Measurements in the Diabetic Foot

D iabetic foot syndrome (DFS) is a complex and heterogeneous disorder that affects 1 out of 5 patients with diabetes at least once in his or her lifetime with relevant consequences both on lower limb survival and general morbidity.¹ Diabetes is the most frequent determinant of lower limb amputations in developed countries, and foot ulcers are the principal cause of amputations in patients with diabetes.² Lower limb complications are major contributors to hospitalization of patients with diabetes, and they account for the vast majority of in-hospital stay and resource consumption in this patient population.³ According to the international consensus guidelines’ protocols,⁴ such a complex pathology necessitates the participation of a multidisciplinary team, including the diabetologist, the podologist, the vascular surgeon, the radiologist, and the infectious disease specialist, to manage and address all the various aspects and presentations of the pathology. The measurements in DFS are of paramount importance to guide clinical judgement and provide quantitative information not only on the nature of the present disease but also on its clinical course and the efficacy of therapeutic interventions. Due to variety in the presentations of the disease and its clinical course, the different techniques of measurements, with their indications and clinical significance, can be better understood if they are preceded by a physiopathologic evaluation and a brief description of the principal clinical presentations with the relative measurements. Pathogenesis, Clinical Presentations, and Natural History of the Diabetic Foot Diabetic foot syndrome is the consequence of the long-term chronic complications of diabetes, peripheral neuropathy and peripheral vascular disease, affecting the lower limbs. By diminishing sensitivity to external trauma, peripheral neuropathy exposes bony prominences to higher pressures, which in turn lead to an increased risk of chronic foot ulceration. Peripheral vascular disease (PVD) interferes with the healing process of ulcers by reducing the amount of tissue oxygen and nutrients thus lengthening ulcer healing time.^5–8 Ulcers, especially those with an ischemic component, are prone to be colonized by bacteria, which can easily complicate the clinical presentation with superficial or deep infections and eventually lead to osteomyelitis. The clustering of these 3 components—peripheral neuropathy, PVD, and infection—compounded with trauma contributes to the progression of the pathology from a nonulcerated condition of an at-risk foot to an acute syndrome characterized by the presentation of a classic diabetic foot ulcer that develops into a chronic condition in the post-ulcerative phase, which can result in minor amputation.⁹ Regardless, the identification of 3 different but inter-related and worsening conditions is important to better identify the measurements that are useful and necessary to manage that particular phase of the syndrome.¹⁰ In the pre-ulcerative phase, the focus will be placed on the identification of risk factors and their quantification in order to create a risk profile and to plan preventive interventions. In the ulcerative phase, the emphasis will be on staging and characterization of the ulcer and its evolution to determine the therapeutic strategy and evaluate the clinical evolution of the conditions. In the post-ulcerative phase, follow-up parameters will be selected to identify possible relapses and adjust the rehabilitative interventions. In each phase, measurement will be performed in various ways to explore neurological, vascular, biomechanical, or infection-related aspects according to the specificity of the actual clinical case.^11–13 Some particular and specific conditions do not fit with this general model of approach and will be described and discussed separately. Measurements in the Pre-ulcerative Phase Up to 15% of patients with diabetes will develop DFS at least once in their lives, but the prevalence of the component causes of DFS is much higher. Peripheral neuropathy has been estimated to affect about 50% of patients, and PVD affects as many as 40% of patients with diabetes with long duration of disease.^1,3 In the pre-ulcerative phase, the goal of measurements is to evaluate patients’ risk profiles for foot ulceration so that higher risk patients can be appropriately followed to ensure proper preventive measures and therapies are performed. According to the international consensus guidelines, the risk profiles for diabetic foot ulcers is composed of neuropathy, presence of deformities and/or peripheral vascular insufficiency, and previous amputations or ulcers.¹⁴ The neuropathic aspect of the pathology can be evaluated by determining the sensitivity to a monofilament that applies a force of 10 g/cm² to specific points on the foot (3 to 9 according to different protocols); insensitivity to the application of the monofilament identifies a condition of risk. The same concept can be applied to determine the vibratory perception threshold (VPT) with a 128 Hz graded diapason or with a bio-esthesiometer, an instrument that allows quantification of the vibration drive applied at the first toe or at the malleolus of the foot. A threshold of 25 V identifies a condition of ulcerative risk. Additionally, the VPT value can be used to quantify and follow-up peripheral neuropathy in order to evaluate the effects of therapies and to predict the evolution of the pathology. This is possible because the fibers that are responsible for the vibratory component of sensations are the Δ fibers, which are faster, more myelinated, and the most precociously involved by the metabolic derangement that is typical of diabetic neuropathy. In this way, a simple, repeatable, and noninvasive test is able to evaluate peripheral nerve damage.