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They reported that over 1-third of the respondents were unaware of the role of vitamin D in the body&#8212;a significant finding in light of the fact that vitamin D levels were insufficient in 40&#37; of a subsample of respondents in whom these were tested&#46; The recent literature includes several interesting new studies linking vitamin D levels with a number of common skin disorders&#46; The aim of the present review is to provide an overview of the relationship between vitamin D and skin disease based on current evidence&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Synthesis</span><p id="par0010" class="elsevierStylePara elsevierViewall">The body obtains vitamin D in two ways&#46; A small amount of active vitamin D in the form of cholecalciferol can be obtained from dietary intake of animal origin&#58; the foods with significant levels are egg yolks and certain blue fish &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>&#41;&#46; Ergocalciferol&#44; another form of pre-vitamin D&#44; is found in small amounts in foods of vegetable origin&#46; The other way the body obtains vitamin D is through exposure to solar radiation&#46; Photons in UV-B radiation photo-isomerize 7-dehydrocholesterol in the epidermis to precholecalciferol&#44; which is then rapidly converted through a heat-mediated reaction to cholecalciferol or vitamin D<span class="elsevierStyleInf">3</span>&#46; Both molecules are hydroxylated in the liver to calcifediol &#40;25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93;&#41;&#44; which is later hydroxylated in the kidneys through the action of the enzyme 25&#40;OH&#41;D-1-hydroxylase to calcitriol&#44; the active metabolite that performs a range of different functions by binding to its cell receptor&#46; Parathyroid hormone &#40;PTH&#41;&#44; calcium&#44; and phosphorus levels are just some of the factors that play a role in the regulation of this process&#44; in addition to transforming growth factor beta &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Vitamin D Levels and Vitamin D Deficiency&#46; Is There Really a Pandemic&#63;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Daily vitamin D requirements are age dependent and different medical associations do not agree on the levels required&#46; According to the Institute of Medicine &#40;IoM&#41;&#44; the daily requirement is 400 IU in the first year of life&#44; 600 IU between 12 months and 70 years of age&#44; and 800 IU in people over 70 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">3</span></a> However&#44; the American Endocrine Society recommends between 400 and 1000&#160;IU&#47;d in the first year of life and 600 to 1000&#160;IU&#47;d thereafter&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2009&#44; 25&#40;OH&#41;D was established as the best blood marker of vitamin D status&#46; <a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">4</span></a> The societies also have different opinions about desirable levels in the body&#46; While the IoM specifies 20&#160;ng&#47;mL as the lower limit indicating healthy and sufficient levels of vitamin D &#40;<a class="elsevierStyleCrossRef" href="#sec0110">Appendix A</a>&#41;&#44; the American Endocrine Society defines a level under 20 ng&#47;mL as deficient and a level between 20 and 30&#160;ng&#47;mL as insufficient&#44; and considers values above 30&#160;ng&#47;mL &#40;75&#160;mmol&#47;L&#41; to be essential for maintaining good health&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">5</span></a> There is currently generalized alarm worldwide about vitamin D deficiency in both the healthy and the sick population&#46; In response to this situation&#44; an article in The New England Journal of Medicine addressed the question of whether or not there is really a pandemic of vitamin D deficiency in the world today&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">6</span></a> Between 35&#37; and 70&#37; of Europeans have 25&#160;&#40;OH&#41;&#160;D levels considered insufficient by some authors&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">7</span></a> By contrast&#44; in Australia and New Zealand&#44; the percentage ranges from 6&#37; to 9&#37;&#46; Publication of these findings might lead to the consideration of the usefulness of screening healthy people for vitamin D deficiency&#46; However&#44; since routine screening is not currently supported by the IoM or the US Preventive Services Task Force&#44; it is not recommended at this time&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Vitamin D toxicity can cause serious health problems&#46; Blood levels persistently above 200&#160;ng&#47;mL are considered toxic&#46; The most frequent symptoms of toxicity are anorexia&#44; weight loss&#44; polyuria&#44; and cardiac arrhythmias&#46; Vitamin D toxicity also increases the risk of kidney stone formation&#44; the calcification of blood vessels and tissues&#44; and the complications associated with both of these alterations&#46; Toxicity can occur when the daily intake of vitamin D exceeds 10&#44;000&#160;IU&#44; giving rise to 25&#40;OH&#41;D levels in excess of 200 to 240&#160;ng&#47;mL&#46; However&#44; most medical societies consider 25&#40;OH&#41;D levels higher than 125 to 150&#160;ng&#47;mL to be unadvisable in order to avoid the adverse effects of a vitamin D excess&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Modifying Factors</span><p id="par0030" class="elsevierStylePara elsevierViewall">Some people are more susceptible than others to developing vitamin D deficiency&#44; defined as a level below the established minimum of 20&#160;ng&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;&#46; Risk factors for susceptibility include obesity&#44;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">8</span></a> smoking&#44;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">9</span></a> a high skin phototype<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">10</span></a> &#40;although this is still controversial&#41;&#44; insufficient sun exposure&#44; and age&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">11</span></a> With age&#44; the skin produces less of the precursor 7-dehydrocholesterol in the epidermis&#44; intestinal absorption of vitamin D declines due to a reduction in the number of vitamin D receptors &#40;VDR&#41; in enterocytes&#44; and the body&#39;s ability to hydroxylate vitamin D in the liver and kidney also decreases&#46; Some clinical conditions predispose patients to inadequate vitamin D levels&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">12</span></a> These include osteoporosis&#44; chronic kidney disease&#44; liver failure&#44; inflammatory bowel disease&#44; hyperparathyroidism&#44; hyperthyroidism&#44; hypogonadism&#44; and celiac disease&#46; Another risk factor is long-term treatment with certain drugs&#44; including anticonvulsants&#44; antiretrovirals&#44; rifampicin&#44; hormonal treatments prescribed for breast and prostate cancer&#44; and&#44; above all&#44; corticosteroids&#46; Pregnancy can also give rise to low 25&#40;OH&#41;D levels&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Functions of Vitamin D&#58; Regulation of Bone Metabolism and Other Pleiotropes</span><p id="par0035" class="elsevierStylePara elsevierViewall">In 2016&#44; Bikle<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">13</span></a> described the principal functions of vitamin D in the body&#46; A more recent article discussed the relationship between vitamin D and the skin&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">14</span></a> Vitamin D has been shown to have antiproliferative properties&#44; including the inhibition of angiogenesis and metastatic capacity in some tumors&#44; and it also participates in DNA repair&#46; A relationship has even been found between certain mutations in the VDR gene and cancer&#46; In the metabolic system&#44; vitamin D plays an important role in glucidic&#44; lipid&#44; arterial&#44; and vascular homeostasis&#46; It also modulates immune responses by regulating the differentiation of T&#160;helper &#40;Th&#41; 1-9-17 cells and by inducing the formation of antimicrobial peptides such as cathelicidin peptides&#46; In dermatology&#44; it is important because of its immunomodulatory effects in keratinocytes&#44; as described by Gilaberte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">15</span></a> Vitamin D plays an important role in the homeostasis of glucose by promoting insulin secretion in pancreatic beta cells&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">16</span></a> which express alpha-1-hydroxylase through cell stimulation by way of high affinity VDR&#46; Moreover&#44; it decreases peripheral insulin resistance by activating peroxisome proliferator-activated gamma receptors in the liver&#44; muscle&#44; and fatty tissue&#46; In view of this relationship&#44; it has been postulated that vitamin D may be a protective factor in the development of type 2 diabetes mellitus&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">17</span></a> In the case of lipid metabolism&#44; vitamin D can also have an indirect effect&#44; not only because it may improve peripheral insulin resistance<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">18</span></a> and reduce PTH levels &#40;shown to have a lipolytic effect&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">19</span></a> but also because it favors higher serum calcium levels&#44; thereby decreasing hepatic triglyceride production&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">20</span></a> In 2010&#44; Pittas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">21</span></a> published a systematic review on the relationship between blood pressure and vitamin D levels&#46; Their conclusion was that deficient vitamin D levels &#40;&#60;&#160;20&#160;ng&#47;mL&#41; were associated with an increased risk of arterial hypertension&#46; Other studies have shown that vitamin D supplementation improved blood pressure in hypertensive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">22</span></a> This improvement is mediated by various effects&#58; direct effects on vitamin D receptors&#44; which decrease vascular inflammation and correct endothelial dysfunction&#59; regulation of the proliferation&#44; migration&#44; and mineralization of vascular muscle cells<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">23</span></a>&#59; and finally&#44; indirectly by decreasing serum levels of PTH&#44; a hormone that acts on the renin-angiotensin-aldosterone system&#46; Furthermore&#44; recent studies have shown that vitamin D stimulates the release of nitric oxide&#44; thereby reducing oxidative stress in the cardiovascular system&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">24</span></a> It is&#44; therefore&#44; clear that vitamin D not only plays a role in bone metabolism but is also involved in many other functions in the body &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Vitamin D and Skin Disease</span><p id="par0040" class="elsevierStylePara elsevierViewall">Vitamin D has been implicated in the pathogenesis and treatment of a wide variety of skin diseases&#46; These are discussed below&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Psoriasis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Krafka<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">25</span></a> and Thacker<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">26</span></a> were the first scientists to postulate a role for vitamin D in psoriasis&#46; The use of oral vitamin D as a treatment for psoriasis failed because of the risk of hypercalcemia&#46; The development of topical vitamin D analogs&#44; such as calcipotriol and tacalcitol&#44; later revolutionized the treatment of the condition&#46; Bergler-Czop and Brzezi&#324;ska-Wcislo<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">27</span></a> observed a correlation between Psoriasis Area and Severity Index &#40;PASI&#41; scores and serum levels of 25&#40;OH&#41;D and reported that patients with lower vitamin D levels had higher PASI scores&#46; Orgaz-Molina et al&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">28</span></a> demonstrated that patients with psoriasis and a body mass index higher than 27 were more likely to have insufficient 25&#40;OH&#41;D levels&#46; The comorbidities of psoriasis &#40;diabetes mellitus&#44; obesity&#44; and metabolic syndrome&#41; have also been linked to diets low in vitamin D&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">29</span></a> Clinicians should recommend diets that