Review

The role of vitamin D in psoriasis: a review

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

1Department 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 inflammatoryskin disorder, which has potential systemic complicationsand is clinically defined by sharply demarcated, erythema-tous patches and plaques covered by a characteristic silverywhite scale. Classically, psoriasis affects the scalp, elbows,knees, umbilicus, and lumbar area, though lesions canoccur anywhere and can cover the entire skin surface.Although psoriasis is a relatively prevalent skin disease, itsdistinct definition by Ferdinand von Hebra dates back onlyto 1841, and estimates of its prevalence, widely quoted as2% in medical textbooks, are based on only a few old pop-ulation studies.1 We now know that prevalence in the gen-eral population is much more varied, based on a variety ofethnic and genetic factors, ranging anywhere from 0.45 to4.6%.13 Though the complex pathogenesis of psoriasisremains incompletely understood, compelling evidence sug-gests that it is a systemic autoimmune disease in which Tlymphocytes play a key central role in the subsequent pro-duction and activation of inflammatory cytokines.1,2,47

Vitamin D has long been known to be a hormone thatregulates calcium homeostasis and maintains the skeletal

system in the human body. Historically associated withchildhood rickets and adult osteomalacia, vitamin D defi-ciency has now been linked to chronic systemic illnesses,including common cancers, autoimmune diseases such asmultiple sclerosis and type 1 diabetes, infectious diseases,as well as cardiovascular neurodegenerative disease.810

Recently it has been discovered that vitamin D may alsoplay a role in the autoimmune diseases of the skin aswell.1,812 The relationship between skin diseases andvitamin D has particularly gained interest in recent litera-ture. In particular, many current studies have focused onthe relationship between vitamin D and psoriasis, andalthough much remains unknown, there have been anincreasing number of publications addressing the variouspossible pathomolecular mechanisms underlying the roleof vitamin D in this particular disease. In this paper, weexplore the role of vitamin D in psoriasis.

Synthesis of vitamin D

There are two forms of vitamin D: ergocalciferol (vitaminD2) and cholecalciferol (vitamin D3). vitamin D2 isderived from the yeast sterol, ergosterol, whereas vitamin

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1

D3 is synthesized in the human skin following ultraviolet(UV) light exposure and can be found in oil-richfish.10,13,14 Unfortunately, very few foods in nature con-tain sufficient quantities of vitamin D. Oil-rich fatty fishsuch as salmon, tuna, and mackerel are among the bestsources of vitamin D, and to a lesser extent in beef liver,cheese, and egg yolks.10,13,14 These animal sources pro-vide vitamin D predominantly in the form of vitaminD3.

10,13,14 Plant sources of vitamin D are predominantlyin the form vitamin D2 and are generally consideredinsufficient in quantity.10,13,14 Plant sources of vitamin Dare formed after exposure of the plant to UV light andcan be artificially enhanced through increased UV expo-sure in controlled settings, as is the case with mushroomsin the USA.10,13,14

In general, fortified foods provide the majority of thevitamin D consumed in the American diet.10,13,14 Forexample, almost all of the US milk supply is voluntarilyfortified with vitamin D, originally as an effort establishedin the 1920s1930s as a way to combat rickets in theUSA.10,13,14 Other dairy products made from milk, such ascheese, yogurt, and ice cream, also contain variable quanti-ties of vitamin D stemming from the milk that was used.Furthermore, ready-to-eat breakfast cereals often containadded 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 interchange-able. However, with the emergence of 25-hydroxyvitaminD as an objective, quantitative measure of vitamin D status,recent studies have demonstrated that vitamin D3 is themore potent form and functionally utilizable form ofvitamin D.13 While both forms are currently available asover-the-counter supplements and despite an emergingbody of evidence suggesting the greater bioefficacy ofvitamin D3, the form of vitamin D most commonly used inmajor preparations of prescriptions in North America isstill remains vitamin D2.

