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Ugeskrift For Laeger Nov 2023Alopecia areata (AA) is an autoimmune disease where inflammation around the lowest part of the hair follicle results in non-scarring hair loss. This review investigates... (Review)
Review
Alopecia areata (AA) is an autoimmune disease where inflammation around the lowest part of the hair follicle results in non-scarring hair loss. This review investigates the course of the disease, its unpredictability and variation from a single patch of scalp hair loss to the loss of all hair on the body. The first drug with AA indication was approved in 2022, the JAK-inhibitor baricitinib. This paves the way for future research that may lead to the development of new effective pathogenesis-specific treatments.
Topics: Humans; Alopecia Areata; Alopecia; Autoimmune Diseases; Janus Kinase Inhibitors
PubMed: 38018739
DOI: No ID Found -
Proceedings of the National Academy of... Jul 2023Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete...
Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete understanding of the immunological underpinnings of disease. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the graft-induced C3H/HeJ mouse model of AA, coupled with antibody-based depletion to interrogate the functional role of specific cell types in AA in vivo. Since AA is predominantly T cell-mediated, we focused on dissecting lymphocyte function in AA. Both our scRNAseq and functional studies established CD8+ T cells as the primary disease-driving cell type in AA. Only the depletion of CD8+ T cells, but not CD4+ T cells, NK, B, or γδ T cells, was sufficient to prevent and reverse AA. Selective depletion of regulatory T cells (T) showed that T are protective against AA in C3H/HeJ mice, suggesting that failure of T-mediated immunosuppression is not a major disease mechanism in AA. Focused analyses of CD8+ T cells revealed five subsets, whose heterogeneity is defined by an "effectorness gradient" of interrelated transcriptional states that culminate in increased effector function and tissue residency. scRNAseq of human AA skin showed that CD8+ T cells in human AA follow a similar trajectory, underscoring that shared mechanisms drive disease in both murine and human AA. Our study represents a comprehensive, systematic interrogation of lymphocyte heterogeneity in AA and uncovers a novel framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.
Topics: Mice; Humans; Animals; Alopecia Areata; Mice, Inbred C3H; Lymphocyte Subsets; Sequence Analysis, RNA
PubMed: 37428932
DOI: 10.1073/pnas.2305764120 -
Journal of the American Academy of... Aug 2022Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA.
OBJECTIVE
To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA.
METHODS
In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks.
RESULTS
A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors.
LIMITATIONS
These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA.
CONCLUSIONS
Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.
Topics: Adult; Alopecia Areata; Cytidine Triphosphate; Humans; Janus Kinase Inhibitors; Pyrimidines; Treatment Outcome
PubMed: 35364216
DOI: 10.1016/j.jaad.2022.03.045 -
Pediatric Dermatology 2023Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited disorder of immunity which leads to increased risk for mucocutaneous candidiasis...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited disorder of immunity which leads to increased risk for mucocutaneous candidiasis and multiorgan autoimmune disease. While alopecia areata (AA) has been described in some patients with APECED, the extent and timing of AA is not well established and extent and timing of concomitant vitiligo and hypothyroidism has not been described. We evaluated an APECED cohort followed at the National Institutes of Health for the timing of development of associated diseases. We found AA occurred earlier in those with APECED than in the general population, was rarely the first sign of APECED, and the timing of AA onset did correlate with the timing of onset of vitiligo or hypothyroidism which also occurred at high rates and early age.
Topics: Humans; Polyendocrinopathies, Autoimmune; Alopecia Areata; Vitiligo; Hypothyroidism
PubMed: 37495514
DOI: 10.1111/pde.15380 -
La Tunisie Medicale Oct 2023Trachyonychia means rough, longitudinally ridged nails with a sandy, brittle and thin aspect. It is a rare condition that occurs mainly in children. Studies on...
INTRODUCTION
Trachyonychia means rough, longitudinally ridged nails with a sandy, brittle and thin aspect. It is a rare condition that occurs mainly in children. Studies on trachyonychia are rare. We aimed to describe the clinical aspects and outcome of trachyonychia, as well as its treatment.
