Charcot Arthropathy

Numerous classification systems based on clinical, radiographic, and anatomic pathology describe Charcot arthropathy. Anatomic classification systems are the most commonly used and have the added benefit of predicting outcome and prognosis. The most commonly used anatomic system is described by Saunders and Mrdjencovich.[3] Based on the location of the arthropathy, their system classifies Charcot arthropathy into the following five patterns:

• Pattern 1 involves the forefoot, which includes the interphalangeal (IP) joints, the phalanges, and the metatarsophalangeal (MTP) joint
• Pattern 2 involves the tarsometatarsal (TMT) joint
• Pattern 3 involves the cuneonavicular, talonavicular, and calcaneocuboid articulations
• Pattern 4 involves the talocrural, or ankle, joint, which is the articulation of the tibia, the fibula, and the talus
• Pattern 5 involves the posterior calcaneus

Studies have shown that patterns 2 and 3 are the most common, with approximately 45% of cases involving pattern 2 and 35% involving pattern 3.

Another commonly used classification system is the Brodsky and Rouse system. This system describes three anatomic Charcot joints (types 1, 2, and 3a and 3b):

• Type 1 involves the midfoot
• Type 2 involves the hindfoot
• Type 3a involves the ankle; type 3b is a pathologic fracture of the os calcis tubercle

The multilevel Schön classification system is also used; it comprises four types and characterizes Charcot joints on the basis of sites and degree of involvement.[4] Each of the four types has three subsets (eg, type IA, IB, IC), which are based on the severity of involvement. The four types are as follows:

• Type I - Lisfranc pattern
• Type II - Cuneonavicular pattern
• Type III - Perinavicular pattern
• Type IV - Transverse tarsal pattern

The Schön classification system allows the prediction of outcomes and the estimation of treatment duration.

The exact nature of Charcot arthropathy remains unknown,[5] but two major theories exist regarding the pathophysiology of this condition: neurotraumatic and neurovascular.

The neurotraumatic theory states that Charcot arthropathy is caused by an unperceived trauma or injury to an insensate foot. The sensory neuropathy renders the patient unaware of the osseous destruction that occurs with ambulation. This microtrauma leads to progressive destruction and damage to bone and joints.

The neurovascular theory suggests that the underlying condition leads to the development of autonomic neuropathy, causing the extremity to receive an increased blood flow. This in turn results in a mismatch in bone destruction and synthesis, leading to osteopenia.

Charcot arthropathy most likely results from a combination of the processes described in the above theories. The autonomic neuropathy leads to abnormal bone formation, and the sensory neuropathy leads to an insensate joint that is susceptible to trauma. The development of abnormal bone with no ability to protect the joint results in gradual bone fracture and in the subluxation of the joint.

Any condition that causes sensory or autonomic neuropathy can lead to a Charcot joint. Charcot arthropathy occurs as a complication of diabetes, syphilis, chronic alcoholism, leprosy, meningomyelocele, spinal cord injury, syringomyelia, renal dialysis, and congenital insensitivity to pain. Diabetes is considered to be the most common cause of Charcot arthropathy.[6, 7] There is also evidence for a relationship between Charcot arthropathy and rheumatoid arthritis (RA).[8]

The prevalence of Charcot arthropathy ranges from 0.1% to as high as 13% in specialized foot clinics. In patients with diabetes, the incidence of Charcot neuroarthropathy of the foot and ankle ranges from 0.1% to 8%.[7]

Epidemiologic studies do not distinguish between acute and postacute disease. Bilateral disease occurs in less than 10% of patients. Recurrence of disease occurs in less than 5% of patients. Some studies indicate that men and women are equally affected, while others report a 3:1 predilection for males.

Outcomes for Charcot arthropathy are based on immediate diagnosis and treatment. A more favorable outcome is elicited when joints are treated within 2 weeks of injury and when there is strict adherence to weightbearing precautions.

Healing times are increased in diabetics. Location of the disease also affects outcome. Forefoot arthropathies heal in less time than midfoot, hindfoot, or ankle arthropathies, as the following list illustrates:

• Ankle - Mean healing time, 83 ± 22 days
• Hindfoot - Mean healing time, 97 ± 16 days
• Midfoot - Mean healing time, 96 ± 11 days
• Forefoot - Mean healing time, 55 ± 17 days

The extent of the injury also affects healing time. The more severe the injury, the longer it takes to heal and the greater the likelihood of permanent deformity. It generally takes 1-2 years to completely heal a Charcot joint, from the active phase to quiescence.

