Abstract
An observational study of 2 years was promoted by the Italian Association for Cutaneous Ulcers (AIUC) in order to monitor the epidemiology of leg ulcers, the trend of healing and the more frequent therapeutic approaches in lower limb ulcers. Fifty‐nine sites in 14 different Italian regions involved in the study, with 1333 enrolled patients (1163 patients fully evaluated and followed up for 9 months). A prevalence of females (62%) was observed with a mean age of 70 years and a high rate of hypertension (62%), diabetes (38%) and obesity (29%). Venous ulcer was most frequent (55%), followed by mixed (25%) and diabetic (8·3%) ulcers. Basically, all patients received a local therapy (LT) (compression and advanced local therapies), while 63% of patients have an associated systemic pharmaceutical treatment. Ulcer healing rates progressively increased throughout the study and despite the type of observational study does not allow conclusions on the treatment, it was observed that the patients receiving additional systemic drugs were associated with a more rapid acceleration of healing rates of ulcers compared to LT alone (3 months: 39·7% versus 29·2%; 6 months: 62·0% versus 47·0%; 9 months: 74·7% versus 63·8%). In particular, the Studio Ulcere Vascolari (SUV) study showed that a combination treatment with sulodexide and compression therapy allows for a greater increase in the healing rates in venous ulcers.
Keywords: Combined therapy, Epidemiology, Healing rates, Lower limbs vascular ulcer, Observational study
Introduction
Ulcers of the lower limbs represent a social problem both in terms of patients' suffering and costs of the national health insurance for treating, preventing or decelerating the progression of the disease 1. The prevalence of lower limb ulceration among the whole population ranges between 0·18% and 2%, but in patients older than 65 years, the prevalence may increase up to 5%. In the USA, it has been recently calculated that just the ulcers secondary to chronic venous disease are responsible for at least 4·6 million lost working days and over 1 billion USD of social costs every year 2.
Ulcers of the lower limbs result from different underlying, often concomitant, pathological conditions, and they are usually classified as of venous, arterial, neurotrophic, lymphatic, malignant, infectious and inflammatory origin 2. Most leg ulcers are caused by venous insufficiency (45–60%), arterial insufficiency (10–20%), diabetes (15–25%) or a combination of all (10–15%) 3, 4. In ulcers particularly caused by chronic venous failure, the important pathophysiological factors are reflux, venous outflow obstruction and inflammatory proteinase activity 5, 6. For what concerning arterial ulcers, although many arterial diseases can lead to ulcers, the most common cause is an arterial obstruction due to peripheral arterial disease (PAD) 3, 4, 7. In the diabetic ulcers, the main pathophysiological factors are neuropathy (60–70%), PAD (15–20%) or a combination of both (15–20%) 3, 4. Finally, several studies have reported that many ulcers have more than one aetiology 8, 9, 10, 11.
The management of the more usual lower leg ulceration is based on treating the underlying disease; however, debate still continues not only about how venous ulcers should be treated but also where they should be treated, although in recent years a better understanding of the pathological mechanisms underlying skin damage in vascular ulcers has allowed more rational pharmacotherapeutic approaches to be made.
Compression therapy (phlebological compression bandages and medical compression stockings) is still considered the basic treatment for venous ulcers, and its ability to heal venous ulcers is clearly supported by a body of evidence from many studies 12, 13, 14. Graduated compression increases venous flow, decreases valvular reflux while walking and increases the effectiveness of the calf muscle pump resulting in a ‘thinning leg’. There is no clear advantage among the various ulcer dressings, although patients may prefer hydrocolloidal occlusive dressings because of their convenience 15. In addition to compression therapy, some systemic therapies may lead to a significant contribution in increasing the rate of healing of venous ulcers. Among these drugs, pentoxifylline, flavonoids and sulodexide are considered as beneficial adjuvant treatment to the compression therapy 16, 17. Finally, arterial ulcer care includes management of identified vascular risk factors, patient education to maximise peripheral perfusion and local dressing routines reflecting the principles of moist wound healing 18, 19.
