British Journal of Dermatology最新文献

Background: Hidradenitis suppurativa (HS) has been associated with increased risk of psychiatric disease (PD) in patients with HS compared with the general population. To our knowledge, no recent comprehensive examination of the prevalence and association between HS and PD has been undertaken.

Objectives: To investigate the association between HS and PD.

Methods: A systematic review and meta-analysis was performed using standard methodologies and was reported in accordance with the PRISMA guidelines. The medical databases PubMed, Embase, PsycINFO, Cochrane, Web of Science and the Directory of Open Access Journals were searched. Studies were included if addressing HS and any PD. Study quality was assessed through the Newcastle-Ottawa Scale (NOS). Certainty of evidence was assessed using the GRADE approach.

Results: A total of 83 studies were included in the narrative analysis of which 76 were included in the quantitative analysis. This study found that patients with HS had higher risk of depression, pooled prevalence 20.9% vs. 8.4%, odds ratio (OR) 2.06 [95% confidence interval (CI) 1.75-2.41], P < 0.001; anxiety, 19.3% vs. 8.1%, OR 1.91 (95% CI 1.64-2.22), P < 0.001; bipolar disorder, 1.0% vs. 0.06%, OR 3.68 (95% CI 1.11-12.20), P = 0.03; schizophrenia, 2.7% vs. 1.2%, OR 2.00 (95% CI 1.21-3.30), P = 0.007; substance use disorder 6.0% vs. 3.1%, OR 3.58 (95% CI 2.01-6.37), P < 0.001; alcohol abuse 4.0% vs. 1.8%, OR 1.88 (95% CI 0.98-3.58), P = 0.06, and completed suicide 0.7% vs. 0.4%, OR 1.56 (95% CI 1.14-2.14), P = 0.005 when compared with the general population. PD was more prevalent in female patients with HS (28.0%, 95% CI 22.5-34.3) compared with males (21.1%, 95% CI 15.6-27.9). Depression increased with increasing Hurley stage [stage I, 19.5% (95% CI 8.3-39.4); stage II, 20.9% (95% CI 11.5-34.9) and stage III, 35.3% (95% CI 16.1-60.8), P < 0.001]. North American studies had higher pooled prevalence of PD compared with European studies [35.4% (95% CI 13.6-65.6) vs. 21.2% (95% CI 11.9-34.7)]. Adults had higher pooled prevalence of depression compared with children [19.1% (95% CI 12.4-28.3) vs. 9.5% (95% CI 6.3-14.1)]. Half of included studies were assessed as high quality (NOS ≥ 7).

Conclusions: This study found a significantly higher risk of several PDs in patients with HS compared with the general population. Our findings reflect a need to raise awareness of psychiatric illnesses in patients with HS to improve patients' quality of life.

Background: Eyebrow and eyelash (EB/EL) involvement is an important consideration in the assessment of alopecia areata (AA) severity.

Objectives: To report on the integrated results from BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259), characterizing EB/EL involvement at baseline in patients with AA and response to baricitinib treatment.

Methods: BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) were randomized double-blind placebo-controlled trials conducted at 169 centres in 10 countries. Patients were randomized to placebo, baricitinib 2 mg or baricitinib 4 mg. Pooled data from patients continually treated with baricitinib through week 52 were included. Outcomes were assessed using a clinician-reported outcome (ClinRO) measure for EB/EL and Severity of Alopecia Tool (SALT) score for the scalp.

Results: At baseline, patients with more severe EB/EL involvement had more severe scalp hair loss, with mean SALT scores ranging from 70.6 to 96.0 for patients with no gaps to complete absence of hair, respectively, at EB/EL sites. EB/EL response rates [ClinRO (0,1) with ≥ 1-point improvement] at week 36 were significantly higher in patients treated with baricitinib 2 mg [EB: 28.2%, odds ratio (OR) 3.27; EL: 25.1%, OR 2.95] and baricitinib 4 mg (EB: 44.3%, OR 6.84; EL: 46.4%, OR 8.21) compared with placebo (EB: 12.6%; EL: 12.4%). There was high concordance between EB response and EL response, with approximately 80% of patients who achieved hair regrowth at one site achieving regrowth at the other, with baricitinib 4 mg. Among scalp responders (SALT score ≤ 20 at week 52), 78.5% (n = 95/121) and 82.6% (n = 100/121) achieved an EB and EL response, respectively, and 71.1% (n = 86/121) of patients achieved EB and EL responses with baricitinib 4 mg. Among scalp nonresponders (SALT score > 20 at week 52), 46.7% (n = 91/195) and 48.7% (n = 95/195) achieved EB and EL responses, respectively, and 35.4% (n = 69/195) achieved responses in both EB and EL. Similar trends but lower response rates were observed with baricitinib 2 mg.

