搜索结果：American journal of clinical dermatology

Ritlecitinib, an oral selective inhibitor of Janus kinase 3 and the TEC family of kinases, has recently been approved for the treatment of severe alopecia areata, but real-world data are still limited. The aim was to evaluate the effectiveness and tolerability of ritlecitinib 50 mg/day after 24 weeks in patients with severe alopecia areata in clinical practice. We performed an Italian observational, retrospective, multicentre study with 24 weeks of follow-up. Patients ≥ 12 years of age with severe alopecia areata (Severity of Alopecia Tool [SALT] ≥ 50) and a disease duration ≥ 6 months who were candidates for systemic therapy were enrolled. Ritlecitinib 50 mg/day was administered according to national guidelines. The primary endpoint was to evaluate the achievement of SALT ≤ 20 at week 24. Secondary endpoints included achievement of SALT ≤ 10; mean change in SALT; trichoscopic improvement; quality of life; psychological impact; efficacy in eyebrows, eyelashes, and nails; and safety profile. A total of 102 patients were included. At week 24, 40.2% of patients achieved SALT ≤ 20, with a greater response in adolescents (48.6%) than in adults (21.9%). The mean SALT score decreased from 86.2 ± 18.5 to 40.8 ± 37.1. Significant improvements were observed in trichoscopic signs and quality of life. The treatment was also effective on eyebrows, eyelashes, and nails. Adverse events were mild (e.g., acne, headache). Ritlecitinib had to be discontinued in only one case of severe anaemia. In this multicentre real-world study, ritlecitinib 50 mg/day was an effective and well-tolerated treatment option for severe alopecia areata. Alopecia areata is a common autoimmune disease that causes hair loss on the scalp and other parts of the body, such as eyebrows, eyelashes, and body hair. It affects people of any age, including adolescents, and often has a strong psycho-emotional impact, reducing quality of life. A new medication for severe alopecia areata, called ritlecitinib, was approved in 2023. Ritlecitinib is a Janus kinase inhibitor that modulates the immune response involved in the pathogenesis of the disease, promoting hair regrowth. However, data on its efficacy in everyday clinical practice have remained limited. To address this, we carried out a retrospective clinical study in Italy involving 20 university dermatology departments. We evaluated 102 adults and adolescents (≥ 12 years) with severe alopecia areata, treated with ritlecitinib 50 mg/day for 24 weeks. After 6 months of treatment, about 40% of patients had major hair regrowth on the scalp (with 80% of the scalp covered by hair). The treatment worked better in adolescents than in adults (48.6 vs 21.9%). Significant improvements were also noted in eyebrows, eyelashes, nail involvement, and quality of life parameters. Ritlecitinib was generally safe and well tolerated. Adverse effects were mild, and only one patient stopped treatment because of anaemia. Overall, our study showed that ritlecitinib was an effective and safe treatment for severe alopecia areata in real-world practice, particularly among adolescents.

Patient-reported outcomes (PROs) help dermatologists better understand patient perspectives to facilitate shared medical decision-making. Despite merit-based incentive payment system (MIPS) measure to collect quality of life assessments at least once every 12 months for patients with chronic skin diseases, routine PRO collection remains uncommon in clinical practice. This semi-structured interview study aimed to elicit key preferences, facilitators, and barriers for routine PRO collection in dermatology practices. Clinicians were recruited from Emory Dermatology, which has implemented routine PRO collection. Verbatim transcripts were coded and analyzed deductively using the Theoretical Domains Framework to generate salient themes. We interviewed nine dermatologists and one advanced practice provider (APP). Professional roles of all interviewed clinicians aligned with PRO collection. Memory, attention, and decision-making requirements for PRO collection by clinicians were minimized via institutional automation in the electronic health record (EHR). Skills in navigating EHR were needed to retrieve PRO data. Environmental factors affecting PRO collection included patient portal access, IT support for EHR integration, institutional interest in PROs, limited clinician oversight on PRO collection by other staff members, and high patient volume in dermatology clinics. Social support between staff could allow workflow division and maximized opportunities for PRO collection, while clinician perceived patient survey fatigue and skepticism on PRO utility affected PRO collection. This study was limited to clinician perspectives in a single clinic. Automating PRO collection and utilization in EHR, demonstrating PRO value, establishing institutional support, and streamlining workflow are needed to broadly implement routine PRO data collection. Patient reported outcomes (PROs) data offers valuable insights from the patient perspective to dermatology clinicians about their skin conditions, facilitating shared medical decision-making. However, most dermatology clinics do not collect PROs. This study explores key preferences, facilitators, and barriers to routine PRO collection among dermatology clinicians within an academic institution that has implemented PRO collection. Through qualitative interviews, the most salient themes identified by our participants include clinician perceived patient value proposition, clinician value proposition, stakeholder engagement and the importance of automated data collection through the electronic health record to minimize disruptions in clinical workflow. Automated, pre-clinical visit PRO collection presents an opportunity to enhance clinical decision making but successful implementation requires recognition of PRO value, institutional support, clear role delineation, clinician, staff and patient education and improved EHR visualization of PRO results.

