There are approximately 29 million people with diabetes in the United States, and approximately 25% of people older the age of 65 have diabetes. The incidence of diabetes worldwide is projected to increase by 55% over the next 20 years, so this problem is only going to get worse. Approximately 70% of people with diabetes have peripheral neuropathy and once peripheral neuropathy develops the annual incidence of ulcer formation increases from less than one percent to greater than 7%. The three-year mortality for people with diabetes increases from 13% to 28% with an ulcer. Osteomyelitis occurs in 15% of ulcers, and 15% of those will go on to require amputation. In fact, approximately 60% of patients undergoing lower extremity amputation have diabetic foot ulcers as the underlying cause. Following a lower extremity amputation, the five-year mortality jumps to 60%. Diabetic foot ulcers are precursors to amputation and mortality, and therefore, every effort should be made to prevent them.
There are multiple forces at work in the development of diabetic foot ulcers. The four main branches of pathophysiology include neuropathy, ischemia, nutritional dysfunction, and infection. A well-perfused foot is more resistant to ulceration and infection than one that is suffering from the peripheral vascular disease. In people with diabetes, this is further complicated by a diminished effectiveness of perfusion caused by autonomic neuropathy where there is less recruitment of capillaries and shunting of blood around capillary beds. Neuropathy also causes not only a diminished sensation but a loss of sweat and oil glands that leads to dry cracking skin and a diminished neuroinflammatory response to noxious stimuli. Additionally, glycosylation of tendons leads to stiffening and shortening that can cause foot deformities (claw toes, hammer toes) and Achille's tendon stiffening which increases pressure on the forefoot.
Diabetic foot infections are common infections in patients with diabetes. The incidence of diabetic foot infections is more common in elderly patients with co-morbidities. Males and females are affected equally.
Mortality is rare, except in unusual circumstances. The mortality risk is higher in patients with chronic osteomyelitis, those with acute necrotizing soft-tissue infections, and in those with additional underlying problems affecting the immune system.
Once a diabetic foot ulcer forms it is a race against the clock to heal it before it gets infected. Like most skin and soft tissue infections, these start out as Staphylococcal or Streptococcal infections, but as the depth and severity of the infection increases, they quickly become polymicrobial infections with gram negative and anaerobic organisms. People with diabetes have a diminished capacity to fight infection and have nutritional deficits that make healing a challenge.
When taking a history from a person with diabetes, it is important to screen for the risk factors of diabetic foot ulcers (history of an ulcer, sensory neuropathy, abnormal pulses, or peripheral vascular disease, foot deformity, age over 65, poor glycemic control, end-organ damage, and renal disease). Patients known to be at risk should be wearing offloading diabetic footwear to protect their feet at all times. Once an ulcer develops it is important to know what they are wearing on their feet, and any treatment strategies tried previously. The physical exam should include a thorough screening for peripheral vascular disease and sensory neuropathy as well as an evaluation of the depth and severity of the ulcer.
Laboratory studies can be helpful in identifying malnutrition (pre-albumin), renal disease (BUN and creatinine), poor glycemic control (Hemoglobin A1C) and screening for osteomyelitis (CRP > 10 and ESR > 40). When cultures are taken, it is important to get a deep tissue culture rather than a superficial swab because most wounds have superficial colonization which is not necessarily representative of the most important infectious cause. Bone cultures are recommended to guide antibiotic selection in cases of osteomyelitis. Plain radiographs should be taken of all diabetic foot ulcers to screen for retained foreign bodies, osteomyelitis, and subcutaneous gas. X-ray findings of osteomyelitis take four to six weeks to develop, therefore, if there is a high index of suspicion of osteomyelitis, an MRI is helpful in making this diagnosis early. CT scans are useful for identifying deep space abscesses when MRI is not readily available. Transcutaneous oxygen measurements (TCOM) can be helpful in risk stratifying these patients. A transcutaneous oxygen tension of at least 40 mmHg is needed for normal wound healing. Most diabetics will have levels lower than this, and hyperbaric oxygen therapy and correction of peripheral vascular disease can increase oxygenation. Transcutaneous oxygen measurements can also be used to predict who will be most likely to benefit from hyperbaric oxygen therapy and who needs critical reperfusion. A transcutaneous oximetry measurement (TCOM) of greater than 200 mmHg under hyperbaric conditions indicates a greater likelihood of healing with a course of hyperbaric oxygen therapy with a sensitivity of 80% and positive predictive value of 88%.
Management strategies for wound care should include maintaining a moist wound environment, treating and preventing infection, off loading the affected area, debridement of necrotic tissue and biofilm, maximization of perfusion, nutrition and oxygen delivery. Offloading strategies include debridement of calluses, padding, orthotics, therapeutic foot wear, walking boots, total contact casts, and Achille's tendon lengthening. The presence of a callous increases the likelihood of ulcer formation 11-fold and debriding the callous lowers the pressure exerted by 26%. The combination of Achille's tendon lengthening and total contact casts have the highest success of healing forefoot ulcers. Superficial wound infections can be treated with topical antimicrobials, however, once cellulitis is present systemic antibiotics will be required. Even mild peripheral vascular disease should be corrected in these patients to optimize their likelihood of healing. Hyperbaric oxygen therapy can prevent amputations in patients with Wagner grade 3 or higher ulcers with a number needed to treat of four. Hyperbaric oxygen does this through a variety of mechanisms including increased oxygen delivery to ischemic/hypoxic tissues, enhanced white blood cell mediated bacterial killing, angiogenesis, accelerated collagen synthesis and fibroblast growth, and decreased edema. Nine randomized controlled trials show the effectiveness of hyperbaric oxygen therapy in these patients in speeding healing, preventing amputations and improved transcutaneous oxygen measurements. Hyperbaric oxygen increases the likelihood of wound healing with an odds ratio of 10. A standard treatment course is 30 to 40 treatments at 2.4 ATA these are given once or twice daily.
In summary, diabetic foot ulcers are precursors to amputations and require aggressive treatment. Patients should be screened for risk factors and referred for diabetic footwear when risk is identified. Staphylococcus aureus is the most important pathogen in diabetic foot infections, but as the depth and severity increase, these become polymicrobial. Surgery is indicated for the reversible peripheral vascular disease. Callouses should be debrided, and a moist wound healing environment should be maintained. Achille's tendon lengthening combined with total contact casting speeds healing and decreases the likelihood of recurrence and hyperbaric oxygen therapy is indicated in selected cases (Wagner grade 3 or higher) to speed healing and prevent amputation.