Hasil untuk "Dermatology"

Silvia Crescioli, Hélène Kaplon, Alicia Chenoweth et al.

The Antibodies to Watch article series provides annual updates on commercial late-stage clinical development, regulatory review, and marketing approvals of antibody therapeutics. Since the first article was published in 2010, the late-stage pipeline has grown from 26 antibody therapeutics to over 200, while during the same time numerous molecules in late-stage studies either transitioned to regulatory review and were approved or were terminated. In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in regulatory review, including the bispecific antibody-drug conjugate izalontamab brengitecan, and predict which molecules of the 209 currently in the commercial late-stage pipeline might transition to regulatory review by the end of 2026. Most antibody therapeutics in the latter category are for non-cancer indications (16/21, 76%) and have a conventional format (13/21, 62%), but the category also includes numerous antibody-oligo or -drug conjugates, such as delpacibart etedesiran, delpacibart zotadirsen, zeleciment rostudirsen, sonesitatug vedotin, trastuzumab pamirtecan, and ifinatamab deruxtecan, as well as the bispecific petosemtamab. As antibody therapeutics development is a global enterprise, we also discuss trends in annual first approvals granted to antibody therapeutics in any country since 2010, stratified by the antibody’s country of origin, documenting the notable increases in the total number of first approvals and those approved first in China. Finally, to benchmark the time typically required for clinical development and regulatory review, we calculated this period for recently approved antibody therapeutic products stratified by their therapeutic area, mechanism of action, format, and country of origin. Our data show that the development and approval period were typically ~6 years, but on average this period was shorter for China-originated products.

Julia Nowowiejska-Purpurowicz, Vincenzo Piccolo, Luigina Urso et al.

Anne Sofie Frølunde, Jan Brink Valentin, Lise Kristensen et al.

Dermatophyte infections are common in general practice and occur more often in individuals with type 2 diabetes (T2D), but whether they signal undiagnosed T2D remains unclear. We conducted a register-based cohort study including positive PCR tests for dermatophyte infection from the feet or nails, matched 1:3 to individuals from the same geographic area in Denmark. Those with known diabetes, type 1 diabetes or aged under 20 were excluded. Incidence rates (IRs) and incidence rate ratios (IRRs) for new-onset T2D were estimated using Poisson regression. The final cohort comprised 78,140 individuals, with a median age of 51 years, and 60.8% were male. The IR for T2D was 9.23 per 100 person-years in the exposed group and 9.00 in the unexposed group, with an adjusted IRR of 1.00 (0.91–1.11, p=0.94), indicating no significant association. In a sensitivity analysis excluding unexposed individuals with prior topical antifungal treatment, the IRR increased to 1.15 (1.08–1.23, p=0.001). While the primary analysis showed no significant association, the sensitivity analysis suggested a modest increased risk when exposure misclassification was reduced, supporting dermatophyte infection as a possible early signal of undiagnosed T2D in selected populations.

Julia Welzel

Shou-En Wu, Wei‑Ming Wang, Chih-Tsung Hung et al.

Abstract Background Dysregulated DNA methylation and hypertension (HTN) are closely associated with the development of psoriasis. However, the impact of the vasodilator hydralazine (HLZ), which also inhibits DNA methyltransferase, on psoriasis risk remains unclear. This study investigated the association of HLZ use with the risk of psoriasis and the severity of incident psoriasis. Methods This nationwide cohort study utilized data from the Taiwan Longitudinal Generation Tracking Database (2000–2015). We compared three propensity score-matched groups: patients with HTN treated with HLZ (HTN and HLZ cohort, n = 61,794), patients with HTN on other antihypertensives (HTN and non-HLZ cohort, n = 247,176), and patients without HTN (non-HTN cohort, n = 247,176). Results Patients with HTN using HLZ exhibited a lower risk of psoriasis than those using other antihypertensive agents [adjusted hazard ratio (aHR): 0.786, 95% CI: 0.535–0.930, p = 0.015]. Furthermore, the HTN and HLZ cohort was associated with a lower likelihood of requiring systemic treatment (aHR: 0.672, 95% CI: 0.522–0.894, p < 0.001) and linked to a lower risk of cause-specific mortality (aHR: 1.531 vs. 1.625, p < 0.001). Conclusions In this large-scale observational study, HLZ use was associated with a lower risk and reduced severity of incident psoriasis in patients with HTN. While these findings cannot establish causality, they provide compelling real-world evidence to support further investigation into repurposing HLZ as a potential epigenetic modulator for psoriasis.

