Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02

Diagnosis of Induced Resistance State in Tomato Using Artificial Neural Network Models Based on Supervised Self-Organizing Maps and Fluorescence Kinetics

The aim of this study was to develop three supervised self-organizing map (SOM) models for the automatic recognition of a systemic resistance state in plants after application of a resistance inducer. The pathosystem Fusarium oxysporum f. sp. radicis-lycopersici (FORL) + tomato was used. The inorganic, defense inducer, Acibenzolar-S-methyl (benzo-[1,2,3]-thiadiazole-7-carbothioic acid-S-methyl ester, ASM), reported to induce expression of defense genes in tomato, was applied to activate the defense mechanisms in the plant. A handheld fluorometer, FluorPen FP 100-MAX-LM by SCI, was used to assess the fluorescence kinetics response of the induced resistance in tomato plants. To achieve recognition of resistance induction, three models of supervised SOMs, namely SKN, XY-F, and CPANN, were used to classify fluorescence kinetics data, in order to determine the induced resistance condition in tomato plants. To achieve this, a parameterization of fluorescence kinetics curves was developed corresponding to fluorometer variables of the Kautsky Curves. SKN was the best supervised SOM, achieving 97.22% to 100% accuracy. Gene expression data were used to confirm the accuracy of the supervised SOMs. © 2022 by the authors

Alopecia areata and risk of common infections:a population-based cohort study

Background. It is not known whether alopecia areata (AA) is associated with a greater or reduced risk for infection. Aim. We undertook a population-based study exploring associations between AA and common infections. Methods. We extracted primary care records from the UK Oxford-Royal College of General Practitioners Research and Surveillance Centre database (trial registration: NCT04239521). The incidence of common and viral infection composite outcomes, and individual respiratory, gastrointestinal (GI), skin, urinary tract, genital and herpes infections, were compared in people with AA (AA group, n=10 391) and a propensity-matched control group (n=41 564). Adjusted hazard ratios (aHRs), controlling for sociodemographic and clinical covariates, and comorbidities were used to estimate the association between AA and each infection over 5 years. Results. The incidence (per 100 person-years) of common infections was slightly higher in the AA group [14.2, 95% confidence interval (CI) 13.8–14.6] than the control group (11.7, 95% CI 11.5–11.9). In adjusted analysis, positive associations were observed for composite outcomes (common infections aHR 1.13, 95% CI 1.09–1.17; viral infections aHR 1.11, 95% CI 1.07–1.16) and with respiratory tract, GI, skin and herpes simplex infections (aHR range 1.09–1.32). Excluding people in the control group without a recent consultation with their general practitioner showed no association between AA and infection (common infections aHR 1.01, 95% CI 0.98–1.05, viral infections aHR 0.99, 95% CI 0.95–1.03). Conclusions. The association between AA and common infection may represent a higher propensity of people with AA to engage with healthcare services (and thereby to have infections recorded), rather than a true association between AA and infection. Overall our findings suggest that AA is not associated with a clinically significantly increased or decreased incidence of common infections.</p

Alopecia areata and risk of atopic and autoimmune conditions:population-based cohort study

