Krafka25 and Thacker26 were the first scientists to postulate a role for vitamin D in psoriasis. The use of oral vitamin D as a treatment for psoriasis failed because of the risk of hypercalcemia. The development of topical vitamin D analogs, such as calcipotriol and tacalcitol, later revolutionized the treatment of the condition. Bergler-Czop and Brzezińska-Wcislo27 observed a correlation between Psoriasis Area and Severity Index (PASI) scores and serum levels of 25(OH)D and reported that patients with lower vitamin D levels had higher PASI scores. Orgaz-Molina et al.28 demonstrated that patients with psoriasis and a body mass index higher than 27 were more likely to have insufficient 25(OH)D levels. The comorbidities of psoriasis (diabetes mellitus, obesity, and metabolic syndrome) have also been linked to diets low in vitamin D.29 Clinicians should recommend diets that provide vitamin D in view of its beneficial effect on many of the comorbidities associated with psoriasis. The use of vitamin D in psoriasis is currently a grade B recommendation with IIa level of evidence.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory disease, initially characterized by pruritus and eczematous lesions. It affects up to 20% of the pediatric population and around 7.2% of adults.30 AD is caused by an alteration in the cutaneous immune system and a defect in the synthesis of the epidermal barrier, which affects mainly filaggrin.31,32 Many authors have studied the association between vitamin D and AD. Kim et al.33 published a meta-analysis and systematic review of 11 articles, 7 observational studies, and 4 clinical trials. Compared to healthy controls, patients with AD had lower levels of vitamin D, especially in the pediatric population. 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 (levels below 20 ng/mL). In a series of 210 adult patients with AD, Van der Schaft et al.34 reported that vitamin D supplementation in patients with deficient levels did not lead to any significant improvement in eczematous lesions. Several studies in the literature report that vitamin D supplementation in children decreased colonization with Staphylococcus aureus, a microorganism that plays a role in outbreaks of DA.35–37 Despite the evidence that vitamin D levels tend to be insufficient in adult patients with AD,38 there is still debate about whether vitamin D supplementation is useful in this age group. In children the use of vitamin D is a grade B recommendation with a IIa level of evidence.

Sethuraman et al.39 reported low levels of 25(OH)D and high levels of PTH in children with ichthyosis congenita. In that study, vitamin D supplementation with 60,000 IU of oral cholecalciferol for 10 days followed by a maintenance regimen of 400 to 600 IU/d achieved a rapid response, with noticeable improvement in the dermatological symptoms by the fifth day in terms of both scaling and stiffness. Of the 7 children studied, 6 had serum 25(OH)D levels under 4 ng/mL. While more studies are needed, these findings open up interesting possibilities in the management of ichthyosis congenita. Lucker et al.40 published the results achieved with topical calcipotriol in patients with ichthyosis congenita (Netherton syndrome, lamellar, ichthyosis bullosa of Siemens, and epidermolytic ichthyosis of Brocq). Scaling and associated redness improved in all but the bullous form of the disease. In ichthyoses in which epidermal hyperproliferation and retention hyperkeratosis do not predominate—such as X-linked ichthyosis, ichthyosis vulgaris, and acquired ichthyosis—topical application of vitamin D analogs has not been shown to be effective.41 Neema et al.42 raised the possibility of combining vitamin D with oral retinoid treatment in patients with low vitamin levels. Despite the published findings, the use of vitamin D supplementation in patients with ichthyosis is a grade C recommendation with a IIIa level of evidence.

Interest in the role of vitamin D in acne first emerged in 1938.43 A comparative study of serum levels of 25(OH)D in adolescents with and without acne was published in PloS One in 2016.44 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. Following 2 months of vitamin D supplementation, the number of inflammatory lesions decreased but no change was observed in non-inflammatory lesions. The role of vitamin D in acne could be explained by a relationship between the vitamin and reduced synthesis of interleukin (IL) 6, IL-8 and metalloproteinase-945 as well as to a reduction in the expression of IL-17 because of its action on Th17 cells.46 Zouboulis et al.47 described the effect of vitamin D on the sebaceous glands and the increase in lipogenesis when vitamin D levels are insufficient, an effect that promotes an increase in inflammatory lesions. The authors of a recent study reported that 25(OH)D levels were higher following treatment than at baseline in patients treated with oral isotretinoin, concluding that the role of vitamin D in the inflammatory pathogenesis of acne is important in the development of lesions.48 The use of vitamin D in acne is currently a grade B recommendation with a IIb level of evidence.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant impact on the patients’ quality of life. Several studies have been published on the relationship between HS and vitamin D levels.49,50 In those studies, the patients with HS had lower vitamin D levels than controls and an inverse correlation was observed between vitamin D levels and disease severity. Following 6 months of vitamin D supplementation, inflammatory nodules improved in 79% of patients (out of the 14 treated); however, as with acne, no significant changes were observed in non-inflammatory lesions. In the opinion of the authors of another study, the endocrinological and metabolic alterations associated with HS make vitamin D a therapeutic target because of its relationship with metabolic syndrome, among other reasons.51 Well-designed studies with a sufficient number of patients are needed to determine the role of vitamin D in HS. The use of vitamin D in HS is currently a grade B recommendation with a III level of evidence.

