Catálogo de publicaciones - libros

Foot ulceration is one of the most common precursors to lower extremity amputations among persons with diabetes (,). Ulcerations are pivotal events in limb loss for two important reasons. They allow an avenue for infection (), and they can cause progressive tissue necrosis and poor wound healing in the presence of critical ischemia. Infections involving the foot rarely develop in the absence of a wound in adults with diabetes, and ulcers are the most common type of wound in this population (). Foot ulcers therefore play a central role in the causal pathway to lower extremity amputation ().

Foot infections are among the most common causes of hospitalization in the diabetic population, accounting for 20% of all diabetes-related admissions. Complicated foot infections may require treatment by amputation—as many as 6–10% of all patients with diabetes will undergo amputation for treatment of infection (–), accounting for 57% of nontraumatic lower extremity amputations (–). The scope of the problem is compelling. Infections and complicated vascular diabetic foot problems result in 50,000 amputations a year in the United States (). The Centers for Disease Control and Prevention estimated the annual treatment cost of amputees within this group at $1.2 billion for the year 1997. However, this figure does not include the cost of rehabilitation, prosthetic devices, or lost income. These treatment costs are likely to escalate as the prevalence of diabetes is on the rise. A recent epidemiology study shows an increase of the overall prevalence of diabetes from 4.9% in 1990 to 6.5% in 1998 ().

The foot of patients with diabetes mellitus is affected by several processes which not only contribute to the development and progression of infection but on occasion alter the appearance of the foot in ways, which may obscure the clinical features of local infection. Neuropathy involving the motor fibers supplying muscles of the foot causes asymmetric muscle weakness, atrophy, and paresis which in turn result in foot deformities and maldistribution of weight (or pressure) on the foot surface. Dysfunction of the sensory fibers supplying the skin and deeper structural elements of the foot allows minor and major injury to these tissues to proceed without appreciation by the patient. As a result of neuropathy, the foot may be dramatically deformed, ulcerate in areas of unperceived trauma (mal perforans), and on occasion be warm and hyperemic in response to deep structural injury (acute Charcot’s disease). This warmth and hyperemia may be misinterpreted as cellulitis and ulceration, whereas a major portal of entry for infection may be uninfected. In the patient with diabetes, peripheral neuropathy may develop in isolation or commonly in parallel with atherosclerotic peripheral vascular disease. The latter involves major inflow vessels to the lower extremity but commonly is associated with occlusive lesions of the tibial and peroneal arteries between the knee and ankle. The resulting arterial insufficiency can alter the appearance of the foot and obscure infection. Rubor may reflect vascular insufficiency rather than inflammation and conversely pallor may mute the erythema of acute infection. Gangrene and necrosis may be primarily ischemic or may reflect accelerated ischemia in the setting of infection. In sum, the diagnosis of infection involving the foot in patients with diabetes requires a careful detailed examination of the lower extremity and its blood supply.

Charcot’s classic work on the “arthropathies of locomotor ataxia”; was first published in 1868 while he was the chief physician at the Salpetriere in Paris (,). In describing the joint affectations of patients with tabes dorsalis, he noted severe deformities, crepitations, and instability with gradual degrees of healing over time. Of primary importance, he believed these changes to be secondary to the underlying disease in which there was an associated nutritive deficiency in the spinal cord. Although lesions in this structure are far less frequently involved in the pathogenesis of neuroarthropathy than peripheral nerve lesions, Charcot was certainly intuitive in this regard. In his own words, “How often have not I seen persons, not yet familiar with this arthropathy, misunderstand its real nature, and, wholly preoccupied with the local affection, even absolutely forget that behind the disease of the joint there was a disease far more important in character, and which in reality dominated the situation. . . .”; ()

