Review

The role of vitamin D in psoriasis: a review

Teo Soleymani1, MD, Tracy Hung2, BS, and Jennifer Soung1, MD

1
Department of Dermatology, University of
California, Irvine School of Medicine, Irvine,
CA, and 2Drexel University College of
Medicine, Philadelphia, PA, USA

Correspondence
Jennifer Soung, MD,
Department of Dermatology
University of California, Irvine School of
Medicine
1001 Hewitt Hall
Irvine
CA 92697-2400
USA
E-mail: jsoung@uci.edu
Conflicts of interest: None.
doi: 10.1111/ijd.12790

Abstract
Background and objective Psoriasis is a common, chronic autoimmune inflammatory
skin disorder, which has potential systemic complications and is clinically defined by
sharply demarcated, erythematous patches and plaques covered by a characteristic silvery
white scale. Topical corticosteroids have widely been regarded as the mainstay first line of
treatment. Recently, topical vitamin D analogs have been added to the first-line treatment
repertoire as well, either as monotherapy or in combination with topical steroids due to
synergistic, complementary effectiveness. In this paper, we review the role of vitamin D in
the pathophysiology and treatment of psoriasis.
Methods A comprehensive search of the Cochrane Library, MEDLINE, and PUBMED
databases were performed to identify relevant basic science and clinical trial literature
investigating the role of vitamin D in psoriasis. Primary endpoints in clinical trials were
largely based on clinical improvement as assessed by the psoriasis area severity index
score or physicians global assessment.
Results and conclusion The role of vitamin D in psoriasis is complex and extensive. Oral
and topical vitamin D therapies provide comparable efficacies to corticosteroids when used
as monotherapy and may be superior when used in combination with a potent topical
steroid. Additionally topical vitamin D analogs demonstrate a favorable safety profile with
steroid-sparing effects. Thus, topical vitamin D derivatives should be considered an
indispensable component of the current physicians arsenal in the treatment of psoriasis.

Introduction
Psoriasis is a common, chronic autoimmune inflammatory
skin disorder, which has potential systemic complications
and is clinically defined by sharply demarcated, erythematous patches and plaques covered by a characteristic silvery
white scale. Classically, psoriasis affects the scalp, elbows,
knees, umbilicus, and lumbar area, though lesions can
occur anywhere and can cover the entire skin surface.
Although psoriasis is a relatively prevalent skin disease, its
distinct definition by Ferdinand von Hebra dates back only
to 1841, and estimates of its prevalence, widely quoted as
2% in medical textbooks, are based on only a few old population studies.1 We now know that prevalence in the general population is much more varied, based on a variety of
ethnic and genetic factors, ranging anywhere from 0.45 to
4.6%.13 Though the complex pathogenesis of psoriasis
remains incompletely understood, compelling evidence suggests that it is a systemic autoimmune disease in which T
lymphocytes play a key central role in the subsequent production and activation of inflammatory cytokines.1,2,47
Vitamin D has long been known to be a hormone that
regulates calcium homeostasis and maintains the skeletal
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system in the human body. Historically associated with

childhood rickets and adult osteomalacia, vitamin D deficiency has now been linked to chronic systemic illnesses,
including common cancers, autoimmune diseases such as
multiple sclerosis and type 1 diabetes, infectious diseases,
as well as cardiovascular neurodegenerative disease.810
Recently it has been discovered that vitamin D may also
play a role in the autoimmune diseases of the skin as
well.1,812 The relationship between skin diseases and
vitamin D has particularly gained interest in recent literature. In particular, many current studies have focused on
the relationship between vitamin D and psoriasis, and
although much remains unknown, there have been an
increasing number of publications addressing the various
possible pathomolecular mechanisms underlying the role
of vitamin D in this particular disease. In this paper, we
explore the role of vitamin D in psoriasis.
Synthesis of vitamin D
There are two forms of vitamin D: ergocalciferol (vitamin
D2) and cholecalciferol (vitamin D3). vitamin D2 is
derived from the yeast sterol, ergosterol, whereas vitamin
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The Role of Vitamin D in Psoriasis

D3 is synthesized in the human skin following ultraviolet

(UV) light exposure and can be found in oil-rich
fish.10,13,14 Unfortunately, very few foods in nature contain sufficient quantities of vitamin D. Oil-rich fatty fish
such as salmon, tuna, and mackerel are among the best
sources of vitamin D, and to a lesser extent in beef liver,
cheese, and egg yolks.10,13,14 These animal sources provide vitamin D predominantly in the form of vitamin
D3.10,13,14 Plant sources of vitamin D are predominantly
in the form vitamin D2 and are generally considered
insufficient in quantity.10,13,14 Plant sources of vitamin D
are formed after exposure of the plant to UV light and
can be artificially enhanced through increased UV exposure in controlled settings, as is the case with mushrooms
in the USA.10,13,14
In general, fortified foods provide the majority of the
vitamin D consumed in the American diet.10,13,14 For
example, almost all of the US milk supply is voluntarily
fortified with vitamin D, originally as an effort established
in the 1920s1930s as a way to combat rickets in the
USA.10,13,14 Other dairy products made from milk, such as
cheese, yogurt, and ice cream, also contain variable quantities of vitamin D stemming from the milk that was used.
Furthermore, ready-to-eat breakfast cereals often contain
added vitamin D, as do some brands of orange juice,
yogurt, margarine, and other food products.10,13,14
Historically, the two forms of vitamin D, D2 and D3,
had been officially regarded as equivalent and interchangeable. However, with the emergence of 25-hydroxyvitamin
D as an objective, quantitative measure of vitamin D status,
recent studies have demonstrated that vitamin D3 is the
more potent form and functionally utilizable form of
vitamin D.13 While both forms are currently available as
over-the-counter supplements and despite an emerging
body of evidence suggesting the greater bioefficacy of
vitamin D3, the form of vitamin D most commonly used in
major preparations of prescriptions in North America is
still remains vitamin D2.10,13
Although vitamin D can be obtained in dietary products, the skin is the major source of vitamin D for the
body.8,10,12,15,16 The keratinocytes of the epidermis are
unique in being not only the primary source of vitamin D
synthesis but also in possessing the enzymatic machinery
needed to metabolize vitamin D to its active metabolite
1,25-dihydroxyvitamin D3 (calcitriol or 1,25(OH)2D).15,17
UVB light (290320 nm) produces a photochemical reaction in the skin, converting 7-dehydrocholesterol to previtamin D3.8,10,11,15,16,18 Both the degree of epidermal
pigmentation and intensity of exposure correlate with the
time required to achieve this maximal concentration of
previtamin D3 but do not alter the maximal level
achieved.15 Melanin in the epidermis, by absorbing UV
irradiation, can reduce the effectiveness of sunlight in
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Soleymani, Hung and Soung

producing vitamin D3 in the skin.15 Once previtamin D3 is

formed in the skin, it undergoes temperature-dependent
thermal isomerization to vitamin D3.11,16,18 Vitamin D3
then binds to vitamin D-binding protein and is then transported to the liver, where it is hydroxylated and converted
to 25-hydroxyvitamin D3 (25(OH)D).1012,18 25(OH)D is
further transported by the vitamin D-binding protein to
the kidney and catalyzed to its hormonally active form
1,25(OH)2D.1012,18 Any excess previtamin D3 or vitamin
D3 is destroyed by sunlight, and thus excessive exposure
to sunlight does not cause vitamin D3 intoxication.10,12,15
Vitamin D deficiency
What was once thought to be a resolved matter given the
fortification of food and the apparent eradication of
childhood rickets, vitamin D deficiency is, in fact, a common problem both in the USA and worldwide.810
According to several recent epidemiological studies,
nearly 4090% of the elderly, 3254% of the healthy
adult population, and 4560% of adolescents in the USA
are deficient in vitamin D.9,10,1921 The total number of
cases of vitamin D deficiency has reached more than one
billion worldwide.8
Approximately 80100% of functionally utilizable vitamin D comes from solar radiation, with only a small fraction coming from diet.8,1012,22,23 Because of this, many
authors hypothesize that the recent epidemic of vitamin D
insufficiency/deficiency is largely attributed to changes in
the patterns of sun exposure, with strict sun protection
and avoidance strategies being a leading cause.8,10,11,22,23
As alluded to earlier, melanin in the epidermis absorbs
UV irradiation and can therefore reduce the effectiveness
of sunlight in producing vitamin D3 in the skin.15 This
has been thought to be the reason behind the lower levels
of vitamin D seen in darker-skinned individuals living in
temperate latitudes.24 In fact, there is a generally held
consensus by many investigators that populations of
dark-skinned individuals, particularly those living closer
to the equator, are clinically deficient in vitamin D, largely because of the impairment of UV conversion due to
the absorption of UV light by the abundant melanin in
their skin.8,10,11,22,24 However, recent studies further analyzing the serum levels of vitamin D and its transporter in
dark-skinned individuals found that although total vitamin D levels were indeed lower, the available free fraction of vitamin D3 was within normal limits, suggesting
that there is no real deficiency after all.8,10,11,24
In the scientific community as well as in the general
public, there is an ongoing debate as to the risks versus
benefits of solar UV exposure. On the one hand, solar UV
radiation represents the most significant environmental
risk factor for the development of non-melanoma skin
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32
33