Ritlecitinib, an oral Janus kinase (JAK) 3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, demonstrated safety in patients aged 12 years and older with alopecia areata (AA) in an initial integrated analysis of 4 clinical studies for up to 2 years. This updated integrated safety analysis evaluated the safety of ritlecitinib up to ~ 5 years in patients aged ≥ 12 years with AA from the ALLEGRO clinical trial program. Safety data were pooled from 4 studies. Two groups were analyzed: patients who received any dose of ritlecitinib (30 mg or 50 mg with or without a 4-week 200 mg loading dose, or 10 mg daily) ("any-ritlecitinib" group) and a subset of the any-ritlecitinib group including only patients who received ritlecitinib 50 mg daily with or without a 4-week 200 mg daily loading dose (ritlecitinib 50 mg ± 200-mg group). Safety data were summarized descriptively. Proportions and incidence rates (IRs; IR/100 patient-years [PYs]) of adverse events (AEs) were evaluated. In the ritlecitinib 50-mg ± 200-mg (N = 1228) and any-ritlecitinib (N = 1294) groups, median duration of exposure was 1197 days (3261.5 PYs) and 1204 days (3539.5 PYs), respectively. AEs occurred in 1070 patients (87.1%; 148.1/100 PYs) in the 50-mg ± 200-mg group and 1158 patients (89.5%; 167.9/100 PYs) in the any-ritlecitinib group. The most common AEs included headache, positive SARS-CoV-2 test, and nasopharyngitis. Serious AEs were reported in 6.8% of patients (2.6/100 PYs) in the 50-mg ± 200-mg group and 6.8% of patients (2.5/100 PYs) in the any-ritlecitinib group. There were two deaths. Overall, 8.1% of patients (3.0/100 PYs) and 8.4% of patients (3.0/100 PYs) in the 50-mg ± 200-mg and any-ritlecitinib groups, respectively, had an AE that led to discontinuation from the study or study drug. IRs for both groups were 0.1/100 PYs for opportunistic infections, 1.0/100 PYs for herpes zoster, 0.3/100 PYs for malignancies (excluding nonmelanoma skin cancer), and 0.2/100 PYs for major adverse cardiovascular events. In this updated integrated safety analysis of the ALLEGRO clinical trials, long-term ritlecitinib treatment was generally well tolerated up to ~ 5 years in patients aged ≥ 12 years with AA. The overall safety profile was consistent with previously reported data. NCT03732807, NCT04006457, NCT04517864, NCT02974868. Video Abstract Updated integrated safety analysis of ritlecitinib up to ~ 5 years in patients with alopecia areata from the ALLEGRO clinical trial program (MP4 407314 KB).

