Cutaneous and Ocular Toxicology最新文献

Background: Combination of targeted therapy and immune checkpoint inhibitors (ICIs) is a leading approach in the treatment of advanced hepatocellular carcinoma (HCC). However, an increased incidence of skin rashes poses a clinical challenge. Understanding the acute cutaneous adverse drug reactions (CADRs) during the early stage of the combination treatment is crucial.

Objective: To investigate the clinical characteristics of acute CADRs in HCC patients undergoing combined targeted agents and ICIs and identify potential risk factors contributing to the development of severe CADRs phenotypes.

Methods: A retrospective analysis of 33 HCC patients with acute CADRs following combination therapy was conducted. Patients were categorized into maculopapular eruption (MPE) group and atypical targetoid eruption (ATE) group based on the rash phenotypes. Clinical characteristics were compared between the subgroups, and the administration pattern of the combination therapy was analyzed.

Results: 16 MPE cases and 17 ATE cases were identified. No other types of acute skin eruptions were documented. Patients with ATE developed rashes with a shorter time latency, experienced more systemic symptoms, showed higher severity grades, had longer disease courses, and demonstrated a lower rate of successful rechallenge compared to patients with MPE. The ATE group displayed a significantly higher percentage receiving full-dose targeted agents and a shorter interval between targeted agents and ICIs upon initiation of combination therapy.

Conclusions: In HCC patients receiving combined regimens, atypical targetoid rashes indicate a more severe CADR. Full-dose targeted agents and shorter intervals between targeted agents and ICIs may contribute to the more severe CADR phenotype.

Objective: This study aimed to assess the potential risk of Bullous pemphigoid (BP) associated with antidiabetic agents, antimicrobials, diuretics, immune checkpoint inhibitors, and biological agents.

Research design and methods: A retrospective pharmacovigilance data analysis was conducted using the FDA Adverse Event Reporting System (FAERS) between Q1/2004 and Q3/2024. Disproportionality analyses, viz. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were performed to identify signals of BP. Additionally, a literature review of case reports of BP was conducted in PubMed, Google Scholar, and Scopus.

Results: Disproportionality analysis identified 61 signals, and the following drugs exhibited the highest number of BP case associations: metformin (596 cases), vildagliptin (406 cases), nivolumab (376 cases), and furosemide (301 cases). Strong statistical correlation for signals was observed for vildagliptin [PRR = 295.8, LB (lower bound) ROR = 287.2, IC₀₂₅ = 7.5], dapsone [PRR = 20.7, LBROR = 14.4, IC₀₂₅ = 3.4], furosemide [PRR = 7.2, LBROR = 6.4, IC₀₂₅ = 2.6], and nivolumab [PRR = 31.5, LBROR = 28.5, IC₀₂₅ = 4.6]. These findings were supported by 106 identified case reports of BP.

Conclusion: This study suggests a strong statistical correlation between vildagliptin, dapsone, furosemide, nivolumab, and the development of BP.

Objective: Scarring alopecias are chronic inflammatory disorders characterised by irreversible hair follicle destruction. In this study, we aimed to evaluate the potential roles of serum ferritin, folate, vitamin B12, vitamin D levels and thyroid function markers in the pathogenesis of scarring alopecias.

Aterials and methods: Between 2020 and 2025, a total of 68 patients over the age of 18 who were diagnosed with scarring alopecia based on clinical and/or histopathological findings and whose medical records were accessible retrospectively were included in the study, along with 68 healthy control subjects. Serum levels of ferritin, folate, vitamin B12, vitamin D, and thyroid function markers were recorded and statistically compared between groups.

