Antipsoriatic Therapy Research Articles

Revealing patient characteristics and treatment outcomes in ultra-long biologic users for psoriasis.

Biologics are effective for psoriasis, but little is known regarding patients treated with one biologic for an "ultra-long" duration. To explore the prevalence, patient and treatment characteristics and treatment outcomes of "ultra-long users" of biologics for psoriasis. From the prospective, multicenter BioCAPTURE cohort, patients with psoriasis who received continuous treatment with the same biologic for ≥10 years were included. Baseline characteristics of these "ultra-long users" were determined and compared to the total BioCAPTURE population. Additionally, the frequency of concomitant systemic treatment use and dose adjustments administered, the trajectory of Psoriasis Area and Severity Index (PASI) scores, and drug survival rates beyond 10 years were analysed. In BioCAPTURE, 30.5% of the patients with the potential to reach a treatment episode of ≥10 years achieved this treatment duration. These patients were treated with ustekinumab, etanercept, adalimumab and infliximab. The proportion of ultra-long users was highest for ustekinumab (37%). The ultra-long user cohort had a slightly longer disease duration at registry entry, and higher proportion of males and patients diagnosed with PsA, compared to the total BioCAPTURE population. A large percentage of ultra-long users (69.5%) had ≥1 comorbidities and 66% used no additional systemic antipsoriatic therapy. Dose adjustments were often applied, varying from dose escalation (30%), dose reduction (41%), or both (14%); only 16% consistently used the standard dose. The median PASI course for ultra-long users from month 6 onwards was continuously <3, with only a small proportion achieving complete clearance of their psoriasis (3.9-13.7% at the various time points). Drug survival beyond 10 years showed >60% was still treated with the same biologic after 15 years. Ultra-long use of the same biologic in patients with psoriasis was common in real-world practice, but varied between biologics. The median PASI was around 2.5 throughout the 10-year treatment course; complete clearance was often not reached. Remarkably, ultra-long use was reached also in patients having multiple comorbidities (including PsA) and a variety of dose adjustments of the biologics was applied. These results provide clinicians with important evidence on ultra-long biological treatment, thereby improving psoriasis care and management of treatment expectations.

RNA-Based Antipsoriatic Gene Therapy: An Updated Review Focusing on Evidence from Animal Models.

Psoriasis presents as a complex genetic skin disorder, characterized by the interaction between infiltrated immune cells and keratinocytes. Substantial progress has been made in understanding the molecular mechanisms of both coding and non-coding genes, which has positively impacted clinical treatment approaches. Despite extensive research into the genetic aspects of psoriasis pathogenesis, fully grasping its epigenetic component remains a challenging endeavor. In response to the pressing demand for innovative treatments to alleviate inflammatory skin disorders, various novel strategies are under consideration. These include gene therapy employing antisense nucleotides, silencing RNA complexes, stem cell therapy, and antibody-based therapy. There is a pressing requirement for a psoriasis-like animal model that replicates human psoriasis to facilitate early preclinical evaluations of these novel treatments. The authors conduct a comprehensive review of various gene therapy in different psoriasis-like animal models utilized in psoriasis research. The animals included in the list underwent skin treatments such as imiquimod application, as well as genetic and biologic injections, and the results of these interventions are detailed. Animal models play a crucial role in translating drug discoveries from the laboratory to clinical practice, and these models aid in improving the reproducibility and clinical applicability of preclinical data. Numerous animal models with characteristics similar to those of human psoriasis have proven to be useful in understanding the development of psoriasis. In this review, the article focuses on RNA-based gene therapy exploration in different types of psoriasis-like animal models to improve the treatment of psoriasis.

Does Systemic Anti-Psoriatic Treatment Impact the Risk of Cardiovascular Disease? A Review Over Cardiovascular Imaging Studies.

Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as theoutcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.

