The Changing Landscape of Alopecia Areata: The Translational Landscape.
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ABSTRACT:
SUBMITTER: Wang ECE
PROVIDER: S-EPMC5504204 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Alopecia areata (AA), a prevalent inflammatory cause of hair loss, lacks FDA-approved therapeutics for extensive cases, which are associated with very poor rates of spontaneous hair regrowth and major psychological distress. Current treatments for severe cases include broad immune-suppressants, which are associated with significant adverse effects, precluding long-term use, with rapid hair loss following treatment termination. As a result of the extent of the disease in severe cases, topical contact sensitizers and intralesional treatments are of limited use. The pathogenesis of AA is not yet fully understood, but recent investigations of the immune activation in AA skin reveal Th1/IFN-γ, as well as Th2, PDE4, IL-23, and IL-9 upregulations. Tissue analyses of both animal models and human lesions following broad-acting and cytokine-specific therapeutics (such as JAK inhibitors and ustekinumab, respectively) provide another opportunity for important insights into the pathogenesis of AA. As reviewed in this paper, numerous novel therapeutics are undergoing clinical trials for AA, emphasizing the potential transformation of the clinical practice of AA, which is currently lacking. Dermatologists are already familiar with the revolution in disease management of psoriasis, stemming from better understanding of immune dysregulations, and atopic dermatitis will soon follow a similar path. In light of these recent developments, the therapeutic arena of AA treatments is finally getting more exciting. AA will join the lengthening list of dermatologic diseases with mechanism-targeted drugs, thus changing the face of AA.
| S-EPMC5504208 | biostudies-literature
Project description:Alopecia areata (AA) is a recurrent autoimmune type of hair loss that affects about 5.3 million people in the United States alone. Despite being the most prevalent autoimmune disease, the molecular and cellular mechanisms underlying this complex disease are still poorly understood, and rational treatments are lacking. Further efforts are necessary to clearly pinpoint the causes and molecular pathways leading to this disease and to find evidence-based treatments for AA. The authors focus on the central role of genetics for gaining insight into disease pathogenesis and setting the stage for the rational development of novel effective therapeutic approaches.
| S-EPMC4362526 | biostudies-literature
Project description:Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
| S-EPMC5573125 | biostudies-other
Project description: Not available
| S-EPMC3230136 | biostudies-literature
Project description:Alopecia areata (AA) is a common disease characterized by nonscarring hair loss. There are no satisfactory therapies for extensive cases. Systemic immune suppressants are usually used despite their nonspecific actions and often associated side effects. Apremilast is an oral, small-molecule, inhibitor of phosphodiesterase 4 approved for the treatment of psoriasis and psoriatic arthritis. Its use in AA has shown variable results. Whereas a recent reduced clinical trial concluded a lack of efficacity, several case reports demonstrate a significant improvement. We report four cases of extensive AA successfully treated with apremilast.
| S-EPMC6830030 | biostudies-literature
Project description:Our goal was to develop a transcriptomic description of affected alopecic scalp skin from patients with alopecia areata. 5 biological replicates of skin samples from 5 separate AA patients compared with 5 similar scalp samples from healthy control patients
2014-08-17 | E-GEOD-45512 | biostudies-arrayexpress
Project description:IntroductionIndividuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA.MethodsScoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged ≥ 18 years, 36 adolescents aged 12-17 years) with Severity of Alopecia Tool (SALT) ≥ 25% scalp hair loss.ResultsExploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (α ≥ 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients ≥ 0.78). All HL item scores demonstrated strong construct validity (r ≥ 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r ≥ 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25-49% SALT subgroup versus those with highest SALT scores (76-100%); however, ES mean domain scores were better in the SALT 76-100% subgroup in the same comparison (p < 0.0001). Using AASIS and MCS score-created subgroups, ES and AL mean domain scores demonstrated hypothesized differences across subgroups (all p values < 0.0001).ConclusionThe AAPPO questionnaire is a reliable, valid disease-specific measure of hair loss severity and impact in individuals with AA.
| S-EPMC8776917 | biostudies-literature
Project description:Alopecia areata (AA) is an immune-mediated disease in which autoantigens play an important part in activating T-lymphocytes. Vitamin D has been associated with various autoimmune diseases, and Vitamin D receptors are strongly expressed in hair follicles and their expression in keratinocytes is necessary for the maintenance of the normal hair cycle.The aim of this study was to find the association between Vitamin D level and AA.This was a hospital-based cross-sectional study in which 50 patients with clinically and trichoscopically diagnosed AA cases, and 35 healthy age- and sex-matched controls were studied in summer months. Blood samples were taken from both cases as well as controls and samples were immediately processed by centrifugation (4000 rpm) at room temperature. Plasma 25-hydroxyvitamin D (25(OH)D) was analyzed by chemiluminescence method. A deficiency in Vitamin D was defined as serum 25(OH)D concentrations <30 ng/ml.The mean body mass index in cases was 20.96 ± 1.91, whereas in controls, it was 21.37 ± 1.70 (P = 0.31). The mean serum 25(OH)D levels of AA patients was 16.6 ± 5.9 ng/ml, whereas in control group, the mean level was 40.5 ± 5.7, the difference being statistically significant (P < 0.001). A significant negative correlation was found between severity of alopecia tool score and Vitamin D level (P < 0.001; r = -0.730) and also between the number of patches and Vitamin D level (P < 0.001, r = -0.670).In our study, we found that the levels of 25(OH)D were low in AA patients when compared to healthy controls. Furthermore, there was a significant negative correlation between the levels of serum Vitamin D and severity of AA. Thus, the study suggests the role of Vitamin D in pathogenesis of AA and hence a possible role of Vitamin D supplementation in treatment of same.Our study was limited by the lesser number of patients and lack of therapeutic trial of Vitamin D for these patients.
| S-EPMC5527723 | biostudies-other
Project description:The role of microbial dysbiosis in scalp disease has been recently hypothesized. However, little information is available with regards to the association between microbial population on the scalp and hair diseases related to hair growth. Here we investigated bacterial communities in healthy and Alopecia areata (AA) subjects. The analysis of bacterial distribution at the genus level highlighted an increase of Propionibacterium in AA subjects alongside a general decrease of Staphylococcus. Analysis of log Relative abundance of main bacterial species inhabiting the scalp showed a significant increase of Propionibacterium acnes in AA subjects compared to control ones. AA scalp condition is also associated with a significant decrease of Staphylococcus epidermidis relative abundance. No significant changes were found for Staphylococcus aureus. Therefore, data from sequencing profiling of the bacterial population strongly support a different microbial composition of the different area surrounded hair follicle from the epidermis to hypodermis, highlighting differences between normal and AA affected the scalp. Our results highlight, for the first time, the presence of a microbial shift on the scalp of patients suffering from AA and gives the basis for a larger and more complete study of microbial population involvement in hair disorders.
| S-EPMC6459526 | biostudies-literature
Project description:The advancement of genetic and preclinical studies has uncovered the mechanisms involved in the pathogenesis of alopecia areata (AA). The development of targeted therapies using small molecules blocking specific pathways for the treatment of AA is underway. By repurposing Food and Drug Administration-approved small molecule JAK inhibitors as treatments for AA, it has been demonstrated that JAK inhibitors can effectively reverse hair loss in patients with moderate to severe AA. In this review, we summarize and discuss the current preclinical and clinical studies on JAK inhibitors, as well as the prospects of using JAK inhibitors for the treatment of AA.
| S-EPMC6475885 | biostudies-literature