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Pharmaceutics May 2020To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers...
To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers were characterized for drug encapsulation efficiency, size, morphology and compatibility between various components. Optimum formulations were dispersed in various gel bases and drug release kinetics were studied. Clinical efficacy and safety of liposomal and ethosomal PluronicF-127 gels were evaluated in patients having psoriasis (clinicaltrials.gov identifier is NCT03348462). Safety was assessed by recording various adverse events. Drug encapsulation efficiency ≥97.2% and ≥77% were obtained for liposomes and ethosomes, respectively. Particle sizes of 116 to 199 nm and 146 to 381 nm were observed for liposomes and ethosomes, respectively. Fourier-Transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the absence of interaction between anthralin and various nanocarrier components. Tested gel bases showed excellent ability to sustain drug release. At baseline, the patients had a median Psoriasis Area and Severity Index (PASI) of 3.4 for liposomes and 3.6 for ethosomes without significant difference. After treatment, mean PASI change was -68.66% and -81.84% for liposomes and ethosomes, respectively with a significant difference in favor of ethosomes. No adverse effects were detected in both groups. Anthralin ethosomes could be considered as a potential treatment of psoriasis.
PubMed: 32403379
DOI: 10.3390/pharmaceutics12050446 -
Paediatric Drugs Jan 2024Psoriasis is a chronic immune-mediated disorder that commonly affects adults and children. In recent years, pediatric psoriasis has increased in prevalence and the... (Review)
Review
Psoriasis is a chronic immune-mediated disorder that commonly affects adults and children. In recent years, pediatric psoriasis has increased in prevalence and the disease is often associated with various comorbidities and psychological distress. The conventional topical treatments for psoriasis, such as corticosteroids, calcineurin inhibitors, vitamin D analogs, anthralin, and coal tar, are often limited by their side effects, tolerability, and/or efficacy, particularly for use in children and on sensitive and intertriginous areas. Recently, the US Food and Drug Administration approved two new topical non-steroidal agents for treating psoriasis that target different pathogenic pathways than the conventional treatments. Roflumilast is a phosphodiesterase type 4 inhibitor approved for the treatment of plaque psoriasis in patients aged 12 years and older. Tapinarof is a novel aryl hydrocarbon receptor modulator approved for adult psoriasis and currently undergoing studies for pediatric psoriasis. Ongoing efforts are also being made to optimize conventional treatments, for instance, a new foam formulation of halobetasol propionate was recently approved for pediatric psoriasis. Clinical trials of various new drugs targeting one or multiple pathogenic pathways of psoriasis, such as Janus kinase inhibitors, different formulations of phosphodiesterase type 4 inhibitors, and aryl hydrocarbon receptor modulators have also been explored. The recent emergence of novel topical agents provides promising new options for managing pediatric psoriasis with the potential to improve clinical outcomes and quality of life. In this article, we review the mechanism of action, efficacy, and safety profile of novel topical agents and discuss their potential roles in the management of pediatric psoriasis.
Topics: Adult; Humans; Child; Receptors, Aryl Hydrocarbon; Quality of Life; Psoriasis; Administration, Topical; Anthralin
PubMed: 37847480
DOI: 10.1007/s40272-023-00592-9 -
JAMA Dermatology Oct 2022Alopecia areata (AA) is an autoimmune disorder of hair loss with a complex and evolving treatment landscape, making it an ideal setting for shared decision-making (SDM)...
IMPORTANCE
Alopecia areata (AA) is an autoimmune disorder of hair loss with a complex and evolving treatment landscape, making it an ideal setting for shared decision-making (SDM) between patients and physicians. Given the varying efficacy, experience, and risks of treatments for AA, we sought to evaluate patient preferences for SDM and the association of SDM with decisional regret.
OBJECTIVE
To evaluate patient preferences for SDM and the association of SDM with decisional regret.
DESIGN, SETTING, AND PARTICIPANTS
A cross-sectional online survey using the validated SDMQ9 scale for shared decision-making and Decisional Regret Scale (DRS) was distributed using the National Alopecia Areata Foundation (NAAF) with the aim of assessing (1) patient preferences in SDM when making treatment decisions, (2) how patients perceived the last decision to have been made, (3) which components of SDM were incorporated into the last decision, and (4) decisional regret related to their last treatment decision. The survey was distributed from July 12, 2021, to August 2, 2021, and data analysis occurred from October 2021 to March 2022.
MAIN OUTCOMES AND MEASURES
Primary outcomes included (1) patient preferences in incorporation of SDM, (2) how patients made their most recent treatment decision, (3) which components of SDM were incorporated into their most recent treatment decision measured with the validated SDMQ9, and (4) an assessment of decisional regret in relation to SDM components and the most recent treatment modality used by the patient as measured by the validated DRS.
