Using Serologic Screening To Identify And Monitor At-Risk Charcot Patients

By Molly S. Judge, DPM

Charcot neuroarthropathy and the complications of longstanding diabetes are perhaps the greatest challenge for the foot and ankle specialist. These conditions are of principal concern given the limb threatening consequences when a diagnosis of Charcot foot is delayed or missed completely. Though there is no modern revelation in identifying the Charcot foot, there has been rejuvenated interest behind the continued study of this neuropathic entity.1-22 Subsequently, the slow rise in the number of reported cases of Charcot neuroarthropathy is likely due more to increased awareness of the disease as opposed to an increased incidence. An increase in the reported incidence of Charcot neuroarthropathy will also likely occur as clinicians emphasize more due diligence in identifying the “at risk” population. Serologic screening is integral to identifying these “at risk” individuals. Indeed, when an acute Charcot flare occurs, there is a disruption of normal homeostasis that is reflected by changes within the blood serum. With this in mind, clinicians should complete a serum screening as soon as possible when they suspect Charcot foot. Given the many possible etiologies for neuroarthropathy, one should pay particularly close attention to determining the cause of the disease among patients who present with clinical and radiographic evidence of an osteolytic process.23,24 Most importantly, one should establish a differential diagnosis, ruling out those diagnoses with the highest associated morbidity including the limb-threatening conditions of septic arthritis, osteomyelitis and Charcot neuroarthropathy. These destructive processes often coexist so one must address the possible combination of a neuropathic osteolytic process and infection. Modern technology allows the study of many serologic markers that flag pertinent systemic changes associated with neuropathic osteolysis and osteomyelitis.25 Such changes are the result of uncontrolled hyperglycemia, bone destruction, inflammation and infection. To help differentiate between bone destruction secondary to Charcot neuroarthropathy and osteolysis due to infection, there are many cursory serologic studies that are commonly utilized. These studies include: leukocyte count with differential, platelet and reticulocyte counts, alkaline phosphatase, calcium, albumin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). There are also studies such as hemoglobin A-1C for assessing the degree of glycemic control. The importance of these studies is well understood and they each have very practical application when one suspects an infection in the Charcot foot. While CRP and ESR are the diagnostic workhorses when it comes to this clinical scenario, the actual physiologic mechanism that drives these studies is often poorly understood. Subsequently, clinicians may mistakenly use these tests interchangeably. What many do not understand is that there is a distinct benefit in monitoring the C-reactive protein when it comes to differentiating between neuropathic osteolysis and infection. Taking A Closer Look At The C-Reactive Protein The C-reactive protein (CRP) is an acute phase reactant synthesized in the liver via cytokine modulation. One can use the CRP, a direct serologic measure of the acute phase response to injury and infection, to aid in screening for the presence of inflammatory diseases, infections, neoplastic diseases and tissue injury. The CRP is also directly involved in the elimination of microorganisms. Acting as an opsonin, the CRP will attach to certain residues and polysaccharides that are found in bacteria, fungi and parasites, and stimulate a cellular response for their removal. The CRP was discovered by Tillett and Francis in 1930 while they were studying the Quellung reaction in cases of pneumonia. Blood serum from these cases precipitated a C-polysaccharide, a polysaccharide from the organism Streptococcus pneumoniae.26 Once patients recovered from their illness, the potential for their sera to precipitate this protein ceased and CRP values promptly returned to normal. What we learned from these studies is that the C-reactive protein (CRP) is the fastest rising acute phase reactant and it returns to normal as abruptly as it had risen as a result of clinical cure. In other words, the CRP closely correlates to the occurrence and resolution of clinical disease.

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