Stark et al performed a 5-year retrospective analysis of 50 patients presenting to a tertiary foot clinic with acute Charcot neuroarthropathy, with the aims of (1) determining whether the initial immobilization approach (total-contact casting [TCC] or use of a removable offloading device) influenced time to resolution, (2) determining the relapse rate after TCC use, and (3) determining whether neuroarthropathy location influenced time to resolution.[9]  Of the 50 patients, 42 went into remission; 36 were treated with both TCC and removable offloading, five with removable offloading only, and one with TCC only.

Median time to resolution for patients initially treated with TCC was 48 weeks, compared with 53 weeks for those initially treated with a removable offloading device; however, the difference was not significant (P = 0.7681).[9] A relapse rate of 34.9% was noted for patients who were treated with TCC at any point. The location of the neuroarthropathy did not have a significant effect on time to resolution in this study.

Lee et al studied factors influencing outcomes after tibiotalocalcaneal fusion using a retrograde intramedullary (IM) nail in 34 patients followed for a minimum of 2 years.[10]  Throughout follow-up, standard ankle radiography was performed along with clinical outcome assessment using a visual analog scale (VAS) for pain, the American Orthopaedic Foot and Ankle Society Ankle-Hind Foot Scale (AOFAS A/H scale) and the Foot and Ankle Outcome Score (FAOS). Demographic factors, preoperative medical status, laboratory markers, and etiology were comprehensively reviewed. The success of the index operation was determined on the basis of clinical and radiologic outcomes.

In a mean of 7 months, 28 of the 34 patients (82%) achieved union on standard radiography.[10] All clinical outcome parameters improved significantly. At final follow-up, five cases of nonunion with AOFAS A/H scale less than 80 and two cases of below-knee amputation due to uncontrolled infection were determined to be failures. Failure was not significantly influenced by etiology, demographics, laboratory markers, or medical status. However, uncontrolled diabetes mellitus significantly increased the failure rate, suggesting that this procedure should be used judiciously in patients with this condition.

The clinical presentation of Charcot arthropathy can vary widely depending on the stage of the disease. Thus, symptoms can range from mild swelling and no deformity to moderate deformity with significant swelling.

Acute Charcot arthropathy almost always presents with signs of inflammation. Profound unilateral swelling, an increase in local skin temperature (generally, an increase of 3-7º above the unaffected foot's skin temperature), erythema, joint effusion, and bone resorption in an insensate foot are present. These characteristics, in the presence of intact skin and a loss of protective sensation, are often pathognomonic of acute Charcot arthropathy.

It is important to distinguish Charcot arthropathy from infection. Failure to do so can lead to complications from inappropriate treatment (eg, unnecessary antibiotic prescriptions), delay the initiation of more appropriate therapy, and possibly accelerate antibiotic resistance.[11]

Pain can occur in more than 75% of patients; however, the pain's severity is significantly less than would be expected from the severity of the clinical or radiographic findings. Instability and loss of joint function also may be present. Passive movement of the joint may reveal a "loose bag of bones." Approximately 40% of patients with acute Charcot arthropathy have concomitant ulceration, which complicates the diagnosis and raises concerns that osteomyelitis may be present.

Charcot fractures that are not identified and treated properly may progress to marked joint deformity and to skin ulceration over a bony prominence. The ulceration can result in a severe infection, which may lead to amputation of the extremity.

An additional complication of Charcot arthropathy is foot collapse leading to the formation of a clubfoot. Another commonly seen deformity is the rocker-bottom foot, in which collapse and inversion of the plantar arch occurs. Acute fracture and dislocation at the Lisfranc joint complex may follow insignificant or unrecognized trauma in patients with Charcot neuroarthropathy.[12]

Further complications include the ossification of ligamentous structures, the formation of intra-articular and extra-articular exostoses, the collapse of the plantar arch, and the development of osteomyelitis.