34

35
36

37

38

39

40

41

42

43

44

45

46

growth and differentiation. Endocr Rev 2002; 23: 763

786.
Hewison M. Vitamin D and immune function: an
overview. Proc Nutr Soc 2012; 71: 5061.
Sato-Deguchi E, Imafuku S, Chou B, et al. Topical
Vitamin D3 analogues induce thymic stromal
lymphopoietin and cathelicidin in psoriatic skin lesions.
Br J Dermatol 2012; 167: 7784.
Chen S, Sims GP, Chen XX, et al. Modulatory effects of
1,25-dihydroxyvitamin D3 on human B cell
differentiation. J Immunol 2007; 179: 16341647.
Boehncke W-H, Dressel D, Zollner TM, et al. Pulling the
trigger on psoriasis. Nature 1996; 379: 777.
Kang S, Yi S, Griffiths CE, et al. Calcipotriene-induced
improvement in psoriasis is associated with reduced
interleukin-8 and increased interleukin-10 levels within
lesions. Br J Dermatol 1998; 138: 7783.
Hegyi Z, Zwicker S, Bureik D, et al. Vitamin D analog
calcipotriol suppresses the Th17 cytokine-induced
proinflammatory S100 alarmins psoriasin (S100A7) and
koebnerisin (S100A15) in psoriasis. J Invest Dermatol
2012; 132: 14161424.
Heilborn JD, Weber G, Gr
onberg A, et al. Topical
treatment with the Vitamin D analogue calcipotriol
enhances the upregulation of the antimicrobial protein
hCAP18/LL-37 during wounding in human skin in vivo.
Exp Dermatol 2010; 19: 332338.
MacLaughlin JA, Gange W, Taylor D, et al. Cultured
psoriatic fibroblasts from involved and uninvolved sites
have partial but not absolute resistance to the
proliferation-inhibition activity of 1,25-dihydroxyvitamin
D3. Proc Natl Acad Sci USA 1985; 82: 54095412.
Morimoto S, Kumahara Y. A patient with psoriasis cured
by 1a-hydroxyvitamin D3. Med J Osaka Univ 1985; 35:
34.
Morimoto S, Yoshikawa K, Kozuka T, et al. An open
study of vitamin D3 treatment in psoriasis vulgaris. Br
J Dermatol 1986; 115: 421429.
Holick MF, Pochi P, Bhawan J. Topically applied and
orally administered 1,25-dihydroxy-Vitamin D3 is a
novel, safe, effective therapy for the treatment of
psoriasis: a three year experience with histologic analysis.
J Invest Dermatol 1989; 92: 446.
Kragballe K, Beck HI, Sogaard H. Improvement of
psoriasis by topical Vitamin D3 analogue (MC 903) in
a double-blind study. Br J Dermatol 1988; 119: 223
230.
Kragballe K, Gjertsen BT, De Hoop D, et al.
Double-blind, right/left comparison of calcipotriol and
betamethasone valerate in treatment of psoriasis vulgaris.
Lancet 1991; 337: 193196.
Miyachi Y, Ohkawara A, Ohkido M, et al. Long-term
safety and efficacy of high-concentration (20 lg/g)
tacalcitol ointment in psoriasis vulgaris. Eur J Dermatol
2002; 12: 463468.
Perez A, Raab R, Chen TC, et al. Safety and efficacy of
oral calcitriol (1,25-dihydroxyvitamin D3) for the

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47

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treatment of psoriasis. Br J Dermatol 1996; 134:

