD is present, successful treatment requires that PAD is diagnosed and treated.

Guideline #1.2: The presence of sensory neuropathy with loss of protective sensation can be determined by using clinical testing with a 10 g Semmes–Weinstein monofilament, a 128 Hz tuning fork or the Ipswich Touch Test. (Level II – unchanged).

Principle: Diabetic sensory neuropathy creates an environment in which repetitive trauma, injury and infection are unrecognised by the patient. Several simple clinical techniques can be used to identify sensory neuropathy with loss of protective sensation. The presence of sensory neuropathy with loss of protective sensation can be determined by testing with a 10 g Semmes-Weinstein monofilament, or a 128 Hz tuning fork, vibration perception threshold testing or a good neurological clinical examination for sensory loss.

Guideline #1.3. Diabetic foot ulcerations should be classified by a system that accounts for size, depth, extent and both infection and ischemia. (Level I).

Principle: Ulcer classifications can improve documentation, direct treatment, and be predictive of outcomes. The University of Texas Diabetic Ulcer Classification system, Wagner Ulcer classification and WIfI (Wound, Ischemia, and foot Infection) Classification are widely used and validated.

5 GUIDELINES FOR OFF-LOADING FOR TREATMENT OF DIABETIC ULCERS

Guideline #2.1: The most effective methods to off-load plantar DFUs are total contact casts and non-removable cast boots followed by removable cast boots, healing sandals, custom shoes and insoles. Post-operative shoes are least effective at off-loading plantar wounds. (Level I).

Principle: Relieving pressure and shear forces at the site of a diabetic foot ulcer is necessary to maximise healing potential.

6 GUIDELINES FOR INFECTION CONTROL AND TREATMENT IN THE MANAGEMENT OF DIABETIC ULCERS

Preamble: All wounds are colonised with microorganisms (Bacteria, Fungi, Archaea, Viruses) but this does not necessarily equate that all wounds will become infected. Infection occurs when microorganisms enter the body, replicate, increase in number, and cause damage to host tissue. Infection plays various roles in aetiology, healing, operative repair, and complications in patients with DFUs. Diabetic foot infections are a major cause of hospital admission and can be limb- and life-threatening.

Guideline #3.1: Evaluation of infection should be based on clinical signs and not based on swab or tissue cultures. (Level II).

Principle: Bacteria (and to a lesser extent fungi) are often identified through microbiological culture in acute and chronic wounds. The presence of bacteria should not be used as a criterion to define infection but as a guide to target antibiotic therapy where clinical infection is present. Infection involves characteristics of the host's immunity and the presence, quantity, and virulence of bacterial pathogens. Therefore, clinical examination is recommended as the basis for diagnosing clinical infection. Diabetic foot infection is established by ≥2 classic findings of inflammation or purulence. Infections should be classified according to the International Working Group on the Diabetic Foot infection classification: mild (superficial and less than 2 cm of erythema), moderate (deeper tissue infected or more than 2 cm of erythema, with or without osteomyelitis) or severe (accompanied by sepsis, with or without osteomyelitis).

Guideline #3.2: Microorganisms can become organised into multicellular, not very metabolically active aggregates in a glycocalyx, commonly referred to as biofilm. Biofilms are identified in many (34% to 78.2%) [1] but certainly not all chronic DFUs, where they may play a role as a cause of infection. Wound biofilms have often been observed as being polymicrobial and tolerant to the host immune system and to various treatments. The scientific evidence for commonly used topical wound antimicrobials is poor [2]. There are limited DFU studies that measure biofilm (or the total amount of microorganisms) pre- and post-treatment to demonstrate that; 1. Biofilm was present before interventions and 2. Anti-biofilm interventions eradicated or changed the biofilm and improved clinical infection or wound healing. (Level II).

Principle: Biofilm has been suggested to impede wound healing through inducing localised infection. In animal studies biofilm has been associated with poor healing and infection. There are small proof of concept studies which have set out to determine the effectiveness of topical wound dressings against biofilm in vivo. However, there is an absence of high-level evidence to support that therapies directed at biofilm are effective to improve DFU healing or infection.