provide vitamin D in view of its beneficial effect on many of the comorbidities associated with psoriasis&#46; The use of vitamin D in psoriasis is currently a grade B recommendation with IIa level of evidence&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Atopic Dermatitis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic and recurrent inflammatory disease&#44; initially characterized by pruritus and eczematous lesions&#46; It affects up to 20&#37; of the pediatric population and around 7&#46;2&#37; of adults&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">30</span></a> AD is caused by an alteration in the cutaneous immune system and a defect in the synthesis of the epidermal barrier&#44; which affects mainly filaggrin&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">31&#44;32</span></a> Many authors have studied the association between vitamin D and AD&#46; Kim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">33</span></a> published a meta-analysis and systematic review of 11 articles&#44; 7 observational studies&#44; and 4 clinical trials&#46; Compared to healthy controls&#44; patients with AD had lower levels of vitamin D&#44; especially in the pediatric population&#46; Oral vitamin D supplements have been associated with reductions in SCORAD and Eczema Area and Severity Index scores in pediatric patients and is considered to be a possible adjuvant treatment in patients with a deficiency &#40;levels below 20&#160;ng&#47;mL&#41;&#46; In a series of 210 adult patients with AD&#44; Van der Schaft et al&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">34</span></a> reported that vitamin D supplementation in patients with deficient levels did not lead to any significant improvement in eczematous lesions&#46; Several studies in the literature report that vitamin D supplementation in children decreased colonization with <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; a microorganism that plays a role in outbreaks of DA&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">35&#8211;37</span></a> Despite the evidence that vitamin D levels tend to be insufficient in adult patients with AD&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">38</span></a> there is still debate about whether vitamin D supplementation is useful in this age group&#46; In children the use of vitamin D is a grade B recommendation with a IIa level of evidence&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ichthyosis Congenita</span><p id="par0055" class="elsevierStylePara elsevierViewall">Sethuraman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">39</span></a> reported low levels of 25&#40;OH&#41;D and high levels of PTH in children with ichthyosis congenita&#46; In that study&#44; vitamin D supplementation with 60&#44;000 IU of oral cholecalciferol for 10 days followed by a maintenance regimen of 400 to 600 IU&#47;d achieved a rapid response&#44; with noticeable improvement in the dermatological symptoms by the fifth day in terms of both scaling and stiffness&#46; Of the 7 children studied&#44; 6 had serum 25&#40;OH&#41;D levels under 4&#160;ng&#47;mL&#46; While more studies are needed&#44; these findings open up interesting possibilities in the management of ichthyosis congenita&#46; Lucker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">40</span></a> published the results achieved with topical calcipotriol in patients with ichthyosis congenita &#40;Netherton syndrome&#44; lamellar&#44; ichthyosis bullosa of Siemens&#44; and epidermolytic ichthyosis of Brocq&#41;&#46; Scaling and associated redness improved in all but the bullous form of the disease&#46; In ichthyoses in which epidermal hyperproliferation and retention hyperkeratosis do not predominate&#8212;such as X-linked ichthyosis&#44; ichthyosis vulgaris&#44; and acquired ichthyosis&#8212;topical application of vitamin D analogs has not been shown to be effective&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">41</span></a> Neema et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">42</span></a> raised the possibility of combining vitamin D with oral retinoid treatment in patients with low vitamin levels&#46; Despite the published findings&#44; the use of vitamin D supplementation in patients with ichthyosis is a grade C recommendation with a IIIa level of evidence&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Acne</span><p id="par0060" class="elsevierStylePara elsevierViewall">Interest in the role of vitamin D in acne first emerged in 1938&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">43</span></a> A comparative study of serum levels of 25&#40;OH&#41;D in adolescents with and without acne was published in PloS One in 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">44</span></a> The patients with acne had lower vitamin D levels than the healthy controls and an inverse relationship was observed between vitamin D levels and the severity and number of inflammatory acne lesions&#46; Following 2 months of vitamin D supplementation&#44; the number of inflammatory lesions decreased but no change was observed in non-inflammatory lesions&#46; The role of vitamin D in acne could be explained by a relationship between the vitamin and reduced synthesis of interleukin &#40;IL&#41; 6&#44; IL-8 and metalloproteinase-9<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">45</span></a> as well as to a reduction in the expression of IL-17 because of its action on Th17 cells&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">46</span></a> Zouboulis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">47</span></a> described the effect of vitamin D on the sebaceous glands and the increase in lipogenesis when vitamin D levels are insufficient&#44; an effect that promotes an increase in inflammatory lesions&#46; The authors of a recent study reported that 25&#40;OH&#41;D levels were higher following treatment than at baseline in patients treated with oral isotretinoin&#44; concluding that the role of vitamin D in the inflammatory pathogenesis of acne is important in the development of lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">48</span></a> The use of vitamin D in acne is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Hidradenitis Suppurativa</span><p id="par0065" class="elsevierStylePara elsevierViewall">Hidradenitis suppurativa &#40;HS&#41; is a chronic inflammatory skin disease with a significant impact on the patients&#8217; quality of life&#46; Several studies have been published on the relationship between HS and vitamin D levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">49&#44;50</span></a> In those studies&#44; the patients with HS had lower vitamin D levels than controls and an inverse correlation was observed between vitamin D levels and disease severity&#46; Following 6 months of vitamin D supplementation&#44; inflammatory nodules improved in 79&#37; of patients &#40;out of the 14 treated&#41;&#59; however&#44; as with acne&#44; no significant changes were observed in non-inflammatory lesions&#46; In the opinion of the authors of another study&#44; the endocrinological and metabolic alterations associated with HS make vitamin D a therapeutic target because of its relationship with metabolic syndrome&#44; among other reasons&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">51</span></a> Well-designed studies with a sufficient number of patients are needed to determine the role of vitamin D in HS&#46; The use of vitamin D in HS is currently a grade B recommendation with a III level of evidence&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Vitiligo</span><p id="par0070" class="elsevierStylePara elsevierViewall">There are more than 300 articles in the literature on the relationship between vitamin D and vitiligo&#46; Karag&#252;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">52</span></a> observed lower serum vitamin D levels in 50 patients with vitiligo compared to healthy controls and an inverse correlation with the extent of disease&#46; In a meta-analysis&#44; Upala and Sanguankeo<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">53</span></a> concluded that the evidence did indicate a clear relationship between vitiligo and low vitamin D levels&#46; Variable results have been reported in cases in which vitiligo was treated with vitamin D analogs either alone<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">54</span></a> or in combination with other treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">55</span></a> However&#44; there are no clinical trials that demonstrate the efficacy of vitamin D supplements in these patients&#46; Khurrum and AlGhamdi<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">56</span></a> found no significant differences in vitamin D levels between patients with vitiligo and healthy controls&#59; in the analysis by subgroups&#44; however&#44; it was observed that in the group of patients with vitiligo&#44; the lowest vitamin D levels were associated with male sex&#44; younger age&#44; a short duration of vitiligo&#44; and not having received treatment with phototherapy&#46; At present&#44; the use of vitamin D in patients with vitiligo is a grade B recommendation with a IIa level of evidence&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Systemic Lupus Erythematosus</span><p id="par0075" class="elsevierStylePara elsevierViewall">Several studies have found a higher prevalence of vitamin D deficiency in patients with systemic lupus erythematosus &#40;SLE&#41; than in the healthy population&#46;<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">57&#44;58</span></a> The authors of a study published in PloS One&#44; which investigated the relationship between vitamin D levels and the severity of SLE&#44; reported that 71&#46;4&#37; of the patients had vitamin D levels under 30&#160;ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">59</span></a> They also observed an association between lower vitamin D levels and poorer scores on the Systemic Lupus Erythematosus Disease Activity Index&#46; However&#44; supplementation with 400 to 1&#44;000 IU&#47;d of vitamin D failed to raise levels above 30&#160;ng&#47;mL&#46; In a comparative study with placebo by Karimzadeh et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">60</span></a> patients with SLE who received vitamin D supplementation showed a significant increase in serum 25&#40;OH&#41;D levels but this was not associated with any effect on disease activity&#46; Some authors defend the usefulness of vitamin D supplementation in these patients on the basis of the protective cardiovascular effect and the possible improvement in systemic symptoms and cognitive development&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">61</span></a> The authors of a recent review article on this topic defend the usefulness of vitamin D in SLE on the basis of its immunomodulatory effects&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">62</span></a> The use of vitamin D in patients with SLE is a grade B recommendation with a IIa evidence level&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Polymorphic Light Eruption</span><p id="par0080" class="elsevierStylePara elsevierViewall">Polymorphic light eruption &#40;PLE&#41; is an idiopathic photosensitivity disorder related primarily with exposure to UV-A and less often with UV-B radiation&#46; It is found more frequently in young women&#46; Schweintzger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">63</span></a> found no significant relationship between vitamin D levels and the number and function of regulatory T cells&#44; concluding that other factors affect the immune response that occurs in PLE&#46; Nevertheless&#44; in another study patients with PLE had lower vitamin D levels than controls and when these were increased by phototherapy with UV-B &#40;311&#160;nm&#41; a correlation was observed between the increase and clinical improvement of the lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">64</span></a> In a placebo-controlled clinical trial&#44; Gruber-Wackernagel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">65</span></a> observed that topical application of calcipotriol 1 week before exposure reduced symptoms in almost 1-third of patients exposed to photoprovocation and suggested this treatment as a possible prophylactic measure&#46; However&#44; there is no consensus in photobiology units on the use of this treatment for PLE&#46; The use of vitamin D in PLE is a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Alopecia Areata</span><p id="par0085" class="elsevierStylePara elsevierViewall">The role of vitamin D in alopecia areata &#40;AA&#41; has