Charcot neuropathic osteoarthropathy is a destructive joint disorder initiated by trauma to a neuropathic extremity. It can lead to dislocations and fractures of the foot. Correct diagnosis and treatment of acute Charcot are imperative to decrease permanent foot deformity and allow for a stable and plantigrade foot that is suitable for ambulation. This review article of Charcot discusses etiology and pathogenesis of the disease, presentation, and treatment options.
Charcot neuropathic osteoarthropathy is seen in the lower extremity and is characterized by bone and joint fragmentation of the foot and ankle in individuals with various peripheral neuropathies. Diabetes, neuropathy, trauma, and metabolic abnormalities of the bone result in an acute localized inflammatory condition. The inflammatory response can permanently disrupt the bony architecture of the foot resulting in abnormal plantar pressures that are at risk for ulceration and amputation.
Charcot is a debilitating condition affecting the lower extremity of patients with established peripheral neuropathy caused by many complicated etiologies; however, diabetic neuropathy has become the most common etiology.
It has been reported that Charcot affects between 0.1% to 0.9% of people with diabetes. An estimated 63% of patients with Charcot neuropathic osteoarthropathy will develop a foot ulcer. McEwen et al. found a significant association between elevated body mass index and Charcot.
There are two commonly accepted theories used to describe the pathogenesis of Charcot: neuro-traumatic and neurovascular. The neuro-traumatic theory proposes neuropathy, and repeated trauma produces joint destruction. The neurovascular theory suggests the increased peripheral blood flow results in osteolysis and demineralization.
Pathophysiologically, key inflammatory markers have been identified that contribute to the development of an acute Charcot foot. Calcitonin gene-related peptide (CGRP) acts typically at the nerve terminal to antagonist the synthesis of nuclear factor-kB ligand (RANKL), a cytokine involved in the inflammatory process. However, in the neuropathic foot, the CGRP is not functioning, and therefore RANKL is synthesized without inhibition. RANKL is a very important marker in the development of Charcot as it is responsible for the proliferation of osteoclastogenesis. The RANKL osteoclastic relationship is normally moderated by osteoprotegerin (OPG) by acting as a decoy receptor to RANKL binding. In the Charcot foot, this relationship between RANKL and OPG is disrupted. The unregulated synthesis of RANKL accounts for the excessive bony turnover and accumulation that is seen in the Charcot limb. Additionally, CGRP may have a further role in Charcot in that it is involved in upholding the integrity of the joint capsule. Therefore, in its absence, it is presumed to lead to joint destruction and dislocation that is characteristic of the Charcot foot.
A high suspicion for Charcot needs to be present to diagnose the condition accurately. Charcot presents as an erythematous foot with edema and color. Often, it is unilateral with a sudden onset of symptoms. Charcot may be initially misdiagnosed as a deep venous thrombosis or cellulitis. Charcot can also be confused with osteomyelitis due to the similar clinical appearance of a red, hot swollen foot with skeletal lysis and often unilateral presentation. Although distinct and separate processes, there is evidence that osteomyelitis can lead to Charcot. This is due to the inflammatory cascade of cytokine release osteomyelitis triggers in the body. This risk of osteomyelitis evolving into Charcot is further escalated if surgical intervention was performed to remove the infected bone. This is because both osteomyelitis and surgery are forms of trauma that promote an inflammatory response which triggers the opportunity for Charcot to manifest.
In addition to the trauma caused by surgery, the changes to the bony architecture of the foot post-surgery can also lead to inflammatory triggering events due to biomechanical and gait alterations in plantar pressures. For example, amputations and other surgical interventions of the foot can lead to altered pressure points for which the foot is unable to compensate. These changes in plantar pressure, even if mild, can cause microtrauma which initiates the inflammatory events that lead to an acute Charcot.
Stages of Charcot
Common classifications that map the phases of Charcot include the Eichenholtz classification and the Sanders and Frykberg classification. Eichenholtz classifications describe the three stages of disease progression based on clinical and radiographic findings. The Sanders/Frykberg classification is used to type and class the five common anatomical locations of Charcot in the foot.
Clinically: Erythema, foot edema, elevated temperature, no pain
Radiographically: Boney debris at joints, fragmentation of subchondral bone, joint subluxation and or fracture dislocation
Clinically: Decreased signs of inflammation
Radiographically: Worsening of stage 1 features. Absorption of boney debris with new bone formation. Coalescence of large fragments with sclerosis of bone ends. Some increased stability
Clinically: Resolution of inflammation. Changes in overall foot architecture due to underlying final bony remodeling that can lead to new pressure points which are at risk of ulceration
Radiographically: Remodeling of affected bones and joints
Sanders and Frykberg
Treatments of Charcot aim to decrease permanent foot deformity and ultimately allow for a stable and plantigrade foot that is stable and suitable for ambulation. In the acute phase, it is imperative to immobilize the foot and restrict weight bearing to prevent permanent deformity. Non-operatively, this is achieved through off weight-bearing via total non-weight bearing or protective weight bearing devices. Assistive devices such as crutches and wheel chairs can aid with non-weight bearing. Total contact casts (TCC) with a controlled ankle motion (CAM) walker can provide protected weight bearing. TCC redistribute and reduce pressures on the plantar foot while allowing ambulation. The hyperemic phase of the Eichenholtz classification can last for weeks. By using these types of protective measures, the foot may heal the fractures in a stable position if the stress does not exceed the rate of healing.
Pharmacological treatments also exist to control the osteoclastic activity including bisphosphonates and calcitonin supplements. Bisphosphonates may help the acute phase of Charcot as they inhibit osteoclastic reabsorption. Calcitonin also serves as an antiresorptive agent. Alternative agents include pamidronate or zoledronic acid which act on new hydroxyapatite crystal by blocking osteoclast precursors in the newly formed bone matrix.
Charcot is a rare but serious complication of peripheral neuropathy that can mimic many other disease processes common in the foot of a patient with diabetes. Correctly diagnosing Charcot osteoarthropathy is imperative due to the risk of permanent foot deformity that can be at risk for ulceration and amputation. For the acute phase, treatment endorses non-weight bearing with immobilization of the affected limb to prevent permanent deformity as the disease progresses through the Eichenholtz stages. However, total non-weight bearing and immobilization cannot always be achieved. Common reasons for nonadherence include the length of time required for non-weight bearing, lack of physical ability, and employment restrictions. Alternative treatment options to total non-weight bearing include administration of offloading ambulating devices. Many offloading ambulating devices exist, such as the controlled ankle motion walker with an offloading insole, total contact cast or assistive devices like knee scooters.