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BackgroundThe 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).ObjectiveThe objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.MethodsTwo 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.ResultsIn 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.ConclusionsRitlecitinib 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 registriesClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).

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]

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]

Solar urticaria is a rare, immunologically mediated photodermatosis in which activation of cutaneous mast cells is triggered by specific wavelengths of solar electromagnetic radiation. This manifests clinically as the rapid development of cutaneous itch, erythema and wheal formation after several minutes of sun exposure. Disease mechanisms in solar urticaria remain incompletely elucidated and there have been few recent investigations of its pathobiology. Historic passive transfer experiments performed during the twentieth century provide support for a 'photoallergy' model of disease pathogenesis, wherein molecular alteration of a putative chromophore by solar electromagnetic radiation produces mast cell activation via an IgE‐dependent mechanism. However, this model does not account for several observations made during passive transfer experiments nor does it explain a range of subsequent clinical and photobiological observations made in solar urticaria patients. Furthermore, increased understanding of the molecular dynamics underpinning cutaneous mast cell responses highlights the need to reformulate our understanding of solar urticaria pathogenesis in the context of this contemporary scientific landscape. In this review, we discuss the current understanding of solar urticaria pathogenesis and, by incorporating recent scientific and clinical observations, develop new hypotheses to drive future investigation into this intriguing disorder. [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]

Nevertheless, major insights into key genetic determinants of contact allergy might be gained by examining those who demonstrate increased risk of contact allergy, irrespective of allergen structure or class. Bryld et al4 also examined nickel contact allergy among 630 Danish female twin pairs, demonstrating a slightly increased odds of nickel contact allergy (adjusted odds ratio 1.28, 95% confidence interval 0.33-5.00) in monozygotic compared with dizygotic twin pairs. Contact allergy occurs due to cutaneous interaction with environmental allergens that result in T-cell-mediated inflammation.1 Exposures to allergens could, therefore, be presumed to be the sole determinant of contact allergy. [Extracted from the article]

Keywords: benzyl salicylate; contact allergy; frontal fibrosing alopecia; patch test EN benzyl salicylate contact allergy frontal fibrosing alopecia patch test 483 484 2 09/21/21 20211001 NES 211001 Pastor-Nieto et al1 report a case series of 36 patients with frontal fibrosing alopecia (FFA) who have undergone patch testing. Subsequently, Pastor-Nieto et al1 propose several hypotheses to account for their observed association between benzyl salicylate sensitivity and FFA, notably suggesting that benzyl salicylate could be a sole or significant factor in FFA pathogenesis. [Extracted from the article]

Background: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden., Objectives: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilisation and work-related outcomes, assessing variation across major sociodemographic subgroups., Methods: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation, and geography. Mental health, healthcare utilisation and work-related outcomes were assessed in the two years after AA diagnosis compared to matched unaffected controls, and stratified by the same sociodemographic subgroups ., Results: 6,961 people developed AA during the study period. Overall lifetime incidence of AA was 2.11% (95% Confidence Interval [CI] 2.06, 2.16%). Females had a higher lifetime incidence 2.35% (95%CI 2.28, 2.43%) than males 1.88% (95%CI 1.81, 1.94%). Lifetime incidence was higher in those of Asian ethnicity 5.87% (95%CI 5.51, 6.24), other 4.47% (95%CI 3.63, 5.31), mixed 4.44% (95%CI 3.50, 5.37) and black 3.03% (95%CI 2.63, 3.42) ethnicity, compared to white ethnicity 1.74% (95%CI 1.68, 1.80). Lifetime incidence was highest in those with the greatest deprivation; most-deprived quintile 2.92% (95%CI 2.77, 3.07%) compared to least-deprived 1.68% (95%CI 1.59, 1.78%). Across sociodemographic subgroups, people with AA of black ethnicity were most likely to have anxiety (adjusted Odds Ratio versus matched controls 2.92, 95%CI 1.71, 4.91), and had the greatest risk of time off work (adjusted Hazard Ratio versus matched controls 2.54, 95%CI 1.80, 3.56)., Conclusions: AA affects around 1 in 50 people over their lifetime. Incidence and the impact of AA on mental health and work outcomes, is highest in ethnic groups other than white. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences.The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (Identifier: NCT05727306)., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)