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Clinical Immunology (Orlando, Fla.) Oct 2023The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized.
BACKGROUND
The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized.
OBJECTIVE
We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA).
STUDY DESIGN
27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis.
RESULTS
The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04).
CONCLUSIONS
Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.
Topics: Humans; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; COVID-19; Alopecia Areata; Vaccination
PubMed: 37586672
DOI: 10.1016/j.clim.2023.109737 -
International Journal of Molecular... Jan 2024We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly...
We had previously investigated the expression and functional role of C-X-C Motif Chemokine Ligand 12 (CXCL12) during the hair cycle progression. CXCL12 was highly expressed in stromal cells such as dermal fibroblasts (DFs) and inhibition of CXCL12 increased hair growth. Therefore, we further investigated whether a CXCL12 neutralizing antibody (αCXCL12) is effective for androgenic alopecia (AGA) and alopecia areata (AA) and studied the underlying molecular mechanism for treating these diseases. In the AGA model, CXCL12 is highly expressed in DFs. Subcutaneous (s.c.) injection of αCXCL12 significantly induced hair growth in AGA mice, and treatment with αCXCL12 attenuated the androgen-induced hair damage in hair organ culture. Androgens increased the secretion of CXCL12 from DFs through the androgen receptor (AR). Secreted CXCL12 from DFs increased the expression of the AR and C-X-C Motif Chemokine Receptor 4 (CXCR4) in dermal papilla cells (DPCs), which induced hair loss in AGA. Likewise, CXCL12 expression is increased in AA mice, while s.c. injection of αCXCL12 significantly inhibited hair loss in AA mice and reduced the number of CD8, MHC-I, and MHC-II cells in the skin. In addition, injection of αCXCL12 also prevented the onset of AA and reduced the number of CD8 cells. Interferon-γ (IFNγ) treatment increased the secretion of CXCL12 from DFs through the signal transducer and activator of transcription 3 (STAT3) pathway, and αCXCL12 treatment protected the hair follicle from IFNγ in hair organ culture. Collectively, these results indicate that CXCL12 is involved in the progression of AGA and AA and antibody therapy for CXCL12 is promising for hair loss treatment.
Topics: Animals; Mice; Alopecia; Alopecia Areata; Androgens; Antibodies, Neutralizing; Hair; Hair Follicle; Skin; Chemokine CXCL12
PubMed: 38338982
DOI: 10.3390/ijms25031705 -
JAMA Dermatology Nov 2023Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis...
IMPORTANCE
Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis (AU). There is a lack of consensus for treatment. Understanding current practice patterns could help the identification of treatment needs and development of standards of care.
OBJECTIVE
To review treatment patterns for adults with AA in the US between 2015 and 2020.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used medicine and pharmacy claims for commercially insured individuals from the IBM MarketScan Research Database to assess adults (≥18 years) newly treated for AA between October 15, 2015, and February 28, 2020. Alopecia areata was identified based on having at least 1 diagnosis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L63.x. Patients were required to have at least 365 days of continuous health plan enrollment before and after the cohort entry date. Patients were required to be free of AA diagnosis codes 365 days before the cohort entry date. Statistical analyses were conducted between 2019 and 2023.
MAIN OUTCOMES AND MEASURES
Main outcomes were treatment patterns for all patients with AA and subgroups of (1) patients with AT or AU and (2) those cared for by a dermatologist on the cohort entry date. Longitudinal therapy course during the first year after the diagnosis was also examined.
RESULTS
The study cohort consisted of 45 483 individuals (mean [SD] age, 43.8 [14.2] years; 29 903 [65.7%] female). During the year of follow-up, 30 217 patients (66.4%) received at least 1 AA treatment. The most common treatments were intralesional (19 014 [41.8%]), topical (18 604 [40.9%]), intramuscular (17 328 [38.1%]), and oral (9378 [20.6%]) corticosteroids. Compared with patients without AT or AU, patients with AT or AU a lower frequency of intralesional steroid (359 [11.1%] vs 18 655 [44.1%], P < .001) and higher frequency of topical corticosteroid (817 [25.4%] vs 17 787 [42.1%], P < .001) use. Almost half of patients (21 489 [47.2%]) received no treatment on the day of diagnosis. By 12 months, 32 659 (71.8%) were not receiving any treatment, making no treatment the largest study group.
CONCLUSIONS AND RELEVANCE
In this large cohort study of commercially insured individuals, corticosteroids were the most commonly used treatment for adults with AA between 2015 and 2020. At 365 days after diagnosis, more than two-thirds of patients were no longer receiving any AA treatment. Further studies are needed to understand the reasons for the absence of treatment.
Topics: Adult; Humans; Female; Male; Alopecia Areata; Retrospective Studies; Cohort Studies; Alopecia; Adrenal Cortex Hormones
PubMed: 37728940
DOI: 10.1001/jamadermatol.2023.3109 -
Journal of Affective Disorders Apr 2024As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been...
BACKGROUND
As research progresses, there has been growing interest in the association between Alopecia areata (AA) and anxiety, as well as depression. However, there have been limited reports on the genetic variation level of AA in relation to mental disorders.
METHOD
We performed large-scale Two sample Mendelian randomization (MR) analyses to examine whether there is a association between AA with anxiety and depression. The data utilized for AA analysis were sourced from the FinnGen release 9 databases, including 682 cases and 361,822 controls. Summary statistics for major depression disorder (MDD) were obtained from a genome-wide meta-analysis dataset, incorporating 170,756 cases and 329,443 controls. The anxiety disorder data was conducted by the Anxiety Neuro Genetics Study Consortium, including 5580 cases and 11,730 controls. We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis.
RESULTS
Genetic liability to AA was associated with an increased risk of Major depression disorder (MDD) and anxiety demonstrated an odds ratio (OR) of 1.01 (βivw = 0.011, PIVW = 0.023) and OR of 1.16 (βivw = 0.150, PIVW = 0.002). Upon conducting the Bonferroni correction, the P-values were 0.046 and 0.004, respectively. For reverse analysis, we observed no significant association between anxiety and MDD with the risk of AA.
CONCLUSIONS
Our research unveil a unidirectional causal association whereby AA exerts a risk effect against MDD and anxiety, which serves as a valuable complement to prior meta-analyses, enriching the existing body of knowledge on the subject matter.
Topics: Humans; Alopecia Areata; Anxiety; Anxiety Disorders; Depression; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Meta-Analysis as Topic
PubMed: 38242214
DOI: 10.1016/j.jad.2024.01.152 -
Journal of Clinical Medicine Jun 2024Alopecia areata (AA) is a common form of non-scarring alopecia characterized by acute hair loss. Nail involvement, though not always present, can occur in AA patients.... (Review)
Review
Alopecia areata (AA) is a common form of non-scarring alopecia characterized by acute hair loss. Nail involvement, though not always present, can occur in AA patients. Nail changes are more frequent in severe forms of AA and in children. Literature related to nail changes in AA was comprehensively reviewed after a search on the PubMed database without time restrictions in order to identify common clinical presentations and associated factors to aid clinicians with the correct evaluation and management of these dystrophies. Nail changes in AA include pitting, trachyonychia, leukonychia, red lunula, and miscellaneous alterations such as longitudinal ridging and brittle nails. Nail changes are usually asymptomatic but, nevertheless, sometimes cosmetically disfiguring and can be associated with a reduced quality of life and impaired daily activities. Nail changes in AA may precede or follow hair loss and can occur as an isolated finding. Diagnosis may require a biopsy for definitive identification. Spontaneous improvement is possible, particularly in children, and treatment is not always necessary. Further research is, however, needed to establish a consensus on treatment approaches according to age and severity.
PubMed: 38893003
DOI: 10.3390/jcm13113292 -
JAMA Dermatology Feb 2024
Topics: Humans; Alopecia Areata; COVID-19; Risk Factors
PubMed: 38198177
DOI: 10.1001/jamadermatol.2023.5559 -
Clinical, Cosmetic and Investigational... 2023Syphilitic alopecia (SA) and alopecia areata (AA) are two distinct conditions that frequently present diagnostic difficulties, especially when differentiating between...
BACKGROUND
Syphilitic alopecia (SA) and alopecia areata (AA) are two distinct conditions that frequently present diagnostic difficulties, especially when differentiating between them due to their similar clinical presentations. Trichoscopy may help in differential diagnosis, but a comparison between trichoscopic features of SA and AA is yet to be researched.