been explored in several studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">66&#8211;69</span></a> Thompson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">70</span></a> analyzed data from a cohort of 55&#44;929 women and found no association between vitamin D supplementation and incident AA&#46; However&#44; other studies have found that vitamin D levels tend to be lower in patients with AA than in healthy controls<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">71</span></a> and even lower in patients with universal AA compared to those with the ophthalmic or plaque forms&#46; Vitamin D levels have not been shown to differ significantly according to age&#44; sex&#44; disease duration&#44; disease recurrence&#44; or family history of AA&#46; However&#44; patients with AA have been found to have a lower number of vitamin D receptors in the blood and tissues than the group of healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">72</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">While topical vitamin D analogs can be used to treat AA&#44;<a class="elsevierStyleCrossRefs" href="#bib0835"><span class="elsevierStyleSup">72&#44;73</span></a> no studies have been carried out which demonstrate that oral supplements with vitamin D are effective in this setting&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The use of vitamin D in patients with AA is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Melanoma and Melanoma Metastasis</span><p id="par0100" class="elsevierStylePara elsevierViewall">The role of vitamin D in melanoma has been investigated in a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">74&#8211;77</span></a> Orlow et al&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">78</span></a> identified certain haplotypes of single nucleotide polymorphisms &#40;SNPs&#41; of the vitamin D receptor gene related to increased survival in patients with melanomas in photoexposed sites &#40;rs1544410&#47;BsmI and rs731236&#47;TaqI&#41;&#46; Subsequent studies have reported an inverse correlation between Breslow thickness and vitamin D levels<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">79</span></a> and a possible relationship between low serum vitamin D levels and ulceration<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">80</span></a> in patients with melanoma&#46; In fact&#44; a worse prognosis was observed in the patients whose vitamin D levels were low when melanoma was diagnosed and also when&#44; even after starting supplementation&#44; the patient did not achieve levels above 20&#160;ng&#47;mL&#46; In a recent study of 3578 patients&#44; however&#44; no significant relationship was found between melanoma survival&#44; determined by the Breslow thickness&#44; number of mitosis&#44; ulceration&#44; and SNPs found in the pathway of vitamin D and its receptor&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">81</span></a> This debate has led to new studies to determine the possible advantage of recommending vitamin D supplementation in patients with melanoma in sun-exposed and sun-shielded sites&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">82</span></a> The use of vitamin D in patients with melanoma is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Nonmelanoma Skin Cancer</span><p id="par0105" class="elsevierStylePara elsevierViewall">The role of vitamin D in carcinogenesis<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">83</span></a> led to the study of its relationship with nonmelanoma skin cancer &#40;NMSC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">84</span></a> The cells of basal cell and squamous cell tumors express VDRs&#46; Eide et al&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">85</span></a> reported an association between high vitamin D levels and an increased risk of keratinocyte carcinoma&#46; Vitamin D is also able to inhibit the Hedgehog signaling pathway in basal cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">86</span></a> Research has shown that patients with the Bsml SNP of the vitamin D receptor have a higher risk of developing NMSC&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">87</span></a> However&#44; in a prospective study with more than 60&#44;000 participants&#44; vitamin D supplementation was not associated with squamous cell carcinoma risk or the incidence of basal cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">88</span></a> Confounding factors such as sun exposure and phototype&#44; among others&#44; have given rise to controversies on this topic and clinical trials are required to gain a better understanding of the role of vitamin D in NMSC&#46; The use of vitamin D in patients with NMSC is a grade B recommendation with a IIb level of evidence&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Vitamin D Supplementation in Patients on Long-Term Treatment with Systemic Corticosteroids</span><p id="par0110" class="elsevierStylePara elsevierViewall">Chronic use of systemic corticosteroids gives rise to complications&#44; which include osteoporosis&#46; This is due to the osteolytic activity observed in the short term&#44; associated with osteoblast and osteocyte apoptosis in long-term treatment&#46; The overall relative risk of fractures associated with corticosteroid treatment is 1&#46;33&#46; The risk is higher for vertebral fractures &#40;RR 2&#46;60&#41;&#44; hip fractures &#40;RR 1&#46;60&#41;&#44; and forearm or Colles fractures &#40;RR 1&#46;09&#41;&#46; Associated risk factors in each patient must be taken into account&#59; these include advanced age&#44; family history of fracture or osteoporosis&#44; early menopause&#44; smoking&#44; and a low body mass index determined by bone densitometry&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">89</span></a> The usefulness of vitamin D supplementation during prolonged treatment with oral corticosteroids is supported by the findings of a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0925"><span class="elsevierStyleSup">90&#44;91</span></a> A meta-analysis by Reid et al&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">92</span></a> revealed a correlation between fracture risk and deficient 25&#40;OH&#41;D levels&#46; In another meta-analysis of 11 clinical trials&#44; which included people over 65 years of age &#40;mostly women&#41; showed that supplementation with 800&#160;IU&#47;d of cholecalciferol reduced the risk of hip fracture by 30&#37; and the risk of non-vertebral fracture by 14&#37;&#44; regardless of whether the patients were also taking calcium supplements&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">93</span></a> In several studies&#44; treatment with anti-resorptive agents&#44; such as risedronate or alendronate&#44; in combination with cholecalciferol supplementation for 13 months was associated with an increase in bone mineral density assessed by densitometry&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">94&#44;95</span></a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 4</a> shows the indications for vitamin D supplementation in patients on chronic corticosteroid treatment&#46; <a class="elsevierStyleCrossRef" href="#tbl0030">Table 5</a> shows the available forms of vitamin D supplements and <a class="elsevierStyleCrossRef" href="#tbl0035">Table 6</a> the recommended dosage according to serum vitamin D levels&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Vitamin D has a multiplicity of functions on the cellular level in the many organs and tissues where there are VDR&#46; It would appear that this hormone is fundamental in dermatology&#44; not only because it is synthesized in the skin&#44; but also because of its multiple actions&#44; which are reflected in the variety of diseases in which it appears to play a role&#46; <a class="elsevierStyleCrossRef" href="#tbl0040">Table 7</a> summarizes the diseases in which serum vitamin D levels should be measured and vitamin D supplementation should be considered&#44; depending on the results and taking into account the level of scientific evidence in each case &#40;<a class="elsevierStyleCrossRef" href="#tbl0045">Table 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><elsevierMultimedia ident="tbl0045"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of Interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres1187718"
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          "identificador" => "xpalclavsec1107566"
          "titulo" => "Keywords"
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          "titulo" => "Resumen"
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          "titulo" => "Palabras clave"
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        4 => array:2 [
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          "titulo" => "Background"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Synthesis"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Vitamin D Levels and Vitamin D Deficiency&#46; Is There Really a Pandemic&#63;"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Modifying Factors"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Functions of Vitamin D&#58; Regulation of Bone Metabolism and Other Pleiotropes"
        ]
        9 => array:3 [
          "identificador" => "sec0030"
          "titulo" => "Vitamin D and Skin Disease"
          "secciones" => array:11 [
            0 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Psoriasis"
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            1 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Atopic Dermatitis"
            ]
            2 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Ichthyosis Congenita"
            ]
            3 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Acne"
            ]
            4 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Hidradenitis Suppurativa"
            ]
            5 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Vitiligo"
            ]
            6 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Systemic Lupus Erythematosus"
            ]
            7 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Polymorphic Light Eruption"
            ]
            8 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Alopecia Areata"
            ]
            9 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Melanoma and Melanoma Metastasis"
            ]
            10 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Nonmelanoma Skin Cancer"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Vitamin D Supplementation in Patients on Long-Term Treatment with Systemic Corticosteroids"
        ]
        11 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conclusion"
        ]
        12 => array:2 [
          "identificador" => "sec0100"
          "titulo" => "Conflicts of Interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
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    "fechaRecibido" => "2018-03-19"
    "fechaAceptado" => "2018-08-02"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:8 [
            0 => "Vitamin D"
            1 => "Lupus erythematosus"
            2 => "Ichthyosis"
            3 => "Atopic dermatitis"
            4 => "Hidradenitis suppurativa"
            5 => "Acne"
            6 => "Alopecia"
            7 => "Melanoma"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1107567"
          "palabras" => array:8 [
            0 => "Vitamina D"
            1 => "Lupus eritematoso"
            2 => "Ictiosis"
            3 => "Dermatitis at&#243;pica"
            4 => "Hidrosadenitis supurativa"
            5 => "Acn&#233;"
            6 => "Alopecia"
            7 => "Melanoma"
          ]
        ]
      ]
    ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In recent years&#44; the growing interest in the role played by vitamin D in skin disease has given rise to the publication of many studies of the relationship between this vitamin and certain skin conditions&#46; As dermatologists&#44; we need to understand&#44; among other aspects&#44; how vitamin D is synthesized and the main sources in humans&#44; as well as plasma levels and the factors that can modify them&#46; Of particular interest are the latest discoveries about the role of vitamin D in skin diseases such as lupus erythematosus&#44; ichthyosis&#44; atopic dermatitis&#44; hidradenitis suppurativa&#44; acne&#44; alopecia areata&#44; androgenetic alopecia&#44; melanoma&#44; and nonmelanoma skin cancer&#46; Also of interest is the importance of vitamin D as adjuvant therapy in patients on long-term treatment with corticosteroids&#46; In this review&#44; we provide an overview of the most important and most recent information regarding the relationship between vitamin D and skin disease and discuss the importance of assessing individual vitamin D status and correcting deficiencies&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El papel de la vitamina D en enfermedades cut&#225;neas ha cobrado inter&#233;s en los &#250;ltimos a&#241;os&#46; La relaci&#243;n entre esta vitamina y algunas dermatosis ha supuesto la publicaci&#243;n de m&#250;ltiples trabajos al respecto&#46; Como dermat&#243;logos&#44; conocer sus principales fuentes&#44; s&#237;ntesis&#44; niveles plasm&#225;ticos y algunos de los factores modificadores son varios de los aspectos a recordar&#46; Asimismo&#44; es preciso resaltar los &#250;ltimos descubrimientos sobre el papel de la vitamina D en las diferentes enfermedades dermatol&#243;gicas&#44; como el lupus eritematoso&#44; la ictiosis&#44; la dermatitis at&#243;pica&#44; la hidrosadenitis supurativa&#44; el acn&#233;&#44; la alopecia areata y androgen&#233;tica&#44; el melanoma y el c&#225;ncer cut&#225;neo no melanoma&#44; as&#237; como la relevancia como terapia adyuvante en pacientes en tratamiento cr&#243;nico con corticoides&#46; Acercamos al lector la informaci&#243;n m&#225;s relevante y reciente de la relaci&#243;n entre la vitamina D y las enfermedades de la piel&#44; as&#237; como la importancia de conocer los niveles de esta vitamina&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Navarro-Trivi&#241;o FJ&#44; Arias-Santiago S&#44; Gilaberte-Calzada Y&#46; Vitamina D y la piel&#46; Una revisi&#243;n para dermat&#243;logos&#46; Actas Dermosifiliogr&#46; 2019&#59;110&#58;262&#8211;272&#46;</p>"
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            "etiqueta" => "Addendum"
            "titulo" => "Serum levels of 25&#40;OH&#41;D"
            "identificador" => "sec0110"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Metabolism&#46; The body acquires vitamin D from certain foods and through a reaction that occurs when the skin is exposed to sunlight in which UV-B radiation converts 7-dehydrocholersterol &#40;synthesized in the skin&#41; to pre-vitamin D<span class="elsevierStyleInf">3</span>&#44; which then becomes inactive vitamin D&#46; This is then converted in the liver to 25&#40;OH&#41;D by way of hepatic hydroxylation&#46; In a second step&#44; 25&#40;OH&#41;D is metabolized in the kidney to the active metabolite 1&#44;25&#40;OH&#41;D&#44; or calcitriol&#44; through the action of renal alpha-1-hydroxylase&#46; This mechanism is regulated by serum levels of calcium and inorganic phosphorus&#44; among others&#44; which are detected by the glands that secrete parathyroid hormone &#40;PTH&#41; and stimulate the activity of alpha-1-hydroxylase&#44; when necessary&#46; Calcitriol concentrations regulate the secretion of PTH&#46; The 1&#44;25&#40;OH&#41;D acts through the vitamin D receptors &#40;VDR&#41; within cells&#44; which activate the transcription and translation of messenger RNA&#44; leading to the synthesis of vitamin D-dependent proteins and their corresponding activity&#44; which depend on the function of the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of 24 renal hydroxylase&#44; which converts 1&#44;25&#40;OH&#41;D to calcitroic acid&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Gilaberte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">15</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Food&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IU per Serving&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cod liver oil &#40;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Salmon &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mackerel &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sardines in oil &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tuna in oil &#40;100&#160;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified milk &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115-124&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified orange juice &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified yoghurt &#40;1&#46;5 L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Margarine &#40;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cereals &#40;fortified&#41; &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eggs &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cheese &#40;28&#160;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6-12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foods Rich in Vitamin D&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk Factors for Hypovitaminosis D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inadequate exposure to sunlight &#40;controversial&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High skin phototype &#40;IV or greater&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Older age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Institutionalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current treatment with corticosteroids&#44; antiepileptics&#44; hormone therapies for breast or prostate cancer&#44; immunosuppressants&#44; or antiretrovirals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic kidney disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liver failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperparathyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypogonadism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Celiac disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026133.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Risk Factors Associated with Low Vitamin D Levels&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Functions of Vitamin D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Role in bone mineral metabolism&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Role in the control of carcinogenesis and metastasis&#46; Inhibits proliferation&#44; stimulates differentiation&#44; promotes apoptosis&#44; inhibits angiogenesis&#44; and contributes to DNA repair&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood sugar regulation&#46; Regulates insulin secretion in the pancreas and decreases peripheral insulin resistance&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lipid synthesis regulation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulation of blood pressure through its effects on the renin-angiotensin-aldosterone system&#46; Inhibits renin expression in the kidneys&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stimulates the synthesis of nitric oxide in the cardiovascular system&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunomodulatory effect in keratinocytes&#46; Regulates initial stages of proliferation and differentiation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulates the growth cycle of hair follicles&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulates innate and adaptive pathways of the immune system&#46; Participates in the proliferation and activation of dendritic cells&#44; regulates the activation of CD4 lymphocytes&#44; reduces the formation of T helper &#40;Th&#41; 1-9-17 cells&#44; and promotes differentiation of Th2 and T regulators&#46; Plays a role in the activation of selective Toll-like receptors &#40;TLR 1&#47;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026136.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Functions of Vitamin D in the Body&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Postmenopausal women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Men and premenopausal women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients who are going to take or are taking over 5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients who are going to take or are taking over 7&#46;5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients who have a bone mineral density T-score below -1&#46;5 and are going to take or are taking over 2&#46;5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients who have a bone mineral density T-score below -1&#46;5 and are going to take or are taking over 5&#160;mg&#47;d of corticosteroid for more than 3&#160;mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">All patients with a history of fractures caused by bone fragility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026129.png"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Indications for Vitamin D Supplementation During Corticosteroid Therapy&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cholecalciferol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Drops&#46; 10&#160;mL vial &#40;20&#44;000 IU&#41;&#58; 0&#46;05&#160;mg&#160;&#61;&#160;400&#160;IU&#160;&#61;&#160;6 drops</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">2&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mL oral solution &#40;25&#44;000 IU&#41; equivalent to 0&#46;625</span><span class="elsevierStyleItalic">mg</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026138.png"
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Calcifediol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Drop&#58; 0&#46;1&#160;mg&#47;mL &#40;6&#46;000&#160;IU&#41;&#59; 240&#160;IU &#40;4&#160;&#956;g&#41;&#160;&#61;&#160;1 drop</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Liquid in ampoules&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>0&#46;266&#160;mg &#40;16&#44;000 IU&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3&#160;mg &#40;180&#44;000 IU&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Soft capsules 0&#46;266</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg &#40;16&#44;000 IU&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026132.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Formulations Available in Spain&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment of deficiency &#40;10-19 ng&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cholecalciferol 25&#44;000 IU weekly for 8 wks and then every 15 d for a further 8 wks&#44; followed by a maintenance regimen of 25&#44;000 IU every 2-4 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Calcifediol 16&#44;000 IU weekly for 10 wks and monthly thereafter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment of severe deficiency &#40;&#60;&#160;10 ng&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cholecalciferol 25&#44;000 IU twice weekly for 6 wks&#44; and then 25&#44;000 IU weekly for 4 wks&#44; followed by a maintenance dose of 25&#44;000 IU every 2-4 wk thereafter&#44; depending on serum levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Shock treatment with calcifediol 3<span class="elsevierStyleHsp" style=""></span>mg &#40;180&#44;000 IU&#41; in a single dose followed by 16&#44;000 IU monthly&#44; depending on serum levels &#40;with a 2-month loading period&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026137.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Supplement Dosages According to 25&#40;OH&#41;D Serum Levels as Specified in the Summary of Product Characteristics&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0040"
        "etiqueta" => "Table 7"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at7"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ichthyosis congenita&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acne&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidradenitis suppurativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Polymorphic light eruption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alopecia areata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nonmelanoma skin cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026131.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Skin Diseases Related to Alterations in Vitamin Levels D&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0045"
        "etiqueta" => "Table 8"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at8"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Skin Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Grade of Recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level of Evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ichthyosis congenita&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acne&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidradenitis suppurativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
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Review
Vitamin D and the Skin: A Review for Dermatologists
Vitamina D y la piel. Una revisión para dermatólogos
F.J. Navarro-Triviñoa,
Autor para correspondencia
fntmed@gmail.com

Corresponding author.
