Heel ulcers don't heal in diabetes. Or do they?

AIM: To obtain information on outcome of heel ulcers in diabetes. METHODS: Data were recorded prospectively on all patients with heel ulcers who were referred to a specialist multidisciplinary clinic between 1 January 2000 and 30 November 2003. Outcomes were assessed on 31 March 2004. RESULTS: There were 157 heel ulcers in the patients referred in the period. Three ulcers were excluded from analysis because of associated osteomyelitis. Of 154 remaining ulcers (121 limbs; 97 patients, 55 male; mean age 68.5 +/- 12.8 sd years), 101 (65.6%) healed after a median (range) 200 (24-1225) days. Of 53 non-healed ulcers, 11 (7.1% of 154) were resolved by major amputation, 30 (19.5% of 154) were unhealed at time of patient's death, and 12 (7.8% of 154) remained unhealed. Ulcers healed in 59 of 97 affected patients (60.8%). Twenty-six patients (26.8% of 97) died during the period, of whom 20 died with ulcers unhealed. Worse outcomes were observed in larger ulcers (P = 0.001, Mann-Whitney U-test = 1883.5) and limbs with clinical evidence of peripheral arterial disease (P = 0.001, Mann-Whitney U-test = 1163.00). Backward step-wise logistic regression analysis showed 70.1% of healing could be predicted from these two baseline characteristics. CONCLUSIONS: The common perception that 'heel ulcers don't heal' is not reflected in clinical practice. Outcome is generally favourable even in a population often affected by serious comorbidity and with limited life expectancy. These data can be used to help define management plans, as well as a basis for counselling of the individual patient.     

Clinical outcome of diabetes patients hospitalized with foot ulcers, Dar es Salaam, Tanzania.

AIMS: To determine the prevalence rate, clinical features, risk factors, and clinical outcome of foot ulcers in diabetes patients admitted to Muhimbili National Hospital, Dar es Salaam, Tanzania. METHODS: A prospective cohort study of newly hospitalized, adult diabetes patients with foot ulcers was conducted during January 1997 to December 1998 (study period). Detailed clinical and epidemiological data were recorded for each patient, followed by a comprehensive physical examination. Clinical outcome was documented. RESULTS: Of 627 diabetes patients evaluated during the study period, 92 (15%) had foot ulcers. Of these 92 patients, 30 (33%) were selected for surgery (minor and major amputations); the rest were managed conservatively. Patients who underwent surgery were more likely than those who did not to have gangrene (P < 0.001) or neuropathy (P < 0.01). On stratification by severity of ulcers, patients with Wagner score > or = 4 were significantly more likely than those < 4 to have neuroischaemic foot lesions (P < 0.001) or delayed presentation to hospital (P < 0.001). The overall mortality rates for amputees and non-amputees were similar (29%); the highest in-patient mortality rate (54%) was observed among patients with severe (Wagner grade > or = 4) ulcers who did not undergo surgery. CONCLUSIONS: Diabetic foot ulcers are associated with significant morbidity and mortality in Tanzania. Mortality rates among patients with severe ulcers remain high despite surgery. Thus, surgery undertaken during the less severe stages of ulcers may improve patient outcome. Education of patients should underscore the importance of foot care and consulting a doctor during the early stages of foot ulcer disease.     

Long-term prognosis for diabetic patients with foot ulcers

Abstract. Objective. To evaluate the recurrence of foot ulcers as well as the cumulative amputation and mortality rates in diabetic patients with previous foot ulcers. Design. A prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer with a median follow-up of 4 years. Setting. A multidisciplinary foot-care team. Population. Five-hundred-and-fifty-eight consecutive diabetic patients with foot ulcers treated between 1 July 1983 and 31 December 1990 were followed to final outcome. Out of these patients, 468 healed either primarily (n = 345) or after minor or major amputations (n = 123) and 90 died before healing had occurred. Those 468 patients who healed were included in this prospective study from the time of healing. Main outcome measures. Patients were followed according to a standardized protocol with registration of foot lesions, amputation, morbidity and mortality. Clinical examination was performed twice yearly. Results. After 1, 3 and 5 years of observation 34%, 61% and 70% of the patients, respectively, had developed a new foot ulcer. The recurrence rate of foot lesions was slightly higher among patients who previously had had an amputation (P < 0.05, P < 0.01 and non-significant, respectively). Among patients with previous primary healing the cumulative amputation rates were 3%, 10% and 12% after 1, 3 and 5 years of follow-up compared with 13%, 35% and 48% among those who previously healed after amputation, irrespective of previous amputation level (P < 0.001 at all time-points). All amputations except three were initiated by a foot ulcer deteriorating to deep infection or progressive gangrene. The long-term survival ratio was lower among patients healed after previous amputation (80%, 59%, 27%) compared with patients with previously primary healing (92%, 73%, 58%) after 1, 3 and 5 years of observation, respectively (P < 0.001. P < 0.01 and P < 0.001 respectively). The mortality rate was twice as high among primarily healed and four times as high among patients with amputation compared to an age- and sex-matched Swedish population. Conclusion. These findings stress the need for life-long surveillance of the diabetic foot at risk and the necessity of preventive foot care among diabetic patients with previous foot lesions, and particularly among those who had had a previous amputation.     

