Skin Reactions Research Articles

Pseudoephedrine-induced Fixed Drug Eruption in a Scuba Diver With Recurrent Palmoplantar Exfoliation.

This report presents a case of pseudoephedrine-induced nonpigmented bullous fixed drug eruption (NBFDE) manifesting as recurrent palmoplantar exfoliation in a scuba diver. It emphasizes the importance of considering drug allergies in the differential diagnosis when divers present with peeling hands and soles. A 38-year-old female scuba diver experiencing recurrent palmoplantar exfoliation underwent a clinical evaluation, patch testing, an interferon-gamma enzyme-linked immunospot (ELISpot) assay, and graded drug challenges with pseudoephedrine and phenylephrine. Patch testing yielded negative results; however, the ELISpot assay indicated a strong immune response to pseudoephedrine. A graded challenge involving pseudoephedrine successfully reproduced the symptoms, confirming a diagnosis of pseudoephedrine-induced NBFDE. Subsequently, a challenge with phenylephrine elicited a milder reaction, suggesting it as a potential alternative medication for the patient. This case highlights NBFDE as a potential cause of skin peeling in scuba divers who are allergic to pseudoephedrine. It emphasizes the importance of considering drug allergies when diagnosing palmoplantar exfoliation in divers and underscores the need for a thorough evaluation of medication use in this group. Alternative medications and management strategies should be considered for divers with a pseudoephedrine allergy to prevent ear barotrauma while minimizing the risk of adverse skin reactions.

A disproportionality analysis of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Objective The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use. Methods AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. Results The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 319, 517, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc. Conclusion CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.

Experimentally investigated “CoronaDerm-PS”-driven SARS-CoV-2-specific cellular immunity and safety

Novel coronavirus disease 2019, caused by the SARS-CoV-2, initiate humoral and cellular immune responses against diverse virus antigens. The assessment of SARS-CoV-2-specific is mainly carried out in routine practice by determining specific immunoglobulins. However, high variability in S-protein structure in new genovariants of SARS-CoV-2 virus and the lack of correlation between specific antibodies and CD8+ T-lymphocytes underlie false negative responses, and mass assessment of cellular immunity is complicated due to the complexity of applying ELISPOT and cytofluorometry techniques. To solve this issue, a diagnostic method was developed for assessing SARS-CoV-2-specific cellular immune response, which is based on a skin test followed by evaluating a delayed-type hypersensitivity reaction involving antigen-specific memory T-lymphocytes. A diagnostic preparation CoronaDerm-PS is based on Cord_PS, which is a hybrid recombinant protein consisting of parts of the SARS-CoV-2 structural proteins S, M, N, E. The specific activity of this chimeric antigen was analyzed in cultured T-lymphocyte activation test by assessing interferon-γ production using cytofluorometry. To investigate the chimeric antigen specific activity, a preclinical safety study with CoronaDerm-PS preparation in experimental animals was conducted. A dose-dependent developing skin reaction was observed in 90–100% of guinea pigs vaccinated by EpiVacCorona, CoviVac, Gam-COVID-Vac, which confirms a potential for assessing post-vaccination cellular immunity using CoronaDerm-PS preparation. Upon this, the presence of functionally active T-cell-antigenic epitopes in the recombinant polypeptide allows to evaluate SARS-CoV-2-specific response illustrated by detected response after Gam-COVID-Vac (S-protein) and EpiVacCorona (N-protein) vaccination. Thus, a skin test based on CoronaDerm-PS preparation may be a promising diagnostic tool for rapid mass screening requiring no specialized laboratory equipment for assessing populational SARS-CoV-2-specific immunity. Such a test is distinguished by advantages such as ease of analysis, high specificity and sensitivity. The final decision-making on using this test in a real-world practice may achieved after conducting further clinical safety and effectiveness trials.