Novel anti-psoriatic nanostructured lipid carriers for the cutaneous delivery of luteolin: A comprehensive in-vitro and in-vivo evaluation

Psoriasis is a prevalent laborious inflammation in skin with alternate phases of remission and relapses. The current study sought to develop nanostructured lipid carriers (NLCs) having enhanced skin deposition as well as augmented anti-inflammatory potential, to repurpose the use of luteolin (Lut), a flavonoid, in the treatment of psoriasis. NLCs were prepared using different oils having reported anti-inflammatory activity and evaluated in terms of size, surface charge, entrapment efficiency, stability upon storage, in-vitro anti-inflammatory potential, surface morphology, in-vitro release profile and release kinetics, and ex-vivo skin deposition. In-vivo animal studies were conducted on the optimized formula using imiquimod-induced psoriasis rat model. The prepared NLCs were nanosized ranging from 202 to 538 nm, negatively charged with values having the range of -13.10 to -19.26 mV with high entrapment efficiency values ranging from 84.21 to 96.53% and high in-vitro anti-inflammatory potential compared to the blank and control formulations. Furthermore, NLCs demonstrated adequate storage stability demonstrated by slightly significant change in their colloidal properties. The prepared nanoparticles exhibited sustained drug release up to 24 h and succeeded in enhancing the skin deposition of Lut by 3.4-fold higher in stratum corneum, epidermis and dermis compared to Lut suspension with minimum transdermal delivery. In-vivo assessment of psoriasis was carried out morphologically, histopathologically and biochemically and results revealed significant augmentation of the anti-psoriatic efficacy of Lut upon its encapsulation in NLCs compared to free Lut suspension. The developed system proved to be an influential drug delivery system providing potent anti-psoriatic therapy, paving the way for futuristic clinical investigations.

Association between cardio-cerebrovascular disease and systemic antipsoriatic therapy in psoriasis patients using population-based data: A nested case-control study.

The effect of antipsoriatic therapy on cardio-cerebrovascular disease (CCVD) is not well described. Thus, we performed a population-based nested case-control study to investigate the effect of systemic antipsoriatic therapy on CCVD in psoriasis patients. Using nationwide cohort data from the Korean National Health Insurance Claims database, newly diagnosed psoriasis patients were identified. Among the enrolled participants, postenrollment development of CCVD events (ischemic heart disease, myocardial infarction, cerebral infarction, and cerebral hemorrhage) was investigated. To evaluate the effect of systemic antipsoriatic therapy on CCVD risk, we calculated the proportion of the treatment period with systemic antipsoriatic therapy during the study period (PTP [%]: the sum of all systemic antipsoriatic therapy durations divided by total observation period). Among 251 813 participants, 6262 experienced CCVD events during the study period (CCVD group). Controls included 245 551 patients without CCVD history during the study period (non-CCVD group). The non-CCVD group had greater PTP than the CCVD group (CCVD 2.12 ± 7.92, non-CCVD 2.64 ± 9.64; P < 0.001). In multiple logistic regression analysis, PTP was inversely associated with the CCVD risk after adjusting for age, sex, diabetes, hypertension, and dyslipidemia. A 10% increase in PTP reduced CCVD risk by 0.96 (95% confidence interval 0.93 to 0.99). Reduced CCVD risk was robust for both conventional antipsoriatic therapy and biologics. Our study found that systemic antipsoriatic therapy use was inversely associated with CCVD risk in psoriasis patients. These findings suggested that systemic antipsoriatic therapy could reduce CCVD development in patients with psoriasis.

Rupioid psoriasis: A complex, multifactorial presentation

Introduction: Secondary syphilis, also termed the great mimicker due to its vast array of clinical presentations, is associated with skin manifestations including rupioid, macular, psoriasiform, and condylomatous lesions. On clinical examination alone, it can be difficult to differentiate between rupioid syphilis and rupioid psoriasis, especially among cases of human immunodeficiency virus (HIV) and syphilis co-infection; however, histologic examination can aid in their differentiation. Additional testing such as serum rapid plasma reagin (RPR), anti-HIV antibody, rheumatoid factor, and fungal cultures should be performed to exclude other causes of rupioid lesions. Case Report: A 19-year-old HIV-positive male developed numerous hyperkeratotic skin lesions involving the head, trunk, and extremities over a 4-week period. His RPR was positive (1:64), suggesting a diagnosis of rupioid syphilis. The patient was treated with doxycycline, given a reported history of penicillin allergy. Rapid plasma reagin titers decreased to 1:2 following treatment; however, the skin eruption did not improve. A biopsy of a lesion demonstrated psoriasiform acanthosis with confluent hyperkeratosis, clusters of intracorneal neutrophils, and negative spirochete immunostaining. Based on histopathology and clinical presentation, a diagnosis of rupioid psoriasis was favored. The patient was started on targeted anti-psoriatic therapy with apremilast and maintains close follow-up with his dermatologist every three months. Conclusion: Although the patient’s presentation was initially presumed to be secondary to syphilis, his lack of response to treatment prompted further workup to assess the etiology of the patient’s skin findings more accurately. In doing so, a diagnosis of rupioid psoriasis was favored based on the histologic findings observed.

Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches.

Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.

Multiarm study comparing patient-reported and clinical outcome measures in patients undergoing antipsoriatic therapy with non-biological systemic agents in a real-world setting

ABSTRACT Background Although the inclusion of patients’ preferences and needs is essential for therapy adherence, the assessment of patient-reported outcome measures in clinical trials is often neglected. Therefore, the aim of this study was to quantify several patient-reported outcome measures in psoriasis patients undergoing systemic therapy in a real-life clinical setting. Methods This clinical trial has been designed as a prospective, multiarm study to investigate the treatment satisfaction, adherence to therapy, quality of life, and clinical response in a real-life clinical setting during the initial six months of treatment with apremilast, methotrexate and fumaric acids in 80 patients suffering from plaque psoriasis. Results The treatment satisfaction for the three systemic therapies was rated “sufficient” with a mean (±SD) Treatment Satisfaction Questionnaire for Medication (TSQM) score of 275.0 (±62.7). Most potential for improvement was seen in the “effectiveness” domain (54.3 ± 21.5). The highest treatment satisfaction level in all four domains (convenience, effectiveness, global satisfaction, side-effects) was seen in the methotrexate group with a mean TSQM score of 306.3 ± 50.9, followed by apremilast (267.1 ± 61.6) and fumaric acids (254.9 ± 65.0; p = 0.005). Analysis of the TSQM revealed a considerable discrepancy between patient-reported clinical response and the actual Psoriasis Area and Severity Index (PASI) reduction. This applies equally to the patient- versus physician-reported side-effects. Conclusions This real-life study demonstrates that an adequate assessment of antipsoriatic drugs by PASI-reduction alone is not sufficient and underlines the importance of patient-reported outcome measures not only in clinical trials, but also for improved patient care.

Age-based treatment differences in and reluctance to treating older adults with systemic antipsoriatic therapy – a mixed-method pilot study

Background Evidence-based guidance in older adults (≥65 years) with psoriasis is sparse and undertreatment might be present. Objectives To assess prescribing patterns, comfort levels, barriers and needs of dermatologists when treating older adults with systemic antipsoriatic therapy. Methods A mixed-methods design was used including a survey among all Dutch dermatologists and residents, followed by semi-structured interviews. Results Most of the survey respondents applied systemic treatment to the same extent in older versus younger patients (n = 49; 67.1%) and weren’t reluctant prescribing systemic therapy (n = 50; 68.5%) in older adults. However, 26% (n = 19) of the respondents treated older adults less often with systemic therapy compared to younger patients and 68.1% (n = 49) performed additional actions in older adults, e.g. intensified monitoring or dose reduction. Based on the survey and interviews (n = 10), the main reasons for these age-based treatment differences were comorbidity, comedication, and fear of adverse events. More evidence-based guidance, education, and time to assess older adults were identified as most important needs, especially regarding frailty screening. Conclusions Age-based treatment differences in and reluctance to treating older adults with systemic antipsoriatic therapy were common. There is a need for more evidence-based guidance, education, and consultation time, to improve treatment in this growing population.

Fatty Acid-Binding Protein 7 (FABP-7), Glutamic Acid and Neurofilament Light Chain (NFL) as Potential Markers of Neurodegenerative Disorders in Psoriatic Patients-A Pilot Study.

Psoriasis and neurodegenerative diseases (NDs) are important medical, social and economic issues. The possible relationship of psoriasis and NDs has not been established yet. This study involved 60 patients with plaque-type psoriasis. Serum concentrations of fatty acid-binding protein 7 (FABP-7), glutamic acid (GA) and neurofilament light chain (NFL), which have been hardly studied in psoriasis before, were measured by ELISA before and after 12 weeks of treatment with acitretin or methotrexate. The concentration of FABP-7 and NFL in patients before the treatment was significantly higher than in the controls (p < 0.01, p < 0.001, respectively). After the treatment their concentration decreased, although FABP-7 did so insignificantly. The concentration of GA did not differ significantly between patients and controls and before and after the treatment but we found its negative correlation with CRP (p < 0.05). The duration of psoriasis does not seem to directly affect the risk of neurodegeneration and the severity only in patients with worse skin condition. Elevated FABP-7 and NFL, which are present in the brain, may be considered as potential indicators of NDs development in psoriatics, although it surely requires further research. GA might correspond with neuroinflammation in psoriasis. Systemic antipsoriatic therapy could be studied in order to improve cognitive impairment through lowering NDs biomarkers in some cases.

