Comparative Clinical Pathology

https://doi.org/10.1007/s00580-018-2651-3

ORIGINAL ARTICLE

Is vitamin D supplement accompanied with narrow band UVB effective

for treatment of vitiligo?
Mohammad Omidian 1 & Nader Pazyar 1 & Zahra-al Sadat Mousavi 1

Received: 28 November 2017 / Accepted: 17 January 2018

# Springer-Verlag London Ltd., part of Springer Nature 2018

Abstract
Vitiligo is an acquired autoimmune depigmenting disorder that is the result of white macules formation in the skin and mucous
membranes, caused by the loss of melanocytes. It has affected 0.4 to 2.0% of world’s population. It has been hypothesized that
Vitamin D is important for skin pigmentation, but the correlation between vitamin D and vitiligo treatment response needs to be
evaluated. To evaluate vitamin D supplementation effect on the vitiligo area severity index in patients treated with narrow band
UVB (NB UVB). This clinical pilot randomized study was carried out on 48 vitiligo patients who admitted to the Department of
Dermatology at Imam Khomeini Hospital. Patients were randomly divided into two groups: intervention group which received
vitamin D supplementation with a dose of 50,000 units once every 2 weeks, for 8 weeks. The rest of the patients were put in
control group and consumed placebo. Treatment with NB UVB irradiation with a starting dose of 0.3 j/CM2 was carried out twice
a week for all patients. Our study included 21 males and 27 females. The mean age of patients was 28.08 years old. The disease’s
duration ranged from 1 to 15 years, with the mean of 4.52 ± 4.2 years. Sex distribution and mean age were not significantly
different in either groups. Vitamin D deficiency was seen in 32 (66.7%) of the patients. Vitiligo area severity index (VASI) score
significantly decreased from 27.14 to 4.4 in intervention group and from 7.7 to 3.28 in control group. The correlation between
mean 25(OH)D serum levels and VASI before and after intervention was statistically insignificant. NB UVB could significantly
improve regimentation in vitiligo patients. Moreover, it significantly increased the serum level of vitamin D. But we have failed to
demonstrate any significant correlation between serum level of vitamin D and VASI score in vitiligo patients.

Keywords NB UVB . Vitiligo . Vitamin D

Introduction (Silverberg 2015). The functionality of melanocytosis is

Vitiligo is an acquired autoimmune depigmenting disorder
that shows different comorbidities. It is clinically presented
by the formation of white macules in the skin and mucous
membranes, caused by loss of melanocytes (Alikhan et al.
2011). The worldwide prevalence of vitiligo can range from
0.4 to 2.0% with female predominance. Moreover, it could
occur at any age, and the disease is divided into two major
groups based on the onset age: (I) patients with vitiligo
incidence who are younger than 12 years old and (II) those
with an onset age occurring after the age of 12 or more
* Zahra-al Sadat Mousavi
Nafmousavi@gmail.com
1
Department of Dermatology, Jundishapur University of Medical
Sciences, Ahvaz 1985717413, Iran
lost in vitiligo but in fact, its real cause is still unknown.
There are some possible conditions that could be related to
vitiligo including family history (genetic), neural, autoim-
munity, oxidative stress, and also viral infections
(Ghafourian et al. 2014). Vitiligo is clinically pictured by
one or more well-delimitated and white maculae that have
advanced in number and size. The macules are typically
asymptomatic. The most common regions of body in which
the lesions usually appear are sun-exposed areas, pressure
sites, or naturally hyperpigmented areas (Moretti n.d.).
A good management of Vitiligo needs appropriate diagnosis
and preferred treatment. The differential diagnosis of vitiligo
must be considered from piebaldism, achromic nevus,
hypomelanosis in birth and childhood, as well as some rare dis-
eases such as Prader–Willi syndrome, post inflammatory dis-
eases, and oculocutaneous albinism (Lotti et al. 2008). There
are a variety of treatments available for Vitiligo including medi-
cal, physical, and surgical treatments (Lotti et al. 2007). Physical

