Abnormalities of vasomotor regulation in the pathogenesis of the acute charcot foot of diabetes mellitus.
The acute Charcot foot complicates distal symmetrical neuropathy but is remarkably rare. This article reviews the multiple processes that may complicate both diabetes and neuropathy and might, in turn, explain the association of features that are typical of this disorder: osteolysis, vascular calcification in association with intact lower limb blood flow, and uncontrolled inflammation. Specifically, it is suggested that the disorder arises because of abnormal expression of the nuclear transcription factor, NFkappaB, in diabetic neuropathy and that this is further enhanced at the onset of the acute arthropathy as a result of the release of proinflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1. These proinflammatory cytokines and RANKL may then enter a cycle of mutual augmentation, and this is a factor that underlies the continuing inflammation that characterizes the disorder. If this hypothesis is confirmed, it would suggest the option of new effective treatments for this sometimes devastating disorder.
Jeffcoate
William J
WJ
Foot Ulcer Trials Unit, Department of Diabetes and Endocrinology, City Hospital, Nottingham, UK. wjeffcoate@futu.co.uk
D000208:Acute Disease; D002352:Carrier Proteins / Q000378:metabolism; D017719:Diabetic Foot / Q000209:etiology* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014666:Vasomotor System / Q000378:metabolism*
D002352:Carrier Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha