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.

Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies.

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.

Optimized dithranol-imiquimod-based transcutaneous immunization enables tumor rejection.

Introduction: Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer. Previously, we reported on the combined application of the TLR7 agonist imiquimod (IMQ) together with the anti-psoriatic drug dithranol as novel TCI platform DIVA (dithranol/IMQ based vaccination). In extension of this work, we further optimized DIVA in terms of drug dose, application pattern and established a new IMQ formulation. Methods: C57BL/6 mice were treated on the ear skin with dithranol and IMQ-containing ointments together with ovalbumin-derived peptides. T cell responses were determined by flow cytometry and IFN-ɤ ELISpot assay, local skin inflammation was characterized by ear swelling. Results: Applying the adjuvants on separate skin sites, a reduced number of specific CD8+ T cells with effector function was detectable, indicating that the local concurrence of adjuvants and peptide antigens is required for optimal vaccination. Likewise, changing the order of dithranol and IMQ resulted in an increased skin inflammatory reaction, but lower frequencies of antigen-specific CD8+ T cells indicating that dithranol is essential for superior T cell priming upon DIVA. Dispersing nanocrystalline IMQ in a spreadable formulation (IMI-Sol+) facilitated storage and application rendering comparable immune responses. DIVA applied one or two weeks after the first immunization resulted in a massive increase in antigen-specific T cells and up to a ten-fold increased memory response. Finally, in a prophylactic tumor setting, double but no single DIVA treatment enabled complete control of tumor growth, resulting in full tumor protection. Discussion: Taken together, the described optimized transcutaneous vaccination method leads to the generation of a strong cellular immune response enabling the effective control of tumor growth and has the potential for clinical development as a novel non-invasive vaccination method for peptide-based cancer vaccines in humans.

A Retrospective Review of Anthralin in Petrolatum in the Treatment of Alopecia Areata in the Pediatric Population.

BACKGROUND/OBJECTIVES: Alopecia areata (AA) is a T-cell driven autoimmune disease, which results in hair loss. This study aims to determine the efficacy, tolerability and safety of different concentrations of anthralin in the treatment of pediatric AA. METHODS: A retrospective cohort study of patients < 18 yo diagnosed with AA treated with anthralin at SickKids Hospital, Toronto dermatology outpatient clinic in 2016 - 2018. Anthralin used at 0.1%, 0.2%, 0.5% and 1% in petrolatum at short contact, at increments of 15 minutes every week until a 1 hr maximum contact achieved. No other treatment was used in conjunction. Severity of Alopecia Tool (SALT) scores (SS) were determined using photographs and descriptions to assess severity of alopecia at baseline and post anthralin treatment. RESULTS: A total of 11 charts were reviewed in this retrospective cohort. Hair loss pattern; 3 patients with patchy, 6 had mixed (patchy and ophiasis), and 2 were totalis. All except for 1 patient had failed traditional treatments. One patient had complete hair regrowth, 3 showed more than 85% hair re-growth and 7 patients showed more than 75% hair regrowth, the average time for this to occur was 6.5 months. None of the patients experience serious side effects. CONCLUSIONS: Our study demonstrated the efficacy and tolerability of topical anthralin 0.1% to 1% in pediatric alopecia areata. In our study, anthralin 0.2% appears to offer the best performance and tolerability profile among the different concentrations used, with treatment course of at least 6 months in order to achieve more than 75% hair regrowth.

Is Balneotherapy Protective Against Oxidative Stress? A Pilot Study.

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.

Prototropy, Intramolecular Interactions, Electron Delocalization, and Physicochemical Properties of 1,8-dihydroxy-9-anthrone-DFT-D3 Study of Substituent Effects.

1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.

Management of Psoriasis With Topicals: Applying the 2020 AAD-NPF Guidelines of Care to Clinical Practice.