10,13

Although vitamin D can be obtained in dietary prod-ucts, the skin is the major source of vitamin D for thebody.8,10,12,15,16 The keratinocytes of the epidermis areunique in being not only the primary source of vitamin Dsynthesis but also in possessing the enzymatic machineryneeded to metabolize vitamin D to its active metabolite1,25-dihydroxyvitamin D3 (calcitriol or 1,25(OH)2D).

15,17

UVB light (290320 nm) produces a photochemical reac-tion in the skin, converting 7-dehydrocholesterol to previ-tamin D3.

8,10,11,15,16,18 Both the degree of epidermalpigmentation and intensity of exposure correlate with thetime required to achieve this maximal concentration ofprevitamin D3 but do not alter the maximal levelachieved.15 Melanin in the epidermis, by absorbing UVirradiation, can reduce the effectiveness of sunlight in

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

formed in the skin, it undergoes temperature-dependentthermal isomerization to vitamin D3.

11,16,18 Vitamin D3then binds to vitamin D-binding protein and is then trans-ported to the liver, where it is hydroxylated and convertedto 25-hydroxyvitamin D3 (25(OH)D).

1012,18 25(OH)D isfurther transported by the vitamin D-binding protein tothe kidney and catalyzed to its hormonally active form1,25(OH)2D.

1012,18 Any excess previtamin D3 or vitaminD3 is destroyed by sunlight, and thus excessive exposureto sunlight does not cause vitamin D3 intoxication.

10,12,15

Vitamin D deficiency

What was once thought to be a resolved matter given thefortification of food and the apparent eradication ofchildhood rickets, vitamin D deficiency is, in fact, a com-mon problem both in the USA and worldwide.810

According to several recent epidemiological studies,nearly 4090% of the elderly, 3254% of the healthyadult population, and 4560% of adolescents in the USAare deficient in vitamin D.9,10,1921 The total number ofcases of vitamin D deficiency has reached more than onebillion worldwide.8

Approximately 80100% of functionally utilizable vita-min D comes from solar radiation, with only a small frac-tion coming from diet.8,1012,22,23 Because of this, manyauthors hypothesize that the recent epidemic of vitamin Dinsufficiency/deficiency is largely attributed to changes inthe patterns of sun exposure, with strict sun protectionand avoidance strategies being a leading cause.8,10,11,22,23

As alluded to earlier, melanin in the epidermis absorbsUV irradiation and can therefore reduce the effectivenessof sunlight in producing vitamin D3 in the skin.

15 Thishas been thought to be the reason behind the lower levelsof vitamin D seen in darker-skinned individuals living intemperate latitudes.24 In fact, there is a generally heldconsensus by many investigators that populations ofdark-skinned individuals, particularly those living closerto the equator, are clinically deficient in vitamin D, lar-gely because of the impairment of UV conversion due tothe absorption of UV light by the abundant melanin intheir skin.8,10,11,22,24 However, recent studies further ana-lyzing the serum levels of vitamin D and its transporter indark-skinned individuals found that although total vita-min D levels were indeed lower, the available free frac-tion of vitamin D3 was within normal limits, suggestingthat there is no real deficiency after all.8,10,11,24

In the scientific community as well as in the generalpublic, there is an ongoing debate as to the risks versusbenefits of solar UV exposure. On the one hand, solar UVradiation represents the most significant environmentalrisk factor for the development of non-melanoma skin

