Serum Vitamin D level - The effect on the clinical course of psoriasis

Abstract

Introduction:
Psoriasis is a hyperproliferative disorder of the skin, and vitamin D analogs are widely used in its treatment. It is evident that ultraviolet radiation enables vitamin D3 (cholecalciferol) formation in the epidermis, and this product is further converted into the active metabolites 25-hydroxycholecalciferol and 1,25-hydroxycholecalciferol, which exert several important effects on the skin. The disruption in proper functioning of the skin which occurs in psoriasis leads to a loss of capacity for cutaneous synthesis of vitamin D3. In consequence, it activates a vicious circle that impairs homeostasis of the skin and results in a progressive decrease in the level of vitamin D in the whole human body.

Aim:
To estimate the prevalence of vitamin D serum deficiency in patients with psoriasis and analyse the association of vitamin D food intake with clinical features.

Material and methods:
Forty adults with psoriasis and 40 healthy subjects (control group) were recruited. Psoriasis plaques were diagnosed and evaluated by the PASI scale. Collected blood samples enabled measurement of serum vitamin D level by assessment with the immunoenzyme technique.

Results:
The analysis with the Mann-Whitney U test revealed a statistically significant difference in 25-hydroxycholecalciferol level between healthy individuals and patients with psoriasis (p = 0.048). In both groups (control and psoriatic) the level of 25-hydroxycholecalciferol was seriously deficient (< 50 nmol/l). There was also a negative correlation of 25-hydroxycholecalciferol serum level with both PASI (r = -0.43) and the duration of psoriasis (r = -0.53).

Conclusions:
It is necessary to bear in mind that not only the ingestion of food rich in vitamin D is necessary, but also the production of vitamin D with sun exposure. The quantity of 25-hydroxycholecalciferol is very important both in the general population and in patients with psoriasis, because these groups have a distinct metabolism.

Full text

Advances in Dermatology and Allergology 6, December / 2016 445
Original paper
Address for correspondence: Beata Bergler-Czop, 2a Leśna St, 42-624 Ossy, Poland, phone/fax: +48 32 284 08 77, e-mail: bettina2@tlen.pl
Received: 21.07.2015, accepted: 26.10.2015.
Serum vitamin D level – the eect on the clinical course
of psoriasis
Beata Bergler-Czop, Ligia Brzezińska-Wcisło
Department of Dermatology, School of Medicine, Medical University of Silesia, Katowice, Poland
Adv Dermatol Allergol 2016; XXXIII (6): 445–449
DOI:10.5114/ada.2016.63883
Abstract
Introduction: Psoriasis is a hyperproliferative disorder of the skin, and vitamin D analogs are widely used in its
treatment. It is evident that ultraviolet radiation enables vitamin D3 (cholecalciferol) formation in the epidermis,
and this product is further converted into the active metabolites 25-hydroxycholecalciferol and 1,25-hydroxychole-
calciferol, which exert several important eects on the skin. The disruption in proper functioning of the skin which
occurs in psoriasis leads to a loss of capacity for cutaneous synthesis of vitamin D3. In consequence, it activates
a vicious circle that impairs homeostasis of the skin and results in a progressive decrease in the level of vitamin D
in the whole human body.
Aim: To estimate the prevalence of vitamin D serum deciency in patients with psoriasis and analyse the associa-
tion of vitamin D food intake with clinical features.
Material and methods: Forty adults with psoriasis and 40 healthy subjects (control group) were recruited. Psoriasis
plaques were diagnosed and evaluated by the PASI scale. Collected blood samples enabled measurement of serum
vitamin D level by assessment with the immunoenzyme technique.
Results: The analysis with the Mann-Whitney U test revealed a statistically signicant dierence in 25-hydroxycho-
lecalciferol level between healthy individuals and patients with psoriasis (p = 0.048). In both groups (control and
psoriatic) the level of 25-hydroxycholecalciferol was seriously decient (< 50 nmol/l). There was also a negative cor-
relation of 25-hydroxycholecalciferol serum level with both PASI (r = –0.43) and the duration of psoriasis (r = –0.53).
Conclusions: It is necessary to bear in mind that not only the ingestion of food rich in vitamin D is necessary, but
also the production of vitamin D with sun exposure. The quantity of 25-hydroxycholecalciferol is very important
both in the general population and in patients with psoriasis, because these groups have a distinct metabolism.
Key words: psoriasis, 25-hydroxycholecalciferol, serum level.
Introduction
Psoriasis is a hyperproliferative disorder of the skin,
and vitamin D3 analogs are widely used in its treatment.
There are several agents, such as tacalcitol, calcipotriol
and the recently approved maxacalcitol, which are ad-
ministered either as monotherapy or in combination
with topical steroids, such as betamethasone dipro-
pionate, in the treatment of psoriasis. These analogs
exert prodierentiating and antiproliferative eects on
keratinocytes, and additionally they manifest important
anti-inammatory properties [1].
The active form of vitamin D3, 1,25-dihydroxyvitamin
D3, is well known for its inuence on bones and control
of calcium and phosphate homeostasis. It is now evi-
dent that 1,25(OH)2D3 exerts much more eects in vari-
ous tissues which express the vitamin D receptor (VDR)
or possess certain enzymes – those necessary for gener-
ation of 1,25(OH)2D3 by activating hydroxylation of vita-
min D3 metabolites. It is believed that most tissues have
the ability to convert vitamin D3 into its active form,
1,25(OH)2D3, which in turn binds to the VDR and forms
the 1,25(OH)2D3/VDR complex, which subsequently reg-
ulates the expression of several genes. Among special
properties of 1,25(OH)2D3 are both a prodierentiating
and an antiproliferative inuence on normal and cancer
cells, as well as some immunomodulatory eects. These
aspects are very desirable; however, excessive doses of
1,25(OH)2D3 are known to result in hypercalcemia. It
could potentially limit the use of 1,25(OH)2D3 analogs
in any therapy, but synthetic analogs are administered
topically, which reduces the risk of calcemic side eects

