What in the world is Charcot Neuroarthropathy?
Welcome to Diabetic Survivor’s Advanced Charcot article. We will skip past some of the basics of this disease, if you need the entry level articles look here and here. By Charcot I am referring to Charcot Neuroarthropathy. Let’s talk about the name briefly. In the article I will refer to the condition as Charcot, but in the medical literature it is called Charcot foot, Charcot neuroarthropathy, Charcot neuropathic osteoarthropathy, Charcot foot syndrome, and others.
I was recently asked on an online forum to discuss further the why of Charcot, that is why do we get it, how do we get it and why. We’ll be exploring all of these questions in further detail in this post, but I want to let you know right at the outset that we (medicine) do not have the full answers to all of these questions. I wish we did.
Not everyone knows about Charcot. Not all doctors know about Charcot. In medical school and then in residency we study thousands of diseases, and we rarely remember all of them. Charcot is better known by podiatric and orthopedic surgeons. It was named for the condition’s discoverer, Jean Martin Charcot, a French surgeon from days long past. It doesn’t help that there are around 100 other diseases or disease processes that also have his name attached to them. Another prominent musculoskeletal disease called Charcot-Marie-Tooth (CMT) is sometimes confused with Charcot neuroarthropathy.
How do you ‘get’ Charcot?
The underlying cause of Charcot is varied and not well understood. Charcot is always preceded by some type of neuropathy, it may be autonomic neuropathy, and/or peripheral neuropathy. Peripheral neuropathy results in loss of protective sensation, especially in the lower extremities including the feet. This is the neuropathy that will result in numbness, and can explain why some sufferers have multiple fractures without any pain. Autonomic neuropathy may affect the skin’s ability to properly regulate moisture, may affect the motion of the gut, and can also affect heart and lung function. Rogers states that there have been no reported cases of CN (Charcot) without neuropathy. [Rogers 2011]
But where does the neuropathy come from?
But where does the neuropathy come from? The most common condition associated with neuropathy prior to having Charcot today is diabetes mellitus. With diabetes the patient with excessive glucose over a long period of time will accumulate advanced glycation endproducts (AGE’s) which break down the small vessels that provide nutrition to some of the sensory nerves. As the vessels are broken down the patient may have a tingling sensation, this may progress to a burning sensation, or an electric shock sensation. Then one day the sensations may go away entirely, so the patient is cured right? Sorry, no. Most likely what has occurred is the nerves that were causing pain have now died back (or degenerated).
Neuropathy with and without diabetes
Even though diabetes is responsible for the lion’s share of the neuropathy that we see clinically with Charcot, there are many other causes of neuropathy. In fact, the number one cause of peripheral neuropathy is idiopathic, which means that it just came on without known cause. Not very comforting, sorry. But there are many other conditions that may contribute or lead to neuropathy, I have listed several below which should not be considered an exhaustive list.
- Heavy metal toxicity (mining, electronics industry)
- Other toxins (including some drugs)
- Rheumatoid arthritis (RA)
- Multiple Sclerosis (MS)
- Poliomyelitis (very common earlier in this century, mostly eradicated in the western world)
- Infection: Hansen’s disease (Leprosy), Tabes dorsalis
- Traumatic injury
- Congenital neuropathy
OK, so we know the patient has neuropathy, but what happens that leads to Charcot? Fortunately Charcot is relatively rare, and most of the individuals that experience neuropathy do not also have Charcot (approximately 1% of those with neuropathy are affected with Charcot). Short answer is we (medicine again) are not sure. Once not long ago there were two theories: neurovascular which was French, and neuro-traumatic which was German. In the neurovascular model there is an increase in blood flow to the affected area, usually one of the lower extremities. It’s not certain why this affects the bone as it does, but this increase in blood flow may increase the inflammation and normal bone remodeling process. This increase in remodeling weakens the bone through a leaching out of minerals [Blume], and predisposes to fractures to one or multiple bones or joints. In the neuro-traumatic model, there was damage in the central nervous system (CNS) which affected the control circuits to the bones. As this neuropathic process proceeded it also resulted in loss of proprioception (sense of where a joint is in space without directly observing it) and then fractures to the affected joints.