, S. Arias-Santiagob, Y. Gilaberte-Calzadac
a Unidad de Dermatología Médico-Quirúrgica y Venereología, Hospital Comarcal Alcalá la Real, Jaén, Spain
b Unidad de Gestión Clínica de Dermatología y Venereología, Hospital Universitario Virgen de las Nieves, Granada, Spain
c Servicio de Dermatología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Metabolism&#46; The body acquires vitamin D from certain foods and through a reaction that occurs when the skin is exposed to sunlight in which UV-B radiation converts 7-dehydrocholersterol &#40;synthesized in the skin&#41; to pre-vitamin D<span class="elsevierStyleInf">3</span>&#44; which then becomes inactive vitamin D&#46; This is then converted in the liver to 25&#40;OH&#41;D by way of hepatic hydroxylation&#46; In a second step&#44; 25&#40;OH&#41;D is metabolized in the kidney to the active metabolite 1&#44;25&#40;OH&#41;D&#44; or calcitriol&#44; through the action of renal alpha-1-hydroxylase&#46; This mechanism is regulated by serum levels of calcium and inorganic phosphorus&#44; among others&#44; which are detected by the glands that secrete parathyroid hormone &#40;PTH&#41; and stimulate the activity of alpha-1-hydroxylase&#44; when necessary&#46; Calcitriol concentrations regulate the secretion of PTH&#46; The 1&#44;25&#40;OH&#41;D acts through the vitamin D receptors &#40;VDR&#41; within cells&#44; which activate the transcription and translation of messenger RNA&#44; leading to the synthesis of vitamin D-dependent proteins and their corresponding activity&#44; which depend on the function of the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of 24 renal hydroxylase&#44; which converts 1&#44;25&#40;OH&#41;D to calcitroic acid&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rickets&#44; a condition caused by vitamin D deficiency&#44; was first described by Glisson&#44; DeBoot and Whistler in the seventeenth century&#46; Subsequently&#44; in 1882&#44; Sniadecki realized the importance of exposure to sunlight for the prevention and cure of rickets&#46; Today&#44; we know that the role of vitamin D in the body goes beyond the regulation of bone mineral metabolism&#44; making the function of this vitamin important to a wide range of medical specialists&#46; Charpy<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">1</span></a> published the first study linking vitamin D levels and lupus vulgaris in 1945&#46; In 2016&#44; Deschasaux et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">2</span></a> published the results of a study based on an online questionnaire designed to investigate the understanding of the role of vitamin D in the general population&#46; They reported that over 1-third of the respondents were unaware of the role of vitamin D in the body&#8212;a significant finding in light of the fact that vitamin D levels were insufficient in 40&#37; of a subsample of respondents in whom these were tested&#46; The recent literature includes several interesting new studies linking vitamin D levels with a number of common skin disorders&#46; The aim of the present review is to provide an overview of the relationship between vitamin D and skin disease based on current evidence&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Synthesis</span><p id="par0010" class="elsevierStylePara elsevierViewall">The body obtains vitamin D in two ways&#46; A small amount of active vitamin D in the form of cholecalciferol can be obtained from dietary intake of animal origin&#58; the foods with significant levels are egg yolks and certain blue fish &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 1</a>&#41;&#46; Ergocalciferol&#44; another form of pre-vitamin D&#44; is found in small amounts in foods of vegetable origin&#46; The other way the body obtains vitamin D is through exposure to solar radiation&#46; Photons in UV-B radiation photo-isomerize 7-dehydrocholesterol in the epidermis to precholecalciferol&#44; which is then rapidly converted through a heat-mediated reaction to cholecalciferol or vitamin D<span class="elsevierStyleInf">3</span>&#46; Both molecules are hydroxylated in the liver to calcifediol &#40;25-hydroxyvitamin D &#91;25&#40;OH&#41;D&#93;&#41;&#44; which is later hydroxylated in the kidneys through the action of the enzyme 25&#40;OH&#41;D-1-hydroxylase to calcitriol&#44; the active metabolite that performs a range of different functions by binding to its cell receptor&#46; Parathyroid hormone &#40;PTH&#41;&#44; calcium&#44; and phosphorus levels are just some of the factors that play a role in the regulation of this process&#44; in addition to transforming growth factor beta &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Vitamin D Levels and Vitamin D Deficiency&#46; Is There Really a Pandemic&#63;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Daily vitamin D requirements are age dependent and different medical associations do not agree on the levels required&#46; According to the Institute of Medicine &#40;IoM&#41;&#44; the daily requirement is 400 IU in the first year of life&#44; 600 IU between 12 months and 70 years of age&#44; and 800 IU in people over 70 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">3</span></a> However&#44; the American Endocrine Society recommends between 400 and 1000&#160;IU&#47;d in the first year of life and 600 to 1000&#160;IU&#47;d thereafter&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2009&#44; 25&#40;OH&#41;D was established as the best blood marker of vitamin D status&#46; <a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">4</span></a> The societies also have different opinions about desirable levels in the body&#46; While the IoM specifies 20&#160;ng&#47;mL as the lower limit indicating healthy and sufficient levels of vitamin D &#40;<a class="elsevierStyleCrossRef" href="#sec0110">Appendix A</a>&#41;&#44; the American Endocrine Society defines a level under 20 ng&#47;mL as deficient and a level between 20 and 30&#160;ng&#47;mL as insufficient&#44; and considers values above 30&#160;ng&#47;mL &#40;75&#160;mmol&#47;L&#41; to be essential for maintaining good health&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">5</span></a> There is currently generalized alarm worldwide about vitamin D deficiency in both the healthy and the sick population&#46; In response to this situation&#44; an article in The New England Journal of Medicine addressed the question of whether or not there is really a pandemic of vitamin D deficiency in the world today&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">6</span></a> Between 35&#37; and 70&#37; of Europeans have 25&#160;&#40;OH&#41;&#160;D levels considered insufficient by some authors&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">7</span></a> By contrast&#44; in Australia and New Zealand&#44; the percentage ranges from 6&#37; to 9&#37;&#46; Publication of these findings might lead to the consideration of the usefulness of screening healthy people for vitamin D deficiency&#46; However&#44; since routine screening is not currently supported by the IoM or the US Preventive Services Task Force&#44; it is not recommended at this time&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Vitamin D toxicity can cause serious health problems&#46; Blood levels persistently above 200&#160;ng&#47;mL are considered toxic&#46; The most frequent symptoms of toxicity are anorexia&#44; weight loss&#44; polyuria&#44; and cardiac arrhythmias&#46; Vitamin D toxicity also increases the risk of kidney stone formation&#44; the calcification of blood vessels and tissues&#44; and the complications associated with both of these alterations&#46; Toxicity can occur when the daily intake of vitamin D exceeds 10&#44;000&#160;IU&#44; giving rise to 25&#40;OH&#41;D levels in excess of 200 to 240&#160;ng&#47;mL&#46; However&#44; most medical societies consider 25&#40;OH&#41;D levels higher than 125 to 150&#160;ng&#47;mL to be unadvisable in order to avoid the adverse effects of a vitamin D excess&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Modifying Factors</span><p id="par0030" class="elsevierStylePara elsevierViewall">Some people are more susceptible than others to developing vitamin D deficiency&#44; defined as a level below the established minimum of 20&#160;ng&#47;mL &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 2</a>&#41;&#46; Risk factors for susceptibility include obesity&#44;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">8</span></a> smoking&#44;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">9</span></a> a high skin phototype<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">10</span></a> &#40;although this is still controversial&#41;&#44; insufficient sun exposure&#44; and age&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">11</span></a> With age&#44; the skin produces less of the precursor 7-dehydrocholesterol in the epidermis&#44; intestinal absorption of vitamin D declines due to a reduction in the number of vitamin D receptors &#40;VDR&#41; in enterocytes&#44; and the body&#39;s ability to hydroxylate vitamin D in the liver and kidney also decreases&#46; Some clinical conditions predispose patients to inadequate vitamin D levels&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">12</span></a> These include osteoporosis&#44; chronic kidney disease&#44; liver failure&#44; inflammatory bowel disease&#44; hyperparathyroidism&#44; hyperthyroidism&#44; hypogonadism&#44; and celiac disease&#46; Another risk factor is long-term treatment with certain drugs&#44; including anticonvulsants&#44; antiretrovirals&#44; rifampicin&#44; hormonal treatments prescribed for breast and prostate cancer&#44; and&#44; above all&#44; corticosteroids&#46; Pregnancy can also give rise to low 25&#40;OH&#41;D levels&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Functions of Vitamin D&#58; Regulation of Bone Metabolism and Other Pleiotropes</span><p id="par0035" class="elsevierStylePara elsevierViewall">In 2016&#44; Bikle<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">13</span></a> described the principal functions of vitamin D in the body&#46; A more recent article discussed the relationship between vitamin D and the skin&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">14</span></a> Vitamin D has been shown to have antiproliferative properties&#44; including the inhibition of angiogenesis and metastatic capacity in some tumors&#44; and it also participates in DNA repair&#46; A relationship has even been found between certain mutations in the VDR gene and cancer&#46; In the metabolic system&#44; vitamin D plays an important role in glucidic&#44; lipid&#44; arterial&#44; and vascular homeostasis&#46; It also modulates immune responses by regulating the differentiation of T&#160;helper &#40;Th&#41; 1-9-17 cells and by inducing the formation of antimicrobial peptides such as cathelicidin peptides&#46; In dermatology&#44; it is important because of its immunomodulatory effects in keratinocytes&#44; as described by Gilaberte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">15</span></a> Vitamin D plays an important role in the homeostasis of glucose by promoting insulin secretion in pancreatic beta cells&#44;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">16</span></a> which express alpha-1-hydroxylase through cell stimulation by way of high affinity VDR&#46; Moreover&#44; it decreases peripheral insulin resistance by activating peroxisome proliferator-activated gamma receptors in the liver&#44; muscle&#44; and fatty tissue&#46; In view of this relationship&#44; it has been postulated that vitamin D may be a protective factor in the development of type 2 diabetes mellitus&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">17</span></a> In the case of lipid metabolism&#44; vitamin D can also have an indirect effect&#44; not only because it may improve peripheral insulin resistance<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">18</span></a> and reduce PTH levels &#40;shown to have a lipolytic effect&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">19</span></a> but also because it favors higher serum calcium levels&#44; thereby decreasing hepatic triglyceride production&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">20</span></a> In 2010&#44; Pittas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">21</span></a> published a systematic review on the relationship between blood pressure and vitamin D levels&#46; Their conclusion was that deficient vitamin D levels &#40;&#60;&#160;20&#160;ng&#47;mL&#41; were associated with an increased risk of arterial hypertension&#46; Other studies have shown that vitamin D supplementation improved blood pressure in hypertensive patients&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">22</span></a> This improvement is mediated by various effects&#58; direct effects on vitamin D receptors&#44; which decrease vascular inflammation and correct endothelial dysfunction&#59; regulation of the proliferation&#44; migration&#44; and mineralization of vascular muscle cells<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">23</span></a>&#59; and finally&#44; indirectly by decreasing serum levels of PTH&#44; a hormone that acts on the renin-angiotensin-aldosterone system&#46; Furthermore&#44; recent studies have shown that vitamin D stimulates the release of nitric oxide&#44; thereby reducing oxidative stress in the cardiovascular system&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">24</span></a> It is&#44; therefore&#44; clear that vitamin D not only plays a role in bone metabolism but is also involved in many other functions in the body &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Vitamin D and Skin Disease</span><p id="par0040" class="elsevierStylePara elsevierViewall">Vitamin D has been implicated in the pathogenesis and treatment of a wide variety of skin diseases&#46; These are discussed