Results: Among patients with scarring alopecia, 91.2% were female (n = 62), with a mean age of 47.25 ± 12.98 years. The average disease duration was 34.37 ± 24.22 months (min: 3, max: 144). The distribution of diagnoses among patients was as follows; lichen planopilaris in 45.6% (n = 21), frontal fibrosing alopecia in 29.4% (n = 20), pseudopelade in 16.2% (n = 11), discoid lupus erythematosus in 7.4% (n = 5), and folliculitis decalvans in 1.5% (n = 1). There were no statistically significant differences between patients with scarring alopecia and the control group regarding serum vitamin B12 (340.19 ± 107.950 vs. 357.04 ± 107.549 ng/L, p = 0.373), folate (11.89 ± 6.11 vs. 12.23 ± 6.53 ng/mL, p = 0.767), ferritin (34.75 ± 38.05 vs. 39.89 ± 66.74 µg/L, p = 0.593), and vitamin D (54.3 ± 26.57 vs. 58.59 ± 37.38 nmol/L, p = 0.434) levels. Thyroid function tests (TSH and free T4) were also similar between the two groups (p > 0.05).

Conclusion: Our study demonstrated that serum ferritin, folate, vitamin B12, vitamin D levels and thyroid function in patients with scarring alopecia were similar to those in the healthy control group.

Purpose: Some preservatives in eye drops induce corneal epithelial damage. Diquafosol sodium, a dry eye treatment drug released in 2022, contains silver nitrate as a preservative. This study examined the effects of diquafosol sodium ophthalmic solution and silver nitrate solution on the barrier function of corneal epithelial cells in rabbit eyes.

Patients and methods: The 14 rabbits included in the study were divided into 7 eye drop treatment groups (4 eyes per group): (1) 3% diquafosol (Diquas) without silver nitrate; (2) 3% Diquas LX containing silver nitrate; (3) 3% Diquas LX without silver nitrate; (4) 0.01% silver nitrate; (5) 0.1% silver nitrate; (6) 1% silver nitrate; and (7) saline. Electrical corneal resistance (CR) was measured using a CR-measuring device (CRD) at 30, 60, and 120 minutes after the final instillation, and CR% was calculated. Corneal epithelial damage was evaluated using fluorescein staining 120 minutes after the final instillation.Corneal tissue obtained 120 minutes post-instillation was fixed in 4% paraformaldehyde, permeabilized, and blocked. Zonula occludens-1 protein, which constitutes tight junctions between epithelial cells, was visualized using whole-mount immunohistochemical staining. To examine the expression of ZO-1 in corneal epithelial cells, photographs of the outermost layer of the cornea were taken.

Results: CR in the Diquas LX group 1 (containing silver nitrate) reached its peak value (114.2 ± 7.1%) 60 minutes after the final instillation, which was comparable to that in the 0.1% silver nitrate group (117.2 ± 17.6%) and significantly higher than that in the Diquas group 3 (without silver nitrate) (98.8 ± 5.8%; P < 0.05). Zonular occludens-1 protein was localized in a continuous linear pattern at the boundary between epithelial cells in all three Diquas groups.

Conclusions: Diquas LX eye drops containing silver nitrate significantly increased CR compared to Diquas eye drops without silver nitrate and improved corneal barrier function. Silver nitrate as a preservative may have contributed to this effect.

Study purpose: Botulinum toxin (BoNT) is commonly used for both cosmetic and medical purposes. However, improper use can lead to iatrogenic botulism. This scoping review aimed to evaluate the systemic and skin-related effects, identify risk factors, and highlight safety gaps in BoNT-related botulism.

Methods: We followed PRISMA-ScR guidelines to search for literature from 1997 to 2024 across PubMed, Scopus, EMBASE, and Google Scholar. Ten case reports (113 patient cases) met the inclusion criteria.

Results: Females accounted for 78.8% of cases. Systemic symptoms typically developed within four days after the injection. Notably, 46% of cases involved unlicensed BoNT products, raising safety concerns. Among the licensed formulations, Abobotulinum toxin A accounted for 33.6% of cases, Onabotulinum toxin A for 10.6%, and other or unspecified products for 9.7%. Doses ranged from 100 to 2000 units (average of 487±312 units). Intramuscular injection was the most common method at 60.2%. Common symptoms included dysphagia in 82.3% of cases, ptosis in 78.8%, and generalized weakness in 65.5%. Respiratory failure occurred in 12.4% of severe cases. Interestingly, there were no consistent reports of skin or injection-site reactions, suggesting potential underreporting of skin-related effects. Treatments included antitoxin in 59.3% of cases and pyridostigmine in 24.8%. The majority of patients, 86.7%, fully recovered, though six experienced symptoms lasting over six months.

