TY - JOUR
AU1 - Schumann, Adelaide D.
AU2 - Paxton, Rebecca L.
AU3 - BEng(IT&T), Nicholas S. Solanki, BSc, BMBS,
AU4 - APD, Rochelle J. Kurmis, BND,
AU5 - FRCS(Plast), Ian P. Mackie, MBBS, MD, AFRCS(Ed),
AU6 - PhD, Alexander H.R. Varey, MBChB, MRCS,
AU7 - FRACS, John Edward Greenwood, AM, BSc(Hons), MBChB, MD, FRCS(Plast),
AB - Abstract Vitamin D deficiency has been reported in pediatric burn patients; however, no formal studies have been conducted in adult burn populations. The available literature on vitamin D status in burn patients has been reviewed. A literature search was conducted using Medline™, the Cochrane central register of controlled trials, and EMBASE to identify any trials of vitamin D deficiency in burn patients. Six published studies regarding vitamin D status in burn patients were found; however, five of these were in pediatric populations and several did not assess vitamin D levels as a major endpoint. Vitamin D deficiency has been demonstrated to result in itching, muscle weakness, and neuropathy, all of which are common postburn sequelae. The major source of vitamin D is synthesis in the skin with a small amount being absorbed through dietary intake. Population groups are at higher risk of vitamin D deficiency if they have inadequate exposure to UV light or reduced biosynthetic capability due to skin damage. Burn patients fall into both risk groups and also suffer common complaints that overlap with those reported by patients with vitamin D deficiency. Further research in adult burn patients is needed to determine the prevalence of deficiency in this population and whether vitamin D deficiency might influence postburn injury symptoms reported by patients. Vitamin D plays a pivotal role in modulating a wide variety of physiological processes, illustrated by the presence of a vitamin D receptor1 in most tissues and cells in the body. The importance of adequate sun exposure and the role of the skin in maintaining adequate levels of serum vitamin D has been well established.1 A number of groups at risk of vitamin D deficiency have been identified within the community2,–7; however, an under-recognized population are adult patients with large burns, given their reduced surface area for cutaneous synthesis of vitamin D and their (iatrogenically) limited exposure to sunlight. Several studies undertaken in pediatric burn patients have demonstrated that low serum vitamin D levels are common,8,–11 but no formal studies of vitamin D deficiency have been conducted in adult burn patients. The available literature on vitamin D status in burn patients has been reviewed. BACKGROUND The term “vitamin D” encompasses two compounds. Ergocalciferol (vitamin D2) is formed following ultraviolet (UV) irradiation of the plant steroid ergosterol1,2,12 which is obtained from dietary sources.2,13 Cholecalciferol (vitamin D3) is both synthesized in the skin, from the cholesterol precursor 7-dehydrocholesterol,1,2,12 and ingested from foods such as oily fish, liver, eggs, and fortified foods (eg, margarine).2,13 Both forms of vitamin D are hydroxylated in the liver to form calcidiol (25(OH)D), which is the major circulating form of the vitamin and is commonly used to determine vitamin D levels.1,12,14 Calcidiol undergoes hydroxylation in the kidneys to form the hormone calcitriol (1,25(OH)2D), which is the biologically active form of vitamin D responsible for its metabolic effects.1,2 The majority of vitamin D is synthesized in the skin, catalyzed by exposure to UV light, and provides approximately 80 to 100% of vitamin D in the body.15 This can be achieved with 10 to 15 minutes of midday sun in the summer (which is comparable to 15,000 IU of oral vitamin D16). It has been recognized recently that the prevalence of vitamin D deficiency in the community is much higher than previously thought.15 Several studies have identified particular groups who are at higher risk and certain medical conditions that predispose to vitamin Ddeficiency.1,–7 One study found that levels of vitamin Dwere insufficient in winter/spring in up to 67.3% of adults living in Australia.17 The prevalence of vitamin Ddeficiency amongst younger adults also appears to be higher than expected, with 43% found to be marginally deficient and up to 8% of Australian women aged 20 to 39 years found to be deficient by the end of winter.18 Definitions of vitamin D deficiency and recommendations