The foot is often the site of clinical manifestations of diabetes mellitus. It is estimated that 5 to 6 percent of the U.S. population has diabetes, with one-half exhibiting some degree of lower-extremity arterial insufficiency. For diabetic patients, 20 percent of their admissions to the hospital are caused by foot-related problems, most commonly infection. In addition, 50 to 70 percent of all lower extremity amputations are performed on patients with diabetes. Annually, such amputations are associated with a 3 to 7 percent mortality rate and a 36 percent complication rate.
A lesion of the foot, such as an ulcer, recurrent fungal infection or paronychia, may be the first clue to the presence of diabetes. Despite the statistics mentioned above, fewer than 20 percent of diabetic patients are given regular foot examinations by their primary care physician. It iS estimated that one-half of all diabetic amputations could be prevented by the early detection and management of clinical manifestations. An aggressive approach that targets risk-factor reduction, optimal glycemic control, patient education and meticulous foot care will minimize the substantial morbidity and mortality associated with diabetic foot disease.
Complex and interrelated, the deleterious effects of diabetes mellitus on the foot can be broadly classified as those caused by neuropathy,[4,5] those caused by angiopathy[6-12] and those caused by immunopathy[9,13] (Figure 1). Combined with environmental factors (e.g., poor hygiene), comorbid states (e.g., dehydration, malnutrition) and trauma (e.g., poorly fitting footwear), the effects of diabetes on the foot can result in secondary pathomechanical deformities. Through a reinjury cycle of repeated ulcer formation, complications such as superinfection, gangrene and limb loss occur.
MAL PERFORANT ULCERATION
In the presence of poor vascularity and impaired sensation resulting from sensory neuropathy, weight bearing remains unrestricted and painless. Continued weight-bearing and pressure of keratotic material on the underlying dermis eventually cause full-thickness necrosis and ulceration. A mal perforant ulcer (Figure 2) is an easy portal of entry for bacteria. Fifteen to 20 percent of persons with diabetes develop a foot ulcer during their lifetime. Ulcers are the leading cause of amputation in the United States and the second leading cause of hospitalization of diabetic patients. Sixty to 70 percent of ulcers are neuropathic in origin, 15 to 20 percent are vascular and 15 to 20 percent are of mixed origin.
CHARCOT'S JOINT DISEASE
Repetitive microtrauma in the setting of long-standing sensory deficits and angiopathic changes can eventually lead to major bone and joint destruction. Diabetes mellitus is the most common cause of Charcot's joint (Figure 3). Lack of proprioceptive protective sensation, excessive and abnormal range of motion in foot joints, destruction of joint cartilage and occult bone microfractures lead to the typical rocker-bottom foot, with subluxation of the midtarsal and/or the metatarsophalangeal structures.
Signs and Symptoms
Shooting pains and paresthesias in the feet and legs often precede the onset of decreased sensation and proprioception. Hyperesthesia of the skin, severe enough to cause pain on contact with bed clothes, is common.
Polyneuropathies cause the "stocking and glove" type of hypoesthesia classically seen in diabetic patients. Frequently, patients do not notice this loss of sensation in their limbs until it is revealed in a physical examination. The earliest sensory losses noted on physical examination are vibratory and position sense of the toes (proprioception). With further progression, a detectable loss of the sensations of pain, touch and heat occurs, as well as a diminution of the Achilles tendon reflex. Motor loss, which is more obvious in mononeuropathy, progresses slowly in the polyneuropathies. Impaired function of the intrinsic muscles of the foot with loss of tone leads to structural deformities such as hammer toes or claw toes, hallux valgus and cavus foot, and frequently causes callus formation (Figures 4 through 7).
Generalized symptoms associated with autonomic neuropathies in patients with diabetes mellitus include nausea, vomiting, diarrhea, impotence and dry, cracked skin that is caused by the cessation of perspiration. In addition, there is an autosympathectomy phenomenon that, in the absence of large-vessel disease, is characterized by increased blood flow secondary to the opening of anatomic arteriovenous shunts. This abnormal vasodilation causes increased skin temperature and prominent dorsal veins when the patient is supine and can ultimately lead to osteopenia and stress fractures.
