CME Diabetic Foot

The Charcot Foot: Overview of Treatment Strategies

Suhad Hadi, DPM

Suhad Hadi, DPM discusses the pathophysiology and theories about Charcot, and the differential diagnoses with both conservative and surgical treatments and goals.

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Goals and Objectives
  1. Review the pathophysiology of Charcot Neuroarthropathy
  2. Define the role of RANK/OPG Pathway as a genetic link to Charcot Neuroarthropathy
  3. Review the differential diagnosis and clinical diagnosis of Charcot Neuroarthropathy
  4. Discuss conservative treatment measures and indications with outcomes
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  • CPME (Credits: 0.75)

    PRESENT eLearning Systems, LLC is approved by the Council on Podiatric Medical Education as a provider of continuing education in podiatric medicine.

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    Release Date: 03/16/2018 Expiration Date: 12/31/2018

  • Author
  • Suhad Hadi, DPM

    Louis Stokes Veterans Administration
    Akron Community Based Outpatient Clinic
    Akron, OH

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    Suhad Hadi has nothing to disclose.

  • Lecture Transcript
  • Male Speaker: As with foot ulcers to really understanding the underlying pathophysiology of what’s going on in Charcot foot because you must understand that if you were to adequately or appropriately treat these patients that are incredibly complex and high risk and have a high five-year mortality rate. I have asked Dr. Hadi to come and give us an overview of the pathophysiology underlying pathology of the Charcot foot as well as to discuss the conservative management principles which I think our first and foremost and should be first and foremost over mine. Let us welcome Dr. Hadi.

    Dr. Hadi: Okay. We’re going to talk a bit the pathophysiology of Charcot where we’ve come with Charcot has been really – we made tremendous strives in attributing factors and theories and combining theories in regards to what can cause Charcot arthropathy in patients. I have nothing to disclose. Again, our learning objective is understanding the pathophysiology of Charcot and the new theories that are being worked on defining the role of the RANKL OPG pathway as a genetic link to Charcot and identifying why certain diabetic populations have Charcot and some don’t. Reviewing the differential diagnosis and clinical diagnosis of Charcot arthropathy and then again reviewing the conservative treatment measures without toe filler, the best first line management in these patients. In understanding the pathophysiology of Charcot, we all know that Charcot has devastating effects on our patients and I think overtime we’ve come to accept the fact that somewhere in the middle between the vascular component and a traumatic component is where the pathophysiology behind Charcot lies. I think the impending question of as to why there’s some patients with neuropathy gets Charcot and others with neuropathy do not get Charcot? Has raised the whole new theory in regards to Charcot and that’s looking more to genetic factors involved in this patient population. The French theory, we all know by Mitchell, describes damage to bone and joint nutrition trophic centers in the spinal cord altering bone nutrition and ultimately did on autonomic neuropathy, the relaxation of the arterial walls resulting in an increase blood flow and osseous or bony wash out which result in the fragmentation and the bony destruction that we see with Charcot has been well described and well accepted over time. The German theory which attributes Charcot neuropathy to patients due to the insensate but who are prone to repetitive microtrauma or trauma and do the foot being insensate this repetitive trauma results in bony fracturing and fragmentation. The reality of it is, is that the theories combined together have been really more predictive of patients or descriptive of why patients get Charcot. Recently in the past probably eight to 10 years, we’ve seen stride made in identifying a genetic component in our patient and the patient population, and identifying the role that the RANKL OPG pathway plays. We’ll talk a little bit more in detail about this but the RANKL OPG pathway plays a dominant role in the process of bone formation and osteolysis and ultimately provides control of osteoclastogenesis. On defining the RANKL OPG pathway, RANKL is the receptor activator, nuclear factor-kappa beta ligand and OPG is osteoprotegerin. It plays again the dominant role of bone formation and osteolysis and then osteoblast and osteoclast function. The coordinated synthesis of these molecules RANKL and OPG is an essential feature in bone remodeling and allows the balance between both lysis and bone formation. Whenever there’s disruption in the system and we’re going to see the mutations that are attributed to this and the imbalance, this is what results an exaggerated bone loss. Quick overview too is remember osteoclast with multinucleated cells that degrade bone matrix. Osteoblast are responsible for bone mineralization and synthesis and bone formation and remodeling. On figure osteoprotegerin, we’ll see as described as the decoy molecule for RANKL of TNF origin and it’s decreasing the absence, sorry, it has the key role in osteoclastogenesis and that serving as the decoy molecule, it binds the RANKL.


    RANKL cannot bind the RANK which is on the membrane surfaces of the osteoclast therefore, not activating them. RANKL, major role is in bone stimulation of osteoclast differentiation. Then RANK is a membrane protein and express on the surface of osteoclast and involved in the activation of osteoclast when that RANKL molecule binds to it. When we look at it in the schematic form, OPGs, the Pac-Man looking molecule for those of you who remember Pac-Man. The red arrow head is the RANK and the yellow arrow is RANKL. OPG binds the RANKL when it’s excess and inhibits it’s binding to the RANK on the osteoclast. Therefore, does not allow initiation of osteoclastic activity. When this system is in imbalance, this is when we see an increase in osteoclastic activity and ultimately, the osseous destruction that comes with Charcot arthropathy. In 2002, Lagdahl described 12 OPG polymorphisms or mutations and it was in 2009 that two of those polymorphisms were identified to be present in patients with Charcot arthropathy to the 1181G and 245T alleles. There was a difference in patients with diabetes and neuropathy and diabetes neuropathy in Charcot. The patients with Charcot had significant differences in these two mutations whereas patients and diabetes without Charcot and the control groups had no differences in these polymorphisms. In 2011, Burakowska, I’m not good at pronouncing these names but went on to look further into these polymorphisms and see if it was really just those two polymorphisms that were attributed to Charcot arthropathy and evaluated five of the polymorphisms and actually found the 245 was still responsible but there was a 12171 that was also responsible allele. But what he found essentially was that he did support the findings of genetic factors that OPG genetic polymorphism is playing important role in development of diabetic Charcot arthropathy patients. But what he also found was there regional differences. There were different allele mutations that were responsible as well but overall, still pointing to this RANKL OPG pathway as a potential predictive indicator or potential screening for patients who could be prone to Charcot arthropathy. Where else do we see associations of the RANKL pathway? Pretty much processes that involve osseous turnover, we see the RANKL pathway affected and things like osteoporosis, rheumatoid arthritis but one major association that we actually see and probably hits the point home with seeing an increase mortality associated, two patients with Charcot arthropathy that is equal to that of patients of diabetic ulcers at 5% is that there is association with vascular calcification. I meant to put the study in here too but there a study by Dr. Andrew Boulton and his group in 2011 that evaluated the RANKL pathway and it’s role in medial arterial calcification in patients and because we see both neuropathy and arterial calcifications in patients with Charcot arthropathy, they further evaluated this link. There’s a recognize association of peripheral neuropathy and increase prevalence in Charcot patients and they work to 78 to 90%. Osteoporosis is greater in diabetes type 1 versus type 2 however, both neuropathy and osteopenia are consistently present in patients with Charcot. Therefore, abnormal function of the system gives some explanation as to the mutual presents in diabetes and neuropathy patients. I think it’s important for us to understand that it’s probably emerging of these three theories because you have to have an inflammatory process that induces the activation of these pathways and then the subsequent osseous breakdown. Where does this genetic theory take us? Is there a potential for treating these patients who have the RANKL pathway affected and causing Charcot arthropathy. Well, there is one medication, denosumab that actually binds to RANKL. It’s actually used in patients to prevent skeletal related events. It’s used in patients with bony metastasis such as giant cell bone tumors and has been shown to have some success. I haven’t found anything that shows any of these medications have been used with Charcot but there is a potential to look into this in the future.


