Diabetic Foot Syndrome

How to Cite This Chapter: Parihar R, Pigeyre M, Rodríguez-Gutiérrez R, Quintanilla-Flores DL, Soto-Garcia AJ, Gonzalez-Gonzalez JG, Sieradzki J, Płaczkiewicz-Jankowska E. Diabetic Foot Syndrome. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.13.4.4. Accessed May 22, 2024.
Last Updated: November 16, 2021
Last Reviewed: November 16, 2021
Chapter Information

Definition, Etiology, PathogenesisTop

Diabetic foot syndrome is defined as infection, ulceration, or destruction of deep tissues of the foot (including bones) in a patient with diabetes mellitus (DM). It affects nearly 6% of individuals with diabetes. Around 0.5% to 1.5% of patients with diabetic foot syndrome require amputation. Most amputations start with ulcerations and can be prevented with good foot care and screening to assess the risk of foot complications. Diabetic foot syndrome is associated with neurologic abnormalities, peripheral artery disease (PAD), and musculoskeletal abnormalities of the lower limbs of varied severity.

Neuropathy as well as vascular and musculoskeletal abnormalities play a role in the development of diabetic foot syndrome (Table 1).

Classification based on pathogenesis includes:

1) Neuropathic foot.

2) Ischemic foot.

3) Neuropathic-ischemic foot.

Differentiation of the neuropathic and the ischemic foot is of great importance, as their treatment differs significantly (Table 6.2-9).

Motor neuropathy results in atrophy of the muscles of the foot, thus disturbing the flexor-extensor balance and leading to contractures. Sensory neuropathy (abnormal sensation of pain, temperature, and touch) exposes the patient to repeated uncontrolled injuries, increasing the risk of ulcerations. Autonomic neuropathy results in the formation of arteriovenous fistulae and trophic changes. Atherosclerosis of the lower extremities results in foot ischemia. All these changes are associated with the development of local osteoporosis and may also lead to osteomyelitis, avascular necrosis, fractures, dislocations, and significant disfigurement of the foot (Charcot foot arthropathy).

Stages of Charcot foot arthropathy:

1) Stage 1: Warmth, redness, and edema of the foot, with features suggestive of tissue inflammation.

2) Stage 2: Bone fractures and joint dislocations.

3) Stage 3: Foot deformation, joint destruction.

4) Stage 4: Ulcerations of the foot arch (bottom foot).

Clinical Features and DiagnosisTop

Inquire about factors known to be associated with foot ulcers: previous foot ulceration, prior lower extremity amputation, Charcot foot arthropathy, long history of diabetes (>10 years), poor glycemic control (glycated hemoglobin [HbA1c] >9.0%), angioplasty or vascular surgery, cigarette smoking, peripheral neuropathy, visual impairment, onychomycosis (fungal infection of the nail), and chronic kidney disease (especially in patients treated with dialysis). Perform a complete foot examination, which should include inspection of the skin, assessment of muscular deformities, and neurologic and vascular evaluations. The neurologic examination performed as part of foot examination is designed to identify loss of protective sensation

(LOPS) rather than early neuropathy. The 10-g monofilament is the most useful and at the same time easy and inexpensive test to diagnose LOPS and an independent predictor of future foot ulcers and lower extremity amputation. Ideally, it should be performed with at least one other assessment (pinprick, temperature or vibration sensation using a 128-Hz tuning fork, or ankle reflexes). Absent monofilament sensation suggests LOPS, while at ≥2 normal test results (and no abnormal results) exclude LOPS. Initial screening for PAD should include history of decreased walking speed, leg fatigue, claudication, and assessment of pedal pulses. Ankle-brachial index (ABI) testing should be performed in patients with symptoms or signs of PAD; note that if the ABI is very high due to calcified vessels in DM, it may be falsely reassuring (false negative) and other tests, such as computed tomography angiography (CTA) or magnetic resonance angiography (MRA), may need to be done to confirm the diagnosis (Table 3).

The Perfusion, Extent, Depth, Infection, and Sensation (PEDIS) classification of the diabetic foot includes assessment of perfusion, size, and depth of ulceration, severity of infection, and presence of sensory neuropathy; this classification is reflected in the Infectious Diseases Society of America (IDSA) classification of diabetic foot infection (Table 4).

