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Search Results (1,099)

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15 pages, 525 KB  
Article
Organ–System Predictors of Immune–Related Adverse Events and Their Prognostic Impact in Immune Checkpoint Inhibitors–Treated Cancer Patients: A MENA Retrospective Cohort
by Ali Awada, Ali Tarhini, Abbas Hammoud, Mohammad Kassem, Joe Rizkallah, Mohammad Al Hajjar, Ali Dakik, Michael Romanos, Sary Faraj, Duha Awada, Lara Soueid, Razane Wehbe, Karim Kalout, Nicole Charbel and Firas Kreidieh
Cancers 2026, 18(13), 2167; https://doi.org/10.3390/cancers18132167 (registering DOI) - 6 Jul 2026
Abstract
Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with immune-related adverse events (irAEs) and variable clinical outcomes. Clinical predictors of organ-specific irAEs remain indeterminate, particularly in real-world populations. Methods: We conducted a retrospective single-center cohort study including 751 adult [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with immune-related adverse events (irAEs) and variable clinical outcomes. Clinical predictors of organ-specific irAEs remain indeterminate, particularly in real-world populations. Methods: We conducted a retrospective single-center cohort study including 751 adult patients with solid tumors treated with ICIs between 2018 and 2025. Clinical, demographic, and treatment-related variables were analyzed. Multivariable logistic regression identified predictors of irAEs, while associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using logistic and Cox regression models. Results: The most frequent irAEs were endocrine (9.9%), dermatologic (9.1%), gastrointestinal (7.6%), and pulmonary (4.7%). Female sex independently predicted endocrine (aOR 1.98, p = 0.007) and rheumatologic irAEs (aOR 4.06, p = 0.007). Combination immunotherapy was associated with increased dermatologic (aOR 2.66, p = 0.013) and gastrointestinal irAEs (aOR 2.65, p = 0.016), while concurrent radiotherapy predicted gastrointestinal toxicity (aOR 1.82, p = 0.044). Atezolizumab was associated with higher pulmonary irAE risk (aOR 2.97, p = 0.048). Endocrine, dermatologic, gastrointestinal, and pulmonary irAEs were independently associated with improved ORR (OR range: 2.53–4.30, all p < 0.01). Conclusions: Organ-specific irAEs exhibit distinct clinical predictors and differential prognostic implications in patients receiving ICIs. Select irAEs are associated with improved treatment response and disease control, yet our results should be regarded as hypothesis-generating requiring further investigation. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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18 pages, 873 KB  
Article
Chronic Skin Disease, Media Use and Health Values in the Quality of Life of Adolescents
by Katalin Julianna Dinnyés and Zsanett Renáta Csoma
Children 2026, 13(7), 899; https://doi.org/10.3390/children13070899 (registering DOI) - 6 Jul 2026
Abstract
Introduction: Chronic dermatological diseases that appear in adolescence, such as acne vulgaris, atopic dermatitis, alopecia areata and psoriasis vulgaris, not only cause physical symptoms but also significantly affect young people’s quality of life, mental state, self-esteem and social relationships. Social media, especially information [...] Read more.
Introduction: Chronic dermatological diseases that appear in adolescence, such as acne vulgaris, atopic dermatitis, alopecia areata and psoriasis vulgaris, not only cause physical symptoms but also significantly affect young people’s quality of life, mental state, self-esteem and social relationships. Social media, especially information spread by influencers, significantly influences adolescents’ body image, health-related attitudes and even the quality of the physician-patient relationship. The aim of our study was to explore the relationships between dermatology-related quality of life, media use, health values, body image and self-esteem among adolescents with chronic dermatological diseases. Methods: In our cross-sectional, quantitative study, we used validated questionnaires (DLQI, EQ-5D-5L, IRVS, Attitude Scale, STAI-Y2, SWLS-H, Rosenberg Scale, BAT), which we supplemented with a media consumption questionnaire of our own design. Structured data collection took place between October 2024 and March 2025, with the participation of 208 adolescents aged 11–18. Data analysis was performed using SPSS 26.0 (Spearman’s correlation, Mann–Whitney test). Differences were considered significant at p < 0.05. Ethical approval: BM/22429-1/2024. Results: Acne vulgaris was the most common diagnosis (65%), followed by atopic dermatitis (22%) and psoriasis (11%). Over a quarter of the adolescents (27%) followed influencers who provided skincare advice. The mean daily screen time was 4.5 h, with 3.7 h on