on supplementation for the United Kingdom, United States of America, and Australia/New Zealand are shown in Tables 1 and 2.19,–24 Table 1. Standardized vitamin D (25-OHD) deficiency levels for the United Kingdom, United States of America, and Australia/New Zealand19,–21 View Large Table 1. Standardized vitamin D (25-OHD) deficiency levels for the United Kingdom, United States of America, and Australia/New Zealand19,–21 View Large Table 2. Vitamin D intake recommendations for the United Kingdom, United States of America, and Australia/New Zealand22,–24 View Large Table 2. Vitamin D intake recommendations for the United Kingdom, United States of America, and Australia/New Zealand22,–24 View Large Patients with large burns commonly experience a range of symptoms that overlap with the symptoms experienced by patients with vitamin D deficiency, including pruritus,25,–28 muscle weakness,29,–34 and peripheral neuropathy.35,–38 Vitamin D deficiency is also known to have a diverse range of effects on the body and causes various known adverse outcomes. These include low bone mineral density,39 increased risk of falls34 and fractures,40,41 impairment in immunological function with impairment of the bacterial killing efficiency of monocytes and macrophages,42,43 and increased mortality from all causes, especially cardiovascular.44,–46 By treating vitamin D deficiency, these adverse effects can potentially be prevented, possibly also improving the common symptoms experienced by burn patients such as itch, muscle weakness, and peripheral neuropathy. METHODS A literature search was conducted using Medline™, the Cochrane central register of controlled trials, and EMBASE to identify any trials of vitamin D deficiency in burn patients. Key medical subject headings search terms used included “burn,” “vitamin D,” and “deficiency.” Reference lists of identified articles were also reviewed to assist identification of related articles not identified in the literature search. RESULTS Six published studies regarding vitamin D status in burn patients were found (Table 3). Five of these were conducted in pediatric populations. In 2002, a group of 24 pediatric patients with burns greater than 40% TBSA were followed up at 2 years (12 patients) and at 7 years (12 patients). They found that in the 2-year group, 10 had low calcidiol levels and 0 had low calcitriol levels. In the 7-year group, they found that 10 had low calcidiol levels and 5 had low calcitriol levels.10 In 2002, a prospective study of 41 pediatric patients with a mean burn size of 52.1% TBSA showed that in the initial week after injury, calcidiol and calcitriol levels were low.47 In 2002, a study of 30 adult burn patients with a mean burn size of 21.1% TBSA examined the endocrine changes after burn injury, in particular looking at bone density. Although not assessing vitamin D levels as a major endpoint, they found that calcidiol levels were usually low or low-normal in their population.48 In 2003, a retrospective review of 104 pediatric patients with burns greater than 40% TBSA was conducted looking for long-bone fractures that developed during the course of healing. Six patients were identified with fractures, and of these four were shown to have low levels of both calcidiol and calcitriol.11 In 2004, a study conducted on 69 pediatric patients with burns greater than 25% TBSA found that 62.3% of all patients had low calcidiol or calcitriol at some point during their admission.8 Another study in 2004, on small numbers of pediatric patients with burns greater than 40% TBSA, looked at skin biopsy samples for vitamin D precursors after exposure to UV-B light. They found that 8 of 11 skin biopsies showed low calcidiol levels.9 Table 3. Results of the literature review on vitamin D deficiency in burn patients View Large Table 3. Results of the literature review on vitamin D deficiency in burn patients View Large DISCUSSION Vitamin D deficiency affects pediatric burn populations, with one study demonstrating that 62.3% had low calcidiol or calcitriol during the acute admission.8 Other studies assessing vitamin D deficiency in pediatric burn populations also revealed its existence, albeit in smaller study groups or retrospectively. Two studies looked at supplementation of vitamin D-deficient patients. One study supplemented ergocalciferol for 2 weeks at 800 IU daily for children younger than 3 years and 