Pathophysiology of Charcot's disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733015/

Charcot arthropathy of the foot is a rare but devastating complication of diabetes that remains to be a challenging issue for the foot and ankle surgeons. Charcot foot fails to be an obvious diagnostic option that comes to mind, even in a pathognomonic clinical appearance. The rarity of the disorder, more common pathologies that mimic the condition, and the self-limiting prognosis deviate the clinician from the right diagnosis. The clinical challenges in the diagnosis of Charcot foot require in-depth investigations of its enigmatic nature to establish useful guidelines. Yet, this goal seems to be beyond reach, without a holistic view of the immense literature concerning the pathophysiology of the disorder.

In recent studies, many authors have emphasized the disturbance of the inflammatory cycle in the core of Charcot foot pathophysiology. Usually minor injuries which are even unrecognized, local infection or a minor surgery may prompt this sequence of events. Without the protective behavior ensured by the pain, in the insensate, neuropathic foot of a diabetic patient this cycle is flared up by repeated traumatic events. Genetic variations that affect the balance between pre- and anti-inflammatory chemo-attractants may predispose a patient to Charcot foot . This theory which has been proposed by two different studies conducted in different populations is a breakthrough for researchers who dedicated their work to Charcot foot. Genetic variations can explain a patient's tendency to pro-inflammatory status, and ultimately may put forth a solid answer why a majority of neuropathic patients are spared from Charcot arthropathy.

Finally, it is often difficult to isolate and experiment the contribution of a single factor in this complex and multifactorial phenomenon. This fact precludes the construction of experimental models to reveal single factor contributions or gathering of adequate (appropriate) control groups for blinded control studies. This suggestion can be adapted to Charcot foot that develops as a result of a subsequent dysfunction concerning different systems which cannot be separated and observed solely. This stalemate can be addressed with prospective studies and a larger number of patients.