CASES
Two boys aged 11 and 14 years old and a girl aged 6 years presented with nail dystrophy of the fingers and toes. Patient 1 had also a scaly patch on the glans penis, and patient 2 was atopic. Trachyonychia associated with psoriasis was suspected in patient 1 and the idiopathic form was retained in the other two patients. All patients were treated with topical steroids for a few months. The patients did not show any improvement at the six-month follow-up. Only one patient was contacted again after two years and showed spontaneous healing.
COMMENTARIES
The diagnosis of trachyonychia is mainly clinical. In the literature, 62% of pediatric patients had an idiopathic form. However, a strong association was observed between trachyonychia and alopecia areata. Trachyonychia of childhood appears to have a good prognosis, with spontaneous improvement within six months to two years. Therapeutic abstention is the rule.
Topics: Male; Female; Humans; Child; Adolescent; Nail Diseases; Alopecia Areata
PubMed: 38465760
DOI: No ID Found -
Current Opinion in Pediatrics Aug 2016Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical... (Review)
Review
PURPOSE OF REVIEW
Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include nontargeted approaches, such as corticosteroids, topical calcineurin inhibitors, narrow band ultraviolet B phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments.
RECENT FINDINGS
Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an interferon (IFN)γ-driven immune response, including IFNγ, IFNγ-induced chemokines, and cytotoxic CD8 T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis.
SUMMARY
The identification of IFNγ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.
Topics: Adaptive Immunity; Alopecia Areata; Autoimmunity; Genome-Wide Association Study; Humans; Immunity, Innate; Immunosuppressive Agents; Immunotherapy; Interferon-gamma; Reactive Oxygen Species; Signal Transduction; Vitiligo
PubMed: 27191524
DOI: 10.1097/MOP.0000000000000375 -
Indian Journal of Dermatology,... 2013Disturbances of hair follicle cycling lie at the heart of most hair growth disorders, and have dramatic effects on visible hair growth and shedding. The two common... (Review)
Review
Disturbances of hair follicle cycling lie at the heart of most hair growth disorders, and have dramatic effects on visible hair growth and shedding. The two common disorders due to aberration in hair follicle cycling are telogen and anagen effluvium. Though a lot of literature addresses the problem of telogen effluvium, there are not many reviews on anagen effluvium or anagen hair loss. Anagen effluvium is considered synonymous with chemotherapy-induced alopecia and other causes are rarely considered. In this review, we try to discuss the etiopathogenesis, clinical presentation, differentials, and management issues in anagen effluvium. Anagen effluvium is the abrupt loss of hairs that are in their growing phase (anagen) due to an event that impairs the mitotic or metabolic activity of hair follicle. Chemotherapy, radiation and toxic chemicals, and sometimes inflammatory diseases like alopecia areata and pemphigus are also capable of diminishing the metabolic activity of hair follicles resulting in anagen hair loss. Although it is reversible, and hair regrowth occurs after a delay of 1-3 months; sometimes it can lead to permanent alopecia and can be psychologically devastating with negative impact on individual perceptions of appearance, body image, sexuality, and self-esteem. For some patients, the emotional trauma may be so severe that it may lead to discontinuing or refusing therapy that might otherwise be beneficial. In such cases, a psychosomatic approach as well as empathic consideration of the patients concerns and fears as well as the provision of practical medical-aesthetic and styling tips are equally important and can be integrated in management.