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Atopic dermatitis (AD) is a chronic inflammatory disease with a high clinical burden and risk of persistence in pediatric patients. To assess safety and efficacy of treatment with dupilumab for up to 2 years in infants and young children with AD. Patients aged 6 months to 5 years who had previously participated in parent studies LIBERTY AD PRESCHOOL Part A or B (NCT03346434), with moderate-to-severe AD at parent study baseline, were enrolled in the ongoing LIBERTY AD PED open-label extension (OLE) study (NCT02612454). Patients initially received weight-based dupilumab (3 or 6 mg/kg once a week); following protocol amendment, patients were switched to a weight-tiered dose every 4 weeks (200 mg for patients weighing 5 to < 15kg; 300 mg for patients weighing 15 to < 30kg). The use of concomitant medications (topical corticosteroids, antihistamines, and topical calcineurin inhibitors) was permitted without restriction, but patients were not permitted to use systemic medication for AD except as rescue treatment. Analyses were descriptive, with no formal statistical hypothesis. This analysis included 180 patients, of whom 106 completed the week 104 visit. A total of 87.8% patients experienced treatment-emergent adverse events (TEAEs; 24.4% mild, 52.2% moderate, 11.1% severe). One serious, drug-related TEAE (pinworm infection) did not lead to treatment discontinuation and resolved over time. One drug-related event of severe urticaria led to permanent treatment discontinuation but was not considered serious and resolved over time. By week 104, 92.1% patients achieved a 75% reduction in Eczema Area and Severity Index from parent study baseline, and the mean reduction in body surface area affected by AD was 49.0% from parent study baseline. In this OLE study, treatment with dupilumab for up to 2 years in infants and young children with AD demonstrated sustained efficacy with a safety profile consistent with prior studies, supporting its long-term continuous use in pediatric patients. ClinicalTrials.gov Identifier: NCT02612454. Atopic dermatitis (AD), a type of eczema, is a common inflammatory skin disease in children worldwide. Children with moderate-to-severe AD often need long-term treatment, as the disease may continue into adolescence and adulthood. In a previous study, treatment with dupilumab for up to 1 year provided sustained benefits and safety in children aged 6 months to 5 years with moderate-to-severe AD. Patients within the same study had the option to continue treatment with dupilumab for up to 2 years, in which they received 200 or 300 mg of dupilumab (depending on body weight) every 4 weeks. Throughout the 2 years, 88% of patients reported health issues, mostly mild or moderate and not related to treatment with dupilumab. Only two patients left the study owing to health issues, including one patient who developed a nonserious skin rash event related to dupilumab that resolved over time. Among the patients with health issues that were considered side effects of dupilumab, only one event was considered serious (pinworm infection), but it did not lead to interruption of treatment. By the end of the 2 years, 92% of patients achieved a 75% improvement in their extent and severity of disease since the beginning of treatment. On average, the body surface area affected by AD reduced by 49%. Most patients also reported improvements in quality-of-life measures. Overall, treatment with dupilumab for up to 2 years was associated with clinical benefits and consistent safety for infants and children with moderate-to-severe AD.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease which imposes a significant burden in terms of pain, disability, and comorbidities. Obesity and metabolic dysfunction are highly prevalent in HS, contributing to disease severity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in type 2 diabetes and obesity, have shown additional anti-inflammatory properties that may be relevant in HS.However, data on their clinical benefit remain limited. We performed a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase through June 2025, following PRISMA guidelines. Studies reporting outcomes in HS patients treated with GLP-1RAs were included. Information on clinical severity, quality of life, metabolism, inflammatory markers, and healthcare use were extracted. Findings were critically assessed and summarized descriptively, with pooled analysis applied where outcomes were consistently reported. This review was registered with PROSPERO (CRD420251110220). Nineteen studies including 67,568 patients were identified. Pooled analysis showed that 60% of patients achieved clinical improvement in Hurley stage (95%&#xa0;CI 52-67). Dermatology Life Quality Index (DLQI) improved by a mean of -3.83 points (95% CI -5.14 to -2.51). Clinical benefit was observed despite modest weight reduction (mean BMI change -2.64&#xa0;kg/m2). Inflammatory and metabolic markers improved, with significant reductions in mean C-reactive protein (-1.35&#xa0;mg/L, 95%&#xa0;CI -2.33 to -0.36) and HbA1c (-0.39%, 95%&#xa0;CI -0.59 to -0.18). Large real-world cohorts showed decreased antibiotic and corticosteroid use and lower hospitalization rates, though results for biologic use, surgical procedures, and cardiovascular outcomes were mixed. Two studies reported reduced risk of major adverse cardiovascular events, while one HS-diabetes cohort suggested persistent excess cardiovascular risk compared with diabetes-only controls. This systematic review suggests that GLP-1RAs are associated with improvements in HS severity, quality of life, metabolic and inflammatory parameters, and may additionally reduce healthcare utilization and cardiometabolic risk, observed alongside weight loss. However, current evidence remains limited and heterogeneous, and the relative contribution of weight-dependent and weight-independent effects cannot be determined. Prospective studies and controlled trials are needed to clarify the role of GLP-1RAs in HS management.

Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease. We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged &#x2265;12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of&#xa0;&#x2264;10 and&#xa0;&#x2264;20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had "some concerns" primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT&#xa0;&#x2264;10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT&#xa0;&#x2264;20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76). Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.

State-level legislation is a principle driver of structural change in American health care; yet, physician participation in the policymaking process remains limited. Using the members-only American Academy of Dermatology Association legislative tracker, we conducted a nationwide cross-sectional analysis of 295 dermatology-related state bills through February 14, 2025. The scope of practice (29.5%) and pharmaceutical reform and drug access (25.1%) were the dominant legislative categories. Physician sponsors were involved in only 7.5% of bills compared with 26.8% sponsored by nonphysician health care professionals; the remaining 62.7% had sponsors with no documented health care background. These findings reflect persistent structural forces, scope of practice expansion, and pharmaceutical policy dysfunction that fundamentally shape dermatologic practice. We discuss the clinical implications of these trends, the organized nonmarket competition facing physician interests, and actionable pathways through which dermatologists can meaningfully engage in the legislative process, including through state dermatology societies, SkinPAC, and grassroots advocacy.

Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, demonstrated efficacy over 48 weeks in patients aged &#x2265;&#x2009;12 years with alopecia areata (AA) in the ALLEGRO phase 2b/3 study and initial extension up to month 24 in the ALLEGRO-LT study. We aimed to evaluate the efficacy of ritlecitinib up to 3 years in patients with AA from the ALLEGRO phase 2b/3 and ongoing phase 3, open-label ALLEGRO-LT studies. Patients aged &#x2265;&#x2009;12 years with AA and &#x2265;&#x2009;50% scalp hair loss who received daily ritlecitinib 50 mg in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued 50 mg) were included. Observed and last observation carried forward (LOCF) data are reported based on the data cutoff (25 June 2024). Variables associated with treatment response were assessed using multivariable logistic regression. A total of 191 patients were included. At 3 years, 65.1% (observed) and 47.1% (LOCF) of patients had Severity of Alopecia Tool (SALT) score &#x2264;&#x2009;20. Among patients with SALT score &#x2264;&#x2009;20 at 1 year, most (88.3-89.6%) maintained this response at 3 years. SALT score &#x2264;&#x2009;10 response rates at 3 years were 52.3% (observed) and 36.7% (LOCF). At 3 years,&#xa0;31.2% (observed) and 22.5% (LOCF) of patients achieved SALT score 0 (complete scalp hair regrowth). Patients' Global Impression of Change response ("moderately" or "greatly" improved) rates at 3 years were 68.4% (observed) and 55.6% (LOCF). Female sex, White race, and less extensive and shorter duration of hair loss at baseline were associated with treatment response. The safety profile was consistent with the known safety profile of ritlecitinib. Ritlecitinib 50 mg demonstrated clinically meaningful clinician- and patient-reported efficacy up to 3 years, with no new safety signals observed. These data support the long-term use of ritlecitinib in patients aged &#x2265;&#xa0;12 years with severe AA. [Graphical abstract and video abstract available online.]. NCT03732807, NCT04006457, NCT04517864, NCT02974868.

Atopic dermatitis is a chronic immune-inflammatory skin disease that significantly impairs quality of life, with itch representing a key, but not exclusive, contributor to this burden. We aimed to evaluate itch relief and quality-of-life improvements with abrocitinib or dupilumab for 16 weeks alongside topical therapy in patients with moderate-to-severe atopic dermatitis. This post hoc analysis included pooled data from patients who received abrocitinib (200 mg/day) or dupilumab (300 mg/every 2 weeks) in phase III JADE COMPARE and JADE DARE. Assessments included proportions of patients achieving a &#x2265; 4-point improvement from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4), itch-free state (PP-NRS 0/1) by baseline itch severity, and proportions of patients with residual itch achieving Dermatology Life Quality Index score of 0/1 (DLQI 0/1), total Patient-Oriented Eczema Measure (POEM) score &#x2264; 2, SCORing Atopic Dermatitis (SCORAD) sleep loss visual analog scale score of 0/1 (SCORAD&#xa0;sleep loss visual analog scale 0/1), and POEM sleep item score of 0 (POEM sleep 0). Among 1196 patients (abrocitinib, n = 588; dupilumab, n = 608), those with greater baseline itch severity experienced greater atopic dermatitis severity and worse quality of life than patients with less severe itch. At week 16, numerically more patients achieved PP-NRS4 (67% vs 63%) and PP-NRS 0/1 (36% vs 27%) with abrocitinib versus dupilumab, respectively, regardless of baseline itch severity, although 95% confidence intervals overlapped for both measures. Median time to achieve PP-NRS4 (11 vs 29 days) and PP-NRS 0/1 (57 vs 139 days) was shorter with abrocitinib versus dupilumab, respectively. Numerically greater proportions of patients achieving PP-NRS 0/1 also achieved DLQI 0/1, POEM &#x2264; 2, SCORAD sleep loss visual analog scale 0/1, or POEM sleep 0 than patients with residual itch (PP-NRS &#x2265; 2). In this post hoc pooled analysis of the JADE COMPARE and JADE DARE trials, the proportion of patients with moderate-to-severe atopic dermatitis achieving clinically meaningful itch responses, including an itch-free state, was generally higher with abrocitinib compared with dupilumab. Median time to achievement of both PP-NRS4 and an itch-free state was shorter with abrocitinib than with dupilumab. Patients who achieved an itch-free state experienced greater improvements in quality of life and sleep compared with patients with residual itch. JADE COMPARE (NCT03720470; registration date: 2018/10/24); JADE DARE (NCT04345367; registration date: 2020/04/10).

Porphyrias are rare metabolic disorders caused by inherited or acquired enzymatic defects in the heme biosynthesis pathway, resulting in the accumulation of heme precursors or toxic porphyrin intermediates. The cutaneous porphyrias arise from enzymatic defects in later steps of the heme biosynthesis pathway, which lead to the build-up of photoactive porphyrins in the skin and liver, such as coproporphyrins, protoporphyrins, and uroporphyrins. These photoactive porphyrins generate reactive oxygen species that drive the characteristic cutaneous manifestations, including painful photosensitivity, skin fragility, and blistering. The cutaneous porphyrias encompass both blistering and non-blistering subtypes, which include erythropoietic protoporphyria, X-linked protoporphyria, congenital erythropoietic porphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria, each distinguished by specific biochemical patterns and clinical features. Acute hepatic porphyrias, which include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficiency porphyria, result in the accumulation of neurotoxic precursors, such as &#x3b4;-aminolevulinic acid and porphobilinogen. While acute neurovisceral attacks predominate in acute hepatic porphyrias, certain subtypes, such as variegate porphyria and hereditary coproporphyria, may present with blistering photosensitivity, creating a significant diagnostic overlap between cutaneous porphyrias and other photodermatoses. This overlap underscores the importance of awareness of acute hepatic porphyrias among dermatologists, who may be the first clinicians to encounter patients with these disorders. In addition, recent treatment breakthroughs will likely bring patients with porphyrias to pursue care, changing the likely underestimated disease prevalence rates. This narrative review provides a comprehensive overview of the pathobiology, clinical features, diagnostic strategies, and management approaches for the cutaneous and acute hepatic porphyrias.

Advanced basal cell carcinoma (aBCC) is an uncommon but severe presentation of basal cell carcinoma, including those with extensive local invasion and metastasis. Curative local treatments are often not feasible for patients with aBCC and the introduction of Hedgehog pathway inhibitors (HHIs) expanded the therapeutic landscape. First-line therapy with the HHIs, vismodegib and sonidegib, provides effective disease control, and may enable the preservation of function in locally complex cases. Also, it offers the possibility to simultaneously treat multiple tumors, such as in patients with basal cell nevus syndrome. However, long-term HHI therapy is limited by toxicity, heterogeneous responses and the emergence of resistance or tolerance. For selected patients with progression or limited tolerability under HHIs, immune checkpoint inhibition has emerged as an established second-line option, offering durable responses in a subset of patients. However, immune-related adverse events remain a concern. To address the shortcomings of systemic therapy and improve the long-term disease control of patients with aBCC, ongoing research focuses on alternative dosing strategies, integration of combination or novel systemic agents and the development of predictive biomarkers. This review provides a comprehensive, clinically oriented overview of the evidence on systemic treatment for aBCC, emphasizing efficacy, safety, resistance mechanisms, and therapeutic strategies.

Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a &#x2265;&#xa0;75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. NCT03624127, NCT03611751, NCT04036435.

Dissecting cellulitis of the scalp is a rare, primary neutrophilic cicatricial alopecia that manifests with painful nodules, abscesses, and interconnected sinus tracts. It predominantly affects young adult men and frequently coexists with other follicular occlusion disorders, including hidradenitis suppurativa and acne conglobata. Clinical evaluation and trichoscopy are key elements of the diagnostic work-up, allowing detection of both early non-scarring inflammatory changes and features of chronic fibrotic disease. Although a wide array of therapeutic options has been explored, which range from oral antibiotics and retinoids to biologic agents, evidence-based guidelines remain lacking, and disease recurrence is common upon treatment cessation. Recent therapeutic advances have identified tumor necrosis factor-&#x3b1;, interleukin-17, and interleukin-23 inhibitors as promising options in recalcitrant cases. Adjunctive modalities such as laser-based therapies, surgical excision, and photodynamic protocols further expand the therapeutic paradigm, particularly for advanced disease. Increasing clinical and pathogenic evidence supports shared inflammatory pathways between dissecting cellulitis of the scalp and hidradenitis suppurativa, suggesting that these entities may represent anatomical variants within the same disease spectrum, driven by follicular occlusion and dysregulated immune responses. This evolving view harbors important implications for disease classification and management. The aim of this review is to provide an updated overview of the latest evidence on dissecting cellulitis of the scalp, encompassing its epidemiology, pathogenesis, clinical presentation, diagnostic algorithm, and therapeutic strategies. Additionally, we critically evaluate the conceptual framework for viewing dissecting cellulitis of the scalp and hidradenitis suppurativa as phenotypic variants of a unified inflammatory disorder and assess the current unmet need and future perspectives in translational research and disease management.

Melanoma is an aggressive skin cancer with limited durable responses despite therapeutic advances. Comprehensive characterization of genomic alterations may improve understanding of disease progression and inform therapeutic strategies. We aimed to characterize genomic alterations in cutaneous melanoma and compare mutation prevalences between primary and metastatic tumors to improve therapeutic strategies. We conducted a systematic review and meta-analysis of genomic data from primary and metastatic cutaneous melanomas to assess the prevalence of gene mutations and copy number alterations. Relevant studies were identified in MEDLINE and Embase up to October 2024 using the search algorithm ((Mutation) OR "Genomics"[Mesh]) AND ("Melanoma"[Mesh]). Data were synthesized using random-effects meta-analyses to estimate the pooled prevalence of gene mutations and copy number variations, with heterogeneity assessed using I2 statistics. This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ninety-nine publications were included, encompassing 10,386 primary cutaneous melanoma samples and 4273 metastatic samples. The most frequently mutated genes in both settings were BRAF, TERT, TP53, NRAS, and NF1. The prevalence of BRAF, NRAS, TERT, CDKN2A, and PTEN mutations was significantly higher in metastatic lesions. NRAS mutations were more common in central nervous system metastases than in other metastatic sites. In contrast, KIT mutations were more common in primary tumors. Acral melanoma exhibited a distinct molecular profile, with an overall lower mutation prevalence, particularly involving BRAF. Chromosomal losses at 9p21.3 and 9p21 were commonly observed in both primary and metastatic tumors, with higher prevalence in primary tumors. Our findings highlight distinct genomic differences between primary and metastatic melanoma, underscoring the value of metastatic tumor biopsies in informing molecularly guided treatment decisions. Cutaneous melanoma is the most serious type of skin cancer. The number of cases is rising, especially among people with fair skin in developed countries, with over 330,000 new cases and more than 58,000 deaths worldwide each year.New treatments have improved survival for many patients. Immunotherapy, which helps the immune system fight cancer, and targeted therapy, drugs that block specific genetic changes in cancer cells, have helped people with advanced melanoma live longer. However, melanoma can eventually stop responding to these therapies, so new treatment targets are urgently needed.In this study, we reviewed data from 99 published studies, including over 10,300 primary melanoma cases and 4200 metastatic cases, to find out how often genetic changes occur and to compare primary tumors with metastatic tumors.We found that several genes were commonly altered, including BRAF, TERT, TP53, NRAS, and NF1, with BRAF being the most frequent, occurring in nearly 40% of cases. Some changes, including BRAF, NRAS, TERT, CDKN2A, and PTEN, were more common in metastatic melanoma. NRAS changes were especially frequent in tumors that spread to the brain. Loss of a chromosome region called 9p21 was also seen in both primary and metastatic tumors, but more often in primary tumors.These findings show clear genetic differences between primary and metastatic melanoma. Testing metastatic tumor samples may provide more accurate information to help guide treatment decisions for patients with advanced disease.