Fig. 1 Before and after treatment
treatment is mostly used and recommended based on cutaneous
involvement; narrow band ultraviolet B microphototherapy (NB
UVB) is used for generalized vitiligo, but monochromatic
excimer light and narrow band ultraviolet B excimer laser could
be suggested in bilateral and segmental vitiligo (< 20% involve-
ment). Moreover, many medical treatments such as topical cor-
ticosteroids, antioxidants, pimecrolimus and tacrolimus, vitamin
D derivatives, and prostaglandin E could be used (Lotti et al.
2009; Husain et al. 2017). Vitamin D, a fat-soluble vitamin,
increases the calcium absorbance and regulates bone metabo-
lism, cell proliferation and differentiation. It also has an important
role in immunoregulation. Vitamin D acts via a nuclear hormone
receptor. Recently, it has been hypothesized that Vitamin D is
important for skin pigmentation (AlGhamdi et al. 2013).
Moreover, low serum level of vitamin D has been reported in
autoimmune diseases and vitiligo patients (Karagün et al. 2016).
Thus, the correlation between vitamin D and vitiligo and also, its
application in vitiligo treatment needs further thorough studies. In
the current study, we have aimed to answer this question: Does
vitamin D supplementation affect the vitiligo area severity index
in patients treated with narrow band UVB?
Material and methods
Study design
This clinical pilot randomized study was carried out on 48
vitiligo patients who admitted to the Department of
Table 1 Patients characteristics
Variables
Age
Gender Male
Female
Vitamin D (before treatment)
VASI (before treatment)
Comp Clin Pathol
Dermatology at Imam Khomeini Hospital from April to
August 2016. Patients who received thiazide diuretic, lith-
ium, systemic form of prednisolon and vitamin D during a
month before the study, renal failure patients, patients
with less than 6 years old, and patients with high Ca
levels were excluded from the study. This study was ap-
proved by the ethics committee of Ahvaz Jundishapur
University of Medical Sciences, Ahvaz, Iran. Informed
consent was signed by all subjects.
Intervention
The patients were randomly divided into two groups: inter-
vention and control. Treatment with NB UVB irradiation in
a Whole Body UV Therapy System (V-care, Surya Series,
India), with a dose of 0.3 j/CM2 was carried out twice a
week for all patients. It has been reported that this dose
could lead to erythema in Asian ethnicity (Al-Jamal et al.
2014). The dose increased by 20% after each visit. If the
treatment caused burning, pain, or erythema, phototherapy
would stop until relieving the effects. After that, radiation
would decrease to 50% of erythema causing dose and in-
crease by 10% after each visit. Phototherapy was continued
for 16 weeks. Vitamin D supplementation (Abidi, Iran) with
a dose of 50,000 units, once every 2 weeks, was prescribed
in interventional group for 8 weeks. Also, patients in con-
trol group consumed Placebos (Cumin Soft Pearl) (Barij
Esans, Iran).
Intervention group Controls P value
n = 24 n = 24
25.54 ± 14.9 30.62 ± 11.94 0.199
12 (50%) 9 (37.5%) 0.281
12 (50%) 15 (62.5)
22.59 ± 12.04 14.5417 ± 14.29 0.003
27.14 ± 19.45 7.7 ± 3.2 < 0.001
Comp Clin Pathol
Table 2 Paired analysis before and after treatments
Variables Before After
Vitamin D Intervention group 22.95 ± 12.04 39.4 ± 14.64
Control 14.54 ± 14.29 27.26 ± 13.72 0.007
VASI Intervention group 27.14 ± 19.45 4.4 ± 6.4
Control 7.7 ± 3.2 7.48 ± 3.64
Measurements
General and local examinations were done for all subjects.
Also, the disease extent and severity were evaluated by vitili-
go area severity index (VASI score). Furthermore, sex, age,
and duration of vitiligo were recorded. Serum 25-hydroxy