Marija Ćorović, Anja Petrov Ivanković, Ana Milivojević et al.

<b>Background/Objectives</b>: Numerous intrinsic and extrinsic stressors can disrupt the balance of the skin microbiome, leading to the development of various skin diseases. It has been proven that coagulase-negative staphylococci (CoNS) are important commensals for maintaining skin microbiome homeostasis and fighting cutaneous pathogens such as <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Here, we examined the influence of polyphenol-rich enzymatic blackcurrant extract (EBCE) on pathogenic coagulase-positive <i>S. aureus</i> strains and beneficial CoNS, like <i>Staphylococcus epidermidis</i> (<i>S. epidermidis</i>), to explore its potential for rebalancing the skin microbiota. <b>Methods</b>: The polyphenol profile of EBCE was determined by ultra-high-pressure liquid chromatography–tandem mass spectrometry. Microwell plate assays were employed to study the effect of EBCE on five <i>S. aureus</i> strains isolated from the skin of atopic dermatitis patients. An in vitro human <i>stratum corneum</i> model was used to test its effect on mixed bacterial cultures. <b>Results</b>: EBCE inhibited the growth of all tested <i>S. aureus</i> strains by 80–100% at the highest tested concentration after 7 h. No microbial growth was observed at the highest tested EBCE concentration using the <i>stratum corneum</i> model inoculated with one selected pathogen (<i>S. aureus</i> SA-DUS-017) and one commensal laboratory strain (<i>S. epidermidis</i> DSM 20044). The lowest tested concentration did not interfere with <i>S. aureus</i> growth but strongly stimulated the growth of <i>S. epidermidis</i> (~300-fold colony forming unit increase). In addition, low EBCE concentrations strongly stimulated CoNS growth in microbiome samples taken from the armpits of healthy volunteers that were spiked with <i>S. aureus</i> SA-DUS-017. <b>Conclusions</b>: These preclinical data support further testing of EBCE-enriched topical preparations as potential cutaneous prebiotics in human studies.

Julia Berner, Malin Sieben, Eric Freund et al.

Abstract Infected skin tumors are challenging to treat and frequently result in tumor progression, relapses, and post-surgical complications. Moreover, bacterial infections significantly contribute to tumor therapy resistance as they release tumor microenvironment (TME)-modulating molecules. Immune or cancer cells can recognize these pathogen-associated molecular patterns (PAMPs), initiating signaling and pro- or antitumoral response. Hence, understanding PAMPs in tumor therapy may improve the understanding and efficacy of cancer treatment. Cold gas plasma treatment has shown promise in treating infected, ulcerative head and neck cancers. Here, we elucidated gas plasma-induced bacterial PAMP release and their combination with direct gas plasma exposure in skin cancer cells in vitro. Evaluating metabolic activity and viability of tumor cells revealed a significantly stronger growth-inhibitory effect of the combinatory treatment, suggesting a relevant contribution of bacterial molecules to tumor toxicity. A synergistic effect was found regarding the oxidative damage marker γH2AX that was elevated in response to the combination treatment. Cancer cells subjected to gas plasma and provoked PAMPs exhibited an altered phenotype that displayed a strikingly different chemokine and cytokine profile. Mass spectrometry analysis showed improved bacterial cell lysis by gas plasma treatment, increasing intracellular protein release of all three tested bacterial strains.

Dario Tomasini, Carlo F. Tomasini, Andrea Michelerio et al.

