Diabetic Foot Problems

• Foot problems are common and feared complications of diabetes mellitus
• They're the leading diabetes-related cause of hospitalization and major cause of lower extremity amputations
• Diabetic foot problems significantly impact healthcare systems
• They increase in-hospital occupancy and length of stay
• The UK 2016 National Diabetes Inpatient Audit (NaDIA) found almost 1 in 10 inpatients (9%) with diabetes had active foot disease on admission
• Almost 1 in 20 inpatients were admitted for active foot disease (4%)
• 1 in 75 patients with diabetes developed a new foot lesion during their hospital stay (1.4%)
• Those with diabetes undergo annual risk screening for foot problems
• Those with risk factors need regular podiatry, education, and instruction in self-care

Foot Ulcers

• Skin ulceration is a common foot complication, usually secondary to diabetic peripheral neuropathy
• It can also be related to peripheral arterial disease
• A diabetic foot ulcer is a localized injury to the skin or underlying tissue below the ankle in a person with diabetes
• The lifetime risk of a person with diabetes developing a foot ulcer is 10-25%
• Foot ulcers precede up to 85% of lower limb amputations
• Diabetics with amputation have a 5-year survival rate of only 30%
• Most excess morbidity and mortality in these patients correlates to cardiovascular disease
• Foot ulcers should heal if pressure is removed from the ulcer site, arterial circulation is sufficient, and infection is managed

SGLT-2 Inhibitors

• Treatment with canagliflozin, a glucose-lowering sodium-glucose co-transporter-2 (SGLT-2) inhibitor, has been linked to increased lower limb amputations that usually affect the mid-foot and toes
• This has led to an FDA "black box" warning in the USA
• Prescribers should consider stopping therapy with SGLT-2 inhibitors if patients with diabetes develop significant foot complications such as infections or diabetic foot ulcers

Charcot Neuroarthropathy

• Those with diabetes with a warm unilateral swollen foot without ulceration should be presumed to have acute Charcot neuroarthropathy (CN) until proven otherwise
• In-hospital foot care should apply to all admissions, not just active foot disease
• Measures include a specific foot history and foot inspection for neuropathy, ischemia, ulceration, inflammation/infection, deformity, or CN
• Healthcare providers and patients need ongoing education about preventing and recognizing diabetes-related foot problems

Introduction

• Foot problems are a common and feared complication of diabetes mellitus
• They are now the leading cause of diabetes-related hospitalization and lower extremity amputations
• Diabetic foot problems have a significant financial impact on healthcare systems by increasing in-hospital occupancy and length of stay
• In England, diabetes-related foot disease costs around £1 billion overall, approximately £1 in every £150 spent by the National Health Service (NHS)
• Worldwide, foot ulcers develop in 9.1 million to 26.1 million diabetics annually
• A diabetes-related lower limb amputation occurs every 30 seconds
• Skin ulceration, usually caused by diabetes-related peripheral neuropathy (loss of protective sensation) and, less frequently, peripheral arterial disease (PAD).
• Diabetics have a 15-25% lifetime risk of developing a foot ulcer
• About half of DFUs are clinically infected at presentation, and these wounds are at increased risk of adverse outcomes

Infections

• Infection is an invasion and multiplication of microorganisms in host tissues that induce a host inflammatory response that is typically followed by tissue destruction
• Infection is typically the final precipitating cause of lower extremity amputations
• Diabetics have an amputation risk 23 times higher
• Persons with diabetes who have an amputation have a 5-year survival rate of only 30%
• Most excess morbidity and mortality in these patients correlates with cardiovascular disease
• Charcot neuroarthropathy (CN), a less common but serious complication of diabetic neuropathy, can lead to foot deformities and ulceration
• In-hospital foot care should apply to all admissions, not just active foot disease
• Taking a specific foot history and an inspection of the feet, looking for evidence of neuropathy, ischemia, ulceration, inflammation, infection, deformity, or CN can help diagnose
• Feet should be inspected daily during the hospital stay alongside new problems

Multidisciplinary Teams

• New problems need management in conjunction with the specialist diabetic foot multidisciplinary team that should include timely access to podiatrist, diabetologist, vascular/orthopedic surgeon, interventional radiologist, tissue viability nurse, infectious disease/microbiologist, diabetes educator/nurse, and orthotist
• The acute diabetic foot includes any foot wound present on admission, any newly acquired foot wound picked up on daily foot checks, suspected CN, any unexplained erythema discoloration or swelling, and a cold pale foot
• The UK 2016 National Diabetes Inpatient Audit (NaDIA) revealed almost 1 in 10 diabetics (9%) had active foot disease on admission
• Almost 1 in 20 inpatients were admitted directly for active foot disease (4%)
• 1 in 75 patients with diabetes developed a new foot lesion during their in-hospital stay (1.4%)

