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American Journal of Clinical Dermatology Nov 2023Alopecia areata is an autoimmune hair loss disease that is non-scarring and is characterized by chronic inflammation at the hair follicle level. Clinically, patients'... (Review)
Review
Alopecia areata is an autoimmune hair loss disease that is non-scarring and is characterized by chronic inflammation at the hair follicle level. Clinically, patients' presentation varies from patchy, circumscribed scalp involvement to total body and scalp hair loss. Current management is guided by the degree of scalp and body involvement, with topical and intralesional steroid injections as primarily first-line for mild cases and broad immunosuppressants as the mainstay for more severe cases. Until recently, the limited number of blinded, randomized, placebo-controlled clinical trials for this disease had made establishing an evidence-based treatment paradigm challenging. However, growing insights into the pathogenesis of alopecia areata through blood and tissue analysis of human lesions have identified several promising targets for therapy. T-helper (Th) 1/interferon skewing has traditionally been described as the driver of disease; however, recent investigations suggest activation of additional immune mediators, including the Th2 pathway, interleukin (IL)-9, IL-23, and IL-32, as contributors to alopecia areata pathogenesis. The landscape of alopecia areata treatment has the potential to be transformed, as several novel targeted drugs are currently undergoing clinical trials. Given the recent US FDA approval of baricitinib and ritlecitinib, Janus kinase (JAK) inhibitors are a promising drug class for treating severe alopecia areata cases. This article will review the efficacy, safety, and tolerability of current treatments for alopecia areata, and will provide an overview of the emerging therapies that are leading the revolution in the management of this challenging disease.
Topics: Humans; Alopecia Areata; Alopecia; Hair Follicle; Scalp; Immunosuppressive Agents; Janus Kinase Inhibitors
PubMed: 37606849
DOI: 10.1007/s40257-023-00808-1 -
Drugs Sep 2023Ritlecitinib (LITFULO), an orally administered kinase inhibitor, is being developed by Pfizer for the treatment of alopecia areata, vitiligo, ulcerative colitis and... (Review)
Review
Ritlecitinib (LITFULO), an orally administered kinase inhibitor, is being developed by Pfizer for the treatment of alopecia areata, vitiligo, ulcerative colitis and Crohn's disease. On 23 June 2023, ritlecitinib received approval in the USA for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Ritlecitinib was approved in Japan on 26 June 2023 for the treatment of alopecia areata (limited to intractable cases involving widespread hair loss). Ritlecitinib has also received a positive opinion in the EU and is under regulatory review in the UK and China. This article summarizes the milestones in the development of ritlecitinib leading to this first approval for severe alopecia areata.
Topics: Adult; Adolescent; Humans; Alopecia Areata; Colitis, Ulcerative; Crohn Disease; China
PubMed: 37556041
DOI: 10.1007/s40265-023-01928-y -
Indian Journal of Dermatology,... 2023The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation,... (Review)
Review
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation, and apoptosis. In addition, JAK signaling pathway plays critical roles in orchestrating immune response through its interactions with the cytokine receptors and the transcriptions factors. Several key cytokines use JAK-STAT signaling proteins to transduce intra-cellular signals which are involved in the pathogenesis of autoimmune and inflammatory diseases such as in psoriatic disease (psoriasis, psoriatic arthritis), atopic dermatitis, alopecia areata, vitiligo, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, Sjogren's syndrome, and other autoimmune diseases. In recent years, understandings of the molecular mechanisms of JAK-STAT pathway in the inflammatory proliferative cascades of autoimmune diseases has led to the development of JAK inhibitors and has opened a new dimension for the treatment of systemic and cutaneous inflammatory diseases. In this symposium we have provided a broad perspective on the use of Janus kinase inhibitors in cutaneous autoimmune diseases.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; STAT Transcription Factors; Signal Transduction; Skin Diseases; Autoimmune Diseases
PubMed: 37609754
DOI: 10.25259/IJDVL_8_2023 -
Journal of the American Academy of... Aug 2023Hair loss is devastating to the patient, but the diagnosis and treatment of alopecia are also difficult for primary care providers and even dermatologists. Given recent... (Review)
Review
Hair loss is devastating to the patient, but the diagnosis and treatment of alopecia are also difficult for primary care providers and even dermatologists. Given recent advances in the field, there has never been a more pressing time to reevaluate and improve upon the significant clinical skills needed to accurately diagnose and treat our patients with hair loss. This CME activity on alopecia is designed to (1) educate dermatologists in a simple, succinct fashion on the identification of, and the distinction between, the diverse types of hair loss and (2) discuss how to manage them.
