The onset of chronic neuropathy is gradual and insidious, and indeed, on occasions, the initial symptoms may go unnoticed by patients.
Typical symptoms, which may be present in up to half of all patients, include paraesthesia, hyperaesthesia, and sharp stabbing, shooting and burning pain, all of which are prone to nocturnal exacerbation.
Whereas in some patients these uncom- fortable symptoms predominate, others may never experience any symptoms.
Clinical examina- tion usually reveals a sensory deficit in a stocking distribution, and signs of motor dysfunction, including small muscle wasting and absent ankle reflexes, are usually present.15 A particularly dangerous situation, originally described by J.D.
Ward, is the ‘painful, painless leg’ in which the patient experiences painful or paraesthetic symptoms, but on examination has severe sensory loss to pain and proprioception; such patients are at great risk of painless injury to their feet.
The threshold of sensation that protects normal feet holds a very delicate balance.
The purpose of pain sensation as described by Brand17 is not to cause pain but to enable the body to use its strength to the maximum short of damage.
Thus, a person who has lost some pain sensation has not totally lost the ability to feel pain , he simply feels pain at a higher level of stress.
Thus it takes more pressure or temperature or more prolonged ischaemia before the residual nerve fibres are activated and warn higher centres.
It must therefore be emphasised that neuropathic ulceration may occur in patients who still have some ability to perceive stimuli to various modalities.
It is extremely difficult in practice to define exactly what a ‘significant’ loss of sensation is, or at what level of sensory loss a patient’s foot becomes ‘at risk’.
There is a spectrum of symptomatic severity in sensorimotor neuropathy: at one extreme, patients experience severe symptoms whereas others experience mild symptoms or even none at all.
Thus, whereas a history of typical symptoms is strongly suggestive of a diagnosis of neuropathy, absence of symptoms cannot exclude neuropathy and must never be equated with a lack of foot ulcer risk.
Therefore, assessment of foot ulcer risk must always include a careful foot examination whatever the history.15, 17
Peripheral Sympathetic Autonomic Neuropathy
Sympathetic autonomic neuropathy affecting the lower limbs leads to reduced sweating and results in both dry skin that is prone to crack and stroke or fissure, and also to increased blood flow (in the absence of large vessel PVD) with arterio-venous shunting leading to the warm foot.
The complex interactions of sympathetic neuropathy and other contributory factors in the causation of foot ulcers are summarised in Figure 5.1.
The warm, insensitive and dry foot that results from a combination of somatic and auto- nomic dysfunction often provides the patient with a false sense of security, as most patients still perceive vascular disease as the main cause of ulcers.
It is such patients who may present with insensitive ulceration, as they have truly painless feet.
Perhaps, the highest risk foot is the pulse- less insensitive foot, because it indicates somatic and autonomic neuropathy together with PVD.
NEUROPATHY: THE MAJOR CONTRIBUTORY FACTOR IN ULCERATION Cross-sectional data from established UK foot clinics in London and Manchester presented in the second edition of this volume suggested that neuropathy was present in up to 90% of foot ulcers in patients attending physician , or podiatrist , led services. Thus, most foot
JWBK089-05 JWBK089-Boulton April 22, 2006 22:1 Char Count= 0
OTHER RISK FACTORS FOR FOOT ULCERATION 55
ulcers were considered to be of neuropathic or neuroischaemic aetiology.
Confirmation of these facts in recent years has come from several European and North American studies.
Patients with sensory loss appear to show an increase in risk of developing ulcers of up to sevenfold, compared with non-neuropathic, diabetic individuals.18, 20 In the large North-West Diabetes Foot Care Study, for example, a cohort of 10 000 patients was followed for 2 years in the community.20 Whereas the overall incidence of new foot ulceration in the cohort was 2.2%, when divided into those with and without neuropathy at baseline, the annual incidence of ulceration was 1.1% in those without neuropathy compared with greater than 6% in those with neuropathy.
Other prospective trials have confirmed the pivotal role of both large-fibre (e.g. proprioceptive deficits) and small-fibre (e.g. loss of pain and temperature sensation) neurological deficits in the pathogenesis of ulceration.18, 21 Poor balance and instability are also increasingly being recognised as troublesome symptoms of peripheral neuropathy, presumably secondary to proprioceptive loss.
