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Vitamin D Deficiency in Burn Patients

Adelaide D. Schumann,* Rebecca L. Paxton,* Nicholas S. Solanki, BSc, BMBS, BEng(IT&T),


Rochelle J. Kurmis, BND, APD, Ian P. Mackie, MBBS, MD, AFRCS(Ed), FRCS(Plast),
Alexander H.R. Varey, MBChB, MRCS, PhD,
John Edward Greenwood, AM, BSc(Hons), MBChB, MD, FRCS(Plast), FRACS
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. (J Burn Care Res 2012;33:731735)

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 community27; 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
From the *Medical School, University of Adelaide, Adelaide, South
Australia; Adult Burn Centre, Royal Adelaide Hospital,
North Terrace, Adelaide, South Australia; and the Department of Plastic and Reconstructive Surgery, Frenchay Hospital,
Bristol, United Kingdom.
Address correspondence to Assoc. Prof. John Edward Greenwood,
AM, Adult Burn Centre, Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia. Email: john.greenwood@
health.sa.gov.au
Copyright 2012 by the American Burn Association.
1559-047X/2012
DOI: 10.1097/BCR.0b013e31824d1c2c

D levels are common,811 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
731

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732 Schumann et al

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 D
deficiency.17 One study found that levels of vitamin D
were insufficient in winter/spring in up to 67.3% of
adults living in Australia.17 The prevalence of vitamin D
deficiency 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 2.1924
Patients with large burns commonly experience a
range of symptoms that overlap with the symptoms
experienced by patients with vitamin D deficiency,
including pruritus,2528 muscle weakness,2934 and
peripheral neuropathy.3538 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.4446 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, vitaminD,
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

Table 1. Standardized vitamin D (25-OHD) deficiency levels for the United Kingdom, United States of America, and
Australia/New Zealand1921
Deficiency Level

UK Reference
Range

USA Reference
Range

Australia/NZ Reference Range

Severe deficiency
Deficient
Mild deficiency
Adequate
Optimal
Upper limit associated with adverse effects

<25 nmol/L
2550 nmol/L
5075 nmol/L
>75 nmol/L

<30 nmol/L
3050 nmol/L
>50 nmol/L

>125 nmol/L

<12.5 nmol/L
12.525 nmol/L
2550 nmol/L
>50 nmol/L (75100 nmol/L if >65 yr of age)

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Schumann et al 733

Table 2. Vitamin D intake recommendations for the United Kingdom, United States of America, and Australia/New
Zealand2224
Age Group
(yr)

UK
(Reference Nutrient Intake)

USA
(Recommended Dietary Allowance)

10 g/d (400 IU)

600 IU
600 IU
600 IU/800 IU

1950
5065
>65/>70

UV-B light. They found that 8 of 11 skin biopsies


showed low calcidiol levels.9

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

Australia/NZ
(Adequate Intake, No Recommended
Dietary Intake Available)
5 g/d (200 IU)
10 g/d (400 IU)
10 g/d (400 IU)/15 g/d (600 IU)

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

Table 3. Results of the literature review on vitamin D deficiency in burn patients

Study

Study
Design

Klein
et al10

Prospective
cohort

Wray
et al47

Prospective
cohort

Population Size
24 pediatric
patients
(12 patients
assessed at
2 yr postburn,
12 patients at
7 yr postburn)
41 pediatric
patients

% TBSA of
Population
>40%

Related
Outcome
Measures
Calcidiol and
calcitriol in
blood

Mean 53.1%

Calcidiol and
calcitriol in
blood

Prospective
30 adult patients
cohort
Retrospective 104 pediatric
review
patients of which
6 had sustained
long-bone
fractures
Gottschlich Prospective
69 pediatric
et al24
cohort
patients

Mean 21.1%

Calcidiol levels

Klein
et al9

Mean TBSA
52%

Dolecek
et al48
Mayes
et al11

Prospective
cohort

11 pediatric
patients

>40%

>25%

Calcidiol and
calcitriol
levels in
blood

Results
2-yr group: 83.3% had
low calcidiol, 0.0%
had low calcitriol;
7-yr group: 90.9%
had low calcidiol,
45.5% had low
calcitriol.
In the initial week,
mean calcidiol was
low at 29 nmol/L,
and mean calcitriol
was low at 33
pmol/L
Calcidiol levels were
low or low-normal
66.7% of those with a
long-bone fracture
had low calcidiol and
calcitriol

Vitamin D Deficiency
Level Used
Calcidiol < 37 nmol/L,
calcitriol < 36 pmol/L

Calcidiol < 37 nmol/L,


calcitriol < 36 pmol/L

Unknown

Low: calcidiol <45 nmol/L,


calcitriol <48 pmol/L,
very low: calcidiol <20
nmol/L, calcitriol
<20.8 pmol/L
Calcidiol and
62.3% had low calcidiol Calcidiol <37.4 nmol/L,
calcitriol levels
or calcitriol
calcitriol <38.8 pmol/L
in blood
Calcidiol and
72.7% had low calcidiol; Calcidiol <37 nmol/L,
calcitriol in
all had normal
calcitriol <12 pmol/L
skin biopsy
calcitriol
samples

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734 Schumann et al

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-
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.
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