In spite of the large panel of available therapeutic approaches, the healing rate of vascular ulcers is far to be acceptable. The healing rate can vary depending on initial ulcer size and duration 20, thus, even a mean 12‐week healing rate of 70% has been reported for small ulcers in specialist leg ulcer clinics 21, but in general, the rates of healing observed usually were in a range that goes from 20% to 60% approximately after 12 weeks of therapy 16, 22, 23, 24. In addition, recurrence rates between 12% and 30% are often reported 21, 22.
Given the heterogeneity of vascular ulcers, the varied therapeutic approaches and the variability of the healing rate, the Italian Association for Cutaneous Ulcers (‘Associazione Italiana per le Ulcere Cutanee’; AIUC) has promoted an observational study of 2 years in Italy – the Study of Vascular Ulcers (‘Studio Ulcere Vascolari’; SUV) – in order to make a recent picture of the vascular ulcers, including the epidemiology of patients, the characteristics of ulcers, the approach in the local and pharmacological treatment of specialists and the ulcer healing rates. The preliminary results of the SUV study have been presented at the XI AIUC National Congress (Rimini, 26–29 September 2012). In this paper, the final and complete results of the SUV study were presented and discussed.
Materials and methods
Objective of the study
The study was aimed at making a picture of the national epidemiology of vascular ulcers of lower limbs (arterial, venous, mixed and diabetic), the features of patients [sex, age, body mass index (BMI) and concomitant diseases] and the characteristics of ulcers (aetiology, location, magnitude, duration, status of the wound, infection and pain). At the same time, the study was designed to provide a feedback on the efficacy of current clinical practice, through the registration of clinical data of ulcer healing since baseline to 3, 6 and 9 months after the enrolment of patients and beginning of therapy.
The main objectives of the SUV study were to determine (i) the pattern and characteristics of treated ulcers; (ii) the rate of ulcer resolution, which was defined as a complete re‐epithelisation of the wound area according to the different therapeutic strategies used by the investigators participating; (iii) the time needed to ulcer healing and (iv) the concomitant diseases, epidemiology and characteristics of patients.
The study design
The observational study was promoted by the AIUC and it was carried out between January 2010 and December 2011. The SUV study involved 59 Italian sites specialised in the treatment of vascular ulcers (Appendix A), which were coordinated by Prof. Alessandro Apollonio, Operative Unit (OU) of Angiology, Hospital Belcolle, Viterbo (Italy). The study protocol was authorised by the local ethics committee.
Patients older than 18 years with leg ulcers of vascular aetiology (i.e. arterial, venous, mixed [arterial–venous] and diabetic) and decubitus leg ulcer, have been enrolled in the study. Patients with leg ulcers of different origins (i.e. neoplastic ulcers or ulcers induced by an autoimmune response) were excluded from the study.
The patients attended the site and participated in the study according to the guidelines and recommendations of the NHS, that is, patients spontaneously required a medical visit by a NHS specialist because of an ulcer of lower limbs, and they received the best available therapy and/or care according to the opinion of each investigator.
At baseline, the investigators have collected the following information for each enrolled patient: demographic data (age, sex, height, weight and calculated BMI); concomitant diseases (such as hypertension, diabetes and obesity); aetiology (venous, mixed, arterial, diabetic, decubitus and combined), number and location (leg, foot and ankle) of lower limb ulcers; signs and symptoms of ulcers, such as size, oedema and wound bed status (eschar, fibrin, granulation and epithelisation); exudates (low, medium and high); ulcer deepness (epidermis, dermis and subcutaneous) and infection. In addition, ulcer pain was assessed by means of a 0–10 cm visual analogue scale (VAS) and the impact of ulcer on daily working activities was assessed (disability).