The relationship between sway, postural instability and foot ulceration has also been confirmed.22 Considering the above data, there can be little doubt that neuropathy causes foot ulcers with or without ischaemia, but it must be remembered that the neuropathic foot does not spontaneously ulcerate; it is the combination of neuropathy and either extrinsic factors (such as ill-fitting footwear) or intrinsic factors (such as high foot pressures, Chapter 6) that results in ulceration.
The other risk factors that are associated with ulceration will now be considered.
OTHER RISK FACTORS FOR FOOT ULCERATION Age and Duration of Diabetes The risk of ulcers and amputation increases two- to fourfold with both age and duration of diabetes.23 The relationship of diabetes duration to prevalence of ulceration and amputation appears to be similar for people with both type 1 and type 2 diabetes.
Sex The male sex has been associated with a 1.6-fold increased risk of ulcers20,23 and an even higher risk of amputation23 in most studies of people with type 2 diabetes. The mechanism by which men are at greater risk of these complications is yet to be explained.
Previous Foot Ulceration Several studies have confirmed that foot ulceration is most common in those patients with a past history of similar lesions or amputation, and also in patients from a poor social background.23 Indeed, in many diabetic foot clinics, more than 50% of patients with new foot ulcers have a past history of similar problems. In one randomised controlled trial, Litzelman found that a history of an ulcer increased the risk of new ulceration 13-fold.21 In another prospective study, the risk of ulceration was highly associated with a history of previous ulcers (odds ratio 56.8).24 Similarly, a history of prior ulceration is associated with a two- to tenfold higher risk of amputation.23
JWBK089-05 JWBK089-Boulton April 22, 2006 22:1 Char Count= 0
56 THE PATHWAY TO ULCERATION
Other Diabetic Microvascular Complications It has been recognised for many years that patients with retinopathy and/or renal impairment are at increased risk of foot ulceration. However, it is now confirmed that patients at all stages of diabetic nephropathy, even microalbuminuria, have an increased risk of foot ulceration.25 In- deed, diabetes was recently shown to be the strongest risk factor for lower extremity amputation in new dialysis patients.26
Race Data from cross-sectional studies in Europe suggest that foot ulceration is commoner in Europid subjects when compared to groups of other racial origins. Recent data from the North-West Diabetes Foot Care Study showed that the age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians and African Caribbeans was 5.5, 1.8 and 2.7%, respectively.27 The reasons for these ethnic differences certainly warrant further investigation. In contrast, in the southern United States, ulceration was much more common in Hispanic Americans and native Americans than in non-Hispanic Whites.28 However, there is no sug- gestion that within Europe the risk is related to any geographical differences: Veves et al., for example, showed no differences in risk factors for ulceration according to location, for different European centres.29
Motor Neuropathy Although the commonest neuropathy of diabetes is ‘chronic sensorimotor neuropathy’, most reviews focus exclusively on the sensory components. Thus, special mention is made here of the motor component: small muscle wasting in the feet is common in neuropathy, and atrophy of foot muscles is closely related to the severity of neuropathy.30 Moreover, small muscle dysfunction secondary to neuropathy may contribute to ulcer risk through altered gait and foot pressure changes.
Oedema The presence of peripheral oedema impairs local blood supply and has been associated with increased risk of ulceration.31
Callus The presence of plantar callus, especially in the neuropathic foot, is associated with an increased risk of ulceration: in one study, the risk was 77-fold in the cross-sectional part, whereas in the prospective follow-up, ulceration occurred only at sites of callus, representing an infinite increase in risk.32
JWBK089-05 JWBK089-Boulton April 22, 2006 22:1 Char Count= 0
ASSESSMENT OF FOOT ULCER RISK 57
Deformity Any deformity occurring in a diabetic foot with other risk factors, such as prominence of the metatarsal heads, clawing of the toes, Charcot prominences or hallux valgus, increases ulcer risk. Evidence to support this statement comes from the prospective North-West Diabetes Foot Care Study in which foot deformities were independently related to the risk of new foot ulcers.20
ASSESSMENT OF FOOT ULCER RISK For one mistake made for not knowing, ten mistakes are made for not looking , J.A. Lindsay