10701078.
Van de Kerkhof PC, Berth-Jones J, Griffiths CE, et al.
Long-term efficacy and safety of tacalcitol ointment in
patients with chronic plaque psoriasis. Br J Dermatol
2002; 146: 414422.
Van de Kerkhof PCM, Van Bokhoven M, Zultak M,
et al. A double-blind study of topical
1,25-dihydroxy-Vitamin D3 in psoriasis. Br J Dermatol
1989; 120: 661664.
Barker JN, Ashton RE, Marks R, et al. Topical
maxacalcitol for the treatment of psoriasis vulgaris: a
placebo-controlled, double-blind, dose-finding study with
active comparator. Br J Dermatol 1999; 141: 274278.
Katayama I, Ohkawara A, Ohkido M, et al.
High-concentration (20 lg/g) tacalcitol ointment therapy
on refractory psoriasis vulgaris with low response to
topical corticosteroids. Eur J Dermatol 2002; 12:
553557.
Green C, Ganpule M, Harris D, et al. Comparative
effects of calcipotriol (MC 903) solution and placebo
(vehicle of MC 903) in the treatment of psoriasis of the
scalp. Br J Dermatol 1994; 130: 483487.
Queille-Roussel C, Duteil L, Parneix-Spake A, et al. The
safety of calcitriol 3 microg/g ointment. Evaluation of
cutaneous contact sensitization, cumulative irritancy,
photoallergic contact sensitization and phototoxicity. Eur
J Dermatol 2001; 11: 219224.
Orgaz-Molina J, Buenda-Eisman A, Arrabal-Polo MA,
et al. Deficiency of serum concentration of
25-hydroxyvitamin D in psoriatic patients: a
case-control study. J Am Acad Dermatol 2012; 67:
931938.
Orgaz-Molina J, Magro-Checa C, Arrabal-Polo MA,
et al. Association of 25-hydroxyvitamin D with metabolic
syndrome in patients with psoriasis: a case-control study.
Acta Derm Venereol 2014; 94: 1425. doi: 10.2340/
00015555-1642. [Epub ahead of print]
Gisondi P, Rossini M, Di Cesare A, et al. Vitamin D
status in patients with chronic plaque psoriasis. Br
J Dermatol 2012; 166: 505510.
Braun-Moscovici Y, Toledano K, Markovits D, et al.
Vitamin D level: is it related to disease activity in
inflammatory joint disease? Rheumatol Int 2011; 31:
493499.
Touma Z, Eder L, Zisman D, et al. Seasonal variation in
Vitamin D levels in psoriatic arthritis patients from
different latitudes and its association with clinical
outcomes. Arthritis Care Res (Hoboken) 2011; 63: 1440
1447.
Ricceri F, Pescitelli L, Tripo L, et al. Deficiency of serum
concentration of 25-hydroxyvitamin D correlates with
severity of disease in chronic plaque psoriasis. J Am Acad
Dermatol 2013; 68: 511512.
Merola JF, Han J, Li T, et al. No association between
vitamin D intake and incident psoriasis among US
women. Arch Dermatol Res 2014; 306: 3057.

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The Role of Vitamin D in Psoriasis

(4 d from basal layer to stratum corneum compared with

28 d in normal skin).1 Abnormal differentiation in psoriatic skin is further evidenced by a delay in the expression
of K1 and K10, seen in normal skin, and an overexpression of K6 and K16, seen in reactive and healing skin.1
At physiological concentrations, vitamin D helps to promote keratinocyte growth and development and protects
them against premature apoptosis; however, at pharmacological concentrations (10 6 M), vitamin D inhibits
keratinocyte proliferation and exerts a selective proapoptotic effect.11,12,28 These effects on keratinocyte growth
and development are essential in the role of vitamin D in
treating psoriasis. Furthermore, as mentioned earlier, vitamin D modulates the expression of K1 and K10 in the
stratum spinosum, two important keratins known to have
delayed expression in psoriatic skin.15,17 Such effects are
thought to be, in part, the mechanisms behind which vitamin D treatment improves psoriasis. Recent studies have
further supported this notion. Immunohistochemical and
biochemical analyses have demonstrated antiproliferative
and pro-differentiating effects in epidermal keratinocytes
along with treatment with 1,25(OH)2D3 or analogs in
vivo.28 Furthermore, in addition to its effects on keratinocyte development and differentiation, vitamin D has been
shown to normalize the distribution of integrins, namely
CD26, ICAM-1, and HLA-DR, along the dermalepidermal junction, which are altered in psoriatic skin.29 It is
hypothesized that the altered localization of integrins
results in the loss of their adhesive ability and overproliferation of keratinocytes in psoriasis.29 Recent studies
comparing the effect of topical vitamin D treatment on
integrin arrangements in lesional psoriatic, non-lesional
psoriatic, and normal-skinned patients found that the integrin subunit staining patterns were normalized in lesional psoriatic skin after treatment, whereas no difference
was seen in non-lesional psoriatic skin compared to normal skin before and after treatment.29,30
As 1,25(OH)2D exerts its effects through binding to
VDR, it has been postulated that the responsiveness to
vitamin D therapy depends on the level of expression of
VDR in keratinocytes.11,12,31 Recent studies have demonstrated that mice, deficient in epidermal VDR, are unable
to respond to vitamin D, suggesting that the improvement
of psoriasis with vitamin D treatment correlates directly
with the level of VDR present in lesional skin.11,31 Moreover, it has been shown that VDR expression is related to
the cell cycle: VDR levels decrease during the arresting
phase and increase once the cell re-enters the cell cycle.31
Thus, it can be inferred that vitamin D would preferentially act on proliferating cells.11,12,31 In addition to their
intrinsic antiproliferative effects, vitamin D analogs have
been shown to upregulate the expression of VDR on
epidermal keratinocytes, thus temporally amplifying their
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own potency and enhancing their regulatory role on cell

