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Original paper

The relationship between severity of disease and vitamin D


levels in children with atopic dermatitis

Ozlem Su1, Anl Glsel Bahal1, Ayegl Doan Demir2, Dilek Byk Ozkaya1, Seluk Uzuner2, Didem Dizman1,
Nahide Onsun1

Department of Dermatology, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey


1

Department of Pediatrics, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey


2

Adv Dermatol Allergol 2017; XXXIV (3): 224227


DOI: https://doi.org/10.5114/pdia.2017.66054

Abstract
Introduction: Atopic dermatitis (AD) is achronic relapsing inflammatory skin disorder. Vitamin D is aliposoluble
vitamin synthesized mainly in the skin. Vitamin D has several effects on the skin.
Aim: To assess the serum level of vitamin D in children with AD and determine its relation to AD severity.
Material and methods: Sixty patients with AD were enrolled in the study. We evaluated disease severity using the
SCORing Atopic Dermatitis (SCORAD) index. The control group consisted of 37 healthy subjects.
Results: The mean serum concentration of 25(OH)D3 in patients with AD was not statistically different from control
subjects (p = 0.065). The vitamin D level was significantly lower in moderate and severe AD compared with mild
AD, and this difference was statistically significant (p = 0.001 and p = 0.004). Vitamin D showed anegative cor-
relation with serum total IgE levels (p = 0.007). There was no significant correlation between total IgE levels and
SCORAD scores (p = 0.089).
Conclusions: This study suggests that alow serum vitamin D level is inversely associated with severity of AD in
children. Vitamin D has not been included in the routine treatment of AD because of the conflicting results of vari-
ous studies. Thus, there is aneed for more detailed and prospective studies.
Key words: atopic dermatitis, vitamin D, SCORing Atopic Dermatitis.

Recently, there have been several reports that low vita-


Introduction
min D plays arole in the pathogenesis of many conditions,
Atopic dermatitis (AD) is achronic relapsing inflam- such as autoimmune diseases, infections, malignancies,
matory skin disorder. It is characterized by pruritus, cardiovascular disease, neuropsychiatric disorders, and
eczematous plaques, and adefective skin barrier. The allergic diseases, including AD [46]. Several studies have
ethiopathogenesis of AD is multicomplex and not yet reported on vitamin D levels in AD patients, vitamin D
fully understood. New concepts have emerged that dem- supplementation in the treatment of AD, and the relation-
onstrate immunological and inflammatory dysfunction ship between vitamin D levels and AD severity. However,
in AD, in addition to the importance of environmental the results have been conflicting [1, 711].
factors.
Vitamin D is aliposoluble vitamin synthesized mainly
in the skin. It is involved in important regulatory mech- Aim
anisms of the innate and adaptive immune system, in In this study, we investigated the correlation between
addition to its roles in calcium homeostasis and bone serum levels of 25-hydroxyvitamin D (25(OH)D3) and AD
metabolism. It also has several effects on the skin, in- severity.
cluding normal keratinocyte development and function,
increased wound-healing, decreased inflammation, and
the stimulation of protein synthesis, such as filaggrin, Material and methods
which is necessary for stratum corneum barrier forma- Sixty patients (age range: 216 years) who were diag-
tion [13]. nosed with AD at an outpatient clinic, and followed regu-

Address for correspondence: Anil Glsel Bahal MD, Department of Dermatology, Medical Faculty, Bezmialem Vakif University,
34093 Fatih, Istanbul, Turkey, phone: +90 212 453 17 00-5912, +90 505 3893280, fax: +90 212 621 75 80, e-mail: [email protected]
Received: 21.12.2015, accepted: 29.04.2016.