Effectiveness of a new brand of stock 'diabetic' shoes to protect against diabetic foot ulcer relapse. A prospective cohort study.

AIMS: Diabetic patients with podopathy (diabetic foot syndrome) may need protective footwear, be it customized or industrially produced stock 'diabetic' shoes (SDS). The effectiveness of each type of 'diabetic' shoe needs to be proven clinically, e.g. in terms of prevention of foot ulceration. The following study assesses a new German SDS, the LucRo shoe, which consists of rocker-shaped walking sole, a standardized shock absorption insole, and soft uppers without stiff toe-caps. The LucRo SDS has been registered as a Medicinal Product according to the European Community Guideline 93/42/EC. PATIENTS AND METHODS: A total of 92 high-risk diabetic patients (mean age 63 years, duration of diabetes 13 years) with healed foot ulcer were recruited prospectively over 31 months; 87 patients suffered from polyneuropathy, 24 patients had peripheral ischaemic vessel disease. One group of patients (n = 60) received the LucRo SDS and wore them, while the remaining patients (n = 32) did not receive the SDS and were forced to use their normal footwear. This allocation reflects the haphazard reimbursement policies of the individual patients' health insurance, and is in accordance with the current German legislation. The patients were followed up for up to 42 months until the first foot ulcer relapse, or the end of the study. RESULTS: There were no differences between the groups concerning age, sex, type and duration of diabetes, prevalence of polyneuropathy and peripheral ischaemic vessel disease, frequency of foot care and mortality rate. The first year annual rate of foot ulcer relapse was significantly different between the groups: 60% without SDS vs. 15% with SDS. The overall cumulative ulcer-free survival was significantly greater with SDS (P < 0.0001, log rank test). CONCLUSION: The LucRo stock 'diabetic' shoe appears effective in the prevention of foot re-ulceration in high-risk patients with diabetic podopathy.     

Diabetic foot ulcers in a multidisciplinary setting An economic analysis of primary healing and healing with amputation

Abstract. Objectives . To perform an economic analysis of primary healing and healing with amputation in diabetic patients with foot ulcers. Design . A retrospective economic analysis based on a prospective study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer. Setting . A multidisciplinary foot-care team. Subjects . A total of 314 consecutively presenting diabetic patients with foot ulcers. Forty patients died before healing occurred. In those patients who healed primarily (n = 197) or after amputation (n = 77), a retrospective economic analysis was performed. Interventions . All patients were treated by a multi-disciplinary foot care team consisting of diabetologist, orthopaedic surgeon, diabetes nurse, podiatrist and orthotist both as in- and out-patients. The patients were followed by the team from admittance until final outcome, i.e. primary healing or healing with amputation or death. Main outcome measures . Data from both the prospectively collected patient material and from patient records were used to estimate the cost for hospital care, antibiotics, surgery, out-patient care, staff attendance, drugs and material for ulcer dressings, and orthopaedic appliances. Results . The total costs were SEK 51000 (3000–808000) for patients with primary healing and SEK 344000 (27000–992000) for healing with amputation. Costs for in-patient care were 37% of total average costs for primary healing and 82% for patients with amputation. The costs for topical treatment of the ulcers in out-patient care were 45% of the total average cost for primary healed and 13% for patients who healed with amputation. The costs for products used for ulcer dressings were 21% of total costs for topical treatment, i.e. 9% and 3% of total average costs for primary healing and healing with amputation, respectively. Costs for visits to the foot care team, antibiotics and orthopaedic appliances were low in relation to total costs. Conclusion . Treatment of diabetic patients with foot ulcers in a multidisciplinary system was associated with relatively low costs. Healing with amputation was associated with high costs mainly due to multiple and extended hospitalization. These findings indicate the potential cost savings of preventive and multi-disciplinary foot care.     

