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Background: Psoriasis is a chronic inflammatory skin disorder characterized by the development of red, scaly patches (National Psoriasis Foundation). It affects a significant portion of the global population, with estimates suggesting around 2% worldwide and 0.44% in India. Acitretin, a second-generation retinoid derived from vitamin A, emerged as a recognized treatment for severe psoriasis following its approval by the US Food and Drug Administration (US-FDA) in 1997. Aim: The objective of this study was to enhance the topical delivery of acitretin by formulating it into a transethosomal gel. Acitretin, being poorly water-soluble, has limited penetration into the deep layers of the skin. The incorporation of transethosomal technology in this formulation aims to enhance acitretin's penetration into the skin and potentially improve its bioavailability. Method: Transethosomes were prepared using the cold method. A 17-batch Box-Behnken design (Design-Expert® software) was employed to optimize the formulation with varying concentrations of lipid, ethanol, and Tween 80. Entrapment efficiency, vesicle size, and zeta potential were determined to characterize the transethosomes. The optimized batch containing acitretin-loaded transethosomes was then incorporated into a xanthan gum gel base. In vitro and ex-vivo and flux studies were conducted to assess drug diffusion and release patterns. Additionally, the formulation's irritancy and anti-psoriatic activity were evaluated in-vivo using Wistar rats. Results: The Box-Behnken design optimization identified a formulation with a combination of 38.1% ethanol, 1.9% lipid, and 0.3% Tween 80 as optimal. This formulation exhibited a vesicle size of 105 nm, an entrapment efficiency of 80.4%, and a zeta potential of -28.25 mV. An optimized transethosome-based gel formulation was developed for its potential application in psoriasis therapy. The gel underwent a comprehensive evaluation of its physicochemical properties (pH, viscosity, spreadability) and in-vitro antimicrobial efficacy against Staphylococcus aureus. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and zone of inhibition assays were employed, demonstrating the gel's potent antibacterial activity. In-vivo studies on Wistar rats were subsequently conducted to evaluate skin irritation and imiquimod-induced anti-psoriatic activity. A pharmacokinetic study further compared the bioavailability of the transethosome gel with a conventional gel formulation. Notably, the results revealed a significant enhancement in bioavailability with the Transethosomal formulation. Conclusion: The acitretin-loaded transethosomal gel demonstrated enhanced skin penetration and efficacy in managing psoriasis, achieving better outcomes than conventional treatments, while maintaining biocompatibility and minimal local side effects such as erythema, edema, and irritation. [ABSTRACT FROM AUTHOR]

Hui Ye,1,2,* Weifeng Chen,1,2,* Wenyan Liu,1,2 Junhui Zhu,1,2 Jingyao Liang,1,2 Xibao Zhang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingyao Liang; Xibao Zhang, Guangzhou Dermatology Hospital, No. 56 hengfu Road, Guangzhou, 510095, People’s Republic of China, Email ljy20221228@163.com; gzpfbfzs@163.comAbstract: Darier’s disease (DD) is a rare chronic keratinizing skin disease characterized by dyskeratosis of epidermal cells. We report a case of DD with a medical history spanning over 20 years and recurring symptoms. Pathologically confirmed DD was treated with a combination of abrocitinib and acitretin, resulting in rapid symptom resolution within 2 weeks. No recurrence was noted in an 11-week follow-up. The mechanism may involve acitretin’s inhibition of proliferation and anti-inflammation, while abrocitinib acts on IL-6 implicated in DD pathogenesis, exerting an immunomodulatory and anti-inflammatory effect, leading to rapid symptom relief. The combination of abrocitinib and acitretin is an effective therapy for DD, offering a promising new option for refractory patients.Keywords: keratosis follicularis, Darier’s disease, abrocitinib, acitretin