RESULTS
Of 1387 individuals who initiated the survey, 1074 completed it and were included in the analysis (77.4% completion rate). Overall, 917 respondents were women (85.4%). There were 5 American Indian or Alaska Native respondents (0.5%), 33 were Asian (3.1%), 112 Black or African American (10.4%), 836 White (77.8%), and 36 were multiracial (3.4%) or other (36 [3.4%]). The mean age (SD) was 49.3 (15.4) years. Most respondents preferred making the final treatment decision themselves after considering their physician's opinion (503 [46.8%]). Of those who preferred to make treatment decisions using SDM, most made the last AA treatment decision with their physician (596 [55%]; 95% CI, 53%-58%; P < .001). The components of SDM implemented by the patients' dermatologists most identified were the physician "explained the advantages and disadvantages of treatment options" (472 [44%]), and the physician "asked me which treatment option I prefer" (494 [45.9%]). Incorporation of SDM by physicians was generally associated with decreased decisional regret (all ORs with 95% CIs greater than 1.1; P < .01). The treatments associated with the lowest decisional regret were Janus kinase (JAK) inhibitors, followed by biologics, and deciding not to treat; whereas, the highest decisional regret was reported with anthralin and minoxidil.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional survey study suggest that patients with AA prefer to make treatment decisions with their dermatologist using SDM. When SDM is used, patients report less decisional regret, indicating that SDM may help improve the patient-reported quality of treatment decisions. Newer, more efficacious therapies such as JAK inhibitors may be related to lower decisional regret. Future studies should seek to devise solutions to implement SDM as the AA treatment landscape continues to evolve.
Topics: Female; Humans; Male; Middle Aged; Alopecia Areata; Anthralin; Biological Products; Cross-Sectional Studies; Decision Making; Emotions; Janus Kinase Inhibitors; Minoxidil; Patient Participation
PubMed: 35976667
DOI: 10.1001/jamadermatol.2022.3025 -
Prague Medical Report 2023Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair... (Review)
Review
Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair loss, which can have huge psychosocial impact for those affected. Treatment modalities which have been used so far included nonspecific immunosuppressive medications, such as corticosteroids, cyclosporine, and methotrexate, or topical immunomodulators, such as diphencyprone, dithranol, and squaric acid dibutylester. The recognition of the importance of Janus kinase pathway in alopecia areata pathogenesis enabled more specific approaches in treatment. Positive outcomes of Janus kinase inhibitors in several trials granted approval for baricitinib which became the first on-label treatment for alopecia areata. The aim of this review is to summarize the role, efficacy and safety of several Janus kinase inhibitors in alopecia areata.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Janus Kinases; Adjuvants, Immunologic
PubMed: 36763827
DOI: 10.14712/23362936.2023.1 -
JAMA Dermatology Jan 2020Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the...
IMPORTANCE
Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the degree of psoriasis clearance and QOL has not been studied to date, especially in the pediatric population.
OBJECTIVES
To identify the association between the degree of psoriasis improvement (as measured by the Psoriasis Area Severity Index [PASI] and body surface area [BSA] response) and QOL (as measured by the Children's Dermatology Life Quality Index [CDLQI]) in pediatric psoriasis, and to assess the association of treatment type with QOL, independent of psoriasis improvement.
DESIGN, SETTING, AND PARTICIPANTS
Data used in this single-center cohort study were extracted from the Child-CAPTURE (Continuous Assessment of Psoriasis Treatment Use Registry), a prospective, observational, daily clinical practice cohort of all children (aged <18 years) with a psoriasis diagnosis who attended the outpatient clinic of the Department of Dermatology at the Radboud University Medical Center in Nijmegen, the Netherlands, between September 3, 2008, and May 4, 2018. All records of treatment episodes with CDLQI, PASI, and BSA scores were included in the analysis.
EXPOSURES
Patients were treated according to daily clinical care. Treatments were clustered into topical, dithranol, conventional systemic, and biological treatments. Because of low numbers of UV-B phototherapy, this treatment was not assessed.
MAIN OUTCOMES AND MEASURES
Primary outcomes were mean change of CDLQI scores per PASI and BSA response categories (0 to <50, 50 to <75, 75 to <90, and ≥90) and mean CDLQI change per treatment categories.
RESULTS
In total, 319 patients (median [interquartile range] age, 10.0 [7.0] years; 183 female [57.4%]) were analyzed for PASI score improvement (399 treatment episodes) and improvement in BSA involvement (366 treatment episodes). The greatest improvements in CDLQI scores were seen in the PASI ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.6 (95% CI, -7.5 to -5.7). The greatest improvements in CDLQI scores were also observed in the BSA ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.8 (95% CI, -7.5 to -6.1). Systemic treatment demonstrated a greater degree of improvement of CDLQI compared with topical treatment, independent of PASI response categories.
CONCLUSIONS AND RELEVANCE
This cohort study in a real-world setting found that the greatest improvements in QOL were associated with PASI 90 or greater, a decrease in BSA involvement of 90% or greater, and systemic treatments. These findings suggest that reaching PASI 90 or greater and decreasing BSA involvement by at least 90% may be clinically meaningful treatment goals that will help pediatric patients with psoriasis reach optimal QOL.
