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Journal of the American Academy of... Jun 2022Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist;... (Review)
Review
BACKGROUND
Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking.
OBJECTIVE
To evaluate the evidence of current treatment modalities for pediatric AA.
METHODS
We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available.
RESULTS
Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab.
LIMITATIONS
English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed.
CONCLUSION
Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.
Topics: Adolescent; Adrenal Cortex Hormones; Alopecia; Alopecia Areata; Autoimmune Diseases; Child; Humans; Janus Kinase Inhibitors; Prospective Studies
PubMed: 33940103
DOI: 10.1016/j.jaad.2021.04.077 -
Drugs in Context 2023Guttate psoriasis is common and affects 0.5-2% of individuals in the paediatric age group. This review aims to familiarize physicians with the clinical manifestations,... (Review)
Review
BACKGROUND
Guttate psoriasis is common and affects 0.5-2% of individuals in the paediatric age group. This review aims to familiarize physicians with the clinical manifestations, evaluation, diagnosis and proper management of guttate psoriasis.
METHODS
A search was conducted in July 2023 in PubMed Clinical Queries using the key term "guttate psoriasis". The search strategy included all observational studies, clinical trials and reviews published within the past 10 years. The information retrieved from the search was used in the compilation of the present article.
RESULTS
Guttate psoriasis typically presents with an abrupt onset of numerous, small, scattered, tear-drop-shaped, scaly, erythematous, pruritic papules and plaques. Sites of predilection include the trunk and proximal extremities. There may be a history of preceding streptococcal infection. Koebner phenomenon is characteristic. Guttate psoriasis may spontaneously remit within 3-4 months with no residual scarring, may intermittently recur and, in 40-50% of cases, may persist and progress to chronic plaque psoriasis. Given the possibility for spontaneous remission within several months, active treatment may not be necessary except for cosmetic purposes or because of pruritus. On the other hand, given the high rates of persistence of guttate psoriasis and progression to chronic plaque psoriasis, some authors suggest active treatment of this condition.
CONCLUSION
Various treatment options are available for guttate psoriasis. Triggering and exacerbating factors should be avoided if possible. Topical corticosteroids alone or in combination with other topical agents (e.g. tazarotene and vitamin D analogues) are the most rapid and efficient treatment for guttate psoriasis and are therefore the first-line treatment for mild cases. Other topical therapies include vitamin D analogues, calcineurin inhibitors, anthralin, coal tar and tazarotene. Ultraviolet phototherapy is the first-line therapy for moderate-to-severe guttate psoriasis, as it is more practical than topical therapy when treating widespread or numerous small lesions. Systemic immunosuppressive and immunomodulatory therapies (e.g. methotrexate, cyclosporine, retinoids, fumaric acid esters and biologics) may be considered for patients with moderate-to-severe guttate psoriasis who fail to respond to phototherapy and topical therapies.
PubMed: 37908643
DOI: 10.7573/dic.2023-8-2 -
Thrombosis and Haemostasis Apr 2021Thrombosis is a leading cause of morbidity and mortality. Fibrinogen, the soluble substrate for fibrin-based clotting, has a central role in haemostasis and 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- 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.
Topics: Animals; Animals, Genetically Modified; Anthralin; Blood Coagulation; Disease Models, Animal; Fibrinogen; Fibrinolytic Agents; Hep G2 Cells; Hepatocytes; Humans; Integrin alpha2; Morpholinos; Mutation; Oligonucleotides, Antisense; Proteomics; Small Molecule Libraries; Tretinoin; Venous Thrombosis; Zebrafish; Zebrafish Proteins
PubMed: 33302304
DOI: 10.1055/s-0040-1718414 -
Frontiers in Immunology 2023Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer....
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.
Topics: Mice; Humans; Animals; Mice, Inbred C57BL; Imiquimod; Anthralin; CD8-Positive T-Lymphocytes; Immunization; Vaccination; Adjuvants, Immunologic; Neoplasms; Dermatitis
PubMed: 37727790
DOI: 10.3389/fimmu.2023.1238861 -
Journal of Cutaneous Medicine and... 2023Alopecia 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...
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.
Topics: Humans; Child; Anthralin; Alopecia Areata; Retrospective Studies; Dermatologic Agents; Petrolatum; Administration, Topical; Alopecia
PubMed: 37559401
DOI: 10.1177/12034754231191060 -
International Journal of Trichology 2022The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA).
Topical diphenylcyclopropenone plus topical 0.5% anthralin versus topical diphenylcyclopropenone alone for the treatment of chronic extensive alopecia areata: A split-scalp, double-blind, controlled study.
BACKGROUND
The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA).
OBJECTIVE
The objective of the study was to compare the efficacy of the combination therapy of topical DCP and topical 0.5% anthralin versus topical DCP alone for the treatment of chronic extensive AA.
MATERIALS AND METHODS
Ten patients were included in the study. Of these, 1, 2, and 7 patients were diagnosed with alopecia totalis, severe AA (>50% hair loss), and alopecia universalis, respectively. For each patient, one side of the scalp was treated with a DCP solution and 0.5% anthralin for 6 months, while the other side was treated with DCP and a cream base for the same duration. The clinical responses were assessed at baseline and then monthly until the end of the 6-month study period using the Severity of Alopecia Tool score. The side effects were evaluated at each follow-up visit.
RESULTS
The difference in the efficacies of the combination treatment and DCP alone was not statistically significant ( = 0.59). Regarding the side effects, DCP plus 0.5% anthralin caused significantly more excessive dermatitis than DCP alone (7 patients vs. 2 patients; = 0.02). Eight patients reported temporary hyperpigmentation at the combination-treatment site, whereas no hyperpigmentation was reported at the DCP-alone site of any patient ( < 0.001).
CONCLUSIONS
The combination of DCP and 0.5% anthralin was not superior to DCP alone for the treatment of chronic extensive AA. An increase in side effects - excessive dermatitis and hyperpigmentation - was observed in the combination-treatment group.
PubMed: 35755959
DOI: 10.4103/ijt.ijt_72_21 -
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