Each patient received the treatments as prescribed by the specialist according to the normal practice of the site, and the treatments were recorded in the patients' charts. Data for the SUV study were collected at regular intervals after the enrolment, that is, 3, 6 and 9 months after the start of therapy. At these times, the healing progress of the ulcers was assessed (number and percentage of patients with healed ulcers) and compared to baseline.
The study was conducted in accordance with current guidelines of good clinical practice (GCP) regulations relating to clinical trials and the Declaration of Helsinki and was approved by the ethics committee.
Statistical analysis
Demographic and clinical data have been summarised and reported as frequency tables or tables with central tendency and dispersion, using the most appropriate indices of the actual distribution of each single variable (mean, standard deviation, min–max range of observed values).
The analysis of the factors that are possibly associated with the outcome (healing) of the wound has been performed by means of the Pearson χ2 test; ‘odds ratio’ has been calculated as well as confidence intervals (CI) at 95%. The continuous variables have been analysed by means of the analysis of variance (ANOVA) and Student's ‘t’ test.
The analysis of Kaplan–Meier has been adopted in order to evaluate the incidence of wound healing after 3, 6 and 9 months after enrolment. The differences between groups have been assessed by means of a log‐rank test. Differences have been considered as significant if P < 0·05. No missing data have been replaced and no replacement policy has been implemented; as a matter of fact, the analysis fully reflects the observed values. The statistical analysis has been performed using the software SPSS Statistical Package, ver. 15.0.
Results
A total of 59 Italian sites (SUV study group) involved in the study, thus representing 14 regions spread throughout the Italian territory (the participating Italian sites are listed in Appendix A). The enrolment and the observation of patients started on January 2010 and ended on December 2011, with a total study period of approximately 24 months. In total, 1333 patients were enrolled, but 170 patients were not evaluated (mostly because of missing data, such as characteristics of the ulcer).
Epidemiology and ulcer characteristics
Baseline characteristics of patients included in the SUV study are reported in Table 1. The finally evaluated population consisted of 1163 patients, which were equally spread throughout the North (327), Central (307) and South Italy and Islands (529). Patients were more females (722; 62·1%) than males (441; 37·9%) with a mean age of 69·6 ± 13·3 years. The venous ulcer resulted to be the most frequent with 54·9% of cases, followed by the mixed arterial–venous ulcer (25·2%), the diabetic ulcer (8·3%) and the arterial ulcer (3·9%). It is noteworthy to mention that a small, but significant, percentage of patients had combined ulcers (4·2%), that is, the simultaneous presence of ulcers of different aetiology in the same patient.
Table 1.
Baseline characteristics of patients
| Evaluated patients | 1163 |
| Age (years) | 69·6 ± 13·3 |
| Sex | |
| Male | 441 (37·9%) |
| Female | 722 (62·1%) |
| Distribution (region) | |
| North Italy | 327 (28·1) |
| Central Italy | 307 (26·4) |
| South Italy and Islands | 529 (45·5) |
| Type of lower limb ulcer | |
| Venous | 639 (54·9%) |
| Mixed | 293 (25·2%) |
| Arterial | 45 (3·9%) |
| Diabetic | 96 (8·3%) |
| Decubitus | 41 (3·5%) |
| Combined | 49 (4·2%) |
Concomitant diseases were shown in Table 2. High frequency of comorbidity was observed, namely 62·9% of hypertension, 38·3% of diabetes and 28·9% of obesity (BMI > 30). These comorbidities were present in different frequencies depending on the type of ulcer, both in the case of hypertension and diabetes (P < 0·001, χ2 test) and obesity (P < 0·01, χ2 test).
Table 2.