Vitamin D3 formation in milk by UV treatment – Novel insights into a rediscovered process

Vitamin D3 is essential for several functions in the human body and the demand is usually covered by natural reactions in skin with UV radiation delivered by the sun. But living beyond a latitude of 35° can lead to a lack of sufficient exposition to the deciding wavelength. Here, many countries fortify their milk prophylactically with artificial vitamin D3. However, the precursor molecule of vitamin D3 (7-deydrocholesterol) is already naturally located in the milk fat globule membrane. Thus, this study deals with the transformation of the naturally occurring 7-dehydrocholesterol into vitamin D3 through UV treatment of the milk - a mechanism that was observed a century ago only indirectly. Different parameters such as temperature (10 - 50°C), fluid flow regimen (turbulent vs. laminar thin film, i.e., 0.6 mm) and wavelength (254, 280 and 313 nm) were investigated in this study for their efficiencies. The UV dose of each experiment was measured with chemical actinometry delivering the actually applied dose reaching the milk. Thus, the connection between applied UV dose and generated vitamin D3 content in the milk measured quantitively with LC-MS/MS was evaluated here that both were not possible a hundred years ago. The experimental results revealed that temperature generally promotes the vitamin D3 formation at 254 nm. Further, a turbulent flow is not as efficiently treated as a laminar thin film flow that is as narrow as 0.6 mm. As expected from absorbance spectra of the precursor molecule 7-dehydrocholesterol, 280 nm turned out to be the most efficient wavelength, followed by intermediate success through irradiation with 254 nm and almost no effect by 313 nm. Generally, it was shown that vitamin D3 concentration of milk was easily increased by UV treatment with today's technologies and that adjustment of certain physical parameters have a significant effect on the efficiency.

Single Nucleotide Polymorphisms in APE1, hOGG1, RAD51 Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients.

Radiotherapy (RT) is a crucial treatment for head and neck cancer however, it causes adverse reactions to the normal tissue and organs adjacent to target tumor. The present study was carried out to investigate possible association of single nucleotide polymorphism in DNA repair genes with toxicity effects of radiotherapy on normal tissue. Three hundred and fifty head and neck cancer patients receiving radiotherapy treatment were enrolled in this study. The adverse after effects of radiotherapy on the normal tissue in the form of skin reactions were recorded. Single nucleotide polymorphisms of APE1 (rs1130409), hOGG1 (rs1052133) and Rad51 (rs1801320, rs1801321) genes were studied by polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing methods and their association with development of severe radio-toxicity effects was evaluated logistic regression analysis. The 172G/T polymorphism of Rad51 was 2.85 times higher and significantly associated with skin reactions (OR=2.85, 95% CI: 1.50-5.41; p=0.001) and severe oral mucositis (OR=4.96, 95% CI: 2.40-10.25; p<0.0001). These results suggested that the polymorphic nature of Rad51 is responsible for risk of radiotherapy adverse effects in HNC patients. The variant 326Cys and heterozygous 326Ser/Cys genotype of hOGG1 was significantly associated with high tumor grade (OR=3.16 95% CI: 1.66-5.99; p=0.0004, and OR=3.97 95% CI: 2.15-7.34; p=<0.0001 respectively). The homozygous variant 172TT genotype of Rad51 showed positive association with poor response of both tumor and nodes towards radiotherapy treatment (p=0.007 and p=0.022). Interpretation of our results revealed significant association of rs1801321 SNP of Rad51 with development of adverse toxicity reactions in normal tissue of head and neck cancer patients treated with radiotherapy.

Effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy.

To find out the effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy. This was a retrospective study. Sixty six patients with nasopharyngeal carcinoma who received radiotherapy in the Affiliated Hospital of Hebei University from March 2021 to March 2022 were included and randomly divided into the observation group and the control group, with 33 cases in each group. Patients in the control group were given conventional care measures, while those in the observation group were given psychological support intervention on top of conventional care measures. The nursing effects between the two groups were compared. After the intervention, the psychological resilience score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). The psychological resilience scores after the intervention were significantly higher in the observation group than before the intervention, and those in the control group were higher than before the intervention, with a statistically significant difference(P<0.05). The overall health score of quality of life in the observation group was significantly higher than that in the control group after the intervention, with a statistically significant difference(P<0.05). Moreover, the skin reaction in the observation group after radiotherapy was significantly better than that of the control group (P<0.01). Psychological support intervention is an effective means to treat patients with nasopharyngeal carcinoma, which results in various benefits such as improving patients' mental resilience and quality of life and reducing the incidence of adverse reactions after radiotherapy.

Maximizing the Use of Ivermectin Transethosomal Cream in the Treatment of Scabies.

In an effort to tackle the skin reactions frequently observed with topical application of ivermectin (IVM), a study was conducted to develop and optimize transethosomes (TESMs) loaded with IVM for scabies treatment. A three-factor, two-level (23) full factorial design was employed. Soyabean phosphatidylcholine concentration (A), ethanol concentration (B) and Span 60 amount (C) were studied as independent factors, while entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and drug release after 6 h (Q6h) were characterized. The skin sensitivity of the optimized formulation was evaluated by skin irritation test and histopathological examination. The EE% ranged from 88.55 ± 0.576% to 94.13 ± 0.305%, PS was from 318.033 ± 45.61 nm to 561.400 ± 45.17 nm, PDI was from 0.328 ± 0.139 to 0.671 ± 0.103, ZP was from -54.13 ± 1.09 mV to -60.50 ± 2.34 mV and Q6h was from 66.20 ± 0.30% to 93.46 ± 0.86%. The IVM-loaded transethosomal cream showed lower skin irritation and a more intact epidermal layer with intact keratinocyte, compared to the marketed cream which showed severe destruction of the keratin layer. Therefore, patient compliance can be improved by encapsulating IVM within TESMs to minimize its skin reactions.

Clinical and pathological characterization of Tebentafusp-associated skin toxicity – a cohort study with 33 patients.

BackgroundTebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects. ObjectivesThe aim of this study was to better characterize these heterogenous cutaneous side effects. MethodsThis prospective cohort study evaluated all patients from a tertiary hospital center who were treated with tebentafusp between January 2019 and June 2023 clinically and assessed skin biopsies histologically. ResultsIn total, 33 patients were analysed. Skin toxicity was observed in 78.8% of patients and was classified in five clinical categories: 1) symmetrical erythematous patches (83.8%), 2) hemorrhagic macules (11.8%), 3) urticarial lesions (7.4%), 4) bullous lesions (1.5%) and 5) skin (8.5%) and hair depigmentation (11.4%). Histopathologic features were focal lymphocytic interface dermatitis with epidermal infiltration of CD8-positive lymphocytes. Patients with skin reactions had a significantly longer median overall survival compared to patients without any cutaneous events (34 versus 4 months, p<0.001). LimitationMonocentric study with a limited number of patients. ConclusionTebentafusp frequently induced cutaneous reactions. Pathogenesis is likely due to binding of tebentafusp to stimulated melanocytes in the skin followed by infiltration and activation of lymphocytes. Development of treatment induced skin reactions may be associated with survival benefit.

Adverse Effects of Gefitinib on Skin and Colon in a Lung Cancer Mouse Model.

Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer. The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice. Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days. Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment. The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study.

Treatment of Canine Leishmaniasis with Meglumine Antimoniate: A Clinical Study of Tolerability and Efficacy.

Antimoniate therapy, in association with allopurinol, is one of the first-line treatments of canine leishmaniasis (CanL). This study evaluates the potential adverse effects associated with aNm in the treatment of CanL through both a retrospective analysis and a long-term prospective study also aimed to investigate its efficacy. The retrospective study reviewed records of 87 dogs with CanL with at least one follow-up available during or at the end of therapy with aNm (Glucantime®) at a dose of 50 mg/kg administered subcutaneously twice a day in association with allopurinol. In total, 29.8% of dogs showed adverse effects during treatment as local reactions at the injection site (n = 6), severe systemic reaction to pain (originating from the inoculation site) with depression and anorexia (n = 4), systemic disease due to renal function worsening (n = 4), acute pancreatitis (n = 1), diarrhea (n = 5), vomiting (n = 3) and severe idiosyncratic skin reactions (n = 3). Of these dogs, 13 (14.9%) required treatment suspension. The prospective study included 16 dogs, selected among the LeishVet stages II and III CKD IRIS stage 1 (International Renal Interest Society staging of canine Chronic Kidney Disease) and treated with the same aNm plus allopurinol protocol as in the retrospective study and observed for 360 days; 2 dogs were excluded for severe reactions at the injection site. Mild and transient adverse events were reported in the other 4 dogs. The criteria used to evaluate the efficacy of treatment with aNm were as follows: a reduction in the clinical score and improvement and/or normalization of laboratory parameters, negativization of PCR on the bone marrow samples and disease-free interval time. The proportion of reduction in the clinical score reached 91.9% at D180. No animals showed clinical laboratory relapse during the whole study duration and interestingly, the PCR results showed complete negativity between D0 and D60 in 78.5% of animals. Veterinarians must be vigilant regarding the potentially serious adverse effects associated with aNm and promptly stop drug administration if unexpected clinical manifestations occur. On the other hand, they should not discard its use for CanL treatment since it is confirmed that aNm in association with allopurinol is highly effective in controlling CanL.