vitamin D levels were measured before treatment and
11 weeks after intervention. Two milliliters of venous blood
sample was collected, and 25-hydroxy vitamin D level was
measured by competitive enzyme-linked immunosorbent as-
say (ELISA) technique. To assess the VASI, the evaluation
was done in five body regions. The VASI was determined
by patient’s hand units (each hand unit defined 1% of depig-
mentation area) using the following formula: VASI = ∑ (hand
units) × (residual depigmentation). VASI can range from 0 to
100%. Moreover, the pictures, before and after treatment, have
been captured from all of the patients (Fig. 1).
Statistical analysis
Statistical analysis was done using SPSS version 19. The nor-
mal distribution was checked by Kolmogorov–Smirnov test.
Also paired and unpaired t test was used to compare the nom-
inal variables. Moreover, Spearman’s correlation was done to
determine the correlation between variables. P value less than
0.05 were considered as statistically significant.
Results
The mean age of patients was 28.08 years old. Our study
included 21 males and 27 females. The oldest patient was
64, and the youngest one was 7 years old. The diseases
Table 3 VASI and vitamin D
level correlation Variables
Before Treatment
After Treatment
duration ranged from 1 to 15 years, with the mean of 4.52 ±
P value 4.2 years. Sex distribution and mean age were not significant-
ly different in either group. Vitamin D deficiency was seen in
0.001 32 (66.7%) of patients. The baseline serum levels of 25(OH)D
in the intervention and control group were 22.59 and 14.54 ng/
< 0.0001 mL, respectively (Table 1).
0.0001 Baseline mean VASI score in the intervention and control
groups was 27.14 ± 19.45 and 7.28 ± 7.48, respectively. The
VASI score decreased from 27.14 to 4.4 and from 7.7 to 3.28
in intervention and control groups, respectively. A paired sam-
ple t test was carried out to compare VASI score levels before
and after treatment. A significant difference was seen in both
groups: intervention group, t (23) = 7.33, p < 0.0001 and con-
trol group, t (23) = 4.66, p < 0.0001(Table 2). Moreover,
25(OH)D serum level in both groups increased significantly
during the study period time.
The spearmen correlation score between mean 25(OH)D
serum levels and VASI before intervention was 0.231 which
was statistically insignificant (p = 0.114). Similarly, VASI
score and 25(OH)D serum levels were not significantly corre-
lated after intervention (Table 3, Figs. 2 and 3).
Discussion
One of the most common dermatologic disorders all over the
world is vitiligo which has affected approximately 0.4 to 2%
of the population (Alikhan et al. 2011). Although distinct
pathogenesis of vitiligo is still unknown, many contributing
factors have been suggested to enroll in its etiopathogenesis
including inherited gene aberrations, neural defects, viral in-
fections, and biochemical imbalance (Mohammed et al.
2015). Imbalances of calcium, polymorphisms of vitamin D
receptor-Apa-1, low expression of vitamin D receptor, mRNA
expression, and also low serum levels of vitamin D are among
the most recently known contributors in vitiligo development
(Aydıngöz et al. 2012; Doss et al. 2015). On the other hand, it
has been recently reported that vitamin D has an important
role in the pigmentation of skin through the increment of the
melanocytes tyrosinase (AlGhamdi et al. 2013). Thus, the
question is how can vitamin D serum level affect the NB
UVB treatment response in vitiligo patients. The current study
aims to find the right question.
Number of patients Spearmen correlation P value
VASI 48 0.231 0.114
Vitamin D
VASI 48 0.219 0.135
Vitamin D

