Diabetic Foot Ulcers Workup

Patient workup for diabetic ulcers includes blood tests, radiography, ankle-brachial index and toe pressure, pulse-volume recording, ultrasonography, computed tomography (CT) scanning or magnetic resonance imaging (MRI), bone scans, and angiography.

IWGDF guidelines

In 2019, the International Working Group on the Diabetic Foot (IWGDF) published an update to its evidence-based guidelines on diabetic foot disease prevention and management. These included the following practical guidelines with regard to assessment of ulcers ^[35] :

• An individual with diabetes who is at very low risk for foot ulceration (IWGDF risk 0) should, to assess the subsequent risk for ulcers, be examined annually for signs or symptoms of protective sensation loss and peripheral artery disease
• A patient with diabetes who has protective sensation loss or peripheral artery disease (IWGDF risk 1-3) should undergo a more comprehensive examination, with the following taken into account: history, vascular status, skin, bone/joint, protective sensation loss, footwear, poor foot hygiene, physical limitations that may hinder self care of the feet (eg, problems with visual acuity, obesity), and foot care knowledge

A complete blood count (CBC) should be performed. Leukocytosis may signal an associated diabetic foot infection. Wound healing is impaired by anemia. In the face of underlying arterial insufficiency, anemia may precipitate rest pain. ^[36]

A comprehensive metabolic panel should also be obtained. Random glucose levels will demonstrate the adequacy of glycemic control and may be elevated in the setting of infection. Creatinine levels will assess renal function. Low albumin levels are associated with a poorer prognosis for wound healing. ^[37]

Blood testing should also include an HbA1c assessment, since a normal value is a surrogate marker for wound healing. ^[38]

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inflammatory markers which are elevated in the setting of infection and osteomyelitis. They can be measured serially to determine the efficacy of treatment.

In the setting of infection with systemic inflammatory responses, obtainment of blood cultures and lactic acid assessment are appropriate.

Plain radiographs should be obtained in the setting of diabetic foot ulcers, as well as pre-ulcerative lesions. Weight-bearing radiographs of the foot are preferred, and three views are typically ordered. Radiography allows clinicians to assess for deformities that may be the driving force for ulcerations. Osteomyelitis can often be detected on plain radiographs; however, the images may appear normal in the first 2 weeks of the disease process. Soft tissue gas may be present in the setting of gas gangrene and necrotizing soft tissue infections, which require prompt surgical intervention.

Radiographs may demonstrate calcifications of extremity vasculature. However, arterial calcification seen on plain radiographs is not a specific indicator of severe atherosclerotic disease. Calcification of the arterial media is not diagnostic of atherosclerosis, and even calcification of the arterial intima, which is diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically significant stenosis.

In the setting of osteomyelitis, MRI is said to be both specific and sensitive. MRI is also useful for evaluating deep space infections, infectious tenosynovitis, myositis, and septic arthritis. However, in the setting of Charcot arthropathy, it is difficult to distinguish that condition from osteomyelitis.

CT scanning can be used to identify osseous changes such as cortical erosions, pathologic fracture, and periosteal reactions. Because of resolution limitations, however, this modality may not be as useful in evaluating soft tissue infection, although injection of intravenous contrast may provide better visualization of deep space abscess formation.

Bone scans can be beneficial when the use of MRI and CT scanning is contraindicated for evaluating osteomyelitis. However, although bone scans have high sensitivity for osteomyelitis, they have low specificity, resulting in an increased number of false-positive scans. Labeling with gallium and indium radionuclides may lead to more specificity for suspected osteomyelitis. ^[39]

The systolic pressure in the dorsalis pedis or posterior artery divided by the upper extremity systolic pressure is called the ankle-brachial index (ABI) and is an indication of severity of arterial compromise. Normal ABI averages 1.0. An ABI less than 0.9 suggests atherosclerotic disease, with a sensitivity of approximately 95%. In general, an ABI below 0.3 suggests a poor chance for healing of distal ischemic ulcerations. Unfortunately, the ABI often is falsely elevated (and thus may be unreliable) if the underlying arteries are heavily calcified, a finding common in diabetic persons.

See recommendations for the workup of patients with atherosclerotic disease of the extremities in the Medscape Reference article Infrainguinal Occlusive Disease.