Recent Advancements in Antipsoriatic Therapy: An Update

Psoriasis is a chronic inflammatory, a multisystem autoimmune disease with extreme pathological features and unsatisfied pharmacotherapeutic needs. Primarily psoriasis is associated with epidermal cells, keratinocyte hyperproliferation, inflammation, dermal capillary dilation, and proangiogenic mechanisms. Compared with other chronic diseases, patients with psoriasis have severe psychological stress and undergo reduced physical activeness, cognitive dysfunctions, and low-quality life. Pathophysiology is complex with the involvement of various mediators like interleukin-(IL)-17, IL-23, tumor necrosis factor-alpha (TNF-α), interferongamma(IFN-γ), and vascular endothelial growth factor (VEGF) that play a significant role in escalation and localizing the inflammation caused in psoriasis. However, acquiring uninterrupted knowledge of psoriasis pathophysiology allows us to identify the novel therapeutic targets that could be explored to overcome personalized psoriasis treatment challenges. Conventional therapy includes corticosteroids, vitamin-D, methotrexate, and cyclosporine, but with low efficacy and severe side effects and sometimes causing disease comorbidities. New biologics approved by FDA during 2016-2019, such as IL-23 blockers risankizumab-rza, guselkumab, and tildrakizumab-asmn, certolizumab pegol targeting TNF-α, IL-17 blockers brodalumab and ixekizumab have revolutionized the treatment of moderate to severe psoriasis due to targeted approach but are reported to possess many side effects leading to low patient compliance. Biosimilars of adalimumab, etanercept, and infliximab, designed by reverse engineering of biologics, are also becoming popular due to their cost-effectiveness. Drug repurposing focuses mainly on defining new medical uses for old drugs. The main focus of drug repurposing is how the drug molecule interacts with various targets and executes its pharmacological action, revealing the new possibilities of designing effective therapeutic agents with low toxicity.

Portraying molecular modulation and therapeutic aspects of psoriasis: Retrospection and current status

• Psoriasis is an autoimmune disease of the skin with chronic inflammatory conditions. • Various signaling pathways are involved in its pathophysiology. • The basis of molecular modulation of psoriasis has been addressed. • Various strategies to counter this complex disease have been discussed in detail. • Recent development in the anti-psoriatic therapy has been discussed. Psoriasis is a hyperproliferative skin disorder which is associated with dysregulation of the immune system. In this genetically transmitted disease, the immune system is activated by various triggers such as genetic predisposition, stress, and pathogenic microbes which in turn stimulate various immunocytes such as keratinocytes, macrophages, monocytes, dendritic cells and T-cells to secrete various pro-inflammatory cytokines that ultimately accelerate inflammation and cause psoriatic plaques. These cytokines are also responsible for T-cell differentiation, keratinocyte hyperproliferation, and accumulation of neutrophils and lymphocytes in the skin. At the molecular level, several pathways have been proposed underlying the pathophysiology of psoriasis that directly or indirectly kindle various psoriatic factors. The most common pathways include PDE-4, ICAM-1, LFA-1 and JAK/STAT pathways. In order to target these pathways, various strategies have been developed that counter moderate to severe psoriasis. The most effective therapies include interleukin inhibitors, TNF-α inhibitors, JAK inhibitors, PDE-4 inhibitors and immunosuppressants such as methotrexate, cyclosporin, tazarotene, and acitretin. Apart from these inhibitors, phototherapy (UV-A and PUVA) and topical therapies (corticosteroids, vitamin D analogs, retinoids, emollients, and keratolytic agents) have also been employed for the treatment of mild to moderate psoriasis. This review provides the retrospective analysis of psoriasis and current therapeutic options which are under development for the amelioration of psoriatic diseases. The information provided in this report may be helpful for the research community engaged in the development of effective novel therapies against psoriasis.

Association of sex and systemic therapy treatment outcomes in psoriasis: a two-country, multicentre, prospective, noninterventional registry study.

