transfer. Eur J Vasc Endovasc Surg 2004;27:635, 639. 37. Wolfle KB. Bruijnen H, Loeprecht H, et al. Graft patency and clinical outcome of femorodistal arterial reconstruction in diabetic and non-diabetic patients: results of a multicentre comparative analysis. Eur J Vasc Endovasc Surg 2003;25:229, 234. 38. Shah DM, Darling RC III, Chang BB, Fitzgerald KM, Paty PS, Leather RP. Long term results of in situ saphenous vein bypass. Analysis of 2058 cases. Ann Surg 1995;222:438, 446.
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22 Charcot Foot: What’s New in Pathogenesis and Medical Management? Edward B. Jude
INTRODUCTION Charcot neuroarthropathy (CN) is a progressive condition affecting the bones and joints of the foot and is characterised by joint dislocation, subluxation and pathologic fractures of the foot of neuropathic patients, often resulting in a debilitating deformity. In developed countries, the condition is most commonly encountered in diabetic individuals.1,2 The development of CN results in a foot that is ‘at risk’ for ulceration and amputation (Figure 22.1).
EPIDEMIOLOGY The incidence of CN in diabetes is reported to be around 0.1, 0.5%.3−5 Bilateral involvement has been reported in up to 30% of patients with Charcot feet.1 There is no sex predilection, and both type 1 and type 2 diabetic patients are at risk. It is commonly seen in the fourth or fifth decades of life and in patients with a long duration of diabetes.3,6 The majority of lesions occur in the midfoot, but any bone or joint in the foot or ankle can be affected.6,7
PATHOGENESIS The association between joint changes and neurological disease was observed as early as 1831 by Mitchell, who described a patient with ‘rheumatism of the lower extremities’ and ‘caries of the spine’.8 He noted the importance of ‘that part of the spine, which supplies with nerves the parts in a state of active inflammation’.
In 1868, Jean-Martin Charcot, a French neurologist, gave a detailed description of the arthropathy occurring in tabes dorsalis and this condition bears his name.9 The association with diabetes was put forward by Jordan when he described a case of Charcot arthropathy in a diabetic patient.10 The aetiopathogenesis of diabetic CN is still unclear.
Two theories have been put forward for the development of this joint condition.
The first theory, known as the French theory, was
The Foot in Diabetes, 4th Edition. Edited by Andrew J.M. Boulton, Peter R. Cavanagh and Gerry Rayman. C 2006 John Wiley & Sons, Ltd. ISBN: 0-470-01504-7
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Figure 22.1 Acute Charcot foot with foot and ankle oedema
initially proposed by Charcot himself.9 He suggested that arthritic changes were the result of damage to the central nervous system within the centres that control bone and joint nutrition.
Therefore, neurological damage preceded the development of, and was in some way directly responsible for, the changes occurring in CN.
The second theory, known as the German theory, was popularised by Volkman and Virchow.11,12 This concept suggests that the changes in the bone were a result of a multiplicity of subclinical traumata, which went unperceived because of the insensitivity of the affected joint.
Peripheral neuropathy and autonomic neuropathy are thought to be the pre-requisites for the initiation and progression of the Charcot process.
Trauma may be an important precipitating factor in its development, although around two thirds of patients do not remember having injured the foot.1,13 Continued weight bearing on the foot can result in a progression of the Charcot changes.14 In a case series of 101 patients with CN, all patients had distal symmetrical sensory neuropathy,3 and this was similarly observed in two other series.6,15 Patients may also have motor nerve involvement, which may be the reason for the ligament stretching and spontaneous dislocations seen commonly in this condition.16,17 However, it is thought that
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autonomic dysfunction leads to some of the circulatory changes that result in the gradual destruction of the foot.
Sympathetic denervation results in increased blood flow to the foot, which has been demonstrated by plethysmography18 and by increased uptake of isotope in patients with CN.19 Changes in the bones of the feet as a result of the peripheral nerve abnormality have been studied using bone turnover markers and bone density studies.
Bone metabolism is characterised by two opposite activities: the formation of new bone by osteoblasts, and the degradation (resorption) of old bone by the osteoclasts.