Fig. 2 The correlation between
baseline vitamin D level and
VASI
Interestingly, our findings showed a significant increase of
vitamin D serum level in patients under NB UVB treatment,
without Vitamin D supplementation. So, it can be concluded that
NB UVB may increase the serum level of vitamin D. Therefore,
it is in line with previous studies. Cicarma et al. showed that
UVB treatment makes a significant increase in vitamin D serum
level status in patients (Cicarma et al. 2010). Furthermore, Gupta
et al. assessed the NB UVB effect on 25(OH)D levels in psoriasis
Fig. 3 The correlation between
vitamin D level and VASI after
intervention
Comp Clin Pathol
patients and showed a significant increase in 25(OH)D serum
level after the treatment by NB UVB (Gupta et al. 2016). Also,
Ryan et al. showed a similar finding (Ryan et al. 2010). Vitamin
D3, also known as calciferol, is formed in the skin. Vitamin D3 is
cutaneously synthesized by the effect of specific UV-B wave-
lengths on vitamin D3 precursor, 7-dehydrocholesterol that pro-
duces pre-vitamin D3. Pre-vitamin D3 is immediately trans-
formed to vitamin D3 (Reichrath 2007). Therefore, it can be
Comp Clin Pathol
hypothesized that NB UVB may help skin repigmentation
through its effect on the serum level of vitamin D. To check
the hypothesis, we analyzed the correlation between vitamin D
level and VASI score.
We found that there is a low positive correlation between
vitamin D serum level and VASI score either before or after
intervention. The correlation was not statistically significant.
In accordance to our findings, Sehrawat et al., in a similar
clinical randomized trial, showed insignificant positive corre-
lation between VASI and vitamin D levels (Sehrawat et al.
2014). Moreover, in another study, Arca et al. compared two
independent treatment groups of vitiligo patients: (I) mono-
therapy of NB UVB and (II) its combination with topical form
of calcipotriol. They found that using topical calcipotriol
along with NB UVB in vitiligo patients does not have any
advantages (Arca et al. 2006). Hartman et al. and also Ada
et al. showed similar findings in line with our results.
However, in another study, Goktas et al. reported different
results. They compared the efficacy of NB UVB and its com-
bination with topical calcipotriol in treatment of vitiligo pa-
tients. The treatment followed up for 6 months and patients
received NB UVB treatment thrice a week as well as topical
calcipotriol on the lesions. Finally, they reported that the com-
bination of NB UVB with topical calcipotriol leads to earlier
pigmentation, less adverse UVB effect, and also shorter treat-
ment duration (Goktas et al. 2006). This contrast between the
last report and other previous studies could be due to longer
patient follow-ups in Goktas’s study. More investigations on
the large cohort of vitiligo patients may resolve this
controversy.
Conclusion
All things considered, our findings indicated that NB UVB
could significantly improve regimentation in vitiligo patients.
Moreover, we found that NB UVB significantly increased the
serum level of vitamin D. However, we failed to demonstrate
any correlation between vitamin D serum level and VASI
score in vitiligo patients. As a result, we are not able to prove
the advantages of vitamin D supplementation in these patients.
Acknowledgements We thank all our colleagues in Imam Khomeini
Hospital, Ahvaz, Iran.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical standards All procedures have been approved by the appropri-
ate ethics committee and have therefore been performed in accordance
with the ethical standards laid down in the 1964 Declaration of Helsinki
and its later amendments.
Informed consent Informed consent was signed prior to participation in
the study.
References
AlGhamdi K, Kumar A, Moussa N (2013) The role of vitamin D in
melanogenesis with an emphasis on vitiligo. Indian Journal of
Dermatology, Venereology, and Leprology 79(6):750. https://doi.
org/10.4103/0378-6323.120720