Comorbidities of the patients by type of aetiology at baseline. Statistical significance was assessed by means of χ2 test
| All ulcers (n = 1163) | Venous (n = 639) | Mixed (n = 293) | Arterial (n = 45) | Diabetic (n = 96) | Decubitus (n = 41) | Combined (n = 49) | P | |
|---|---|---|---|---|---|---|---|---|
| Hypertension | 62·9% | 55·3% | 77·4% | 81·8% | 76·1% | 67·5% | 87·2% | <0·001 |
| Diabetes | 38·3% | 24·3% | 48·5% | 50·0% | 100% | 37·8% | 77·6% | <0·001 |
| Obesity | 28·9% | 34·5% | 27·2% | 10·5% | 25·0% | 23·1% | 28·9% | <0·01 |
The characteristics of the ulcers by type of aetiology at the baseline are reported in Table 3. Females prevailed on males in venous, mixed, arterial and decubitus ulcers, while diabetic and combined ulcers were slightly more frequent in male patients. The mean age of patients ranged between 67·5 years for venous ulcers and 73·8 years for combined ulcers. About half of all ulcers observed were located on legs (49·2%); other locations were ankle (31·4%), foot (14·3%) and multiple locations (5·1%). Considering the data by type of ulcer, the most of venous and mixed ulcers were located at ankle and legs, while arterial, decubitus and combined aetiology ulcers were more frequently located at legs and foots; the diabetic ulcers showed a preferential location on foot (74·7%). At the baseline visit, ulcers lasted since almost 1 year on average (mean: 11·3 ± 41·0 months), but arterial ulcers were present since a mean period of 8 months while decubitus leg ulcers were present since almost 18 months. A single ulcer was present in about 70% of cases, while two or more ulcers were present in 26·3% of patients; the pattern of multiple ulcers was less frequent in venous types (21·1%) and more frequent in the decubitus ulcers (41·0%). Considering the size of all the ulcers, the maximum and minimum diameter observed was 4·6 ± 3·8 cm and 2·7 ± 2·3 cm, respectively. In particular, the average frequency of ulcers of maximum diameter greater than 4 cm was of 35·6%, in a range between 22·3% of diabetic ulcers and 51·2% of those combined.
Table 3.
Characteristics of the ulcers by type of aetiology at baseline
| Venous (n = 639) | Mixed (n = 293) | Arterial (n = 45) | Diabetic (n = 96) | Decubitus (n = 41) | Combined (n = 49) | |
|---|---|---|---|---|---|---|
| Sex | ||||||
| Males | 34·0% | 37·5% | 48·9% | 54·2% | 36·6% | 51·0% |
| Females | 66·0% | 62·5% | 51·1% | 45·8% | 63·4% | 49·0% |
| Age (years) | 67·5 ± 13·8 | 73·5 ± 11·8 | 70·6 ± 13·1 | 70·3 ± 11·4 | 69·1 ± 14·9 | 73·8 ± 12·7 |
| Ulcer sites | ||||||
| Ankle | 39·1% | 27·9% | 15·6% | 9·5% | 23·1% | 16·3% |
| Leg | 54·9% | 57·7% | 35·6% | 11·6% | 20·5% | 32·7% |
| Foot | 3·2% | 7·2% | 46·6% | 74·7% | 43·6% | 30·6% |
| Combined (≥ 2) | 2·8% | 7·2% | 2·2% | 4·2% | 12·8% | 20·4% |
| Ulcer present since month | 11·9 ± 46·8 | 11·0 ± 32·3 | 8·0 ± 11·0 | 6·7 ± 13·0 | 17·2 ± 67·6 | 13·7 ± 23·6 |
| Multiple ulcers | 21·1% | 33·7% | 31·8% | 25·8% | 41·0% | 100% |
| Size | ||||||
| < 2 cm | 21·8% | 15·7% | 29·5% | 28·7% | 13·2% | 23·3% |
| 2–4 cm | 43·3% | 38·2% | 31·8% | 48·9% | 55·3% | 25·6% |
| > 4 cm | 34·9% | 46·1% | 38·6% | 22·3% | 31·6% | 51·2% |
| Oedema | 88·0% | 86·0% | 56·8% | 63·6% | 80·0% | 85·7% |
| Wound bed | ||||||
| Eschar (black) | 13·5% | 18·8% | 44·4% | 31·3% | 46·3% | 28·6% |
