Overview on diabetic foot: a dangerous, but still orphan, disease

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1 European Heart Journal Supplements (2015) 17 (Supplement A), A64 A68 The Heart of the Matter doi: /eurheartj/suv023 Overview on diabetic foot: a dangerous, but still orphan, disease Luca Dalla Paola*, Anna Carone, Lucian Vasilache, and Marco Pattavina Diabetic Foot Unit, Maria Cecilia Hospital - GVM Care & Research, Via Corriera 1, Cotignola, RA 48010, Italy KEYWORDS Diabetic foot; Amputation; Diabetic ulceration; Critical limb ischaemia; Diabetic foot surgery; Revascularization Introduction Diabetic foot must be considered as a syndrome. Two types are recognized: neuropathic foot and neuroischaemic foot. 1 Both kinds have different pathophysiological causes, diagnostic-therapeutic phases, and outcomes. It is only by recognizing the factors capable of negatively influencing prognosis and correcting them (e.g. critical ischaemia and revascularization, osteomyelitis and its surgical treatment, compartmental syndrome, and emergency surgery) that we can reduce the number of amputations in the target diabetic population. During the last 20 years, pathophysiological * Corresponding author. Tel: , Fax: , ldallapaola@libero.it Diabetic foot disease is a major health problem that concerns 15% of the 200 million patients with diabetes worldwide. More than 60% of non-traumatic amputations in the western world are performed in the diabetic population. Many patients who undergo an amputation have a history of ulceration. Treatment of foot complications is one of the main items of consumption of economic and health resources in diabetic patients. Over recent years, knowledge about the physiopathological pathways of this complication has increased significantly, together with improvements in diagnostic techniques and, above all, the establishment of a standardized conservative therapeutic approach, which allows limb salvage in a high percentage of cases. An important prelude to diabetic foot treatment is the differential diagnosis between neuropathic and neuroischaemic foot, which is essential for effective treatment. Ulceration in neuropathic foot is due to biomechanical stress and high pressure, which involves the plantar surface of the toes and metatarsal heads. In the diabetic population, peripheral vascular disease (PVD) is the main risk factor for amputation. In diabetic patients, PVD is mostly distal, but often fully involves the femoral, popliteal, and tibial vessels. It can be successfully treated with either open surgical or endovascular procedures. If PVD is ignored, surgical treatment of the lesion cannot be successful. Infection is a serious complication of diabetic foot, especially when neuroischaemic: phlegmon and necrotizing fascitis are not only limb-threatening problems, but also life-threatening. In this case, emergency surgery is needed. The aim of this review is to describe the therapeutic strategies for the various types of diabetic foot syndrome. knowledge and treatment methods for diabetic foot have progressively advanced. The percentage increase of limb salvation in patients treated in multidisciplinary units is linked to improved treatment techniques for an acutely infected foot, neuropathic foot, and the critical ischaemic conditions of neuroischaemic foot. The aim of this review is hence to define the therapeutic strategies for the various types of diabetic foot syndrome. Epidemiology of diabetic foot syndrome Around 15% of diabetics encounter a foot ulcer at some point in their lives. 2 The reported incidence and prevalence of the diabetic ulcer varies depending on the Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com

2 Overview on diabetic foot A65 population and the method of survey used. Studies carried out in the UK have shown a prevalence of this lesion between 5.3 and 7.4%. 3,4 In the USA, Ramsey et al. 5 observed a cumulative incidence rate of 5.8% of ulcerated lesions in patients discharged from the hospital over a period of 3 years. In Sweden, the yearly incidence rate of ulceration has been reported to be 3.6%, 6 whereas in Holland a yearly incidence of 2.1% of ulcers in type II diabetic patients was shown. 7 The natural history of diabetic foot syndrome is usually rapidly progressive and complex. Foot wounds can quickly progress to gangrene. Neuropathy, critical limb ischaemia, and infection can come together in the diabetic foot, and this combination can defeat any health system in the world. Successful management of this disease requires an organized multidisciplinary expert team. One of the major clinical complications of diabetes is foot ulceration 8 (Figure 1). During their lifetime, one of the seven diabetic patients develops foot ulcers, which are highly susceptible to infection. Infection may spread rapidly leading to overwhelming tissue destruction and amputation: 85% of amputations are preceded by an ulcer. Foot ulcers have important effects on the quality of life of both patients and caregivers, and are associated with major healthcare costs. Rates of amputation vary between countries, racial groups, and within countries, and may exceed 20 per inhabitants. Ulcerations and above all amputations are made worse by incorrect prognosis. Morbidity and mortality rates are higher in the patient population with ulcerations. Mortality in the perioperative period is high, e.g. 9% in a Dutch study 9 and 10 15% in the UK. 10 A retrospective study by Aulivola et al. 11 has shown the rate of mortality within 30 days of a major amputation (above or below the knee) to reach 10%. In a follow-up study of an amputated population, we have shown a 5-year survival rate of 50%. 