Essential tests

The white blood cell (WBC) count with differential often is ordered to help distinguish between Charcot arthropathy and osteomyelitis. The WBC count is elevated when infection is present, and often, a left shift is revealed with infection. However, the WBC count is a nonspecific marker for inflammation, and the results may be elevated in patients with Charcot arthropathy.

The erythrocyte sedimentation rate (ESR) is used to help distinguish between Charcot arthropathy and osteomyelitis and is often elevated in infection; however, it is a nonspecific marker for inflammation.

The basic metabolic profile (Chem 7) is ordered to identify the underlying etiology. Elevated levels of creatine and of blood urea nitrogen (BUN) could suggest renal disease, whereas an elevated glucose level could suggest diabetes.

Other tests

Additional tests may be ordered, depending on the patient's history, physical examination results, and risk factors.

Glycosylated hemoglobin (HbA1c) indicates the level of hyperglycemic control in diabetes. Elevated HbA1c indicates poor hyperglycemic control. Hyperglycemia can cause nonenzymatic collagen glycosylation, which can lead to laxity in ligaments and unstable joints.

Levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone (PTH) can help the physician to identify bone diseases, such as Paget disease. Hypercalcemia may be indicative of cancer or metastases.

Vitamn B12/folate deficiency could suggest an etiology of peripheral neuropathy. This deficiency also could suggest chronic alcoholism.

Findings of liver function tests/coagulation studies may suggest chronic alcoholism.

Rapid plasma reagin (RPR)/fluorescent treponemal antibody–absorption (FTA-ABS) tests aid in the diagnosis of syphilis.

Plain radiographs (see the image below) are used for the following purposes:

• To help stage disease (see Anatomy)
• To help determine if active disease is present or if the joint is stable (monitor serial radiographs)
• To help identify osteopenia, periarticular fragmentation of bone, subluxations, dislocations, fractures, and generalized destruction

Whenever possible, radiographs should be obtained with the patient bearing weight.

In a study of 35 patients who had midfoot Charcot neuroarthropathy (CN) with either lateral- or medial-column deformities, Lopez-Moral evaluated radiographic predictors of foot ulceration.[13]  They found that in patients with medial deformities, a lateral talar–first metatarsal angle more negative than –27.5º was the greatest predictor of midfoot ulceration, whereas in those with lateral deformities, a calcaneal pitch more negative than –5º and a cuboid height more negative than –1.5º were the greatest predictors of midfoot ulceration.

Bone scanning (not always ordered) may help differentiate between Charcot arthropathy and osteomyelitis. An indium-111 WBC scan often is used because it is more specific than the technetium-99m scan.

Magnetic resonance imaging (MRI)[14] allows anatomic imaging of the area and may help distinguish between osteomyelitis and Charcot arthropathy.

Doppler ultrasonography is used to rule out deep vein thrombosis.

Lumbar puncture is used if the RPR test is positive. An FTA-ABS test is ordered if tertiary syphilis/tabes dorsalis is suggested.

Bone probing is done with a blunt, sterile surgical probe. If the probe can be passed down to bone or if the underlying bone is exposed at the base of an ulcer or sinus, the bone is infected; this establishes the diagnosis of osteomyelitis.

Portable infrared dermal thermometry is used for skin temperature assessment. It can be used to monitor active inflammation. A 3-5° difference is generally seen in the acute stage.

Joint aspiration is used to help rule out a septic joint.

Synovial biopsy can be helpful. Small fragments of bone and cartilage debris are embedded in the synovium because of joint destruction. Some state that this is pathognomonic, whereas others state that it is highly suggestive of Charcot arthropathy.

Treatment of Charcot arthropathy has been primarily nonoperative. Treatment is carried out in two phases: an acute phase and a postacute phase. Management of the acute phase includes immobilization and reduction of stress (see Medical Therapy below).[15]

Surgery is warranted in fewer than 25% of cases and generally is used as a preventive measure. Surgery is performed when a deformity places the extremity at risk of ulceration and when the extremity cannot be safely protected in accommodative footwear. The goal of reconstruction is to create a stable, plantigrade foot that can be appropriately protected in accommodative footwear and that can support ambulation.[16]  Surgery is indicated for malaligned, unstable, or nonreducible fractures or dislocations, as well as for cases in which nonsurgical means fail.