The rate of bone formation or resorption can be assessed either by measuring a prominent enzymatic activity, such as alkaline and acid phosphatase activity, of the bone-forming or resorbing cells, or by measuring bone matrix components released into the circulation during formation or resorption.
Bone turnover markers have been shown to be increased in acute CN, indirectly indicating increased bone metabolism.
Gough et al. measured pyridinoline cross-linked carboxy-terminal telopeptide domain of type 1 collagen (1CTP) and carboxy-terminal propeptide of type 1 collagen (PICP) as possible markers of bone resorption and bone formation, respectively, in diabetic patients with acute Charcot, chronic Charcot and in control subjects, in the systemic circulation (from a forearm vein) and in the foot.20 They found an increase in the bone turnover marker 1CTP in patients with acute CN but no difference in the bone formation markers.
In a similar study, Selby et al. measured urinary deoxypyridinoline (bone resorption marker) and bone-specific alkaline phosphatase (bone formation marker) in patients with acute CN and non-Charcot diabetic patients and found an increase in both these markers thus indicating an ongoing remodelling process, bone resorption and formation.21 Edelson and colleagues employing a different urinary marker of bone resorption, cross-linked N-telopeptides of type I collagen (NTx), demonstrated increased levels of collagen breakdown in subjects with CN.22 Therefore, a possible logical step in the treatment would be to dampen down this enhanced bone remodelling and hence retard the progression of the Charcot process.
In addition, studies have shown that there is reduced bone density in the foot in patients with diabetic CN.23 Only one study has demonstrated, in a small group of patients presenting with a hot swollen foot, that reduced bone mineral density (using bone densitometry) in the lower limb led to subsequent development of CN, compared to patients with higher bone mineral density at baseline.24 Broadband ultrasound attenuation studies have shown a reduction in bone density in the calcaneus in patients with CN.25,26 The latter study by Jirkovska et al. also demonstrated an increase in 1CTP in patients with acute CN and a direct correlation between plasma 1CTP and bone density in the calcaneus.26
CLINICAL FEATURES AND DIAGNOSIS Acute CN can be misdiagnosed as cellulitis, osteomyelitis or inflammatory arthropathy, and therefore a high index of suspicion is necessary so that appropriate treatment can be instituted immediately to prevent the severe deformities seen in this condition.
The earliest manifes- tation of CN is swelling of the affected foot with pain or discomfort.
On examination, the foot is generally warm, may be inflamed and swollen.
There is a temperature differential of >2◦ C when compared with the contralateral foot.
Although patients have severe peripheral neuropathy, pain is the most common feature followed by discomfort in the foot.6,27 In the acute state, the Charcot foot may be mistaken for gout, cellulits and osteomyelitis.3 Sometimes, CN can be a diagnosis of exclusion, as most investigations in the early stages can be normal (see below).
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Once the acute phase has subsided, which can take months, the foot then progresses into a chronic stage.
The chronic Charcot foot is painless, without a temperature differential in a deformed foot.
It can frequently become reactivated if there is further trauma to the foot, in which case differentiating it from osteomyelitis can be challenging.
Therefore, long-term follow-up is necessary, as these patients are at high risk for reactivation of the Charcot process, foot ulceration as well as amputation.28
Investigations CN can be diagnosed in the majority by plain X-rays, but at times specialised investigations may be required.
Plain X-rays of the involved foot will reveal bone and joint destruction, fragmentation and remodelling in the advanced cases, but early changes may be subtle or undetectable.29 The joints commonly involved are those of the phalanges and metatarsals and tarsal bones, but ankles can occasionally also be affected.
Three-phase 99m Tc bisphosphonate bone scans demonstrate an early increase in bone uptake, which is due to the increase in blood flow through the bone that accompanies the active Charcot process.
Although a radiological diagnosis can be made with some confidence, it may be difficult to rule out osteomyelitis, especially in the presence of a foot ulcer.
To exclude incidental osteomyelitis, 111 In-labelled leucocyte scans and magnetic resonance imaging may be required.29,30