Few systematic data on sex-related treatment responses exist for psoriasis. To evaluate sex differences with respect to systemic antipsoriatic treatment. Data from patients with moderate-to-severe psoriasis in the PsoBest or Swiss Dermatology Network of Targeted Therapies (SDNTT) registries were analysed. Treatment response was defined as achieving a≥75% reduction in Psoriasis Area and Severity Index (PASI 75) or PASI ≤ 3 at treatment months 3, 6 and 12, supplemented by patient-reported outcomes [i.e. Dermatology Life Quality Index (DLQI) ≤ 1 and delta DLQI ≥ 4]. In total, 5346 patients registered between 2007 and 2016 were included (PsoBest, n=4896; SDNTT, n=450). The majority received nonbiological treatment (67·3% male, 69·8% female). Women showed slightly higher PASI response rates after 3 (54·8% vs. 47·2%; P≤0·001), 6 (70·8% vs. 63·8%; P≤0·001) and 12months (72·3% vs. 66·1%; P≤0·004). A significantly higher proportion of women achieved a reduction in DLQI ≥ 4 [month 3: 61·4% vs 54·8% (P≤0·001); month 6: 69·6% vs. 62·4% (P≤0·001); month 12: 70·7% vs. 64·4% (P≤0·002)]. Regarding PASI ≤ 3, women on biologics showed a significantly superior treatment response compared with men at 3 (57·8% vs. 48·5%; P≤0·004) and 6months (69·2% vs. 60·9%; P≤0·018). Women in the nonbiological treatment group had a significantly better treatment response (PASI response, PASI 75 and PASI ≤ 3) over 12months compared with men. We provide evidence that women experience better treatment outcomes with systemic antipsoriatic therapy than men.

Influence of an adjuvant treatment with an emollient containing 10 % urea, ceramides, glycerin und glyceryl glucoside in patients with psoriasis vulgaris

Guidelines generally recommend an adjuvant treatment with emollients for patients suffering from psoriasis. However evidence for this purpose is limited. We performed aprospective observational study with an emollient containing 10% urea, ceramides, glycerin and glyceryl glucoside in patients suffering from mild to moderate psoriasis. The patients had to be stable for at least 12weeks on prior antipsoriatic therapy including topical therapy, systemic treatment or phototherapy which was continued during the trial. A4-week daily application of the emollient resulted in significant improvement regarding quality of life (measured by DLQI, Dermatology Life Quality Index) and clinical outcome (measured by local PASI, Psoriasis Area and Severity Index) among the treated patients. The trial results show that adaily adjuvant treatment with emollients can support abasic antipsoriatic therapy both in aspects of clinical efficacy and quality of life in mild to moderate patients suffering from psoriasis.

Biological anti-psoriatic therapy profoundly affects high-density lipoprotein function

Psoriasis is a common chronic inflammatory skin disease linked to increased cardiovascular risk. Functional impairment of high-density lipoprotein (HDL) may contribute to excessive cardiovascular mortality in psoriasis patients. Anti-cytokine therapies with biologics have been efficiently used for the management of psoriasis, however little data is available on the effects of biologic anti-psoriatic therapies on the composition and functionality of HDL. Blood samples were taken from 17 healthy volunteers and from 27 real-world psoriasis patients at baseline (no therapy with biologics) and after short-term (3 to 6 months) and intermediate-term (1 to 2 years) therapy. The biologics used included anti-interleukin (IL)-12/23p40 (ustekinumab), anti-IL17A (secukinumab) or anti-tumor necrosis factor-α (etanercept or adalimumab) antibodies. We observed that in psoriasis patients at baseline, metrics of HDL function including cholesterol efflux capacity of apolipoprotein B-depleted serum (p = 0.021), paraoxonase (p < 0.001) and lecithin-cholesterol acyltransferase (p < 0.001) activities were impaired, when compared to controls. Unexpectedly, we observed that short- and especially intermediate-term therapy with biologics markedly reduced HDL cholesterol efflux capacity (p < 0.001) and rendered HDL pro-inflammatory (p < 0.001), but increased paraoxonase (p = 0.009) and lecithin-cholesterol acyltransferase (p = 0.019) activities. All biologics caused similar changes in HDL composition, subclass distribution and cholesterol efflux capacity. Our results provide evidence that anti-psoriatic therapy with biologic agents is associated with changes in HDL functionality, particle composition and subclass distribution.