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Review The Role of Vitamin D in Psoriasis Soleymani, Hung and Soung2

cancer.11,22,23 Consequently, UV protection is an impor-tant measure to prevent these malignancies, particularlyin high-risk groups. On the other hand, however, approx-imately 90% of all vitamin D needed by the human bodyhas to be formed in the skin through the action of UVradiation.8,1012,22,23 This dilemma represents a seriousproblem, given the prevalence of vitamin D deficiencyand its associated chronic diseases. As such, it has beenassumed that for the general population in the USA, Eur-ope, and other countries, the net effects of solar UVBradiation on human health are beneficial at or near cur-rent levels.22 Additionally, recent studies have confirmedthat strict sun exposure prevention causes vitamin D defi-ciency and that the detection and treatment of it in sun-deprived risk groups is of high importance.11,22,23 It isimportant to note, however, that this does not mean thatwearing sunscreen causes vitamin D deficiency. The stud-ies demonstrating the development of vitamin D defi-ciency as a result of strict sun exposure preventionexamined collective efforts in avoiding UV exposure,including wearing clothing that blocked UV absorption,wearing hats, staying indoors at certain times of the day,in addition to wearing sunscreen (hence the term strictsun exposure prevention).8,1012,22,23 It was never sug-gested that sunscreen alone, or any one single method ofUV avoidance, was the sole culprit leading to lower vita-min D levels but rather the collective and combinedefforts of strict sun avoidance strategies together thatcould impair vitamin D synthesis and lead to a clinicallysignificant deficiency. Additionally, as alluded to earlier,neither sun exposure itself nor diet alone provides enoughvitamin D alone as a single source.The US Endocrine Society guidelines have defined a

vitamin D level of 2129 ng/ml as insufficient and

(4 d from basal layer to stratum corneum compared with28 d in normal skin).1 Abnormal differentiation in psori-atic skin is further evidenced by a delay in the expressionof K1 and K10, seen in normal skin, and an overexpres-sion of K6 and K16, seen in reactive and healing skin.1

At physiological concentrations, vitamin D helps to pro-mote keratinocyte growth and development and protectsthem against premature apoptosis; however, at pharmaco-logical concentrations (106 M), vitamin D inhibitskeratinocyte proliferation and exerts a selective proapop-totic effect.11,12,28 These effects on keratinocyte growthand development are essential in the role of vitamin D intreating psoriasis. Furthermore, as mentioned earlier, vita-min D modulates the expression of K1 and K10 in thestratum spinosum, two important keratins known to havedelayed expression in psoriatic skin.15,17 Such effects arethought to be, in part, the mechanisms behind which vita-min D treatment improves psoriasis. Recent studies havefurther supported this notion. Immunohistochemical andbiochemical analyses have demonstrated antiproliferativeand pro-differentiating effects in epidermal keratinocytesalong with treatment with 1,25(OH)2D3 or analogs invivo.28 Furthermore, in addition to its effects on keratino-cyte development and differentiation, vitamin D has beenshown to normalize the distribution of integrins, namelyCD26, ICAM-1, and HLA-DR, along the dermalepider-mal junction, which are altered in psoriatic skin.29 It ishypothesized that the altered localization of integrinsresults in the loss of their adhesive ability and overprolif-eration of keratinocytes in psoriasis.29 Recent studiescomparing the effect of topical vitamin D treatment onintegrin arrangements in lesional psoriatic, non-lesionalpsoriatic, and normal-skinned patients found that the in-tegrin subunit staining patterns were normalized in lesion-al psoriatic skin after treatment, whereas no differencewas seen in non-lesional psoriatic skin compared to nor-mal skin before and after treatment.29,30

As 1,25(OH)2D exerts its effects through binding toVDR, it has been postulated that the responsiveness tovitamin D therapy depends on the level of expression ofVDR in keratinocytes.11,12,31 Recent studies have demon-strated that mice, deficient in epidermal VDR, are unableto respond to vitamin D, suggesting that the improvementof psoriasis with vitamin D treatment correlates directlywith the level of VDR present in lesional skin.11,31 More-over, it has been shown that VDR expression is related tothe cell cycle: VDR levels decrease during the arrestingphase and increase once the cell re-enters the cell cycle.31

Thus, it can be inferred that vitamin D would preferen-tially act on proliferating cells.11,12,31 In addition to theirintrinsic antiproliferative effects, vitamin D analogs havebeen shown to upregulate the expression of VDR onepidermal keratinocytes, thus temporally amplifying their

own potency and enhancing their regulatory role on celldifferentiation and proliferation.11,12,30,31

Much work has been done to elucidate the immuno-modulatory role of vitamin D within the skin. Recent lit-erature has shown that vitamin D plays a critical role inregulating both cellular and humoral immunity throughthe suppression of T-cell proliferation, preferential devel-opment of T-helper (Th)2 cells, induction of regulatory Tcells, modulation of cytokine production and activation,as well as regulating dendritic cell maturation and migra-tion.12,26,27,32,33 Recent studies have also demonstratedthat vitamin D regulates B-cell development by inducingapoptosis in activated B cells and inhibits their prolifera-tion but has no effect on non-stimulated B cells.34

In psoriatic skin, T lymphocytes play a key centralrole in the subsequent production and activation ofinflammatory cytokines.1,2,47,35 Eloquent immunologicalstudies have demonstrated that psoriasis is a processbased on T-cell dysregulation, even without previous epi-thelial abnormalities.1,6,7 Additionally, psoriasis may bethe model example of a disorder that clearly shows acentral role of cytokines and chemokines in the patho-genesis of this disease.1 Cytokine dysregulation mayexplain, at least in part, the complex tissue alterationsseen in psoriatic skin.1,2,4,6,35,36 Proinflammatory chemo-tactic cytokines, particularly tumor necrosis factor-a,interferon-c, interleukin (IL)-2, and IL-8, have beenextensively implicated in the pathogenesis of psoriasis,playing critical roles in the T-cell-mediated inflammatoryprocess.1,2,4,6,35 Studies examining the role of vitamin Don the cutaneous immune system have demonstrated itsability to inhibit the production of cytokines needed forTh1 and Th17 differentiation, stimulate T cells to pro-duce anti-inflammatory Th2 cytokines such as IL-10,and thus reduce the production of inflammatory cyto-kines such as IL-2, IL-8 interferon-c, and tumor necrosisfactor-a, as well as reduce the density of major histo-compatibility complex class II molecules on dendriticcells.4,11,12,25,26,32,33,36 Such profound effects on T-celldevelopment and cytokine production in part underliethe mechanisms behind the therapeutic action of vitaminD on psoriatic skin.Moreover, vitamin D analogs have been shown to sup-

press the Th17 cytokine-mediated production of psoriasinand koebnerisin, two antimicrobial chemoattractant pep-tides that amplify inflammation in psoriasis.37 Vitamin Dhas also been shown to induce the antimicrobial peptidecathelicidin (LL-37) in keratinocytes.33,38 Cathelicidinserves as a first-line defense mechanism in the innateimmune system, and has anti-inflammatory effects thatblunt activation of macrophages.33,38 Cathelicidinremains at a low level in normal skin and is upregulatedin wound healing and tissue repair.38 A recent study

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Review The Role of Vitamin D in Psoriasis Soleymani, Hung and Soung4

demonstrated that thymic stromal lymphopoietin, a cyto-kine known to induce Th2 differentiation and inhibitIL-12/23 production, as well as cathelicidin were bothsignificantly upregulated following topical application ofcalcitriol and calcipotriol on psoriatic lesions.33 Ascathelicidin is usually overexpressed in psoriatic skin, itwas suggested that the cathelicidin induced by the topicaltreatment acted as an inhibitor of inflammation in psori-atic skin rather than an exacerbator.33

Vitamin D in the treatment of psoriasis

In 1985, two important observations in psoriasis researchwere made. One was made by MacLaughlin et al., whoreported that psoriatic fibroblasts were partially sensitiveto the antiproliferative effects of 1,25(OH)2D, promptingthem to investigate the role of calcitriol in the treatmentof hyperproliferative diseases, namely psoriasis.28,39 Theother, almost serendipitous observation was made byMorimoto and Kumahara, who noted that a patient beingtreated orally with 1-hydroxyvitamin D3 for osteoporosishad remission of their psoriatic skin lesions.40 They fol-lowed this observation with a study of 17 patients withpsoriasis and demonstrated that nearly 80% of theirpatients treated orally with 25-hydroxyvitamin D3showed clinically significant improvement.41