Advances in Dermatology and Allergology 6, December / 2016446
Beata Bergler-Czop, Ligia Brzezińska-Wcisło
and simultaneously preserves all benecial eects of
1,25(OH)2D3 [1–4].
There has been a lot of speculation in evaluation of the
optimal concentration of vitamin D and a threshold below
which a vitamin D insuciency is recognized. The reference
concentration for vitamin D (25-hydroxycholecalciferol) is
considered to be 30–50 ng/ml (75–125 nmol/l), while a se-
rum level below 20 ng/ml (or 50 nmol/l) indicates vitamin
D deciency. The problem of vitamin D insuciency seems
to be very common in Europe and the USA, and some es-
timations suggest its prevalence in the general population
to be as high as 50%. Undoubtedly, the low level of vitamin
D leads to a pathological condition with muscle weakness,
rickets or osteomalacia, which are complications of poor
prognosis [5].
The role of vitamin D is considered to vary, and
some evidence suggests vitamin D to be a modulatory
factor of the activity in dendritic cells and keratino-
cytes, or the proliferation in T-cells. All metabolites of
vitamin D act via the VDR, which is expressed in many
tissues, including the skin. It is evident that ultraviolet
radiation enables vitamin D3 (cholecalciferol) formation
in the epidermis, and this product is further converted
to the active metabolites 25-hydroxycholecalciferol and
1,25-hydroxycholecalciferol3, which have an inuence
on cutaneous functions. One of these metabolites,
25-hydroxycholecalciferol, manifests double activity in
keratinocytes, by inhibition of their proliferation and
enhancement of the maturity. Taking such influence
on keratinocytes into consideration, a deficiency in
25-hydroxycholecalciferol could be a risk factor for the
development of psoriasis with possible involvement of
disturbances in the cellular immune system (T lympho-
cytes), as well as in angiogenesis [1, 5, 6]. It is believed
that psoriasis could activate a vicious circle with severe
impairment of cutaneous functions and, secondarily,
a progressive decrease in the level of vitamin D3 deriva-
tives in the whole human body, including the skin.
Aim
The aim of this study was to estimate the prevalence
of vitamin D serum deciency in patients with psoriasis
and perform further analysis of the association of vita-
min D food intake with clinical features.
Material and methods
Forty adults with psoriasis and 40 subjects (healthy
control group) were recruited. All patients with psoriasis
and all control group subjects agreed to participate in the
study. Informed consent was obtained from all subjects.
For publication of patient photos, consent to publish was
obtained. All the participants were asked to complete
the specic questionnaire. The obtained data included
age, gender, duration of psoriasis, concomitant diseases
and medications. In the group of patients psoriasis was
moderate to severe. Psoriasis plaques were diagnosed
and evaluated by a specialized medical team with as-
sessment of the Psoriasis Area and Severity Index (PASI).
All patients were seen by a dermatologist, who collected
data considering the demographic, health status and
any other relevant details. Cases were age- and gender-
matched for comparison. Collected blood samples en-
abled measurement of the serum level of a vitamin D3
derivative (25-hydroxycholecalciferol) using an immuno-
enzyme assessment technique (25(OH)-Vitamin D Xpress
ELISA kit Immundiagnostik AG, Germany). Sensitivity of
the method is 6.2 nmol/l, in-series error 6%, inter-series
error 7.4%.
All measurements were conducted during winter
months to avoid the inuence of sun exposure on syn-
thesis of vitamin D3 and its derivative 25-hydroxychole-
calciferol (Table 1).
The results were referred to normal serum ranges
of 25-hydroxycholecalciferol according to the American
Society for Bone and Mineral Research 2011: deciency
(seriously deficient): < 50 nmol/l; insufficiency (defi-
cient): 50–74 nmol/l; suciency (adequately supplied):
> 75 nmol/l.
Statistical analysis
Initially, all results obtained from patients and
healthy controls were compared using the Shapiro-Wilk
test. Subsequently, the Mann-Whitney U test was used
to compare the quantitative variables. Correlations were
estimated by nonparametric Spearman’s rank test. In
this study, a p-value of < 0.05 was considered to be sta-
tistically signicant.
Results
Results was presented in Tables 2–4.
The analysis with the Mann-Whitney U test revealed
a statistically signicant dierence in 25-hydroxychole-
Table 1. Reference intervals for 25(OH)-vitamin D3 (ng/ml),
males and females
Age N2.5% 97.5%
0 to < 3 months 131 5 42
3 to < 6 months 135 9 60
6 months to < 1 year 147 18 58
1 to < 3 years 394 15 54
3 to < 10 years 619 14 46
10 to < 13 years 286 11 50
13 to < 15 years 275 10 44
15 to < 18 years 390 8 45
< 18 years 421 8 56
Conversion factor: 1 ng/ml = 2.5 nmol/l, 1 nmol/l = 0.4 ng/ml.