Topical medications have high utility in the treatment of psoriasis because of their localized effect and ability to be used as both monotherapy and adjunctive therapy. The American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) published guidelines in 2020 regarding the management of psoriasis with topical therapies. These guidelines are a framework that assist clinicians treating psoriasis patients with topical agents including steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar). This review presents these evidence-based recommendations in a form that dermatologists can readily apply to their clinical practice. The selection of an appropriate topical therapy, effective combination therapies, duration of use, and adverse events are addressed.

Shared Decision-Making, Therapeutic Choice, and Decisional Regret in Patients With Alopecia Areata.

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.

In situ electrochemical recomposition of decomposed redox-active species in aqueous organic flow batteries.

Aqueous organic redox flow batteries offer a safe and potentially inexpensive solution to the problem of storing massive amounts of electricity produced from intermittent renewables. However, molecular decomposition represents a major barrier to commercialization-and although structural modifications can improve stability, it comes at the expense of synthetic cost and molecular weight. Now, utilizing 2,6-dihydroxy-anthraquinone (DHAQ) without further structural modification, we demonstrate that the regeneration of the original molecule after decomposition represents a viable route to achieve low-cost, long-lifetime aqueous organic redox flow batteries. We used in situ (online) NMR and electron paramagnetic resonance, and complementary electrochemical analyses to show that the decomposition compound 2,6-dihydroxy-anthrone (DHA) and its tautomer, 2,6-dihydroxy-anthranol (DHAL) can be recomposed to DHAQ electrochemically through two steps: oxidation of DHA(L)2- to the dimer (DHA)24- by one-electron transfer followed by oxidation of (DHA)24- to DHAQ2- by three-electron transfer per DHAQ molecule. This electrochemical regeneration process also rejuvenates the positive electrolyte-rebalancing the states of charge of both electrolytes without introducing extra ions.

A systematic review on the treatment of pediatric severe alopecia areata by topical immunotherapy or Anthralin (contact sensitization) or low-level light/laser therapy (LLLT): focus on efficacy, safety, treatment duration, recurrence, and follow-up based on clinical studies.

INTRODUCTION: Alopecia areata (AA) in its extensive and severe forms is treatment-challenging, especially in pediatrics. METHOD: A PRISMA-compliant systematic review of seven electronic databases was searched by the terms "alopecia areata," "pediatric," "topical immunotherapy," "Anthralin," and "light therapy" from inception until March 2021. All the alternative names of the disease and therapies have been included in the search terms. 790 articles went to title abstract review by two independent reviewers. In the subsequent level, a review of the full text of studies was conducted. RESULTS: Finally, 10 relevant articles in terms of content structure, subject coverage, and purpose, were selected for further review. The highest percentages of complete hair regrowth were 79.6% and 63.61% by SADBE (topical immunotherapy) and laser therapy. By Anthralin (contact sensitization), the complete response rate was below 50% (between 30 and 35%). Regarding average response, the most effective methods were local immunotherapy (with an average effectiveness of 53.8%), laser therapy (52.55%), and the use of Anthralin-induced contact dermatitis (30.86%), respectively. However, recurrence rate-after treatment with induced contact dermatitis by topical medications like Anthralin (contact sensitization)-was lower (mean 43.53%) in comparison with local immunotherapy (57%). In topical immunotherapy, light base therapy, and contact sensitization, the highest percentage of complete hair regrowth and the average response rate were (63.61% and 52.55%), (79.6% and 53.8%) and (32% and 30.8%), respectively. These methods are considered safe in children. CONCLUSION: A high and more than 50% efficacy in hair regrowth could be expected by topical immunotherapy and light/laser therapy method. No serious side effects have been observed by these methods that are well tolerated in children. Therefore, a combination of local immunotherapy and light/laser therapy could be suggested for the treatment of extensive AA in children. The use of Anthralin could be associated with a lower but more durable response. These points are important for patient selection in individualized situations.