    Whether we can potentially use it to slow down the process or inhibit it or delay it all together if we can identify these patients. Again, ideally I think understanding all the theories involved I think there is a convergence of the theories that takes place in these patients though there is the predilection of certain patients based on genetic factors that will predispose some as supposed to others to having Charcot arthropathy. That’s the pathophysiology kind of in a nutshell. When we look at Charcot arthropathy, we definitely want to be able to have a good differential diagnosis. When we see patients of neuropathy coming in with the red, hot swollen but we tend to automatically assume that these patients have Charcot but don’t forget to rule out processes such as gout. DVT is probably a big one also. Then the presence of a portal of entry and ulceration, a puncture wound or some other traumatic wound. Don’t be too nonchalant and not work up cellulitis and osteomyelitis and again, the Charcot neuroarthropathy in these patients. They can all have similar appearance so your biggest diagnostic tool is your clinical suspicion most often especially in patients who have neuropathy and the vascular calcification. Clinical science, again, marked increase in swelling, I think everybody today is familiar with the DermaTemp and taking skin temperature measurements. When you compare to the contralateral limb, you want to make sure that there is none of a skin temperature gradient difference of four degrees. You’ll start seeing now, two degrees is probably the indicated skin temperature difference you want from monitoring maybe in an effort to identify earlier and not return to weightbearing too soon. Increased warmth of the foot, again, in the absence of portal infection our suspicion has to be raised at these patients or potentially having a Charcot event. Pain and discomfort is always alarming to me in the diabetic neuropathic patient especially one who comes in with a red, hot, swollen foot. It’s not something we should ignore and it’s definitely a red flag. I had a nurse from our lymphedema clinic, walk over in my clinic and tell me that I had to see that patient because he came in with the red, hot, swollen foot but it was so painful and they sent him there for a lymphedema management. She said when she was evaluating the foot, she could feel bones grinding and he came over and thought he was having Charcot event which sure enough. Thanks to her, it was caught in advance and he was given appropriate treatment but the pain and discomfort is really what alarmed her aside from the swelling and usually we do find these patients have pedal pulses present. My findings, I don’t think there is one lab test that is diagnostic alone for Charcot arthropathy. You’ll probably see the inflammatory markers elevated. There’s a question as to whether or not CRP is less elevated in patients with Charcot as oppose to patients with osteomyelitis. White blood cell count can be helpful especially if you’re working to rule out an infectious process as oppose to osteomyelitis. Imaging, plain films even in the absence of bony destruction or collapse, I think are important, we need to obtain plain films especially when our suspicion is raised for Charcot event, they serve as a great baseline for progress deformity during the course of your treatment plan especially with good sequential radiographic monitoring. Bone scans will definitely tell you that there’s an active process, they’re definitely not diagnostic alone. MRI is a bit iffy. There are some clues that you could incorporate with an MRI so should you get an MRI they try to rule out Charcot versus infection. Excuse me, they’re both are going to show an increase in bone marrow edema. Usually, Charcot tends to be more diffuse across the joint, usually more mid foot. Usually, if there’s an ulceration, it’s usually in the pressure area, it’s usually under a metatarsal head or a focus of pressure, you can, start to rule out factors that way, MRI is definitely going to tell you that there’s a process going on, I think there are some other findings they have to correlate with the MRI study and not just used it as an independent factor for diagnosis and then there is some reports about PET scans and bone mineral density which I don’t have too much experience with. In classifying Charcot arthropathy, there’s an anatomic classification. I think it’s a good to know the stages as well as anatomical classification. I find the anatomic classification actually will give a predictor outcome and morbidity associate with the Charcot arthropathy. Pattern one is usually the metatarsal and interphalangeal joints.