Topics: Humans; Alopecia; Clinical Competence
PubMed: 37591559
DOI: 10.1016/j.jaad.2023.05.048 -
Anais Brasileiros de Dermatologia 2023The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs... (Review)
Review
The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; Dermatology; Signal Transduction; STAT Transcription Factors; Vitiligo
PubMed: 37230920
DOI: 10.1016/j.abd.2023.03.001 -
Journal of Dermatological Science Dec 2023Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases.... (Review)
Review
BACKGROUND
Alopecia areata (AA) is a common, acquired, and nonscarring type of hair loss that affects people of every generation and is intractable in severe and relapsing cases. Patients with AA, especially those with greater scalp involvement, have poor health-related quality-of-life scores.
PURPOSE
Following our previous review article in the April 2017 issue of the Journal of Dermatological Science, we aim to provide a pair of review articles on recent progress in multidisciplinary approaches to AA.
MAIN FINDINGS
We found more than 1800 publications on AA from July 2016 to December 2022.
CONCLUSIONS
In this review, we focused on the latest information on the epidemiology, comorbidities, and pathogenesis of AA.
Topics: Humans; Alopecia Areata; Alopecia; Comorbidity; Quality of Life; Recurrence
PubMed: 37833164
DOI: 10.1016/j.jdermsci.2023.09.008 -
International Journal of Molecular... Jul 2023Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely... (Review)
Review
Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely related to emotional stress and influenced by psychological factors as part of its pathophysiology; however, its etiology remains predominantly unknown. This review aimed to elucidate the association between AA occurrence and the neuropeptide substance P (SP) and corticotropin-releasing hormone (CRH), which are secreted during emotional stress, and have been understood to initiate and advance the etiopathogenesis of AA. Therefore, this review aimed to explain how SP and CRH initiate and contribute to the etiopathogenesis of AA. To assess the etiopathogenesis of AA, we conducted a literature search on PubMed and ClinicalTrials.gov. Overall, several authors described interactions between the hair follicles (HFs) and the stress-associated signaling substances, including SP and CRH, in the etiology of AA; this was attributed to the understanding in that AA can occur without the loss of HFs, similar to that observed in hereditary hair loss with age. Most studies demonstrated that the collapse of "immune privilege" plays a crucial role in the development and exacerbation of the AA; nonetheless, a few studies indicated that substances unrelated to autoimmunity may also cause apoptosis in keratocytes, leading to the development of AA. We investigated both the autoimmune and apoptotic pathways within the etiology of AA and assessed the potential interactions between the key substances of both pathways to evaluate potential therapeutic targets for the treatment of AA. Clinical trials of marketed/unreviewed intervention drugs for AA were also reviewed to determine their corresponding target pathways.
Topics: Humans; Alopecia Areata; Corticotropin-Releasing Hormone; Autoimmunity; Substance P; Stress, Psychological; Hair Follicle
PubMed: 37511468
DOI: 10.3390/ijms241411711 -
Journal of the European Academy of... Apr 2024Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete... (Review)
Review
Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA-approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA-approved for patients with severe alopecia areata. Other systemic medications used off-label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.
Topics: Adult; Adolescent; Child; Humans; Alopecia Areata; Quality of Life; Alopecia; Minoxidil; Azathioprine; Janus Kinase Inhibitors
PubMed: 38169088
DOI: 10.1111/jdv.19768