Since then, several landmark clinical trials have demon-strated the excellent efficacy and safety profiles of vitaminD analogs in the treatment of psoriasis.28,4248 Numerousstudies have shown that analogs such calcitriol, calcipotriol,tacalcitol, hexafluoro-1,25(OH)2D, and maxacalcitol areeffective and safe in the topical treatment of psoria-sis.28,4248 In these clinical trials, measures of efficacy werelargely based on psoriasis area severity index (PASI) scoresand total body surface involvement, and safety wasassessed by a variety of laboratory markers, includingserum levels of calcium, parathyroid hormone, calcitonin,1,25(OH)2D (calcitriol), urinary calcium, creatinine, cal-cium/creatinine ratio in spot and 24-hour urine and uri-nary alpha1-microglobulin.

28,4248

Calcipotriol

Calcipotriol has been demonstrated to be a very safe andeffective topical treatment for psoriasis.28,44 In a largerandomized, double-blinded, multicenter comparisonstudy, it was shown that calcipotriol ointment, whenapplied at a dosage of 50 lg/g twice a day, was statisti-cally more effective in reducing erythema, lesional thick-ness, scaling, and overall PASI score as compared to atwice-daily treatment of 0.1% betamethasone 17-valerateointment.44 Adverse events were equally common in bothgroups (

psoriasis, 88.0% showed some improvement in their dis-ease, while 26.5%, 26.3%, and 25.3% had complete,moderate, and slight improvement in their disease, respec-tively.28,46 The biggest concern with oral vitamin D sup-plementation is its effects on calcium absorption in thegut and subsequent calcium homeostasis systemically.Vitamin D enhances the absorption of calcium within theintestinal tract, and hypercalcemia secondary to excessvitamin D intake is of real concern. To avoid its effectson enhancing dietary calcium absorption, it is suggestedto take calcitriol at night.28,46 The study demonstratedthat utilizing a night-time dosing technique and maintain-ing a calcium intake of no more than 1 g/day resulted inexcellent tolerance of calcitriol doses from 2 to 4 lg/daywithout any serious adverse side effects.28,46

Patients with psoriasis may need intermittent treatmentfor their whole lives. It is now accepted that vitamin Danalogs are effective and safe for the topical treatment ofskin and are particularly useful for hard-to-treat areassuch as the face or inguinal regions that are sensitive tosteroid-induced atrophy.28,43,44,47 Vitamin D analogs donot exhibit tachyphylaxis as seen with corticosteroids,and topical treatment can be continued indefinitely with-out serious adverse side effects.28 Additionally, they areeffective in the treatment of psoriatic skin lesions in chil-dren and in patients with HIV.28 In a recent analysis ofvitamin D analogs for irritancy, phototoxicity, and pho-toallergic contact sensitization, it was shown that calcitri-ol at a dose of 3 lg/g ointment was non-irritatingcompared to calcipotriol, tacalcitol ointment was slightlyirritating, and calcipotriol was moderately irritating.28,52

Using standard photoallergenicity testing methodology,no skin reactions of a photoallergic nature werefound.28,52 Additionally, combined topical treatmentusing calcipotriol ointment at a dose of 50 lg/g withbetamethasone ointment was shown to cause less skinirritation and to be slightly more effective than calcipotri-ol used twice daily.28,30,52

Given our advancements in understanding the role ofvitamin D in skin disease combined with our progres-sively expanding knowledge base regarding the pathogen-esis of psoriasis, it is evident that not only are vitamin Danalogs excellent treatment options for the managementof psoriasis but that the inherent presence or absence ofvitamin D in the body itself may alter the severity andprogression of the disease. Emerging literature supportsthis hypothesis. A recent casecontrol study compared theserum levels of 25(OH)D in patients with psoriasis withmatched controls, looking at comparisons in PASI score,body mass index (BMI), C-reactive protein, and othermarkers of inflammation and metabolic derangement.53