Advances in Dermatology and Allergology 6, December / 2016
Serum vitamin D level – the eect on the clinical course of psoriasis
447
calciferol level between healthy individuals and patients
with psoriasis (p = 0.048) (Figure 1). In both groups (con-
trol and psoriatic) the level of 25-hydroxycholecalciferol
was seriously deficient (< 50 nmol/l). There was also
a negative correlation of 25-hydroxycholecalciferol se-
rum level with both PASI (r = –0.43) and the duration of
psoriasis (r = –0.53) (Figure 2).
Discussion
Vitamin D3 and its analogs exhibit a strong antiprolif-
erative and prodierentiating inuence on both normal
and malignant cell types. Several vitamin D3 analogs have
been approved for the treatment of psoriasis, osteopo-
rosis or secondary hyperparathyroidism, and frequently
they comprise the rst or second-line treatment option.
The exact mechanism of action of vitamin D analogs
still requires further elucidation. Undoubtedly, the reason
why specic analogs manifest superagonistic activity in
specic tissues remains unknown, although several stud-
ies have tried to clarify the mechanisms behind these
tissue-specic eects. Moreover, since some cell types
22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
25-hydroxycholecalciferol
Table 2. Serum level of 25-hydroxycholecalciferol, PASI, age and duration of psoriasis in patient group and control group
Parameter N Mean Median Min. Max. SD
Study group 40 32.25 29.75 23.59 48.12 6.79
PASI 40 10.36 11.15 1.20 28.00 6.26
Age 40 41.55 41.50 18.00 76.00 14.42
Duration of psoriasis 40 12.89 11.50 0.50 40.00 9.01
D_control 40 56.13 55.34 49.65 86.57 6.82
Table 3. 25-hydroxycholecalciferol serum level in male group
Group N Mean Median Min. Max. SD
Study 19 31.97 29.77 23.59 44.81 6.16
D_control 19 57.62 56.18 50.33 86.57 8.16
Table 4. 25-hydroxycholecalciferol serum level in female group
Group N Mean Median Min. Max. SD
Study 21 32.50 28.91 24.58 48.12 7.46
D_control 21 54.77 53.55 49.65 71.23 5.17
Figure 2. Negative correlation between 25-hydroxychole-
calciferol serum level and PASI (r = –0.43) and psoriasis
duration (r = –0.53)
Figure 1. Signicant dierence between 25-hydroxycho-
lecalciferol serum level in control group and in group of
patients with psoriasis (p = 0.048)
80
70
60
50
40
30
20
10 25-hydroxycholecalciferol Control
Mean Mean ± SD Mean ±1.96 × SD
Serum level
13
12
11
10
9
8
7
6
5
4
3
PASI
r = –0.4127
0.95% CI