12 The neuropathic foot In diabetes, there are two main types of diabetic foot, each of which has a characteristic form of ulceration: neuropathic and neuroischaemic foot. 13 Neuropathic foot develops ulceration at the sites of high mechanical pressure on the plantar surface. Neuropathic ulcers also result from thermal or chemical injuries that are unperceived by the patients because of loss of pain sensation. Neuropathy is associated with an 8- to 18-fold higher risk of ulceration and a 2- to 15- fold higher risk of amputation. The mechanisms through which neuropathy acts as a pathogenetic event for ulceration, and thus amputation, are complex and different. Above all, the reduction of protective sensitivity (including sensitivity to pain and heat) leads to a reduction in the perception of pain stimuli. Moreover, the motor component of neuropathy involves a progressive weakening of the intrinsic muscle component made up of interosseous and lumbrical muscles. It reveals itself as a deformation in toe flexion and the formation of overloaded plantar areas, identifiable from under the metatarsal heads and the tips of the toes (Figure 2). The autonomous component of neuropathy causes anhydrosis and dry, flaky skin, as well as an increase in arterio-venous shunting, leading to altered skin and bone perfusion. It has been widely demonstrated that a biomechanical foot alteration, which includes an increase in plantar pressures, bone abnormalities, mobility limitations, and equinus, is all linked to a significant increase in the risk of ulceration. The clinical characteristics of the neuropathic lesion are the development of an overloaded area surrounded by a callous formation before the development of the lesion, without painful symptoms. The risk of the lesion worsening in terms both of progressive deep tissue destruction and of infection is linked to the co-existence of an ischaemic component. Therefore, PVD must be excluded in the Figure 1 Diabetic foot ulcer in the plantar aspect of the foot. Figure 2 Neuropathic foot.

3 A66 L. Dalla Paola et al. initial assessment of an ulcerated lesion, verifying that its clinical characteristics are proper to those of a neuropathic lesion. The literature clearly highlights how offloading is essential in cases of plantar neuropathic lesion. Simple offloading techniques are multifaceted and include casts and boots, sandals, half shoes, or felted foam dressings. The use of a non-removable cast has recently been shown to be faster treatment for plantar neuropathic ulcers than a half-shoe. The first step in treating an uncomplicated ulcerated neuropathic lesion is local debridement, dressing, and offloading. However, clinical conditions exist in which surgery becomes the treatment of choice. Indications for the surgical treatment of plantar neuropathic ulcers are essentially: (i) co-existence of osteomyelitis; (ii) plantar exostosis that puts healed wounds at a high risk of recurrence; and (iii) chronically ulcerated wounds resistant to conservative therapy. The neuroischaemic foot The neuroischaemic foot has both neuropathy and ischaemia. It develops ulcers on the margins of the foot and toes, often at sites of pressure from poorly fitted shoes (Figure 3). This pressure is unperceived because of a coexisting neuropathy. 14 The main characteristic of PVD in diabetics is the morphological and clinical presentation. 15 Painful symptoms are often reduced or absent due to the coexistence of neuropathic sensitivity, and medial arterial calcinosis is common. These features make PVD in diabetics more difficult to diagnose and therapy more problematic than in non-diabetics. They also mean that PVD plays a fundamental role in the prognosis of major amputation. Nevertheless, since the 1990s, revascularization procedures have been demonstrated to be feasible options, contrary to the initial thinking. Procedures ranging from distal revascularization to angioplasty and bypass interventions have all shown that they can change the original prognosis for amputation. Certainly, endoluminal or surgical revascularization is the only treatment capable of reducing the number of major amputations significantly. Revascularization can restore direct arterial flow where it has been interrupted or significantly reduced. This is an indispensable condition for healing a wound in an ischemic foot without resorting to amputation. Treatment of infection There is increasing recognition of the importance and impact of diabetic foot infection in terms of both healthrelated quality-of-life issues and associated economic burden. 16 Diabetic foot infections are one of the most common diabetes-related causes of hospitalization in the USA, accounting for 20% of all hospital admissions. Readmission rates for diabetic foot infection are 40% and nearly one of six patients dies within 1 year of the infection (Figure 4). Accordingly, prompt diagnosis and treatment of infection is crucial. Guidelines on the diagnosis and treatment of diabetic foot infection have been issued by the Infectious Diseases Society of America (IDSA). 17 Cases of serious soft tissue destruction, osteomyelitis, and compartmental syndrome (progressive infection through plantar and dorsal compartments) are true medical and surgical emergencies (Figure 5). Infections of soft tissues, progressive compromise of deep tissues, and the development of osteomyelitic foci are the points which separate conservative treatment from a more aggressive surgical approach. This stage must include careful therapeutic planning, which should be based on microbiological examination after exclusion of the ischaemic component. Clearly revascularization must be postponed until after acute treatment of infection. Infections that do not pose an immediate threat of limb loss are defined as non-limb-threatening, and are Figure 3 Neuroischaemic foot. Figure 4 Infected diabetic foot.