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish–brown papules. Four main types of DDD with variable clinical presentations likely related to the heterogeneity of the gene variant landscape have been implicated. Pathogenic keratin 5 gene K5 gene variants favor a reticular distribution with predominant fold involvement, whereas pathogenic variants in POGLUT1 lead to a widespread form with acantholytic features previously named Galli–Galli disease, now belonging to the disease spectrum of DDD and renamed DDD type 4. This study details the clinical and histopathological features associated with the sequence variant c.205C>T, p.(Arg69∗) in POGLUT1 of 2 families from northern Italy affected by DDD4. Despite sharing the same variant, clinical manifestations varied among the affected members of the 2 families. Environmental factors probably contributed to phenotypic variability and symptoms exacerbation. Histopathology was sustained by digitiform rete ridges, suprabasal acantholysis, and dyskeratosis. Moreover, we detected aberrant keratin 5 gene K5 expression in 2 biopsies. A review of the literature on POGLUT1-related DDD subtypes contextualizes these findings. The fact that several patients have been reported to carry the variant c.205C>T, p.(Arg69∗) might point to a potential mutational hotspot.

L. Parish

Hiroshi Ohguro, Megumi Watanabe, Tatsuya Sato et al.

Cell culture methods are indispensable strategies for studies in biological sciences and for drug discovery and testing. Most cell cultures have been developed using two-dimensional (2D) culture methods, but three-dimensional (3D) culture techniques enable the establishment of <i>in vitro</i> models that replicate various pathogenic conditions and they provide valuable insights into the pathophysiology of various diseases as well as more precise results in tests for drug efficacy. However, one difficulty in the use of 3D cultures is selection of the appropriate 3D cell culture technique for the study purpose among the various techniques ranging from the simplest single cell type-derived spheroid culture to the more sophisticated organoid cultures. In the simplest single cell type-derived spheroid cultures, there are also various scaffold-assisted methods such as hydrogel-assisted cultures, biofilm-assisted cultures, particle-assisted cultures, and magnet particle-assisted cultures, as well as non-assisted methods, such as static suspension cultures, floating cultures, and hanging drop cultures. Since each method can be differently influenced by various factors such as gravity force, buoyant force, centrifugal force, and magnetic force, in addition to non-physiological scaffolds, each method has its own advantages and disadvantages, and the methods have different suitable applications. We have been focusing on the use of a hanging drop culture method for modeling various non-cancerous and cancerous diseases because this technique is affected only by gravity force and buoyant force and is thus the simplest method among the various single cell type-derived spheroid culture methods. We have found that the biological natures of spheroids generated even by the simplest method of hanging drop cultures are completely different from those of 2D cultured cells. In this review, we focus on the biological aspects of single cell type-derived spheroid culture and its applications in <i>in vitro</i> models for various diseases.

Li Jie Helena Yoo, Nekma Meah, Dmitri Wall et al.

Introduction: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia that represents a form of follicular lichen planus. Case Presentation: We describe a case of coexisting diffuse LPP and female pattern hair loss masquerading as diffuse alopecia areata in a 32-year-old female. Discussion: In complex cases such as this, dermoscopy-guided vertical and horizontal biopsies from androgen sensitive and insensitive areas are helpful in increasing diagnostic yield. Prompt initiation of treatment is key to halting disease progression. Long-term follow-up is important as resolution of clinical signs does not always correlate with the absence of disease progression.

Zhiqiang Zhang, Weiwei Shi, Ruzhi Zhang

Key Clinical Message Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that can be easily misdiagnosed in its early stages. Clinicians should maintain a high index of suspicion for rapidly growing skin lesions in elderly patients and promptly investigate with histopathology and immunohistochemistry. Treatment for MCC should be individualized, considering the patient's age, overall health, and quality of life. Close follow‐up is essential to detect recurrence or metastasis early.

Kamina Wilkerson, BS, Flora E. Bradley, MD, Ernest Y. Lee, MD, PhD et al.

