British Journal of Dermatology最新文献

Background: Atopic dermatitis (AD) is an inflammatory skin disorder that is common in children and associated with medical and psychosocial comorbidities. Previous studies have shown that there are significant racial disparities in healthcare utilization in children with AD; however, the literature on disparities in dermatology access is limited.

Objectives: To identify differences in the diagnosis of AD and access to dermatological care by race and ethnicity in infants with AD.

Methods: We conducted a retrospective chart review of infants diagnosed with AD at Boston Children's Hospital from 1 January 2015 to 31 December 2019. Race and ethnicity were categorized as per the US Office of Minority Health data collection standards as Native American or Alaska Native; Asian; non-Hispanic Black or African American; Hispanic or Latino; Native Hawaiian or Other Pacific Islander; non-Hispanic White; and a final group which we called 'Other' (this encompassed all individuals who did not identify with the other groups listed). Outcomes included time to diagnosis and dermatology visit from rash onset, and were analysed utilizing a Kruskal-Wallis test. Severity of presentation at first dermatology visit, presentation to the emergency department (ED), medications prescribed and follow-up were analysed using χ 2 tests.

Results: Significantly more non-Hispanic White infants received a prescription from their paediatrician for AD than Hispanic infants (P = 0.002). Non-Hispanic Black and Asian infants waited significantly longer to see a dermatologist after receiving a prescription for AD from their paediatrician (P < 0.001) compared with non-Hispanic White patients (P = 0.007). Significantly more non-Hispanic Black and Hispanic infants presented to the ED for AD within the first year of life (P < 0.001) than non-Hispanic White patients (P = 0.003).

Conclusions: Our study suggests disparities in diagnosis and access to care for non-Hispanic Black and Hispanic infants with AD, with differences in prescriptions, time to see a dermatologist and presentation to the ED vs. non-Hispanic White infants.

Background: Therapeutic options for mild hidradenitis suppurativa (HS) represent a significant gap in the current treatment landscape, with no FDA approved therapies for early stage HS. Topical JAnus Kinase inhibitors (JAKi) are a compelling option due to the known upregulation of inflammatory JAK signaling in HS lesions and the recent success of systemic JAKi for moderate to severe HS.

Objectives: This is a pilot, single-site, open-label, prospective 24-week clinical trial with topical ruxolitinib (NCT04414514). The goals of this study were to assess clinical efficacy in a pilot cohort and investigate the underlying biological mechanisms associated with clinical response.

Methods: Male and female patients with mild HS (Hurley stage I or II), with active inflammatory nodules, were recruited. All subjects were observed for 8 weeks to monitor lesion counts (observational phase), then proceeded with active therapy (treatment phase) for 16 weeks. 1.5% topical ruxolitinib cream was applied twice daily, covering the entirety of each HS-affected body site. Clinician and patient reported outcome measures were recorded throughout the study. Lesional skin punch biopsies were obtained at the start and end of therapy for downstream mechanistic RNA-seq and histological analyses.

Results: Ten subjects enrolled in this study, four subjects dropped out of the study before the treatment phase of the trial. Six individuals with Hurley stage I (no tunnels) completed the entire study, with five of six successfully achieving HiSCR through 16 weeks of therapy. In this interim analysis, differential gene expression and gene set enrichment analyses revealed reduced activation of JAK-dependent IFN, IL-6, IL-2, and EGFR signaling, antimicrobial responses, and keratinocyte responses. In contrast, signatures of wound healing and lipid metabolism were increased following JAKi treatment, indicating a return toward homeostasis. Histological analyses revealed that clinically-responsive patients had significantly reduced epidermal and dermal inflammation. Affected inflammatory infiltrate included neutrophils, T cells, and plasma cells, with the predominantly affected cell types specific to the patient.

Conclusions: Collectively, the broad activity of topical ruxolitinib on inflammatory signaling processes resulted in promising efficacy, even with heterogeneity in baseline inflammation, in this pilot cohort. Importantly, topical treatment not only resolved epidermal inflammation, but also cleared deeper inflammatory infiltrate. The efficacy observed in this trial provides rationale to further investigate topical JAKi and other novel topical therapies in HS.

Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.

Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.

Methods: This phase 3, randomized, placebo-controlled study enrolled patients ≥6 to <18 years of age with moderate-to-severe plaque psoriasis. In Part 1 (Week [W]0-W16), patients were randomized to receive guselkumab, placebo, or open-label etanercept (active reference arm). At W16, Part 1 patients entered a guselkumab withdrawal/retreatment period or continued/crossed over to receive guselkumab (W16-W52). Co-primary endpoints were Investigator's Global Assessment (IGA) 0/1 and Psoriasis Area and Severity Index (PASI)75 (or United States Food and Drug Administration-required PASI90 co-primary endpoint) responses at W16 of Part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0-W52).

Results: Of 92 and 28 patients enrolled in Parts 1 and 2, respectively, 86% and 96% continued treatment through W52. In Part 1, at W16, significantly higher proportions of guselkumab-treated than placebo-treated patients achieved IGA 0/1 (66% vs 16%; P<0.001), PASI75 (76% vs 20%; P<0.001), and PASI90 (56% vs 16%; P<0.01). More than one-third of guselkumab-treated patients achieved clear skin (IGA 0: 39% vs 4% placebo; PASI100: 34% vs 0% placebo; both P<0.01). In Part 2, at W52, 86%, 93%, and 82% of guselkumab-treated patients achieved IGA 0/1, PASI75, and PASI90, respectively. Through W16 of Part 1, 42%, 68%, and 58% of guselkumab-, placebo-, and etanercept-treated patients, respectively, had adverse events (AEs). Rates of AEs with guselkumab were similar through W52 in Parts 1 and 2; common AEs included nasopharyngitis, upper respiratory tract infection, and COVID-19. No serious or opportunistic infections occurred.

Conclusions: Guselkumab demonstrated significant and clinically meaningful responses in pediatric patients with moderate-to-severe plaque psoriasis and all co-primary and major secondary endpoints were met. Guselkumab safety outcomes were similar to placebo; no new safety signals were identified. These findings support the use of guselkumab to treat pediatric patients with moderate-to-severe plaque psoriasis.