224 Advances in Dermatology and Allergology 3, June / 2017


The relationship between severity of disease and vitamin D levels in children with atopic dermatitis

larly from December 2013 to March 2015, were enrolled min D levels according to season, there was asignificant
in the study. Clinical evaluation, the SCORAD index, and difference within the AD group, with mean levels in the
laboratory analysis results, including the level of total IgE, winter/spring period much lower than for the summer/
and 25(OH)D3 serum concentration, were collected retro- fall period (p = 0.008), but there were no differences in
spectively from the patients records. Patients with miss- the control group (p = 0.855).
ing records were excluded from the study. The control On the SCORAD examination, 31 patients had mild
group consisted of 37 healthy subjects with no history or AD, 20 had moderate AD, and 6 had severe AD. Asignifi-
symptoms of allergic disease. The diagnosis of AD was cant inverse relationship between SCORAD scores and
based on the criteria of Hanifin and Rajka. The severity vitamin D levels was found (Figure 1). Also, the relation-
of AD was assessed by the same dermatologist using the ship between vitamin D levels and SCORAD scores was
scoring atopic dermatitis (SCORAD) index: mild AD (15), assessed among patients with mild, moderate, and se-
moderate AD (1540), and severe AD (> 40). Although vere AD. The vitamin D level was significantly lower in
there is currently no consensus for optimal levels, vita- moderate and severe AD compared with mild AD, and
min D levels were categorized as sufficient (2580 ng/ this difference was statistically significant (p = 0.001
ml), insufficient (1024 ng/ml), or deficient (010 ng/ml). and p = 0.004). However, there was no difference be-
The patients and controls were also categorized accord- tween the moderate and severe groups (p = 0.992). The
ing to season: winter/spring (December 1 to May 31) and mean serum IgE level of the AD patients was 520.27, with
summer/fall (June 1 to November 30). aminimum of 1.00 and amaximum of 4,181. Vitamin D
The 25(OH)D3 serum concentrations in the AD pa- showed anegative correlation with serum total IgE levels
tients were compared with acontrol group. The level of (Figure 2) (p = 0.007). There was no significant correla-
vitamin D was evaluated in relationship to the severity of tion between total IgE levels and SCORAD scores (p =
AD and the total IgE. The age, sex, and seasonal charac- 0.089) (Figure 3).
teristics of the groups in relationship to vitamin D were
investigated.
Discussion
Statistical analysis There have been several reports on the association
Specific information was presented as means, per- between allergic disease and vitamin D. Recent data have
centages, and standard deviations. Categorical variables shown that vitamin D affects immune mechanisms, ke-
were compared using the 2 test, and the averages of the ratinocytes, and skin barrier function. Vitamin D is con-
two subgroups were assessed with at-test. When the ef- sidered to play an important role in the development of
fect of age was evaluated as acovariate, the same com- allergic skin diseases, including AD, due to these effects.
parison was measured by acovariance test. Statistical Although the majority of studies have demonstrated an
analyses were conducted using IBM SPSS version 20.0. inverse relationship between vitamin D levels and the
Ap-value of 0.05 was considered significant. prevalence or severity of AD, there is no consensus about
the results of previous studies. Some studies have sug-
gested that ahigh intake of vitamin D or an elevated se-
Results rum vitamin D level in infancy or during gestation can be
Sixty patients (30 males and 30 females) with AD associated with the development of eczema and asthma
were enrolled in the study. The patients age ranged later in childhood. Thus, some studies have shown that
between 2 and 16 years (mean: 8.37 years). The control vitamin D is aprotective factor for allergic disease, while
group was composed of 37 patients (16 males and 21 fe- others have shown that it is arisk factor for AD [1, 1214].
males), aged 214 years (mean: 6.54). The differences In the literature, Cheon et al., Wang et al., and Han
for age between the groups were eliminated by analy- et al. have reported that the level of 25(OH)D was signifi-
sis of covariance. No significant relationship was found cantly lower in patients with AD than in control groups.
between the vitamin D level and age. The mean serum Samochocki et al. observed no statistically significant
levels of vitamin D in the patients with AD and in the differences in the level of serum vitamin D in adult AD
control group were 16.13 6.72 and 19.76 10.4 ng/ml, patients when compared with controls. Thuesen et al.
respectively, with no statistically significant difference investigated 2308 patients with an allergic disease such
between the groups (p = 0.065). as asthma, atopy or atopic dermatitis. They found no
With regard to the assessment according to season, significant associations between vitamin D and these
43 of the AD patients were enrolled in the winter/spring, allergic diseases. In our study, we found that vitamin D
and 17 were enrolled in the summer/fall. In the control levels were lower in AD patients, but not statistically sig-
group, 21 patients were enrolled in the winter/spring, and nificantly [3, 911, 15].
16 in the summer/fall. There were no significant differ- Afew studies have shown that vitamin D deficiency
ences between the AD and control groups with respect is associated with greater severity of AD, whereas others
to sex or seasonality. In the assessment of serum vita- revealed no correlation. Peroni et al. reported an inverse

