DM is the leading cause of nontraumatic lower extremity amputation in the United States. Foot ulcers and infections are also a major source of morbidity in individuals with DM. The reasons for the increased incidence of these disorders in DM involve the interaction of several pathogenic factors: neuropathy, abnormal foot biomechanics, PAD, and poor wound healing. The peripheral sensory neuropathy interferes with normal protective mechanisms and allows the patient to sustain major or repeated minor trauma to the foot, often without knowledge of the injury. Disordered proprioception causes abnormal weight bearing while walking and subsequent formation of callus or ulceration. Motor and sensory neuropathy lead to abnormal foot muscle mechanics and to structural changes in the foot (hammer toe, claw toe deformity, prominent metatarsal heads, Charcot joint). Autonomic neuropathy results in anhidrosis and altered superficial blood flow in the foot, which promote drying of the skin and fissure formation. PAD and poor wound healing impede resolution of minor breaks in the skin, allowing them to enlarge and to become infected.
Many individuals with type 2 DM develop a foot ulcer (great toe or metatarsophalangeal areas are most common), and a significant subset who develop an ulceration will ultimately undergo amputation (14–24% risk with that ulcer or subsequent ulceration). Risk factors for foot ulcers or amputation include male sex, diabetes for >10 years, peripheral neuropathy, abnormal structure of foot (bony abnormalities, callus, thickened nails), PAD, smoking, history of previous ulcer or amputation, visual impairment, and poor glycemic control. Large calluses are often precursors to or overlie ulcerations.
TREATMENT Lower Extremity Complications
The optimal therapy for foot ulcers and amputations is prevention through identification of high-risk patients, education of the patient, and institution of measures to prevent ulceration. High-risk patients should be identified during the routine, annual foot examination performed on all patients with DM (see “Ongoing Aspects of Comprehensive Diabetes Care” in Chap. 24). If the monofilament test or one of the other tests is abnormal, the patient is diagnosed with loss of protective sensation (LOPS; Chap. 23). Providers should consider screening for asymptomatic PAD in individuals >50 years of age who have diabetes and other risk factors using ankle-brachial index testing in high-risk individuals. Patient education should emphasize (1) careful selection of footwear, (2) daily inspection of the feet to detect early signs of poor-fitting footwear or minor trauma, (3) daily foot hygiene to keep the skin clean and moist, (4) avoidance of self-treatment of foot abnormalities and high-risk behavior (e.g., walking barefoot), and (5) prompt consultation with a health care provider if an abnormality arises. Patients at high risk for ulceration or amputation may benefit from evaluation by a foot care specialist. Calluses and nail deformities should be treated by a podiatrist. Interventions directed at risk factor modification include orthotic shoes and devices, callus management, nail care, and prophylactic measures to reduce increased skin pressure from abnormal bony architecture. Attention to other risk factors for vascular disease (smoking, dyslipidemia, hypertension) and improved glycemic control are also important.
Despite preventive measures, foot ulceration and infection are common and represent a serious problem. Due to the multifactorial pathogenesis of lower extremity ulcers, management of these lesions is multidisciplinary and often demands expertise in orthopedics, vascular surgery, endocrinology, podiatry, and infectious diseases. The plantar surface of the foot is the most common site of ulceration. Ulcers may be primarily neuropathic (no accompanying infection) or may have surrounding cellulitis or osteomyelitis. Cellulitis without ulceration is also frequent and should be treated with antibiotics that provide broad-spectrum coverage, including anaerobes (see below).
An infected ulcer is a clinical diagnosis, because superficial culture of any ulceration will likely find multiple possible bacterial species. The infection surrounding the foot ulcer is often the result of multiple organisms, with aerobic gram-positive cocci (staphylococci including MRSA, Group A and B streptococci) being most common and with aerobic gram-negative bacilli and/or obligate anaerobes as co-pathogens.
Gas gangrene may develop in the absence of clostridial infection. Cultures taken from the surface of the ulcer are not helpful; a culture from the debrided ulcer base or from purulent drainage or aspiration of the wound is the most helpful. Wound depth should be determined by inspection and probing with a blunt-tipped sterile instrument. Plain radiographs of the foot should be performed to assess the possibility of osteomyelitis in chronic ulcers that have not responded to therapy. Magnetic resonance imaging (MRI) is the most specific modality, with nuclear medicine scans and labeled white cell studies as alternatives. Surgical debridement is often necessary.
Osteomyelitis is best treated by a combination of prolonged antibiotics (IV, then oral) and/or possibly debridement of infected bone. The possible contribution of vascular insufficiency should be considered in all patients. Peripheral arterial bypass procedures are often effective in promoting wound healing and in decreasing the need for amputation of the ischemic limb.
A consensus statement from the ADA identified six interventions with demonstrated efficacy in diabetic foot wounds: (1) off-loading, (2) debridement, (3) wound dressings, (4) appropriate use of antibiotics, (5) revascularization, and (6) limited amputation. Off-loading is the complete avoidance of weight bearing on the ulcer, which removes the mechanical trauma that retards wound healing. Bed rest and a variety of orthotic devices or contact casting limit weight bearing on wounds or pressure points. Surgical debridement is important and effective, but clear efficacy of other modalities for wound cleaning (enzymes, soaking, whirlpools) is lacking. Dressings such as hydrocolloid dressings promote wound healing by creating a moist environment and protecting the wound. Antiseptic agents should be avoided. Topical antibiotics are of limited value. Referral for physical therapy, orthotic evaluation, and rehabilitation should occur once the infection is controlled.
Mild or non-limb-threatening infections can be treated with oral antibiotics directed predominantly at methicillin-susceptible staphylococci and streptococci (e.g., dicloxacillin, cephalosporin, amoxicillin/clavulanate). However the increasing prevalence of MRSA often requires the use of clindamycin, doxycycline, or trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole exhibits less reliable coverage of streptococci than the β-lactams, and diabetic patients may develop adverse effects including acute kidney injury and hyperkalemia. Surgical debridement of necrotic tissue, local wound care (avoidance of weight bearing over the ulcer), and close surveillance for progression of infection are crucial. More severe infections require IV antibiotics as well as bed rest and local wound care. Urgent surgical debridement may be required. Optimization of glycemic control should be a goal. IV antibiotics should provide broad-spectrum coverage directed toward Staphylococcus aureus, including MRSA, streptococci, gram-negative aerobes, and anaerobic bacteria. Initial antimicrobial regimens include vancomycin plus a β-lactam/β-lactamase inhibitor or carbapenem or vancomycin plus a combination of quinolone plus metronidazole. Daptomycin, ceftaroline, or linezolid may be substituted for vancomycin. If the infection surrounding the ulcer is not improving with IV antibiotics, reassessment of antibiotic coverage and reconsideration of the need for surgical debridement or revascularization are indicated. With clinical improvement, oral antibiotics and local wound care can be continued on an outpatient basis with close follow-up.