The major contraindication for surgery is active inflammation. Studies have shown less favorable outcomes when surgery is performed on an acute joint.

Several authors, including Simon et al,[17] have suggested that early surgical treatment in the acute phase may be a feasible alternative to nonoperative management. However, the optimal timing of surgery remains to be determined.[18]

Immobilization usually is accomplished by casting. Total contact casting (TCC) has been shown to allow patients to ambulate while preventing the progression of deformity. Casts must be checked weekly to evaluate for proper fit, and they should be replaced every 1-2 weeks. Patients with concomitant ulceration must have their casts changed weekly for ulcer evaluation and debridement.

Wang et al studied 21 patients with plantar ulceration associated with diabetic Charcot midfoot neuroarthropathy who were treated either with TCC alone or with TCC plus extended medial column arthrodesis.[19]  Although healing times did not differ significantly between the two groups, patients in the TCC + arthrodesis group had fewer lesions after treatment, and they had no recurrences after 12 months (compared with a 33.3% recurrence rate in the group treated with TCC alone).

Serial plain radiographs should be taken approximately every month during the acute phase to evaluate progress. Casting usually is necessary for 3-6 months and is discontinued on the basis of clinical, radiographic, and dermal thermometric signs of quiescence. Other methods of immobilization include metal braces and ankle-foot orthoses (AFOs), but they may prolong healing times.

Reduction of stress is accomplished by decreasing the amount of weightbearing on the affected extremity. Total nonweightbearing (NWB) is ideal for treatment; however, patients are often not compliant with this treatment. Studies have shown that partial weightbearing (PWB) with assistive devices (eg, crutches, walkers) also is acceptable without compromising healing time. However, full weightbearing (FWB) in the acute phase tends to lengthen total time in the cast.

Healing time varies according to the location of the disease. Pattern 1, or forefoot pathology, heals in two thirds the time needed for pattern 3 or pattern 4. One study revealed that the mean time in a cast is 18.5 weeks, whereas another study showed that the acute phase lasts 12.5 weeks.

Management following the removal of the cast includes lifelong protection of the involved extremity. Patient education and professional foot care on a regular basis are integral aspects of lifelong foot protection. After cast removal, patients should wear a brace to protect the foot. Many types of braces may be used, including a patellar tendon-bearing brace, accommodative footwear with a modified AFO, a Charcot restraint orthotic walker (CROW), and a double metal upright AFO.[20]

Custom footwear includes extra-depth shoes with rigid soles and a plastic or metal shank. If ulcers are present, a rocker-bottom sole can be used. Also, Plastazote inserts can be used for insensate feet. This regimen may be eliminated after 6-24 months, depending on clinical, radiographic, and dermal thermographic findings. Continued use of custom footwear in the postacute phase for foot protection and support is essential.

The total healing process typically takes 1-2 years. Preventing further injury, noting temperature changes, checking feet every day, reporting trauma, and receiving professional foot care also are important tenets of treatment.

Although immobilization and NWB on the affected extremity remain the mainstays of therapy, other treatment options are being tested.[5] One option is the use of bisphosphonates, which are potent inhibitors of bone resorption that have minimal effect on bone formation.[21, 22]  This action stops the osteoclastic activity of bone breakdown, promotes healing, and decreases local inflammation. However, only a few case reports have examined this treatment as an alternative.

Another therapy of interest is low-intensity ultrasound.[23]  Pulsed low-intensity ultrasound has been shown to transmit micromechanical force and strains to the fracture site and to promote bone formation. Studies have demonstrated an acceleration in healing and an increase in strength at the callus site.

Finally, the use of electrical stimulation and of magnetic field therapy to stimulate bone formation has been discussed in a few case reports. These therapies have shown some benefit in accelerating healing times. However, no prospective studies indicate a positive effect.

Surgical procedures and techniques used to treat Charcot arthropathy vary, depending on the location of the disease and on the surgeon's preferences and experience with this condition. Such procedures have had excellent results, and it has been argued that they may be underused.[24] Patients treated with surgery have longer healing times than those treated medically.[15]

Surgical procedures that may be considered include the following:

• Exostosectomy of bony prominence
• Osteotomy
• Arthrodesis
• Screw and plate fixation
• Open reduction and internal fixation (ORIF)
• Reconstructive surgery
• Fusion with Achilles tendon lengthening
• Autologous bone grafting
• Amputation

The superconstruct reconstruction has yielded promising early results. Frokjaer reported a 95% rate of satisfactory results in a group of 20 patients with midfoot Charcot neuroarthropathy, while noting the potential for incisional wound problems and the risk of overloading the ankle and thereby giving rise to a new Charcot attack.[25] The technique is demanding, and there remains a need for further studies.

