Retrospective and prospective studies have shown that elevated plantar pressure is a causative factor in the development of many plantar ulcers in diabetic patients and that ulceration is often a precursor of lower-extremity amputation. Herein, we review the evidence that relieving areas of elevated plantar pressure (off-loading) can prevent and heal plantar ulceration.
There is no consensus in the literature concerning the role of off-loading through footwear in the primary or secondary prevention of ulcers. This is likely due to the diversity of intervention and control conditions tested, the lack of information about off-loading efficacy of the footwear used, and the absence of a target pressure threshold for off-loading. Uncomplicated plantar ulcers should heal in 6 to 8 weeks with adequate off-loading. Total-contact casts and other nonremovable devices are most effective because they eliminate the problem of nonadherence to recommendations for using a removable device. Conventional or standard therapeutic footwear is not effective in ulcer healing. Recent US and European surveys show that there is a large discrepancy between guidelines and clinical practice in off-loading diabetic foot ulcers. Many clinics continue to use methods that are known to be ineffective or that have not been proved to be effective while ignoring methods that have demonstrated efficacy.
A variety of strategies are proposed to address this situation, notably the adoption and implementation of recently established international guidelines, which are evidence based and specific, by professional societies in the United States and Europe. Such an approach would improve the often poor current expectations for healing diabetic plantar ulcers. (J Am Podiatr Med Assoc 100(5): 360–368, 2010)
Skin ulcers can be very painful and detrimental in patients with systemic sclerosis, or systemic scleroderma. A brief review of scleroderma skin ulcers is presented, as well as a case study that demonstrates the effectiveness of becaplermin gel supplemented by oral immunosuppressive agents in the treatment of ulcers resulting from systemic sclerosis. The time to healing (approximately 3 months) was comparable to that associated with the oral agents and surgical interventions specifically designed to help heal scleroderma ulcers. Except for incisional biopsy, no surgical procedures were performed. (J Am Podiatr Med Assoc 92(6): 350-354, 2002)
It is well known that interleukin-18 (IL-18) plays a key role in the inflammatory process. However, there are limited data on the role IL-18 plays with diabetic foot ulcers, an acute and complex inflammatory situation. Therefore, we aimed to evaluate serum IL-18 levels of diabetic patients with foot ulcers.
Twenty diabetic patients with acute foot ulcers, 21 diabetic patients without a history of foot ulcers, and 21 healthy volunteers were enrolled in our study. Circulating levels of IL-18, and other biochemical markers are parameters of inflammation and were measured in all three groups.
Diabetic patients both with and without foot ulcers had high IL-18 concentrations (P < 0.001 and P = 0.020, respectively) when compared with the nondiabetic volunteers. Those with foot ulcers had higher levels of IL-18 level (P < 0.001), high-sensitivity C-reactive protein (hsCRP) (P = 0.001), and erythrocyte sedimentation rate (ESR) (P < 0.001) than those without foot ulcers.
We found that serum IL-18 concentrations were elevated in diabetic patients with acute diabetic foot ulcers. However, these findings do not indicate whether the IL-18 elevation is a cause or a result of the diabetic foot ulceration. Further studies are needed to show the role of IL-18 in the course of these ulcers.
Background: We assessed the tolerability and efficacy of autologous skin cell grafts in older type 2 diabetic patients with chronic foot ulcers.
Methods: Treatment with Hyalograft 3D and Laserskin Autograft was proposed to a consecutive series of type 2 diabetic patients older than 65 years affected by long-standing (>6 months) foot ulcers with an area greater than 15 cm2. Ulcer healing rates and measurements of ulcer area were determined monthly for 12 months.
Results: Seven patients with 12 ulcers, nine of which received the described treatment, were enrolled. During 12-month follow-up, all of the ulcers healed except one. In the remaining eight ulcers, the median healing time was 21 weeks (interquartile range, 4–29 weeks).
Conclusions: Autologous skin cell grafts are feasible, well tolerated, and apparently effective in the treatment of diabetic ulcers of the lower limbs in advanced age. Age did not seem to moderate healing times. (J Am Podiatr Med Assoc 101(1): 55–58, 2011)
The Management of Diabetic Foot Ulcers Through Optimal Off-Loading
Building Consensus Guidelines and Practical Recommendations to Improve Outcomes
We sought to develop a consensus statement for the use of off-loading in the management of diabetic foot ulcers (DFUs).
A literature search of PubMed for evidence regarding off-loading of DFUs was initially conducted, followed by a meeting of authors on March 15, 2013, in Philadelphia, Pennsylvania, to draft consensus statements and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to assess quality of evidence and develop strength of recommendations for each consensus statement.
Evidence is clear that adequate off-loading increases the likelihood of DFU healing and that increased clinician use of effective off-loading is necessary. Recommendations are included to guide clinicians on the optimal use of off-loading based on an initial comprehensive patient/wound assessment and the necessity to improve patient adherence with off-loading devices.
The likelihood of DFU healing is increased with off-loading adherence, and, current evidence favors the use of nonremovable casts or fixed ankle walking braces as optimum off-loading modalities. There currently exists a gap between what the evidence supports regarding the efficacy of DFU off-loading and what is performed in clinical practice despite expert consensus on the standard of care.
