**UVB and Vitamin D in Psoriasis**

A. Osmancevic

*Dept of Dermatology, Sahlgrenska University Hospital, Gothenburg, Sweden* 

### **1. Introduction**

120 Psoriasis

Wu, JJ. & Tsai, TF. (2008). Recurrent hyperglycemia during adalimumab treatment in a

Psoriasis is a chronic, inflammatory disease affecting the skin and potentially the joints. Both genetic and environmental factors are important in the etiology of the disease. Psoriasis is characterized by keratinocyte hyperproliferation, abnormal keratinocyte differentiation, and immune-cell infiltration into the epidermis and dermis.

Disease management is dependent on severity, psychosocial effects and the patient's lifestyle. Currently, psoriasis may be treated with phototherapy or by using various topical, systemic, and biologic drug treatments. Topical treatments include creams and ointments containing tar, dithranol, corticosteroids, salicylic acid or vitamin D-related compounds.

Vitamin D3 analogs inhibit proliferation, induce terminal differentiation of human keratinocytes and exhibit immunomodulating properties. Several studies have shown vitamin D analogs to be a safe, efficacious and long-term treatment option for psoriasis. Vitamin D3 analogs are also used in combination with phototherapy.

Phototherapy (broadband UVB, narrowband UVB (NBUVB) and heliotherapy – treatment with natural sunlight) is a commonly used treatment modality for widespread psoriasis. A similar wavelength spectrum of UVB (280-315 nm) is responsible for vitamin D synthesis in the skin. Vitamin D3, or cholecalciferol, is produced from 7-dehydrocholesterol in the basal epidermis when exposed to UVB, and is then hydroxylated in the liver into 25 hydroxyvitamin D [25(OH)D], which is the major circulating metabolite. Further hydroxylation into 1,25-dihydroxyvitamin D [1,25(OH)2D] occurs primarily in the kidneys. Hydroxylation in the kidneys is stimulated by parathyroid hormone (PTH) and suppressed by phosphate. Homeostatic mechanisms include parathyroid activity, serum calcium and serum 1,25(OH)2D3 itself. Vitamin D is an essential steroid not only for calcium homeostasis and skeletal health, but also for regulation of cellular growth, cell proliferation and cell differentiation. Vitamin D is obtained by skin production in response to UVB or by intake of vitamin D rich food or supplements. Vitamin D status is measured by serum/blood concentration of its metabolite 25(OH)D.

The wavelength spectrum of UVB responsible for vitamin D synthesis (broadband UVB, 290-320 nm) has been used successfully for years to treat psoriasis and other chronic inflammatory skin disorders. This chapter aims to increase knowledge about the effects of UVB on vitamin D production during treatment with phototherapy in patients with psoriasis and to investigate the impact of UVB-induced vitamin D on psoriasis, bone, lipid

UVB and Vitamin D in Psoriasis 123

major circulating metabolite. Further hydroxylation into 1,25-dihydroxyvitamin D [1,25(OH)2D or calcitriol] occurs primarily in the kidneys (Figure 1). Hydroxylation in the kidneys is stimulated by parathyroid hormone (PTH) and suppressed by phosphate. Homeostatic mechanisms include parathyroid activity, serum calcium and serum 1,25(OH)2D itself. Conversion of vitamin D to 25(OH)D is mediated by the enzyme vitamin D-25-hydroxylase (CYP27A1). The synthesis and degradation of calcitriol are regulated by the enzymes 25(OH)D-1-α-hydroxylase (CYP27B1) and 25(OH)2D-24-hydroxylase (CYP24A1), respectively. The combined activity of these enzymes is an important factor in determining the circulating concentrations of 25(OH)D, and 1,25(OH)2D(1). In addition to the kidney, other tissues and cells, including keratinocytes and immune cells, contain these