AbstractOral vitamin-A derivative acitretin treats severe psoriasis. Oral capsules are commercially available preparation and have severe systemic adverse effects. This research involved the development, optimization, and characterization (in vitro and ex vivo) of a topical gel formulation of solid lipid nanoparticles (SLNPs) for the efficient delivery of acitretin to the skin. SLNPs with acitretin were prepared using hot homogenization with compritol ATO 888 and Tween 80. Optimization was done via a 32 factorial Box–Behnken design. SLNPs exhibit a vesicle size within the range of 181.53 ± 1.727 to 409 ± 1.019 nm, with a prominent encapsulation efficiency of 78.82% ± 2.1% to 85.73% ± 1.6%. Moreover, the developed SLNPs and SLNPs-based gel formulation demonstrate reliable storage stability over 3-month duration. The ex vivo skin permeation and deposition studies were conducted using cellophane membrane and rat skin, respectively. The results demonstrated a sustained release of the SLNP-based gels over an 8-h period, as well as a higher skin deposition compared to the plain acitretin gel. The acitretin SLNP in vitro release study demonstrated an 86.83% sustained drug release within 8 hours, whereas a plain gel exhibited a 92.5% drug release within 4 hours. Ex vivo drug deposition testing of SLNP-based gel formulation demonstrate a total of 0.056 mg/cm2 of acitretin skin deposition, while the commercially available gel had only 0.012 mg/cm2. Acitretin SLNPs show promising potential for treating psoriasis more effectively, offering a safe alternative to topical acitretin administration with enhanced pharmacological effects and reduced systemic toxicity compared to oral intake. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP), being a chronic inflammatory systemic disease, significantly reduces the quality of life of patients, leads to disability and increases the risk of mortality. Representing one of the most severe variants of the disease, GPP has its own features of pathogenesis, which distinguish it from plaque and other forms of dermatosis. Presently, the key factor in the development of the systemic process in GPP is considered to be a decrease in the expression or activity of IL-36ra receptor antagonists due to mutation of the IL-36RN gene, and as a result of this, excessive activity of IL-36 agonists and accumulation of neutrophil granulocytes in the epidermis. Based on the features of clinical manifestations in the form of multiple painful pustules accompanied by fever up to 40° C, characteristic changes in laboratory parameters in the form of increased markers of inflammation (leukocyte levels with neutrophil shift in peripheral blood, C-reactive protein), GPP needs to be differentiated from a number of diseases accompanied by similar symptoms: subcorneal pustular dermatosis Sneddon–Wilkinson, Sweet's syndrome, a herpes infection. The features of the pathogenesis of GPP determine the difficulties in the treatment of medicines that are successfully used in the treatment of plaque psoriasis, including methotrexate, cyclosporine, retinoids, TNF-α inhibitor, interleukin-17 and -23 inhibitors, as well as their combinations. A clinical case of a severe continuously recurrent resistant to therapy with cytostatics and genetically engineered preparations is presented, the diagnosis of which was complicated by a contradictory pathomorphological picture.

Abstract Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

Objectives Methods Results Conclusions Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by the accumulation of hyaline‐like material in the skin, oral mucosa, larynx, and brain. This study aimed to evaluate the dermatological findings and treatment responses of patients diagnosed with LP.This retrospective study included 41 patients diagnosed with LP at our clinic between May 2018 and January 2023. The diagnosis of LP was established in 22 patients by detecting mutations in the ECM1 gene. In comparison, in 19 patients, it was based on typical clinical findings and histopathological examination of lesioned skin. Clinical and demographic data such as dermatological findings, treatments received, and responses to treatment were recorded from patient files.All patients exhibited skin thickening and acneiform scars. The most commonly observed additional dermatological findings were moniliform blepharosis (60.9%), varioliform scars (29.2%), waxy papules and plaques (24.3%), and blisters with crusts (19.5%). Verrucous lesions, diffuse yellow plaques, and scarring alopecia were observed in adult patients, while hypopigmented lesions and blisters with crusts were seen in the pediatric age group. The most frequently used treatments were acitretin (14.6%) and systemic steroids (9.7%). No improvement in skin lesions was observed in patients treated with acitretin, whereas complete resolution of blisters with crusts was noted in patients treated with systemic steroids.In addition to the existing literature on dermatological manifestations of LP, hypopigmented lesions and atrophoderma vermiculatum‐like lesions can also be observed in these patients. We believe that short‐term systemic steroid therapy for vesiculobullous lesions can be considered for treatment. We think prospective studies with more patients and requiring long‐term follow‐up are needed regarding the effectiveness of acitretin treatment. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. Studies regarding infection rates after vaccination are lacking. Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases. [ABSTRACT FROM AUTHOR]