Background: A comparison of the cost-effectiveness of becaplermin plus good wound care (BGWC) versus good wound care (GWC) alone in treating patients with diabetic foot ulcers (DFUs) may enable physicians and health-care decision makers in the United States to make better-informed choices about treating DFUs, which currently contribute to a substantial portion of the economic burden of diabetes.
Methods: Data from three phase III trials were used to predict expected 1-year costs and outcomes, including the average percentage reduction from baseline in wound surface area (WSA), the direct costs of DFU therapy, and the cost per cm2 of WSA reduction.
Results: At 20 weeks, the BGWC group had a statistically greater probability of complete wound closure than the GWC group (50% versus 35%; P = .015). Based on reported WSA reduction rates, DFUs in the BGWC group were predicted to close by 100% at 27 weeks, and those in the GWC group were predicted to close by 88% at 52 weeks. The GWC group had higher total estimated 1-year direct cost of DFU care ($6,809 versus $4,414) and higher cost per cm2 of wound closure ($3,501 versus $2,006).
Conclusions: Becaplermin plus good wound care demonstrated economic dominance compared with GWC by providing better clinical outcomes via faster reduction in WSA and higher rates of closure at a lower direct cost.
Background: People with diabetic foot ulcers report poor quality of life. However, prospective studies that chart quality of life from the onset of diabetic foot ulcers are lacking. We describe change in quality of life in a cohort of people with diabetes and their first foot ulcer during 18 months and its association with adverse outcomes.
Methods: In this prospective cohort study of adults with their first diabetic foot ulcer, the main outcome was change in Medical Outcomes Study 36-Item Short Form Health Survey scores between baseline and 18-month follow-up. We recorded baseline demographics, diabetes characteristics, depression, and diabetic foot outcomes and mortality at 18 months.
Results: In 253 people with diabetes and their first ulcer, there were 40 deaths (15.8%), 36 amputations (15.5%), 99 recurrences (43.2%), and 52 nonhealing ulcers (21.9%). The 36-Item Short Form Health Survey response rate of survivors at 18 months was 78% (n = 157). There was a 5- to 6-point deterioration in mental component summary scores in people who did not heal (adjusted mean difference, −6.54; 95% confidence interval, −12.64 to −0.44) or had recurrent ulcers (adjusted mean difference, −5.30; 95% confidence interval, −9.87 to −0.73) and a nonsignificant reduction in those amputated (adjusted mean difference, −5.00; 95% confidence interval, −11.15 to 1.14).
Conclusions: Quality of life deteriorates in people with diabetes whose first foot ulcer recurs or does not heal within 18 months. (J Am Podiatr Med Assoc 99(5): 406–414, 2009)
We sought to evaluate the relationship between baseline hemoglobin A1c (HbA1c) level and clinical outcomes, including foot ulcer outcome (resolved versus unresolved) and wound-healing time, in individuals with type 2 diabetes.
A prospective observational study was conducted on 99 patients presenting with a diabetic foot ulceration. Patient and ulcer characteristics were recorded. Patients were followed up for a maximum of 1 year.
After 1 year of follow-up, 77% of ulcers healed and 23% did not heal. Although this study demonstrated that the baseline HbA1c reading was not a significant predictor of foot ulcer outcome (P = .603, resolved versus amputated), on further statistical analyses, when HbA1c was compared with the time taken for complete ulcer healing in the resolved group (n = 77), it proved to be significant (P = .009).
These findings have important implications for clinical practice, especially in an outpatient setting. Improving glycemic control may improve ulcer outcomes. Prediction of outcome may be helpful for health-care professionals in individualizing and optimizing clinical assessment and management of patients. Identification of determinants of outcome could result in improved health outcomes, improved quality of life, and fewer diabetes-related foot complications.
Neuropathic foot ulcers are a common complication in patients with diabetes. These ulcers are often slow to heal and can lead to infection, further tissue destruction, osteomyelitis, and amputation. These patients pose a challenge to clinicians who must determine the best treatment options while balancing the risks, benefits, and costs. Conservative therapies often present disappointing results, and a number of newer “biologic bandages” have been developed to better assist the healing process. We describe results from diabetic patients with neuropathic foot ulcers treated with a new amniotic membrane–based allograft.
The increasing resistance of bacteria to antibiotics and the frequency of comorbid conditions of patients make the treatment of diabetic foot infections problematic. In this context, photodynamic therapy could be a useful tool to treat infected wounds. The aim of this study was to evaluate the effect of repeated applications of a phthalocyanine derivative (RLP068) on the bacterial load and on the healing process.
The present analysis was performed on patients with clinically infected ulcers who had been treated with RLP068. A sample for microbiological culture was collected at the first visit before and immediately after the application of RLP068 on the ulcer surface, and the area was illuminated for 8 minutes with a red light. The whole procedure was repeated three times per week at two centers (Florence and Arezzo, Italy) (sample A), and two times per week at the third center (Stuttgart, Germany) (sample B) for 2 weeks.
Sample A and sample B were composed of 55 and nine patients, respectively. In sample A, bacterial load decreased significantly after a single treatment, and the benefit persisted for 2 weeks. Similar effects of the first treatment were observed in sample B. In both samples, the ulcer area showed a significant reduction during follow-up, even in patients with ulcers infected with gram-negative germs or with exposed bone.
RLP068 seems to be a promising topical wound management procedure for the treatment of infected diabetic foot ulcers.