Topics: Alopecia Areata; Diagnosis, Differential; Humans; Loose Anagen Hair Syndrome; Pemphigus; Scalp
PubMed: 23974578
DOI: 10.4103/0378-6323.116728 -
Psychiatria Polska 2015The problems of mental disorders and psychological aspects in the condition referred to as alopecia areata in the Polish context are not well researched yet. The... (Review)
Review
The problems of mental disorders and psychological aspects in the condition referred to as alopecia areata in the Polish context are not well researched yet. The objective of our analyses is to present the results of the review of literature devoted to the occurrence of mental disorders and the participation of psychological factors in the aetiology of alopecia areata. Preparing the review of the research conducted hitherto and concerning the participation of psychological factors in the pathogenesis and the course of alopecia areata, it is indicated that stress, a traumatic situation, a high level of neuroticism and alexithymia, may influence the occurrence, duration and exacerbation of the condition in question. Mental disorders occurring most frequently amongst individuals suffering from alopecia areata are: depression, increased level of anxiety, generalized anxiety disorder, social phobia, post-traumatic stress disorder, and suicidal thoughts.
Topics: Alopecia Areata; Anxiety Disorders; Comorbidity; Depression; Humans; Mental Disorders; Phobic Disorders; Risk Factors
PubMed: 26688846
DOI: 10.12740/PP/39064 -
International Journal of Molecular... Apr 2024Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment... (Review)
Review
Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.
Topics: Alopecia Areata; Humans; Vitiligo; Animals; Immune Privilege; Cytokines
PubMed: 38673994
DOI: 10.3390/ijms25084409 -
Journal of Managed Care & Specialty... Jul 2023Alopecia areata (AA) is an autoimmune disease with a complex pathophysiology resulting in nonscarring hair loss in genetically susceptible individuals. We aim to provide...
Alopecia areata (AA) is an autoimmune disease with a complex pathophysiology resulting in nonscarring hair loss in genetically susceptible individuals. We aim to provide health care decision makers an overview of the pathophysiology of AA, its causes and diagnosis, disease burden, costs, comorbidities, and information on current and emerging treatment options to help inform payer benefit design and prior authorization decisions. Literature searches for AA were conducted using PubMed between 2016 and 2022 inclusive, using search terms covering the causes and diagnosis of AA, pathophysiology, comorbidities, disease management, costs, and impact on quality of life (QoL). AA is a polygenic autoimmune disease that significantly impacts QoL. Patients with AA face economic burden and an increased prevalence of psychiatric disease, as well as numerous systemic comorbidities. AA is predominantly treated using corticosteroids, systemic immunosuppressants, and topical immunotherapy. Currently, there are limited data to reliably inform effective treatment decisions, particularly for patients with extensive disease. However, several novel therapies that specifically target the immunopathology of AA have emerged, including Janus kinase (JAK) 1/2 inhibitors such as baricitinib and deuruxolitinib, and the JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor ritlecitinib. To support disease management, a disease severity classification tool, the Alopecia Areata Severity Scale, was recently developed that evaluates patients with AA holistically (extent of hair loss and other factors). AA is an autoimmune disease often associated with comorbidities and poor QoL, which poses a significant economic burden for payers and patients. Better treatments are needed for patients, and JAK inhibitors, among other approaches, may address this tremendous unmet medical need. Dr King reports seats on advisory boards for and/or is a consultant and/or clinical trial investigator for AbbVie, Aclaris Therapeutics Inc, AltruBio Inc, Almirall, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Meyers Squibb, Concert Pharmaceuticals Inc, Dermavant Sciences Inc, Eli Lilly and Company, Equillium, Incyte Corp, Janssen Pharmaceuticals, LEO Pharma, Otsuka/Visterra Inc, Pfizer, Regeneron, Sanofi Genzyme, TWi Biotechnology Inc, and Viela Bio; and speakers bureaus for AbbVie, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi Genzyme. Pezalla is a paid consultant to Pfizer for market access and payer strategy concerns; Fung, Tran, Bourret, Takiya, Peeples-Lamirande, and Napatalung are employees of Pfizer and hold stock in Pfizer. This article was funded by Pfizer.
Topics: Humans; United States; Alopecia Areata; Quality of Life; Managed Care Programs; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Cost of Illness; Pharmaceutical Preparations
PubMed: 37219075
DOI: 10.18553/jmcp.2023.22371