Besides being an essential steroid for calcium homeostasis and skeletal health, vitamin D also plays a role in regulation of cellular growth, cell proliferation and cell differentiation. Vitamin D also regulates the immune system, controls cancer cell growth and plays a role in the regulation of blood pressure(6). These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex interacts with vitamin D responsive elements on the target gene. Alterations in calcitriol levels and polymorphisms of the VDR gene have been shown to be associated with several malignant and autoimmune diseases including psoriasis vulgaris(7). 25(OH)D is used clinically to measure vitamin D status. The cut-off level for serum 25(OH)D, which is used as a diagnostic marker for vitamin D deficiency, has varied over the years(8-10). The early biochemical changes in vitamin D insufficiency include a rise in serum PTH, which begins to increase as serum 25(OH)D levels fall below 30 ng/ml or 75 nmol/l(9). This level of 25(OH)D has become the suggested cut-off point for vitamin D deficiency or inadequacy(9, 11-13). At the present time, there is no clear consensus regarding levels of 25(OH)D for optimal health but levels of > 50 nmol/l (20 ng/ml)(14) and > 75 nmol/l (30 ng/ml) have been based on considering the outcomes of bone health, fracture prevention and colorectal cancer(15,16). Sun exposure is the strongest factor influencing 25(OH)D. The serum concentrations of 25(OH)D vary seasonally, with maximum and minimum values in the late summer and winter respectively(17). The extent of this seasonal variation depends on factors such as latitude, skin pigmentation, clothing, and the use of

Currently, limited data is available on the role of vitamin D deficiency in the pathogenesis or outcomes of psoriasis. The lack of conclusive data combined with vitamin D's immunomodulatory role, warrants further research investigating the role of vitamin D insufficiency in chronic diseases as well as monitoring 25(OH)D levels in children and

Vitamin D has pleotropic functions; it acts as a hormone by controlling calcium homeostasis as well as exerting autocrine/paracrine effects on tissues that express CYP27B1 and VDR. Besides its local effects, calcitriol may also act in psoriasis through its immunomodulatory properties by inhibiting T-cell proliferation and Th1 development, modulating antigenpresenting cell (APCs) function, inducing hyporesponsiveness to antigens, inhibiting

adults of all ages as a part of routine physical examinations.

**2.2 The effects of vitamin D in psoriasis** 

enzymes and are able to convert 25(OH)D to active 1,25(OH)2D(5).

sunscreen(18).

and carbohydrate status in psoriasis patients. A review of the published studies will be used to accomplish this task. In our previously published studies, the serum concentrations of 25(OH)D, 1,25(OH)2D, PTH, calcium and creatinine were measured before and after phototherapy in Caucasian patients with moderate to severe active plaque psoriasis. Bone mineral density (BMD) was examined using dual-energy X-ray absorptiometry (DEXA) at the hip and lumbar spine in a group of postmenopausal women with psoriasis. Lipid and carbohydrate status were assessed in patients treated with heliotherapy.

We found that UVB/heliotherapy improved the psoriasis score and lipid and carbohydrate status of the patients, increased serum 25(OH)D synthesis and reduced serum PTH concentrations. Vitamin D production in psoriasis patients increased less with narrowband UVB than with broadband UVB phototherapy. There was no correlation between the dose of UVB and the increase in 25(OH)D. The ratio of low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol decreased, and the levels of glycosylated hemoglobin A1c (HbA1c) also decreased in psoriasis patients during heliotherapy. Postmenopausal women with psoriasis had higher BMD than age-matched controls, a finding that could be related to their higher body weight, levels of physical activity and UVB exposure.

The changes in serum concentrations of vitamin D metabolite 25(OH)D were not related to the degree of improvement in psoriasis severity. This can be explained by the fact that 25(OH)D is biologically inert. It is unclear if the serum 25(OH)D level is linked to the level of the active form of vitamin D3 (1,25(OH)2D) present in the skin. It has been suggested that cutaneous conversion of 25(OH)D to 1,25(OH)2D does not play a role because the amount of free 25(OH)D3 that penetrates the cell membrane of epidermal keratinocytes is too small to produce sufficient amounts of 1,25(OH)2D. Therefore, of great interest will be the study of UVB induced local effects on vitamin D synthesis and metabolism in psoriatic skin.
