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Commentary to the review article: Subedi S, Yu Q, Chen Z, Shi Y. Management of pediatric psoriasis with acitretin: A review. Dermatol Ther. 2018 Jan;31(1)

Acitretin is a second-generation of synthetic monoaromatic retinoid and a free acid form and active metabolite of its precursor etretinate widely used for the treatment of psoriasis (Chiricozzi et al., 2017; Ortiz, Nijhawan, & Weinberg, 2013). In advantage over its precursor, acitretin is less lipophilic and clears rapidly from the body and possesses shorter elimination half-life. Acitretin binds to the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), modulating the transcription of genes coding various proteins involved in the pathogenesis of psoriasis. Thus, from one side, acitretin acts as antagonist for a number of transcription factors, which can have other target genes with respect to retinoids; from another side, acitretin indirectly inhibits certain genes that regulate proliferation, angiogenesis, and inflammation in psoriasis (Carretero et al., 2013). In the present review (Subedi, Yu, Chen, & Shi, 2018), the authors highlight a convincing number of clinical trials and case articles where acitretin was used for psoriasis treatment in children. Acitretin was also shown to be more effective in pustular and erythrodermic psoriasis with respect to the plaque psoriasis in children. Nevertheless, cautions should be exercised using acitretin in childhood due to the number of possible dose-dependent side effects of this retinoid. Mucocutaneous side effects can be treated symptomatically, and if severe effects occur, the dose reduction can be tried before the discontinuation of the drug. To avoid skeletal abnormalities correlated to the use of acitretin the regular monitoring of child health and timely investigations should be performed in case of long term treatments. Finally, a synergetic effect of acitretin and NB-UVB treatment was showed. Interestingly, in their conclusion, the authors suggest that acitretin can be used in the treatment of recalcitrant type of psoriasis which cannot be controlled by other therapies (topical and phototherapy) and significantly improves psychosocial state of the child. An interesting observation comes from the data of other authors about the redox modulating properties of acitretin. Bohne and coworkers (Bohne, Story, Gerber, & Gollnick, 1997) initially showed that acitretin inhibits superoxide anion formation and a more recent work (Hadjipavlou-Litina, Magoulas, Krokidis, & Papaioannou, 2010) proved the antioxidant properties of acitretin. In particular, the present study demonstrated that acitretin and its synthetic analogues significantly inhibit lipoperoxidation as well as lipoxygenase (LOX) activity. Briefly, the reducing activity of the stable radical 1,l-diphenyl-2-picrylhydrazyl radical (DPPH), the 2,20-Azobis(2-amidinopropane) dihydrochloride (AAPH)-induced inhibition of lipid peroxidation as well as LOXmediated conversion of sodium linoleate to 13-hydroperoxylinoleate were measured in vitro by spectrophotometric assay in the presence of acitretin and its analogues. In agreement with this observation, another study showed that the treatment with etretinate (the ethyl ester of acitretin) significantly increased erythrocyte membrane fluidity, superoxide dismutase (SOD) and catalase activities and decreased lipid peroxidation in erythrocytes from psoriatic patients (Gornicki & Gutsze, 2001). It is well-known that oxidative stress, together with autoimmune mechanisms, plays a crucial role in the pathogenesis of psoriasis. Indeed, our recent data showed an altered redox status in blood and white blood cells (WBCs) of psoriatic patients, as proved by increased plasma levels of malondialdehyde and protein carbonyl content, enhanced blood cell ROS production and lipoperoxidation, and reduced glutathione content (Barygina et al., 2013; Becatti et al., 2018). Parallelly, total antioxidant capacity in both plasma and WBC were significantly decreased in psoriatic patients with respect to controls. Interestingly, for the first time, we identified NADPH oxidase as an important ROS source in WBC of psoriatic patients. Received: 11 May 2018 Accepted: 10 July 2018 DOI: 10.1111/dth.12700