Pulse-volume recording (PVR), or plethysmography, uses pneumatic cuffs encircling the thighs, calves, ankles, feet, and, occasionally, toes to sense segmental volume changes with each pulse beat. The resulting tracings provide useful information about the hemodynamic effects of the arterial disease at each level. In severe disease, tracings at the transmetatarsal level may become nearly flat. In mild disease, particularly involving the aortoiliac segment, PVR tracings may appear normal at rest and become abnormal only after the patient walks until symptoms occur.

PVR is noninvasive and rapid and, therefore, may be repeated frequently to help assess the overall hemodynamic response to medical or surgical treatment. Ordinarily, if pedal pulses are satisfactory, arterial evaluation PVR provides no useful information.

Duplex ultrasonography can provide images of arterial segments that help localize the extent of disease, and simultaneous Doppler measurement of flow velocity can help estimate the degree of stenosis. Duplex scanning is quite useful in visualizing aneurysms, particularly of the aorta or popliteal segments. Use of this technique probably is best left to the discretion of the vascular specialist.

A handheld Doppler scanner may be used to assess arterial signals, to localize arteries to facilitate palpation of pulses, or to determine the loss of Doppler signal as a proximal blood pressure cuff is inflated (as in measurement of systolic pressure in extremity arteries).

Laser Doppler studies also have been used but may not be reliable.

Transcutaneous oxygen levels of 40 mmHg or greater in people with diabetes demonstrate the ability to heal from a perfusion standpoint. Transcutaneous tissue oxygen studies are often reserved for borderline situations in which the advisability of arterial bypass surgery may be unclear.

If vascular or endovascular surgical treatment is contemplated, angiography is needed to delineate the extent and significance of atherosclerotic disease. Major risks associated with conventional contrast-injection angiography are related to the puncture and to the use of contrast agents. See also Infrainguinal Occlusive Disease.

Technique

Typically, a catheter is inserted retrograde via a femoral puncture, and contrast is power-injected into the infrarenal aorta. Films are taken as the contrast is followed down to both feet. In certain cases, as with aortic occlusion, a femoral approach to the aorta may not be possible. In this case, the interventionalist (interventional cardiologist, vascular surgeon, or interventional radiologist) may use an alternative entry point, such as via the brachial or axillary artery. The arterial catheter is usually passed through a 5F sheath that is 1.6 mm in diameter. This is a sizable hole in the femoral artery, which may be only 6-10 mm in diameter. After the catheter is removed, gentle pressure must be applied to the puncture site for approximately 30 minutes. In most cases, the physician performing the angiogram may elect to use a small device to aid in closing the puncture site (“closure device”). Successful deployment of these devices eliminates the need for prolonged pressure application.

Puncture-related complications

Risks associated with catheter insertion include hemorrhage, pseudoaneurysm formation, and clotting or dislodgement of an intimal flap, which may acutely occlude the artery at or near the entry site. Use of percutaneous closure devices on the puncture sites has significantly reduced site complication rates.

Contrast-related risks

Angiographic contrast material is nephrotoxic. The risk of precipitating acute renal failure is highest in patients with underlying renal insufficiency and those with diabetes. Patients with both of these risk factors have a 30% rate of acute renal failure following contrast angiography. Hence, an acceptable serum creatinine level must be confirmed prior to elective angiography. Avoid contrast angiography (if possible) for patients with any significant degree of renal impairment. If contrast angiography is absolutely required despite renal impairment, use a minimal volume of contrast material. In addition, providing adequate hydration prior to, during, and after the procedure is essential. Oral administration of the antioxidant acetylcysteine (Mucomyst) the night prior to and then just before angiography may be protective of renal function for patients at risk of contrast-induced nephropathy. ^[9]

Metformin warning

To prevent the possibility of fatal lactic acidosis, patients with diabetes who are taking metformin (Glucophage) must not take this medication immediately following contrast angiography. Patients may resume taking the medication when normal renal function is confirmed 1-2 days after contrast exposure.

Magnetic resonance angiography

Magnetic resonance angiography (MRA) is an alternative for patients who are allergic to iodinated contrast material. MRA is not innocuous. Gadolinium chelates, the contrast agents used in MRA, have been linked recently to 3 potentially serious side effects in patients with renal insufficiency: acute renal injury, pseudohypocalcemia, and nephrogenic systemic fibrosis. MRA is contraindicated in patients with implanted hardware such as a hip prostheses or pacemakers.