4 Overview on diabetic foot A67 Figure 5 generally characterized by the absence of signs of systemic intoxication. Infections defined as limb-threatening show extended cellulitis, deep abscesses, osteomyelitis, or gangrene. Ischaemia characterizes a superficial lesion as limbthreatening. Acute infection (phlegmon, abscess, and necrotizing fasciitis) is an emergency condition that can threaten not only the limb but also the patient s life. It requires evaluation, and immediate hospitalization and treatment. The infection may be due to progressive destruction of soft tissues, or involvement of bone, and requires surgical treatment, and possibly amputation. The development of infection constitutes a foot care emergency, which requires referral to a specialized foot care team within 24 h. Surgical management of moderateto-severe diabetic foot infection is often required and includes aggressive incision, drainage, and debridement of non-viable soft tissue and bone. Multiple debridements are often necessary to provide adequate drainage and control of infection. In many cases, rapid treatment is absolutely essential in effectively treating an acute wound in a diabetic foot. Recourse is often necessary to surgical treatment, carried out in emergency, without considering limiting factors such as metabolic compensation, or the patient s nutritional state or vascular condition. In this specific environment, surgical debridement presents advantages over other forms of debridement (enzymatic, physical, and chemical). In less urgent cases, patients can be treated in the ward or in bed, without need of anaesthesiological support. In cases of wider and deeper infections, an operating theatre is required for adequate debridement and drainage. This is especially so in cases with bone involvement. Care organization Necrotizing fasciitis of foot and ankle. The diagnostic paths and treatments outlined above are the fruit of a multidisciplinary approach. The optimal means for improving prevention and treating patients with diabetic foot complications is through setting up an independent and dedicated multidisciplinary team. 14,18 In many contexts, where the social health impact of the problem has become manifest, the decisive step towards facing the problem in a new way has been the creation of specialized centres. The so-called foot clinics have varying characteristics depending on the healthcare environment in which the various specialists work. Our Diabetic Foot Unit is part of the Cardiothoracic and Vascular Surgery Department of Maria Cecilia Hospital, and similar units are being set up in other centres of the GVM Care & Research hospital group. The 23-bed unit includes dedicated operating theatres and an outpatient service for the management of patients on the waiting list for admission or in the course of post-surgery follow-up. The healthcare team is composed of diabetologists, cardiologists, and vascular surgeons. The multidisciplinary nature of the care is manifested through the shared diagnostic-treatment paths involving specialists in infective diseases and microbiology, radiology, and haemodynamics. The clinical activity includes, besides non-invasive and invasive vascular diagnosis, both percutaneous and surgical revascularization treatments. Approximately 700 treatments of transcatheter peripheral revascularization of the lower limbs are carried out yearly on diabetic patients referred to the Foot Unit. Ample space is reserved for surgical treatments, both emergency and elective, on peripheral trophic problems. Of particular note are the areas of osteomyelitis surgery and neuropathic arthropathy (Charcot joint disease). The phase of reconstruction is performed with use of both plastic surgery techniques (skin grafts and free flap procedures) and techniques of tissue engineering. These areas of clinical activity are also our areas of research, with studies linked to limb salvaging in diabetic patients affected by lower limb complications. Current lines of research include: (1) New surgical techniques for the conservative treatment of bone and soft tissue infection in patients with or without chronic critical limb ischaemia. (2) Evaluation of the impact of new biotechnologies on tissue reconstruction after the treatment of ischaemia and infection. (3) Innovation in the conservative surgical treatment of complicated neuropathic arthropathy (Charcot joint disease or Charcot arthropathy) through the use of new external stabilization devices. Conflict of interest: none declared. References 1. Edmonds ME. Progress in care of the diabetic foot. Lancet 1999;354: Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg 1998;176:5S 10S. 3. Kumar S, Ashe HA, Parnell LN, Fernando DJ, Tsigos C, Young RJ, Ward JD, Boulton AJ. 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