To systematically synthesise the benefits and harms of add-on oral antihistamines for managing atopic dermatitis (eczema). Systematic review and network meta-analysis of randomised trials. Medline, Embase, CENTRAL, the United States Food and Drug Administration, and the European Medicines Agency databases from database inception to 5 May 2025. Randomised trials assessing add-on oral H1 antihistamines, H2 blockers, mast cell stabilisers (nedocromil sodium and sodium cromoglycate), or their combinations. Paired reviewers independently screened records, extracted data, and assessed risk of bias using a modified Cochrane Risk of Bias tool version 2. Random effects bayesian meta-analyses synthesised atopic dermatitis severity (oSCORAD-objective scoring atopic dermatitis, 0-83; minimal important difference 8.2; lower better), itch severity (numerical rating scale, 0-10; minimal important difference 3; lower better), sleep disturbance, atopic dermatitis related quality of life, and harms. The network meta-analysis GRADE (Grading of Recommendations Assessment, Development and Evaluation) and Core GRADE approaches informed certainty of evidence ratings. 47 trials enrolled 6230 children and adults with primarily moderate to severe atopic dermatitis. With moderate certainty, compared with placebo, adding a first generation or second generation H1 antihistamine likely resulted in a small reduction in atopic dermatitis severity (mean difference -1.87, 95% credible interval -3.47 to -0.27) and itch severity (-0.89, -1.41 to -0.37). Although statistically detectable, these effects are well below established minimal important differences (smallest change in an outcome that a patient would identify as important). With low certainty, all studied interventions may not improve sleep disturbance or reduce atopic dermatitis exacerbations. First generation agents probably increase cognitive impairment and may increase treatment discontinuation because of adverse events (risk difference 66 more per 1000, 95% credible interval 0 to 231 more; moderate certainty). Second generation agents differ in their risk of cognitive impairment (range of mean effects 0 more per 1000 for loratadine, 16 more per 1000 for levocetirizine, and 17 more per 1000 for cetirizine). Among patients with atopic dermatitis, adding H1 antihistamines probably results in a clinically unimportant reduction in atopic dermatitis severity and itch severity, and may not reduce sleep disturbance or atopic dermatitis exacerbations. First generation agents increase cognitive impairment and may increase treatment discontinuation because of adverse events. Cognitive impairment risk differs among second generation agents. These findings provide evidence against routine antihistamine use in atopic dermatitis management and will inform updated clinical guidelines. PROSPERO CRD42022345643.

Certain skin conditions are proven indicators of underlying systemic disease. Specifically, acanthosis nigricans (AN) is commonly associated with type 2 diabetes and insulin resistance. However, AN may also be a marker of metabolic syndrome (MS). MS is linked to several health conditions leading to death. Therefore, early identification of MS is crucial in preventing disease progression. While AN may provide a visual cue for MS risk, its utility as a clinical screening tool remains underexplored. To address this, we conducted a systematic review to evaluate the association between AN and MS. We systematically searched PubMed, Embase, and Cochrane Review using the term "acanthosis nigricans," identifying 656 articles, including 322 case reports, that reported AN in association with at least one MS criteria, as defined by the American Heart Association. Article quality was determined using the Strength of Recommendation Taxonomy (SORT) grading system. Across the 656 included articles, the unweighted mean proportion of study participants with AN was 70.8% (standard deviation of 34.9%), reflecting that many studies evaluated broader patient populations in which AN was one of several conditions assessed. Of all MS criteria, insulin resistance showed the highest mean prevalence of AN at 72.6%. Within all articles, 65.9% met more than one MS criterion, with co-occurrence of insulin resistance and increased body mass being the most common combination (25.5%). In a subanalysis of non-case-report studies in which all participants had AN, 67.4% met the full criteria for MS, with increased body mass being the most frequently reported individual criterion (89.7% of cases). This review provides a better estimate of AN observed in individuals with MS or in those at risk for MS. Integrating dermatologic examination for AN into primary care and preventive health may improve early detection of MS, reduce costs and unnecessary testing, and promote targeted interventions. Educational efforts are needed to increase clinician awareness of the association between AN and MS.