smartphones. A longer screen time was significantly correlated with poorer dermatological quality of life. Greater dermatology-related quality of life impairment (higher DLQI scores) was associated with poorer general quality of life (EQ-5D-5L). Following skincare-related influencers was significantly associated with dermatology-related quality of life and anxiety. Conversely, stronger health values were significantly linked to more favourable health behaviors. Conclusions: In this sample, greater dermatology-related quality-of-life impairment was associated with poorer psychosocial outcomes. Longer screen time was associated with poorer dermatology-related quality of life and less favourable psychosocial outcomes. The novelty of our study lies in the use of a self-developed media consumption questionnaire, which is suitable for the complex mapping of psychological and quality-of-life factors in adolescents. Full article
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12 pages, 1660 KB  
Review
Recognizing the Clinical and Pathophysiologic Overlap Between Allergy and Lupus
by Veena Patel
Allergies 2026, 6(3), 24; https://doi.org/10.3390/allergies6030024 (registering DOI) - 6 Jul 2026
Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by diverse and evolving clinical manifestations, often resulting in delayed diagnosis and increased morbidity. Although traditionally viewed as distinct, allergic and autoimmune diseases share overlapping immunologic pathways and clinical features. Symptoms commonly encountered [...] Read more.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by diverse and evolving clinical manifestations, often resulting in delayed diagnosis and increased morbidity. Although traditionally viewed as distinct, allergic and autoimmune diseases share overlapping immunologic pathways and clinical features. Symptoms commonly encountered in allergy practice, including urticaria, angioedema, and pruritus, may represent early or coexisting manifestations of underlying lupus rather than primary allergic disease. This narrative review examines the clinical and pathophysiologic overlap between allergy and lupus, with a focus on presentations that may bring patients with undiagnosed SLE to the allergy setting. Shared mechanisms, including complement dysregulation, autoreactive IgE, and mast cell activation, are discussed as contributors to overlapping symptomatology. Key clinical features that distinguish lupus-associated presentations from primary allergic conditions are outlined, along with associated systemic findings that should prompt further evaluation. A practical approach to assessment is emphasized, including targeted history, judicious use of serologic testing, and indications for dermatologic and rheumatologic referral. Improved recognition of these patterns in allergy practice may facilitate earlier diagnosis, reduce unnecessary testing, and improve patient outcomes. Full article
(This article belongs to the Section Physiopathology)
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11 pages, 223 KB  
Review
Medical and Surgical Management of Hidradenitis Suppurativa
by John W. Frew and Falk G. Bechara
J. Clin. Med. 2026, 15(13), 5238; https://doi.org/10.3390/jcm15135238 (registering DOI) - 4 Jul 2026
Abstract
Background: HS is a chronic inflammatory skin disease in which inflammatory nodules and abscesses coexist with tunnels, fibrosis, and scarring. This dual biology explains why medical therapy often improves inflammatory dissease activity without fully addressing fixed tissue damage, whereas surgery can achieve durable [...] Read more.
Background: HS is a chronic inflammatory skin disease in which inflammatory nodules and abscesses coexist with tunnels, fibrosis, and scarring. This dual biology explains why medical therapy often improves inflammatory dissease activity without fully addressing fixed tissue damage, whereas surgery can achieve durable local control but does not treat diffuse inflammatory burden. Contemporary international guidelines increasingly endorse multimodal and medicosurgical care. Objective: To critically compare the evidence supporting medical and surgical management of HS, with emphasis on outcomes, indications, limitations, and clinical decision-making relevant to contemporary practice. Methods: A structured review was undertaken using PubMed/MEDLINE, the Cochrane Library, and major dermatology guideline sources, with searches updated to 7 May 2026. Priority was given to clinical guidelines, systematic reviews and meta-analyses, randomized controlled trials, and higher-quality observational studies. Evidence was synthesized narratively because endpoints, populations, and follow-up intervals differed markedly across medical and surgical studies. Results: Medical evidence is strongest for biologic therapy in moderate-to-severe