Prevention

• Vascular complications are a major cause of morbidity and mortality in diabetic patients
• Results from interactions between systemic metabolic abnormalities such as hyperglycemia, dyslipidemia, genetic/epigenetic modulators, and local body tissue responses to toxic metabolites
• Smoking is an important risk factor
• Macrovascular complications (PAD) and microvascular complications (peripheral/autonomic neuropathy) are common, and both are important in the pathophysiology of diabetic foot problems
• Examples include: motor nerve dysfunction that results in disturbances in posture and balance that can lead to increased pressures within the foot or loss of sensory perception that results in inability to feel pain, thus inhibiting any preventative action from being taken
• Loss of autonomic function in the lower limbs leads to loss of sweating and hence dry skin predisposes to infection
• Autonomic dysregulation alters microvascular flow leading to arteriovenous "shunting" with tissue hypoxia and paradoxically warm feet
• Infection can proceed rapidly and the end-stage of tissue death is quickly reached
• Managing glycemic control, hypertension, dyslipidemia, smoking cessation, weight management, use of antiplatelet agents, and addressing other modifiable risk factors are important to prevent or slow any progression of vascular complications

SGLT-2 Inhibitors

• The glucose-lowering sodium-glucose co-transporter-2 (SGLT-2) inhibitor, canagliflozin, has been associated with an increase in lower limb amputations that usually affect the mid-foot and toes in two large clinical trials
• This may be a SGLT-2 class effect but more information is needed
• The canagliflozin-prescribing information now has a FDA "black box" warning
• Amputations happen about twice as often as in the control group
• The risk for lower limb amputations happens in 3–7.5 patients per 1000 over a year's time
• Prescribers should consider stopping therapy with this agent in diabetics who develop significant foot complications such as infection or DFU
• Most foot complications are potentially preventable
• Identifying the “at-risk” population during comprehensive foot evaluation is the first step in prevention that is performed at least annually in all adults with diabetes

Risk Factors

• Risk for ulcers or amputation is increased in people with poor glycemic control, peripheral neuropathy with loss of protective sensation (LOPS), cigarette smoking, foot deformities, Charcot foot, pre-ulcerative callus or corn, PAD, history of foot ulcer, previous amputation, visual impairment, and diabetic kidney disease, especially patients on dialysis
• Foot examination should include general inspection of skin integrity and musculoskeletal deformities

Management

• Vascular: inspection and palpation of pedal pulses, capillary refill, foot temperature, and ankle-brachial pressure index
• Neurological: designed to identify LOPS rather than early neuropathy
• LOPS (large-fiber function) indicates the presence of distal sensorimotor polyneuropathy
• It is a risk factor for diabetic foot ulceration and amputation
• The 10-g monofilament is the most useful test to diagnose LOPS and is done on four sites on each foot
• Patients with diabetes and high-risk foot conditions (hx of ulcer/amputation, deformity, LOPS, and/or PAD) and their families get education about risk factors and appropriate management
• Instructions on access urgent/emergency foot care is critical
• Regular podiatry review is needed
• Appropriate footwear that includes an orthotist review and footwear behaviors at home and also in the hospital setting is needed
• The UK National Diabetes Foot Care Audit (NDFA) 2014–2016 data of 11,000 people with acute foot ulcers showed one-third of ulcer episodes self-referred for expert assessment
• Two-fifths (40%) of ulcer episodes referred by a clinician (i.e., those not self-referring) had an interval of two or more weeks to first expert assessment

Classification

• Classification schemes have been published over the past three decades
• 2004 guidelines devoted to diabetic foot infections (DFI) were published
• Multidisciplinary panels of experts from the Infectious Diseases Society of America (IDSA) and the International Working Group on the Diabetic Foot (IWGDF) created the guidelines
• IDSA were updated in 2012
• The IWGDF in 2016 updated the "infection" part of the PEDIS classification (Perfusion, Extent, Depth, Infection and Sensation)
• IDSA/IWGDF scheme defines infection and classifies its severity
• DFIs are diagnosed clinically, based on the presence of clinical signs and symptoms of inflammation (i.e., redness, warmth, swelling, pain/tenderness) or purulent secretions, but not the results of cultures of wounds