differentiation and proliferation.11,12,30,31
Much work has been done to elucidate the immunomodulatory role of vitamin D within the skin. Recent literature has shown that vitamin D plays a critical role in
regulating both cellular and humoral immunity through
the suppression of T-cell proliferation, preferential development of T-helper (Th)2 cells, induction of regulatory T
cells, modulation of cytokine production and activation,
as well as regulating dendritic cell maturation and migration.12,26,27,32,33 Recent studies have also demonstrated
that vitamin D regulates B-cell development by inducing
apoptosis in activated B cells and inhibits their proliferation but has no effect on non-stimulated B cells.34
In psoriatic skin, T lymphocytes play a key central
role in the subsequent production and activation of
inflammatory cytokines.1,2,47,35 Eloquent immunological
studies have demonstrated that psoriasis is a process
based on T-cell dysregulation, even without previous epithelial abnormalities.1,6,7 Additionally, psoriasis may be
the model example of a disorder that clearly shows a
central role of cytokines and chemokines in the pathogenesis of this disease.1 Cytokine dysregulation may
explain, at least in part, the complex tissue alterations
seen in psoriatic skin.1,2,4,6,35,36 Proinflammatory chemotactic cytokines, particularly tumor necrosis factor-a,
interferon-c, interleukin (IL)-2, and IL-8, have been
extensively implicated in the pathogenesis of psoriasis,
playing critical roles in the T-cell-mediated inflammatory
process.1,2,4,6,35 Studies examining the role of vitamin D
on the cutaneous immune system have demonstrated its
ability to inhibit the production of cytokines needed for
Th1 and Th17 differentiation, stimulate T cells to produce anti-inflammatory Th2 cytokines such as IL-10,
and thus reduce the production of inflammatory cytokines such as IL-2, IL-8 interferon-c, and tumor necrosis
factor-a, as well as reduce the density of major histocompatibility complex class II molecules on dendritic
cells.4,11,12,25,26,32,33,36 Such profound effects on T-cell
development and cytokine production in part underlie
the mechanisms behind the therapeutic action of vitamin
D on psoriatic skin.
Moreover, vitamin D analogs have been shown to suppress the Th17 cytokine-mediated production of psoriasin
and koebnerisin, two antimicrobial chemoattractant peptides that amplify inflammation in psoriasis.37 Vitamin D
has also been shown to induce the antimicrobial peptide
cathelicidin (LL-37) in keratinocytes.33,38 Cathelicidin
serves as a first-line defense mechanism in the innate
immune system, and has anti-inflammatory effects that
blunt activation of macrophages.33,38 Cathelicidin
remains at a low level in normal skin and is upregulated
in wound healing and tissue repair.38 A recent study
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demonstrated that thymic stromal lymphopoietin, a cytokine known to induce Th2 differentiation and inhibit
IL-12/23 production, as well as cathelicidin were both
significantly upregulated following topical application of
calcitriol and calcipotriol on psoriatic lesions.33 As
cathelicidin is usually overexpressed in psoriatic skin, it
was suggested that the cathelicidin induced by the topical
treatment acted as an inhibitor of inflammation in psoriatic skin rather than an exacerbator.33
Vitamin D in the treatment of psoriasis
In 1985, two important observations in psoriasis research
were made. One was made by MacLaughlin et al., who
reported that psoriatic fibroblasts were partially sensitive
to the antiproliferative effects of 1,25(OH)2D, prompting
them to investigate the role of calcitriol in the treatment
of hyperproliferative diseases, namely psoriasis.28,39 The
other, almost serendipitous observation was made by
Morimoto and Kumahara, who noted that a patient being
treated orally with 1-hydroxyvitamin D3 for osteoporosis
had remission of their psoriatic skin lesions.40 They followed this observation with a study of 17 patients with
psoriasis and demonstrated that nearly 80% of their
patients treated orally with 25-hydroxyvitamin D3
showed clinically significant improvement.41
Since then, several landmark clinical trials have demonstrated the excellent efficacy and safety profiles of vitamin
D analogs in the treatment of psoriasis.28,4248 Numerous
studies have shown that analogs such calcitriol, calcipotriol,
tacalcitol, hexafluoro-1,25(OH)2D, and maxacalcitol are
effective and safe in the topical treatment of psoriasis.28,4248 In these clinical trials, measures of efficacy were
largely based on psoriasis area severity index (PASI) scores
and total body surface involvement, and safety was
assessed by a variety of laboratory markers, including
serum levels of calcium, parathyroid hormone, calcitonin,
1,25(OH)2D (calcitriol), urinary calcium, creatinine, calcium/creatinine ratio in spot and 24-hour urine and urinary alpha1-microglobulin.28,4248
Calcipotriol
Calcipotriol has been demonstrated to be a very safe and
effective topical treatment for psoriasis.28,44 In a large
randomized, double-blinded, multicenter comparison
study, it was shown that calcipotriol ointment, when
applied at a dosage of 50 lg/g twice a day, was statistically more effective in reducing erythema, lesional thickness, scaling, and overall PASI score as compared to a
twice-daily treatment of 0.1% betamethasone 17-valerate
ointment.44 Adverse events were equally common in both
groups (<5%), although the most common adverse event,
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which was mild skin irritation, was slightly greater on the

