Charcot arthropathy of the foot and ankle is a severe complication of peripheral neuropathy and is most commonly seen in the developed world in association with diabetes mellitus. Correct diagnosis and differentiation from osteomyelitis of the foot and ankle are critical to guide treatment. It can exist concomitantly with osteomyelitis, typically in the setting of an advanced midfoot ulcer. Simple plain radiographs and contrasted MRI studies often yield inconclusive or confusing data. Correct use of imaging studies and a clinical algorithm can be effective tools to help make accurate and early diagnoses and guide clinical interventions for these conditions.
Key points
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Charcot arthropathy of the foot and ankle can be difficult to differentiate from osteomyelitis.
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Appropriate use of imaging studies, including plain radiographs, MRI, and nuclear medicine studies can aid greatly in diagnosis and treatment guidance of these conditions.
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Early identification and treatment of both Charcot arthropathy and osteomyelitis can lead to better outcomes and patient satisfaction.
J.M. Charcot first described arthropathy associated with tabes dorsalis in the foot and ankle 140 years ago. Despite the passage of 140 years, Charcot disease of the foot and ankle remains a poorly understood condition with little consensus on evaluation or management. Although Charcot and colleagues first described this condition in relation to tertiary syphilis, it was not until 1936 that W.R. Jordan first established the association between neuro-arthropathy and diabetes mellitus, which is the leading cause in the developed world today.
The economic impact of diabetes mellitus and its complications are staggering. It is estimated that the prevalence of Charcot arthropathy in the general diabetic population is 0.08%, but in high-risk patients can range as high as 13%. When encountered in the presence of severe infection, the morbidity and mortality rates from complications can exceed 35% even if the infection is managed well. Early and correct diagnosis and management are key factors in successful treatment.
Diabetes and peripheral neuropathy may contribute to the formation of Charcot arthropathy through a variety of mechanisms. Osteopenia, reactive oxygen species, and oxidized lipids may all upregulate RANKL expression in diabetic patients. Still other causes may be hypervascularity of the bones and local inflammation caused by trauma, ulceration, or recent infection. Whatever the cause, the end result is fragmentation and destruction of joint architecture leading to collapse of the foot or ankle and ulceration, which then results in osteomyelitis.
Clinical presentation
Charcot arthropathy typically presents with a warm, swollen foot and ankle that cannot be differentiated easily from infection. Many times the patient has been evaluated for a deep venous thrombosis and undergone oral or parenteral antibiotic therapy for cellulitis before a clinician obtains a radiograph or MRI that suggests the presence of Charcot arthropathy or osteomyelitis. A study by Chanteleau showed that 19 (80%) of 24 patients with Charcot arthropathy were initially misdiagnosed with gout, deep venous thrombosis, or cellulitis. Patients with Charcot arthropathy may have a history of antecedent trauma, but typically present before ulceration of the foot or ankle. By contrast, osteomyelitis is typically caused by exposure of the bone to the environment, although it may more rarely be spread to bone by traveling through the bloodstream from another source. Twenty percent of diabetic patients will develop osteomyelitis and many of these will succumb to amputation as a result. The diagnostic challenge is made even harder by cases in which both Charcot and arthropathy are present concomitantly due to a history of infection or surgery to the affected joints. A systematic approach to evaluation and management of the patient, although not perfect, can help the clinician identify the correct diagnosis and treatment in most cases.
Clinical presentation
Charcot arthropathy typically presents with a warm, swollen foot and ankle that cannot be differentiated easily from infection. Many times the patient has been evaluated for a deep venous thrombosis and undergone oral or parenteral antibiotic therapy for cellulitis before a clinician obtains a radiograph or MRI that suggests the presence of Charcot arthropathy or osteomyelitis. A study by Chanteleau showed that 19 (80%) of 24 patients with Charcot arthropathy were initially misdiagnosed with gout, deep venous thrombosis, or cellulitis. Patients with Charcot arthropathy may have a history of antecedent trauma, but typically present before ulceration of the foot or ankle. By contrast, osteomyelitis is typically caused by exposure of the bone to the environment, although it may more rarely be spread to bone by traveling through the bloodstream from another source. Twenty percent of diabetic patients will develop osteomyelitis and many of these will succumb to amputation as a result. The diagnostic challenge is made even harder by cases in which both Charcot and arthropathy are present concomitantly due to a history of infection or surgery to the affected joints. A systematic approach to evaluation and management of the patient, although not perfect, can help the clinician identify the correct diagnosis and treatment in most cases.