¹⁵ Peripheral vascular disease can be assessed clinically by testing peripheral pulses but can be better quantified by measuring ankle and toe pressure and calculating the ankle/brachial pressure index (ABPI)—the ratio between the highest systolic pressure at the ankle and the systolic brachial pressure. A value > 0.9 identifies a normal condition, a value between 0.9 and 0.5 is indicative of the presence of PVD, and a value 1.3 is frequently related to medial artery calcification (Monckeberg sclerosis), which is an indirect sign of autonomic neuropathy.¹⁶ In any case of suspected peripheral vascular impairment, transcutaneous oxygen tension (TcpO₂) measurement is an indirect but precise evaluation of the concentration of oxygen present in a determined area, which is directly dependent on the amount of blood in that area (Figure 1). A TcpO₂ pressure 17 Deformities of the foot can be clinically evaluated and described as either present or not present, especially when evaluating the forefoot. Even more important is to measure the degree of motion of the joints and to test if a limited joint motility condition is present (LJM), which can enhance the exposure of bones and joints to hyperpressures and, consequently, ulceration risk. These measurements can then be used to compose an integrated ulcerative risk score according to the international guidelines (Table 1), which identify 4 different classes, from 0 (risk absent) to 3 (very high risk), so that patients in higher risk classes may be followed more closely. Measurements in the Ulcerative Phase The presence of an acute lesion transforms the at-risk foot into an acute clinical emergency with a potentially very poor outcome. In the ulcerative phase, evaluating the condition of the ulcer is the main objective for the clinician, since further management of the patient is based on this evaluation. The cornerstones of this process are staging of the lesion, evaluating for the presence of infection, and assessing the potential for eventual involvement of bones in the lesion. Staging the lesion is the first step of this complex evaluation. The University of Texas staging system is a novel staging scale specifically developed to assess and grade diabetic foot ulcers (Table 2).¹⁸ The scale was developed to assign increasing figures from 0 (no lesions) to III (lesion penetrating to bone or joint) according to the progressive involvement of deeper structures in the lesion. A letter is then assigned to form a bidimensional score: A is when neither ischemia nor infection is present, B is for infection present, C is for ischemia present, and D is when both infection and ischemia are present. To assess the depth of a lesion, a simple clinical exploration is sufficient in the vast majority of cases, while in a minority of ulcers, it may be useful to employ more sophisticated diagnostic instruments, such as magnetic resonance imaging (MRI). Ischemia is evaluated with TcpO₂ according to the previously described procedure, while infection is evaluated by the presence of clinical signs and bacteria, which will be discussed. To stage the lesion according to such a system is useful not only for diagnosis but also for prognostic purposes. It has been demonstrated that poorer scores are associated with poorer prognoses.¹⁹ Though dimensions are not the major determinants of an ulcer’s clinical behavior, it has been demonstrated that in absence of external complicating factors, the healing time of a diabetic foot ulcer is related to its size and depth.²⁰ To assess the area of the ulcer, many different and sometimes complicated and expensive tools have been proposed, which use different technology, from laser scanning to radar application. For clinical purposes, simplicity and repeatability are 2 key factors that ensure the actual measurement is performed regularly. It is important to focus on the fact that measurements, in this case, are aimed to evaluate not only the actual size of the lesions but also their behavior during the healing process. This should be considered a dynamic measurement that indicates whether the ulcer is reducing or enlarging in dimension. For this purpose, the simple pencil tracing of the ulcer on a polyurethane sheet can be useful to compare the shape and size of the ulcer from visit to visit (Figure 2). To assess the area, a good approximation to the real dimension can be obtained from multiplying the major diameter by the major orthogonal diameter. Determining the potential for eventual bone or joint involvement in the lesion is of crucial importance in deciding the future management of the condition. The exposition of such structures in the lesions is significantly associated with the presence of osteomyelitis or septic arthritis; thus, conservative treatments without the use of surgical removal of the infected bone or joint will most likely fail. The first step in such an evaluation consists of the careful exploration of the ulcer with a blunt probe. Finding a bone or a joint exposed in the ulcer has a positive predictive value of 89% for the presence of osteomyelitis, while the absence of such findings is paralleled by the absence of osteomyelitis only in 55% of cases (Figure 3).²¹ The apparent absence of bone or joint inside the lesion should be confirmed with radiography and eventually confirmed by MRI. Since at least 50% of bone mass has to be destroyed before it can be recognized by exam, if the first result is negative in the presence of clinical signs indicative of infection, it is important to repeat the exam after at least 15 days and compare the 2 results, searching for structural modifications that can eventually emerge. Infection is evaluated mainly by its clinical appearance, since no definite quantitative screening test has been validated to identify its presence inside the tissues.²² Infection is suspected if any 3 of the following signs are present: redness, swelling, tenderness, secretion, increased local temperature, increased white blood cells count, and fever. In patients with diabetes, in the presence of neuropathy and a reduced immune response, local and systemic signs of infection can be reduced or even absent but, when present, are highly indicative of infection.