calcipotriol side.44
Maxacalcitol
In a large, double-blind, placebo-controlled active comparator study, treatment of patients with psoriasis with
maxacalcitol ointment at a dose of 25 lg/g once daily
was shown to be more effective in reducing erythema and
scaling than once-daily calcipotriol ointment at a dose of
50 lg/g.28,49 Adverse effects were similar, and the most
common adverse event observed in the maxacalcitol treatment group was skin irritation.28,49 For three of four
patients developing this side effect, symptoms were severe
enough to recommend discontinuation of the treatment.28,49
Tacalcitol
The efficacy and safety of daily treatment with tacalcitol
ointment at a dose of 4 lg/g and 20 lg/g has been demonstrated as well.28,45,47,50 In one recent study, topical
treatment with tacalcitol was generally well tolerated,
with no serious adverse events reported. However, discontinuation of the treatment due to skin irritation was
seen in 5.9% of the patients.28,47 The greatest incidence
of cutaneous side effects occurred during initial treatment
and decreased markedly with continued use.47
Treatment of scalp psoriasis
Calcipotriol solution has been shown an effective topical
treatment option in scalp psoriasis.28,51 In a double-blind,
randomized multicenter study, 49 patients were treated
twice a day over four weeks, and 60% of patients on calcipotriol showed clearance or marked improvement versus 17% in the placebo group, with no major side effects
reported.28,51
Treatment of nail psoriasis
In general, psoriatic nails are very difficult to treat.
Although it has been reported that calcipotriol ointment
is effective in the treatment of nail psoriasis, there has
been no conclusively effective treatment for psoriatic nails
to date.28
Oral treatment with vitamin D and analogs
The efficacy and safety of oral calcitriol as a potential
treatment of psoriasis has been demonstrated as
well.28,42,46 In a long-term study of 85 patients receiving
oral calcitriol for 36 months for the treatment of
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The Role of Vitamin D in Psoriasis