Factors contributing to the presentation of diabetic foot ulcers

We have undertaken a prospective study of the presentation of all 669 ulcers seen in a specialist multidisciplinary foot clinic between 1 January 1993 and 1 August 1996, with particular reference to the factors which precipitated ulceration as well as to any delays in referral. Nearly two-thirds (61.3 %) of all lesions were first detected by the patient or a relative, and the remainder by a healthcare professional. The median (range) time which elapsed between ulcer onset and first professional review was 4 (0–247) days, and the median time between first review and first referral to the specialist clinic was 15 (0–608) days. Significant delays were judged to have occurred in 39 instances. The most common precipitant of ulceration was rubbing from footwear, which was responsible for 138 (20.6 %). Fifty-eight (8.7 %) were the result of immobilization from other illness, and a further 24 were the consequence of surgery. Overall, professional factors contributed to the development or deterioration of 106 lesions (15.8 % total). These results should form the basis of strategies designed to minimize the onset of ulceration in those known to be at risk: educational strategies need to be directed at professionals as much as at patients. © 1997 John Wiley & Sons, Ltd.     

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: A systematic review

Clinical outcomes of patients with diabetes, foot ulceration, and peripheral artery disease (PAD) are difficult to predict. The prediction of important clinical outcomes, such as wound healing and major amputation, would be a valuable tool to help guide management and target interventions for limb salvage. Despite the existence of a number of classification tools, no consensus exists as to the most useful bedside tests with which to predict outcome. We here present an updated systematic review from the International Working Group of the Diabetic Foot, comprising 15 studies published between 1980 and 2018 describing almost 6800 patients with diabetes and foot ulceration. Clinical examination findings as well as six non‐invasive bedside tests were evaluated for their ability to predict wound healing and amputation. The most useful tests to inform on the probability of healing were skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg, or TcPO₂ ≥ 25 mmHg. With these thresholds, all of these tests increased the probability of healing by greater than 25% in at least one study. To predict major amputation, the most useful tests were ankle pressure < 50 mmHg, ABI < 0.5, toe pressure < 30 mmHg, and TcPO₂ < 25 mmHg, which increased the probability of major amputation by greater than 25%. These indicative values may be used as a guide when deciding which patients are at highest risk for poor outcomes and should therefore be evaluated for revascularization at an early stage. However, this should always be considered within the wider context of important co‐existing factors such as infection, wound characteristics, and other comorbidities.     

Does close glycaemic control promote healing in diabetic foot ulcers? Report of a feasibility study

AIM: To undertake a pilot study to determine the feasibility of a definitive trial of the effect of close glycaemic control on healing of foot ulcers in diabetes. METHODS: All patients attending a dedicated multidisciplinary clinic for the management of established ulcers over a 20-week period were systematically screened for inclusion in a randomised, single-blinded study. FINDINGS: Two hundred individuals with foot ulcers attended the clinic during the recruitment period, but only nine met the predefined inclusion and exclusion criteria. One of these was withdrawn because of an adverse event immediately before recruitment, two proved incapable of administering insulin injections and were withdrawn prior to randomization. Four withheld consent, and one was advised to withhold consent by his community nurse. One was randomised and completed the 3-month study. The study was abandoned at 20 weeks when it was decided that it would be unlikely that a sufficient number of suitable patients would ever be recruited, and that it would therefore be unethical to approach further subjects. CONCLUSIONS: It was concluded that although evidence is required to guide future practice in this field, the study design chosen was not feasible.     

Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers.

AIMS: To study the distribution of transforming growth factor-beta (TGF-beta) 1, 2 and 3, and TGF-beta receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF-betas with those of chronic venous ulcers. METHODS: Skin biopsies were obtained from the leg or the foot of non-diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-beta 1, 2 and 3 and TGF-beta receptors (RI and RII) was done by staining 8-microm skin sections using appropriate antibodies. Protein levels of TGF-beta were measured by Western blot analysis. RESULTS: TGF-beta3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF-beta1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers. CONCLUSION: The lack of TGF-beta1 up-regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity.     

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.     

Validation of a system of foot ulcer classification in diabetes mellitus

Objective The lack of a simple, robust classification of diabetic foot ulcers has critically hampered research into optimum patterns of care. We have therefore attempted validation of the previously published S(AD) SAD system, which is based on grading of ulcer features using simple clinical methods. Research design and methods This was a prospective study in which 300 people with ulcers newly referred to a hospital‐based multidisciplinary clinic between 1 January 2000 and 1 July 2002 were classified at the time of their first assessment. If a patient had more than one episode, the last to occur was selected as the index ulcer. If two or more ulcers were registered simultaneously, the one which was regarded as the more significant was chosen. Ulcers were categorized according to area, depth, sepsis, ischaemia and neuropathy. All patients were followed for at least 6 months, or until death if earlier. Outcome criteria used were healed and unhealed (unhealed persisting, unhealed at amputation or death) and were cross‐tabulated with different baseline variables. Results Ulcers healed in 209 of the 300 patients (69.7%), while 30.0 (10%) had been resolved by amputation (eight major; 22 minor) and 32 (10.7%) by death. Twenty‐nine (9.7%) persisted unhealed. There were significant differences in outcome according to area (χ² = 25.9, P < 0.001), depth (χ² = 33.8, P < 0.001), sepsis (χ² = 13.5, P = 0.004) and arteriopathy (χ² = 33.7, P < 0.001), but not to denervation (χ² = 5.1, P = 0.16). The strength of these associations was confirmed using Somers d: area (r_s = ?0.24, P < 0.001), depth (r_s = ?0.32, P < 0.001), sepsis (r_s = ?0.15, P < 0.01), arteriopathy (r_s = ?0.30, P < 0.001), denervation (r_s = ?0.10, P = 0.08). Logistic regression analysis using area, depth, sepsis and arteriopathy as independent variables, and those which contributed significantly to the model were area (P = 0.01), depth (P < 0.001) and arteriopathy (P < 0.001). Conclusions These data demonstrate that simple clinical methods can be used to categorize features of individual ulcers, and that area, depth and arteriopathy contribute independently to a model to predict outcome. A system of classification such as this is an essential requirement for the categorization of populations with similar features and similar prognosis, which may then be used as the basis for prospective research into optimal wound management.     

Becaplermin gel in the treatment of diabetic neuropathic foot ulcers

Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery.     

The Charcot foot.

AIMS: To review the clinical manifestations of the Charcot foot in diabetes mellitus, with particular reference to theories concerning aetiology. METHODS: Systematic review of the published literature, searching for the keywords 'Charcot', 'foot and diabetes' and 'neuropathy' on Medline, as well as by examination of the references in recent published reviews. CONCLUSIONS: The Charcot foot of diabetes mellitus is a common problem, and yet is not widely recognized by non-specialists. The failure of professionals to identify the condition in its early phases is probably largely responsible for the gross deformity which follows continued weight-bearing. The condition is confined to those with severe peripheral neuropathy. It is thought to result from three factors: motor neuropathy leading to the development of abnormal forces within the foot, subsequent disorganization of the foot as a result of associated osteopenia and progressive destruction from continued weight-bearing, enabled by reduced pain sensation. The cause of the osteopenia is not known, but it is associated with increased bone blood flow, which may be mainly the result of loss of sympathetic innervation. The importance of increased limb blood flow in the pathogenesis of the Charcot foot has been recognized for over a century. Paradoxically, the increased flow is associated with evidence of macrovascular disease, in that the prevalence of vascular calcification of pedal vessels approaches 90%. After an interval of many months, the condition tends to evolve: the increased blood flow lessens, the osteopenia is reduced and the disorganized bones become sclerotic. This tendency for the condition to evolve remains unexplained, since it would not be expected if the condition was caused solely by progressive denervation. As a result, it is suggested that another factor may be involved in the pathogenesis of the Charcot foot: an abnormal vasomotor reflex, analogous to reflex sympathetic dystrophy, occurring against a background of severe peripheral neuropathy. The resolution of the condition occurs because it is the reflex component of the hyperaemia which proves self-limiting.     