Alikhan A, Felsten LM, Daly M, Petronic-Rosic V (2011) Vitiligo: a
comprehensive overview: part I. Introduction, epidemiology, quality
of life, diagnosis, differential diagnosis, associations, histopatholo-
gy, etiology, and work-up. J Am Acad Dermatol 65(3):473–491.
https://doi.org/10.1016/j.jaad.2010.11.061
Al-Jamal MS, Griffith JL, Lim HW (2014) Photoprotection in ethnic skin.
Dermatol Sin 32(4):217–224. https://doi.org/10.1016/j.dsi.2014.09.
001
Arca E, Taştan HB, Erbil AH, Sezer E, KoÇ E, Kurumlu Z (2006)
Narrow-band ultraviolet B as monotherapy and in combination with
topical calcipotriol in the treatment of vitiligo. J Dermatol 33(5):
338–343. https://doi.org/10.1111/j.1346-8138.2006.00079.x
Aydıngöz İE, Bingül İ, Doğru-Abbasoğlu S, Vural P, Uysal M (2012)
Analysis of vitamin D receptor gene polymorphisms in vitiligo.
Dermatology 224(4):361–368. https://doi.org/10.1159/000339340
Cicarma E, Mørk C, Porojnicu AC, Juzeniene A, Tam TT, Dahlback A,
Moan J (2010) Influence of narrowband UVB phototherapy on vi-
tamin D and folate status. Exp Dermatol 19(8)
Doss RW, El-Rifaie AA, Gohary YM, Rashed LA (2015) Vitamin D
receptor expression in vitiligo. Indian journal of dermatology
60(6):544–548. https://doi.org/10.4103/0019-5154.169123
Ghafourian E, Ghafourian S, Sadeghifard N, Mohebi R, Shokoohini Y,
Nezamoleslami S, Hamat RA (2014) Vitiligo: symptoms, pathogen-
esis and treatment. Int J Immunopathol Pharmacol 27(4):485–489.
https://doi.org/10.1177/039463201402700403
Goktas EO, Aydin F, Senturk N, Canturk MT, Turanli AY (2006)
Combination of narrow band UVB and topical calcipotriol for the
treatment of vitiligo. J Eur Acad Dermatol Venereol 20(5):553–557.
https://doi.org/10.1111/j.1468-3083.2006.01546.x
Gupta A, Arora TC, Jindal A, Bhadoria AS. Efficacy of narrowband
ultraviolet B phototherapy and levels of serum vitamin D3 in psori-
asis: a prospective study. Indian. dermatology online journal 2016;
7(2):87, 92, DOI: https://doi.org/10.4103/2229-5178.178081
Husain MA, Alam MN, Rahim R, Joarder Y, Ferdous M (2017) Efficacy
and safety of topical tacrolimus (0.03%) in the treatment localized
vitiligo. Medicine Today 29(1):1–5. https://doi.org/10.3329/
medtoday.v29i1.33850
Karagün E, Ergin C, Baysak S, Erden G, Aktaş H, Ekiz Ö (2016) The role
of serum vitamin D levels in vitiligo. Advances in Dermatology and
Allergology/Post py Dermatologii i Alergologii 33(4):300–302.
https://doi.org/10.5114/pdia.2016.59507
Lotti T, Prignano F, Buggiani G (2007) New and experimental treatments
of vitiligo and other hypomelanoses. Dermatol Clin 25(3):393–400.
https://doi.org/10.1016/j.det.2007.04.009
Lotti T, Gori A, Zanieri F, Colucci R, Moretti S (2008) Vitiligo: new and
emerging treatments. Dermatol Ther 21(2):110–117. https://doi.org/
10.1111/j.1529-8019.2008.00178.x
Lotti T, Berti S, Moretti S (2009) Vitiligo therapy. Expert Opin
Pharmacother 10(17):2779–2785. https://doi.org/10.1517/
14656560903357509
Mohammed GF, Gomaa AH, Al-Dhubaibi MS (2015) Highlights in path-
ogenesis of vitiligo. World Journal of Clinical Cases: WJCC 3(3):
221–230. https://doi.org/10.12998/wjcc.v3.i3.221

Moretti DS (n.d.) Creation date: October 2003 Scientific editor: Professor
Benvenuto Giannotti. Available at: https://www.orpha.net/data/
patho/GB/uk-vitiligo.pdf
Reichrath J (2007) Vitamin D and the skin: an ancient friend, revisited.
Exp Dermatol 16(7):618–625. https://doi.org/10.1111/j.1600-0625.
2007.00570.x
Ryan C, Moran B, McKenna MJ, Murray BF, Brady J, Collins P, Rogers S,
Kirby B (2010) The effect of narrowband UV-B treatment for psori-
asis on vitamin D status during wintertime in Ireland. Arch Dermatol
146(8):836–842. https://doi.org/10.1001/archdermatol.2010.195
Comp Clin Pathol
Sehrawat M, Arora TC, Chauhan A, Kar HK, Poonia A, Jairath V (2014)
Correlation of vitamin D levels with pigmentation in vitiligo patients
treated with NBUVB therapy. ISRN dermatology 2014:1–6. https://
doi.org/10.1155/2014/493213
Silverberg NB (2015) The epidemiology of vitiligo. Current
Dermatology Reports 4(1):36–43. https://doi.org/10.1007/s13671-
014-0098-6