David Levy, MD, FRCP
Charcot neuroarthropathy is a serious and poorly understood condition associated with rapid destruction of bones and joints and resulting in bone fragmentation. It occurs only in patients with advanced sensory and autonomic neuropathy, and is characteristic of long-duration type 1 diabetes with other microvascular complications, especially nephropathy and laser-treated retinopathy, but it is also seen in type 2 diabetes. Mid-foot bones are characteristically involved, but the metatarsophalangeal joints and even the ankle can be affected. A common presentation is with a tarsometatarsal fracture/dislocation. ‘Silent’ stress bone injuries in the foot, detectable on MRI but not plain radiography, may precipitate the acute joint disorganization. When presented with an acute diabetic foot, especially if there is no ulceration, always consider a Charcot process; diagnosis is often delayed many weeks, by which time considerable joint destruction may already have occurred ….
Clinically, they present with painless inflammatory swelling – the affected foot is usually several degrees warmer than the contralateral foot – but some patients complain of a poorly localized dull ache, another reason for routinely requesting and carefully scrutinizing radiographs of the foot in all patients, and repeating at weekly or 2-weekly intervals if clinical suspicion is high. The difficult differentiation from osteomyelitis is another reason for taking frequent radiographs; both processes can progress rapidly. Infection usually involves phalanges, metatarsals or calcaneum, rather than the midfoot. FDG-PET scanning may differentiate osteomyelitis and Charcot neuroarthropathy more reliably than MRI, but there are few studies . Coexisting acute Charcot neuroarthropathy and osteomyelitis from an adjacent ulcer is uncommon, but poses a very difficult diagnostic and therapeutic problem. If there is no recent history of ulceration, a Charcot foot is more likely than osteomyelitis. The more common problem is the reverse: the severely disorganized bony anatomy of a chronic Charcot foot leading to ulceration at a bony prominence, often the medial arch (Fig. 10.3).
Immobilize the foot with total contact casting or Aircast boot as soon as the diagnosis is suspected. Specialist input from podiatrist, orthopedic surgeon and radiologist is needed. Bisphosphonate treatment with a single intravenous infusion of pamidronate 90 mg should be given, though higher doses have been used, for example 30 mg, 60 mg, and 60 mg at 2-weekly intervals. Bisphosphonates reduce symptoms and markers of bone turnover and destruction, though the long-term benefits are not known, and the fall in bone alkaline phosphatase is not prognostic. The Charcot foot is not osteoporotic after the acute episode, and though long-term oral bisphosphonates are often given, no trials have been performed. However, think of bone health in all patients with diabetes, measure vitamin D levels and supplement appropriately, and request DEXA scans in patients with other risk factor for osteoporosis, for example type 1 patients with eating disorders.
After the acute phase, custom footwear is vitally important. Seek expert advice on surgical correction of deformity, especially plantar and medial bony protuberances, which predispose to ulceration. The role of more extensive surgery, involving internal fixation, is contentious and requires highly specialized orthopedic input.
Painful diabetic neuropathy
A distressing syndrome of distal leg and foot pain that occurs in 5–7.5% of a clinic population, though some studies report much higher prevalence rates, up to 15%. The impression is that painful neuropathy is now less common than 10–20 years ago, and this may be due to improv- ing multimodal management of type 2 diabetes. However, it is still probably under-recognized. The pathophysiology is unknown, but the defect may lie in the spinal cord. Poor glycemic control is common, but by no means invariable. Pain resolves in a minority, and about three- quarters have chronic symptoms lasting several years. Acute pain in the feet and legs (‘insulin neuritis’) occurs shortly after the start of insulin treatment. Although uncommon now, it is still occasionally seen in people with very high starting HbA1c levels. It resolves spontaneously after a few months. Chronic painful neuropathy seems to be most common in older type 2 patients, but is well described in young women with type 1 diabetes with eating disorders, especially anorexia nervosa . Clinical features are outlined in Box 10.2. These, together with the numbness of coexisting polyneuropathy, give the particularly distressing combination of lancinating pains apparently emanating from an insensitive foot. Making the diagnosis is not always easy, as it is purely clinical, so remember other painful syndromes in diabetes. Patients often hang feet out of bed, out of contact with bedclothes, and find ways of providing counter-irritants, for example soaking their feet in cold water or having their legs massaged.