OBJECTIVE
To compare trichoscopic features between SA and AA and determine their discriminative values.
METHODS
Electronic medical records and trichoscopic images of patients diagnosed with SA or AA between January 2000 and February 2022 were retrieved. Trichoscopic features were statistically compared, and their discriminative values were demonstrated as sensitivity, specificity, predictive value, likelihood ratio, and area under the receiver operating characteristic curve (AUC).
RESULTS
A total of 69 patients were included: 23 SA and 46 AA cases were matched with a 1:2 ratio. Black dots, broken hairs, pigtail hairs, exclamation mark hairs, tapered hairs, angulated hairs, and non-pigmented regrowing hairs were significantly more prevalent in AA than in SA (all P<0.05), whereas erythematous background was more prevalent in SA than in AA patients (P=0.008). Among the aforementioned trichoscopic features, exclamation mark hairs and non-pigmented regrowing hairs had a high positive likelihood ratio for AA (16.17 and 8.34, respectively); however, only exclamation mark hairs revealed high AUC (AUC=0.816).
CONCLUSION
Despite the presence of several similar trichoscopic features between SA and AA, trichoscopy can aid in distinguishing between the two diseases. Exclamation mark hairs are the only trichoscopic feature that can be used to differentiate patients with clinically suspicious SA from those with AA.
PubMed: 37608922
DOI: 10.2147/CCID.S424054 -
Therapeutic Delivery Mar 2024Alopecia areata (AA) is a kind of alopecia that affects hair follicles and nails. It typically comes with round patches and is a type of nonscarring hair loss. Various... (Review)
Review
Alopecia areata (AA) is a kind of alopecia that affects hair follicles and nails. It typically comes with round patches and is a type of nonscarring hair loss. Various therapies are accessible for the management and treatment of AA, including topical, systemic and injectable modalities. It is a very complex type of autoimmune disease and is identified as round patches of hair loss and may occur at any age. This review paper highlights the epidemiology, clinical features, pathogenesis and new treatment options for AA, with a specific emphasis on nanoparticulate drug-delivery systems. By exploring these innovative treatment approaches, researchers aim to enhance the effectiveness and targeted delivery of therapeutic agents, ultimately improving outcomes for individuals living with AA.
Topics: Humans; Alopecia Areata; Hair Follicle; Nails; Autoimmune Diseases
PubMed: 38449420
DOI: 10.4155/tde-2023-0071 -
Acta Dermato-venereologica Sep 2023Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and... (Review)
Review
Alopecia areata (AA) is a common cause of hair loss in children. Despite numerous therapeutic options for paediatric AA, none have been found to be both effective and safe. Recent studies have demonstrated the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in adult patients with AA, whereas data on paediatric patients with AA in real-world practice are limited. This was a single-centre, retrospective study that included 11 pre-adolescent patients with AA treated with tofacitinib between December 2021 and September 2022. Clinical characteristics of patients, clinical response and adverse events were evaluated. Overall, 82% (9/11) of patients experienced hair regrowth and 64% (7/11) of patients experienced over 50% improvement in their Severity of Alopecia Tool (SALT) scores. Adverse events were mild. In the literature, tofacitinib has been used to treat AA in 31 children ≤12 years of age who failed to respond to prior treatments. Eighty-seven percent (27/31) of these patients showed significant responses based on changes in their SALT scores. This case series demonstrates that oral tofacitinib is an effective and safe treatment option for paediatric AA, particularly for children who have failed to respond to traditional treatments or are not suitable for such treatments.
Topics: Adult; Humans; Adolescent; Child; Alopecia Areata; Retrospective Studies; Piperidines; Janus Kinase Inhibitors
PubMed: 37731213
DOI: 10.2340/actadv.v103.13418 -
American Journal of Clinical Dermatology Mar 2024The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥... (Clinical Trial)
Clinical Trial
BACKGROUND
The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).
OBJECTIVE
The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.
METHODS
Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.
RESULTS
In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.
CONCLUSIONS
Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).
TRIAL REGISTRIES
ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).
Topics: Humans; Alopecia Areata; Antineoplastic Agents; Carbazoles; Janus Kinase 3; Protein Kinase Inhibitors; SARS-CoV-2; Treatment Outcome; Tryptamines
PubMed: 38263353
DOI: 10.1007/s40257-024-00846-3