A Severe Reaction After Phototherapy in a Neonate With X-Linked Protoporphyria.

Protoporphyria is a subtype of porphyria characterized primarily by painful phototoxic skin reactions after light exposure at specific wavelengths. Historically, phototherapy is not contraindicated in patients with protoporphyria since there have not been any reports of phototoxic reactions. However, patients with protoporphyria are advised to avoid direct sunlight. In this case report, we describe a neonate not known to have X-linked protoporphyria who received phototherapy for 1 to 2 hours. Within hours after initiation of phototherapy, this neonate developed a life-threatening reaction consisting of rash over the distribution of phototherapy, acute liver failure with coagulopathy, diffuse hypotonia with diaphragmatic failure, and subsequent acute respiratory failure that required mechanical ventilation. As in this case, patients with protoporphyria-related acute liver failure can have signs and symptoms similar to that of an acute hepatic porphyria attack. Neither neonatal reactions to phototherapy nor liver failure temporally associated with phototherapy have been reported in patients with X-linked protoporphyria. Early recognition of this entity is crucial in light of potential life-threatening complications. Therefore, providers must react quickly when neonates have abnormal reactions to phototherapy and consider protoporphyria in the differential diagnosis.

Acute toxicities in proton therapy for head and neck cancer – A matched analysis of the DAHANCA 35 feasibility study

Background and purposeAs preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. ResultsBaseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01–3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3–1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. ConclusionProton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

Thermovisiographic Study of Epicutaneous Testing with Dental Haptens in Different Concentrations

Dental haptens are used to study sensitization to their respective dental materials. The concentration of haptens is important for the diagnostic process, as different concentrations lead to different severity of skin reactions. The aim of the study was to examine the dermal reactivity to 15 dental haptens in two different concentrations after the Patch test, by thermal imaging and calculating the temperature parameters of the respective reactions. The present study included 15 haptens from five different categories of dental materials, each with two different concentrations, with the objective to examine the results ensuring the Patch test. Thirty-three patients were included in the study. A total of 990 skin reactions were observed. They were subject to standard and thermal imaging evaluation. Approximately 5% of reactions were positive. The thermovisiographic indicator `dT' confirms the results of the standard readings, as its values vary from 0 to 0.8 ⁰C in the case of positive reactions. The study observed no significant differences in the results based on gender, both in the standard and in the thermal imaging examination. The study also confirms that it is necessary to apply certain concentrations of each hapten depending on its nature.

Newly Developed Semi-Solid Formulations Containing Mellilotus officinalis Extract: Characterization, Assessment of Stability, Safety, and Anti-Inflammatory Activity.