Advances in Dermatology and Allergology 6, December / 2016448
Beata Bergler-Czop, Ligia Brzezińska-Wcisło
prefer specic catabolism pathways and enzymes above
others, the degradation process may also contribute to
the tissue-specic activity of vitamin D analogs. The af-
nity for the vitamin D binding protein (DBP) may also
play a role in the activity of vitamin D analogs, because
it regulates the bioavailability of vitamin D for tissues [1,
7, 8]. The relation between 25-hydroxycholecalciferol and
psoriasis has been studied since the 1930s. A chance dis-
covery was reported in 1985 by Morimoto et al., who no-
ticed that the administration of vitamin D3 could improve
psoriasis in some cases [8]. The new synthetic analogs
of vitamin D, such as tacalcitol and calcipotriol, present
lower hypercalcemic activity with simultaneously preser-
vation of all biological eects considering the regulation
of epidermal cell proliferation and dierentiation, the in-
hibition of angiogenesis and the modulation of cytokine
production [9–14].
In our study, the serum level of 25-hydroxycholecal-
ciferol stayed below the normal serum range recom-
mended by the American Society for Bone and Mineral
Research, in both groups (controls and patients). The
concentration of 25-hydroxycholecalciferol was signi-
cantly lower in patients with psoriasis than in healthy
individuals, and the lowest measure was obtained
from patients with severe psoriasis. These results cor-
relate with similar observations of other authors. Both
the studies of Ricceri et al. and Orgaz-Molina et al. re-
vealed a high prevalence of insuciency and deciency
in serum 25-hydroxycholecalciferol, which was greater
in patients with psoriasis than in control subjects [15,
16]. Additionally, comparatively to our observations,
signicantly lower values of 25-hydroxycholecalciferol
were reported by Ricceri et al., and these concentrations
negatively correlated with PASI [15]. An interesting ob-
servation was made in the study of Orgaz-Molina et al.,
who reported a higher risk of 25-hydroxycholecalciferol
insuciency in psoriatic patients with a body mass index
of 27 or more. A possible explanation for such a relation-
ship was the lower physical activity level and therefore
reduced sun exposure of heavier psoriatic patients. An-
other possible mechanism is the increased sequestration
of vitamin D3 in fat, which could result in its reduced bio-
availability in serum [16].
The main source of vitamin D3 is its cutaneous syn-
thesis, which is activated by UV radiation; however, the
safe dose of exposure to UV radiation, which does not
cause the development of skin cancer, has remained
controversial. The current trends in lifestyle involve only
minimal sun exposure through most of the year but with
excessive sunbathing during the holiday period, which
undoubtedly implies a risk for the development of cu-
taneous neoplasia, including melanoma [1, 2, 9, 17, 18].
The impact of light exposure on the synthesis of
25-hydroxycholecalciferol has been evaluated in several
clinical studies. Ala-Houhala et al. analyzed the inuence
of narrow-band ultraviolet B (UVBnb) phototherapy on
the serum level of 25-hydroxycholecalciferol and the se-
verity of skin lesions in patients with psoriasis. In that
study, the response to UVBnb was assessed in 12 pa-
