British Journal of Dermatology最新文献

In 2019, a group of experts published the first European guidelines for the management of congenital ichthyoses after a multidisciplinary expert meeting held in 2016. An update of these guidelines and literature search was planned every 5 years, given the clinical, molecular and therapeutic advances, including the use of biologic therapies. We present here updated guidelines that have been developed by a reorganized multidisciplinary group of international experts after systematic review of recent literature, discussions, and consensus reached at an expert conference held in June 2023. The guidelines provide summarized evidence and expert-based recommendations that aim to guide clinicians in the management of these rare and often complex diseases. These guidelines consist of two sections. This Part II covers the management of complications (eye, Ear-Nose-Throat, pruritus, pain, cutaneous infections, vaccinations, growth failure and nutritional deficiency, hair and nail anomalies, reaction to hot and cold climates, physical limitations, comorbidities) and the particularities of the neonatal period and Netherton syndrome.

Since the 2010 classification of ichthyoses, our understanding of hereditary epidermal differentiation disorders (EDDs) has markedly increased, allowing consideration of new therapeutic targets based on disease pathogenesis. A new gene- and protein product function-based classification focuses on shared mechanisms of disease pathogenesis, with the possibility that grouped disorders may respond similarly to new therapeutics. These EDDs have been subdivided into syndromic (sEDD), nonsyndromic with features limited to skin and appendages (nEDD), and predominantly palmoplantar skin involvement (pEDD, nonsyndromic and syndromic). The sEDDs have clinically important extracutaneous features related to the gene alteration. Often, recognition based on skin manifestations facilitates early gene-based diagnosis, discussion of prognosis, genetic counseling, and initiation of therapy. All sEDDs are rare, the most common of which are STS-sEDD (formerly known as X-linked ichthyosis) and SPINK5-sEDD (formerly known as Netherton syndrome). Given the rarity, frequent association with early demise, and variable clinical features of sEDDs, their disease natural history with advancing age and genotype-phenotype relationships are poorly defined. Among the 51 sEDDs, associated neurologic (71%) and/or ophthalmologic (49%) findings are most common, and 39% have hair abnormalities. The widespread use of topical lovastatin-cholesterol for cholesterol synthesis-related sEDDs represents the prototype of pathogenesis-based therapy. This concept of upstream inhibition to prevent metabolite accumulation and supplementation with pathway end product potentially applies to other sEDDs, such as those affecting ceramide synthesis and transport. Topical or systemically administered inhibition of activated pathways is another potential approach, exemplified by the emerging treatment with kallikrein inhibitors for SPINK5-sEDD. Many sEDDs may be amenable to gene editing or introduction of functional cDNA. However, even systemic treatments targeting cutaneous diseases may not address extracutaneous manifestations that arise during embryologic development.

Background: Comprehensive Quality-of-Life Measure for Acne (CompAQ) is a patient reported outcome measure (PROM) assessing health-related quality of life (HRQoL) among patients with acne. The measure is one of two acne-specific PROMs which had the strongest evidence to support its use in a recent COSMIN systematic review.

Objective: To build on prior validation studies of CompAQ by confirming several of its known measurement properties in a cohort of patients with acne at three international sites; and, to establish the responsiveness of the measure during acne treatment.

Methods: Adults being seen for routine acne treatment at dermatology clinics in Canada, the United States, and Singapore were recruited between July 2022 and September 2024 to participate in this cohort study. At each visit, participants completed CompAQ, which consists of twenty items representing five domains (i.e., emotions, social judgement, social interaction, treatment, and symptoms domains), and several other relevant measures. Structural validity was assessed by confirmatory factor analysis, internal consistency by calculating Cronbach alpha values, and construct validity by known groups and convergent validity hypothesis testing. We further evaluated for differential item functioning (DIF) across study site, sex, and age. In addition, we assessed responsiveness by change-score validity hypothesis testing and calculating standardized response means (SRM).

Results: Our study included 315 participants (mean [SD] age, 25.2 years [6.1 years]; 219 females [69.8%]), and data was collected from a total of 588 visits. CompAQ was found to have sufficient structural validity, internal consistency, and construct validity among patients at each study site and in the combined cohort. In addition, no statistically significant uniform or non-uniform DIF was flagged for most items when analyzing DIF by site, sex, and age. Based on SRM estimates, the emotions (SRM = 0.927) and symptoms (0.914) domains had the largest responsiveness while the social judgement (0.606), social interaction (0.522), and treatment (0.787) domains had more moderate responsiveness.

Conclusions: CompAQ represents a useful and responsive PROM to evaluate HRQoL among those with acne in clinical trials and clinical practice. Future studies are needed to evaluate the interpretability of the measure (i.e., identifying severity strata and minimally important differences).

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

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

Methods: BRAVE-AA1 and BRAVE-AA2 were randomised, double-blind, placebo-controlled trials conducted at 169 centres in 10 countries. Patients were randomised 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 the Clinician-Reported Outcome (ClinRO) measure for EB/EL and Severity of Alopecia Tool (SALT) score for 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 both baricitinib 2 mg (28.2%, odds ratio [OR]=3.27, 25.1% OR=2.95) and baricitinib 4 mg (44.3% OR=6.84, 46.4% OR=8.21) as compared with placebo (12.6%, 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% and 82.6% achieved an EB and EL response, respectively, and 71.1% of patients achieved a response in both EB and EL with baricitinib 4 mg. Among scalp nonresponders (SALT score >20 at Week 52), 46.7% and 48.7% achieved EB and EL responses, respectively, and 35.4% 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 parallels that of the scalp. Baricitinib was efficacious in achieving holistic response across all three hair-bearing sites in a 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.

Trial registration number: BRAVE-AA1, ClinicalTrials.gov number, NCT03570749, start date, September 24, 2018; BRAVE-AA2, ClinicalTrials.gov number, NCT03899259, start date, July 8, 2019.