| Fibrin (yellow) | 66·8% | 64·8% | 46·7% | 60·4% | 43·9% | 71·4% |
| Granulation (red) | 23·6% | 18·1% | 17·6% | 18·8% | 19·5% | 18·4% |
| Epithelisation (pink) | 2·7% | 6·1% | 4·4% | 2·1% | 0·0% | 4·1% |
| Exudate | ||||||
| Low | 32·7% | 26·7% | 41·9% | 37·5% | 36·6% | 16·7% |
| Medium | 42·6% | 49·1% | 41·9% | 45·8% | 46·3% | 47·9% |
| High | 24·7% | 24·2% | 16·3% | 16·7% | 17·1% | 35·4% |
| Wound depth | ||||||
| Epidermis | 16·3% | 11·5% | 7·1% | 6·3% | 7·9% | 7·3% |
| Dermis | 63·5% | 54·2% | 52·4% | 46·9% | 52·6% | 39·0% |
| Subcutaneous | 20·1% | 34·4% | 40·5% | 46·9% | 39·5% | 53·7% |
| Infection | 7·7% | 7·3% | 11·4% | 12·6% | 7·5% | 20·8% |
| Pain (visual analogue scale) | 5·0 ± 2·6 | 5·7 ± 2·6 | 6·3 ± 2·5 | 5·0 ± 3·2 | 4·4 ± 2·5 | 5·4 ± 2·7 |
| Disability | 15·1% | 20·9% | 45·2% | 33·7% | 56·8% | 43·2% |
The oedema was largely present in all ulcers observed, with a frequency ranging from 56·8% of patients with arterial ulcers to 88% of those with venous ulcers. The status of the wound bed observed was predominantly with fibrin with a frequency varying from 44% to 71% of cases, according to different aetiologies. The presence of eschar was observed in percentages higher in diabetic (31·3%), arterial (44·4%) and decubitus ulcers (46·3%), while venous or mixed ulcers had eschar in a 13·5% and 18·8% of the cases, respectively. The granulation tissue was very low, with a frequency ranging from around 17% to 23%. The exudate was present in all the ulcers, mainly of medium grade with a frequency that ranged from 41·9% (arterial ulcers) to 47·9% (ulcers combined).
The depth of the wound was predominantly at the level of the dermis, with frequencies ranging from 46·5% (diabetic ulcer) to 63·5% (venous ulcers), with the exception of combined ulcers where in most cases it has been observed as a deepest wound, type of subcutaneous (53·7%). Venous and mixed ulcers were those less deep with subcutaneous tissues interested in 20·1% and 34·4% of the cases, respectively.
Infected ulcers were observed in a variable range from 7·3% to 12·6%, with the exception of combined ulcers that were the most infected with 20·8% of cases.
The observed ulcers were particularly painful, with a mean VAS score of 5·2 ± 2·6, ranging from 4·4 ± 2·5 (decubitus) to 6·3 ± 2·5 (arterial). In addition, a severe disability, defined as impairment in working activities, was observed in all ulcers with a wide variation depending on the aetiology of ulcer observed. In particular, ulcers with greater frequency of disability were those of decubitus (56·8%), arterial (45·2%) and combined (43·2%), while the less disabling were those of venous (15·1%) or mixed (20·9%).
Ulcer treatments and healing rate
All the patients received a local treatment for their leg ulcers in order to accelerate the healing of ulcer wound, which more often consisted either elastic or non‐elastic bandage and advanced local therapies aimed to stimulate the granulation process and the riephitelisation of the wound. In 725 patients (63% of population), the local treatment was joined with a systemic treatment that consisted of different drugs, including glycosaminoglycans, heparins, antibiotics, anti‐hypertensives, anti‐thrombotic, anti‐diabetic and anti‐inflammatory. The more used drug was glycosaminoglycan sulodexide, used in 637 patients (54·7%).
