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Hypotrichosis 12 (HYPT12) is a form of autosomal dominant nonsyndromic hypotrichosis previously linked to a pathogenic missense variant in the I RPL21 i gene. A 44-year-old White British man presented with hair loss affecting the scalp, eyebrows, eyelashes and body (Figure 1a). [Extracted from the article]

Introduction/Background The oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and safety in patients aged ≥12 years with alopecia areata (AA) with ≥50% hair loss in the ALLEGRO phase 2b/3 study. ALLEGRO-LT is an ongoing phase 3 open-label study investigating the long-term safety and efficacy of ritlecitinib in patients aged ≥12 years with AA with ≥25% hair loss. Objectives This post hoc analysis of ALLEGRO-LT evaluated the efficacy of ritlecitinib through Month 15 in patients with AA by the extent of scalp hair loss at baseline. Methods The open-label, multicenter, long-term ALLEGRO-LT study (NCT04006457) enrolled patients into two arms: (1) roll-over patients who had received study intervention in either the ALLEGRO phase 2a study (NCT02974868) or phase 2b/3 study (NCT03732807), and (2) de novo patients who were aged ≥12 years with AA with ≥25% scalp hair loss at baseline and had not participated in either study. This post hoc analysis only included patients in the de novo cohort. All patients received an initial 4-week loading dose of ritlecitinib 200 mg once-daily (QD) followed by ritlecitinib 50 mg QD. Outcomes included median Severity of Alopecia Tool (SALT) score over time and the proportions of patients with SALT score ≤20 (≤20% scalp hair loss) and ≤10 at Month 15. Patients were stratified by extent of scalp hair loss at baseline (measured by SALT score) as follows: 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100. Analyses were based on observed data. Results 1052 patients were enrolled in ALLEGRO-LT, of whom 447 patients received ritlecitinib in the de novo arm. Of the 447 de novo patients, 26.6% (n=119), 16.8% (n=75), 9.2% (n=41), 2.9% (n=13), and 44.5% (n=199) had baseline SALT scores 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100, respectively. Patients with baseline SALT score ≥95 generally had longer mean duration of AA episode (3.47 years) and disease duration (10.86 years) than patients with SALT score <50 at baseline (2.53 and 8.79 years, respectively). A greater proportion of patients with baseline SALT score <50 had active shedding at baseline (49.6%) vs patients with baseline SALT score ≥95 (11.6%). Across all groups, median SALT scores improved (decreased) from baseline through Month 15. At Month 15, median SALT scores were 1.0, 1.2, 1.4, 2.4, and 30.9 for the 25 to <50, 50 to <75, 75 to <90, 90 to <95, and 95 to 100 groups, respectively. At Month 15, 93.0% (93/100), 87.7% (57/65), 88.2% (30/34), 83.3% (10/12), and 43.9% (68/155) of patients, respectively, achieved SALT scores ≤20, and 81.0% (81/100), 76.9% (50/65), 73.5% (25/34), 75.0% (9/12), and 33.5% (52/155) of patients, respectively, achieved SALT score ≤10. Conclusions After 15 months of ritlecitinib treatment, patients with less than 95% hair loss at baseline reached median SALT scores of <2.4, reflecting almost complete scalp hair regrowth. More refractory disease was seen in the subset of patients with extensive (≥95%) hair loss at baseline; however, over one third of these patients achieved clinically meaningful SALT response (SALT ≤20 and SALT ≤10) at Month 15. Overall, ritlecitinib was efficacious in patients with AA with ≥25% hair loss including those with extensive hair loss at baseline. [ABSTRACT FROM AUTHOR]

Her scalp hair density and thickness were normal at birth, but she developed progressively finer hair with an inability to grow scalp hair beyond a certain length from the age of 8 years (Figure 1a, b). Physical examination demonstrated short, fine scalp hair with no hair shaft defects on trichoscopy. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is a common cause of nonscarring hair loss that can have a profound psychological impact. Objectives: To assess the co‐occurrence of depression and anxiety in adults with AA compared with the general population, and to evaluate the mental health treatment burden and impact on time off work and unemployment. Methods: In total, 5435 people with newly diagnosed AA in UK primary care were identified from the Oxford Royal College of General Practitioners Research and Surveillance Centre network database, and matched to 21 740 controls. In cases and controls, we compared the prevalence and incidence of depressive episodes, recurrent depressive disorder and anxiety disorder, 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. This observational was registered with ClinicalTrials.gov (NCT04239521). Results: Depression and anxiety were more prevalent in people diagnosed with AA than in controls (P < 0·001). People with AA were also more likely to subsequently develop new‐onset depression and anxiety: adjusted hazard ratio (aHR) for recurrent depressive disorder 1·38 [95% confidence interval (CI) 1·13–1·69], depressive episodes aHR 1·30 (95% CI 1·04–1·62) and anxiety disorder aHR 1·33 (95% CI 1·09–1·63); to be issued time off work certificates (aHR 1·56, 95% CI 1·43–1·71); and to 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. Conclusions: 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 programmes are needed for people with AA. [ABSTRACT FROM AUTHOR]

(b) Histopathology of horizontal sections of the scalp and hair follicle isthmus showing follicular units with partial reduction of sebaceous glands, perifollicular fibrosis and a mild perifollicular lymphoid cell infiltrate. Lichen planopilaris (LPP), or follicular lichen planus (LP), is a primary lymphocytic cicatricial alopecia, which may present as classic (multifocal) LPP, frontal fibrosing alopecia, the somewhat archaic Graham-Little-Piccardi-Lassueur syndrome, or the recently described fibrosing alopecia in a pattern distribution.[1],[2] Genetic susceptibility,[3] immune privilege collapse[4] and immune dysregulation are thought to promote T-cell mediated destruction of the hair follicle in LPP. (d) Vertical sections of the vertically oriented scalp biopsy disclosing interfollicular epidermal atrophy with vacuolar-interface change and a mild papillary dermal lichenoid lymphoid cell infiltrate, consistent with lichen planopilaris. [Extracted from the article]