Blood flow in the foot,polyneuropathy and foot ulceration in diabetes mellitus

Summary Comparable groups of diabetic patients asymptomatic of neuropathy (Group A), with chronic painful polyneuropathy (Group B) and painless polyneuropathy causing recurrent foot ulceration (Group C) were studied for differences in pedal blood flow, peripheral somatic and autonomic neuropathy and vascular calcification. Blood flow abnormalities detected by doppler waveform analysis, and consistent with reduced peripheral vascular resistance, were found in all three diabetic patient groups. The abnormalities were of similar severity in Group A and B but generally more marked in Group C. Tests of peripheral somatic nerve function became progressively more abnormal from Group A to Group C. Autonomic neuropathy was equally severe in Groups B and C, although mild abnormalities were recorded in diabetic patients asymptomatic of neuropathy. A similar pattern was seen for vascular calcification in the tarsal and metatarsal arteries: marked in both neuropathic groups (B and C) but mild in Group A. It was concluded that abnormal blood flow consistent with reduced peripheral vascular resistance is very common in the feet of diabetic patients whether or not they are symptomatic of neuropathy, and is most severe in those with chronic painless polyneuropathy and recurrent foot ulceration. No clear relationship was found between autonomic nerve dysfunction and the degree of abnormality of blood flow.     

Why do foot ulcers recur in diabetic patients?

AIM: To investigate factors predisposing to recurrent foot ulceration in patients with diabetes mellitus. METHODS: Two groups of patients who had attended a specialist Diabetes Foot Centre were assessed: relapsers (n = 26), whose foot ulceration had recurred at least twice, and nonrelapsers (n = 25), whose initial ulcer had not recurred for at least 2 years. RESULTS: In the relapser group 10/26 patients waited at least 24 h before reporting symptoms compared with only 2/25 in the nonrelapser group (P < 0.05). Vibration perception threshold (volts) was 38 +/- 12 (mean +/- SD) in relapsers compared with 25 +/- 13 in nonrelapsers (P < 0.005). Cold perception threshold (degrees C) was 9.1 +/- 4.6 in relapsers compared with 5.1 +/- 3.5 in nonrelapsers (P<0.005). HbA1c (%) was significantly raised at 8.5 +/- 1.7 in relapsers compared with 7.6 +/- 1.2 in nonrelapsers (P = 0.03). Alcohol intake was 0.5 (median, interquartile range 0-2) units per day in relapsers compared with 0.0 (median, interquartile range 0-0.25) units in nonrelapsers (P = 0.04). Smoking habits, housing conditions, visual acuity, threshold for warm perception and the Doppler pressure index were not significantly different in the two groups. CONCLUSIONS: Patients who develop recurrent foot ulceration delay in reporting symptoms, when compared with diabetic patients whose foot ulceration does not recur. The relapsers also have evidence of poorer glycaemic control, more neuropathy and increased alcohol intake.     

The effects of ulcer size and site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers.

AIMS: The outcome of foot ulcers is affected by wound depth, infection, ischaemia and glycaemic control. The aim of this study was to determine the effects of ulcer size, site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers. METHODS: Diabetic patients with new foot ulcers presenting during a 12-month period had demographics and ulcer characteristics recorded at presentation. Ulcers were followed-up until an outcome was noted. RESULTS: One hundred and ninety-four patients (77% males) with a mean (+/- SD) age and duration of diabetes of 56.6 +/- 12.6 and 15.4 +/- 9.9 years, respectively, were included in the study. The majority of ulcers were neuropathic (67.0%) and present on the forefoot (77.8%) with a median (interquartile range) area of 1.5 (0.6-4.0) cm2. Amputations were performed for 15% of ulcers; 65% healed; 16% remained unhealed and 4% of patients died. The median (95% confidence interval) time to healing was 10 (8.8-11.6) weeks. Ulcer area at presentation was greater in the amputation group compared to healed ulcers (3.9 vs. 1.2 cm2, P < 0.0001). Ulcer area correlated with healing time (rs = 0.27, P < 0.0001) and predicted healing (P = 0.04). Patient's age, sex, duration/type of diabetes, and ulcer site had no effect on outcome. CONCLUSIONS: Ulcer area, a measure of ulcer size, predicts the outcome of foot ulcers. Its inclusion into a diabetic wound classification system will make that system a better predictor of outcome.