tients who were concomitantly supplemented with oral
cholecalciferol, 20 µg daily. At baseline, the serum level of
25-hydroxycholecalciferol was 74.14 nmol/l (much higher
than in our study), and it increased by 49.4 nmol/l above
baseline at the 18th exposure of UVBnb [11]. In another
study, Feldmeyer et al. compared the dierences in se-
rum concentrations of 25-hydroxycholecalciferol which
occurred after phototherapy with dierent light spectra.
The group of 116 dermatologic patients included several
disease entities (atopic dermatitis, psoriasis, morphea,
and others), and all individuals underwent UVA1 (n = 38),
UVBnb (n = 48) or combined UVA/UVBnb (n = 30) pho-
totherapy with the frequency of 2 to 3 times a week for
53 to 90 days. It was observed that phototherapy with
UVBnb and UVA/ UVBnb increased the 25-hydroxychole-
calciferol serum level signicantly, whereas UVA1 therapy
alone induced a reduction in serum 25-hydroxycholecal-
ciferol concentrations [19].
A considerable source of vitamin D3 that enables limi-
tation of sun exposure seems to be its additional food in-
take, in the form of certain foods or dietary supplements.
Unfortunately, most meals contain only a little vitamin
D3, and those rich in vitamin D3 are eaten irregularly,
which may be an important explanation of why both
study groups do not consume adequate quantities of vi-
tamin D3 [1, 2, 9, 20, 21]. In a pilot study, Finamor et al. ob-
served that prolonged high-dose vitamin D3 administra-
tion could be very benecial for patients with psoriasis.
It was found that treatment with vitamin D3 (35,000 IU
daily) resulted in a signicant increase in serum level of
25-hydroxycholecalciferol, which correlated with a sig-
nicant improvement in the PASI score of all patients.
Essentially, all patients presented low vitamin D status
(serum 25-hydroxycholecalciferol ≤ 30 ng/ml) at baseline,
which is in agreement with our results [22].
The benet/risk ratio should be taken into account,
since the sun exposure is undoubtedly crucial in support-
ing an adequate level of vitamin D3. Overall, moderate
sun exposure throughout the year and a balanced diet
should be the recommended practice to support a suf-
cient amount of vitamin D3 metabolites with mainte-
nance of the serum 25-hydroxycholecalciferol within
reference limits. In addition, new studies that determine
both the intake and blood levels of 25-hydroxycholecalcif-
erol in psoriasis patients are required [1, 2, 23].
Conclusions
The considerably low serum content of vitamin D3 in
both psoriasis patients and the control group indicate the
need for more research to evaluate the vitamin D3 status
of our population.

Advances in Dermatology and Allergology 6, December / 2016
Serum vitamin D level – the eect on the clinical course of psoriasis
449
It is necessary to bear in mind that not only meals
rich in vitamin D, but also sun exposure, are essential to
maintain an adequate level of this vitamin.
Although the food intake of vitamin D3 is very im-
portant for both the general population and psoriasis
patients, these groups manifest altered metabolism of
vitamin D3 and, in consequence, dierent vitamin D3 re-
quirements.
Acknowledgments
This study was funded by statutory grant KNW-1-
119/N/4/0.
Conict of interest
The authors declare no conict of interest.
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