below&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Psoriasis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Krafka<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">25</span></a> and Thacker<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">26</span></a> were the first scientists to postulate a role for vitamin D in psoriasis&#46; The use of oral vitamin D as a treatment for psoriasis failed because of the risk of hypercalcemia&#46; The development of topical vitamin D analogs&#44; such as calcipotriol and tacalcitol&#44; later revolutionized the treatment of the condition&#46; Bergler-Czop and Brzezi&#324;ska-Wcislo<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">27</span></a> observed a correlation between Psoriasis Area and Severity Index &#40;PASI&#41; scores and serum levels of 25&#40;OH&#41;D and reported that patients with lower vitamin D levels had higher PASI scores&#46; Orgaz-Molina et al&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">28</span></a> demonstrated that patients with psoriasis and a body mass index higher than 27 were more likely to have insufficient 25&#40;OH&#41;D levels&#46; The comorbidities of psoriasis &#40;diabetes mellitus&#44; obesity&#44; and metabolic syndrome&#41; have also been linked to diets low in vitamin D&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">29</span></a> Clinicians should recommend diets that provide vitamin D in view of its beneficial effect on many of the comorbidities associated with psoriasis&#46; The use of vitamin D in psoriasis is currently a grade B recommendation with IIa level of evidence&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Atopic Dermatitis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic and recurrent inflammatory disease&#44; initially characterized by pruritus and eczematous lesions&#46; It affects up to 20&#37; of the pediatric population and around 7&#46;2&#37; of adults&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">30</span></a> AD is caused by an alteration in the cutaneous immune system and a defect in the synthesis of the epidermal barrier&#44; which affects mainly filaggrin&#46;<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">31&#44;32</span></a> Many authors have studied the association between vitamin D and AD&#46; Kim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">33</span></a> published a meta-analysis and systematic review of 11 articles&#44; 7 observational studies&#44; and 4 clinical trials&#46; Compared to healthy controls&#44; patients with AD had lower levels of vitamin D&#44; especially in the pediatric population&#46; Oral vitamin D supplements have been associated with reductions in SCORAD and Eczema Area and Severity Index scores in pediatric patients and is considered to be a possible adjuvant treatment in patients with a deficiency &#40;levels below 20&#160;ng&#47;mL&#41;&#46; In a series of 210 adult patients with AD&#44; Van der Schaft et al&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">34</span></a> reported that vitamin D supplementation in patients with deficient levels did not lead to any significant improvement in eczematous lesions&#46; Several studies in the literature report that vitamin D supplementation in children decreased colonization with <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; a microorganism that plays a role in outbreaks of DA&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">35&#8211;37</span></a> Despite the evidence that vitamin D levels tend to be insufficient in adult patients with AD&#44;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">38</span></a> there is still debate about whether vitamin D supplementation is useful in this age group&#46; In children the use of vitamin D is a grade B recommendation with a IIa level of evidence&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ichthyosis Congenita</span><p id="par0055" class="elsevierStylePara elsevierViewall">Sethuraman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">39</span></a> reported low levels of 25&#40;OH&#41;D and high levels of PTH in children with ichthyosis congenita&#46; In that study&#44; vitamin D supplementation with 60&#44;000 IU of oral cholecalciferol for 10 days followed by a maintenance regimen of 400 to 600 IU&#47;d achieved a rapid response&#44; with noticeable improvement in the dermatological symptoms by the fifth day in terms of both scaling and stiffness&#46; Of the 7 children studied&#44; 6 had serum 25&#40;OH&#41;D levels under 4&#160;ng&#47;mL&#46; While more studies are needed&#44; these findings open up interesting possibilities in the management of ichthyosis congenita&#46; Lucker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">40</span></a> published the results achieved with topical calcipotriol in patients with ichthyosis congenita &#40;Netherton syndrome&#44; lamellar&#44; ichthyosis bullosa of Siemens&#44; and epidermolytic ichthyosis of Brocq&#41;&#46; Scaling and associated redness improved in all but the bullous form of the disease&#46; In ichthyoses in which epidermal hyperproliferation and retention hyperkeratosis do not predominate&#8212;such as X-linked ichthyosis&#44; ichthyosis vulgaris&#44; and acquired ichthyosis&#8212;topical application of vitamin D analogs has not been shown to be effective&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">41</span></a> Neema et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">42</span></a> raised the possibility of combining vitamin D with oral retinoid treatment in patients with low vitamin levels&#46; Despite the published findings&#44; the use of vitamin D supplementation in patients with ichthyosis is a grade C recommendation with a IIIa level of evidence&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Acne</span><p id="par0060" class="elsevierStylePara elsevierViewall">Interest in the role of vitamin D in acne first emerged in 1938&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">43</span></a> A comparative study of serum levels of 25&#40;OH&#41;D in adolescents with and without acne was published in PloS One in 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">44</span></a> The patients with acne had lower vitamin D levels than the healthy controls and an inverse relationship was observed between vitamin D levels and the severity and number of inflammatory acne lesions&#46; Following 2 months of vitamin D supplementation&#44; the number of inflammatory lesions decreased but no change was observed in non-inflammatory lesions&#46; The role of vitamin D in acne could be explained by a relationship between the vitamin and reduced synthesis of interleukin &#40;IL&#41; 6&#44; IL-8 and metalloproteinase-9<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">45</span></a> as well as to a reduction in the expression of IL-17 because of its action on Th17 cells&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">46</span></a> Zouboulis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">47</span></a> described the effect of vitamin D on the sebaceous glands and the increase in lipogenesis when vitamin D levels are insufficient&#44; an effect that promotes an increase in inflammatory lesions&#46; The authors of a recent study reported that 25&#40;OH&#41;D levels were higher following treatment than at baseline in patients treated with oral isotretinoin&#44; concluding that the role of vitamin D in the inflammatory pathogenesis of acne is important in the development of lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">48</span></a> The use of vitamin D in acne is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Hidradenitis Suppurativa</span><p id="par0065" class="elsevierStylePara elsevierViewall">Hidradenitis suppurativa &#40;HS&#41; is a chronic inflammatory skin disease with a significant impact on the patients&#8217; quality of life&#46; Several studies have been published on the relationship between HS and vitamin D levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">49&#44;50</span></a> In those studies&#44; the patients with HS had lower vitamin D levels than controls and an inverse correlation was observed between vitamin D levels and disease severity&#46; Following 6 months of vitamin D supplementation&#44; inflammatory nodules improved in 79&#37; of patients &#40;out of the 14 treated&#41;&#59; however&#44; as with acne&#44; no significant changes were observed in non-inflammatory lesions&#46; In the opinion of the authors of another study&#44; the endocrinological and metabolic alterations associated with HS make vitamin D a therapeutic target because of its relationship with metabolic syndrome&#44; among other reasons&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">51</span></a> Well-designed studies with a sufficient number of patients are needed to determine the role of vitamin D in HS&#46; The use of vitamin D in HS is currently a grade B recommendation with a III level of evidence&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Vitiligo</span><p id="par0070" class="elsevierStylePara elsevierViewall">There are more than 300 articles in the literature on the relationship between vitamin D and vitiligo&#46; Karag&#252;n et al&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">52</span></a> observed lower serum vitamin D levels in 50 patients with vitiligo compared to healthy controls and an inverse correlation with the extent of disease&#46; In a meta-analysis&#44; Upala and Sanguankeo<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">53</span></a> concluded that the evidence did indicate a clear relationship between vitiligo and low vitamin D levels&#46; Variable results have been reported in cases in which vitiligo was treated with vitamin D analogs either alone<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">54</span></a> or in combination with other treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">55</span></a> However&#44; there are no clinical trials that demonstrate the efficacy of vitamin D supplements in these patients&#46; Khurrum and AlGhamdi<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">56</span></a> found no significant differences in vitamin D levels between patients with vitiligo and healthy controls&#59; in the analysis by subgroups&#44; however&#44; it was observed that in the group of patients with vitiligo&#44; the lowest vitamin D levels were associated with male sex&#44; younger age&#44; a short duration of vitiligo&#44; and not having received treatment with phototherapy&#46; At present&#44; the use of vitamin D in patients with vitiligo is a grade B recommendation with a IIa level of evidence&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Systemic Lupus Erythematosus</span><p id="par0075" class="elsevierStylePara elsevierViewall">Several studies have found a higher prevalence of vitamin D deficiency in patients with systemic lupus erythematosus &#40;SLE&#41; than in the healthy population&#46;<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">57&#44;58</span></a> The authors of a study published in PloS One&#44; which investigated the relationship between vitamin D levels and the severity of SLE&#44; reported that 71&#46;4&#37; of the patients had vitamin D levels under 30&#160;ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">59</span></a> They also observed an association between lower vitamin D levels and poorer scores on the Systemic Lupus Erythematosus Disease Activity Index&#46; However&#44; supplementation with 400 to 1&#44;000 IU&#47;d of vitamin D failed to raise levels above 30&#160;ng&#47;mL&#46; In a comparative study with placebo by Karimzadeh et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">60</span></a> patients with SLE who received vitamin D supplementation showed a significant increase in serum 25&#40;OH&#41;D levels but this was not associated with any effect on disease activity&#46; Some authors defend the usefulness of vitamin D supplementation in these patients on the basis of the protective cardiovascular effect and the possible improvement in systemic symptoms and cognitive development&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">61</span></a> The authors of a recent review article on this topic defend the usefulness of vitamin D in SLE on the basis of its immunomodulatory effects&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">62</span></a> The use of vitamin D in patients with SLE is a grade B recommendation with a IIa evidence level&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Polymorphic Light Eruption</span><p id="par0080" class="elsevierStylePara elsevierViewall">Polymorphic light eruption &#40;PLE&#41; is an idiopathic photosensitivity disorder related primarily with exposure to UV-A and less often with UV-B radiation&#46; It is found more frequently in young women&#46; Schweintzger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">63</span></a> found no significant relationship between vitamin D levels and the number and function of regulatory T cells&#44; concluding that other factors affect the immune response that occurs in PLE&#46; Nevertheless&#44; in another study patients with PLE had lower vitamin D levels than controls and when these were increased by phototherapy with UV-B &#40;311&#160;nm&#41; a correlation was observed between the increase and clinical improvement of the lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">64</span></a> In a placebo-controlled clinical trial&#44; Gruber-Wackernagel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">65</span></a> observed that topical application of calcipotriol 1 week before exposure reduced symptoms in almost 1-third of patients exposed to photoprovocation and suggested this treatment as a possible prophylactic measure&#46; However&#44; there is no consensus in photobiology units on the use of this treatment for PLE&#46; The use of vitamin D in PLE is a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Alopecia