inflammatory HS. Weekly adalimumab improved week-12 HiSCR in the phase 3 PIONEER trials; secukinumab improved week-16 and week-52 outcomes in SUNSHINE/SUNRISE; and bimekizumab improved week-16 HiSCR50 in BE HEARD I/II. Surgical evidence is strongest for wide excision in structurally advanced disease, particularly when compared with local excision or incision and drainage. Meta-analytic data consistently show lower recurrence after wide excision than after local excision, and lower recurrence after flap or graft reconstruction than after primary closure. Combined therapy is increasingly supported: peri-operative adalimumab improved outcomes in SHARPS, and surgery plus adalimumab outperformed adalimumab alone in a pragmatic 12-month RCT. Conclusions: HS is best managed by matching treatment to disease phenotype. Medical therapy is essential for inflammatory control; surgery is essential for persistent tunnels, fibrosis, and scarred regional disease. The strongest overall clinical position is an integrated, multidisciplinary model in which systemic therapy reduces inflammatory load and surgery definitively treats irreversible tissue damage. Full article
13 pages, 6354 KB  
Case Report
Hydroxychloroquine-Induced AGEP with Positive Rechallenge: A Case Report and Mini Review of the Literature
by Kristijan Jovanović, Tamara Umeljic Sočević, Milos Stepovic, Jovana Milosavljević, Jovica Tomović, Miroslav M. Sovrlić, Marko Folić, Miloš N. Milosavljević, Dalibor Jovanović and Nevena Folić
Dermatopathology 2026, 13(3), 30; https://doi.org/10.3390/dermatopathology13030030 - 3 Jul 2026
Viewed by 113
Abstract
Background/Objectives: Hydroxychloroquine is widely used in the treatment of autoimmune and dermatologic diseases; however, it may rarely induce severe cutaneous adverse reactions. Acute Generalized Exanthematous Pustulosis is an uncommon, acute pustular eruption most frequently associated with antibiotics. Hydroxychloroquine-induced AGEP remains relatively rare and [...] Read more.
Background/Objectives: Hydroxychloroquine is widely used in the treatment of autoimmune and dermatologic diseases; however, it may rarely induce severe cutaneous adverse reactions. Acute Generalized Exanthematous Pustulosis is an uncommon, acute pustular eruption most frequently associated with antibiotics. Hydroxychloroquine-induced AGEP remains relatively rare and diagnostically challenging due to its atypical and prolonged clinical course. Case presentation: We report the case of a 45-year-old woman with rheumatoid arthritis and a complex medical history who developed generalized urticarial and pustular dermatosis following re-exposure to hydroxychloroquine. Notably, the patient had experienced a similar cutaneous reaction after previous exposure to the same medication several years earlier. Ten days after completing a treatment course of hydroxychloroquine, she developed rapidly progressive pruritic erythematous and urticarial plaques that evolved into generalized annular lesions with peripheral scaling and grouped sterile pustules. Laboratory evaluation demonstrated leukocytosis, intermittent eosinophilia, and elevated IgE levels, while the infectious workup was negative. Histopathological examination revealed subcorneal pustules with neutrophilic infiltration, mild spongiosis, and scattered individual eosinophils, perivascular inflammatory infiltrates, findings consistent with AGEP. Retrospective assessment using the EuroSCAR scoring system classified the reaction as probable AGEP, while the Naranjo adverse drug reaction scale supported a probable causal relationship with hydroxychloroquine. Clinical improvement was achieved after withdrawal of the drug and treatment with systemic corticosteroids and supportive therapy. Conclusions: This case highlights the importance of recognizing atypical presentations compatible with hydroxychloroquine-induced probable AGEP and emphasizes the diagnostic value of a positive rechallenge as supportive evidence of drug causality. Early recognition and prompt discontinuation of the offending agent are essential to prevent severe complications and recurrence. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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6 pages, 634 KB  
Proceeding Paper
Wood’s Lamp: A Valuable Tool for Diagnosing Dermatological Diseases and Assessing Facial Skin Hydration Levels
by Nina Lazar, Roxana Gheorghita, Florin Filip, Ruxandra Filip and Roxana Filip
Eng. Proc. 2026, 148(1), 8; https://doi.org/10.3390/engproc2026148008 - 30 Jun 2026
Viewed by 80
Abstract
The skin, as the body’s largest organ, reflects overall health and is shaped by factors such as diet, habits, work environment, and lifestyle. A Wood’s lamp offers significant advantages for assessing skin health. Our study leveraged Wood’s lamp to evaluate facial skin hydration [...] Read more.