Background. Alopecia areata (AA) has features of both autoimmune and atopic pathogenesis, but information on the risk of people with AA developing autoimmune and atopic conditions is limited. Objective. To assess the prevalence and incidence of atopic and autoimmune conditions in people with AA. Methods. This was a population-based cohort study of 8051 adults with newly diagnosed AA (AA group) and 32 204 adults in the matched control group, using the UK Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network primary care database, 2009–2018 (trial registration number: NCT04239521). Baseline prevalence of common atopic and autoimmune conditions, and risk of new-onset atopic and autoimmune disease, were estimated. Results. Atopic and autoimmune conditions were more prevalent in the AA group than the control group (atopic 37.2% vs. 26.7%, autoimmune 11.5% vs. 7.9%). The AA group were 43% more likely to develop any new-onset atopic condition [adjusted hazard ratio (aHR) 1.43. 95% confidence interval (CI) 1.28–1.61] and 45% more likely to develop any autoimmune condition (aHR 1.45, 95% CI 1.28–1.66) compared with the control group. When examining individual conditions, the AA group were at increased risk of atopic dermatitis (aHR 1.91, 95% CI 1.67–2.19), allergic rhinitis (aHR 1.32, 95% CI 1.14–1.54), autoimmune hypothyroidism (aHR 1.65, 95% CI 1.35–2.02), systemic lupus erythematosus (aHR 4.51, 95% CI 1.88–10.82) and vitiligo (aHR 2.39, 95% CI 1.49–3.82). There was no evidence for a higher incidence of other conditions examined. Conclusion. People with AA have an increased burden of atopic and autoimmune comorbidity. This supports previous work suggesting that both T helper cell (Th)1 and Th2 immune responses may be implicated in the pathogenesis of AA.</p

The associated burden of mental health conditions in alopecia areata:a population-based study in UK primary care

Background Alopecia areata (AA) is a common cause of non-scarring hair loss that can have a profound psychological impact. Objective To assess the co-occurrence of depression and anxiety in adults with AA compared to the general population, and evaluate the mental health treatment burden and impact on time-off work and unemployment. Methods 5,435 people with newly-diagnosed AA in UK primary care were identified from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, and matched to 21,740 controls. In cases and controls, we compared prevalence and incidence of depressive episodes (DE), recurrent depressive disorder (RDD) and anxiety disorder (AD), rates of time off work and unemployment, and, in those with pre-existing mental health conditions, rates of mental health related prescribing and referral rates. Results Depression and anxiety were more prevalent in people diagnosed with AA compared to controls (p<0.001). People with AA were also more likely to subsequently develop new onset depression and anxiety (adjusted hazard ratio [aHR] DE 1.38 [95%CI 1.13-1.69], RDD aHR 1.30 [95%CI 1.04-1.62], AD aHR 1.33 [95%CI 1.09-1.63]), be issued time-off work certificates (aHR 1.56, 95%CI 1.43-1.71), and be recorded as unemployed (aHR 1.82, 95%CI 1.33-2.49). Higher rates of antidepressant prescribing were also seen in people with AA. Conclusion People with AA have higher rates of depression and anxiety than those without AA. This impacts deleteriously on mental health treatment burden, time-off work, and unemployment. Evidence-based mental health treatment programs are needed for people with AA

The epidemiology of alopecia areata:a population-based cohort study in UK primary care

BACKGROUND: There is a lack of population‐based information on the disease burden and management of alopecia areata (AA). OBJECTIVES: To describe the epidemiology of AA, focusing on incidence, demographics and patterns of healthcare utilization. METHODS: Population‐based cohort study of 4·16 million adults and children, using UK electronic primary care records from the Oxford‐Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, 2009–2018. The incidence and point prevalence of AA were estimated. Variation in AA incidence by age, sex, deprivation, geographical distribution and ethnicity was examined. Patterns of healthcare utilization were evaluated in people with incident AA. RESULTS: The AA incidence rate was 0·26 per 1000 person‐years. AA point prevalence in 2018 was 0·58% in adults. AA onset peaked at age 25–29 years for both sexes, although the peak was broader in females. People of nonwhite ethnicity were more likely to present with AA, especially those of Asian ethnicity [incidence rate ratio (IRR) 3·32 (95% confidence interval 3·11–3·55)]. Higher AA incidence was associated with social deprivation [IRR most vs. least deprived quintile 1·47 (1·37–1·59)] and urban living [IRR 1·23 (1·14–1·32)]. People of higher social deprivation were less likely to be referred for specialist dermatology review. CONCLUSIONS: By providing the first large‐scale estimates of the incidence and point prevalence of AA, our study helps to understand the burden of AA on the population. Understanding the variation in AA onset between different population groups may give insight into the pathogenesis of AA and its management