Clinical diagnostic criteria for infection of the soft tissues of the foot: Acute ulceration with classic inflammation signs (redness, pain, warming, swelling, lymphangitis, phlegmon, purulent discharge or abscess), fluctuance, increased discharge, friable or discolored granulation tissue, undermining of wound edges, and foul odor. Deep ulceration reaching the bone (visible or confirmed at clinical examination using a sterile probe) indicates a risk of bone infection; in such cases perform magnetic resonance imaging (MRI), nuclear white blood count (WBC) scan, or histologic examination of bone samples.

Microbiologic examination of soft tissues is not used to confirm the diagnosis of infection but to establish its etiology and provide treatment guidance. Specimens for culture should be obtained prior to starting empiric antibiotic therapy, if possible. Make sure the samples are collected in an appropriate way; optimally, they should be obtained from deeper parts of the wound during tissue biopsy or curettage after the wound has been cleansed and debrided. Superficial smears are insufficient, as they reveal the colonizing flora and are of little diagnostic value. Mild (superficial and limited) infection is generally caused by staphylococci and streptococci, while chronic and severe infections are often polymicrobial and involve aerobic gram-negative rods and anaerobes.


1. Examine or inspect the feet at every visit (usually every 3 months) for structural abnormalities (eg, calluses, hammer or claw toes, flat feet, bunions), reduced joint mobility, dry or fissured skin, tinea or onychomycosis, loss of protective sensation, diminished arterial supply, and improper footwear. Determine the risk of diabetic foot syndrome during the annual complete foot examination and schedule further control foot examinations at intervals depending on the presence of abnormalities found. Assess the ABI (see Lower Extremity Peripheral Artery Disease) as clinically indicated.

2. Instruct the patient with diabetic neuropathy, foot deformities, exostosis, peripheral ischemia, or prior ulcers to do the following:

1) Inspect the feet daily, including interdigital spaces (if the patient is not capable of self-inspection, they should ask for assistance).

2) Wash the feet regularly with water (<37 degrees Celsius) and dry them thoroughly, paying special attention to the interdigital spaces.

3) Avoid walking barefoot or using footwear without socks. Change socks daily. Wear socks and stockings with seams turned inside out, or optimally use seamless hosiery. Perform daily visual and manual inspection of the inner surfaces of footwear.

4) Clip toenails straight. Visually impaired patients should not clip toenails by themselves.

5) Avoid cutting hard skin and calluses by the patients themselves (including the use of chemical preparations and patches).

6) Seek medical attention immediately in case of blisters, cuts, scratches, or ulcerations.

7) Ensure follow-up with a foot specialist, eg, foot clinic professional, podiatrist, chiropodist.

8) Use proper footwear that adequately protects the feet from even minor injuries.


1. Multidisciplinary approach to treat diabetic foot is essential.

2. Good control of DM is of key importance for all patients.

3. Treatment aimed at optimizing cardiovascular function: see Lower Extremity Peripheral Artery Disease.

4. Management of an uninfected foot: Ensure appropriate foot care procedures, patient education, and avoidance of weight-bearing of the foot. Do not use antimicrobial treatment. Perform repeated foot assessments including effects of treatment and perfusion and search for features of infection. Hyperbaric oxygen therapy (HBOT) in patients with diabetic foot ulcerations has mixed and nondefinitive evidence supporting its use as adjunctive treatment to enhance wound healing and prevent amputation.Evidence 1Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and heterogeneity. Zhao D, Luo S, Xu W, Hu J, Lin S, Wang N. Efficacy and Safety of Hyperbaric Oxygen Therapy Used in Patients With Diabetic Foot: A Meta-analysis of Randomized Clinical Trials. Clin Ther. 2017 Oct;39(10):2088-2094.e2. doi: 10.1016/j.clinthera.2017.08.014. Epub 2017 Sep 19. PubMed PMID: 28935291. O'Reilly D, Pasricha A, Campbell K, et al. Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta-analysis. Int J Technol Assess Health Care. 2013 Jul;29(3):269-81. doi: 10.1017/S0266462313000263. Review. PubMed PMID: 23863187. With the high cost and burden of therapy, HBOT should be a topic of shared decision-making before treatment is considered for selected patients with diabetic foot ulcerations.

5. Treatment of an infected foot:

1) In patients who are not treated with insulin, consider insulin therapy if glycemic control is suboptimal.

2) Reduce weight-bearing on the foot, for instance, by using molded footwear inserts, crutches, or offloading contact casts, with the latter being proven to deliver better outcomes than others.

3) Ensure restoration of skin perfusion. Implement measures focused on cardiovascular risk reduction: cessation of smoking, treatment of hypertension and dyslipidemia, use of acetylsalicylic acid/antiplatelets. Consider revascularization in patients with an ABI <0.6 (see Lower Extremity Peripheral Artery Disease), toe pressures <50 mm Hg, or transcutaneous partial pressure of oxygen <30 mm Hg.