Guidelines #3.3: In the absence of clinical infection, systemic antibiotics do not improve wound healing or reduce the incidence of clinical infections. (Level I – unchanged).

Principle: Systemically administered antibiotics do not remove or reduce all microorganisms present in a wound. In the absence of clinical infection signs and symptoms, systemic antibiotics have not been shown to reduce or prevent clinical infection and/or improve wound healing. However, unnecessary or overuse of systemic antibiotics will increase the risk of developing antibiotic resistant bacteria.

Guidelines #3.4: Topical antimicrobial and antiseptic therapies may improve wound healing by affecting microorganisms in the wound bed. (Level II).

Principle: Clinical infection may decrease healing. However, there is no evidence that products designed to reduce bioburden translate into a reduction in clinical infections. More wounds may heal when treated with an antimicrobial dressing than with a non-antimicrobial dressing, but the quality of the evidence is not strong.

Guideline #3.5: For acute diabetic foot infections, surgical incision and drainage of abscess or debridement of infected tissue is often necessary and performed in combination with systemic antibiotics. Cellulitis and soft tissue infection should be stratified by severity and initially treated empirically with systemic antibiotics. Cultures of wound bed biopsies or curettages are the preferred culture method to define pathogens of infection and to implement culture directed therapy. (Level II – unchanged).

Principle: Systemic antibiotics have been demonstrated to be effective in treating acute diabetic foot infections. Cultures of wound bed biopsies or curettages are more helpful than wound swabs in determining pathogens of infection and thus in directing antibiotic therapy.

Guideline #3.6: If osteomyelitis is suspected, appropriate diagnostic measures include bone biopsy, probing the wound area to the bone with a sterile instrument, serial plain radiographs, MRI, CT, radionuclide scans, 18F-fluorodeoxyglucose (FDG) PET/CT, and Tc99m white blood cell labelled SPECT/CT. (Level II – unchanged).

Principle: Bone underlying a diabetic ulcer may become infected. Biopsy of the bone gives a definitive diagnosis, but less invasive techniques can be useful in establishing a diagnosis with a high degree of specificity and sensitivity.

Guideline #3.7: In patients with osteomyelitis, determine the bacterial pathogens and resistance patterns to antibiotics by bone culture. (Level II – unchanged).

Principle: Culture-directed antibiotic treatment seems to provide better clinical outcomes than empiric therapy. If diabetic foot osteomyelitis (DFO) is suspected, bone specimens should be obtained to identify the bacterial pathogens and to direct antibiotic therapy. The specimens should be taken with aseptic measures through sterilised skin adjacent to the wound or during a surgical procedure to prevent contamination.

Guideline #3.8: Osteomyelitis can be treated with antibiotics alone or with surgery to excise the infected bone. When there is residual osteomyelitis following minor amputation to treat osteomyelitis, 3 weeks of additional antibiotic therapy is recommended. When chosen for antibiotic therapy alone, 6 weeks of therapy is recommended. (Level III).

Principle: Osteomyelitis underlying a diabetic ulcer, can be treated medically or surgically. Comparable results have been reported with both approaches. It is widely accepted that diabetic foot osteomyelitis should be treated with 6 weeks of antibiotics. However, no clear evidence exists on the duration of treatment. Two recent randomised clinical studies have demonstrated that there was no difference in patients treated with 6 versus 12 weeks of antibiotic therapy and three versus 6 weeks of antibiotic therapy for diabetic foot osteomyelitis.

7 GUIDELINES FOR WOUND BED PREPARATION IN THE TREATMENT OF DIABETIC ULCERS

Preamble: Wound bed preparation is defined as the management of the wound to accelerate endogenous healing or facilitate the effectiveness of other therapeutic measures. The aim of wound bed preparation is to convert the biological and cellular environment of a chronic wound to that of an acute healing wound and to remove non-viable tissue and bacteria.