Murad Alam

Arjan F Theil, Alex Pines, Tuğba Kalayci et al.

Abstract The brittle hair syndrome Trichothiodystrophy (TTD) is characterized by variable clinical features, including photosensitivity, ichthyosis, growth retardation, microcephaly, intellectual disability, hypogonadism, and anaemia. TTD‐associated mutations typically cause unstable mutant proteins involved in various steps of gene expression, severely reducing steady‐state mutant protein levels. However, to date, no such link to instability of gene‐expression factors for TTD‐associated mutations in MPLKIP/TTDN1 has been established. Here, we present seven additional TTD individuals with MPLKIP mutations from five consanguineous families, with a newly identified MPLKIP variant in one family. By mass spectrometry‐based interaction proteomics, we demonstrate that MPLKIP interacts with core splicing factors and the lariat debranching protein DBR1. MPLKIP‐deficient primary fibroblasts have reduced steady‐state DBR1 protein levels. Using Human Skin Equivalents (HSEs), we observed impaired keratinocyte differentiation associated with compromised splicing and eventually, an imbalanced proteome affecting skin development and, interestingly, also the immune system. Our data show that MPLKIP, through its DBR1 stabilizing role, is implicated in mRNA splicing, which is of particular importance in highly differentiated tissue.

J. Heinlin, G. Isbary, Wilhelm Stolz et al.

Somenath Sarkar, Tanusree Sarkar, Aparesh C Patra et al.

Background: Leprosy is a chronic granulomatous disease mainly affecting the peripheral nerves and skin. Any communities including the tribals are susceptible to leprosy. Very few studies on clinico-epidemiological patterns of leprosy have been reported in the tribal population, especially in the Choto Nagpur plateau. Aims: To observe clinical types of newly diagnosed leprosy cases among the tribal population and demonstrate bacteriological index, frequency of deformity, and lepra reaction at presentation. Methods: An institution-based cross-sectional study was conducted with consecutive newly diagnosed tribal leprosy patients attending the leprosy clinic of a tribal-based tertiary care center of Choto Nagpur plateau of eastern India, from January 2015 to December 2019. Thorough history taking and clinical examination were done. A slit skin smear for AFB was performed to demonstrate the bacteriological index. Results: There was a steady rise in total leprosy cases from 2015 to 2019. Borderline tuberculoid (BT) was the commonest form of leprosy (64.83%). Pure neuritic leprosy was not uncommon (16.26%). Multibacillary leprosy was noted in 74.72% of cases and childhood leprosy was observed in 6.70% of cases. The commonest nerve involved was the ulnar nerve. Garde II deformity was noted in around 20% of cases. AFB positivity was observed in 13.73% of cases. A high bacteriological index (BI ≥3) was noted in 10.65% of cases. Lepra reaction was observed in 25.38% of cases. Conclusion: BT leprosy, pure neuritic leprosy, childhood leprosy, grade II deformity, and higher AFB positivity were prevalent in this study. The tribal population required special attention and care for the prevention of leprosy amongst them.

C. Bichakjian, A. Halpern, T. Johnson et al.

Daniela Antoniali, Andrezza Telles Westin, Fernanda André Martins Cruz et al.

Abstract Monilethrix is a rare defect of the hair shaft, with most cases showing an autosomal dominant pattern of inheritance and variable clinical expression. It is characterized by hypotrichosis secondary to hair fragility. The diagnosis is made through trichoscopy, detecting typical findings such as periodic narrowing at regular intervals, giving the hair the appearance of beads in a rosary. This article reports the case of six members of a family diagnosed with monilethrix with alopecia of varying degrees.

Pumori Saokar Telang

Vitamin C is a potent antioxidant drug that can be used topically in dermatology to treat and prevent changes associated with photoageing. It can also be used for the treatment of hyperpigmentation. Because it is unstable and difficult to deliver into the dermis in the optimum dosage, research is being directed to find stable compounds of Vitamin C and newer methods of delivery of Vitamin C into the dermis.