Overview

Diabetic foot ulcers (DFUs) are arguably among the most difficult types of wounds to manage; the etiology of these wounds poses some of the greatest clinical challenges for healing, considering the multifaceted nature of diabetes mellitus (DM). Multiple patient-related factors must be addressed and controlled through faithful adherence to the prescribed plan of care, which is developed by both the patient and clinicians to ensure success.

Standard of Care for Diabetic Foot Ulcers

Treatment of DFUs requires multidisciplinary provider involvement (podiatry, vascular, infectious disease, internal medicine or family practice, endocrinology, cardiology, nephrology, and physical therapy). The standard of care for patients with DFUs includes medical management of chronic disease, including nutrition and glucose control, routine wound assessments with ulcer grading and risk stratification, topical wound management with attention to serial debridements and moist wound healing, treatment of infection, mechanical offloading of the affected extremity, edema management, surgical correction of biomechanical deformities, revascularization, and patient education.

Topical Management: No topical dressing has been proven superior, and primary dressings are mainly selected based on wound assessment, availability, cost, patient considerations, and providers’ preference. Antimicrobial agents should be added only when standard of care has failed to show wound progress.

Offloading: Evidence for offloading is applicable to non-ischemic, non-infected DFUs. The gold standard for offloading interventions includes use of non-removal devices such as total contact casts.

Infections: The Infectious Diseases Society of America (IDSA) cautions against treating patients with clinically uninfected wounds with antibiotics. If there is suspected clinical infection based on thorough assessment, prescribe antibiotics based on quantitative tissue culture and sensitivity. If empiric antibiotics must be initiated, consider factors such as current histology data, history of previous similar infection, and severity of infection. Regarding osteomyelitis, in the absence of ischemia or fulminant necrotizing infections, clinicians may elect to treat surgically versus medically (surgical excision with shorter course of antibiotics if surgical margin is clear of infection versus longer course of antibiotics).¹

Intervention with Advanced Therapies

The IDSA 2012 practice guidelines and the 2016 Joint guidelines of the Society for Vascular Medicine (SVM) and the American Podiatric Medical Association (APMA) for management of the diabetic foot recommend adjunctive therapies for DFUs that fail to demonstrate greater than 50% reduction in surface area after four weeks of standard therapy.^1,2 This recommendation is reflected in most insurance payer structures for approval of such therapies. Current evidence does not support use of advanced therapies earlier in the course of treatment for DFUs; they have the potential to increase cost of care if they are utilized inappropriately, and they should not be used before attempting lower-cost, evidence-based modalities.²

Negative Pressure Wound Therapy (NPWT): NPWT for DFUs decreases length of hospital stay and complication rates. It has been shown in randomized controlled trials to reduce time to closure and cost of treating DFUs and other wounds left open to heal by secondary intention.^{3, 4} The guidelines of the Society for Vascular Surgery (SVS) in collaboration with the APMA and the SVM suggest reserving NPWT for DFUs not responding to standard or advanced wound dressings four to eight weeks after initiation of a therapeutic plan of care.

Cellular and/or Tissue-Based Products (CTPs): These products include human skin allografts and composite, allogeneic, and acellular matrices. Some evidence suggests decreased risk for amputation and improved rate of closure compared with standard care.⁵ The SVS/SVM/APMA guidelines recommend use of composite fibroblast-containing matrix, acellular allograft, or porcine tissue for DFUs refractory to standard therapy. Results of multiple studies have been discounted or downgraded to low levels of evidence for high risk of bias as a result of non-blinding of outcomes for some CTPs. This adjunctive therapy should be seen in terms of risk-to-benefit ratio and cost containment, while keeping the individual patient’s needs in mind.²

Growth Factors (GFs): GFs are available as adjunctive therapies to standard wound healing modalities, with varying levels of evidence supporting their use. There is some evidence to suggest higher rates of DFU closure with use of GFs, notably platelet-derived GF (PDGF).⁶ Meta-analyses of trials using growth factors (e.g., vascular endothelial GF, fibroblast GF) demonstrated more patients with complete wound healing in the groups receiving versus not receiving GFs. Numerous studies, both industry-sponsored and wound center initiated, have demonstrated varying benefits in time to closure, but there is not sufficient evidence to suggest that application of GF is ubiquitously beneficial as part of the plan of care or generalized recommendations for healing refractory DFUs. The 2016 International Working Group on the Diabetic Foot (IWGDF), the 2016 Wound Healing Society (WHS) guidelines, and the 2016 SVS and APMA guidelines do not share consensus on the use of GFs for healing of refractory DFUs.

Hyperbaric Oxygen Therapy (HBOT): Studies show decreased time to closure and reduced chance of amputation in DFUs in which at least 30 days of standard therapy have failed in patients with improved transcutaneous oxygen pressure (TcPO2; tissue oxygenation) testing after HBOT.⁷ The evidence for HBOT is conflicting, with some studies citing decreased incidence of amputation, and others showing similar rates of healing in groups without HBOT versus groups with HBOT. The SVS/SVM/APMA guidelines recommend HBOT for patients with DFUs who have adequate perfusion and fail to respond to standard of care treatment.

Conclusion

There is an upward trend in use of advanced treatment options with the increase in research, clinicians’ training and comfort with therapies, and clinicians’ education, as well as an increase in prevalence and complexity of DFUs. No ubiquitous consensus has been reached on recommendation of these therapies for regular use in routine care of the DFU. The decision to use advanced therapies should be based on a combination of clinical findings, access to products or therapies, cost, and clinician skillset. Order of use of the therapies described previously is not clinically relevant, and no specific guideline recommends utilizing these therapies in specific chronological order. However, repeated evaluations of the patient and the wound status are paramount to success with any therapy. This includes reassessment of the presence of developing infection, vascular status, adherence to mechanical offloading therapy, and overall medical management of chronic conditions.

References

1. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54:e132–73.

2. Hingorani A, LaMuraglia GM, et al. The management of diabetic foot: a clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg. 2016;63(2 Suppl):3S–21S.

3. Armstrong DG, Lavery LA, Abu-Rumman P, et al. Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot. Ostomy Wound Manage. 2002;48:64.

4. Philbeck TE, Schroeder WJ, Whittington KT. Vacuum-assisted closure therapy for diabetic foot ulcers: clinical and cost analysis. Home Health Consultant. 2001;8:1.

5. Santema TB, Poyck PP, Ubbink DT. Skin grafting and tissue replacement for treating foot ulcers in people with diabetes. Cochrane Database Syst Rev. 2016;(2):CD011255.

6. Martí-Carvajal AJ, Gluud C, Nicola S, et al. Growth factors for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2015;(10):CD008548.

7. Alavi A, Sibbald RG, Mayer D, et al. Diabetic foot ulcers: part II. Management. J Am Acad Dermatol. 2014;70(1):21.e1–24; quiz 45.