The ulcer healing rates by treatments and by ulcer aetiology are reported in Table 4. As a result of the treatment (either local or local plus systemic), a consistent percentage of patients showed an improvement of the wound with an increasing incidence of ulcer healing. By stratifying patients according to the therapeutic approach, it has been found that patients receiving drugs in association with local therapy (LT) showed a significantly (P = 0·001) higher rates of healed ulcers (all types of ulcers) compared to patients given LT alone at the follow‐up visits of 3 months (39·7% versus 29·2%), 6 months (62·0% versus 47·0%) and 9 months (74·7% versus 63·8%).
Table 4.
Ulcer healing. Number of patients visited, the number of drop outs at each follow‐up visit and the frequency of patients healed. The percentage of patients with healed ulcers is reported according to the therapeutic approach (LT) and the type of ulcer
| 3 months | 6 months | 9 months | P * | |||
|---|---|---|---|---|---|---|
| No. of patients | 997 | 660 | 560 | |||
| No. of drop outs | 166 | 503 | 603 | |||
| Percentage of patients with healed ulcers | All ulcers | LT (n = 314) | 29·2 | 47 | 63·8 | |
| LT + drugs (n = 725) | 39·7 | 62 | 74·7 | 0·001 | ||
| Venous ulcers | LT (n = 152) | 31·7 | 49·3 | 64·7 | ||
| LT + drugs (n = 423) | 44·1 | 69·0 | 77·1 | 0·001 | ||
| Mixed ulcers | LT (n = 86) | 33·1 | 53·4 | 60·6 | ||
| LT + drugs (n = 169) | 36·1 | 56·5 | 77·8 | n.s. | ||
| Arterial and diabetic ulcers | LT (n = 40) | 22·0 | 45·0 | 65·0 | ||
| LT + drugs (n = 88) | 28·0 | 45·0 | 62·0 | n.s. | ||
| Combined ulcers | LT (n = 17) | 7·0 | 7·0 | 54·0 | ||
| LT + drugs (n = 26) | 41·0 | 56·0 | 85·0 | n.s.** | ||
| Decubitus ulcers | LT (n = 19) | 26·0 | 32·0 | 40·0 | ||
| LT + drugs (n = 19) | 40·0 | 40·0 | 70·0 | n.s.** | ||
LT, local therapy; n.s., not significant.
Log‐rank test (Mantel–Cox);
Whilst observing percentage differences quite important among the therapies, the limited numerosity of the groups of patients do not allow to detect if the differences between treatments are statistically significant (power of the study).
The data about the treatments and the healing observed showed, however, different outcomes depending on the type of ulcer considered. The beneficial effects of an associated systemic treatment were mostly evident in patients with venous ulcers, which achieved a complete wound healing in 44·1%, 69·0% and 77·1% of cases, respectively, after 3, 6 and 9 months compared to 31·7%, 49·3% and 64·7% of patients receiving LT only, at the same follow‐up times (P = 0·001). In venous ulcer treatments, the adjuvant systemic therapy was mainly represented by the use of sulodexide (82·7%). The analysis of these patients by Kaplan–Meier curve, shown in Figure 1, suggests that treatment with LT plus sulodexide more rapidly accelerates the healing time of venous leg ulcers compared with only local treatment (incidence of healing 44·3% versus 31·7% at 3 months, 68·8% versus 49·3% at 6 months and 76·9% versus 64·7% at 9 months).
Figure 1.
Kaplan–Meier curve: cumulative incidence of healed venous ulcers in patients receiving only local therapy (LT) or LT plus sulodexide as pharmacological treatment. Log‐rank test (Mantel–Cox): P = 0·001.
In mixed, arterial and diabetic ulcers, the diversity in treatment does not seem to make a difference in terms of healing frequencies, but still have excellent healing rate in all cases comparable with those obtained in venous leg ulcers. The small sample of decubitus and combined ulcers does not allow a reliable statistical evaluation; however, the combination of local treatment plus systemic drugs appears to be more effective than that with only LT, because comparing the two treatments (LT plus drug versus LT) after 9 months of observation recorded a healing frequency of 85% versus 54% in combined ulcers and 70% versus 40% in decubitus ulcers.