Today it is more accepted that both processes play a role concurrently. There is some CNS deficit leading to loss of proprioception and worsening autonomic and/or sensory polyneuropathy. The affected individual has microvascular disease, which means clogging (with debris or via calcification) or decreased functionality of the smaller vessels. If the patient has diabetes they will always have a glucose level that is far above the non-diabetic normal range. Although the functionality of the small vessels is decreased, they persist in a hypervascular state. Blood flow in charcot patients has been shown to be as much as five times the non-charcot flow level. [BLUME] This hypervascularity is often palpable clinically, and should be a clue to the examining physician that all is not normal in the examinee. As mentioned above, the increased vascular flow may accelerate the natural osteoclastic functions in bone, increasing bone absorption without a concurrent increase in new bone being laid down.
Our bones are constantly in a state of remodeling. There are cells which lay new bone down called osteoblasts, and there are cells which take up old bone in order to facilitate remodeling called osteoclasts. These processes are usually in balance with one another, unless some process such as trauma has occurred. If a bone has recently undergone acute stress out of the normal range, then the bone may be actively inflamed. This will result in an increase in osteoclast and osteoblast activity. It has also been noted that in charcot the osteoclasts are more aggressive. This results in more bone being stripped away than is being laid down, upsetting the balance in the bone. In part due to this, over time the bone becomes osteopenic, or minerally deficient and weak. This predisposes the osteopenic bones to fracture. Occasionally, usually in the very aged, osteopenic bone will fracture when normal or minimal stress is applied, if a fracture occurs this is termed a pathological fracture. This is similar to what occurs in charcot, but in charcot it can happen in multiple bones simultaneously, and in charcot there may be no pain noted.
What is RANKL
We do know that the next step involves inflammation which the body is not able to effectively regulate. Extensive research is being conducted right now on some of the inflammatory chemical communication pathways, especially concerning a molecule called receptor activator of nuclear factor kappa-beta ligand (RANKL). After a fracture there should be a short duration of release of pro-inflammatory cytokines (cytokines are signaling molecules) which will activate the inflammatory phase of healing. In charcot these pro-inflammatory cytokines are present for a longer duration, these cytokines also signal to have increased osteoclasts. Peptides secreted by nerve terminals called calcitonin gene-related peptide (CGRP) usually halt or check the synthesis of RANKL, if the nerves have been damaged, the CGRP may not be released so RANKL increases or stays at an increased level in the area of damage. (This is a complicated process that has been simplified, read the references at the end for a more thorough discussion.)
What happens in active charcot?
Clinically Charcot will either be referred to as active or stable (inactive, chronic, etc). If you are having your first Charcot event, you are in the active stage. In active Charcot the affected area will usually be red, hot and swollen. Radiographically there will be dislocation and/or fractures noted. As discussed above Charcot is an excessive inflammatory process, so some of the things that may trigger or precipite active Charcot are inflammatory conditions. The common question you might hear in clinic is ‘How did this happen?’ So what everyone wants to know is what massive trauma precipitated the fractures that are one sign of Charcot. Unfortunately what caused the fractures is often unknown to the patient, it might be trauma such as hitting your foot on furniture or during a fall. But it can also be much smaller amounts of trauma such as normal walking, a brief slip (without a fall), excessive microtrauma (walking too far or too long). Other inflammatory conditions or conditions which exhibit excessive local inflammation in or near the foot may also cause a patient to enter active Charcot. However, a systemic inflammatory condition does not have the same effect, and markers of acute systemic inflammation will not be elevated. [Wukich]
Differentiating Cellulitis from Charcot
Most notably the presence of infection should always cause a massive inflammatory reaction in the area, this happens as the immune system responds to the infection and attempts to halt it. Some conditions such as a diabetic foot infection, or other ulceration or break in the skin should also stimulate an immune mediated response which will also have an inflammatory element. So in these areas the pro-inflammatory cytokines are already present, and they may have been present for days, weeks or longer. As noted above in the case of Charcot this may result in damage to the structure of bone predisposing the patient to a fracture, or a series of fractures. This makes differentiation difficult, and a full description of how to differentiate clinically is beyond the scope of this article.