A randomized trial of diphenylcyclopropenone (DPCP) combined with anthralin versus DPCP alone for treating moderate to severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disorder. Finding the best treatment regimen for it remains a challenge. Currently, one of the best documented treatment modalities for AA is topical immunotherapy. AIM: To evaluate the safety and efficacy of combined DPCP and anthralin versus standard protocol (DPCP alone). METHODS: A prospective randomized clinical trial was conducted on 50 patients with Alopecia areata who received DPCP alone (group D) or in combination with anthralin (group D/A). Percentage of hair regrowth after 6 months of treatment and the incidence of drug-related adverse effects were evaluated and compared between the two groups. RESULTS: Complete hair regrowth was observed among three patients in each group (18.75% in Group D and 15.79% in Group D/A) after 6 months. Moreover, 25% and 31% of patients in group D and 21% and 47% of patients in group D/A had > 75% and > 50% hair regrowth respectively at the end of the study (P-value: 0.696). In addition, earlier age of onset, chronicity of lesions, nail involvement, facial hair loss and extensive lesions at baseline were associated with poor clinical outcome. CONCLUSION: DPCP and anthralin was as effective as DPCP alone and anthralin did not add to the effect of DPCP in treating AA.

Induction of IL-1ß and antimicrobial peptides as a potential mechanism for topical dithranol.

Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1ß to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata.

Chemical Modulators of Fibrinogen Production and Their Impact on Venous Thrombosis.

Thrombosis is a leading cause of morbidity and mortality. Fibrinogen, the soluble substrate for fibrin-based clotting, has a central role in haemostasis and thrombosis and its plasma concentration correlates with cardiovascular disease event risk and a prothrombotic state in experimental models. We aimed to identify chemical entities capable of changing fibrinogen production and test their impact on experimental thrombosis. A total of 1,280 bioactive compounds were screened for their ability to alter fibrinogen production by hepatocyte-derived cancer cells and a selected panel was tested in zebrafish larvae. Anthralin and all-trans retinoic acid (RA) were identified as fibrinogen-lowering and fibrinogen-increasing moieties, respectively. In zebrafish larvae, anthralin prolonged laser-induced venous- occlusion times and reduced thrombocyte accumulation at injury sites. RA had opposite effects. Treatment with RA, a nuclear receptor ligand, increased fibrinogen mRNA levels. Using an antisense morpholino oligonucleotide to deplete zebrafish fibrinogen, we correlated a shortening of laser-induced venous thrombosis times with RA treatment and fibrinogen protein levels. Anthralin had little effect on fibrinogen mRNA in zebrafish larvae, despite leading to lower detectable fibrinogen. Therefore, we made a proteomic scan of anthralin-treated cells and larvae. A reduced representation of proteins linked to the canonical secretory pathway was detected, suggesting that anthralin affects protein secretion. In summary, we found that chemical modulation of fibrinogen levels correlates with measured effects on experimental venous thrombosis and could be investigated as a therapeutic avenue for thrombosis prevention.

The African natural product knipholone anthrone and its analogue anthralin (dithranol) enhance HIV-1 latency reversal.

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.

Childhood Alopecia Areata: An Overview of Treatment and Recent Patents.