In the two populations of ulcers more observed, namely venous and mixed, the effect of comorbidity on wound healing was investigated, as shown in Table 5. In venous ulcers, blood hypertension was reported to significantly delay the healing of ulcer with an odds ratio (OR) of 1·45 (CI at 95%: 1·07–2·06; P < 0·02), while obesity showed OR of 1·46 (CI 95%: 1·04–2·04; P = 0·03). Obesity represented a detrimental factor for the healing of mixed ulcers also, with an OR of 1·73 (CI 95%: 1·01–2·97; P < 0·05).
Table 5.
Concomitant diseases and their effect on the outcome (healing) of venous and mixed ulcers*
| Disease | Odds Ratio | CI 95% | P | |
|---|---|---|---|---|
| Venous | Hypertension | 1·45 | 1·07–2·06 | < 0·02 |
| Ulcers | Diabetes | 1·25 | 0·86–1·82 | n.s. |
| Obesity | 1·46 | 1·04–2·04 | 0·03 | |
| Mixed | Hypertension | 1·24 | 0·71–2·17 | n.s. |
| Ulcers | Diabetes | 1·13 | 0·70–1·82 | n.s. |
| Obesity | 1·73 | 1·01–2·97 | < 0·05 |
n.s., not significant.
Statistical significance was assessed by means of χ2 test.
Discussion
The SUV study is certainly one of the most important epidemiological investigations on vascular ulcers of lower limbs carried out in Italy in the recent years, because of the high quantity of data collected (1163 patients, of whom about 50% followed up until 9 months after start of therapy) and the widespread presence of participating centres (59 centres representing 14 Italian regions). Published epidemiological studies have been performed recently in leg ulcers in Romania 25 and New Zealand 26, in diabetic ulcers in China 27, in hypertensive leg ulcers in France 28 and in chronic leg wounds in Denmark 29; to our knowledge, however, the SUV study is the only one that has involved more than one thousands patients affected by different types of leg ulcers (venous, arterial, diabetic, mixed, etc.).
The analysis of the data collected during the study showed some interesting confirmations and news. First of all, the SUV study confirmed that about 80% of the totally observed ulcers are either of venous (55%) or mixed (25%) origin. In a similar epidemiological study in 489 consecutive patients with 639 chronic foot and leg ulcers, half of the wounds were made by diabetic foot ulcers (309), followed by venous leg ulcers (188), arterial ulcers (109) and vasculitis (33) 29. In another survey, the estimated prevalence of chronic leg and foot ulcers was 0·19%, being venous ulcers the most common (38%), of which 87% were treated with some form of compression therapy, followed by ulcers with missing or unknown aetiology ranging between 6% and 31% 30. An important new feature of the SUV study is, however, the observation of a small but very critical group of patients, such as 49 cases (4·2%), with the simultaneous presence of combinations of different cause's ulcers.
The SUV epidemiological study also confirmed that the lower limb ulcers represent a social problem, both in terms of patients' suffering (strong pain and reduced mobility) and social impact (severe disability), with a high rate of comorbidity among patients with vascular ulcers of the lower limbs. In particular, arterial hypertension, diabetes and obesity results as major diseases and they could be unfavourable prognostic factors that could complicate the normal process of re‐epithelisation of ulcers. In particular, it is observed that obesity is a negative risk factor for the healing of both venous leg ulcers (OR = 1·46) and mixed ulcers (OR = 1·73) and that hypertension may be associated with a greater prognosis unfavourable in the healing of venous leg ulcers (OR = 1·45). Data particularly interesting that should be confirm in a future with a proper study.
In terms of healing, the data recorded at 3, 6 and 9 months after the start of treatment showed an incidence of healing varying according to the type of ulcers observed and, in some cases, also to the type of therapy used. Considering all the ulcers observed, the frequencies of healing vary according to the time of treatment in a range between 29% and 39% (3 months), 47% and 62% (6 months), and 63% and 74% (9 months), showing at the same time a good increase in healing rate over time and also an important percentage of unhealed ulcers.