Advances in Dermatology and Allergology 3, June / 2017 225


Ozlem Su, Anl Glsel Bahal, Ayegl Doan Demir, Dilek Byk Ozkaya, Seluk Uzuner, Didem Dizman, Nahide Onsun

correlation between the serum concentration of 25(OH)D3


35
and severity of AD in 37 children [16]. According to the
30
results of Wangs study, the severity of AD was inversely
correlated with vitamin D deficiency in Chinese children
25
living in Hong Kong. In contrast to our findings, Chiu et
al. evaluated 94 children with AD, but they found no sta-
Vitamin D

20
tistically significant correlation between vitamin D level
and severity of disease [17]. The same results of no sig-
15
nificant correlation were reported by Han et al. and by
Samochocki et al. [3, 911, 16, 17].
10 In this study, we demonstrated that vitamin D lev-
els were significantly lower in moderate and severe AD
5 compared with mild AD. This finding is the same as the
results of El Taieb et al., who reported anegative correla-
0 20 40 60 80 tion between vitamin D and severity of AD. In fact, these
SCORAD
results support our other findings as reported above [18].
Figure 1. Inverse correlation between severity of atopic der- Vitamin D has asignificant role in Th1-Th2 balance. In
matitis and vitamin D addition, it has been reported that vitamin D receptor ago-
nists suppress IgE production in cultured human B cells
and in an allergy mouse model. Brehm et al. reported that
35 lower vitamin D levels are associated with increased al-
lergy markers, such as total IgE, in children with asthma. In
30 studies on AD patients, Wang et al. and Cheon et al. found
an inverse correlation between vitamin D and total IgE,
25 similar to our findings [9, 10, 12, 19, 20].
We did not find asignificant correlation between
Vitamin D

20 SCORAD and IgE. In contrast, Cheon et al. found that the


SCORAD index was positively correlated with total IgE
15 levels [10]. Total IgE may not be high in all patients with
AD [21].
10 Several studies have reported an inverse association
between sunlight exposure and AD severity. Thus, the
5 severity of AD might increase during the winter period.
0 1000 2000 3000 4000 5000 Vitamin D levels are affected by seasonal differences,
IgE and are much lower in winter than in summer because
Figure 2. Inverse correlation between total IgE and vitamin D sunlight UVB exposure increases vitamin D serum lev-
els. This idea is supported by clinical observations. In
2014, Camargo et al. investigated the role of oral vitamin
D supplementation in children with winter-related AD.
5000 They reported that this treatment led to clinical improve-
ment in AD [2, 7, 22]. In our study, patients who were
evaluated during the winter/spring had higher SCORAD
4000
indices and lower vitamin D levels. This result was not
surprising due to much less exposure to solar radiation
3000 during this season.
There are studies that assessed the association be-
IgE

2000 tween vitamin D treatment and AD. The results are con-
flicting. Di Filippo et al. investigated 39 children with AD.
The patients were treated with 1,000 IU/day (25 mg/day)
1000
oral vitamin D for 3 months. They evaluated the vitamin D
serum levels and SCORAD index before and after treat-
0 ment. They reported that vitamin D treatment may be
0 20 40 60 80
an effective way for reducing AD severity. Also, Ameste-
SCORAD jani et al. reported arandomized, double-blind, placebo-
controlled study in which 60 patients with AD were en-
Figure 3. No correlation between SCORAD and IgE
rolled. The patients were divided into two groups. One

226 Advances in Dermatology and Allergology 3, June / 2017


The relationship between severity of disease and vitamin D levels in children with atopic dermatitis