4) Consider hospitalization in all patients with severe infection or sepsis, selected patients with moderate infection and complicating features (eg, severe peripheral arterial disease or lack of home support), and any patient unable to comply with the required outpatient treatment regimen for psychological or social reasons.

5) Antimicrobial treatment: The guidelines specific for diabetic wound infections (IDSA 2012) recommend that clinically uninfected wounds do not get treated with antibiotics; if the wounds are infected, antibiotic treatment should be supported by debridement as needed and wound care. In patients with cellulitis surrounding a wound that is mild in severity, start empiric treatment by targeting Staphylococcus aureus and group A streptococcus by using cloxacillin or dicloxacillin, a first-generation cephalosporin (eg, cephalexin [INN cefalexin] 500 mg qid), or amoxicillin/clavulanate 875/125 mg bid. Other options are clindamycin, levofloxacin, and doxycycline or trimethoprim/sulfamethoxazole for potential or confirmed methicillin-resistant S aureus (MRSA) infections.

Broader coverage is indicated in patients with moderate to severe deep wound infection, where polymicrobial infection is more likely. Therapy could include ceftriaxone (1 g IV or IM) and metronidazole (500 mg orally or IV every 12 hours), ampicillin/sulbactam (1.5 g IM every 6 hours), and piperacillin/tazobactam (4.5 g IV qid). Other options include clindamycin/ciprofloxacin (600 mg orally tid/500 mg bid), levofloxacin (750 mg orally once daily), or a carbapenem (eg, meropenem 500 mg IV tid); however, these should be used judiciously to avoid contributing to fluoroquinolone and carbapenem resistance. If there has been a recent known exposure to MRSA or in centers where exposure is likely (eg, local MRSA incidence >10%), consider adding vancomycin for empiric therapy. If results of susceptibility testing are available, use targeted antimicrobial treatment (eg, in patients with laboratory-confirmed MRSA infection, use vancomycin [1 g IV bid]).

The duration of antibiotic treatment can be variable and depends on a number of factors, with the evidence base for duration being very poor. Patients with complicated infections should be seen by an infectious disease specialist who would determine treatment duration. As a rough approximation, the usual duration of antimicrobial treatment in patients with a PEDIS grade 2 infection (Table 4) is 1 to 2 weeks, and in patients with PEDIS grade 3 or 4 infection, 2 to 4 weeks, until the infection resolves; do not continue treatment until ulceration is healed. In patients with infection of bones and joints, the duration of treatment is usually as follows: in patients after amputation (indications: see below) with no residual infection, 5 days; in patients with bone infections without a residual sequestrum, 4 to 6 weeks; in patients with bone infection and residual sequestrum after surgical treatment, >3 months.

6) Drainage, incision, and debridement of necrotic tissues or surrounding callus: Debridement should be aimed at removing debris, eschar, and surrounding callus. Urgent surgical intervention should be offered to patients with foot infections accompanied by gas in the deeper tissues, abscess, or necrotic fasciitis.

7) Dressings: Adjust the type of dressing to the stage of wound healing. The choice of dressing should be based on the size, depth, and nature of the ulcer (eg, dry, exudative, purulent).

8) Intravascular and surgical procedures may be used in patients with clinical or imaging evidence of significant ischemia or PAD in the infected limb.

9) Amputation: An absolute indication for amputation is life-threatening extensive necrosis with inflammation. Relative indications include distal phalangeal osteomyelitis of the foot and liquefactive necrosis. Additional signs of a possibly imminently limb-threatening infection include evidence of a systemic inflammatory response, rapid progression of infection, extensive necrosis or gangrene, crepitus on examination, tissue gas on imaging, extensive ecchymoses or petechiae, new-onset wound anesthesia, pain out of proportion to clinical findings, recent loss of neurologic function, critical limb ischemia, extensive soft tissue loss, extensive bony destruction, or failure of infection to improve with appropriate therapy. In patients with coagulative necrosis, watchful waiting for spontaneous amputation is recommended.

6. Treatment of acute Charcot arthropathy: Avoiding weight-bearing of the affected foot until resolution of the acute phase of arthropathy (cast or orthesis). Consider bisphosphonates combined with vitamin D and calcium supplements (long-term treatment, not always effective).