psoriasis, 88.0% showed some improvement in their disease, while 26.5%, 26.3%, and 25.3% had complete,
moderate, and slight improvement in their disease, respectively.28,46 The biggest concern with oral vitamin D supplementation is its effects on calcium absorption in the
gut and subsequent calcium homeostasis systemically.
Vitamin D enhances the absorption of calcium within the
intestinal tract, and hypercalcemia secondary to excess
vitamin D intake is of real concern. To avoid its effects
on enhancing dietary calcium absorption, it is suggested
to take calcitriol at night.28,46 The study demonstrated
that utilizing a night-time dosing technique and maintaining a calcium intake of no more than 1 g/day resulted in
excellent tolerance of calcitriol doses from 2 to 4 lg/day
without any serious adverse side effects.28,46
Patients with psoriasis may need intermittent treatment
for their whole lives. It is now accepted that vitamin D
analogs are effective and safe for the topical treatment of
skin and are particularly useful for hard-to-treat areas
such as the face or inguinal regions that are sensitive to
steroid-induced atrophy.28,43,44,47 Vitamin D analogs do
not exhibit tachyphylaxis as seen with corticosteroids,
and topical treatment can be continued indefinitely without serious adverse side effects.28 Additionally, they are
effective in the treatment of psoriatic skin lesions in children and in patients with HIV.28 In a recent analysis of
vitamin D analogs for irritancy, phototoxicity, and photoallergic contact sensitization, it was shown that calcitriol at a dose of 3 lg/g ointment was non-irritating
compared to calcipotriol, tacalcitol ointment was slightly
irritating, and calcipotriol was moderately irritating.28,52
Using standard photoallergenicity testing methodology,
no skin reactions of a photoallergic nature were
found.28,52 Additionally, combined topical treatment
using calcipotriol ointment at a dose of 50 lg/g with
betamethasone ointment was shown to cause less skin
irritation and to be slightly more effective than calcipotriol used twice daily.28,30,52
Given our advancements in understanding the role of
vitamin D in skin disease combined with our progressively expanding knowledge base regarding the pathogenesis of psoriasis, it is evident that not only are vitamin D
analogs excellent treatment options for the management
of psoriasis but that the inherent presence or absence of
vitamin D in the body itself may alter the severity and
progression of the disease. Emerging literature supports
this hypothesis. A recent casecontrol study compared the
serum levels of 25(OH)D in patients with psoriasis with
matched controls, looking at comparisons in PASI score,
body mass index (BMI), C-reactive protein, and other
markers of inflammation and metabolic derangement.53
With no major difference in vitamin D intake between
the two groups, and vitamin D supplementation being an
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exclusion criterion, it was found that patients with psoriasis had significantly lower serum 25(OH)D concentrations than control subjects.53 Even after adjusting for
possible confounding variables, the study was still able to
demonstrate that serum 25(OH)D levels were significantly
lower in patients with psoriasis than in control subjects
and that the 25(OH)D levels were negatively associated
with C-reactive protein, a marker of inflammatory activation, and with BMI.53 Additionally, patients with psoriasis with BMI 27 kg/m2 were found to have a higher risk
of 25(OH)D insufficiency.53 A follow-up study by the
same investigators looked specifically at the relationship
between vitamin D levels, psoriasis, and the metabolic
syndrome. The studys findings corroborated their earlier
results, demonstrating that patients with psoriasis had significantly lower levels of 25(OH)D than controls, patients
with metabolic syndrome had significantly lower serum
levels of 25(OH)D than those without, and a negative
correlation was seen between 25(OH)D and waist circumference, diastolic blood pressure, fasting glucose, and triglyceride levels.54 Another recent cross-sectional study yet
again demonstrated similar findings between patients with
psoriasis and vitamin D levels, showing that serum levels
of 25(OH)D were significantly lower in patients with psoriasis than in control subjects, and that the prevalence of
vitamin D deficiency, defined as a serum level <20 ng/ml,
was significantly higher among patients with psoriasis
compared with the other control groups.55 Interestingly
in this study, the investigators compared patients with
psoriasis to not only healthy controls but also to matched
patients with rheumatoid arthritis, as a positive control
for the effect modifier of autoimmune disease. The
authors stated that the rationale for comparing patients
with psoriasis to those with rheumatoid arthritis was to
have a control with another chronic immune-mediated
inflammatory disease that has already been associated
with vitamin D deficiency. When they compared the two
groups, they found no significant difference in 25(OH)D
levels between patients with psoriasis and those with
rheumatoid arthritis. This supports the notion that vitamin D is a critical component in global immune homeostasis, that its absence or presence is not only implicated
in the pathogenesis of psoriasis but that its role in inflammatory pathology and autoimmune disease is far more
intrinsically essential and widespread.
Based on conclusions from studies such as those
described earlier, it is reasonable to hypothesize that the
seasonal variation in disease severity seen in patients with
psoriasis may be at least partially attributable to the concurrent seasonal variations in vitamin D levels. The crosssectional study described earlier attempted to confirm this
hypothesis. The study demonstrated that not only was
vitamin D deficiency significantly more prevalent in
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Review

The role of vitamin D in psoriasis: a review

Teo Soleymani1, MD, Tracy Hung2, BS, and Jennifer Soung1, MD

1
Department of Dermatology, University of
California, Irvine School of Medicine, Irvine,
CA, and 2Drexel University College of
Medicine, Philadelphia, PA, USA

Correspondence
Jennifer Soung, MD,
Department of Dermatology
University of California, Irvine School of
Medicine
1001 Hewitt Hall
Irvine
CA 92697-2400
USA
E-mail: jsoung@uci.edu
Conflicts of interest: None.
doi: 10.1111/ijd.12790