The skin, as the body’s largest organ, reflects overall health and is shaped by factors such as diet, habits, work environment, and lifestyle. A Wood’s lamp offers significant advantages for assessing skin health. Our study leveraged Wood’s lamp to evaluate facial skin hydration and the impact of a diet rich in water, fruits, and vegetables. Conducted with 14 women, the study included the assessment of skin hydration levels. Remarkable improvements were observed in 13 participants, including enhanced skin hydration, reduced surface lesions, and better-regulated sebum levels. Full article
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23 pages, 22562 KB  
Article
The Natural Phloroglucinol α-Pyrone Arzanol Protects HaCaT Keratinocytes from Lipopolysaccharide and Polyriboinosinic-Polyribocytidylic Acid-Induced Damage and Promotes Reparative Mechanisms
by Franca Piras, Valeria Sogos, Aurora Camola, Federica Pollastro and Antonella Rosa
Appl. Sci. 2026, 16(13), 6472; https://doi.org/10.3390/app16136472 - 29 Jun 2026
Viewed by 208
Abstract
The protective effect of arzanol, a natural prenylated phloroglucinol α-pyrone from the Helichrysum microphyllum subsp. tyrrhenicum, was investigated in HaCaT keratinocytes exposed to two inflammatory stimuli: lipopolysaccharide (LPS, 0.5–75 µg/mL), a component of gram-negative bacteria, and polyriboinosinic-polyribocytidylic acid (poly I:C, 0.5–50 µg/mL), [...] Read more.
The protective effect of arzanol, a natural prenylated phloroglucinol α-pyrone from the Helichrysum microphyllum subsp. tyrrhenicum, was investigated in HaCaT keratinocytes exposed to two inflammatory stimuli: lipopolysaccharide (LPS, 0.5–75 µg/mL), a component of gram-negative bacteria, and polyriboinosinic-polyribocytidylic acid (poly I:C, 0.5–50 µg/mL), a synthetic viral RNA analog. LPS and poly I:C significantly decreased HaCaT cell viability (18–93% reduction in the 5–75 μg/mL LPS range and 25% at 50 μg/mL poly I:C, MTT assay) and increased apoptosis and cell death (NucView 488 and propidium iodide assay) after 3 h and 24 h of exposure. Arzanol (1 h of pre-incubation, 5–25 μM) showed a significant protective effect against LPS and poly I:C-induced damage, preserving cell viability (25% of viability increase at 5 μg/mL LPS concentration, and 30% at 50 μg/mL of poly I:C) and decreasing apoptosis/cell death. Western blot analysis demonstrated the ability of arzanol (5 μM) to reduce the apoptotic protein Bax and the inflammatory cytokine IL-1β levels in HaCaT keratinocytes exposed for 3 h to 5 and 10 μg/mL LPS. Moreover, scratch assay showed the arzanol reparative effect on HaCaT cells. Our results qualified arzanol as a protective drug for dermatological applications in human skin diseases. Full article
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27 pages, 561 KB  
Review
Toxicities of Antibody–Drug Conjugates in Breast Cancer: From Mechanistic Insights to Clinical Management
by Luisana Sisca, Mariam Grazia Polito, Arianna Travisani, Fernando Zannino, Michele Iuliani, Giuseppe Tonini and Francesco Pantano
Pharmaceutics 2026, 18(7), 792; https://doi.org/10.3390/pharmaceutics18070792 - 28 Jun 2026
Viewed by 211
Abstract
Background/Objectives: Antibody–drug conjugates (ADCs) have transformed the therapeutic landscape of breast cancer, expanding treatment opportunities across multiple disease settings. However, their increasing clinical use has revealed a heterogeneous spectrum of toxicities that extends beyond conventional chemotherapy-related adverse events. Emerging evidence suggests that ADC-associated [...] Read more.
Background/Objectives: Antibody–drug conjugates (ADCs) have transformed the therapeutic landscape of breast cancer, expanding treatment opportunities across multiple disease settings. However, their increasing clinical use has revealed a heterogeneous spectrum of toxicities that extends beyond conventional chemotherapy-related adverse events. Emerging evidence suggests that ADC-associated toxicities are driven by a complex interplay between ADC structural characteristics, including target antigen expression, payload properties, linker stability, drug-to-antibody ratio, and patient-related susceptibility factors. This review aims to provide a comprehensive overview of ADC-related toxicities in breast cancer, integrating mechanistic insights with clinical management strategies and risk-adapted approaches. Methods: A narrative review of the literature was conducted focusing on clinical trials, real-world studies, translational investigations, and mechanistic evidence related to ADC-associated toxicities in breast cancer. Particular attention was given to the relationship between ADC design, toxicity mechanisms, patient-specific risk factors, and clinical management. Results: ADC-related toxicities encompass a broad range of adverse events, including hematologic toxicity, interstitial lung disease, gastrointestinal complications, hepatotoxicity, peripheral neuropathy, stomatitis, ocular toxicity, dermatologic adverse events, and cardiovascular manifestations. Current evidence indicates that toxicity profiles differ substantially across ADCs and are influenced by multiple factors, including payload class, linker chemistry, target biology, intracellular trafficking, bystander effects, systemic payload exposure, and host-related characteristics. While several toxicities can be anticipated through careful monitoring and early intervention, clinically significant variability remains, and validated predictive biomarkers are largely lacking. Emerging real-world evidence further highlights the importance of individualized toxicity assessment and multidisciplinary management. Conclusions: ADC-related toxicity should be viewed as a multifactorial biological process resulting from the interaction between ADC design and host susceptibility rather than as a uniform class effect. A mechanistic understanding of toxicity pathways may improve risk stratification, toxicity monitoring, and personalized management strategies. Future research should focus on the development of predictive biomarkers, pharmacologic risk models, and next-generation ADC platforms with improved therapeutic indices. This review proposes an integrated framework linking ADC structural determinants, toxicity mechanisms, and clinical management to support safer and more individualized use of ADCs in breast cancer. Full article
(This article belongs to the Special Issue Recent Advances in Antibody–Drug Conjugates for Cancer Therapy)
35 pages, 1486 KB  
Review
Copper Complexes: Emerging Micro- and Nanosystems for Dermatological Treatment
by Ireri Hernández-Rojas, Javier Aguila-Rosas, Oswaldo Castañeda Hernández, Carlos Martínez-Armenta, Verónica Barón-Flores, Betzabeth A. García-Martínez and Camilo Rios
Pharmaceutics 2026, 18(7), 784; https://doi.org/10.3390/pharmaceutics18070784 - 26 Jun 2026
Viewed by 221
Abstract
The use of copper complexes as pharmacotherapy represents an emerging strategy with multiple therapeutic advantages, including their enhanced bioavailability, antimicrobial activity, and ability to participate in diverse cellular processes. These molecules, combined with micro- and nanosystems, offer an advanced approach to the sustained [...] Read more.
The use of copper complexes as pharmacotherapy represents an emerging strategy with multiple therapeutic advantages, including their enhanced bioavailability, antimicrobial activity, and ability to participate in diverse cellular processes. These molecules, combined with micro- and nanosystems, offer an advanced approach to the sustained delivery of copper, optimizing its absorption while potentially reducing adverse effects. In this review, we highlight the application of copper complexes reported in recent studies for dermatological diseases and infection management. Furthermore, evidence indicates that copper promotes cell regeneration in wounds and burns, accelerating wound healing. However, their clinical translation requires careful consideration of copper homeostasis, as dysregulation may lead to oxidative stress and toxicity. In perspective, the combination of micro- and nanoformulations with specific copper complexes offers new opportunities for tailored therapies, as well as for the optimization of pharmacokinetics, positioning copper as a multifunctional therapeutic agent in regenerative and supplementation medicine. However, further investigation is required to establish safety, optimal dosing, and long-term effects. Full article
15 pages, 1133 KB  
Article
Psychiatric Comorbidity in Hidradenitis Suppurativa—A Large-Scale Retrospective Cohort Study
by Beata Jastrząb-Miśkiewicz, Jacek C. Szepietowski and Piotr K. Krajewski
J. Clin. Med. 2026, 15(13), 4982; https://doi.org/10.3390/jcm15134982 - 26 Jun 2026
Viewed by 175
Abstract
Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric burden, but longitudinal data on incident psychiatric outcomes remain limited. This study aimed to evaluate incident psychiatric disorders in adults with HS compared with matched non-HS controls and to [...] Read more.
Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric burden, but longitudinal data on incident psychiatric outcomes remain limited. This study aimed to evaluate incident psychiatric disorders in adults with HS compared with matched non-HS controls and to assess sex-specific risk. Methods: We conducted a retrospective propensity score–matched cohort study using the TriNetX Global Collaborative Network. Adults with at least two HS diagnoses and no prior psychiatric diagnosis were compared with non-HS controls with repeated general health examination encounters and no psychiatric history. Time-to-event analyses estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses used a 30-day lag and restriction to the most recent 5-year period. Results: After matching, 37,964 pairs were retained for the primary individual-outcome analysis. Median follow-up was shorter in the HS cohort than in matched controls (844 vs. 1505 days). HS was associated with increased risk of any psychiatric disorder (12.3% vs. 5.8%; HR 3.17, 95% CI 3.01–3.34) and severe psychiatric illness (0.6% vs. 0.1%; HR 6.70, 95% CI 4.77–9.41). Elevated risks were observed for bipolar/manic disorders, personality disorders, substance use disorders, psychotic disorders, suicidal ideation, depression, eating disorders, anxiety, and insomnia/parasomnia. Women had higher hazards of depression and anxiety, whereas men had higher hazards of substance use disorders; insomnia/parasomnia showed a nominal association with higher hazard in men. Conclusions: In this observational EHR-based study, HS was associated with broad incident psychiatric morbidity. These findings support consideration of proactive mental health assessment and integrated dermatologic–psychiatric care in patients with HS. Full article
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32 pages, 1475 KB  
Review
Explainable Artificial Intelligence for Skin Lesion Classification: A Comprehensive Review of Methods and Challenges
by Jennifer Whewell, Rebecca Peters and Janusz Kulon
Technologies 2026, 14(7), 391; https://doi.org/10.3390/technologies14070391 - 25 Jun 2026
Viewed by 368
Abstract
The rapid advancement of machine learning and artificial intelligence (AI) has created new opportunities to enhance diagnostic accuracy in dermatology, particularly within primary care settings. Computer-aided diagnosis (CAD) systems have demonstrated potential to support General Practitioners (GPs) by enabling earlier and more consistent [...] Read more.
The rapid advancement of machine learning and artificial intelligence (AI) has created new opportunities to enhance diagnostic accuracy in dermatology, particularly within primary care settings. Computer-aided diagnosis (CAD) systems have demonstrated potential to support General Practitioners (GPs) by enabling earlier and more consistent identification of skin diseases. This review critically examines the literature on explainable artificial intelligence (XAI) for skin disease classification, with a specific focus on the evolution of explainability frameworks and the methodological implications of dataset selection. A comprehensive review of studies published between 2020 and 2025 was conducted across multiple academic databases, encompassing research on skin lesion detection, classification, and monitoring. The analysis reveals that deep learning architectures, particularly those leveraging transfer learning with models such as EfficientNet, ResNet, and Xception, frequently report high classification accuracies—often exceeding 90% when evaluated on single benchmark datasets. However, studies employing multiple datasets consistently demonstrate more stable and generalisable performance, albeit with modest reductions in reported accuracy, highlighting a critical trade-off between performance optimisation and real-world robustness. The review further identifies a clear temporal progression in the adoption of XAI techniques. Early studies relied on a broader range of post hoc explainability while later work increasingly consolidated around Grad-CAM, SHAP, and related attribution techniques, followed by gradual diversification into more specialised frameworks such as TCAVs (Testing with Concept Activation Vectors) and Prototype-based Networks. Despite these advances, the lack of clinically grounded explanations, limited integration of ethical considerations, and reliance on non-clinical imagery continue to constrain clinical applicability which we have explored using a GRADE-style narrative. Notably, evidence suggests that CAD systems can improve GP diagnostic accuracy for conditions such as melanoma and seborrhoeic keratosis; however, sustained clinical adoption remains contingent on transparent, reliable, and context-aware explainability mechanisms. Full article
(This article belongs to the Special Issue AI-Enabled Smart Healthcare Systems)
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22 pages, 924 KB  
Review
Resistance and Recalcitrance in Dermatophytosis: Mechanistic and Clinical Considerations for Keratinized Tissues
by Alfredo Valdez-Martinez, Roberto Arenas, Andrea Moreno-Salinas, Mariana Perez-Tristan, Maria Jose Gomez-Rico, Ivette Torres-Olguín, Claudia Erika Fuentes-Venado, Fernando Bastida-González, Erick Martínez-Herrera and Rodolfo Pinto-Almazán
Antibiotics 2026, 15(7), 634; https://doi.org/10.3390/antibiotics15070634 - 24 Jun 2026
Viewed by 179
Abstract
Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by [...] Read more.
Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by diagnostic uncertainty, corticosteroid-modified disease, reinfection, inadequate exposure, poor adherence, and limited drug delivery within keratinized tissues. This narrative review was developed to clarify the distinction between true antifungal resistance and clinical recalcitrance, with particular attention to terbinafine-resistant Trichophyton species, Trichophyton indotineae, tinea incognito, onychomycosis, dermatophytoma, and high-barrier skin and nail infections. We synthesized peer-reviewed literature and guideline-level evidence addressing epidemiology, molecular mechanisms of resistance, clinical phenotypes of recalcitrance, diagnostic escalation, therapeutic decision-making, and antifungal delivery in keratinized tissues. The review contributes a dermatology-centered conceptual framework in which persistent dermatophytosis is interpreted through both microbiological resistance and modifiable recalcitrance drivers. This approach emphasizes confirmation of fungal disease when indicated, phenotypic and anatomic classification, avoidance of inappropriate corticosteroid combinations, optimization of dose, duration, vehicle, and adherence, measures to improve drug access and reduce protected fungal burden in high-barrier disease, and prevention of reinfection from reservoirs. The proposed framework may support more rational antifungal use and reduce unnecessary escalation; however, it is based on narrative synthesis rather than a systematic review or prospective validation. Additional studies are needed to determine how such structured clinical approaches affect clinical outcomes, relapse rates, antifungal exposure, and resistance emergence in real-world dermatology practice. Full article
(This article belongs to the Section Fungi and Their Metabolites)
12 pages, 230 KB  
Article
Long-Term Real-World Effectiveness and Response Trajectories of Dupilumab in Paediatric Atopic Dermatitis
by Małgorzata Ponikowska, Emilia Kucharczyk, Karol Biliński, Danuta Nowicka and Łukasz Lewandowski
J. Clin. Med. 2026, 15(13), 4862; https://doi.org/10.3390/jcm15134862 - 23 Jun 2026
Viewed by 210
Abstract
Background/Objectives: Long-term real-world data on dupilumab effectiveness and response trajectories in paediatric atopic dermatitis (AD) remain limited. This study evaluated long-term effectiveness, safety, response durability, and treatment trajectories in paediatric patients with moderate-to-severe AD treated with dupilumab. Methods: This retrospective single-centre cohort study [...] Read more.
Background/Objectives: Long-term real-world data on dupilumab effectiveness and response trajectories in paediatric atopic dermatitis (AD) remain limited. This study evaluated long-term effectiveness, safety, response durability, and treatment trajectories in paediatric patients with moderate-to-severe AD treated with dupilumab. Methods: This retrospective single-centre cohort study included 55 paediatric patients with moderate-to-severe AD treated with dupilumab. Clinical outcomes, including Eczema Area and Severity Index (EASI), body surface area (BSA), and Children’s Dermatology Life Quality Index (CDLQI), were assessed longitudinally throughout treatment. The primary endpoint was the achievement of EASI-75 over the course of treatment, including timing of response onset. Secondary endpoints included EASI-90 achievement, longitudinal changes in disease severity and quality of life, treatment durability, safety, and response trajectory analyses. Patients were additionally classified into mutually exclusive trajectory groups based on timing and durability of EASI-75 achievement. Results: Dupilumab treatment was associated with rapid and sustained clinical improvement. Some patients achieved EASI-75 as early as week 4, highlighting interindividual variability in response kinetics. At week 16, EASI-75 was achieved in 85.5% of patients and EASI-90 in 47.3%. Clinical effectiveness further improved during long-term follow-up, with EASI-75 achieved in 96.2% and EASI-90 in 86.5% of patients at the last available follow-up. Median CDLQI decreased from 22.0 at baseline to 3.0 during follow-up, indicating marked improvement in quality of life. Most patients (83.6%) were classified as early responders, while 10.9% demonstrated delayed but clinically meaningful improvement during continued treatment. Loss of response after initial EASI-75 achievement was uncommon (3.7%). Adverse events were predominantly mild, with eosinophilia and conjunctivitis representing the most frequently observed findings. Conclusions: Overall, dupilumab demonstrated high long-term effectiveness and favourable tolerability in paediatric patients with moderate-to-severe AD. Trajectory analyses revealed clinically meaningful heterogeneity in response kinetics despite favourable long-term outcomes, highlighting that delayed responders may still achieve substantial benefit during continued therapy. Full article
(This article belongs to the Special Issue Innovative Systemic Treatments for Atopic Dermatitis)
15 pages, 2361 KB  
Article
A Multicenter Analysis of Patients with Bullous Pemphigoid: Clinical Characteristics and Insights into Drug-Associated Disease
by Aleksandra Małolepsza, Aleksandra Kośny, Katarzyna Juczyńska, Joanna Czerwińska, Magdalena Jałowska, Marian Dmochowski, Aleksandra Dańczak-Pazdrowska, Agnieszka Owczarczyk-Saczonek, Irena Walecka, Cezary Kowalewski, Katarzyna Woźniak, Radosław Zajdel and Agnieszka Żebrowska
Int. J. Mol. Sci. 2026, 27(12), 5587; https://doi.org/10.3390/ijms27125587 - 20 Jun 2026
Viewed by 277
Abstract
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients with multiple comorbidities. This multicentre retrospective cohort study aimed to characterize the clinical profile, treatment patterns, and drug-associated cases of BP in a real-world setting. The study included [...] Read more.