BACKGROUND: Alopecia Areata (AA) is a systemic autoimmune condition that usually starts in childhood. OBJECTIVE: This article aims to review genetics, therapy, prognosis, and recent patents for AA. METHODS: We used clinical queries and keywords "alopecia areata" AND "childhood" as a search engine. Patents were searched using the key term "alopecia areata" in Patents.google.com and freepatentsonline. com. RESULTS: Due to an immune-mediated damage to the hair follicles, hair is lost from the scalp and other areas of the body temporarily or even permanently. Children with AA are generally healthy. Evidence of genetic association and increased predisposition for AA was found by studying families with affected members. Pathophysiologically, T- lymphocytes attack hair follicles and cause inflammation and destruction of the hair follicles and hair loss. In mild cases, there would be well-demarcated round patchy scalp hair loss. The pathognomonic "exclamation mark hairs" may be seen at the lesion periphery. In more severe cases, the hair loss may affect the whole scalp and even the whole body. The clinical course is also variable, which may range from transient episodes of recurrent patchy hair loss to an indolent gradually deteriorating severe hair loss. The treatment of AA depends on factors including patients' age, the extent of the hair loss, duration of disease, psychological impact, availability and side effect profile of the treatments. For localized patchy alopecia, topical application of corticosteroids and/or intralesional corticosteroids are the treatment of choice. Other topical treatments include minoxidil, anthralin, coal tar and immunotherapy. In severe resistant cases, systemic immunosuppressants may be considered. Although herbal medicine, acupuncture, complementary and alternative medicine may be tried on children in some Asian communities, the evidence to support these practices is lacking. To date, only a few recent patents exist in topical treatments, including Il-31, laser and herbal medications. Clinical efficacy is pending for these treatment modalities. CONCLUSION: None of the established therapeutic options are curative. However, newer treatment modalities, including excimer laser, interleukin-31 antibodies and biologics, are evolving so that there may be significant advances in treatment in the near future. AA can be psychosocially devastating. It is important to assess the quality of life, degree of anxiety, social phobia and mood of the patients and their families. Psychological support is imperative for those who are adversely affected psychosocially.

Topical immunotherapy in combination with anthralin in the treatment of refractory alopecia areata.

BACKGROUND: Treatment is often challenging in patients with alopecia areata. We often try topical immunotherapy to treat alopecia areata in Japan. Anthralin is sometimes used in other countries. OBJECTIVES: The aim of this study was to examine effectiveness of combination therapy with both topical immunotherapy with squaric acid dibutylester or diphenylcyclopropenone and anthralin in the treatment of refractory alopecia areata. METHODS: We treat four patients with refractory alopecia areata by topical immunotherapy and anthralin. Two patients had alopecia areata multilocularis and the other two patients had alopecia totalis. The entire scalp was treated with weekly application of squaric acid dibutylester or diphenylcyclopropenone and daily 0.5% anthralin ointment. Patients were followed up weekly, and adverse effects were recorded. RESULTS: One patient with multifocal patches of alopecia areata got complete hair regrowth at week 30, the other patient with multifocal patches of alopecia areata turned for the worse at week 30 and recovered at week 52. Hair regrowth was not seen in the other two patients with alopecia totalis. Localized pruritis and hyperpigmentation of the scalp were seen in two patients. CONCLUSIONS: To treat alopecia areata unresponsive to topical immunotherapy alone, topical immunotherapy in combination with anthralin is worth a try.

Dithranol: An Insight into its Novel Delivery Cargos for Psoriasis Management.

OBJECTIVE: Dithranol (DTH) is a well-known moiety that has long been used promisingly to impede and treat skin disorders, particularly psoriasis. Nowadays, a rekindled interest in the use of DTH for this disorder has been observed. Side effects associated with conventional topical formulations of this moiety have aroused the interest of the scientific community in investigating novel cargos of DTH for psoriasis management. RESULTS: Previous research has evidenced the anti-inflammatory and anti-proliferating potential of DTH. Numerous studies have indicated that DTH inhibits polymorphonuclear (PMN) leucocyte, modulates epidermal cell receptors and promotes anti-psoriatic action. However, some deterrent factors like poor solubility, stability, toxicity, staining and skin irritation hamper its use as a potential therapeutic agent. With the adoption of novel drug delivery technologies, the above mentioned inherent limitations of DTH have been compensated to reestablish this drug moiety. CONCLUSION: This article reviews novel drug delivery aspects, safety concerns, clinical evidence, current status, and future opportunities of DTH in the management of psoriasis. Further, it will update researchers on this promising drug moiety, which is free from systemic adverse responses in comparison to other therapeutic molecules like steroids, for psoriasis treatment.