Topics: Administration, Oral; Administration, Topical; Adolescent; Biological Products; Child; Child, Preschool; Dermatologic Agents; Female; Follow-Up Studies; Humans; Injections; Male; Netherlands; Prospective Studies; Psoriasis; Quality of Life; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy
PubMed: 31774449
DOI: 10.1001/jamadermatol.2019.3717 -
The Journal of Biological Chemistry Oct 2020A sterilizing or functional cure for HIV is currently precluded by resting CD4 T cells that harbor latent but replication-competent provirus. The "shock-and-kill"...
A sterilizing or functional cure for HIV is currently precluded by resting CD4 T cells that harbor latent but replication-competent provirus. The "shock-and-kill" pharmacological ap-proach aims to reactivate provirus expression in the presence of antiretroviral therapy and target virus-expressing cells for elimination. However, no latency reversal agent (LRA) to date effectively clears viral reservoirs in humans, suggesting a need for new LRAs and LRA combinations. Here, we screened 216 compounds from the pan-African Natural Product Library and identified knipholone anthrone (KA) and its basic building block anthralin (dithranol) as novel LRAs that reverse viral latency at low micromolar concentrations in multiple cell lines. Neither agent's activity depends on protein kinase C; nor do they inhibit class I/II histone deacetylases. However, they are differentially modulated by oxidative stress and metal ions and induce distinct patterns of global gene expression from established LRAs. When applied in combination, both KA and anthralin synergize with LRAs representing multiple functional classes. Finally, KA induces both HIV RNA and protein in primary cells from HIV-infected donors. Taken together, we describe two novel LRAs that enhance the activities of multiple "shock-and-kill" agents, which in turn may inform ongoing LRA combination therapy efforts.
Topics: Anthracenes; Anthralin; Drug Evaluation, Preclinical; HIV Infections; HIV-1; Humans; Jurkat Cells; Virus Latency
PubMed: 32788215
DOI: 10.1074/jbc.RA120.013031 -
NPJ Vaccines Sep 2022Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our...
Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8 T cells and CD4 T cells with a T cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.
PubMed: 36153349
DOI: 10.1038/s41541-022-00530-9 -
Frontiers in Medicine 2021SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease...
SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease furin have been associated with severe course of COVID-19. Furin and angiotensin converting enzyme 2 (ACE2) play a major role in viral host cell entry of SARS-Cov2. To evaluate mRNA expression of Furin and ACE2 from blood cells in psoriasis patients, and whether systemic or topical treatment reduces expression levels. This observational translational study analyzed blood samples from patients from a clinical trial and samples retrieved from the biobank of the Psoriasis Registry Austria (PsoRA). Furin and ACE2 expression levels were analyzed prior to as well as 3 and 12-24 months after start of biologic treatment with either ustekinumab or secukinumab. Additionally, the study analyzed expression levels prior to, 6 days after start of dithranol treatment and 4-6 weeks after end of dithranol treatment. Furin mRNA expression was significantly increased at baseline in the biologic (4.9 ± 2.6 fold, < 0.0001) and in the dithranol group (2.7 ± 1.4 fold, < 0.001) compared to controls. There was a trend for arthritis patients to express more furin than patients with psoriatic skin involvement only (5.26 ± 2.30 vs. 3.48 ± 2.27, = 0.078). Analyzing furin mRNA expression after treatment initiation with secukinumab or ustekinumab revealed a normalization of levels after 3 and 12 to 24 months. Similar findings were obtained for patients treated with dithranol, with significantly decreased expression levels 6 days after start of dithranol treatment and also at follow-up, (4-6 weeks after dithranol treatment had been terminated). ACE2 expression levels did not differ from controls at any timepoint, regardless of biologic or topical treatment. Significantly overexpressed levels of furin were observed in untreated patients, and, thus, these patients may be at risk for infection and a severe course of COVID-19. However, the data indicate that successful therapeutic intervention in psoriasis, by systemic biologic or topical treatment, can efficiently reduce furin levels in blood cells, possibly limiting the risk of psoriasis patients for a severe COVID-19 course. ClinicalTrials.gov, identifier NCT02752672.
PubMed: 33644099
DOI: 10.3389/fmed.2021.624462 -
International Journal of Nanomedicine 2024Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly...
Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.
PURPOSE
Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential.
METHODS
Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes.
RESULTS
Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration.
CONCLUSION
The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.
Topics: Humans; Animals; Mice; Anthralin; Cyclosporine; Phospholipids; Ceramides; Administration, Cutaneous; Psoriasis; Skin; Disease Models, Animal
PubMed: 38344440
DOI: 10.2147/IJN.S443812 -
In Vivo (Athens, Greece) 2023This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIM
This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup.
PATIENTS AND METHODS
Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol.
RESULTS
The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049).
CONCLUSION
The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.
Topics: Humans; Pilot Projects; Anthralin; Oxidative Stress; Balneology; Psoriasis; Water
PubMed: 36881082
DOI: 10.21873/invivo.13153