Clascoterone cream 1% is a topical androgen receptor inhibitor approved for the treatment of acne vulgaris in patients &ge;12 years of age. The American Academy of Dermatology recommends topical combination therapy using medications that target different mechanisms of acne pathogenesis. This 20-week, open-label, pilot study (NCT06336603) evaluated the efficacy and safety of clascoterone cream 1% combined with adapalene gel 0.3% in patients with acne. Patients aged &ge;12 years with moderate-to-severe acne applied clascoterone cream 1% twice daily and adapalene gel 0.3% once daily for 16 weeks. Efficacy assessments included Investigator's Global Assessment (IGA) score; inflammatory, noninflammatory, and total lesion counts; and Dermatology Life Quality Index (DLQI) through week 16. Tolerability and safety were assessed from local skin reactions and adverse events through week 20. Twenty patients were enrolled; 17 completed the study (female, 53%; mean [standard deviation (SD)] age, 22 [10] years). At week 16, 65% of patients achieved an IGA score of clear (0) or almost clear (1). From baseline to week 16, there were significant reductions in lesion counts (mean [SD] percent reduction: inflammatory, 90.5 [10.1]; noninflammatory, 84.8 [13.5]; total, 87.3 [11.4]; all P<0.001) and DLQI score (mean [SD] reduction, 3.7 [6.2]; P=0.02). Treatment was well tolerated, with most local skin reactions reported as absent or trace, and no adverse events reported. This open-label pilot study shows promising results for combination treatment with clascoterone cream 1% and adapalene gel 0.3% for the treatment of patients with acne. &nbsp.

Ruxolitinib cream (1.5%) has demonstrated efficacy and safety in patients aged &#x2265;&#xa0;2 years with mild-to-moderate atopic dermatitis. We aimed to further investigate the safety and efficacy of ruxolitinib cream in adolescents with atopic dermatitis in an open-label study. Patients aged 12-17&#xa0;years with atopic dermatitis, an Investigator's Global Assessment score of 2/3, and 3-20% affected body surface area applied twice-daily 1.5% ruxolitinib cream for an 8-week continuous treatment period, followed by a 44-week long-term safety period in which ruxolitinib cream was applied twice daily as needed. Safety was the primary endpoint. Secondary endpoints included plasma trough concentrations of ruxolitinib. Affected body surface area, &#x2265;&#xa0;75% improvement from baseline in Eczema Area and Severity Index, achievement of Investigator's Global Assessment score of 0/1, and &#x2265;&#xa0;4-point improvement from baseline in the itch Numerical Rating Scale were exploratory endpoints. Of 103 patients, 59.2% had a baseline Investigator's Global Assessment of 3. Mean baseline body surface area and Eczema Area and Severity Index scores were 8.9% and 6.4, respectively. Over 52 weeks, 42 patients (40.8%) had treatment-emergent adverse events, most commonly upper respiratory tract infection (10.7%) and nasopharyngitis (8.7%). Three patients (2.9%) had grade &#x2265;&#xa0;3 treatment-emergent adverse events; all were considered unrelated to treatment by the investigator. Steady-state ruxolitinib plasma concentrations during the continuous treatment period were low (geometric mean [geometric coefficient of variation], 14.2 [169] nM), consistent with the lack of observed treatment-emergent adverse events associated with systemic Janus kinase inhibition. Clinical improvements occurred during the continuous treatment period and were maintained or improved with as-needed treatment through the long-term safety period to week 52 (mean affected body surface area, 1.3%; &#x2265;&#xa0;75% improvement from baseline in Eczema Area and Severity Index, 87.0%; Investigator's Global Assessment 0/1, 82.6%; &#x2265;&#xa0;4-point improvement from baseline in&#xa0;itch Numerical Rating Scale, 41.7%). Ruxolitinib cream (1.5%) was well tolerated and efficacious with long-term as-needed use in adolescents with mild-to-moderate atopic dermatitis, consistent with safety and efficacy findings reported in previous phase III studies in adolescents and adults. Clinicaltrials.gov identifier, NCT05456529 (registered 13 July, 2022).