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JAMA Dermatology May 2024Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal...
IMPORTANCE
Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, ST3GAL1, and SEMA4B. However, CYP1B1, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A>G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies.
OBJECTIVE
To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in CYP1B1 (c.1358A>G, p.Asn453Ser) on FFA risk.
DESIGN, SETTING, AND PARTICIPANTS
This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023.
MAIN OUTCOME AND MEASURE
The main outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model.
RESULTS
Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34 254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31 177 (91.0%). An association between female FFA and the CYP1B1 risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; P = 8.41 × 10-8) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; P = .39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P = .02).
CONCLUSIONS AND RELEVANCE
This gene-environment interaction analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of CYP1B1 was associated with increased odds of FFA only in participants with OCP history.
PubMed: 38809548
DOI: 10.1001/jamadermatol.2024.1315 -
Archives of Dermatological Research May 2024Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for...
Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active β-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3β and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/β-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.
Topics: Humans; Hair Follicle; Cell Proliferation; Wnt Signaling Pathway; Interferon-gamma; beta Catenin; Alopecia Areata; Cells, Cultured; Glycogen Synthase Kinase 3 beta; Intercellular Signaling Peptides and Proteins; Janus Kinases; Dermis; Phosphorylation; STAT3 Transcription Factor; Hair; Wnt-5a Protein; Janus Kinase 1; Signal Transduction; STAT Transcription Factors
PubMed: 38809465
DOI: 10.1007/s00403-024-02977-3 -
Italian Journal of Dermatology and... Jun 2024Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the...
BACKGROUND
Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA.
METHODS
The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients.
RESULTS
The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life.
CONCLUSIONS
AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.
Topics: Alopecia Areata; Humans; Registries; Italy; Male; Female; Adult; Middle Aged; Adolescent; Young Adult; Child; Quality of Life; Aged; Child, Preschool
PubMed: 38808459
DOI: 10.23736/S2784-8671.24.07934-9 -
Advances in Therapy Jul 2024Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological...
INTRODUCTION
Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel.
METHODS
This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD).
RESULTS
In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated.
CONCLUSION
Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options.
Topics: Humans; Vitiligo; Male; Female; Retrospective Studies; Adult; Israel; Middle Aged; Prevalence; Comorbidity; Incidence; Young Adult; Adolescent; Child; Aged; Child, Preschool
PubMed: 38802636
DOI: 10.1007/s12325-024-02875-0 -
Journal of Cutaneous and Aesthetic... 2024Alopecia areata (AA) is an autoimmune disease characterized most commonly by patchy nonscarring hair loss which may progress to alopecia totalis which has poor...
Alopecia areata (AA) is an autoimmune disease characterized most commonly by patchy nonscarring hair loss which may progress to alopecia totalis which has poor prognosis. Platelet-rich plasma (PRP) therapy along with intralesional triamcinolone acetonide that is modified PRP proved to be beneficial in the case of alopecia totalis and helps in weaning patient off oral immunosuppression.
PubMed: 38800816
DOI: 10.4103/JCAS.JCAS_101_22 -
JAAD International Sep 2024Alopecia areata (AA) and atopic dermatitis (AD) are chronic skin diseases where the suboptimal medication adherence (MA) may result in poor clinical outcomes.
Adult patients with alopecia areata report a significantly better medication adherence compared to those with atopic dermatitis: Results from a large cross-sectional cohort study.
BACKGROUND
Alopecia areata (AA) and atopic dermatitis (AD) are chronic skin diseases where the suboptimal medication adherence (MA) may result in poor clinical outcomes.
OBJECTIVE
To assess the impact of AA on MA among adults compared to AD.
METHODS
Patient reported MA of adults with AA were compared with AD. Patients were identified from the Danish Skin Cohort, a nationwide prospective cohort of dermatological patients in Denmark. We used the Medication Adherence Report Scale- 5, a self-reporting questionnaire, to assess MA. Demographic and disease characteristics were collected. Logistic regression was conducted.
RESULTS
Patients with AA reported higher MA than AD (mean 21.81 vs 18.29). Logistic regression analyses showed AA diagnosis had a statistically significant positive effect on MA (odds ratio = 3.94, 95% CI 2.01-8.89). Men reported significantly higher MA (odds ratio = 1.49, 95% CI 1.14-1.94). Current disease severity did not impact MA.
LIMITATIONS
Data were self-reported by patients. Data regarding the specific treatment undergone by patients were not available.
CONCLUSION
Patients with AA have significantly higher MA compared to patients with AD. The stability of AA patients' symptoms may lead to higher MA due to a desire for disease control. Conversely, the sporadicity of AD symptoms could negatively affect adherence, causing fluctuations in medication use.
PubMed: 38800704
DOI: 10.1016/j.jdin.2024.03.026 -
Archives of Dermatological Research May 2024Although there are now two Food and Drug Administration (FDA)-approved treatments for severe alopecia areata (AA), many patients still resort to non-medical therapies...
Although there are now two Food and Drug Administration (FDA)-approved treatments for severe alopecia areata (AA), many patients still resort to non-medical therapies and lifestyle modifications such as diet and nutrition. The goal of this study was to evaluate the sources and types of dietary and nutritional advice for patients with AA. We distributed a cross-sectional national survey using the National Alopecia Areata Foundation's email list-serv between August 2022 and January 2023. Most respondents were White (76.3%), employed (58.3%) females (84.4%) with a mean age of 52 years. 163 (19.1%) respondents reported receiving diet and/or nutritional advice and 418 (49.5%) respondents reported searching for diet and/or nutritional advice to help with their AA; the most common source of advice was online. The most common dietary changes were the use of vitamins or supplements (30.6%), adherence to diets (23.2%), and the addition of specific foods (21.4%). 209 (50.2%) respondents reported no change in their disease and 197 (47.4%) respondents reported no change in how they felt about their disease compared to before they tried the change. Many AA patients search for or receive unsolicited dietary and nutritional advice and subsequently modify their behavior to manage their disease. However, the efficacy of these changes is unclear. Providers should be mindful of the sources through which patients obtain treatment information as well as the lifestyle changes patients make to counsel patients with evidence-based information. Further investigation is needed to better characterize the direct and indirect costs of dietary and nutritional modification in the treatment of AA.
Topics: Humans; Alopecia Areata; Female; Male; Middle Aged; Cross-Sectional Studies; Adult; Dietary Supplements; Young Adult; Aged; Diet; Surveys and Questionnaires; Vitamins; Patient Education as Topic; United States
PubMed: 38796551
DOI: 10.1007/s00403-024-02940-2 -
Archives of Dermatological Research May 2024Biologics and Janus kinase (JAK) inhibitors are immunomodulating and immunosuppressing medications utilized to treat atopic dermatitis (AD), psoriasis (PSO), psoriatic...
Biologics and Janus kinase (JAK) inhibitors are immunomodulating and immunosuppressing medications utilized to treat atopic dermatitis (AD), psoriasis (PSO), psoriatic arthritis (PsA), and alopecia areata (AA). Special recommendations must be considered when prescribing vaccinations in this population, as the pneumococcal and herpes zoster vaccine are recommended to patients ≥ 19-years-old (rather than ≥ 65-years-old and ≥ 50-years-old as in the general population, respectively), along with a yearly influenza and up to date COVID-19 vaccination. Additionally, TNF-α and JAK-inhibitors may increase the risk of latent Hepatitis B virus (HBV) reactivation among high-risk patients. Prior to prescribing these medications, a quantitative HepB Surface Antibody (HepB SA) test is performed to determine immunity. This study utilized the SlicerDicer function on EPIC Medical Records to search for any patient ≥ 19-years-old prescribed a biologic or JAK inhibitor for AD, PSO, PsA, or AA between 10/2003 and 10/2023 at a large tertiary institution. Vaccination rates among patients on biologics and JAK inhibitors were low, with rates being significantly lower in patients 19-64 years-old, compared to those ≥ 65 years-old for most disease states (p < 0.01). Among AD, PSO/PsA, and AA patients, on average, 9.39% were vaccinated for influenza, 6.76% for herpes zoster, 16.56% for pneumococcal pneumonia, and 63.98% for COVID-19. Only 3.16% of patients were adequately vaccinated for HepB after an abnormal HepB SA test. Here, extremely low rates of vaccination among patients on biologics and JAK inhibitors at our institution were highlighted, emphasizing the imperative need for ensuring vaccination in this group.
Topics: Humans; Middle Aged; Dermatitis, Atopic; Male; Adult; Female; Alopecia Areata; Biological Products; Aged; Young Adult; Arthritis, Psoriatic; Vaccination; Janus Kinase Inhibitors; Psoriasis; COVID-19; Retrospective Studies; SARS-CoV-2
PubMed: 38796548
DOI: 10.1007/s00403-024-03037-6 -
Journal of the American Academy of... May 2024
Review
PubMed: 38796079
DOI: 10.1016/j.jaad.2024.05.037 -
Archives of Dermatological Research May 2024In the field of alopecia areata research, various focuses including risk factors, epidemiology, molecular pathways, and treatment were constantly improving. However, to...
In the field of alopecia areata research, various focuses including risk factors, epidemiology, molecular pathways, and treatment were constantly improving. However, to date, a bibliometric analysis summarizing the research trend is not available to date. The main objective of this study was to provide researchers with an overview of the research trend on alopecia areata in the past two decades. In Web of Science database, screening and extraction of studies related to alopecia areata has been performed. Within studies related to alopecia areata, the most cited 100 studies were appraised and the information of articles, including the citation amounts, keywords and publication types, was extracted for analyses. On average, each study in the top 100 list was cited 104.72 times. Within the top 100 list, the most focused fields were on the management of alopecia areata (34%), molecular mechanisms (28%) and epidemiological issues (23%). Approximately one third of the management-associated studies focused on Janus kinase (JAK) inhibitors (10 studies) and 5 studies focused on the efficacy of corticosteroids for alopecia areata. According to the results of the keyword analysis, JAK inhibitors had become the most mentioned keywords in the field of alopecia areata research since 2016. The top 100 most referenced papers in the field of alopecia areata mostly focused on essential aspects such as treatment options, pathogenesis, risk factors, and comorbidities. The results of the current study could be considered a potential resource for future research and patient care information.
Topics: Alopecia Areata; Humans; Bibliometrics; Cross-Sectional Studies; Janus Kinase Inhibitors; Adrenal Cortex Hormones; Biomedical Research
PubMed: 38795240
DOI: 10.1007/s00403-024-03092-z