Pain is a common symptom of ischemia in the lower extremities. The classic symptom of macrovascular disease, intermittent claudication, occurs four times more frequently in persons with diabetes than in persons who do not have diabetes.[1,16] It is a reproducible symptom affecting the limb typically one joint below the site of anatomic arterial obstruction. Limb-threatening ischemia is characterized by pain that is constant, present at rest and somewhat improved by foot dependency. It is important to differentiate the severe aching pain of ischemia from the burning pain of a polyneuropathy that is present during the day and worsens at night.
The feet of patients with diabetes, as well as the footwear, should be inspected at every office visit. Pulses should be palpated, capillary refill checked, skin examined (including nails and interspaces) and deep tendon reflexes evaluated. Pin-prick, temperature and vibration sensation of the feet should be assessed at least annually. Unilateral foot or ankle swelling with localized erythema and warmth without abrasions or portals of entry are hallmarks of Charcot's disease. Crepitus may be palpable as the degenerative joint surfaces and fractures move against one another during range of motion exercise (i.e., bag of bones" effect).
The clinical manifestations of diabetic angiopathy include the six P's of peripheral vascular disease: (1) pain (pain at rest, nocturnal pain or claudication); (2) pulselessness (foot pulses absent but popliteal pulses often strong and palpable) 3) poikilothermy (inability to compensate for changes in ambient temperature, usually noticed as a decrease in skin temperature that must be assessed bilaterally); (4) pallor of the feet on elevation and rubor on dependency; (5) paresthesias and (6) paralysis (which represents a sign of irreversible tissue ischemia). Signs of arterial insufficiency include trophic changes of the skin, such as a shiny surface, hair loss and nail thickening.
Noninvasive tests for evaluating arterial insufficiency typically include use of a Doppler probe to assess systolic blood pressure at various sites and calculation of the ankle-to-arm index pressure ratio (which also provides a useful guide to healing). Normally, the ratio of the ankle (dorsal pedis) systolic pressure to the arm (brachial artery) systolic pressure is at least 1.0. Ratios less than 0.5 are associated with severe peripheral vascular disease on angiography. Ratios in the range of 0.3 are associated with rest pain and limb-threatening ischemia. An ankle systolic pressure of less than 70 mm Hg usually indicates perfusion inadequate for healing of foot ulcers. The usual Doppler technique can be unreliable, however, because of noncompressible arteries.
Diabetic patients may have artificially elevated systolic pressures (greater than 250 mm Hg) as a result of medial arterial calcification or Monckeberg's arteriosclerosis  (Figure 8). The condition is commonly observed initially in the foot and progresses proximally.
Other technologies, such as photoplethysmography, transcutaneous oxygen tension determination ([TcPO.sub.2]) and pulse volume recording are also useful in tracking this condition. Toe systolic pressure greater than 30 mm Hg indicates adequate perfusion. The chance that infections and surgical incisions will heal is 80 percent if the [TcPO.sub.2] at the site is above 35 mm Hg, but only 20 percent if the [TcPO.sub.2] is less than 20 mm Hg. When the [TcPO.sub.2] is less than 5 mm Hg, the tissue is ischemic beyond salvage, and amputation is the only recourse. A vascular surgeon should be consulted if poor perfusion or equivocal results are found.
Arteriography, performed either conventionally or with computed digital subtraction technology (Figure 9), is indicated for patients being considered for vascular reconstruction. Arteriography should be considered in the presence of foot ulceration and absent foot pulses (Figure 10). Patency of the distal vessels must be arteriographically demonstrated before bypass surgery is performed. Many patients with diabetic angiopathy have concomitant renal insufficiency and require special follow-up after arteriography, because of the nephrotoxicity associated with contrast media. Magnetic resonance angiography has been used experimentally to assess angiopathy; it has the distinct advantage of avoiding the use of injectable contrast material, but it may overestimate the degree of vessel stenosis.
Plain films are helpful in the evaluation of possible osteomyelitis, although both sensitivity and specificity are suboptimal (Figure 11). If radiographs reveal osteomyelitis, further studies are unnecessary, unless multifocal involvement or neuropathic bone changes are suspected. The ability to advance a sterile surgical probe through an ulcer to underlying bone has been shown to be highly specific for the diagnosis of osteomyelitis.
Radionuclide scans using technetium pyrophosphate, gallium-67 citrate and indium-111 may be used to supplement plain radiographs, since increased uptake allows earlier detection of osteomyelitis (Figure 12). Technetium scans can be positive as early as 48 hours after the onset of infection. These scans are highly sensitive but not very specific. Gallium scans have intermediate sensitivity and specificity in detecting soft tissue inflammation. Indium scans have the highest specificity. All of the radionuclide scans share the disadvantages of significant expense and limited availability.
The value of superficial ulcer cultures obtained by the swab method is a matter of controversy. Cultures obtained by curettage of ulcers, needle aspiration of an abscess or purulent drainage are more accurate than swab cultures and nearly match the accuracy of cultures obtained surgically. Blood tests (i.e., complete blood cell count with differential, erythrocyte sedimentation rate and blood cultures) should also be performed if deep infection or osteomyehtis is suspected.
Many diabetic patients can avoid the occurence of foot ulcers if physicians stress preventive management, which includes regular office visits, patient education and footwear modification. A comprehensive approach to the management of diabetic foot ulcers includes careful glycemic control (i.e., insulin, oral hypoglycemic agents), weight reduction, exercise as tolerated and smoking cessation. Nutritional and metabolic states are often important factors in a successful outcome. Consideration of a nutritional laboratory assessment is appropriate and includes an absolute lymphocyte count and determination of serum albumin level; the latter test is readily available, and most of the data in the nutritional assessment is based on results of this measurement. Good wound healing requires albumin levels of 3.5 g per dL (35 g per L) and an absolute lymphocyte count above 1,500 mm[3.3] Management of more advanced foot ulcers requires prompt institution of medical and surgical interventions to avoid life-threatening disease that might necessitate amputation (Table 1).
Treatment Protocol for Diabetic Foot Ulcers
1. Control local and systemic sequelae of infection, including hyperglycemia.
2. Promptly drain all closed-space infections and debride all necrotic material from bleeding margins.
3. Promote a moist wound environment by using wet dressings, changed twice daily.
4. Guide antibiotic therapy by appropriately obtained culture results whenever possible.
5. Evaluate all foot ulcerations for ischemia, even in the presence of infection or neuropathy.
6. Consider foot casting or booting to avoid pressure on the ulcer site during ambulation.
7. If surgery is considered, perform arteriography to determine status of foot vessels, even if tibial and peroneal arteries in the leg are completely occluded.
8. Perform distal arterial reconstruction when appropriate to restore maximum perfusion to the foot.
Treatment of diabetic foot infections varies, depending on the severity of the infectious process, from mild forms of cellulitis and paronychia to limb- or life-threatening infections such as sepsis, myonecrosis, gangrene (Figure 13) and osteomyelitis. Generally speaking, all but the most superficial and mild infections must be evaluated for deeper involvement. Hospitalization is warranted for patients with complicated infections, inability to establish glycemic control or systemic toxicity.
Outpatient management is reserved for patients who can care for themselves or have available help at home and for whom an appropriate oral antibiotic is available. Follow-up office visits should occur every few days. Although repeated dressings with peroxide, povidone-iodine or other antiseptics kill bacteria, fibroblasts within the wounds are also killed, and the surrounding skin becomes dry and cracked. The application of gauze dressings dampened with normal saline and changed twice daily will preserve a moist environment and gently debride granulating wounds.
Soaking the foot should be avoided. Topical antibiotic solutions or ointments are effective against some superficial strains of staphylococci and are nontoxic to host cells. Deeper skin and soft tissue infections (i.e., cellulitis) are usually managed in the office setting with oral antibiotics. Deep, malodorous infections or bone infections (osteomyelitis) require in-hospital care. Any significant infection should prompt a simultaneous assessment for limb ischemia. Depending on the degree of angiopathy present, surgical options range from debridement of soft tissue to potential revascularization to amputation.
Antibiotics are also essential for the management of infected ulcerations. Because such infections are often polymicrobial, a broad-spectrum agent should be chosen initially. Empiric antibiotics must adequately cover staphylococci and streptococci, since these organisms are present in most lesions (Table 2). Anaerobes are more prevalent in chronic wounds and are suggested by the presence of foul-smelling pus or gas in the deeper tissues. Recent antibiotic treatment and complicated infections are more frequently associated with Pseudomonas and Enterobacteriaceae species. In severe cases an infectious-disease consultation may be necessary. The antibiotic agents chosen should be non-nephrotoxic when possible. Large doses and a prolonged course of therapy (four or more weeks) are often necessary in more serious infections, especially osteomyelitis. Duration of antibiotic therapy depends on response to treatment, severity of infection and causative organism. A period of one to two weeks of therapy is usually sufficient for superficial soft tissue infections, while osteomyelitis may require several months of therapy. Bone cultures should be obtained to direct antibiotic therapy in patients with osteomyelitis.
Topical application of growth factors derived from the patient's platelets and other blood components has been used experimentally to promote healing.
Optimal wound healing is compromised by weight bearing on the wound area; however, bed rest for extended periods is usually impractical and may lead to deterioration in other factors essential for healing, such as glycemic control.
Use of an Unna boot or total-contact casting for four to eight weeks may be appropriate. Total-contact casting promotes an equal distribution of weight over the entire foot surface through the snug application of plaster on every part of the foot. Stockinette is used, and felt pads are placed around the malleoli and the bony prominences. The patient should be made aware of the treatment plan, the prolonged time required for healing and the consequences of noncompliance.
Curing osteomyelitis in the diabetic patient is extremely difficult because of associated immunopathy and angiopathy. Bacteremia may lead to dissemination of infection to bony sites far from the active infection. The focal point of infection may be inaccessible to antibiotics or debridement. If the osteomyelitis is superficial and if enough viable soft tissue is available for coverage, cortical bone can be surgically debrided (Figure 14). Aggressive debridement and long-term antibiotics may successfully treat the infection, but failure is common in the presence of ischemia and advanced infection.
Mechanical debridement of the ulcer and surrounding hyperkeratotic tissue to healthy bleeding tissue and removal of all necrotic material and eschar are essential. Chemical debridement and whirlpool soaks have limited to no usefulness.
More aggressive surgical treatment is indicated for ulcerations or infections that do not improve with appropriate medical therapy, debridement and casting. Options include arterial reconstruction (angioplasty or bypass grafting), thromboembolectomy when applicable and, rarely, sympathectomy. Three-year patency rates after bypass grafting are 85 to 90 percent, with comparable limb salvage rates.[25, 26] Revascularization techniques are technically difficult, since diabetic angiopathy usually affects smaller vessels below the trifurcation.
Amputation (a 1 percent incidence rate per year among diabetic patients) is often ultimately necessary in patients with end-stage vascular disease or advanced osteomyelitis. Immediate postamputation mortality is 20 percent; 60 percent of patients survive three years, and 45 percent are alive at five years. Within three years, 49 percent of surviving patients have a second amputation, and within five years, 55 to 60 percent have a second amputation. Amputation exacts a heavy psychologic toll. Careful preoperative counseling is essential, and psychosocial support is crucial postoperatively.
Careful daily foot hygiene is essential to decrease the risk of foot ulcer in the diabetic patient. Use of densely padded socks and well-fitting shoes should be emphasized. Feet should be gently but thoroughly cleaned and inspected on a daily basis. Hot water, soaking of feet and vigorous massage are all detrimental and should be avoided. Use of topical moisturizers should be encouraged in patients with chronically dry, cracked skin resulting from autonomic neuropathy.
Disorders such as hypertrophic, mycotic nails can be managed with routine aseptic debridement using a clipper or an electric grinder (Figures 15 and 16). Ingrown toenails may require local anesthesia before removal. Before nail removal, the physician should be certain the vascular supply to the affected digit is adequate for wound healing. If the circulation is insufficient, a vascular surgeon should be consulted, because a minor surgical procedure on a poorly vascularized diabetic foot can result in significant complications, such as gangrene. Corns and calluses should be debrided routinely every six to eight weeks. If left untreated, these benign lesions may progress to mal perforant ulcers. The patient should be instructed about sound foot care, with the warning that careless self-treatment of corns and calluses may result in complicating infections.
Specialized footwear is currently covered by Medicare. The primary care physician must address this important but often neglected aspect of treatment by explaining to the patient that proper footwear can substantially reduce the development of skin ulcers, thereby avoiding significant expense and morbidity over the long term.