As regards the treatments, while emphasising and remembering that this is an observational study with descriptive purposes, it is seen that in the venous leg ulcers the use of combined therapy consisting of local treatment plus sulodexide is associated with a more rapid (P = 0·001) acceleration of the healing rate, in agreement with what has already been documented in the past with randomised double‐blind studies 16, 31, 32.
Sulodexide, a drug with known anti‐thrombotic and pro‐fibrinolytic properties, probably helps in healing of ulcers due to the ability of modulation of matrix metalloproteinases (MMPs) as recently demonstrated 33.
In conclusion, 1163 patients affected by vascular ulcers of the lower limbs and coming from different regions of Italy were observed for 9 months. From epidemiology point of view, the data showed the prevalence of female patients (62%), with a mean age of 70 years, with predominance of venous ulcer (55%) or mixed ulcer (25%) and with significant rate of comorbidity (hypertension, obesity and diabetes), pain and disability. After 9 months of therapy, the healing rates observed were ranging from 63·8% to 74·7%, based on the type of treatment carried out, supporting, in particular in venous ulcers, the importance of the use of the combination therapy (local plus systemic).
Acknowledgements
The authors state that they have no conflict of interest to declare.
SUV Study Group Investigators (n. 59)
Aiello Alessandro (Catania), Aliquò Maria Stella (Palermo); Aloisi Daniele (Bologna); Amitrano Sergio (Napoli); Antignani Pier Luigi, Schachter Ilana (Roma); Apollonio Alessandro (Viterbo); Battaglia Luigi (Catanzaro); Benazzi Silvia (Verona); Bevilacqua Andrea (Frosinone); Bonasso Carlotta (Torino); Branca Giuseppe, Bruni Sergio (Firenze); Calcopietro Francesco (Catanzaro); Capasso Liliana (Napoli); Cardinale Antonio (Matera); Carnali Maurizio (Ancona); Catalano Francesco (Bari); Conti Angela (Cosenza); De Santis Francesco (Napoli); Del Genio Francesco (Napoli); Di Donna Vincenzo (Foggia); Di Mezza Giovanni (Napoli); Donnola Giancarlo (Taranto); Faella Fausto (Napoli); Fonti Massimo (Ancona); Formentano Vittorio (Milano); Garozzo Salvatore (Catania); Ghirarduzzi Angelo (Reggio Emilia); Giacinto Francesco (Cosenza); Giffoni Gianfranco (Alessandria); Guarnaccia Demetrio (Napoli), Kouloubis Panagiote (Latina); Lania Marcello (Roma); Lapidari Marco (Alessandria); Lauletta Vincenzo (Taranto); Longobardi Pasquale (Ravenna); Maiello Antonio (Napoli); Mazzei Antonio (Napoli); Mezzacasa Silvana (Verona); Miglioranzi Renzo, Nasole Emanuele (Verona); Mongiardino Vittorio (Torino); Musso Alberto (Torino); Palumbo Paolo (Palermo); Pastorino Sandro (Genova); Polidoro Raffaele (Latina); Prisco Vincenzo, Greco Rosaria (Salerno); Rescigno Enrico, Rosa Giorgio (Genova); Ricci Elia, Moffa Fabrizio (Torino); Sciarrone Roberto (Taranto); Segramora, Vittorio (Milano); Serantoni Simone, Gazzabin Luca, Procacci Tiziana (Prato); Spirito Gianpietro (Savona); Talarico Francesco (Caltanissetta); Tarantini Salvatore (Rimini); Tarantini Vincenzo (Bari); Trama Paolo Antonio (Trapani); Trulli Raffaele (Chieti); Vena Pasquale, D'Armenzo Anna (Matera); Vetruccio Francesco (Lecce); Vettorello Gianfranco (Udine).
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