Acitretin is a synthetic, second-generation retinoid mainly used for the treatment of Darier's disease (DD), which impacts biological processes by binding to a nuclear receptor from the corticosteroid/thyroid receptor superfamily, thereby altering gene expression. Our report outlines the case of a 41-year-old male patient who has received a clinical diagnosis of DD and does not exhibit any other coexisting comorbidities, who developed hypothyroidism posttreatment with acitretin, an unusual and rare side effect of the drug. His baseline routine investigations fell within normal limits before the initiation of acitretin. Acitretin-induced hypothyroidism was treated with thyroxine. Although a good therapeutic response was seen with acitretin, it could not be continued due to the development of side effects and was continued on topical therapy. This case emphasizes the likelihood of adverse effects linked to therapeutic levels of acitretin in patients without any prior history and signifies the critical importance of consistent blood monitoring throughout drug therapy. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment. [ABSTRACT FROM AUTHOR]

Background: Plantar warts are benign epithelial tumors that are forced inward due to pressure on the toes or sole of the foot and may become very painful if not treated. Many treatment options are available including topical treatments, lasers, and immunotherapy. However, data about systemic therapies are lacking. Objective: To compare the efficacy and safety of acitretin versus oral isotretinoin in the treatment of multiple plantar warts. Patients and methods: This randomized comparative double-blinded study included 80 adult patients with multiple plantar warts. The cases were divided into two groups: acitretin group (40 cases with a dose of 0.5 mg/kg/day) and isotretinoin group (40 cases with a dose of 0.5 mg/kg/day). The reduction in wart size and photographic comparisons at the beginning and every 2 weeks for 3 months were used to assess the treatment efficacy in the two groups. After therapy ended, a follow-up was conducted every month for 6 months to observe any recurrence. Results: Complete response was observed in 30%, partial response in 55%, and no response in 15% of patients of acitretin group while complete response was achieved in 15%, partial response in 45%, and no response in 40% of patients of isotretinoin group with statistically significant difference in favor of acitretin (P=0.03). Compared with acitretin, oral isotretinoin was associated with a shorter duration to a complete response (83.3% of cases achieved complete response in <2 months compared with only 16.7% in acitretin group) (P=0.006). Conclusion: Acitretin is superior to oral isotretinoin as a therapeutic option for plantar warts, but both are effective and safe. Since they are resistant to other traditional therapy techniques, they can be seen as valuable therapeutic choices for multiple plantar warts. [ABSTRACT FROM AUTHOR]

Introduction: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn’s life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome. Genetic testing of SPINK5 gene is key to confirming the diagnosis and starting early treatment. Case Presentation: We present a case report of NS in a 6-year-old boy who suffered from generalized erythroderma and desquamation of the skin from birth. The patient has atopic diathesis, recurrent skin infections, increased levels of IgE, and delayed physical development. Two genetic variants in SPINK5 gene with clinical significance were identified. The first detected variant is a nonsense mutation, predicted to cause loss of normal protein function either by protein truncation or by nonsense-mediated mRNA decay. The second variant is a likely pathogenic frameshift mutation that truncates the protein in 5 amino acids. The child was treated with acitretin, without satisfactory effect. Conclusion: The genetic variant we have described correlates with a severe clinical phenotype of NS. The second genetic variant of the SPINK5 gene, inherited from the father in our case, is novel and has never been published in the literature.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by infiltration of periodic acid schiff (PAS)-positive diastase-resistant hyaline material in the skin, oral cavity, and larynx caused by a mutation in the extracellular matrix 1 gene. Clinically characterized by beaded eyelid papules, waxy papules, nodules, plaques, and acneiform pock-like scars over the face and body. We report a case of LP, with involvement of the skin, eyes, brain, oral mucosa, and larynx, histopathologically confirmed by PAS-positive and diastase-resistant deposition in the dermis. The patient showed good response in skin lesions and quality of speech with 6-month of therapy of acitretin 0.5 mg/kg/day and followed up for 1 year without recurrences. As there is no curative and specific therapy for LP, acitretin is a very useful drug in improving quality of life, speech, and cosmetic appearance.