Conclusion: Both licensed and unlicensed BoNT products can lead to iatrogenic botulism. Inconsistent reporting of skin complications highlights a gap in safety data. Adhering to proper injection protocols and thoroughly documenting adverse events is crucial for enhancing patient safety.

Introduction: Teledermatology, which utilizes communication technologies to remotely assess skin lesions, has become a vital tool in healthcare. This study aimed to compare the diagnostic accuracy of teledermatology versus face-to-face examination and explore factors influencing accuracy, such as teledermatoscopy use, dermatoscopy type, and clinical experience.

Methods: Fifty-seven cutaneous tumors were evaluated using handheld or digital dermatoscopy in face-to-face examinations, and preliminary diagnoses were recorded. A definitive diagnosis was established through histopathological examination, which served as the reference standard. Macro and dermatoscopic images were then sent to six teledermatologists for remote diagnosis, and findings were analyzed statistically.

Results: The preliminary diagnosis matched the histopathological diagnosis in 84.2% of face-to-face cases. Teledermatologists achieved 63.7% accuracy with macro images alone, increasing to 70.8% with dermatoscopic images. Teledermatology showed lower accuracy than face-to-face examination, regardless of whether teledermatoscopy was used (p < 0.05), but accuracy significantly improved with dermatoscopic images (p = 0.004). The teledermatology's accuracy for malignancy prediction was comparable to face-to-face examination (p > 0.05). Dermatoscopy type did not significantly impact accuracy (p > 0.05), while longer clinical experience correlated with higher accuracy (p < 0.05). Interrater reliability was poor for specific diagnoses but improved when categorizing lesions as malignant or benign (κ = 0.192, κ = 0.683).

Conclusion: Although teledermatology performed below face-to-face examination in terms of specific diagnoses, it remained effective in distinguishing between benign and malignant cutaneous tumors. The inclusion of teledermatoscopy and longer clinical experience enhanced diagnostic accuracy.

Objective: Wound repair remains a significant challenge in the field of regenerative medicine. Notably, while numerous studies have investigated the effects of isolated nicotine or chlorogenic acid, the systematic evaluation of tobacco ethanol extract (TEE) on cutaneous wound healing has remained uncharted territory. Therefore, this study aims to systematically explore TEE's multifaceted effect on wound healing.

Methods: The hepatorenal toxicity of 5% TEE was evaluated in 6-7-week-old ICR mice. Subsequently, full-thickness 6 mm wounds were created, and images were captured on days 0, 3, 6, 9, and 12. Tissues were collected for H&E staining, Masson trichrome staining, and immunohistochemistry to assess wound healing.

Results: The TEE we prepared showed little hepatorenal toxicity (p > 0.05). By day 12, the wound closure rate in the TEE group reached 95.26%, significantly higher than that in the vehicle group (89.20%, p < 0.05). Histopathological analysis demonstrated that TEE reduced neutrophil infiltration in the wound tissues, accelerated granulation tissue formation, and increased collagen content by 20.99% compared to the vehicle group (p < 0.05). Immunohistochemical staining revealed that on day 6, the positive areas of IL-6 and TNF-α in the TEE group were 5.91% and 4.87% lower than those in the vehicle group (p < 0.05), respectively. On day 9, CD31 expression in the TEE group (8.58%) was significantly higher than that in the vehicle group (5.54%) (p < 0.05).

Conclusion: This study reveals that TEE accelerates wound healing, providing new insights into effective topical therapies for skin wounds while highlighting the potential for tobacco waste valorization.