With no major difference in vitamin D intake betweenthe two groups, and vitamin D supplementation being an

exclusion criterion, it was found that patients with psori-asis had significantly lower serum 25(OH)D concentra-tions than control subjects.53 Even after adjusting forpossible confounding variables, the study was still able todemonstrate that serum 25(OH)D levels were significantlylower in patients with psoriasis than in control subjectsand that the 25(OH)D levels were negatively associatedwith C-reactive protein, a marker of inflammatory activa-tion, and with BMI.53 Additionally, patients with psoria-sis with BMI 27 kg/m2 were found to have a higher riskof 25(OH)D insufficiency.53 A follow-up study by thesame investigators looked specifically at the relationshipbetween vitamin D levels, psoriasis, and the metabolicsyndrome. The studys findings corroborated their earlierresults, demonstrating that patients with psoriasis had sig-nificantly lower levels of 25(OH)D than controls, patientswith metabolic syndrome had significantly lower serumlevels of 25(OH)D than those without, and a negativecorrelation was seen between 25(OH)D and waist circum-ference, diastolic blood pressure, fasting glucose, and tri-glyceride levels.54 Another recent cross-sectional study yetagain demonstrated similar findings between patients withpsoriasis and vitamin D levels, showing that serum levelsof 25(OH)D were significantly lower in patients with pso-riasis than in control subjects, and that the prevalence ofvitamin D deficiency, defined as a serum level

patients with chronic plaque psoriasis than in controls butthat the prevalence of vitamin D deficiency was signifi-cantly higher in winter than in summer.55 Furthermore,the association between vitamin D deficiency and psoriasiswas independent of confounding variables such as age,sex, BMI, PASI score, parathyroid hormone as well as theseason in which the serum sample was taken.55 However,despite these findings, the authors were not able to demon-strate a direct causal or linearly temporal relationshipbetween the seasonal variance in vitamin D levels andchanges in PASI scores.55 Though many studies haveshown that patients with psoriasis have lower levels ofvitamin D than control subjects, as illustrated above, untilrecently, no studies have demonstrated a direct linear cor-relation between serum vitamin D levels and psoriasisseverity measured through the PASI score.26,53,5557 How-ever, a recent casecontrol study that examined 68patients with chronic plaque psoriasis and 60 healthy con-trols demonstrated not only a high prevalence of vitaminD deficiency in patients with psoriasis but more impor-tantly demonstrated a statistically significant inverse linearcorrelation between patients vitamin D levels and theirPASI scores.58 This supports the hypothesis that vitamin Dlevels may affect a patients psoriasis severity and mayexplain in part why we see such seasonal variation in dis-ease activity even in the face of consistent, compliant treat-ment. With numerous studies demonstrating therelationship between vitamin D levels and psoriasis asdescribed above, it would not be unreasonable to thereforehypothesize that vitamin D supplementation could bepotentially beneficial as a preventative measure in thedevelopment of psoriasis. Interestingly, however, arecently published large prospective study illustrated thatthis was in fact not the case. The study looked at 70,437US females over a span of 14 years, examining vitamin Dintake levels and the incidence of psoriasis in the popula-tion.59 After adjusting for confounding variables, the studyfound that there was no significant association betweenvitamin D intake (dietary, supplementary, and total vita-min D) and the risk of incident psoriasis.59 Thus theauthors proposed that there appeared to be no preventiverole of dietary or supplemental vitamin D intake in thedevelopment of psoriasis.59