Psoriasis is a chronic immune-mediated disease that affects 2-5% of the world’s population. Most patients with moderate to severe psoriasis require systemic treatment. Despite the development of biological therapy, traditional systemic drugs remain an important therapeutic option due to their efficacy and affordability. The most commonly used traditional drugs are methotrexate, ciclosporin, acitretin, and fumarate. One of the disadvantages of traditional systemic medication is the possibility of side effects, which can be successfully controlled with regular patient monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn's life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome. Genetic testing of SPINK5 gene is key to confirming the diagnosis and starting early treatment. Case Presentation: We present a case report of NS in a 6-year-old boy who suffered from generalized erythroderma and desquamation of the skin from birth. The patient has atopic diathesis, recurrent skin infections, increased levels of IgE, and delayed physical development. Two genetic variants in SPINK5 gene with clinical significance were identified. The first detected variant is a nonsense mutation, predicted to cause loss of normal protein function either by protein truncation or by nonsense-mediated mRNA decay. The second variant is a likely pathogenic frameshift mutation that truncates the protein in 5 amino acids. The child was treated with acitretin, without satisfactory effect. Conclusion: The genetic variant we have described correlates with a severe clinical phenotype of NS. The second genetic variant of the SPINK5 gene, inherited from the father in our case, is novel and has never been published in the literature. [ABSTRACT FROM AUTHOR]

Abstract Background Limited research has been conducted on whether advances in novel biologics and biosimilars have improved the treatment journey preceding biologics. Objectives To map the overall treatment journey preceding the initiation of first biologic therapy in patients with psoriasis (PsO) and psoriatic arthritis (PsA), as well as the changes over time. Methods Using Danish nationwide registries, we included all patients treated with a first‐time biologic (2010–2018) for either PsO or PsA and reported the medical treatment journey. We used Sankey diagrams to illustrate the flow of treatment series. Results The study included 2082 patients with PsO (62.5% male) and 1831 patients with PsA (42.3% male). Before biologics, 49.5% treated for PsO and 36.8% treated for PsA received ≥2 type therapies and 59.3% with PsO and 25.5% with PsA received ≥3 treatment series. Median time from first systemic therapy to a biologic was 3.9 years (Q1–Q3, 1.3–4.1) for PsO and 2.1 years (Q1–Q3, 0.6–5.8) for PsA. The majority of patients with PsO (1174 [56.4%]) received multiple treatment series with the same drug, while almost a third of patients with PsA (572 [31.2%]) did the same. Twelve percent of patients with PsO and 6.4% of patients with PsA repeated treatment with a drug they had already stopped for an alternative treatment. Conclusions Although most patients are adequately managed, our findings suggest the possibility of a yet too long and complicated treatment journey before starting biologics.

Globally, endometrial cancer (EC) is the six most common cancers related to female reproductive. EC incidence and mortality rates have increased over the last decade. Cytotoxic therapy with carboplatin or paclitaxel is the recommended first-line treatment for EC patients. However, the options for following therapy are limited. The latest advances in molecular studies have uncovered the nature of genetic alterations in EC, compelling methods for further research into the treatment of EC since they may disclose to tailored pharmacological therapy. The aim of this study was to identify novel drug candidates in treating EC using genomics variants and biological pathway. The genomic variants of EC were downloaded from cBioportal database. We established connection between the biological EC risk genes from cBioportal database and the DrugBank database. Finally, we used Connectivity Map (CMap) analysis to identify possible drugs whose mechanisms coincided with therapeutic targets and rank them in accordance to scoring criteria. We identified novel conceivable candidate drugs for EC, they are Bosutinib, Acitretin and Nilutamide. These drugs exhibit robust scores in the CMap analysis compare to paclitaxel. We also discovered BCR-ABL1 and AR as potential biomarker-driven therapy in EC. This study demonstrates the possibility of using genetic network analysis combined with bioinformatics to repurpose drugs for the treatment of EC. Further investigation will be undertaken to explore the mechanisms involved in the application of BCR-ABL1 and AR for treating of EC.