Guideline #4.1: A holistic examination of the patient is important to evaluate and correct causes of poor healing. This includes factors such as: systemic diseases, medications, and nutrition. (Level III).

Principle: A general medical history will help to identify systemic causes of impaired healing. The presence of a major illness or systemic disease and drug therapies such as immunosuppressive drugs and systemic steroids will interfere with wound healing by alterations in immune functioning, metabolism, inflammation, nutrition, and tissue perfusion. Autoimmune diseases such as rheumatoid arthritis or vasculitis can all delay healing and may require systemic steroids or immunosuppressive agents before local wound healing can occur.

Guideline #4.2: The evidence for nutritional interventions from RCTs to increase the incidence of DFU healing and reduce complications is not clear. (Level I).

Principle: Some studies show a correlation between poor nutritional status and impaired wound healing. However, the operational definitions used to determine the state of being malnourished are variable. The studies are small and use different nutritional interventions and different definitions for wound healing. It is also uncertain whether there is a difference in outcomes and complications between groups treated with nutritional interventions and no interventions.

Guideline #4.3: Cessation of smoking and the use of other nicotine products should be prioritised in lifestyle recommendations. Patients need to be educated on the negative impact on tissue oxygenation, wound healing, and limb amputation and offered assistance or referred to a cessation program. (Level I – unchanged).

Principle: Tissue oxygenation is a central tenet of wound healing. Macro and Microvascular disease is common in people with DFUs, and PAD is one of the most important risk factors for poor healing and amputation. Smoking decreases the oxygen delivery to the tissue and causes peripheral vasoconstriction and local wound hypoxia in the short-term and decreasing overall blood flow by causing PAD in the long-term. Smoking is also a major risk factor for amputation in patients with DFUs, quitting smoking reduces the risk of amputation. For optimal tissue perfusion, patients with a wound (if not all persons) should be advised to stop smoking.

Guideline #4.4: Debridement is required to remove non-viable or necrotic tissue, microorganisms, and cellular burden of dead and senescent cells. The health care provider can choose different debridement methods including surgical, sharp conservative, enzymatic, mechanical, biological, or autolytic. Limited evidence has identified that more frequent debridement reduces the time to wound healing. More than one debridement method may be appropriate. Sharp surgical debridement is preferred. The evidence for other debridement techniques is limited. (Level III).

Principle: Non-viable tissue, necrotic tissue, excessive microbial burden, senescent cells, and cellular debris can all inhibit wound healing. The debridement method may depend on the wound's status, the health provider's capability, the patient's overall condition, and professional licensing restrictions.

Guideline #4.5: Wounds should be cleansed initially and at each dressing change. The type of cleansing agents should be based on the wound presentation. Dirty (contaminated/foreign bodies) or infected wounds with excessive slough may require more aggressive mechanical cleaning with surfactant and/or antiseptic solutions. There is little evidence that the cleaning approach impacts wound healing or prevents infection. (Level III – unchanged).

Principle: Irrigating and cleansing the wound removes loose impediments to wound healing. Sterile saline or water is usually recommended. Tap water should only be used if the water source is reliably clean. Experimental data suggest that a nontoxic surfactant may be useful as may fluid delivered by increased intermittent pressure.

Guideline #4.6: There should be an ongoing and consistent documentation of wound history, recurrence, and characteristics (location, size, base, exudates, condition of the surrounding skin, staging, and pain) to evaluate wound bed preparation. The rate of wound healing should be evaluated to determine whether treatment is optimal. (Level III).

Principle: Ongoing evaluation of wound is necessary to evaluate changes in wound characteristics, monitor infection, and evaluate the effectiveness of therapies. Risk factors for poor healing include the duration, size, and depth of the wound.

Guideline #4.7: Patients who fail to show a reduction in ulcer size by 50% or more after 4 weeks of therapy should be reevaluated and other treatments, disease processes, and adherence should be considered. (Level II).

Principle: Percent change in wound area of DFUs over 4 weeks of treatment is a good predictor of effectiveness of therapy and likelihood of healing.

