# Soriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics
## 3 Current Marketed Therapies  
As psoriasis is a chronic disease, long-term therapy is usually necessary. Depending on different factors, such as disease severity or comorbidities, there is a wide range of treatments that have different responses depending on the patient. There are different grades of psoriasis, measured by different factors, such as severity of lesions, percentage of affected surface area, and quality of life [35]. One of the most widely used criteria is the Psoriasis Area and Severity Index (PASI), being the most accurate. The PASI allows comparisons between clinical trials and objectively evaluates the effectiveness of different antipsychotic drugs. Following these criteria, there are several grades of psoriasis, from mild to moderate to severe psoriasis. Almost 80% of psoriasis patients have mild to moderate psoriasis, which can be treated with topical treatments [36; 37]. In moderate cases, there are some topical treatments, based on corticosteroids, used in combination with other drugs, such as vitamin D, or alone, such as vitamin D derivatives, vitamin A, and anthralin, which are examples of actual topical treatments. Vitamin D3 analogues constitute the first line topical treatment for plaque psoriasis and moderately severe scalp psoriasis [38; 39]. The beneficial effects of vitamin D induced by exposure to sunlight in the treatment of psoriasis has been known for decades [40; 41; 42]. However, vitamin D has shown a relevant yet controversial role in psoriasis, as well as other skin diseases [43; 44]. In this area, [PERSON] et al. aimed to shed some light by confirming reduced vitamin D levels in psoriatic patients and stablishing a relationship between vitamin D levels and psoriasis length [45]. Moreover, [PERSON] et al. also confirmed lower presence of 25-hydroxyvitamin D (25 OHD) in psoriasis patients, 25 OHD being an possible indicator of the amount of stored Vitamin D [46; 47]. However, there is little evidence that the increase in 25 OHD after phototherapy correlates with improved disease severity [48]. Moreover, Vitamin D is involved in the proliferation of keratinocytes (Figure 3). In fact, the precursor of vitamin D, 7-DHC, is localized in the keratinocyte membrane, and, by the UVB activation, it is transformed into pre-vitamin D3 or cholecalciferol, which is later converted first to 25 OHD by the enzymes CYP2/A1 and CYP2R1 and then to 1,25(OH)D or calcitriol, the active form of vitamin D [1; 49; 50; 51; 52]. Calcitriol regulates differentiation and proliferation of keratinocytes, as well as the balance of the cutaneous immune system and cellular apoptosis. Interestingly, at low vitamin D concentrations, a promotion of keratinocyte differentiation is found, whereas, at high concentrations, an inhibitory effect occurs [43]. Due to the regulation of calcium exerted by vitamin D through calcium receptor induction and phospholipase C enzymes, calcitriol and its analogues (calcitriol, calcipotriol, tacalcitol, hexafluoro-1,25(OH)D, and maxcalcitol) have demonstrated interesting features. In fact, in vitro studies demonstrated that they were able to reduce the psoriatic upregulated levels of S100A7 and regulate cell proliferation in the stratum basale in addition to increasing keratin synthesis and regulating glycoceramides production. Therefore, a decrease in calcitriol or a loss of function of its receptor causes epidermis disruption that results in hyperproliferation of the basal layer [43]. The anti-inflammatory effect attributed to vitamin D may also result from inhibition of production of IL-2, IL-6, and interferon-gamma (IFN-\(\gamma\)). Furthermore, topical calcipotriol inhibits human beta defensin and proinflammatory cytokines, which are increased in psoriatic lesions [43]. Moreover, calcitriol, as well as novel vitamin D3 derivatives, inhibit the transcriptional activity of NFkappaB, a major inducer of inflammation [41]. Interestingly, several studies identified an association between polymorphisms of vitamin D receptor (VDR) and psoriasis susceptibility [43].