History and physical examination
Diabetic foot infections are almost always caused by bacteria from infections in the adjacent soft tissues. A history of a local ulceration or a “sausage toe” is characteristic of infection. Patients with osteomyelitis of the foot and ankle are largely afebrile and the wounds may not show any local signs of inflammation, particularly as the wounds are often present chronically. Ertugrul and colleagues found that ulcer size greater than 2 cm 2 carries a 56% sensitivity and a 96% specificity for the presence of osteomyelitis. Some investigators have described the “probe-to-bone” test for ulcers, in which a blunt metal probe is introduced into the wound to see if bone is palpable. The sensitivity and specificity of this test are widely variable in studies, but it is perhaps reasonable that if you can probe bone, then so can a colonizing bacteria. Indeed, Lavery and colleagues demonstrated in their study of 1666 patients that a positive probe-to-bone test increases the probability of osteomyelitis greater than 50%, whereas a negative test is a strong predictor of absence of infection. The use of a “dependent rubor” test also has been suggested. With this test, if the erythema in an affected foot and ankle resolves with elevation, this suggests Charcot arthropathy, whereas persistence of erythema with elevation of the leg suggests an infection is present.
Hematologic studies
Routine laboratory testing for infection markers should be a part of the initial infection workup for any patient with a foot wound that is suspicious for osteomyelitis. Routine complete blood count with differential, a C-reactive protein, and an erythrocyte sedimentation rate (ESR) can all yield clues in the workup. Many investigators have concluded that an ESR that is substantially elevated (>70 mm/h) strongly supports a diagnosis of osteomyelitis and tends to slowly decline with appropriate therapy. It should be noted, however, that many patients with histologically proven osteomyelitis may be afebrile and have a normal white blood cell count, so that using hematologic studies without other correlating factors may not be a useful tool to aid in differentiating Charcot arthropathy from osteomyelitis.
Bone biopsy
Butalia and colleagues have suggested that surgical percutaneous bone biopsy after a 14-day antibiotic-free period represents the gold standard for diagnosis and management of osteomyelitis of the foot. Other studies have shown that an antibiotic holiday of as little as 48 hours is sufficient before biopsy, however. The importance of histologic analysis in addition to microbiology is important, as several studies have shown that 40% to 60% of histologically proven cases of osteomyelitis at surgery or biopsy of the foot and ankle are negative at culture. Many patients with a diabetic foot wound and suspected osteomyelitis will have undergone swab cultures of the wound before consultation with an orthopedic surgeon. Although these cultures are often used to guide treatment, their actual utility is quite suspect. Senneville and colleagues compared the diagnostic value of swab cultures to percutaneous bone biopsy for diabetic foot osteomyelitis. Their study showed only 17.4% of patients had both biopsy and swab cultures that were identical and that the overall concordance of isolates was only 22.5%. The use of ulcer swab cultures alone should therefore be treated with caution in guiding diagnosis and treatment. Additionally, patients with suspected osteomyelitis who have a negative percutaneous bone biopsy have a 25% chance of developing osteomyelitis within 2 years of biopsy. Whether or not biopsy can be considered the gold standard to diagnose osteomyelitis of the foot and ankle remains unclear. The data obtained from this procedure can clearly have utility, however, when guiding decisions of antimicrobial therapy or internal versus external fixation of a Charcot foot and ankle deformity.
Imaging studies
Plain radiography of the involved area should be requisite in the investigation of Charcot arthropathy and osteomyelitis of the foot and ankle. The accuracy of plain radiography itself in correctly differentiating osteomyelitis from Charcot arthropathy is only approximately 50% to 60%, with the findings of demineralization, periosteal reaction, and cortical destruction being most diagnostic. Problematically, however, these findings may not appear until 2 to 3 weeks after onset of clinical symptoms and require a loss of 40% to 50% of bone mass to see a difference. Despite these limitations, the information gained from standing plain radiographs can be invaluable when taken in the context of the patient’s clinical presentation when making diagnostic or treatment decisions ( Table 1 ).
| Osteomyelitis | Charcot Arthropathy |
|---|---|
| Periosteal reaction or elevation Loss of cortex with bony erosion New bone formation Sequestrum: devitalized bone with radiodense appearance that has become separated from normal bone Involucrum: layer of new bone growth outside existing bone |
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MRI with contrast has become a useful tool in the evaluation of diabetic foot infections and helpful in differentiating from Charcot arthropathy. Evidence now shows that proper application of this imaging modality can be superior to nuclear imaging tests in aiding diagnosis. The mere presence of bone marrow edema in both of these conditions is a very nonspecific finding. The pattern of bone marrow edema, clinical correlation, and other factors must be taken into account for an MRI to be of maximal value. Osteomyelitis of the foot and ankle tends to have a focal involvement of one weight-bearing joint, whereas Charcot arthropathy tends to involve several joints or bones. The presence of an adjacent fluid collection, sinus tract, or soft tissue infection strongly suggests osteomyelitis is present and can improve diagnostic accuracy. MRI has limitations in patients with recent surgery, retained hardware, presence of a pacemaker, or aneurysm clips or renal insufficiency that does not allow contrasted studies to be completed safely. A recent meta-analysis has shown that the sensitivity of MRI to diagnose osteomyelitis in the foot and ankle stands at 90% with a specificity of 79%, but that its ability to differentiate infection from Charcot arthropathy may not be superior to nuclear imaging studies ( Table 2 ).
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