Other painful neuromyopathic syndromes in diabetes
These include proximal motor neuropathy (syn. diabetic amyotrophy, diabetic neuropathic cachexia), meralgia paresthetica, diabetic myonecrosis, truncal neuropathy, and ‘insulin neuritis’.
Podiatric supervision and foot education where there is distal polyneuropathy. Improving glycemic control in chronic painful neuropathy has no proven value, but it should be attempted nonetheless.
Medication and other strategies (Table 10.1)
Studies with many drugs have shown statistically significant pain relief beyond the large placebo effect, but this is not always translated into useful therapeutic benefit in the individual patient. Considerable patience is required from the diabetes team and patient while attempting to optimize pain relief. Painful neuropathy is undertreated.
Vitamins and other dietary supplements do not help unless there is documented vitamin deficiency or alcoholism. The efficacy of simple analgesics such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) is not supported by meta-analysis, but it would be remiss not to suggest them. Use the second-line analgesics with care, but they are almost as effective as tricyclic antidepressants. Tramadol can be started at 50 mg b.d., increasing to 200 mg b.d., but it has opiate side-effects, including dependency and tolerance. Oxycodone is similar; use a modified-release preparation (e.g. OxyContin) starting at 10 mg daily .
Antidepressants are used for their analgesic effects. Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs), often preferred because of their better side-effect profile and simpler dosage titration, are less effective than tricyclics [number needed to treat (NNT) 2 vs. 6]. Sub-antidepressant doses of amitriptyline are effective in neuropathic pain; start at 10 mg nocte, increasing to a maximum of about 100 mg. They are not well tolerated at high doses, with prominent anticholinergic symptoms. See Table 10.1 for doses of other antidepressant analgesics. They can cause ECG changes, particularly at high doses (heart block, ventricular premature beats, prolonged QT interval); request periodic ECGs.
Conventional anticonvulsants (carbamazepine, phenytoin) are effective, but require dose titration and do not seem to be very well tolerated. The centrally acting ‘)-aminobutyric acid (GABA) antagonists gabapentin, and its derivative pregabalin, have NNTs of about 4, between those of the tricyclic antidepressants and the SSRIs. Gabapentin has a wide dose range, and should be started at a low dose (e.g. 300 mg daily), increasing slowly up to 2.4 g daily. Side-effects (dizziness, somnolence, headache and diarrhoea) occur in 10–20% of patients, and frequently limit its use, despite its efficacy. Pregabalin is also licensed for use in neuropathic pain, and is usually effective at a dose of 150–300 mg daily, though it can be used up to 600 mg daily. Because of their side-effect profile, slow titration is better than rapid dose escalation over a few days.
Combination therapies may be valuable (see Table 10.1), but at this stage ask the pain team for advice.
The evidence base for topical treatments in painful neuropathy is weak, but because they do not have systemic effects they are valuable as additional treatments, especially when systemic agents are limited by side- effects (even generous use of capsaicin cream gives systemic exposure that is much less than found in chilli-eaters worldwide).
- OpSite dressing (Flexigrid) or spray is non-pharmacological and is free from side-effects, and is worthwhile trying on this basis alone. It presumably acts by reducing contact discomfort and allodynia.
- Isosorbide dinitrate spray (Isocard 30 mg/dose, one spray to each leg at bedtime) may act by local vasodilatation or nitric oxide donation.
- Topical 0.075% capsaicin cream (Axsain) is pharmacologically sound (it depletes sensory nerve endings of substance P, which may account for exacerbation of pain at the start of treatment). However, it requires three or four applications a day for maximum efficacy (and to reduce the initial pain), which is difficult to sustain.
- Lignocaine 5% in large patches (e.g. Versatis, UK) is useful in post- herpetic neuralgia, and though currently unlicensed may also be valuable in painful neuropathy. Up to three patches, applied to the point of maximum pain, can be used for up to 12 hours a day.
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David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK
This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)