Areata</span><p id="par0085" class="elsevierStylePara elsevierViewall">The role of vitamin D in alopecia areata &#40;AA&#41; has been explored in several studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0805"><span class="elsevierStyleSup">66&#8211;69</span></a> Thompson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">70</span></a> analyzed data from a cohort of 55&#44;929 women and found no association between vitamin D supplementation and incident AA&#46; However&#44; other studies have found that vitamin D levels tend to be lower in patients with AA than in healthy controls<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">71</span></a> and even lower in patients with universal AA compared to those with the ophthalmic or plaque forms&#46; Vitamin D levels have not been shown to differ significantly according to age&#44; sex&#44; disease duration&#44; disease recurrence&#44; or family history of AA&#46; However&#44; patients with AA have been found to have a lower number of vitamin D receptors in the blood and tissues than the group of healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">72</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">While topical vitamin D analogs can be used to treat AA&#44;<a class="elsevierStyleCrossRefs" href="#bib0835"><span class="elsevierStyleSup">72&#44;73</span></a> no studies have been carried out which demonstrate that oral supplements with vitamin D are effective in this setting&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The use of vitamin D in patients with AA is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Melanoma and Melanoma Metastasis</span><p id="par0100" class="elsevierStylePara elsevierViewall">The role of vitamin D in melanoma has been investigated in a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">74&#8211;77</span></a> Orlow et al&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">78</span></a> identified certain haplotypes of single nucleotide polymorphisms &#40;SNPs&#41; of the vitamin D receptor gene related to increased survival in patients with melanomas in photoexposed sites &#40;rs1544410&#47;BsmI and rs731236&#47;TaqI&#41;&#46; Subsequent studies have reported an inverse correlation between Breslow thickness and vitamin D levels<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">79</span></a> and a possible relationship between low serum vitamin D levels and ulceration<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">80</span></a> in patients with melanoma&#46; In fact&#44; a worse prognosis was observed in the patients whose vitamin D levels were low when melanoma was diagnosed and also when&#44; even after starting supplementation&#44; the patient did not achieve levels above 20&#160;ng&#47;mL&#46; In a recent study of 3578 patients&#44; however&#44; no significant relationship was found between melanoma survival&#44; determined by the Breslow thickness&#44; number of mitosis&#44; ulceration&#44; and SNPs found in the pathway of vitamin D and its receptor&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">81</span></a> This debate has led to new studies to determine the possible advantage of recommending vitamin D supplementation in patients with melanoma in sun-exposed and sun-shielded sites&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">82</span></a> The use of vitamin D in patients with melanoma is currently a grade B recommendation with a IIb level of evidence&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Nonmelanoma Skin Cancer</span><p id="par0105" class="elsevierStylePara elsevierViewall">The role of vitamin D in carcinogenesis<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">83</span></a> led to the study of its relationship with nonmelanoma skin cancer &#40;NMSC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">84</span></a> The cells of basal cell and squamous cell tumors express VDRs&#46; Eide et al&#46;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">85</span></a> reported an association between high vitamin D levels and an increased risk of keratinocyte carcinoma&#46; Vitamin D is also able to inhibit the Hedgehog signaling pathway in basal cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">86</span></a> Research has shown that patients with the Bsml SNP of the vitamin D receptor have a higher risk of developing NMSC&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">87</span></a> However&#44; in a prospective study with more than 60&#44;000 participants&#44; vitamin D supplementation was not associated with squamous cell carcinoma risk or the incidence of basal cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">88</span></a> Confounding factors such as sun exposure and phototype&#44; among others&#44; have given rise to controversies on this topic and clinical trials are required to gain a better understanding of the role of vitamin D in NMSC&#46; The use of vitamin D in patients with NMSC is a grade B recommendation with a IIb level of evidence&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Vitamin D Supplementation in Patients on Long-Term Treatment with Systemic Corticosteroids</span><p id="par0110" class="elsevierStylePara elsevierViewall">Chronic use of systemic corticosteroids gives rise to complications&#44; which include osteoporosis&#46; This is due to the osteolytic activity observed in the short term&#44; associated with osteoblast and osteocyte apoptosis in long-term treatment&#46; The overall relative risk of fractures associated with corticosteroid treatment is 1&#46;33&#46; The risk is higher for vertebral fractures &#40;RR 2&#46;60&#41;&#44; hip fractures &#40;RR 1&#46;60&#41;&#44; and forearm or Colles fractures &#40;RR 1&#46;09&#41;&#46; Associated risk factors in each patient must be taken into account&#59; these include advanced age&#44; family history of fracture or osteoporosis&#44; early menopause&#44; smoking&#44; and a low body mass index determined by bone densitometry&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">89</span></a> The usefulness of vitamin D supplementation during prolonged treatment with oral corticosteroids is supported by the findings of a number of studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0925"><span class="elsevierStyleSup">90&#44;91</span></a> A meta-analysis by Reid et al&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">92</span></a> revealed a correlation between fracture risk and deficient 25&#40;OH&#41;D levels&#46; In another meta-analysis of 11 clinical trials&#44; which included people over 65 years of age &#40;mostly women&#41; showed that supplementation with 800&#160;IU&#47;d of cholecalciferol reduced the risk of hip fracture by 30&#37; and the risk of non-vertebral fracture by 14&#37;&#44; regardless of whether the patients were also taking calcium supplements&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">93</span></a> In several studies&#44; treatment with anti-resorptive agents&#44; such as risedronate or alendronate&#44; in combination with cholecalciferol supplementation for 13 months was associated with an increase in bone mineral density assessed by densitometry&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">94&#44;95</span></a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 4</a> shows the indications for vitamin D supplementation in patients on chronic corticosteroid treatment&#46; <a class="elsevierStyleCrossRef" href="#tbl0030">Table 5</a> shows the available forms of vitamin D supplements and <a class="elsevierStyleCrossRef" href="#tbl0035">Table 6</a> the recommended dosage according to serum vitamin D levels&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusion</span><p id="par0115" class="elsevierStylePara elsevierViewall">Vitamin D has a multiplicity of functions on the cellular level in the many organs and tissues where there are VDR&#46; It would appear that this hormone is fundamental in dermatology&#44; not only because it is synthesized in the skin&#44; but also because of its multiple actions&#44; which are reflected in the variety of diseases in which it appears to play a role&#46; <a class="elsevierStyleCrossRef" href="#tbl0040">Table 7</a> summarizes the diseases in which serum vitamin D levels should be measured and vitamin D supplementation should be considered&#44; depending on the results and taking into account the level of scientific evidence in each case &#40;<a class="elsevierStyleCrossRef" href="#tbl0045">Table 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><elsevierMultimedia ident="tbl0045"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of Interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Background"
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          "identificador" => "sec0010"
          "titulo" => "Synthesis"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Vitamin D Levels and Vitamin D Deficiency&#46; Is There Really a Pandemic&#63;"
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        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Modifying Factors"
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          "identificador" => "sec0025"
          "titulo" => "Functions of Vitamin D&#58; Regulation of Bone Metabolism and Other Pleiotropes"
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          "titulo" => "Vitamin D and Skin Disease"
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              "identificador" => "sec0035"
              "titulo" => "Psoriasis"
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            1 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Atopic Dermatitis"
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            2 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Ichthyosis Congenita"
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            3 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Acne"
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            4 => array:2 [
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              "titulo" => "Hidradenitis Suppurativa"
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              "titulo" => "Vitiligo"
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              "titulo" => "Systemic Lupus Erythematosus"
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              "titulo" => "Polymorphic Light Eruption"
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              "titulo" => "Alopecia Areata"
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              "titulo" => "Melanoma and Melanoma Metastasis"
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              "titulo" => "Nonmelanoma Skin Cancer"
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          "titulo" => "Vitamin D Supplementation in Patients on Long-Term Treatment with Systemic Corticosteroids"
        ]
        11 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conclusion"
        ]
        12 => array:2 [
          "identificador" => "sec0100"
          "titulo" => "Conflicts of Interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-03-19"
    "fechaAceptado" => "2018-08-02"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1107566"
          "palabras" => array:8 [
            0 => "Vitamin D"
            1 => "Lupus erythematosus"
            2 => "Ichthyosis"
            3 => "Atopic dermatitis"
            4 => "Hidradenitis suppurativa"
            5 => "Acne"
            6 => "Alopecia"
            7 => "Melanoma"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1107567"
          "palabras" => array:8 [
            0 => "Vitamina D"
            1 => "Lupus eritematoso"
            2 => "Ictiosis"
            3 => "Dermatitis at&#243;pica"
            4 => "Hidrosadenitis supurativa"
            5 => "Acn&#233;"
            6 => "Alopecia"
            7 => "Melanoma"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">In recent years&#44; the growing interest in the role played by vitamin D in skin disease has given rise to the publication of many studies of the relationship between this vitamin and certain skin conditions&#46; As dermatologists&#44; we need to understand&#44; among other aspects&#44; how vitamin D is synthesized and the main sources in humans&#44; as well as plasma levels and the factors that can modify them&#46; Of particular interest are the latest discoveries about the role of vitamin D in skin diseases such as lupus erythematosus&#44; ichthyosis&#44; atopic dermatitis&#44; hidradenitis suppurativa&#44; acne&#44; alopecia areata&#44; androgenetic alopecia&#44; melanoma&#44; and nonmelanoma skin cancer&#46; Also of interest is the importance of vitamin D as adjuvant therapy in patients on long-term treatment with corticosteroids&#46; In this review&#44; we provide an overview of the most important and most recent information regarding the relationship between vitamin D and skin disease and discuss the importance of assessing individual vitamin D status and correcting deficiencies&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El papel de la vitamina D en enfermedades cut&#225;neas ha cobrado inter&#233;s en los &#250;ltimos a&#241;os&#46; La relaci&#243;n entre esta vitamina y algunas dermatosis ha supuesto la publicaci&#243;n de m&#250;ltiples trabajos al respecto&#46; Como dermat&#243;logos&#44; conocer sus principales fuentes&#44; s&#237;ntesis&#44; niveles plasm&#225;ticos y algunos de los factores modificadores son varios de los aspectos a recordar&#46; Asimismo&#44; es preciso resaltar los &#250;ltimos descubrimientos sobre el papel de la vitamina D en las diferentes enfermedades dermatol&#243;gicas&#44; como el lupus eritematoso&#44; la ictiosis&#44; la dermatitis at&#243;pica&#44; la hidrosadenitis supurativa&#44; el acn&#233;&#44; la alopecia areata y androgen&#233;tica&#44; el melanoma y el c&#225;ncer cut&#225;neo no melanoma&#44; as&#237; como la relevancia como terapia adyuvante en pacientes en tratamiento cr&#243;nico con corticoides&#46; Acercamos al lector la informaci&#243;n m&#225;s relevante y reciente de la relaci&#243;n entre la vitamina D y las enfermedades de la piel&#44; as&#237; como la importancia de conocer los niveles de esta vitamina&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Navarro-Trivi&#241;o FJ&#44; Arias-Santiago S&#44; Gilaberte-Calzada Y&#46; Vitamina D y la piel&#46; Una revisi&#243;n para dermat&#243;logos&#46; Actas Dermosifiliogr&#46; 2019&#59;110&#58;262&#8211;272&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0130" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></p>"