Guideline #4.8: Optimising glucose control improves wound healing. (Level II – unchanged).

Principle: Wound healing is more likely to be optimal in the setting of good diabetes management. Patients benefit from a team-approach which includes tight glucose control.

8 GUIDELINES FOR WOUND CARE DRESSINGS OR THERAPIES IN THE TREATMENT OF DIABETIC ULCERS

Preamble: There are many topical therapies available for DFUs. Most dressings are used in combination with off-loading, debridement, and infection control. It is thought that a moist wound environment physiologically favours cell migration and matrix formation. There are several criteria that should be considered when selecting a dressing including the cost, potential for iatrogenic injury, and wound exudate management. First, dressings should not damage the wound. Wound dressings or therapies should also not impede the cellular or biological phases of wound healing, which can occur if a dressing or therapy proves to be cytotoxic to host cells. Furthermore, a dressing should be used for its intended purpose otherwise issues may arise such as If the wound and surrounding tissue have continuous contact with wound exudate, the local tissue can become macerated and impede healing. Likewise, dressings that are not secure can cause friction injuries to the surrounding skin or wound bed. The cost of health care provider time, healing rate, and the unit cost of dressings should be considered when determining cost efficacy.

Guideline #5.1: Use a dressing that will maintain a moisture-balanced wound-healing environment, absorbs excess exudate and protects the peri-ulcer skin. (Level III – unchanged).

Principle: A moist wound environment physiologically favours cell migration and matrix formation while accelerating healing of wounds by promoting autolytic debridement. Wet-to-dry dressings are not considered continuously moist. Continuously moist saline gauze dressings are as effective as other types of moist wound healing in terms of healing rate.

Guideline #5.2: Select a dressing that is cost effective. (Level II).

Principle: Because of their low unit cost, moist saline gauze dressings are often viewed as the least expensive and, therefore, the most cost-effective dressing. However, when determining cost efficacy, it is important to consider the care provider's time, ease of use, and healing rate, and the unit cost of the dressing.

9 GUIDELINES FOR SURGERY IN THE TREATMENT OF DIABETIC ULCERS

Preamble: Even with optimal care of a DFU (debridement, dressings, and offloading), successful healing of diabetic ulcers may not occur. Even with robust prevention services, the incidence of re-ulceration is high. Multiple surgical procedures have been attempted to treat diabetic foot ulcers with varying degrees of success. RCTs comparing operative techniques are difficult, but data are available supporting surgery in selected patients. The focus of elective surgery is to increase range of motion or correct structural deformity to reduce pressure at the site of foot ulcers. In selected patients these types of procedures have been shown to be safe and effective to heal ulcers and prevent re-ulceration.

Guideline #6.1: Achilles tendon lengthening improves healing of diabetic forefoot wounds. (Level II) Lengthening the Achilles tendon reduces pressure on forefoot plantar ulcers in patients with limited dorsiflexion of the ankle joint. Achilles tendon lengthening has been associated with a reduction in ulcer recurrence. (Level I – unchanged).

Principle: Limited joint mobility of the toes, metatarsophalangeal joints and ankle contribute to increased forefoot pressures and ulceration. Specific procedures to lengthen tight tendons or correct structural deformities can reduce pressure and shear forces on forefoot plantar ulcers.

Guideline #6.2: Flexor tenotomy for hammertoe correction improves healing for ulcers on the tip of digits and reduces the risk of re-ulceration. (Level II).

Principle: Ulcers on the tip of patient's toes are often due to hammertoes associated with tight flexor tendons. Lengthening the tendon or cutting the tendon corrects the deformity and allows the DFU to heal.

Guideline #6.3: Arthroplasty of the great toe increases the incidence of plantar hallux ulcer healing and reduces the incidence of infection and recurrent ulcers compared to offloading alone. (Level III).

Principle: Ulcers on the interphalangeal joint of the great toe are often associated with limited motion of the first metatarsophalangeal joint. Resection of the base of the proximal phalanx of the great toe increases the first metatarsophalangeal joint range of motion, and it reduces pressures on the interphalangeal joint of the great toe. This allows these ulcers to heal and reduces the risk of re-ulceration.