UV phototherapy, including psoralen plus UVA, broad-band UVB (BUVB), and narrowband UVB (NBUVB), is awell established and safe treatment option for psoria-sis.1,18,60,61 Additionally, the role of UV radiation incutaneous vitamin D synthesis is a well-known phenome-non.10,16,6164 Though it is well recognized that UV ther-apy works in part by inhibiting cutaneous immunefunction, its therapeutic efficacy in psoriasis, particularlyof the UVB class, may be at least in part due to increasedvitamin D synthesis as well.1,26,28,60 Several recent studies

have put this concept to the test, demonstrating thatincreases in vitamin D post-UVB treatment correlatedwith clinical improvement of psoriasis and PASIscores.1,26,61,64 Recently, the use of UVB has mostlyreplaced the use of psoralen plus UVA due to its lowerrisk in developing skin cancer.18 Furthermore, as NBUVBis easier to handle and better tolerated than BUVB, it ismore commonly used in the clinical setting.64,65 Thoughseveral studies have suggested that that BUVB is able toinduce higher levels of vitamin D than NBUVB treatment,both treatment modalities have demonstrated similar effi-cacy in their ability to reduce PASI scores.61,64,65

Seasonal variations in vitamin D levels also play a con-founding role in examining the exact role of vitamin D inthe treatment of psoriasis with UV therapy.18,62,63 Onerecent study looked at the changes in 25(OH)D levels fol-lowing NBUVB treatment in two groups of patients, oneduring the summer and one during the winter.63 It wasnoted that patients in the winter group had a significantlylower baseline level of 25(OH)D as compared to patientsin the summer group (37.2 ng/ml) and responded morerobustly to NBUVB treatment with an increase in 25(OH)D that was significantly higher (68% increase) thanin the summer group (20%).63 However, the study wasnever able to demonstrate conclusively whether thegreater variance in vitamin D levels of the winter groupbefore and after treatment as compared to the summergroup resulted in any meaningful or clinically significantimprovement in psoriasis area or severity.63

As topical vitamin D analogs have been shown to bevery effective monotherapies in the treatment of psoriasis,combination treatments targeting both immune-mediatedinflammation along with epidermal changes may provideimproved efficacy and safety versus monotherapy. Combi-nation therapy consisting of topical vitamin D analogscombined with UV phototherapy is a well-establishedtreatment regimen for psoriasis.1,65,66 Of note, a recentstudy took 30 patients with psoriasis and divided theminto three groups: NBUVB treatment only; combinationtherapy with topical 8-methoxypsoralen gel; and in com-bination with calcipotriol ointment.65 It was found thatthe group of patients who received combination treatmentof UVB and calcipotriol ointment had the largest reduc-tion in PASI, while there was no statistically significantdifference in improvement between the group thatreceived UVB treatment alone and those who received acombination of UVB and psoralen gel.65 On a technicalnote, it is important to recognize that when using combi-nation treatment consisting of a topical vitamin D analogwith UV phototherapy, the topical medication must beapplied after phototherapy and not before, as the medica-tion will be inactivated by the UV light if applied beforephototreatment.

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Soleymani, Hung and Soung The Role of Vitamin D in Psoriasis Review 7

Conclusion

The role of vitamin D on the skin is multifaceted andinherently complex. Vitamin D and its analogs have beenshown to regulate cellular differentiation, proliferation,and apoptosis, as well as modulate both the humoral andcellular immune systems. Within the past 2030 years, ithas convincingly been shown that vitamin D compoundsare safe and effective in the topical treatment of psoriasis.Currently they are considered first-line therapy, both asmonotherapy and in combination with topical corticoster-oids. With todays rapidly advancing research and prom-ising clinical trials, the future of vitamin D therapy oncutaneous diseases looks very promising. Todays vitaminD analogs are more effective than those of yesterday,exerting antiproliferative and anti-inflammatory proper-ties while minimizing their calcemic activity. Though theexact role of vitamin D in the pathogenesis and severityof psoriasis remains unclear, further studies exploring thecomplex connection will help elucidate this importantrelationship.

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