of the groups was treated with vitamin D (1,600 IU/day), 6. Kucharska A, Szmuro A, Siska B. Significance of diet in
the other was treated with placebo. After 60 days, they treated and untreated acne vulgaris. Adv Dermatol Allergol
found that supplementation with oral vitamin D signifi- 2016; 33: 81-6.
7. Camargo CA Jr, Ganmaa D, Sidbury R, et al. Randomized trial
cantly improved disease severity in patients according to of vitamin D supplementation for winter-related atopic der-
SCORAD and TIS (Three Item Severity score) [8, 23]. matitis in children. J Allergy Clin Immunol 2014; 134: 831-5.
In the literature, different data were reported in the 8. Amestejani M, Salehi BS, Vasigh M, et al. Vitamin D supple-
results of many studies. These conflicting results may be mentation in the treatment of atopic dermatitis: aclinical
associated with geographic location, age, season, ethnic- trial study. J Drugs Dermatol 2012; 11: 327-30.
9. Wang SS, Hon KL, Kong AP, et al. Vitamin D deficiency is
ity, and environmental factors. Most vitamin D functions
associated with diagnosis and severity of childhood atopic
occur through vitamin D receptors (VDR). It is known that dermatitis. Pediatr Allergy Immunol 2014; 25: 30-5.
VDR may have effects on the regulation of the epidermal 10. Cheon BR, Shin JE, Kim YJ, et al. Relationship between serum
barrier function and cutaneous immune responses. Heine 25-hydroxyvitamin D and interleukin-31 levels, and the se-
et al. showed that VDR gene polymorphisms in patients verity of atopic dermatitis in children. Korean J Pediatr 2015;
with severe AD. Hallau et al. reported that altered vitamin 58: 96-101
11. Samochocki Z, Bogaczewicz J, Jeziorkowska R, et al. Vitamin
D metabolism due to genetic variances have impacts on
D effects in atopic dermatitis. Am Acad Dermatol 2013; 69:
the pathogenesis of AD. VDR gene variations may result 238-44.
in altered responsiveness to vitamin D [2, 24, 25]. In ad- 12. Dbiska A, Sikorska-Szaflik H, Urbanik M, Boznaski A. The
dition, there were several limitations among previous role of vitamin D in atopic dermatitis. Dermatitis 2015; 26:
studies on the relationship between vitamin D and AD, 155-61.
such as alack of standardization for serum vitamin D 13. Gale CR, Robinson SM, Harvey NC, et al.; Princess Anne Hos-
pital Study Group. Maternal vitamin D status during preg-
measurements. In addition, the diagnosis and severity
nancy and child outcomes. Eur J Clin Nutr 2008; 62: 68-77.
of AD was evaluated by different physicians, which may 14. Bck O, Blomquist HK, Hernell O, Stenberg B. Does vitamin
contribute to the differing results. D intake during infancy promote the development of atopic
allergy? Acta Dermatol Venereol 2009; 89: 28-32.
15. Thuesen BH, Heede NG, Tang L, et al. No association be-
Conclusions tween vitamin D and atopy, asthma, lung function or atopic
Vitamin D has not been included in the routine treat- dermatitis: aprospective study in adults. Allergy 2015; 70:
1501-4.
ment of AD because the conflicting results of various
16. Peroni DG, Piacentini GL, Cametti E, et al. Correlation between
studies are still controversial. Certain studies in the litera- serum 25-hydroxyvitamin D levels and severity of atopic der-
ture, as well as our findings, have shown that there is an matitis in children. Br J Dermatol 2011; 164: 1078-82.
inverse correlation between vitamin D and the severity 17. Chiu YE, Havens PL, Siegel DH, et al. Serum 25-hydroxyvita-
of AD. This is true especially during winter, when patients min D concentration does not correlate with atopic derma-
have lower vitamin D levels and higher SCORAD indices. titis severity. J Am Acad Dermatol 2013; 69: 40-6.
18. El Taieb MA, Fayed HM, Aly SS, Ibrahim AK Assessment of
Thus, we think that vitamin D supplementation for the serum 25-hydroxyvitamin D levels in children with atopic
treatment of AD would be useful, especially during the dermatitis: correlation with SCORAD index. Dermatitis 2013;
winter period. However, there is aneed for more detailed 24: 296-301.
and prospective studies. 19. Hartmann B, Heine G, Babina M, et al. Targeting the vitamin
D receptor inhibits the B cell-dependent allergic immune re-
sponse. Allergy 2011; 66: 540-8.
Conflict of interest 20. Brehm JM, Celedn JC, Soto-Quiros ME, et al. Serum vita-
min D levels and markers of severity of childhood asthma
The authors declare no conflict of interest. in Costa Rica. Am J Respir Crit Care Med 2009; 179: 765-71.
21. Ahmed I, Nasreen S. Frequency of raised serum IgE level in
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