Scoring Systems

• In judging severity, rule out other causes of inflammatory skin response - trauma, gout, acute CN, fracture, thrombosis/venous stasis
• Other classification systems: SINBAD and Wagner score system
• SINBAD: recommended by UK NICE
• Ulcer severity is recorded using the SINBAD scoring system, scoring an ulcer between 0 (least severe) and 6 (most severe) based on the presence of each element
• The six SINBAD elements are: Site (on hindfoot) ulcer penetrates the hindfoot (rear of the foot); Ischemia
• Impaired circulation in the foot; Neuropathy – LOPS in the foot; Bacterial infection – signs of bacterial infection of the foot ; Area (≥1 cm²) – ulcer > 1 cm²; and Depth (to tendon/bone) – ulcer penetrates to tendon or bone
• Ulcer with SINBAD score of ≥3 is a severe ulcer, less than 3 is a less severe ulcer
• The UK National Diabetes Foot Care Audit (NDFA) 2014–2016 data showed severe ulcer grades in almost half (46%) of ulcer episodes at first expert assessment
• Clinicians assessing a patient presenting with a DFI should consider the problem at three levels:
  • The whole patient cognitive, metabolic, and fluid status
  • The affected limb includes presence of neuropathy and vascular insufficiency); and
  • The wound
• Measure vital signs, palpate pedal pulses, check for peripheral neuropathy, debride and probe any open wounds
• Special attention should be paid to detecting crepitus, bullae, new onset tenderness or anesthesia, rapidly advancing cellulitis or gangrenous tissue.
• Presence of these findings should prompt consultation the experienced foot surgeon
• In addition to basic hematology and blood chemistry tests, patients with a foot wound have a plain radiograph of the foot look for gas, foreign body or bone lesions

Imaging

• Indications for MRI of the diabetic foot: suspicion of deep infection; as an aid to diagnosing CN; establishing the extent when plain X-ray is equivocal or even negative; diagnosing mid-foot and metatarsal fractures that are not clear-cut on plain X-ray
• Classifying the severity of a DFI helps to determine hospitalization and broad-spectrum IV antibiotic therapy, which is usually required for severe infections but rarely for mild (or many moderate) infections

Multidisciplinary Teams

• Early and continued care is associated with better outcomes, reduces likelihood of major lower extremity amputation
• Key criterion for membership is expertise and interest (6, 15)
• DFI guidelines talk of the critical role of multidisciplinary teams, which have only been established in large hospitals in resource-rich countries (12,16,17)
• The UK 2016 National Diabetes Inpatient Audit (NaDIA) has data that multidisciplinary foot teams in hospitals had better outcomes. It also highlighted that almost one quarter of hospital sites involved in the audit did not have a multidisciplinary foot team
• Establishing a robust diabetic foot care pathway with clear antibiotic protocols enables most of patients in the hospital setting to get immediate appropriate treatment with a clear plan of action

Antibiotics

• Clinically uninfected wounds do not need a culture and no evidence has been found that treating colonization with antibiotics will improve wound healing or prevent infection
• Infected wounds, however, virtually always require antibiotic therapy.
• Bacteria associated with the infection of treatment requires understanding of the formation and composition of the DFU microbiota
• Obtaining a tissue sample for culture from any clinically infected wound, preferably before starting empirical antibiotic therapy, is a crucial step toward ensuring the select the correct agent
• Wound specimens should be taken only after careful cleaning and debriding
• Specimens of deep tissue obtained by biopsy or curettage or aspirations of purulent secretions are more apt to grow the true pathogens and less likely to yield colonizing microorganisms
• Swabs should be avoided, blood cultures are rarely positive, except in patients with evidence of systemic sepsis
• Choosing empiric antibiotic(s) should be based on most likely pathogens
• Severity of the infection, local knowledge of their probable antibiotic susceptibility pattern

DFU Microbiota

• Gram-positive cocci (especially Staphylococcus aureus/streptococci) are targeted for patients with mild/moderate DFIs
• When the infection is chronic or treated with antimicrobials, aerobic gram-negative organisms often join the gram-positives
• Empirical antibiotic therapy should be administrated parenterally and be broad-spectrum, covering staphylococci, streptococci and commonly reported gram-negatives covering
• initial empiric antibiotic choices need adaptation based on results of culture and sensitivity tests
• If the patient is clinically responding, there is no need to cover all isolates as long as they are especially relatively avirulent organisms (e.g., coagulase-negative staphylococci/enterococci) isolated from an imperfect wound specimen
• Antibiotic therapy doesn't need extension until full healing unless infectious signs and symptoms need resolution
• The typical amount of time taken for soft tissue infection is 1 to 2 weeks