Abstract
Background and objective Psoriasis is a common, chronic autoimmune inflammatory
skin disorder, which has potential systemic complications and is clinically defined by
sharply demarcated, erythematous patches and plaques covered by a characteristic silvery
white scale. Topical corticosteroids have widely been regarded as the mainstay first line of
treatment. Recently, topical vitamin D analogs have been added to the first-line treatment
repertoire as well, either as monotherapy or in combination with topical steroids due to
synergistic, complementary effectiveness. In this paper, we review the role of vitamin D in
the pathophysiology and treatment of psoriasis.
Methods A comprehensive search of the Cochrane Library, MEDLINE, and PUBMED
databases were performed to identify relevant basic science and clinical trial literature
investigating the role of vitamin D in psoriasis. Primary endpoints in clinical trials were
largely based on clinical improvement as assessed by the psoriasis area severity index
score or physicians global assessment.
Results and conclusion The role of vitamin D in psoriasis is complex and extensive. Oral
and topical vitamin D therapies provide comparable efficacies to corticosteroids when used
as monotherapy and may be superior when used in combination with a potent topical
steroid. Additionally topical vitamin D analogs demonstrate a favorable safety profile with
steroid-sparing effects. Thus, topical vitamin D derivatives should be considered an
indispensable component of the current physicians arsenal in the treatment of psoriasis.

Introduction
Psoriasis is a common, chronic autoimmune inflammatory
skin disorder, which has potential systemic complications
and is clinically defined by sharply demarcated, erythematous patches and plaques covered by a characteristic silvery
white scale. Classically, psoriasis affects the scalp, elbows,
knees, umbilicus, and lumbar area, though lesions can
occur anywhere and can cover the entire skin surface.
Although psoriasis is a relatively prevalent skin disease, its
distinct definition by Ferdinand von Hebra dates back only
to 1841, and estimates of its prevalence, widely quoted as
2% in medical textbooks, are based on only a few old population studies.1 We now know that prevalence in the general population is much more varied, based on a variety of
ethnic and genetic factors, ranging anywhere from 0.45 to
4.6%.13 Though the complex pathogenesis of psoriasis
remains incompletely understood, compelling evidence suggests that it is a systemic autoimmune disease in which T
lymphocytes play a key central role in the subsequent production and activation of inflammatory cytokines.1,2,47
Vitamin D has long been known to be a hormone that
regulates calcium homeostasis and maintains the skeletal
2015 The International Society of Dermatology

system in the human body. Historically associated with

childhood rickets and adult osteomalacia, vitamin D deficiency has now been linked to chronic systemic illnesses,
including common cancers, autoimmune diseases such as
multiple sclerosis and type 1 diabetes, infectious diseases,
as well as cardiovascular neurodegenerative disease.810
Recently it has been discovered that vitamin D may also
play a role in the autoimmune diseases of the skin as
well.1,812 The relationship between skin diseases and
vitamin D has particularly gained interest in recent literature. In particular, many current studies have focused on
the relationship between vitamin D and psoriasis, and
although much remains unknown, there have been an
increasing number of publications addressing the various
possible pathomolecular mechanisms underlying the role
of vitamin D in this particular disease. In this paper, we
explore the role of vitamin D in psoriasis.
Synthesis of vitamin D
There are two forms of vitamin D: ergocalciferol (vitamin
D2) and cholecalciferol (vitamin D3). vitamin D2 is
derived from the yeast sterol, ergosterol, whereas vitamin
International Journal of Dermatology 2015

Review

The Role of Vitamin D in Psoriasis

Conclusion
The role of vitamin D on the skin is multifaceted and
inherently complex. Vitamin D and its analogs have been
shown to regulate cellular differentiation, proliferation,
and apoptosis, as well as modulate both the humoral and
cellular immune systems. Within the past 2030 years, it
has convincingly been shown that vitamin D compounds
are safe and effective in the topical treatment of psoriasis.
Currently they are considered first-line therapy, both as
monotherapy and in combination with topical corticosteroids. With todays rapidly advancing research and promising clinical trials, the future of vitamin D therapy on
cutaneous diseases looks very promising. Todays vitamin
D analogs are more effective than those of yesterday,
exerting antiproliferative and anti-inflammatory properties while minimizing their calcemic activity. Though the
exact role of vitamin D in the pathogenesis and severity
of psoriasis remains unclear, further studies exploring the
complex connection will help elucidate this important
relationship.

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