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The Charcot Foot: A Missed Diagnosis Can Cost a Limb

The Charcot Foot: A Missed Diagnosis Can Cost a Limb

Charcot neuroarthropathy—an enigmatic, destructive, and deforming condition—most often affects persons who have diabetes mellitus (DM). Although the disorder was identified more than a century ago, misdiagnosing or overlooking it is easy because the initial signs often are subtle and misinterpreted. The consequences can be devastating, including ulceration, infection, loss of mobility and limb and, ultimately, an early demise.

The main reason why clinicians do not recognize Charcot neuroarthropathy is that the clinical presentation often is similar to that of more common conditions. Its acute stage appears similar to that of cellulitis, and the chronic Charcot foot resembles osteomyelitis. Both conditions are well documented among patients with DM.

In this 2-part article, we focus on the signs of Charcot that affect the foot and ankle. This first part describes identification and diagnosis of the disorder and how to distinguish it from these other conditions. The second part will discuss management of this complex neuropathic condition.


In the literature, the prevalence of Charcot foot varies from 0.08% in the general DM population to 13% in high-risk DM clinics.1 These are probably underestimates because many cases are misdiagnosed.2

First identified by Jean-Marie Charcot in 1883, Charcot neuroarthropathy causes inflammatory changes, subluxation, and dislocations, ultimately leading to significant deformities. Patients with DM are affected most often, although other peripheral neuropathies have been implicated.

Several theories have been proposed to explain the pathogenesis of Charcot neuroarthropathy. Do degenerative changes to the CNS lead to a neurogenic loss of osseous nutrition and, consequently, to arthritis? Does the hypervascular reflex secondary to autonomic neuroarthropathy lead to bone loss, ultimately weakening bones and causing fractures and dislocations? Or does repetitive microtrauma from weight bearing on an insensate foot cause instability, subluxation, and destruction of bone?

Most likely a combination of all 3 phenomena lead to the development of Charcot foot, causing an acute inflammatory response during which cytokines, interleukins, and tumor necrosis factors (TNFs) are released. TNFs express the receptor activator of nuclear factor-κB ligand, which binds to the receptor activator of nuclear factor-κB, causing maturity of precursor osteoclastic cells into osteoclasts, thus increasing bone resorption and demineralization.

These events are well understood from the study of basic research of fractures, where immobilization usually controls the inflammatory process, and osteoporosis. In the case of Charcot neuroarthropathy, small fractures often go unnoticed and an uncontrolled inflammatory phase perpetuates the osteolytic process.

Endothelial nitric oxide synthase (eNOS) also contributes to the cytokine-mediated pathway by regulating nitric oxide, an important free radical that limits osteoclastic resorption. Decreased expression of eNOS has been observed in bone specimens from patients with Charcot neuroarthropathy, potentially implicating eNOS as another factor in the development of Charcot foot.3 Reduction of eNOS decreases nitric oxide expression, leading to increased osteoclastic activity.


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