[1.] Ritz G, Friedman S, Osbourne A. Diabetes and peripheral vascular disease. Clin Podiatr Med Surg 1992;9:125-37. [2.] Boulton AJ, Connor H. The diabetic foot. Diabet Med 1988;5:796-8. [3.] Sussman KE, Reiber G, Albert SF. The diabetic foot problem - a failed system of health care? Diabetes Res Clin Pract 1992;17:1-8. [4.] Boulton AJ, Ward JD. Diabetic neuropathies and pain. Clin Endocrinol Metab 1986;15(4):917-32. [5.] Greene DA, Lattimer S, Ulbrecht J, Carroll P. Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care 1985;8:290-9. [6.] Colwell JA, Winocour PD, Lopes-Virella M, Halushka PV. New concepts about the pathogenesis of atherosclerosis in diabetes mellitus. Am J Med 1983;75:67-80. [7.] Edmonds ME. The diabetic foot: pathophysiology and treatment. Clin Endoednol Metab 1986;15:889-916. [8.] Lopes-Virella MF. Clinical implications of atherosclerosis research. Pract Diabet 1992;11:8-11. [9.] Banson BB, Lacy PE. Diabetic microangiopathy in human toes. Am J Pathol 1964;45:41-58. [10.] Barner HB, Kaiser GC, Willman VL. Blood flow in the diabetic leg. Circulation 1971;43:391-4. [11.] Lepantalo M, Kangas T, Pietila J, Scheinin T, Scheinin TM. Non-invasive characterization of angiopathy in the diabetic foot. Eur J Vasc Surg 1988;2:41-5. [12.] Irwin ST, Gilmore J, McGrann S, Hood J, Allen JA. Blood flow in diabetics with foot lesions due to small vessel disease. Br J Surg 1988;75:1201-6. [13.] Grunfeld C. Diabetic foot ulcers: etiology, treatment, and prevention. Adv Intern Med 1992;37: 103-32. [14.] Bays HE, Pfeifer MA. Peripheral diabetic neuropathy Med Clin North Am 1988;72:1439-64. [15.] O'Brian JT, Massey EW. Mononeuropathy in diabetes mellitus: a phenomenon easily overlooked. Postgrad Med 1979;65(5):128,130-2,135-6. [16.] Elkeles RS, Wolfe JH. ABC of vascular diseases. The diabetic foot. BMJ 1991;303:1053-5. [17.] Everhart JE, Pettitt DJ, Knowler WC, Rose FA, Bennett PH. Medial arterial calcification and its association with mortality and complications of diabetes. Diabetologia 1988;31:16-23. [18.] Keenan AM, Tindel NL, Alavi A. Diagnosis of pedal osteomyelitis in diabetic patients using current scintigraphic techiques. Arch Intern Med 1989;149: 2262-6. [19.] Kaschak TJ, Laine W. Radiology of the diabetic foot. Clin Podiatr Med Surg 1988;5(4):849-57. [20.] Grayson ML, Balogh K, Levin E, Karchmer AW. Probing to bone - a useful clinical sign of osteomyelitis in diabetic fetid feet [Abstract]. In: Program and abstracts of the thirtieth Interscience Conference on Antimicrobial Agents and Chemotherapy; Oct 21-24; Washington, D.C.: American Society for Microbiology, 1990:127. 21. Harrelson JM. Management of the diabetic foot. Orthop Clin North Am 1989;20(4):605-19. [22.] Fylling CP, Knighton Dr, Gordinier RH. The use of comprehensive wound care protocol including topical growth factor therapy in treatment of diabetic neuropathic ulcers. In: Ward JD, Goto Y, eds. Diabetic neuropathy. New York: Wiley, 1990:567-78. [23.] Joseph WS. Treatment of lower extremity infections in diabetics. Drugs 1991,42:984-96. [24.] Novick A, Birke JA, Graham SL, Koziatek E. Effect of a walking splint and total contact casts on plantar forces. J Prosthet Orthot 1991;3:168-78. [25.] LoGerfo FW, Gibbons GW, Pomposelli FB Jr, Campbell DR, Miller A, Freeman DV, et al. Trends in the care of the diabetic foot. Expanded role of arterial reconstruction. Arch Surg 1992;127:617-20. [26.] Pomposelli FB Jr, Jepsen SJ, Gibbons GW, Campbell DR, Freeman DV, Gaughan BM, et al. A flexible approach to infrapopliteal vein grafts in patients with diabetes mellitus. Arch Surg 1991;126:724-7. [27.] Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation. Basis for prevention. Diabetes Care 1990;13:513-21. [28.] Levin ME, Sicard GA. Evaluating and treating diabetic peripheral vascular disease. Pts. I and II. Clin Diabetes 1987;5-8:62-93.
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