    Pattern two is at Lisfranc joint and three is at the cuneonavicular, talonavicular and calcaneocuboid joints. Fourth at the ankle subtalar joints and five at the calcaneus and a classically as you progress further along in the Charcot in terms of anatomic location, the more severe it tends to be and the more disabling, it tends to be and a greater risk for amputation in these patients if reconstruction is not viable or successful. Stages in regards to Eichenholtz stage zero are patients who may have a trauma, inflammation, redness but no real active bony process identified. Stage I are the patients who have the erythema, edema, increased warmth, usually absence of pain and they do demonstrate some level of bony fragmentation. Coalescence is when you start to see some reduction in your erythema, some reduction in the edema and potentially some early consolidation of the osseous fragmentation that’s taken place in the bony process and then ultimately the reconstructive phase. Remembering that these phases vary in time and length and it’s important to educate the patients on this and let them know. I have a patient who came into my clinic who had bilateral Charcot and the reason we were alerted that it might be bilateral is because we took skin temperatures there actually equal but he had a red swollen foot and dorsal dislocation on the one side of his Lisfranc joint. And when we x-rayed the other foot concerned because we weren’t getting a temperature gradient, we actually found that he had fractured of the metatarsal shafts three, four and five. He had bilateral process going on. In bilateral case, definitely want to tell them to that this could be a prolonged course for recovery and treatment. Treatment options, I think the reality of this, there are conservative options and surgical options and there is, we were discussing earlier, there is a place for both I think that initial treatment really is should always be conservative and then surgical should be in the recalcitrant patients who have severe enough deformity. The goals of treatment whether surgical or conservative are always to offload the foot, treat the bone disease and prevent them at further fracture deformity. Ideally, you want to achieve a plantigrade foot that allows the patient to be functional and to some level remain in the community as an ambulator. When we talked about offloading, and TCC seems to be coming up a lot today but again, it is the gold standard and I even hesitate to use gold standard anymore. I’d almost like the advanced therapy description given by Dr. Navone [phonetic]. The offloading boot, wheelchairs, new rollers, crutches, again, referring back to the talk I gave earlier today, what fits your patient best? It’s best not to be rigid in your treatment and say only this option is going to work for you. Some patients, again, can’t wear cast but they can use a wheelchair and still allows them to be part of what they need to do. And that stay off a bit as long as you really educate these patients as to what’s staying off of it means and what the consequences are. Medical management and conservative management long term for these patients and then surgical reconstruction options. Again, offloading TCC, offloading sandal, CROW boot, CAM walker and shoe gear, immobilizing patients ideally we’d like to put these patients in a total contact cast until he get later into that phase of the Charcot process and then progress them into something that allows them a level of ambulation such as a CAM walker or CROW boot. The CROW boots have been found to be most successful when the patient is about stage II, where you see a decrease in the erythema, decrease in the edema. We’ll talk a little bit about the CROWs in a minute too. Once you get pass the active process of Charcot, you really need to consider bracing options to really further offload any deformity that maybe residual due to the Charcot process. Some options include the AFO brace, double upright brace and again the CROW walker. When you use to consider an AFO on the long term for these patients or have residual deformity, what you’re really doing is controlling both medial and lateral motion dorsiflexion and plantarflexion. You’re getting multiplantar limitation and motion and due to the having a molded foot bed, you can work to offload, certain areas of stress based on the osseous prominence or deformity that resulted. Patients tend to find an AFO the most cosmetically pleasing because they can slip it in to some level of a shoe whether it has to be customized or not and they can wear it and not feel, so lack of a better word, disabled in anyway. The problem with AFOs is that some are concerned that because the full contact AFOs that sometimes you get more pressure areas of irritation especially at the ankles, at the malleoli.


    These can be areas that constantly have to be revised or adjusted for these patients and she’s have to be aware to recognize that for them. Saltzman did a study with the AFOs and found that in more severe deformities that the patients did re-ulcerate. Again, be careful of that. The CROW boot do not meant to be a long term brace, again, works well when patients get in to a phase of their Charcot process where they can ambulate. I think it’s more aggressive offloading and immobilization. For some reason, I don’t know too, like I don’t like the label populations but the VA population, the patients love to begin a CROW boot as oppose to anything else. And they love to use it long term, I don’t know if it’s because they get these great decorative patterns on them or what it is but once I put patients in a CROW boot, they seem more protective and that they seem like they are able to ambulate in it. They seem to want to use it long term even though it’s really not intended for that, I think it’s in medicine today and then what we do today it’s found a places a long term device and I, I do use it that way. The metal high bridge shoe brace is nice because again, less skin contact, it’s also little bit more cost and adequately pleasing for patients because again, it does afford them a shoe to wear with the good molded insole to offload any residual deformity. And it’s also nice because less contact, less chance of skin irritation, skin ulceration, less chance of pressure areas at the malleoli or in the lower leg. We really are limiting motion also in the medial lateral and sagittal plane as well. But the nice thing this affords you to is that you can provide, allow for some motion in dorsiflexion and plantarflexion and palpations maintain some of their inherent motion and not really limit them completely resulting in atrophy of the cuff muscles and allowing to keep some of their strength. Figure accommodations, again, custom molded insole are rigid shoe with a rocker and shoes with bracing like I mentioned with the patient earlier today for those of you who were here. I think we, in general, are really good at prescribing shoes insoles and anything that we put patients in long term. I think where we may lack is following these up in patients and feeling the need to assess them, in them and making sure that they are providing them in an appropriate foot that they aren’t irritation in them. And not solely relying on only the prosthetist who dispense the shoe if that too you’re using to be the long term evaluator of it. I always make the patients come in, anticipating the timeframe that they’re going to get their shoe and evaluate their shoe and make sure that what I ordered was appropriate and that what I got is what I ordered. It’s a two-way street. Pharmacologic agents on the bisphosphonates and supplementations to increase bone integrity. There are some, there are studies of the bisphosphonates. Overall, they’ve been found to reduce skin temperature, reduce the bony turnover but they have not been found to reduce or shorten immobilization time. There are some factors that have to be controlled medically with putting patients on this and there has not been really again, nothing that has been positive in regards to sorting the period as well as potentially has been found to lengthen the actual resolution phase. We mentioned denosumab as a RANKL inhibitor, again, I think there’s potential for looking into this in the future especially with where we’ve come and identifying the RANKL pathway as a genetic factor contributing to Charcot arthropathy in our patients and really answering the question as to why some patients get Charcot and some patients don’t despite all having neuropathy. Again, it’s the one medication that actually binds to RANKL preventing activation of RANK and therefore preventing osteoclast activation. This is just that’s cut away. Again, treatment options immobilization, bracing, shoe gear accommodations, potential for pharmacologic agents and then surgery. Again, Saltzman retrospective review how affective is conservative management in patients with Charcot arthropathy and is it the main stay of treatment. Hundred fifteen patients, a 127 limbs to try to identify if an intense conservative approach was beneficial to these patients. What they were looking for in terms of outcome variables was how many patients had to undergo amputations, how many needed long term bracing. How many were also rated and how many ended up having to have surgery? And what they found was about 3% of the patients with Charcot ended up with the amputation end of course of the year.


