Management of Psoriasis

Abstract

Oral synthetic retinoids have been established as effective systemic therapy for psoriasis since their introduction for clinical use in the 1970s; a compound for topical use, tazarotene has been recently marketed. Despite the demonstrated clinical success of retinoid therapy in psoriasis, its mechanism of action has not been fully elucidated, and investigators are confronted with two paradoxes. One is that the binding of retinoids to nuclear retinoic acid receptors (RARs) does not match their therapeutic efficacy: acitretin activates the three receptor subtypes, RAR-alpha, -beta and -gamma, without measurable receptor binding, whereas tazarotene preferentially binds to and activates RAR-beta and -gamma in preference to RAR-alpha. The other is that there is already increased formation of retinoic acid in the psoriatic lesion. Answering these questions should result in better use of these drugs in the treatment of psoriasis. Oral administration of acitretin remains one of the first therapeutic choices for severe psoriasis, particularly in association with ultraviolet light therapy, of which it may decrease the carcinogenic risk. Topical tazarotene is suitable for moderate plaque psoriasis. Its efficacy and tolerability can be enhanced by the addition of topical corticosteroids; its irritative potential is counterbalanced by a sustained therapeutic effect after the treatment is stopped.

Genetic Influences on Pharmacological Interventions in Psoriasis

“…Retinoids are synthetic analogues of vitamin A, a fat soluble vitamin that reacts with the nuclear retinoic acid receptor (RARs) [24]. Retinoids affect keratonocyte behavior and differentiation, and help prevent hyperproliferation and inflammation [24].…”

“…Retinoids are synthetic analogues of vitamin A, a fat soluble vitamin that reacts with the nuclear retinoic acid receptor (RARs) [24]. Retinoids affect keratonocyte behavior and differentiation, and help prevent hyperproliferation and inflammation [24]. In pustular psoriasis, retinoids are considered the drug of choice [24], but with plaque psoriasis, the most common form, response is variable to retinoids [24].…”

“…In pustular psoriasis, retinoids are considered the drug of choice [24], but with plaque psoriasis, the most common form, response is variable to retinoids [24]. Vitamin A analogues can cause side effects such as hepatotoxicity and are contraindicated in pregnancy due to their teratogenicity [24].…”

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients

“…Acitretin combines with the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR) and regulates transcription factors, such as signal transducer and activator of transcription 1 and nuclear factor-κB 4,5 . Acitretin induces keratinocyte differentiation and reduces epidermal hyperplasia, leading to slowing of cell reproduction 6 .…”

“…Thus, a low dosage (<50 mg/day) of acitretin is recommended 8–10 . Approximately, 23–52% of patients achieve a 75% improvement iof the psoriasis area severity index (PASI75) from baseline to after treatment, and 66–85% of patients show a 50% improvement of the PASI after 8–12 weeks of treatment 4,11 . Therefore, the efficacy of acitretin varies significantly among psoriasis patients.…”