Kaposi sarcoma (KS) is a vascular tumour with four main clinical types-classic, endemic, iatrogenic, and epidemic-all linked to infection by human herpesvirus 8 (HHV-8). This retrospective cohort study assessed the relationship between demographic factors and clinical characteristics in 73 patients with biopsy-proven KS treated at a single dermatology centre between 2009 and 2023. Demographic and clinical data, including age, gender, birthplace, blood type, smoking, alcohol use, HIV status, tumour site, and disease stage, were collected and statistically analysed. Most patients were male (77%), with a mean age of 61 years, and the classic KS subtype predominated (86%). The majority (75%) had tumours localised to the extremities. HIV-positive status was diagnosed in 14% of cases and was strongly associated with non-extremity tumour location and increased visceral involvement. Notably, blood type showed a significant association with tumour localisation: 0Rh- and ARh- blood groups were less common in KS patients with extremity tumours. This is the first study to demonstrate a significant relationship between blood group and KS tumour site, introducing a novel epidemiological association. Smoking and alcohol consumption were each significantly linked to higher HIV positivity rates. Patients from the Mediterranean region had a higher frequency of HIV-positive KS, although birthplace did not correlate with disease stage. No associations were observed between gender and disease type. The study is limited by its retrospective design and missing data for certain variables, but it identifies potentially novel patterns-including a possible link between blood group and tumour location-and confirms known associations, such as HIV status with advanced disease. These findings underscore the complexity of KS presentation and suggest that demographic, clinical, and lifestyle factors may shape disease patterns. Prospective, multicentre studies are needed to validate these findings and guide personalised approaches to KS management.

Background: LUXTURNA^® (voretigene neparvovec-rzyl) is the first FDA-approved gene therapy for inherited retinal dystrophies caused by biallelic RPE65 mutations. While pivotal clinical trials established its safety and efficacy, there has been no formal analysis of real world data to date.

Methods: We reviewed published literature and regulatory safety databases, including the FDA Adverse Event Reporting System and EudraVigilance, to assess clinical outcomes and adverse event reporting associated with LUXTURNA^®.

Results: Clinical trials demonstrated durable functional vision improvements, with approximately 70% of patients maintaining gains up to four years post-treatment. Adverse events reported in trials were largely mild to moderate, such as conjunctival hyperemia, cataract, and transient intraocular pressure elevation. Post-marketing surveillance, however, revealed additional safety concerns, most notably chorioretinal atrophy (CRA), which has been reported in 13-50% of treated eyes, particularly in younger patients and often near the injection site. Disproportionality analyses confirmed CRA as the most prominent adverse event, alongside elevated risks for retinal tears or detachment, intraocular pressure changes, ocular hemorrhage, and inflammation. Despite these findings, central visual acuity was generally preserved, and no systemic toxicity was identified.

Conclusions: LUXTURNA^® provides meaningful and durable visual benefits for patients with RPE65-related disease, but long-term monitoring is essential to address its emerging ocular safety profile. Our data represent the first comprehensive pharmacovigilance review of LUXTURNA^®, providing critical insights for clinical practice and post-marketing surveillance.

Background: Anogenital warts (AGWs) are typically caused by low-risk HPV types. Coinfection with EBV and CMV may influence disease progression, especially under immunosuppression. This study aimed to detect HPV, EBV, and CMV in tissue samples from AGW patients. This descriptive, retrospective, single-center study aimed to detect HPV, EBV, and CMV DNA in paraffin-embedded tissue samples from patients with AGWs.

Material and methods: Paraffin-embedded tissues from 24 AGW patients were analyzed using real-time PCR and pyrosequencing for HPV, EBV, and CMV DNA. Demographic and viral data were statistically evaluated. Degraded or insufficient DNA samples were excluded following quality control assessment. Descriptive and comparative statistical analyses were performed using SPSS v22.0.

Results: HPV was detected in 62.5% of patients, most commonly type 6, followed by types 40, 87, and 16. EBV was found in 2 patients (8.3%), both with HPV coinfection. HPV. CMV was not detected in any samples. No statistically significant associations were found between demographic or clinical parameters and viral positivity.

Conclusion: The study identified rare EBV and HPV coinfections in AGWs but no CMV positivity. These findings are descriptive, and the small sample size limits generalization. The presence of EBV in immunosuppressed individuals may suggest immunotoxic mechanisms affecting viral persistence in the skin. Further studies with larger cohorts are warranted.