Surgical methods can be based on Schön's classification system. The following recommendations may be made:

• Augmented ORIF should be used for an ankle with displaced fractures
• Ankle arthrodesis is necessary in patients with tibiotalar destruction
• In cases in which the hindfoot has avascular necrosis of the talus, a talectomy with tibiocalcaneal fusion is necessary
• Arthrodesis may be necessary for patients with hindfoot involvement
• For a midfoot pattern, surgical correction of rocker-bottom deformity and osteotomies for bony prominences are used
• If there is an associated hindfoot/ankle equinus contracture, then a posterior release/Achilles tendon lengthening procedure is required
• For forefoot patterns, patients with bony prominences or recurrent ulcerations may need a resection arthroplasty or cheilectomy

Wirth et al reported on the use of the Ilizarov ring fixator for surgical treatment of Charcot arthropathy,[26] citing results from their own experience and from the literature. The concluded that the Ilizarov ring fixator is a viable method for preserving the affected foot in patients with Charcot neuro-osteopathy. They recommend that in assembling the apparatus, the principles of Ilizarov be followed to avoid failure and that a detailed preoperative analysis of corrective osseous and soft tissue interventions be undertaken.

Sohn et al performed a retrospective study to compare the risks of lower-extremity amputation in patients with Charcot arthropathy alone and those with diabetic foot ulcers.[27] They found that Charcot arthropathy by itself does not pose a serious amputation risk, but amputation risk is multiplied in the presence of ulcer complications. In patients younger than 65 years, amputation risk was seven times higher for patients with ulcer alone than for those with Charcot arthropathy alone, and 12 times higher for those with Charcot and ulcer.

Della Paola et al evaluated, as an alternative to amputation in patients with Charcot arthropathy, surgical treatment of osteomyelitis of the midfoot or the ankle and stabilization with external fixation.[28] Of the 45 patients studied, 39 healed when treated with emergency surgery to drain an acute infection with maintenance of fixation (average, 25.7 weeks); two were treated with intramedullary nails in follow-up surgery; and in four, infection could not be controlled and amputation was still necessary.[28]

Hegewald et al retrospectively assessed the clinical and radiographic outcomes of combined internal and external fixation for reconstruction in 22 patients with diagnosed diabetes mellitus and documented peripheral neuropathy.[29]  During a mean follow-up period of 58.60 ± 42.37 weeks (range, 16-164), limb salvage was achieved in 20 patients, and below-the-knee amputation was required in two. Wound dehiscence occurred in eight, pin tract infection in 10, and superficial wound infection in nine. On radiographic analysis of pre- versus postoperative alignment, statistically significant changes were noted in the lateral talar–first metatarsal angle and the lateral talar declination angle.

In a systematic review of surgical management of Charcot neuroarthropathy, Bajuri et al recommended hybrid fixation (ie, combined internal and external fixation) in the settings of ulceration and more complex deformity, on the grounds that this will improve the rate of limb salvage while causing less irritation of soft tissues.[30]

In a study that included 23 patients with severely infected ulcerated and stable Charcot neuropathy of the ankle, Galhoum found that aggressive open debridement of ulcers and joint surfaces, followed by external fixation with an Ilizarov device and early weightbearing, could be successfully used to salvage the ankle, rendering amputation unnecessary in 91.3% of cases.[31]

A study by Tiruveedhula et al (N = 33) assessed the use of tendo Achillis lengthening (TAL) followed by a weightbearing TCC to treat midfoot Charcot neuroarthropathy in the outpatient setting.[32] At 12 months' follow-up, the disease had either stopped progressing or regressed in 30 patients. Only three patients were not able to return to their preprocedure level of mobilization with their usual aids. No complications (eg, nonhealing wound, complete transection of a tendon, or deep vein thrombosis) were reported.