            "etiqueta" => "Addendum"
            "titulo" => "Serum levels of 25&#40;OH&#41;D"
            "identificador" => "sec0110"
          ]
        ]
      ]
    ]
    "multimedia" => array:10 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1462
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            "Tamanyo" => 252455
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Metabolism&#46; The body acquires vitamin D from certain foods and through a reaction that occurs when the skin is exposed to sunlight in which UV-B radiation converts 7-dehydrocholersterol &#40;synthesized in the skin&#41; to pre-vitamin D<span class="elsevierStyleInf">3</span>&#44; which then becomes inactive vitamin D&#46; This is then converted in the liver to 25&#40;OH&#41;D by way of hepatic hydroxylation&#46; In a second step&#44; 25&#40;OH&#41;D is metabolized in the kidney to the active metabolite 1&#44;25&#40;OH&#41;D&#44; or calcitriol&#44; through the action of renal alpha-1-hydroxylase&#46; This mechanism is regulated by serum levels of calcium and inorganic phosphorus&#44; among others&#44; which are detected by the glands that secrete parathyroid hormone &#40;PTH&#41; and stimulate the activity of alpha-1-hydroxylase&#44; when necessary&#46; Calcitriol concentrations regulate the secretion of PTH&#46; The 1&#44;25&#40;OH&#41;D acts through the vitamin D receptors &#40;VDR&#41; within cells&#44; which activate the transcription and translation of messenger RNA&#44; leading to the synthesis of vitamin D-dependent proteins and their corresponding activity&#44; which depend on the function of the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of 24 renal hydroxylase&#44; which converts 1&#44;25&#40;OH&#41;D to calcitroic acid&#46;</p>"
        ]
      ]
      1 => array:8 [
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Gilaberte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">15</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Food&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IU per Serving&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cod liver oil &#40;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Salmon &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mackerel &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sardines in oil &#40;100 g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tuna in oil &#40;100&#160;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified milk &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115-124&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified orange juice &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fortified yoghurt &#40;1&#46;5 L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Margarine &#40;5&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cereals &#40;fortified&#41; &#40;250&#160;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Eggs &#40;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cheese &#40;28&#160;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6-12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026135.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foods Rich in Vitamin D&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Risk Factors for Hypovitaminosis D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inadequate exposure to sunlight &#40;controversial&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High skin phototype &#40;IV or greater&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Older age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Institutionalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current treatment with corticosteroids&#44; antiepileptics&#44; hormone therapies for breast or prostate cancer&#44; immunosuppressants&#44; or antiretrovirals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic kidney disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liver failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperparathyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypogonadism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Celiac disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026133.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Risk Factors Associated with Low Vitamin D Levels&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Functions of Vitamin D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Role in bone mineral metabolism&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Role in the control of carcinogenesis and metastasis&#46; Inhibits proliferation&#44; stimulates differentiation&#44; promotes apoptosis&#44; inhibits angiogenesis&#44; and contributes to DNA repair&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood sugar regulation&#46; Regulates insulin secretion in the pancreas and decreases peripheral insulin resistance&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lipid synthesis regulation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulation of blood pressure through its effects on the renin-angiotensin-aldosterone system&#46; Inhibits renin expression in the kidneys&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stimulates the synthesis of nitric oxide in the cardiovascular system&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunomodulatory effect in keratinocytes&#46; Regulates initial stages of proliferation and differentiation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulates the growth cycle of hair follicles&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Regulates innate and adaptive pathways of the immune system&#46; Participates in the proliferation and activation of dendritic cells&#44; regulates the activation of CD4 lymphocytes&#44; reduces the formation of T helper &#40;Th&#41; 1-9-17 cells&#44; and promotes differentiation of Th2 and T regulators&#46; Plays a role in the activation of selective Toll-like receptors &#40;TLR 1&#47;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2026136.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Functions of Vitamin D in the Body&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at4"
            "detalle" => "Table "
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Postmenopausal women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Men and premenopausal women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients who are going to take or are taking over 5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients who are going to take or are taking over 7&#46;5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Patients who have a bone mineral density T-score below -1&#46;5 and are going to take or are taking over 2&#46;5&#160;mg&#47;d of a corticosteroid for more than 3 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients who have a bone mineral density T-score below -1&#46;5 and are going to take or are taking over 5&#160;mg&#47;d of corticosteroid for more than 3&#160;mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">All patients with a history of fractures caused by bone fragility&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026129.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Indications for Vitamin D Supplementation During Corticosteroid Therapy&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cholecalciferol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Drops&#46; 10&#160;mL vial &#40;20&#44;000 IU&#41;&#58; 0&#46;05&#160;mg&#160;&#61;&#160;400&#160;IU&#160;&#61;&#160;6 drops</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">2&#46;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mL oral solution &#40;25&#44;000 IU&#41; equivalent to 0&#46;625</span><span class="elsevierStyleItalic">mg</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026138.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Calcifediol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Drop&#58; 0&#46;1&#160;mg&#47;mL &#40;6&#46;000&#160;IU&#41;&#59; 240&#160;IU &#40;4&#160;&#956;g&#41;&#160;&#61;&#160;1 drop</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Liquid in ampoules&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>0&#46;266&#160;mg &#40;16&#44;000 IU&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3&#160;mg &#40;180&#44;000 IU&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Soft capsules 0&#46;266</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg &#40;16&#44;000 IU&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026132.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Formulations Available in Spain&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment of deficiency &#40;10-19 ng&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cholecalciferol 25&#44;000 IU weekly for 8 wks and then every 15 d for a further 8 wks&#44; followed by a maintenance regimen of 25&#44;000 IU every 2-4 wks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Calcifediol 16&#44;000 IU weekly for 10 wks and monthly thereafter&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment of severe deficiency &#40;&#60;&#160;10 ng&#47;mL&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cholecalciferol 25&#44;000 IU twice weekly for 6 wks&#44; and then 25&#44;000 IU weekly for 4 wks&#44; followed by a maintenance dose of 25&#44;000 IU every 2-4 wk thereafter&#44; depending on serum levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Shock treatment with calcifediol 3<span class="elsevierStyleHsp" style=""></span>mg &#40;180&#44;000 IU&#41; in a single dose followed by 16&#44;000 IU monthly&#44; depending on serum levels &#40;with a 2-month loading period&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026137.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Supplement Dosages According to 25&#40;OH&#41;D Serum Levels as Specified in the Summary of Product Characteristics&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0040"
        "etiqueta" => "Table 7"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at7"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ichthyosis congenita&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acne&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidradenitis suppurativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Polymorphic light eruption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alopecia areata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nonmelanoma skin cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026131.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Skin Diseases Related to Alterations in Vitamin Levels D&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0045"
        "etiqueta" => "Table 8"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at8"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Skin Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Grade of Recommendation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level of Evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atopic dermatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ichthyosis congenita&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acne&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidradenitis suppurativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Polymorphic light eruption&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alopecia areata&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nonmelanoma skin cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2026134.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Vitamin D Supplementation in Skin Diseases&#58; Grades of Recommendation and Levels of Evidence&#46;</p>"
        ]
      ]
      9 => array:5 [
        "identificador" => "tbl0005"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">1 nmol&#47;L&#47;L equals 0&#46;4 ng&#47;mL&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Institute of Medicine&#44; Food and Nutrition Board&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">3</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">nmol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Health Status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60; 30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60; 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Associated with vitamin D deficiency&#44; which causes rickets in infants and children and osteomalacia in adults&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">30-50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12-20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Generally considered inadequate for bone health&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805; 50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805; 20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Generally considered appropriate for bone and general health in healthy individuals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#62; 125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62; 50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Emerging evidence links such high levels with potential adverse effects&#44; particularly &#62; 150 nmoL&#47;L &#40;&#62; 60 ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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