Dermatological conditions such as anhydrosis (lack of sweat production), xerosis (abnormal dryness and scaling of skin), callous and fissuring increase the risk of ulceration in diabetic autonomic neuropathy. Patient education and topical application of emollients are effective in the prevention of these conditions, and may reduce the associated risk of ulceration. However, patient compliance is often difficult to achieve and multiple daily applications of emollient are considered demanding and inconvenient.With this in view, the use of an emollient that is effective in preventing dermatological conditions with a once-daily topical application may improve patient compliance and reduce the risk of diabetic ulceration.This review will consider the risk factors of and the causal pathways towards diabetic foot ulceration, and will discuss the clinical effectiveness of urea-based emollients as a targeted preventative intervention. Jackie Locke, Stuart Baird, Gordon Hendry CLINICAL REVIEW 26 Dermatological Nursing, 2012, Vol 11, No 2 et al, 1990). Arterio-venous shunts are hallmarks of autonomic neuropathy and lead to increased blood flow characterised by a bounding pulse and skin rubor. Arterio-venous shunting results in capillary bypass, decreased capillary bed perfusion and ultimately potential tissue hypoxia (Day, Harkless, 1997, Birke et al, 1992). Day and Harkless (1997) proposed that a reduction in tissue oxygenation and a deficiency of nutrients may alter the robust properties of the skin, putting it at risk of breakdown and ulceration.These complications can result in detrimental effects upon the structural integrity of skin in diabetic foot disease. Diminished perspiration as a result of autonomic neuropathy results in excessive anhydrosis, scaling and xerosis of the skin (Boyko et al, 1999, Day, Harkless, 1997, Birke et al, 1992, Ryder et al, 1990).The plantar aspect of the foot is vulnerable to the consequences of diminished perspiration since the plantar pedal skin lacks sebaceous glands and relies solely on eccrine sweat fluid as its primary source of hydration (Baird et al, 2003). Sato et al (1998) found that dry skin conditions lead to abnormal desmosomal degradation, and subsequently concluded that stratum corneum water content is an important factor in desmosomal degradation.This suggests that dry skin conditions lead to an accumulation of squamous epithelial cells in the stratum corneum. Indeed, diabetes has been associated with thickening of the skin which is measurable via ultrasonography (Van Hattem et al, 2008). Increased skin thickness coupled with anhydrosis appears to be linked to diminished elasticity of the skin in people with diabetes (Yoon et al, 2002). A process known as non-enzymatic glycation (NEG) may also occur in people with diabetes. NEG is where free circulating glucose (where blood glucose is elevated) binds to proteins such as collagen and keratin (Hashmi, 2000, Bennett et al, 1996).This results in a waxy appearance, increased thickness, and a loss of elasticity in the dermis and epidermis due to the cross linking of the skin’s protein molecules (Reihsner et al, 2000, Hashmi, 2000, Schnider, Kohn, 1980). As such, it has been suggested that NEG may lead to the development of soft-tissue contractures of the digits in some people with diabetes (Hashmi, 2000, Bennett et al, 1996).This puts patients with diabetes at further risk as digital deformities often lead to elevated plantar pressures, soft tissue lesions and subsequent ulceration (Yu et al, 2011, Bus et al, 2005). NEG may also impact upon the plantar skin of the foot, leading to alterations in the mechanical properties of the stratum corneum where there is excess thickness as a result of callous formation (Hashmi, 2000). NEG appears to be more common in patients with diabetes who have a history of ulceration compared to those with no history of ulceration (Bennett et al, 1996). Fissures Fissures are small vertical cracks in the epidermis, extending into the dermis, that are usually found in inelastic, thickened skin such as the plantar aspect of the foot and over synovial joints (Zaidi, Lanigan, 2010, Lucke et al, 2006). In patients who have diabetes, fissures can provide portals of entry for fungal or bacterial infection. As such, fissures are considered the main complication of anhydrosis and are implicated in the causal pathways to foot ulceration in patients with diabetes and autonomic neuropathy (O’Donnell et al, 2006, Boyko et al, 1999, Birke et al, 1992). At present, it is unclear how many diabetic foot ulcers are preceded by anhydrotic fissures. However, fissures affecting the foot appear to be common in patients with diabetes. Several cross-sectional studies from the Middle East and Asia