A large systematic review by Ha et al (N = 1089; 1116 feet) examined outcomes of different reconstruction methods used to treat Charcot foot.[33]  Internal fixation was performed in 65% of the feet, external fixation in 31%, and simultaneous internal and external fixation in 44%. The overall bone fusion rate was 86.1%. The postreconstruction amputation rate was only 5.5%, with 91% of patients returning to ambulation. The authors did not find any single technique to have any significant advantages over the others; however, they noted that the quality of the evidence was low. 

Minimally invasive approaches

A small study by Lamm et al found minimally invasive arthrodesis plus gradual Charcot foot correction with the Taylor spatial frame to be an effective treatment. This technique may aid in the avoidance of incomplete deformity correction, fixation failure, infections, shortening of the foot, and the use of long-term casts or braces.[34]

Neuropathic minimally invasive surgeries (NEMISIS) were described by Miller in a 2016 review.[35]  Among the potential advantages suggested for this approach are that the percutaneous incisions employed cause minimal damage to soft tissues and are made away from blood vessels (thereby lowering the risk of nonhealing wounds, tissue necrosis, and major amputation). Patients with a recurrent ulcer, a deformity that is at risk for ulceration, or progressive joint destruction on serial radiographs may be considered for NEMISIS.

Nonunion has been reported to occur in 5-10% of patients who undergo midfoot arthrodesis, and the rate appears to be higher in those with neuroarthropathy.[36]  A study by Siddiqui et al (N = 15) found that performing distal tibial distraction osteogenesis simultaneously with tibiotalocalcaneal or tibiocalcaneal fusion in patients with Charcot neuroarthropathy yielded a high arthrodesis rate of 93.3% (14 patients), with one patient having a hypertrophic nonunion at the regeneration site.[37]

A retrospective study of ankle and hindfoot arthrodesis in 44 patients (46 operated sites) with diabetic Charcot neuroarthropathy reported infections in 13% and symptomatic radiologic nonunion at one or more joints in 26%.[38]  Primary union was achieved in 65%, with radiologic fusion apparent at an average 6.8 months post surgery; asymptomatic radiologic partial nonunion at one or more joints was seen in 8.5%, but clinical union was noted. A low-energy spiral fracture of the tibia proximal to the locking plate used for fusion occurred in 8.3%. Overally, complete deformity correction with a plantigrade foot was achieved in 69.5% (32 cases). 

The National Institute for Health and Care Excellence (NICE) of the United Kingdom has published a guideline for the prevention and management of diabetic foot disorders.[39] Recommendations specifically relevant to Charcot arthropathy in diabetes are as follows.

Investigation

It must be kept in mind that if a person with diabetes fractures a foot or ankle, the fracture may progress to Charcot arthropathy.

Acute Charcot arthropathy should be suspected if redness, warmth, swelling, or deformity (particularly if the skin is intact) is noted, especially in the presence of peripheral neuropathy or renal failure. Acute Charcot arthropathy should be considered even when deformity is not present or pain is not reported.

For confirmation of the diagnosis of acute Charcot arthropathy, the patient should be referred within 1 working day to the multidisciplinary foot care service for triage within 1 further working day. Nonweightbearing (NWB) treatment should be offered until the multidisciplinary foot care service can initiate definitive treatment.

If acute Charcot arthropathy is suspected, a weightbearing radiograph of the affected foot and ankle should be obtained. Magnetic resonance imaging (MRI) may be considered if the radiograph is normal but Charcot arthropathy is still suspected.

Treatment

If the multidisciplinary foot care service suspects acute Charcot arthropathy, treatment with a nonremovable offloading device should be offered. If the use of such a device is inadvisable because of clinical or patient circumstances, treatment with a removable offloading device should be considered.

The use of bisphosphonates to treat acute Charcot arthropathy is not warranted, unless as part of a clinical trial.

Treatment of acute Charcot arthropathy should be monitored via clinical assessment, to include measurement of foot-skin temperature difference and serial radiographs until the acute Charcot arthropathy resolves. Resolution is likely when there is a sustained temperature difference of less than 2º between the two feet and when radiographic changes show no further progression.

People who have a foot deformity that may be the result of a previous Charcot arthropathy are at high risk of ulceration and should be cared for by the foot protection service.