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients with multiple comorbidities. This multicentre retrospective cohort study aimed to characterize the clinical profile, treatment patterns, and drug-associated cases of BP in a real-world setting. The study included 156 patients newly diagnosed with BP between 2020 and 2024 in four dermatology departments in Poland. Diagnosis was based on clinical features, and immunological assessment, including direct immunofluorescence (DIF), ELISA, and BIOCHIP-based indirect immunofluorescence. The mean age at diagnosis was 75.5 ± 10.9 years, and 78.85% of patients had at least one comorbidity, most commonly arterial hypertension, type 2 diabetes mellitus, and dyslipidemia. Severe pruritus was reported in 74.14% of evaluated patients. Blisters and erosions were the predominant clinical manifestations. Topical glucocorticosteroids were the most frequently used treatment, followed by systemic glucocorticosteroids and methotrexate. New drug exposure within 6 months before disease onset was identified in 14.74% of patients and was associated with a shorter time to diagnosis. Drug-associated cases showed lower BP180 ELISA positivity, although this did not remain significant after correction for multiple testing. These findings highlight the clinical complexity of BP and the importance of medication review and direct immunofluorescence in diagnostic evaluation. Full article
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Article
Clinical Outcomes of Once-Weekly Hypofractionated Intensity-Modulated Radiation Therapy with Concurrent α-Sulfoquinovosyl-Acylpropanediol for Modified Adams Stage 4 Canine Intranasal Tumors: A Retrospective Case Series
by Akihiro Ohnishi, Yuko Mizutani, Saki Kageyama, Shinya Mizutani and Taketoshi Asanuma
Vet. Sci. 2026, 13(6), 601; https://doi.org/10.3390/vetsci13060601 - 20 Jun 2026
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Abstract
We described tumor response and survival in dogs with modified Adams stage 4 intranasal tumors treated with once-weekly hypofractionated radiation therapy (RT) combined with the radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP), and compared linear and volumetric response assessments. Twenty dogs treated with intensity-modulated RT (8 Gy [...] Read more.
We described tumor response and survival in dogs with modified Adams stage 4 intranasal tumors treated with once-weekly hypofractionated radiation therapy (RT) combined with the radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP), and compared linear and volumetric response assessments. Twenty dogs treated with intensity-modulated RT (8 Gy per fraction, once weekly) and concurrent SQAP were included in this retrospective case series. Tumor response was assessed using RECIST-like linear measurements and volumetric analysis on contrast-enhanced computed tomography. Overall survival (OS) was estimated using Kaplan–Meier analysis. Of the 20 dogs, 4 were classified as stage 4a and 16 as stage 4b. The best RECIST-like responses were complete response (CR) in 5 dogs, partial response (PR) in 12, and stable disease (SD) in 4. Volumetric responses were CR in 5 dogs, PR in 11, and SD in 5. No cases demonstrated progressive disease as the best response. The median OS for all dogs was 342 days (95% confidence interval [CI], 206–419 days). Censoring one non-tumor-related death yielded a median OS of 356 days (95% CI, 231–419 days). Exploratory analysis revealed median OS of 393 and 297 days for stage 4a and 4b dogs, respectively. Volumetric assessment appeared more sensitive for detecting tumor regrowth in selected cases. Dermatologic adverse events were limited to alopecia within the radiation field, and no complete vision loss was observed. Seizure activity was documented in eight dogs. In conclusion, once-weekly hypofractionated intensity-modulated RT combined with concurrent SQAP was associated with clinically meaningful survival outcomes in dogs with advanced intranasal tumors. However, because no radiotherapy-alone control group was available, the independent contribution of SQAP to these outcomes could not be determined. Full article
(This article belongs to the Special Issue Advanced Therapy in Companion Animals—3rd Edition)
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