have demonstrated that fissures affect the feet in 40-60% of patients with diabetes (Zimmo, 2007, Alavi, 2007,Viswananthan et al, 2000). Xerosis Xerosis, or xeroderma is a dry scaling of the skin, which can occur as part of the ageing process, or in patients with diabetic neuropathy (Baker et al, 2005). Normal skin possesses a lipid content on the surface, and intercellular lipid lamellae which acts as ‘cement’ between corneocytes (Butcher, Brown, 2005). These lipids contribute to the skin’s ability to retain moisture (Buraczewska, 2007) and prevent corneocytes from separation and subsequent fissuring of the epidermis (Butcher, Brown, 2005). Sakai et al (2005) demonstrated that impaired hydration and decreased skin surface lipid content was Jackie Locke is a Lecturer in Podiatry at Glasgow Caledonian University and Associate Teacher at the Department of Podiatry, Southern General Hospital, Glasgow. Stuart A Baird is Professor of Podiatric Medicine at Glasgow Caledonian University. Gordon Henry is a Lecturer in Podiatry at the School of Science and Health, University of Western Sydney, Australia Introduction Increasing evidence suggests that prevention of disease-related foot complications can significantly reduce the costs associated with long-term wound care and surgical amputation (Driver et al, 2010).The World Health Organisation (WHO) and World Diabetes Foundation (WDF) estimate that over 220 million people worldwide (6.4% of the adult population) currently suffer from diabetes. Further, in excess of 2.5 million people The use of urea-based creams in the prevention of diabetic ulceration have been diagnosed with diabetes within the United Kingdom (Diabetes UK, 2010). As such, the economic impact of diabetes and related complications is substantial. The economic cost to the National Health Service is estimated at approximately £9 billion annually (10% of its overall outgoings). Foot infections and ulcerations are common manifestations of diabetes and are considered to be the commonest cause of disease related hospitalisations (Boulton et al, 2005). Diabetes UK (2010) identified that 10% of all people admitted to hospital had diabetes, and that foot disease comprised 25% of all direct hospital costs related to diabetes.The incidence of type 1 and type 2 diabetes is increasing and by the year 2030 an estimated 360 million people are expected to suffer from diabetes (Robertson et al, 2010). Moreover, the incidence of diabetic foot disease is set to rise, since 10% of patients with type 2 diabetes present with major risk factors including peripheral neuropathy and/or vascular disease at diagnosis (Boulton et al, 2005). Macro and micro arterial disease, as well as peripheral motor, sensory and autonomic neuropathies are major risk factors in the pathogenesis of diabetic foot disease.The National Institute for Clinical Excellence (NICE) reports a 20- 40% likelihood that people with diabetes will develop peripheral neuropathy, while 20-40% will develop peripheral vascular disease, and 5% will develop foot ulcers (NICE, 2004).The Scottish Intercollegiate Network Guidelines (SIGN) also identify features such as a history of previous foot ulceration, amputation and the presence of callous as risk factors associated with the development of foot ulcers (SIGN, 2010). The effects of peripheral arterial disease and motor and sensory neuropathies are well documented in the literature that describes the causal pathways for development of diabetic foot disease (see Figure 1). In recent times, the role of autonomic neuropathy has also been identified as a major risk factor for foot ulceration due to its negative impact on microneurovascular function and on the structure and function of the skin (Boyko et al, 1999). Autonomic neuropathy Autonomic neuropathy results in the loss of eccrine sweat gland function, arterio-venous shunts, impairment of the cutaneous hyperaemic response to injury, and impairment of the vasoregulatory response to temperature change (Boyko et al, 1999). Increased venous pressure and stasis also occurs due to loss of the vasomotor reflex.This results in peripheral tissue oedema, which further inhibits the healing process (Birke et al, 1992, Ryder CLINICAL REVIEW 27 Dermatological Nursing, 2012, Vol 11, No 2 KEY WORDS Diabetic autonomic neuropathy Ulceration Urea-based emollients Patient compliance Targeted preventative intervention Figure 1. The causal pathways towards diabetic foot ulceration. (Merza, Tesfaye, 2003, with kind permission.) Peripheral vascular disease Orthopaedic problems Limited joint mobility Raised foot pressure Motor Small muscle wasting Sensory Decreased pain and properioception Autonomic Dry skin Callus Ischaemia Neuropathy DIABETES MELLITUS FOOT ULCERATION