When charcot becomes active, and when the patient begins to have destruction of bone and joints, some amount of pain or discomfort may filter through the neuropathic screen. However, the amount of pain noted will usually be much less than would be felt by someone without peripheral neuropathy. If you have ever had a fracture, perhaps you remember how painful it was to move the affected bone. The sensation of bone grinding on bone is not one I care to remember, although it is also very difficult to forget. The individual without neuropathy to shield or mask the pain will not need to be told to seek medical attention, or to limit motion in the affected area. But the patient with neuropathy may continue to not only move the bone or joints involved, but may continue walking on the fractures. Imaging having a broken bone in your foot, now imaging putting on your shoes and going to the grocery store and shopping for an hour, all the time walking on the fracture. The pain should be intolerable, yet this can (and does) happen to patients with Charcot. The result is that what began as a single fracture or dislocation may now be several fractures or dislocations, and the fractures may be broken into many pieces (comminuted). This is much harder to treat than a single isolated fracture or dislocation.
Charcot by the numbers
Blume writing in 2014 gave some recent statistics on diabetes and Charcot. Up to 77% of patients with diabetes suffer from neuropathy, and up to 11% of those without diabetes have neuropathy. Within the diabetic subgroup Charcot estimates range from <1% up to 13% in high risk diabetic patients. [Blume] It has been estimated that approximately 1% of patients with diabetes may also have Charcot. Wukich also touches on where it is found, stating unilateral (one side only) involvement is most common, but in the literature bilateral involvement ranges from 5-39%. Fortunately simultaneous bilateral involvement is less than 1% [Wukich].
Variation in Charcot statistics
I cite these numbers as they are current, but different studies can cite wildly different incidence rates for Charcot with or without diabetes. This makes it difficult to compare studies, as some studies appear to have dealt with a population suffering much more from the disease than other studies. One wonders however if the more affected populations are actually occurring in areas serviced by physicians who are trained to look for Charcot, this would account for the higher numbers of Charcot diagnoses. To look at the scale of the problem, there are over 400 million people with diabetes worldwide. The American Diabetes Association estimates that about half of those with diabetes will experience neuropathy. So just with the diabetic neuropathic population alone, and that is not the full neuropathic population, about one percent of 200 million will have Charcot, resulting in two million with Charcot.
Evaluating for Charcot Clinically
Charcot is still primarily a clinical diagnosis. One challenge is that Charcot neuroarthropathy is still not well understood, but also that it is rare enough that not all medical staff are acquainted with it. This would only be inconvenient if an acute Charcot foot did not resemble a cellulitic diabetic foot. As it does resemble an acutely infected foot, emergency personnel may immediately rush to treat the infection. (Read more on a diabetic foot infection here)
In cases where deformity, or neuropathy, has resulted in an ulceration the patient presentation will even more closely resemble diabetic foot infection. As noted above the largest population with Charcot is those with diabetes. These facts together make a rush to treat a diabetic foot ulcer seem much more reasonable. In cases where the foot infection looks, or is, well progressed, this may result in a recommendation for debridement and possibly amputation.
Vital signs such as temperature and blood pressure will not be elevated in Charcot, where they may be elevated in an infection. Some diabetics can have moderate to severe foot infections and still have stable vital signs.
Laboratory values will differ between Charcot and infection. With an infection the white blood cell count will almost always be elevated, and it will not be elevated if you have acute Charcot without the presence of infection. Acute inflammatory markers may be elevated in both conditions. Blood glucose may be elevated in either condition, although it is usually much higher in acute infection.
I hope this article has been informative and has answered some of your questions. I have attempted to describe some of the where and when and how of Charcot. There is much more to the Charcot story, including grading or staging, medical treatment, surgical treatment, and various types of offloading. Please comment below if you have specific questions or if you would like further topics addressed. There are links below to our previous articles on Charcot, articles on neuropathy, and also references for further reading. Please join our newsletter to keep updated as new information or articles are published on DiabeticSurvivor.com.
Diabetic Survivor Articles on Charcot
Charcot – The Painless Road To Amputation by Valerie Marmolejo, DPM
Signs I May Be Having An Early Charcot Event by Valerie Marmolejo, DPM
Diabetic Survivor Articles on Neuropathy
Diabetic Neuropathy and The Gift of Pain by Jacob Panici, DPM
Diabetic Autonomic Neuropathy by Jacob Panici, DPM
The Charcot Foot in Diabetes. Rogers et al. Diabetes Care, 34: 2123-2129. 2011.
Charcot Neuroarthropathy of the Foot and Ankle. Diagnosis and Management Strategies. Blume, P. A., et al. Clinics in Podiatric medicine and Surgery, 31: 151-172. 2014.
Charcot arthropathy of the foot and ankle: modern concepts and management review. Wukick D. K., Sung, W. Journal of Diabetes and Its Complications. 23 (6) 409-26. 2009