Abstract Acitretin (ACT) is a second-generation systemic retinoid used to treat severe psoriasis. However, its poor aqueous solubility and systemic adverse effects make it impractical for oral administration. The primary objective of this research is to prepare, optimize, and evaluate a nanogel consisting of acitretin-loaded ethosomes (ACT-ETH) for its anti-psoriatic potential. A 32 full factorial design was employed for optimization. Thin-film hydration was adopted to prepare ACT-ETH, and then their physicochemical characteristics were tested. The optimized ACT-ETH was converted into a carbopol gel and then evaluated for cytotoxicity, skin irritation, and anti-psoriatic properties. The vesicle size, zeta potential (ZP), and percent entrapment efficiency (% EE) of the optimal ACT-ETH are 147 ± 2.15 nm, −11.5 ± 0.25 mV, and 90.70 ± 0.89%, respectively. The fluorescence microscopy study has shown that ethosomes may go deeper into the skin layers. Compared to plain gel, ACT-ETH gel greatly increased skin permeability and deposition in the ex-vivo skin permeation and deposition tests. The in vitro cytotoxicity investigation revealed that the cytotoxicity of ACT against normal cells (L-929) was significantly reduced by ACT-ETH gel compared to plain ACT gel. The skin irritation study proved that ACT-ETH gel was well tolerated and safe for use on the skin. The in vivo anti-psoriatic study showed that using ACT-ETH gel to treat psoriasis on the skin led to a significant improvement in the therapeutic response. Based on these results, ACT-ETH gel has the potential to increase the topical anti-psoriatic action of ACT by mitigating its known drawbacks. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis caused by CERS3 mutations is extremely rare in clinical practice. We recently identified a family of autosomal recessive congenital ichthyosis and performed multigene exome sequencing for hereditary skin diseases to identify causative genes. Mutation analysis revealed compound heterozygous mutations of c.746A>G(from the mother) and exon12 deletion(from the father)in CERS3 were detected in the proband, which were verified by Sanger sequencing and co-segregated with the ichthyosis phenotype in the proband and her parents. These mutations were both reported for the first time. For the treatment, the proband received an oral acitretin capsules of 20 mg once daily. After 3-month follow up, the patient's lesion improved significantly.

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.

A 52-year-old male presented with multiple tender, plum-coloured facial plaques following the treatment with acitretin 50 mg/day for his psoriasis. The lesions subsided over 3 months. Acitretin was restarted at 20 mg/day as psoriasis flared. A week later, the patient presented with fever and a symmetrically distributed, tender, livid, hemorrhagic papulopustular eruption and large violaceous ulcerated plaques on both soles. Within a week, the patient developed abdominal pain and distension. CT scans of the abdomen showed segments of small bowel wall thickening. Chest X-ray showed consolidation and nodularity of the lung bases. Histopathology demonstrated findings consistent with a diagnosis of Sweet’s syndrome. The diagnosis of drug-induced Sweet’s Syndrome was established. The patient was treated with a combination of intravenous methylprednisolone and cyclophosphamide. Drug-induced SS has been reported to be associated with many drugs, especially granulocyte-monocyte-colony-stimulating-factor and all-trans-retinoic acid. Although very rare, acitretin-induced SS should be considered in a patient who develops pustulonecrotic skin lesions and systemic upset after intake of acitretin.

Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome. [ABSTRACT FROM AUTHOR]

Background: Acitretin has been linked to the development of psychiatric disturbance. Objectives: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs). Methods: This is a nationwide matched cohort study. From Taiwan's National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs). Results: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23–1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56–4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75–5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age. Conclusions: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common chronic, disfiguring, inflammatory skin condition in which both genetic and environmental influences play a critical role. It is clinically characterised by sharply demarcated, erythematous, silvery-white, scaly, indurated plaques mainly distributed over extensor surfaces, the lower back, and the scalp. The present study compared acitretin and methotrexate in patients with psoriasis. Aims and objectives: The present study compared acitretin and methotrexate in patients with psoriasis. Materials & Methods: 100 patients with palmoplantar psoriasis of both genders were divided into 2 groups. Each group consisted of 50 patients. Group I patients were given oral acitretin 0.5 mg/kg daily for 3 months, and patients in group II were given oral methotrexate 15 mg/week for 3 months. A modified psoriasis area severity index (MPASI) score was recorded in both groups. Results: Group I had 25 males and 25 females, and Group II had 22 males and 28 females. The mean MASI score at baseline, 1 month, 2 months, and 3 months was 61.4, 41.6, 33.4, and 21.8 in group I, respectively. The mean MASI score in group II was 57.8, 37.4, 24.6, and 15.4 at baseline, 1 month, 2 months, and 3 months, respectively. The difference was significant (P <0.05). Efficiency was excellent in 95 in group I and 97 in group II, good in 5 in group I and 3 in group II, and fair in 1 in group II. The difference was non- significant (P> 0.05). Conclusion: Acitretin and oral methotrexate were found to be efficient in treating palmoplantar psoriasis. The efficacy of both drugs was found to be comparable. [ABSTRACT FROM AUTHOR]

Systemic capillary leak syndrome (SCLS) is a potentially life-threatening condition characterized by recurrent episodes of massive plasma sequestration into the interstitial space causing vascular collapse. SCLS is a rare syndrome where only a few cases are published in literature. The etiology being either idiopathic (Clarkson's disease) or secondary to underlying causes such as sepsis and drugs and diagnosis is often missed due to nonspecific presentation. We hereby present a case of pustular psoriasis on acitretin who developed SCLS after increasing the dose and eventually succumbed. Acitretin is considered the drug of choice in extensive psoriasis despite having side effect profiles. Although most of them are dose dependent and not life threatening. This is one of the rare complications where early detection of the condition, withdrawal of the drug, and appropriate management can be lifesaving.

Pembrolizumab is the first anti-programmed death protein-1 agent approved by the US Food and Drug Administration. It has demonstrated efficacy in melanoma, lung cancer, and other advanced solid tumours and hematologic malignancies. Various dermatological side effects including pruritus, maculopapular rash, vitiligo, lichenoid skin reactions, psoriasis, and rarely life-threatening conditions like bullous pemphigoid, Stevens-Johnson syndrome, and drug rash with eosinophilia and systemic symptoms have been reported. We report a case of pembrolizumab-induced lichen planus in a 54-year-old female who was receiving pembrolizumab for management of lung metastasis from squamous cell carcinoma of the buccal mucosa. The lichen planus responded to acitretin and pembrolizumab was continued safely.

Introduction/Background: Acitretin is a second-generation systemic retinoid. Its clinical applications are virtually exclusively limited to dermatology. It has anti-inflammatory, antiproliferative, and antikeratinizing effects. However, there is a lack of articles summarizing the relevant literature in a systemic way. Methods: A PubMed search was performed using keywords such as “retinoids,” “acitretin,” “etretinate,” and “retinoid embryopathy” to identify relevant original articles, case series, and case reports. Results: The most commonly used application of acitretin, a second-generation systemic retinoid is in the treatment of psoriasis. It has been used in various other dermatological disorders (keratoderma, ichthyosis, pityriasis rubra pilaris, and lichen planus) as a stand-alone therapy or may be combined with other topical and systemic agents. As the drug is not an immunosuppressive agent, hence can be given safely to patients suffering from human immunodeficiency virus and taking highly active antiretroviral therapy. The drug can be given safely in the pediatric as well as the adult population. Although adverse effects are common usually minor and self-limiting and can be managed easily without stopping the drug. The main side effects of the drug include teratogenicity, hepatotoxicity, and hyperlipidemia which should be monitored regularly. It should be avoided or used cautiously in patients taking methotrexate, cyclosporine, and corticosteroids. Conclusions: This article has discussed various uses of acitretin in dermatology, its side effect profile, indication, contraindication, and drug interactions. The drug can be administered safely and successfully with the right patient selection, progressive dose increase, careful monitoring, and appropriate patient counseling.

Xianjie Yang,&ast; Juan Wang,&ast; Huan Wang, Minmin Kong, Qiquann Chen Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiquann Chen, Email chenqq0548@163.comAbstract: Acute generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis, characterized by an acute eruption of extensive erythema with numerous non-follicular pustules. In rare cases, local pustular psoriasis like acrodermatitis continua of Hallopeau (ACH) may progress into acute GPP if improperly treated. ACH and GPP are rare in the clinic and their treatment is more complex and often treatment-resistant compared to psoriasis vulgaris (PV). A variety of anti-psoriasis biologics emerging in recent years have been reported for the treatment of ACH and acute GPP. Biologics is considered to be an upgraded treatment option for traditional anti-psoriasis agents. But there are few reports of GPP patients developing resistance to biologics, or what if biologics fails. Herein, we report a case of acute GPP that developed from ACH, initially responded extremely well to adalimumab, but the treatment failed when the patient treated with the drug again, which is thought to have developed resistance to adalimumab, finally successfully treated with narrowband ultraviolet B (NB-UVB) and acitretin.Keywords: acute generalized pustular psoriasis, acrodermatitis continua of hallopeau, adalimumab, narrowband ultraviolet B, acitretin