Conclusions: Baseline severity of EB/EL involvement paralleled that of the scalp. Baricitinib was efficacious in achieving a holistic response across all three hair-bearing sites in the majority of week-52 scalp responders. These data detail the benefits of baricitinib across important hair-bearing sites involved in AA and highlight that individual patient treatment success should account for the totality of the clinical presentation.

Background: Keloids are severe dermal fibrotic disorders caused by excessive deposition of collagen. Current therapies have high recurrence rates, and there is a clinical need for a new, fundamental approach. We focused on inhibiting proline, an essential amino acid for collagen biosynthesis. We developed DWN12088, a drug that downregulates prolyl-tRNA synthetase (PRS), an enzyme involved in proline ligation.

Objectives: To investigate the antifibrotic activity of selective PRS inhibitors and elucidate the importance of DWN12088 as a first-in-class therapeutic agent for keloids.

Methods: Patient-derived keloid fibroblasts (KFs) and keloid tissues were obtained to observe PRS upregulation. In addition, the antifibrotic activity of selective PRS inhibitors was studied using KFs, and their treatment efficacy further validated in vivo using a KF xenograft severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemistry analyses were performed with human-derived keloid tissues. Additional experiments included immunocytochemistry, cell viability analysis, migration analysis and Western blotting of KFs. Human KFs were injected into SCID mice to study nodule formation and histological characteristics.

Results: Compared with normal fibroblasts and healthy skin tissues, PRS was overexpressed in KFs and keloid tissues. A selective PRS inhibitor downregulated fibrotic markers, reduced migration capacity and lowered collagen production in KFs. In a KF xenograft SCID mouse model, a selective PRS inhibitor effectively suppressed keloid formation and mitigated inflammation and fibrosis.

Conclusions: DWN12088, a selective PRS inhibitor, may be a novel first-in-class treatment modality that effectively prevents keloid development. Further clinical trials are required to verify the safety and clinical efficacy of PRS inhibitors for keloids. We believe that our study has applicability across several fibrotic wound problems such as hypertrophic scars.

Background: Hormone therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies.

Objectives: To investigate the association between HT and the risk of psoriasis in reproductive-age and postmenopausal women.

Methods: This study utilized both nationwide cohort design and target trial emulation, analysing data from Taiwan's National Health Insurance Database (2001-2021). Women over 20 years old without a prior history of psoriasis, ovarian cancer or breast cancer were included, and categorized into reproductive-age (≤ 50 years) and postmenopausal (> 50 years) groups. Women who initiated HT were assigned as the exposed group, while women without HT formed the comparison group. The primary outcome was the incidence of psoriasis over a 5-year period. The study applied inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to enhance the robustness of the findings.

Results: In the postmenopausal cohort, comprising 1 482 302 HT users and 1 313 799 nonusers, the IPTW-adjusted HR for psoriasis in the ITT analysis was 1.48 [95% confidence interval (CI) 1.44-1.52]. The PP analysis indicated a more pronounced risk, with an HR of 5.93 (95% CI 5.66-6.22). Among the reproductive-age cohort, which included 3 849 721 HT users and 1 585 461 nonusers, the IPTW-adjusted HR in the ITT analysis was 1.93 (95% CI 1.90-1.99). In the PP analysis, the risk increased, showing an HR of 7.85 (95% CI 7.56-8.15). These findings highlight the significantly elevated psoriasis risk associated with HT, especially in younger women.

Conclusions: This study establishes an association between HT and an increased risk of psoriasis in both reproductive-age and postmenopausal women using a nationwide cohort design and target trial emulation. These findings further highlight the potential influence of hormonal factors on psoriasis development. Clinicians should remain attentive to early signs of psoriasis in women receiving HT to ensure timely recognition and management.