Over the last few years, substantial advances have been made in our understanding of diabetic foot ulcers, the importance of thorough surgical debridement, and how this standard therapeutic modality impacts on wound bed preparation. Importantly, wound bed preparation is revolutionizing the way we approach nonhealing or difficult to heal wounds. Much of what we do clinically, from elimination of bacterial burden, to debridement, and to the use of new technologies to heal diabetic foot ulcers, can now be seen as helping wound bed preparation and facilitating the process of healing. From a therapeutic standpoint, at least in the United States, large multicenter clinical trials have led to the regulatory approval of topically applied platelet-derived growth factor (PDGF)-BB (Regranex, Ortho McNeill, NJ) and bioengineered skin (Apligraf, Organogenesis, Canton, MA; Dermagraft, Smith & Nephew, Largo, FL), and have dramatically increased the number of available therapeutic options. However, not to be forgotten are advances that these and other clinical trials have brought to the standard of care for treating neuropathic diabetic foot ulcers. Indeed, these improvements in standards of care for diabetic foot ulcers have raised the bar for proving the effectiveness of new treatments. Stated differently, it has become harder to prove the effectiveness of new therapeutic agents. Thus, from now on we may be looking for “quantum”; jumps in therapeutic efficacy in the treatment of diabetic foot ulcers.

The ideal wound environment can be described as moist, warm, and clean. There is no single dressing that is suitable for all wounds or even for the same wound at different stages in the healing process. Successful wound management involves the use of dressing or agents to control moisture content, insulate the wound from its surroundings, and provide an environment that reduces inflammation and bacterial burden without harming the cells involved in the repair process. Therefore, wound-dressing functions will vary depending on the type of wound and the particular stage of repair. For example, during the inflammatory phase of wound healing, the ideal dressing should provide an environment that would limit or control vascular leakage, proteolytic degradation of the provisional matrix, free radical generation, oxygen consumption, and breakdown products of nonviable tissue (). All of these are disruptive to the wound and any measure that limits or controls inflammation should promote wound healing, provided that it does not compromise the ability to resist infection nor leukocyte and macrophage function. Throughout the inflammatory phase wounds are most vulnerable to infection, especially in the patient with diabetes (). Therefore, the goals are to control infection, and reduce bacterial burden by the removal of nonviable tissues and the use of antibacterial agents. During the regenerative phase (granulation and re-epithelialization) the environment should be moist, warm and protective to endothelium, fibroblasts, and keratinocytes. After the wound has resurfaced (and for a period of weeks thereafter), the wound is particularly vulnerable to reinjury because the epithelium is thin and immature. During this last phase of tissue remodeling the wound dressing environment should provide protection from pressure and friction while controlling edema. During this third phase, the clinician should begin to plan for prevention of ulcer recurrence.

Foot ulceration with infection is one of the leading causes of hospitalization for patients with diabetes mellitus. Although solid data on the true incidence and prevalence of diabetic foot ulcerations do not exist, it is believed that approx 15% of patients with diabetes will develop a foot or leg ulceration in their lifetime (). The rate of recidivism is also staggering in this population with 50% of ulcerations recurring within 18 months. The number of lower extremity amputations among patients with diabetes has been well documented for years. Patients with diabetes are 15 times more likely to undergo a major lower extremity amputation than patients without diabetes, with the total number of major limb amputations being more than 50,000 ().

Amputation of the foot may be indicated when neuropathy, vascular disease, and ulcerative deformity have led to soft tissue necrosis, osteomyelitis, uncontrollable infection, or intractable pain.

Diabetic foot and ankle wounds usually occur because of acute or repetitive trauma in an insensate and biomechanically unstable foot. The body is unable to heal the wound owing to persistent trauma, biomechanical abnormality, infection, inadequate blood flow, ineffective immune system, or poor nutrition and the acute wound converts into a chronic wound. The goal is to transform the chronic wound into an acute healing wound with healthy granulation tissue, neoepithelialization, and wrinkled skin edges. The steps to achieve a healthy healing wound include establishing a correct diagnosis, ensuring a good local blood supply, debriding the wound to a clean base, correcting the biomechanical abnormality, and nurturing the wound until it shows signs of healing. The subsequent reconstruction can then usually be accomplished by simple techniques 90% of the time and complex flap reconstruction in 10% of cases. It may involve partial foot amputation to develop a sufficient tissue envelope to close the wound or to stabilize the foot biomechanically.

Wound healing is the process of tissue repair and the tissue response to injury. It is a complex biological process involving chemotaxis, cellular reproduction, matrix protein production and deposition, neovascularization, and scar remodeling (). Growth factors are polypeptides that control the growth, differentiation, and metabolism of cells, and regulate the process of tissue repair (,). The role of growth factors in wound healing and specifically in diabetic ulcer healing is the subject of this chapter.