7. Long-term treatment to reduce the risk of ulcerations: Educate the patients and their family or caregivers on appropriate foot hygiene, necessity of daily foot inspections, and avoidance of foot injury. Use special orthopedic footwear with wide toe box, soft cushioned soles, and extra depth to accommodate any orthoses, if required, or appropriate inserts allowing correction of deformities and reducing excessive load-bearing in the foot and laces or Velcro closure for fitting and adjustments. Refer the patient to a foot care specialist.


Table 6.2-8. Pathogenesis of diabetic foot syndrome

Causative factors

Contributory factors

– Peripheral neuropathy: present in 50% of patients with diabetes aged >60 years; increases risk of foot ulceration 7-fold

– Excessive plantar pressure: related to limited joint mobility and foot deformities

– Repetitive trauma

– Atherosclerotic peripheral vascular disease affecting femoropopliteal and smaller vessels below the knee

– Several intrinsic wound-healing disturbances: impaired collagen cross-linking and metalloproteinase function, immunologic perturbances, higher rates of onychomycosis and toe-web tinea infections

– Obesity and poor vision leading to impaired self-care

Table 6.2-9. Differential diagnosis of neuropathic and ischemic foot


Foot ischemia

Neuropathic foot

Pain on movement


Pain at rest

+++ (if severe)


Sensory abnormalities


Pulse on the lower extremity






Bone structure



Lesion type



Lesion location

Depends on location of arterial lesions

Depends on internal and external pressure areas


Increases with physical activity

Increases with rest, usually appears at night

Table 6.2-10. Tools for identification of the at-risk foot


Identifying tool


Loss of protective sensation


Performed using 10-g (5.07 Semmens-Weinstein) monofilament. Inspect 8-10 anatomic sites and 4 plantar sites


Used to assess vibration perception thresholds. Reading >25 V has sensitivity of 83%, specificity of 63%, positive LR of 2.2, and negative LR of 0.27 for predicting foot ulceration over 4 years

Tuning fork

Performed using 128 Hz tuning fork. Abnormal response occurs when patient loses vibratory sensation while it is still perceived by examiner

Peripheral vascular disease

Clinical features

History of decreased walking speed, leg fatigue, claudication; assessment of pedal pulses

ABI (see Lower Extremity Peripheral Artery Disease)


In DM ABI may be falsely elevated due to arterial calcification




Mild arterial obstruction


Moderate obstruction


Severe obstruction

Arterial oxygen supply


Transcutaneous oximetry >30 mm Hg correlates with high likelihood of wound healing


Contrast-enhanced CTA is used to identify the area of blockage; gold standard test for evaluation of critical limb ischemia

ABI, ankle-brachial index; CTA, computed tomography angiography; DM, diabetes mellitus; LR, likelihood ratio.

Table 6.2-11. Classification of diabetic foot infection according to the Infectious Diseases Society of America (IDSA) and International Working Group on the Diabetic Foot (2012)

Clinical manifestation of infection

PEDIS grade

IDSA infection severity

No symptoms or signs of infectiona



Local infection involving only skin and subcutaneous tissue (no involvement of deeper tissues or systemic signs described below); if erythema is present, it must be >0.5 cm to ≤2 cm around the ulcer

Exclude other causes of an inflammatory skin response (eg, trauma, gout, acute Charcot arthropathy, fracture, thrombosis, venous stasis)



Local infection (as above) with erythema >2 cm or involving structures deeper than skin and subcutaneous tissues (eg, abscess, osteomyelitis, septic arthritis, fasciitis) and no systemic inflammatory response signs (see below)



Local infection (as above) with signs of SIRSb



a Infection defined as the presence of ≥2 of the following: local swelling or induration; erythema; local tenderness or pain; local warmth; purulent discharge (thick, opaque to white or sanguineous secretion).

b At least 2 of the following: temperature >38°C or <36°C; heart rate >90 bpm; respiratory rate >20 breaths/min or PaCO2 <32 mm Hg; white blood cell count >12×109/L or <4×109/L or ≥10% immature (band) forms.

c Ischemia may increase the severity of any infection, and the presence of critical ischemia often makes the infection severe. Systemic infection may sometimes manifest with other clinical findings, such as hypotension, confusion, vomiting, or evidence of metabolic disturbances, such as acidosis, severe hyperglycemia, and new-onset azotemia.

Adapted from Clin Infect Dis. 2012;54(12):e132-73.

IDSA, Infectious Diseases Society of America; PaCO2, partial pressure of arterial carbon dioxide; PEDIS, perfusion, extent, depth, infection, and sensation; SIRS, systemic inflammatory response syndrome.

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