    About half of the patients ended up needing surgical reconstruction, 25% needed long term bracing which I think in general is a small price to pay in terms of limb salvage if they have to wear an AFO. Forty nine percent of the ones who did not undergo initial surgery for their Charcot ended up re-ulcerating and of that population those who went and had realignment arthrodesis or fusion or surgery, none of them required amputation. Therefore supporting I think the benefits of surgery in the right patient population and at the right time. See, this is just again, identifying some of the main stay treatments and factors diagnosing Charcot, your imaging, identifying the class of your Charcot and then a few thoughts in regards to some etiology and the pathophysiology of Charcot. Blood flow as the predictor of incidence, if there is an inciting trauma that increases blood flow to the area. The inflammatory cytokines that might initiate the cascade of the RANKL pathway underlying going quality, raises the question if RANKL is also a factor in osteoporosis is bone density and option in this patients as an identifying factor without having to do serum draws and identifying the OPG polymorphisms in these patients and then again, identifying the genetic predisposition. The consensus report, Dr. Rogers actually talked about it a little bit earlier, I’ll brief through it. The keys are to offload the acute active stages, monitor skin temperatures within two degrees of the contralateral limb before you progress these patients to full weightbearing and back into shoe gear. The cognizant of the duration of your nonweightbearing, don’t be too premature to remove your nonweightbearing devices and again, if need be, be aggressive with the TCCs as opposed to something that’s removable. Do aggressive radiographic monitoring for example, the patient that I discussed earlier equals in temperatures for also dislocation and subluxation, noted of the foot and deformity on one side and the other side equal temperature and a subtle metatarsal fracture at the base and no dislocation or deformity. Radiographic evaluation and monitoring consolidation is important and then progression to footwear, the schematic kind of summarizes everything we discussed in the pathways to treatment considerations whether surgical or conservative. Surgical conditions considerations I won’t harp on. You have two great speakers coming up on that topic. Again, the indications are for recurrent ulceration despite conservative measures, unstable foot or ankle deformity and outweighing the risks and benefits. I think regardless of the treatment implemented, the quality of life always has to be taken into account. It’s a factor and overall treatment planning. Diabetic patients with Charcot have lower physical scores than any other major illness and lower than other patients of diabetes in general. You’re goals of therapy, achieving minimal deformity. A foot that’s easy to place in foot wear, a plantigrade foot, reduction of ulcer risk, affording the patient a reasonable gait and activity level with little to no reduction in their quality of life. I’m getting the cut off from Dr. Frykberg. I think we’re done. Thank you, any questions? I’ll be hanging around.