Melilotus officinalis has been traditionally used as an anti-inflammatory agent; nevertheless, a comprehensive evaluation of its efficacy and safety and comparison with standard drugs are lacking. Taking into consideration concerns with current therapies, like efficacy limitations, side effects, and resistance, we aimed to develop a natural gel and cream based on Melilotus officinalis extract and explore their anti-inflammatory potential. After the chemical analysis of the extract confirmed the presence of coumarin, p-coumaric acid, gallic acid, and quercetin, formulations were prepared and subjected to physical and chemical stability evaluations over 6 months. The safety potential was tested in rats, while the anti-inflammatory activity was assessed both via in silico tests and in a rat model of inflammation. The examined formulations showed stable physical characteristics at the defined storage conditions and did not exert any sign of adverse skin reaction. The gel formulation exhibited a remarkable effect in inflammation reduction comparable with hydrocortisone. The in silico results suggest that coumarin, p-coumaric, and gallic acid bind to COX-1 and COX-2 with a lower affinity compared to diclofenac. On the other hand, quercetin demonstrated comparable inhibitory activity and stronger interaction compared to the control drug. Our results indicate that the examined formulations are stable and safe and may be promising dermal products for the alleviation of inflammatory skin conditions.

Novel insights into the heterogeneity of FOXP3 + Treg cells in drug-induced allergic reactions through single-cell transcriptomics.

This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.

Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.

Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.

Unwanted Skin Reactions to Acrylates: An Update

Unwanted Skin Reactions to Acrylates: An Update

Sensitization to Lanolin in North-Eastern Italy, 1997-2021: Prevalence, Risk Factors and the Impact of Occupation.

Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997-2021. Methods: European baseline and extended Triveneto series were applied on the upper part of patients' back and removed after 48 h. Risk factors for lanolin sensitization were investigated by multiple logistic regression analysis, reporting adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Results. Overall lanolin patch test positive ratio (PTPR) was 1.64% (=501/30,629), with variability over time and by research center. The body area most frequently affected by CD were hands (36.32%), followed by face (19.52%) and legs (8.09%), with a lanolin PTPR of 1.68%, 1.37% and 3.07%, respectively. Prevalence of occupational CD was 8.24%, and 1.83% patients with occupational CD patch tested positive against lanolin. Lanolin sensitization was significantly higher in males (aOR = 1.34; 95%CI: 1.08; 1.65) and among patients with leg CD aged 49-60 years (aOR = 2.34; 95%CI: 1.20; 4.57) or older than 60 (aOR = 4.21; 95%CI: 2.59; 6.85). Sub-group analysis confirmed the significantly higher sensitization rate of older patients with leg CD, with much stronger effect size in females 61+ years old (aOR = 5.33; 95%CI 2.87; 9.89) than males in the same age group (aOR = 2.92; 95%CI: 1.34; 6.39). Moreover, female house painters were more likely to test positive to lanolin. Conclusions: The variability of lanolin PTPR over time and by research center endorsed the ongoing debate on the relevance of the respective skin reaction. Clinicians assessing patients with dermatitis should collect information on potential risk factors for lanolin sensitization, particularly use of skin care products containing the hapten. Occupational exposure to lanolin-containing varnishes should also be considered.

Off-Label Uses of Upadacitinib

Background: Janus Kinase (JAK) inhibitors interfere with the JAK-STAT signaling pathway, which is vital in regulating inflammation and immune function. Notably, upadacitinib, a JAK inhibitor, has been increasingly used as a treatment modality for refractory inflammatory diseases. Methods: A literature review was conducted on Pubmed and Clinical Trials.gov using the keywords “upadacitinib” combined with “off-label”, “dermatology”, “skin”, or “cutaneous” from October 1st, 2021, to October 1st, 2023. 941 articles were reviewed, and 50 articles were included. Results: The systematic search revealed 20 different dermatology conditions treated with off-label use of upadacitinib. Most of these conditions showed drastic improvement by actively decreasing the inflammatory response involved in the pathogenesis of that condition. The most common side effects reported for the medication were elevated creatine kinase, headaches, urinary tract infections, and acne. Patients should also be advised to consider the shingles vaccines prior to upadacitinib treatment. Conclusion: Upadacitinib shows potential utility in the treatment of refractory inflammatory dermatologic conditions, treatment-resistant pruritus, and medication-induced skin reactions. Further large-scale, controlled clinical trials are needed to evaluate the further indications of upadacitinib and its safety profile.

Peripheral whole blood microRNA expression in relation to vascular function: a population-based study

BackgroundAs key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis.MethodsPeripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module’s expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis.ResultsFour modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion.ConclusionsWe identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.