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 ≥ 75
Excessive scarring (ES), including keloids and hypertrophic scars, impairs function, appearance, and quality of life in children. Its pediatric comorbidity spectrum is not well defined, limiting anticipatory guidance and multidisciplinary care. This research aims to investigate comorbidities of ES in a diverse pediatric cohort using a phenome-wide association study (PheWAS). This population-based study leveraged longitudinal electronic health record (EHR) data from participants enrolled in the Children’s Hospital of Philadelphia (CHOP) from 2006. Diagnosis codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] and Tenth Revision [ICD-10-CM]) were mapped to 3109 phenotype codes (PheCodes). PheWAS analyses were conducted using logistic regression, with Bonferroni correction applied to account for multiple testing. Among 86,092 pediatric participants, 662 (0.77
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
Skin aging is characterized by progressive structural and biochemical changes that impair epidermal barrier function, alter the cutaneous microbiome, and predispose to chronic pruritus. Epidermal thinning, reduced lipid synthesis, and slowed barrier repair increase transepidermal water loss and vulnerability to irritation. Concurrently, age-related disruption of the acid mantle leads to elevation of skin surface pH, impairing acid-dependent lipid-processing enzymes while enhancing serine protease activity. These changes disrupt lamellar organization, weaken stratum corneum cohesion, and further compromise barrier integrity. Elevated pH and barrier dysfunction also reshape the skin microbiome. These changes favor alkalinity-tolerant and proinflammatory species while reducing protective commensals, thereby reinforcing inflammation and sensory irritation. Barrier impairment, dysbiosis, and pH-driven protease activation converge with neuroimmune dysregulation to sensitize peripheral nerves and promote chronic itch. Important contributors include kallikrein–protease-activated receptor-2 (PAR2) signaling and cytokines such as interleukin-31. This review highlights the pH–protease–itch axis as a unifying framework for pruritus in aging skin and discusses restoration of physiological acidity as a rational therapeutic strategy.
Bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin are distinct chronic skin diseases with a high disease burden and an ongoing need for safe and effective therapies. Advances in our understanding of disease mechanisms have highlighted convergent type 2-associated neuroimmune pathways that may contribute to chronic itch and skin lesions across these conditions. In bullous pemphigoid, autoantibody binding of two dermal–epidermal junction proteins followed by complement system activation shapes the local immune environment to favor T helper cell 2 polarization and perpetuation of type 2 inflammation. In chronic spontaneous urticaria, mast cell activation and downstream mediators, including type 2 cytokines, may contribute to amplification of inflammation and itch. In prurigo nodularis, chronically activated itch sensory neurons induce an itch-scratch cycle with T-cell activation in parallel to mast cell degranulation, resulting in neurogenic inflammation that sustains the itch-scratch cycle. The pathogenesis of chronic prurigo of unknown origin is not well understood, but evidence to date points to interactions between skin barrier defects and immune and neural dysregulation triggering T helper cell 2 polarization. In this review, we discuss the role of type 2 inflammation in bullous pemphigoid, chronic spontaneous urticaria, prurigo nodularis, and chronic prurigo of unknown origin, and how this understanding is currently translated into new targeted therapeutic options.
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
With more than 300,000 new cases diagnosed in 2022 and a projected rise in incidence until the year 2040, malignant melanoma remains a major global health challenge. Of note, immunotherapy has substantially improved survival outcomes, even in advanced stages. Nevertheless, reliable biomarkers for early relapse detection, risk stratification, and treatment monitoring remain an unmet clinical need. Conventional surveillance tools, including imaging, lactate dehydrogenase (LDH), and S100B, are limited by their sensitivity and specificity, particularly in patients with low tumor burden. The use of liquid biopsy, the analysis of body fluids such as blood, with its wide range of analytes and highly sensitive analysis methods, may represent a novel strategy to overcome the limitations of conventional biomarkers. In particular, the analysis of circulating cell-free nucleic acids from the tumor released to the blood, referred to as circulating tumor DNA (ctDNA), has emerged as a minimally invasive approach capable of capturing tumor-derived molecular information from plasma in solid tumors. ctDNA holds promise as a tool for the detection of minimal residual disease (MRD), early relapse, clonal evolution, and actionable genomic alterations. Technological advances have expanded ctDNA applications from single-mutation assays to comprehensive personalized NGS strategies and multi-modal approaches incorporating methylation profiling and fragmentomics. Clinical studies increasingly demonstrate that ctDNA detection and ctDNA dynamics provide prognostic and potentially predictive information across both (neo)adjuvant and advanced melanoma settings. In this review, we summarize the current methodological approaches and clinical evidence supporting ctDNA as a biomarker for prognosis, risk stratification, and therapy monitoring in melanoma.
Atopic dermatitis is a common inflammatory disorder affecting the skin, often associated with a strong disease burden and a long-term impact on patients’ quality of life. Although most treatments for atopic dermatitis have been mainly focusing on alleviating symptoms, emerging therapies and approaches may offer the potential to modify the disease course, thereby leading to off-treatment remission and prevention of comorbidities. However, a consensus on the definition of disease modification in atopic dermatitis is yet to be reached. The aim of this article is to review the concept of disease modification in atopic dermatitis and its different dimensions, including underlying pathophysiology, disease control, atopic and nonatopic comorbidities, subclinical biomarkers, and the importance of early therapeutic intervention. Ultimately, identifying therapies with long-lasting effects on atopic dermatitis progression could alleviate the global health burden of atopic diseases.
Atopic dermatitis (AD) is a chronic inflammatory skin disease, driven by barrier and immune dysregulation, which causes significant impairment in quality of life. The introduction of biologics and oral small molecules has substantially improved treatment outcomes. However, achieving complete and durable clinical clearance for most patients remains challenging, and concerns related to long-term safety and healthcare burden persist as key unmet needs. These limitations have catalyzed a new phase of therapeutic innovation in AD. Next-generation biologics targeting type 2 cytokines are being refined through advances in antibody bioengineering, including high binding affinity and fragment crystallizable modification, with the aim of enhancing efficacy while achieving extended dosing intervals. In parallel, bispecific and multispecific antibodies, designed to simultaneously engage multiple epitopes on the same or distinct antigens, are increasingly being evaluated in inflammatory skin diseases after initial development in oncology, offering the potential for synergistic immunomodulatory effects. This evolving landscape is further complemented by evidence from T-cell rebalancing strategies that showed durable off-treatment responses, positioning these approaches as potential game changers in long-term disease control. Lastly, emerging oral small-molecule agents that inhibit intracellular signaling downstream of multiple cytokines are supported by favorable safety profiles in early-phase trials. Overall, this review synthesizes current translational and clinical advances shaping the evolving pipeline, highlighting how both novel ways of modulating established pathways and the identification of new targets may transform the future management of AD.
Head and neck atopic dermatitis represents a common and clinically challenging phenotype of atopic dermatitis, characterized by anatomical selectivity, chronicity, and variable therapeutic response. Increasing evidence indicates that head and neck atopic dermatitis is not merely a regional extension of generalized disease, but a distinct phenotype shaped by the convergence of regional barrier fragility, a lipid-rich sebaceous microenvironment, microbiome imbalance, particularly involving Malassezia species, and a mixed immune signature integrating type 2, type 17, and type 22 inflammatory pathways. These factors promote persistent inflammation, psoriasiform features, and relative treatment refractoriness in the head and neck region. The clinical relevance of this phenotype has increased in the era of targeted therapies, as persistent or de novo facial involvement has been reported during biologic treatment, most notably with interleukin-4Rα blockade. Dupilumab-associated head and neck dermatitis exemplifies a pathway shift characterized by suppression of type 2 inflammation alongside exaggerated interleukin-22 and aryl hydrocarbon receptor-driven epithelial stress responses, providing mechanistic insight into paradoxical inflammation and incomplete regional control. Advances in immunobiology are beginning to translate into more tailored therapeutic strategies. Interleukin-13-selective biologics, systemic and topical Janus kinase inhibitors, and emerging agents targeting tissue-resident memory T-cell pathways offer new opportunities to address the dominant inflammatory circuits active in this region. Although comparative data remain limited, these approaches raise the possibility of improved control in selected patients with difficult-to-treat head and neck involvement. This review synthesizes current evidence on the pathogenic hallmarks of head and neck atopic dermatitis, integrates emerging mechanistic and clinical data, and discusses evolving therapeutic strategies aimed at phenotype-driven region-specific management of this complex manifestation of atopic dermatitis.
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
It is well established that a complete package of photoprotection includes staying in the shade, wearing photoprotective clothing, hat, and sunglasses, and on otherwise exposed sites, applying sunscreen. Recent advances have modified photoprotection through new active ingredients, innovative formulations, complementary oral strategies, and personalized approaches. This review aims to summarize the latest new developments in photoprotection. A narrative review of the literature was conducted from January 2010 to October 2025 using terms related to photoprotection, sunscreen innovation, visible light, oral photoprotection, microbiome interaction, climate change, and personalized approaches. Articles in English and Spanish were selected based on scientific relevance. Advances in photoprotection include the development of new topical filters targeting UVA1 and visible light, as well as the incorporation of iron oxides and, in some formulations, pigmentary titanium dioxide in tinted sunscreens to enhance protection against visible light. In addition, the use of antioxidants and DNA repair enzymes has been explored to mitigate oxidative stress and address field cancerization. Natural and eco-friendly bioactive ingredients derived from botanical and marine sources show growing potential as photoprotective agents. Additional considerations such as the role of skin microbiome, and personalized photoprotection strategies tailored to skin phototype, lifestyle, diseases, and high-exposure conditions further refine preventive practice. Photoprotection is evolving into a multidimensional approach that integrates advanced topical formulations, oral agents, and individualized recommendations. This paradigm offers improved prevention of photoaging, pigmentary disorders, and photocarcinogenesis while promoting safer and more sustainable photoprotection practices.
Primary cutaneous cryptococcosis (PCC) is a rare, localized fungal infection caused by Cryptococcus species, typically following direct inoculation of the yeast into the skin in immunocompetent individuals. Unlike disseminated cryptococcosis, which is more common in immunocompromised hosts, PCC remains confined to the skin and often arises after minor trauma or environmental exposure. Although traditionally associated with Cryptococcus neoformans (C. neoformans), Cryptococcus gattii (C. gattii) is also increasingly recognized in immunocompetent hosts. Dermatologists are crucial in the early identification of PCC, as its clinical presentation can resemble other dermatologic conditions such as bacterial cellulitis, pyoderma gangrenosum, or atypical mycobacterial infections. This review provides a comprehensive overview of the epidemiology, clinical features, diagnostic methods, and management strategies for PCC. It emphasizes the importance of differentiating PCC from disseminated cryptococcosis and other mimicking conditions. Treatment with oral azoles, such as fluconazole, is typically effective, with a favorable prognosis for most immunocompetent patients. The review also includes practical diagnostic algorithms to assist clinicians in the accurate and timely management of PCC, ultimately improving patient outcomes and reducing unnecessary interventions.
Post-inflammatory hyperpigmentation and post-inflammatory erythema are common sequelae of acne, particularly affecting individuals with skin of color. Up to 85% of patients with Fitzpatrick phototypes IV-VI develop post-inflammatory hyperpigmentation following inflammatory acne lesions. Acne-induced hyperpigmentation (AIH) results from increased melanin production and deposition triggered by inflammatory mediators, while acne-induced macular erythema reflects vascular alterations. Both AIH and acne-induced macular erythema can persist for months or even years, significantly contributing to the psychosocial burden of acne and negatively impacting patients' quality of life - sometimes to a greater extent than active acne itself. Female individuals, darker skin color, severe acne, facial sites, excessive sunlight exposure, and traumatized lesions are important risk factors for AIH. Diagnosis relies on visual inspection, acne history, and skin phototype assessment. Treatment options include topical agents such as azelaic acid, retinoids, antioxidants, and hydroquinone, as well as systemic therapies such as isotretinoin, oral antibiotics, and oral tranexamic acid. Chemical peeling and energy-based devices, including lasers and microneedling, offer additional therapeutic avenues. Photoprotection is crucial in managing AIH, particularly in skin of color patients. Despite the high prevalence of AIH, there is a lack of validated patient-reported outcome measures specific to AIH/acne-induced macular erythema, highlighting the need for further research and standardized assessment tools. This article provides a practical approach, highlighting therapeutic strategies and recommendations for AIH across all skin types.
T-cell engager therapies, including bispecific T-cell engagers and the immune-mobilizing monoclonal T-cell receptor against cancer tebentafusp, are an emerging class of anticancer immunotherapy, with rapid expansion of the class since initial approval of blinatumomab in 2014 and with distinct dermatologic adverse events increasingly recognized across agents. Tebentafusp and talquetamab demonstrate highest rates of notable dermatologic toxicity reflecting on-target off-tumor cutaneous effects. Tebentafusp produces dermatologic adverse events in the majority of treated patients, characterized by diffuse erythematous and frequently photodistributed eruptions. Talquetamab is notable for a characteristic constellation of cutaneous, nail, and oral toxicities linked to target G protein-coupled receptor class C group 5 member D expression in keratinized tissues. Subcutaneous cluster of differentiation (CD)20- and B-cell maturation antigen-targeted agents frequently cause injection-site reactions, generally low-grade and self-limited. Blinatumomab and other CD19- and CD20-directed agents have been associated with a spectrum of heterogeneous rashes. Across agents, most dermatologic adverse events can be managed with topical corticosteroids, emollients, antihistamines, or brief courses of systemic corticosteroids without requiring treatment discontinuation. Recognition of these agent-specific and mechanistically linked patterns is essential for dermatologists as T-cell engager therapies become increasingly integrated into oncology practice.
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 δ-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.
Dermatophytoses (synonymous with tinea) are superficial fungal infections of the skin, hair, and nails, typically caused by dermatophytes in the genera of Trichophyton and Microsporum. Dermatophyte infections are common and are estimated to affect roughly 20-25% of the global population. Historically, tinea infections have been treated with short courses of topical and/or oral antifungal therapies, however, the last decade has seen increasing antifungal treatment failure. Trichophyton (T.) indotineae (previously termed Trichophyton mentagrophytes-genotype VIII) has emerged as the primary species driving antifungal treatment failure worldwide. Clinically, T. indotineae infection may present as a typical dermatophyte infection, or atypically may mimic eczema, psoriasis, or other inflammatory dermatoses. Patients are often strikingly itchy and may be using topical steroid creams inappropriately in combination with antifungal and antibiotic agents. Terbinafine, once considered a first-line oral agent for tinea infections, often fails against T. indotineae, for which prolonged courses of itraconazole (often at higher than typical dermatophyte dosing) are now regarded as the treatment of choice. Fluconazole and griseofulvin demonstrate limited efficacy. Antifungal susceptibility testing may guide treatment choices but is not well established for dermatophytoses. Dermatologists should be aware of an approach to evaluating and treating refractory dermatophyte infections. Increased awareness among clinicians, including in infectious diseases, primary care, and the emergency room, is also important to facilitate early recognition, appropriate management, and timely referral. Dermatologists may play a key role in promoting antifungal stewardship and educating other clinician groups about emerging dermatophyte infections. In this review, we detail T. indotineae with a focus on clinical presentation, diagnostic confirmation, and treatment.
Artificial intelligence technology is being widely developed in dermatology. However, there remains a lack of comprehensive data analyzing the diagnostic performance of artificial intelligence in skin cancer. We aimed to evaluate the diagnostic accuracy of artificial intelligence in skin cancer detection. MEDLINE, Embase, Cochrane library, Web of Science, and Scopus were searched from database inception to 9 April, 2025. Studies were included if they exclusively assessed the diagnostic accuracy of artificial intelligence for primary cutaneous malignancies. The artificial intelligence performance in skin cancer diagnosis was evaluated using accuracy, area under the curve value, sensitivity, and specificity. Twenty-eight systematic reviews and meta-analyses were included. Across the studies, reported sensitivity ranged from 83.7 to 94.4
BACKGROUND:Ruxolitinib cream (1.5%) has demonstrated efficacy and safety in patients aged ≥ 2 years with mild-to-moderate atopic dermatitis. OBJECTIVE:We aimed to further investigate the safety and efficacy of ruxolitinib cream in adolescents with atopic dermatitis in an open-label study. METHODS:Patients aged 12-17 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, ≥ 75% improvement from baseline in Eczema Area and Severity Index, achievement of Investigator's Global Assessment score of 0/1, and ≥ 4-point improvement from baseline in the itch Numerical Rating Scale were exploratory endpoints. RESULTS: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 ≥ 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%; ≥ 75% improvement from baseline in Eczema Area and Severity Index, 87.0%; Investigator's Global Assessment 0/1, 82.6%; ≥ 4-point improvement from baseline in itch Numerical Rating Scale, 41.7%). CONCLUSIONS: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. CLINICAL TRIAL REGISTRATION:Clinicaltrials.gov identifier, NCT05456529 (registered 13 July, 2022).