1600 IU daily for those older.8 The supplemental dose was doubled every 2 weeks up to a maximum dose of 4000 IU daily if vitamin D levels failed to respond. They found that patients having vitamin D supplementation had consistently lower levels of calcidiol and calcitriol compared with patients not having supplementation and concluded the presence of a malabsorptive defect or an inability to hydroxylate vitamin D. The other study assessing supplementation in pediatric patients with vitamin D deficiency employed 400 IU of ergocalciferol daily.49 This similarly demonstrated that this dose failed to correct the deficiency. Both these studies may have been limited by their choice of vitamin D supplementation, as ergocalciferol is less effective than cholecalciferol on raising serum levels. No studies on isolated vitamin D deficiency in adult burn patients have been conducted; however, the one study of adult burn patients reported that the patients in their population had low or low-normal levels of calcidiol. There are a number of mechanisms by which these patients could become deficient in vitamin D and possibly compounded by deficiency on admission. They receive limited UV radiation during prolonged institutionalisation in the acute burn period and are advised to avoid sun exposure on discharge to prevent or minimise scar hyperpigmentation. Furthermore, the use of pressure garments and wound dressings limit the area of skin available for sun exposure and hence vitamin D production.50 The biosynthetic functions of skin are known to be impaired after burn injury; in both burn skin and adjacent normal skin, levels of 7-dehydrocholesterol are decreased, as well as its subsequent conversion to cholecalciferol following exposure to UV light.9 Abnormalities in the calcium-parathyroid hormone (Ca-PTH) axis postburn are also thought to lead to decreased levels of vitamin D.51 The proinflammatory state induced by burn injury leads to upregulation of PTH calcium receptor52 which in turn leads to inappropriately low levels of circulating PTH and decreased action of 1-α hydroxylase in the kidney. This results in a deficiency of metabolically active vitamin D.51,52 A recent review suggests that replenishment of vitamin D levels can be considered in two phases, restoration and maintenance.53 Restoration of vitamin D levels requires larger doses to be given than for maintenance, because the body stores have a large volume of distribution. However, recent research suggests that giving large doses of vitamin D may itself cause adverse effects.54 Treatment of vitamin D deficiency may also improve common symptoms suffered by burn patients, such as pruritis. A retrospective case series of patients with idiopathic pruritis, rashes, and angioedema treated with vitamin D led to complete resolution of symptoms in a significant proportion of the cohort.55 This has the potential to improve patient quality of life, in addition to the prevention of deficiency-related complications. CONCLUSION Further investigation is required into the prevalence of vitamin D deficiency in adult burn patients. Although numerous studies focus on the effect of vitamin D deficiency on bone quality in postburn injury patients,39,42 there are little data available on the correlation between decreased vitamin D levels and the common postburn sequelae of itch, muscle weakness, and peripheral neuropathy. Symptom relief in the acute care setting also requires investigation as possible outcome measures for deficiency. Further studies are also needed to determine the most appropriate form of supplementation, adequate dosing regimens, and potential need for long-term supplementation. A trial is planned to further investigate these issues. REFERENCES 1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81. 2. Nowson CA, Diamond TH, Pasco JA, Mason RS, Sambrook PN, Eisman JA. Vitamin D in Australia. Issues and recommendations. Aust Fam Physician. 2004;33:133–8. 3. Flicker L, Mead K, MacInnis RJ, et al. Serum vitamin D and falls in older women in residential care in Australia. 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TI - Vitamin D Deficiency in Burn Patients
JF - Journal of Burn Care & Research
DO - 10.1097/BCR.0b013e31824d1c2c
DA - 2012-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/vitamin-d-deficiency-in-burn-patients-3VYuNYlrwP
SP - 731
EP - 735
VL - 33
IS - 6
DP - DeepDyve
ER -