Pregnancy outcomes in women with psoriatic arthritis

Psoriasis is a chronic inflammatory disease that has important physical and psychological consequences. It is characterized by uncontrolled inflammation and excess cytokines that cause endothelial dysfunction and systemic and placental vasculopathy. Approximately 20-30% of the psoriasis patients will develop psoriatic arthritis. Fetal risks during pregnancy occur both due to maternal diseases and due to drugs used to control the illness. Most pregnancies in women with psoriatic arthritis are uneventful. Psoriatic arthritis is a disease that rarely develops in pregnant women. During some pregnancies, psoriasis and psoriatic arthritis to a lesser extent improve thanks to the immunological changes, but sometimes pregnancy may be a triggering factor for the articular disease. Pregnant women with psoriatic arthritis may have a higher risk of preterm birth, elective or emergency caesarean delivery. Placental vasculopathy seems to be responsible for intrauterine growth retardation and low birth weight. Preconception counseling in order to improve maternal, pregnancy and birth outcomes is beneficial in women with psoriasis and psoriatic arthritis. The management of psoriasis and psoriatic arthritis in pregnancy is challenging because the use of systemic antipsoriatic therapy may be unavoidable.

Enhanced transdermal efficiency of curcumin-loaded peptide-modified liposomes for highly effective antipsoriatic therapy.

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.

Design & development of nanosponge loaded topical gel of curcumin and caffeine mixture for augmented treatment of psoriasis.

Combination of curcumin with anti-inflammatory drug like caffeine shows augmented antipsoriatic action compared to curcumin alone and reduce the time taken for treatment of Psoriasis. The objective of the present study was to develop nanosponge (NS) based topical gel of curcumin (CUR) and caffeine (CFN) combination that acts as a potential system for the treatment of psoriasis. NS composed of dimethyl carbonate (DMC) as crosslinker and beta-cyclodextrin (β-CD) as polymer were prepared by hot melt method and incorporated in topical gels. Factorial design (32) was constructed in a fully randomized manner to study all nine possible experimental runs. The gels were prepared by varying the content of carbopol-934 (gelling agent) (X1) and guar gum (polymer) (X2). The effect of these two independent variables on viscosity (Y1) and in vitro percent drug release (Y2) of prepared gels was evaluated. Other evaluation studies for NS and nanogels were conducted. In vivo animal studies were carried out for optimized formulation using mouse model of imiquimod-induced psoriasis. The physical and chemical characteristics exhibited by the prepared NS and gels (F1-F9) were found to be optimal. The optimization resulted in achieving formulation N10 with 69.72% in vitro drug release and 12,329.78cp viscosity. Histopathology studies revealed that prepared nanogel has promising anti-psoriatic activity. The results concluded that CUR and CFN combination has reduced the time required for showing anti-psoriatic activity to 10days when compared to CUR alone that took around 20days. Moreover, the nanogel has depicted sustained drug release till 12h. From the experimental findings it has been concluded that CUR and CFN combination significantly augmented the anti-psoriatic efficacy with respect to individual components and also reduced the time required for onset of effect. Thus, the proposed nanogel would be an imperative drug delivery system for more effective anti-psoriatic therapy. Graphical abstract.

Development of flavanone and its derivatives as topical agents against psoriasis: The prediction of therapeutic efficiency through skin permeation evaluation and cell-based assay.

Flavonoids inhibit skin inflammation. Previous study suggests that the flavonoids with flavanone backbone were beneficial to penetrate into the skin. We aimed to investigate the possibility of psoriasis treatment by topically applied flavanone and its derivatives including naringenin, hesperetin, 6-hydroxyflavanone, flavanone, and 6-bromoflavone. The skin absorption of the compounds was determined by Franz cells. Molecular modeling was used to compute the physicochemical and molecular parameters of the penetrants in order to elucidate the correlation between structure and permeation. Among the compounds tested, flavanone showed the greatest skin absorption. The in vitro skin absorption predicted efficient skin targeting of 6-bromoflavone with minimal risk of circulation absorption. The permeation of naringenin was remarkably enhanced 13-fold in the barrier-defective skin mimicking inflamed skin. The penetrants with fewer hydrogen bond number, total polarity surface, and molecular volume were advantageous for facile skin absorption. In the cell-based study, IL-1β inhibition in imiquimod (IMQ)-stimulated keratinocytes was increased following the increase in compound lipophilicity. Naringenin, a flavanone analog with three hydroxyl moieties, could suppress IL-6 overexpression to baseline control. We assessed the anti-inflammatory potency of the chemicals in comparison with tacrolimus as reference in a psoriasis-like mouse model. Flavanone was found to mitigate scaling and epidermal hyperplasia at a higher level than naringenin. Flavanone lessened IL-6 overexpression by 80% in the psoriasiform plaque. The skin barrier function recorded by transepidermal water loss (TEWL) was recovered by naringenin but not flavanone. The experimental data indicate that naringenin and flavanone are potential candidates for anti-psoriatic therapy.

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa