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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).

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]

(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]

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]