The resolution provided by MRA may be inadequate for the vascular surgeon in planning reconstructive procedures, particularly in the smaller infrapopliteal arteries, although MRA technology and contrast agents continue to improve. ^[10]

Multidetector CT angiography

Multidetector CT (MDCT) angiography avoids arterial puncture. By using precisely timed intravenous contrast injection, multidetector (16 or 64 channel) CT scanners can generate angiographic images of excellent resolution and at a relatively high acquisition speed. MDCT angiography carries the contrast-related risks described above. ^[40]

Carbon dioxide angiography

Carbon dioxide angiography is an alternative for patients with renal insufficiency; however, it is not widely available and requires some iodinated contrast material in addition to the carbon dioxide gas in order to provide useful images.

Diabetic foot ulcers can be staged using the WIfi threatened-limb system. This system allows communication between providers and provides risk stratification for major amputation ^[5]

Wound classification is as follows:

• Grade 0 – Rest pain; no wound, no ulcer, no gangrene.
• Grade 1 – Small shallow ulcer(s) on distal leg or foot; any exposed bone is only limited to distal phalanx; no gangrene (ie, minor tissue loss: limb salvage possible with simple digital amputation [1 or 2 digits] or skin coverage)
• Grade 2 – Deeper ulcer on distal leg or foot with exposed bone, joint, or tendon, or shallow heel ulcer without involvement of the calcaneus; gangrenous changes confined to the digits (ie, major tissue loss: salvageable with ≥3 digital amputations or standard transmetatarsal amputation [TMA] plus skin coverage)
• Grade 3 – Extensive deep ulcer of the forefoot and/or midfoot or full-thickness heel ulcer with or without involvement of the calcaneus (ie, extensive tissue loss: salvageable only with complex foot reconstruction or nontraditional TMA [eg, Chopart or Lisfranc amputation])

Classification of Ischemia is as follows:

• Grade 0 – ABI ≥0.8, ankle systolic pressure >100 mmHg, toe pressure (TP)/transcutaneous oxygen (TcPO2) ≥60
• Grade 1 – ABI 0.6-0.79, ankle systolic pressure 70-100 mmHg, TP/TcPO2 40-59
• Grade 2 – ABI 0.4-0.59, ankle systolic pressure 50-70 mmHg, TP/TcPO2 30-39
• Grade 3 – ABI ≤0.39, ankle systolic pressure < 50 mmHg, TP/TcPO2 < 30

Classification of foot infection is as follows:

• Grade 0 – No symptoms or signs of infection
• Grade 1 – Infection is present, and at least two of the following are present: local swelling or induration, erythema >0.5 to ≤2 cm around ulcer, local tenderness or pain, local warmth, or purulent discharge; other causes of an inflammatory response of the skin have been excluded (eg, gout, fracture)
• Grade 2 – Local infection is present as defined for grade 1 but extends >2 cm around ulcer or involves structures deeper than the skin and subcutaneous tissues (eg, abscess, osteomyelitis, septic arthritis, fasciitis); no clinical signs of systemic inflammatory response
• Grade 3 – Local infection is present as defined for grade 2, but clinical signs of systemic inflammatory response are present as manifested by two or more of the following: temperature >38°C or < 36°C; heart rate >90 beats per minute, respiratory rate >20 breaths per minute or partial pressure of carbon dioxide (PaCO ₂) < 32 mmHg; white blood cell count >12,000 or < 4000 (cu/mm) or 10% immature band forms present

Wound cultures

A multicenter, prospective, cross-sectional study by Nelson et al indicated that the use of tissue samples is superior to that of wound swabs in identifying pathogens in infected diabetic foot ulcers. The investigators found that pathogens were more often identified, and nonpathogens less often identified, using tissue samples than wound swabs, with antibiotic regimen changes more frequently recommended by blinded clinicians in response to the results of tissue samples than to those of swabs. ^[41]

Probe to bone test

Using a sterile, solid instrument, the wound should be probed deeply without using force. If there is a rough, coarse feel, this establishes a clinical diagnosis of osteomyelitis. Specificity and sensitivity for the probe to bone test for confirmed osteomyelitis are as high as 0.83 and 0.87, respectively. ^[42]

Bone biopsy

If osteomyelitis is suspected, a bone biopsy is the gold standard for confirming the diagnosis. Bone biopsies are performed either through open technique or percutaneously, with or without the assistance of fluoroscopy. Osseous specimens are sent for histologic and microbiologic evaluation.

Skin biopsy

In the setting of a nonhealing, chronic wound, it is advisable to send a skin biopsy for histopathologic examination to rule out malignancy. Skin biopsies may also be beneficial to rule out other differential diagnoses such as calciphylaxis, vasculitis, and venous stasis. The wound biopsy can be incisional, excisional, or performed via punch biopsy.