Abstract
Introduction: Alopecia areata (AA) is an autoimmune dermatological condition that has attracted increasing interest within the scientific community. Its symptoms include hair loss, anxiety, and depression. Currently, the treatment of AA is challenging and often unsatisfactory. Therapeutic options include topical medications, corticosteroid injections, and, in more severe cases, immunosuppressive therapies. Objective: To review the current evidence on the causes and contributing factors of the disease, explore available therapeutic options, and evaluate the effectiveness and challenges associated with each treatment. Methods: A narrative review was conducted using the Google Scholar, ScienceDirect, PubMed, and Medscape databases, including studies published between 2009 and 2020. The search terms used were “AA” and “treatments”; “AA” and “molecular pathways”; “AA” and “genetics”; and “AA” and “genome.” The analysis included review articles addressing therapies currently used in clinical practice or studies evaluating new medications, especially biologic agents, and their outcomes. Articles describing novel molecular and genetic findings that may contribute to the development of highly specific, effective, and safe therapies—which are not yet established or available for individuals affected by alopecia areata—were also included. Results: A total of 49 studies were included in this review. The findings highlight advances in understanding the immunological mechanisms of alopecia areata, particularly the involvement of the JAKSTAT pathway, natural killer (NK) cells, and autoantigens such as ULBP3/6. AA disrupts the hair cycle, especially the anagen phase, through an immune response mediated by genetic and environmental factors. The hair follicle loses its immune privilege and becomes a target of CD8+, CD4+, and NK cells, which produce IFNγ and activate the JAKSTAT pathway, intensifying inflammation. Biopsies reveal lymphocytic infiltrates surrounding the hair bulb. The disease is associated with susceptibility loci such as NKG2D and genes involved in the JAKSTAT pathway. Proteins such as CIRP and VIP influence the maintenance of immune privilege, with CIRP emerging as a potential marker of disease activity. AA shares pathogenic mechanisms with other autoimmune diseases, including Graves’ disease, rheumatoid arthritis, and type 1 diabetes. Psychophysiological factors, such as substance P, and psychiatric comorbidities, including depression and suicidal ideation, are common in severe forms of the disease. Treatment is currently based on drug repurposing due to the lack of diseasespecific medications. Existing therapies are nonspecific, used offlabel, costly, and largely inaccessible within the public healthcare system, contributing to the neglect of AA in public health policies. Low therapeutic efficacy and inadequate pharmaceutical formulations further compromise outcomes, worsening the biopsychosocial burden experienced by patients. Conclusions: Advances in understanding the pathophysiology of AA have driven the development of more targeted therapeutic approaches. However, robust clinical trials and public policies that expand access to effective treatments are still needed.