Guideline #6.4: For isolated ulcers under a metatarsal head, metatarsal head resection increases the incidence of ulcer healing and reduces the incidence of infection and recurrent ulcers compared to offloading alone. (Level I).

Principle: Isolated ulcers on the ball of the foot are associated with dislocated metatarsophalangeal joints, resecting the metatarsal head eliminates high pressure areas on the sole of the foot, so DFU can heal.

Guideline #6.5: For ulcers under the metatarsal heads, pan-metatarsal head resection surgery may increase the incidence of ulcer healing and reduce the incidence of infection and recurrent ulcers compared to standard ulcer treatments (Level I).

Principle: When ulcers on the ball of the foot are associated with dislocated metatarsophalangeal joints, resecting the metatarsal heads eliminates high pressure areas on the sole of the foot, so DFUs can heal.

10 GUIDELINES FOR THE USE OF ADJUNCTIVE AGENTS AND TOPICAL DEVICES IN THE TREATMENT OF DIABETIC FOOT ULCERS

Preamble: Many agents or devices have been suggested to be used as adjuvants to debridement and off-loading therapy to treat DFUs. These adjuvant agents can be divided into topical agents to be applied to the ulcer, devices aimed at accelerating ulcer healing, and systemic drugs to treat the patient. Several of these agents have enough evidence to allow guidelines regarding their use.

11 GUIDELINES FOR PREVENTION OF RECURRENCE OF DIABETIC FOOT ULCERS

Preamble: Diabetic foot ulcerations are most commonly a result of sensory neuropathy and repetitive moderate stress/trauma on pedal skin. Ulcerations are often associated with foot deformities causing moderate to high pressures or limited joint mobility. Off-loading devices reduce pressure on the foot's sole and often reduce the patient's activity level. Off-loading the area of high pressure has been the mainstay to heal and to prevent re-ulceration. After a DFU is healed, the recurrence rates are remarkably high and costly. However, when effective prevention strategies are implemented, the incidence of re-ulceration is cut in half.

Guideline #8.1: Protective footwear should be prescribed in any patient at high-risk for ulceration (end-stage renal disease, previous amputation, previous ulcer, and previous Charcot neuro-osteo-arthropathy). Protective footwear results in a reduction of recurrent ulcerations in high-risk patients with a previous foot ulcer or amputation. (Level I – unchanged).

Principle: The aetiology of many foot ulcers involves a biomechanical component. Most treatments do not eliminate the underlying biomechanical aetiology of the ulcer. Abnormal pressure and shear stress is still present, so long-term off-loading and accommodation is necessary. By reducing pressure and shear forces on the sole of the foot, repetitive injury to the foot is reduced, and high-risk areas are protected from recurrent ulcers.

Guideline #8.2: Good foot care and daily inspection of the feet will not reduce the recurrence of diabetic ulceration alone. (Level I – unchanged).

Principle: There is contradictory data regarding the effectiveness of good foot care including proper bathing, nail trimming will reduce ulceration in diabetic feet. Self-care behaviours such as good foot care, proper bathing and nail care should be included as part of a comprehensive care program that includes professional foot care, education and therapeutic shoes and insoles.

Guideline #8.3: Preventative programs which utilise home monitoring of foot temperatures reduce re-ulceration risk. (Level I – unchanged).

Principle: Local areas of increased temperature are a sign of inflammation and deep tissue injury that precede the development of ulceration. By daily assessment of foot temperature with the calculation of asymmetry between feet, an early warning of tissue inflammation can occur up to 1 month before re-ulceration. Interventions such as activity reduction, footwear modification, and off-loading, can avert the development of ulceration which can result in a reduction of hospitalizations and significant savings to the system.

CONFLICT OF INTEREST STATEMENT

LAL, MAS, CEA, GEK, PAC, EJP, LER have no disclosures. MM is employment with molnlycke healthcare post completion of the guidelines.