²³ To confirm the presence of infection and to ascertain the species of microorganism(s) responsible, material from the ulcer should be cultured and the sensitivity of antimicrobial agents tested adequately.²⁴ The sample for such examination should be taken from the base of the lesion, possibly after having been flushed of any superficial contaminants, eventually biopsying the tissue involved in the lesion. Purulent discharge should be aspired directly from the ulcer with a sterile syringe. In all cases, the samples should be inseminated in mediums for aerobes and anaerobes as soon as possible. Measurements in the Post-ulcerative Phase Once the acute phase has passed, ending in either healing or amputation, the foot is no longer the same as it was before the lesion occurred, since its anatomy and function have been altered by the occurrence of the ulcer and the related treatments that have been prescribed to prevent recurrences or new pathologies. Since foot biomechanics are mainly involved in the post-ulcerative phase, to simplify the evaluation approach, one can refer to the general equation of foot biomechanics: W = P x T _______ S where W is work, and it is the result of a force (pressure, P) multiplied by the time of application (T) and divided by the surface of application (S). Usually work, which is expressed in kilopascals (KPa), is well distributed under the plantar surface of the foot because the neuromuscular control of the gait and the intact structure of the normal foot ensure that these items are carefully addressed. In neuropathic feet, pressures increase due to lack of sensation, especially in cases where some structural damage occurred due to a previous ulceration. Time increases as well, reflecting the loss of gait control, while surface reduces as a consequence of decreased muscular control (causing deformities in the foot) and surgical intervention (removal of bone segments), which may predispose the surrounding areas to increased workloads resulting in transferral ulcers.²⁵ To evaluate the amount of risk of re-ulceration to a foot in the post-ulcerative phase, more complex measurements may be performed. The determination of skin hardness with an instrument called a durometer can identify the areas of the plantar skin in which hyperkeratosis is prone to develop due to the increased pressure.²⁶ The evaluation of plantar pressure in static and dynamic conditions can be very useful to identify and quantify such hyperpressures, both in terms of force (kg/cm²) and workload (kgmin/m² – Kpa). Although it is not possible to identify a protection threshold against developing lesions, it is unlikely that they would occur if the workload under the foot does not reach 200 KPa. With recent technological advancements it is possible to repeat such measurements after applying orthesis protection to the feet, so management of the chronic foot can be prospectively evaluated and eventually corrected.¹¹ Joint motility is another crucial measurement essential to evaluate the response of the foot to applied force. Though mainly qualitative, this evaluation can be quantitative once joint motion is expressed in degrees. Especially in the case of the ankle joint, a reduced degree of motion is associated with an increased occurrence of ulceration of the forefoot; thus, if the degree of motion is less than 10 degrees of dorsiflexion, tenotomy of the Achilles tendon is indicated to prevent re-ulceration of the forefoot in these patients^.6 Measurements in Specific Clinical Conditions Charcot’s foot is a relatively frequent, worsening, and misdiagnosed condition that complicates the neuropathic foot of patients with diabetes and can lead to amputation without necessarily passing through an ulcerative phase.^27,28 Charcot’s foot is caused by the progressive destruction of bones and joints in the neuropathic foot secondary to the inflammatory process following traumas that are not identified or recognized by the patients. The foot passes through consecutive phases of acute inflammation and sclerosis, which heavily deform its architecture with dramatic consequences. The main factors in this worsening process are the reduced capacity of the bone to resist stresses and the activation of an inflammatory process, which increases the bone resorption and exposes the foot to new traumatic events. To properly assess this condition, bone structure must be measured and inflammation monitored. Bone structure can be explored with imaging techniques (x-ray, MRI), biochemical markers (eg, bone alkaline phosphatase, C-telopeptide of procollagen, osteocalcin), and densitometry with x-ray absorption techniques or ultrasound.^29–31 Inflammation can be monitored with complex techniques, such as the gadolinium curves evaluation with MRI or labelled granulocyte bone scintigraphy, or with simple methods, such as the evaluation of local temperature with an infrared thermometer. It has been demonstrated that a difference > 2?C from the contralateral foot is indicative of an acute phase, and more sophisticated instrumental evaluations are indicated. In pancreas-transplant patients, a higher rate of foot fractures and Charcot’s joint have been observed, probably due to long-lasting steroid therapy, which heavily reduces the resistance of the bone and exposes it to the consequences of even trivial traumas.³² In such patients, a serial evaluation of bone density and bone metabolism parameters is mandatory to prevent such events. Conclusions Measurement in DFS is an essential part of diagnosis and treatment of patients and should be considered an integral part of the therapeutic approach to this complex and difficult-to-manage condition. Measurements differ according to their application within phases of the pathology, and their values increase if they are repeated during the course of the pathology. These measurements constitute a point of referral on which to build the judgement of the actual condition of the case and its management.