There are more than 300 articles in the literature on the relationship between vitamin D and vitiligo. Karagün et al.52 observed lower serum vitamin D levels in 50 patients with vitiligo compared to healthy controls and an inverse correlation with the extent of disease. In a meta-analysis, Upala and Sanguankeo53 concluded that the evidence did indicate a clear relationship between vitiligo and low vitamin D levels. Variable results have been reported in cases in which vitiligo was treated with vitamin D analogs either alone54 or in combination with other treatments.55 However, there are no clinical trials that demonstrate the efficacy of vitamin D supplements in these patients. Khurrum and AlGhamdi56 found no significant differences in vitamin D levels between patients with vitiligo and healthy controls; in the analysis by subgroups, however, it was observed that in the group of patients with vitiligo, the lowest vitamin D levels were associated with male sex, younger age, a short duration of vitiligo, and not having received treatment with phototherapy. At present, the use of vitamin D in patients with vitiligo is a grade B recommendation with a IIa level of evidence.

Several studies have found a higher prevalence of vitamin D deficiency in patients with systemic lupus erythematosus (SLE) than in the healthy population.57,58 The authors of a study published in PloS One, which investigated the relationship between vitamin D levels and the severity of SLE, reported that 71.4% of the patients had vitamin D levels under 30 ng/mL.59 They also observed an association between lower vitamin D levels and poorer scores on the Systemic Lupus Erythematosus Disease Activity Index. However, supplementation with 400 to 1,000 IU/d of vitamin D failed to raise levels above 30 ng/mL. In a comparative study with placebo by Karimzadeh et al.,60 patients with SLE who received vitamin D supplementation showed a significant increase in serum 25(OH)D levels but this was not associated with any effect on disease activity. 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.61 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.62 The use of vitamin D in patients with SLE is a grade B recommendation with a IIa evidence level.

Polymorphic light eruption (PLE) is an idiopathic photosensitivity disorder related primarily with exposure to UV-A and less often with UV-B radiation. It is found more frequently in young women. Schweintzger et al.63 found no significant relationship between vitamin D levels and the number and function of regulatory T cells, concluding that other factors affect the immune response that occurs in PLE. Nevertheless, in another study patients with PLE had lower vitamin D levels than controls and when these were increased by phototherapy with UV-B (311 nm) a correlation was observed between the increase and clinical improvement of the lesions.64 In a placebo-controlled clinical trial, Gruber-Wackernagel et al.65 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. However, there is no consensus in photobiology units on the use of this treatment for PLE. The use of vitamin D in PLE is a grade B recommendation with a IIb level of evidence.

The role of vitamin D in alopecia areata (AA) has been explored in several studies.66–69 Thompson et al.70 analyzed data from a cohort of 55,929 women and found no association between vitamin D supplementation and incident AA. However, other studies have found that vitamin D levels tend to be lower in patients with AA than in healthy controls71 and even lower in patients with universal AA compared to those with the ophthalmic or plaque forms. Vitamin D levels have not been shown to differ significantly according to age, sex, disease duration, disease recurrence, or family history of AA. However, 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.72

While topical vitamin D analogs can be used to treat AA,72,73 no studies have been carried out which demonstrate that oral supplements with vitamin D are effective in this setting.

The use of vitamin D in patients with AA is currently a grade B recommendation with a IIb level of evidence.

The role of vitamin D in melanoma has been investigated in a number of studies.74–77 Orlow et al.78 identified certain haplotypes of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene related to increased survival in patients with melanomas in photoexposed sites (rs1544410/BsmI and rs731236/TaqI). Subsequent studies have reported an inverse correlation between Breslow thickness and vitamin D levels79 and a possible relationship between low serum vitamin D levels and ulceration80 in patients with melanoma. In fact, a worse prognosis was observed in the patients whose vitamin D levels were low when melanoma was diagnosed and also when, even after starting supplementation, the patient did not achieve levels above 20 ng/mL. In a recent study of 3578 patients, however, no significant relationship was found between melanoma survival, determined by the Breslow thickness, number of mitosis, ulceration, and SNPs found in the pathway of vitamin D and its receptor.81 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.82 The use of vitamin D in patients with melanoma is currently a grade B recommendation with a IIb level of evidence.

The role of vitamin D in carcinogenesis83 led to the study of its relationship with nonmelanoma skin cancer (NMSC).84 The cells of basal cell and squamous cell tumors express VDRs. Eide et al.85 reported an association between high vitamin D levels and an increased risk of keratinocyte carcinoma. Vitamin D is also able to inhibit the Hedgehog signaling pathway in basal cell carcinoma.86 Research has shown that patients with the Bsml SNP of the vitamin D receptor have a higher risk of developing NMSC.87 However, in a prospective study with more than 60,000 participants, vitamin D supplementation was not associated with squamous cell carcinoma risk or the incidence of basal cell carcinoma.88 Confounding factors such as sun exposure and phototype, among others, 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. The use of vitamin D in patients with NMSC is a grade B recommendation with a IIb level of evidence.