Saikosaponin A Recovers Impaired Filaggrin Levels in Inflamed Skin by Downregulating the Expression of FRA1 and c-Jun.

Filaggrin (FLG) is an essential structural protein expressed in differentiated keratinocytes. Insufficient FLG expression contributes to the pathogenesis of chronic inflammatory skin diseases. Saikosaponin A (SSA), a bioactive oleanane-type triterpenoid, exerts anti-inflammatory activity. However, the effects of topically applied SSA on FLG expression in inflamed skin remain unclear. This study aimed to evaluate the biological activity of SSA in restoring reduced FLG expression. The effect of SSA on FLG expression in HaCaT cells was assessed through various biological methods, including reverse transcription PCR, quantitative real-time PCR, immunoblotting, and immunofluorescence staining. TNFα and IFNγ decreased FLG mRNA, cytoplasmic FLG protein levels, and FLG gene promoter-reporter activity compared to the control groups. However, the presence of SSA restored these effects. A series of FLG promoter-reporter constructs were generated to investigate the underlying mechanism of the effect of SSA on FLG expression. Mutation of the AP1-binding site (mtAP1) in the -343/+25 FLG promoter-reporter abrogated the decrease in reporter activities caused by TNFα + IFNγ, suggesting the importance of the AP1-binding site in reducing FLG expression. The SSA treatment restored FLG expression by inhibiting the expression and nuclear localization of FRA1 and c-Jun, components of AP1, triggered by TNFα + IFNγ stimulation. The ERK1/2 mitogen-activated protein kinase signaling pathway upregulates FRA1 and c-Jun expression, thereby reducing FLG levels. The SSA treatment inhibited ERK1/2 activation caused by TNFα + IFNγ stimulation and reduced the levels of FRA1 and c-Jun proteins in the nucleus, leading to a decrease in the binding of FRA1, c-Jun, p-STAT1, and HDAC1 to the AP1-binding site in the FLG promoter. The effect of SSA was evaluated in an animal study using a BALB/c mouse model, which induces human atopic-dermatitis-like skin lesions via the topical application of dinitrochlorobenzene. Topically applied SSA significantly reduced skin thickening, immune cell infiltration, and the expression of FRA1, c-Jun, and p-ERK1/2 compared to the vehicle-treated group. These results suggest that SSA can effectively recover impaired FLG levels in inflamed skin by preventing the formation of the repressor complex consisting of FRA1, c-Jun, HDAC1, and STAT1.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a pilot study.

PURPOSE: Previous literature has produced heterogeneous results on StrataXRT for prevention of acute radiation dermatitis (RD) in breast cancer. This pilot study aimed to assess the feasibility and efficacy of StrataXRT in a cancer center. METHODS: The study consisted of five cohorts: (1) patients with large breasts treated with local radiation therapy (RT) either in the supine position or (2) the prone position, (3) patients receiving locoregional breast RT with any breast size, and (4) patients receiving chest wall RT, either locally or (5) locoregionally. The primary endpoint of the study was RD grade as assessed using the Common Terminology Criteria for Adverse Events. Secondary endpoints included incidence of moist desquamation (MD), patient- and clinician-reported skin assessments, patient quality of life as assessed by the Skindex-16, and patient satisfaction. These outcomes were compared with those from a published trial from the same institution assessing standard of care and Mepitel Film (MF) as prevention of breast RD. RESULTS: Forty-five patients receiving RT to the breast or chest wall were enrolled. Two withdrew, leaving 43 evaluable patients. Overall, two (4.7%) patients had grade 3 RD, 14 (32.6%) had grade 2 RD, and 27 (62.8%) had grade 1 RD. Ten patients (23.3%) developed MD during/after RT. CONCLUSION: StrataXRT is effective in preventing grade 3 RD in patients, and the most promising results were observed within the prone cohort. Further research includes evaluating the efficacy of StrataXRT against the standard of care for the prophylaxis of RD. TRIAL REGISTRATION: The study protocol was registered at ClinicalTrials.gov (identifier: NCT05594498) on October 13, 2022.

Mapping the relationship between atopic dermatitis and gut microbiota: a bibliometric analysis, 2014-2023.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition affecting a significant portion of the population, with prevalence rates of 25% in children and 7-10% in adults. AD not only poses physical challenges but also profoundly impacts patients' mental well-being and quality of life. The stability of gut microbiota is crucial for overall health and can influence AD progression by modulating immune function, skin barrier integrity, and neuroendocrine signaling, which may be an effective target for the prevention and treatment of AD. Thus, exploring the interactions between AD and gut microbiota, particularly in infants, can provide insights into potential preventive and therapeutic strategies. This study aimed to explore the correlation between AD and gut microbiota while providing an overview of current research trends and emerging areas of interest in this field. Methods: A comprehensive search was conducted on the Web of Science Core Collection (WOSCC) for relevant publications from January 1, 2014, to December 31, 2023. English-language articles and reviews were included. Two investigators independently screened the publications, and visual analysis was performed using CiteSpace, VOSviewer, Scimago Graphica, and Microsoft Excel software. Results: A total of 804 articles were included, showing a significant increase in publications over the past decade. The United States, Wageningen University, and University Ulsan (represented by Hong SJ) had the highest number of published papers. Nutrients was the journal with the most publications, while the Journal of Allergy and Clinical Immunology had the highest number of citations and centrality among co-cited journals. Keyword visualization analysis identified "atopic dermatitis" and "gut microbiota" as central themes. Notably, there has been a notable shift in research focus over the years, with early studies concentrating on "Fecal microbiota," "caesarean section," and "first 6 months," while recent studies have highlighted the roles of "cells," "dysbiosis," and "prebiotics." This shift indicates growing interest in the underlying mechanisms and potential therapeutic interventions related to the intestinal microecology in AD treatment. Conclusion: The field of AD and gut microbiota research has evolved significantly, with an increasing focus on understanding the intricate interactions between gut microbiota and AD pathogenesis. Recent years have witnessed increased interest in understanding the relationship between AD and gut microbiota, with researchers conducting extensive studies exploring various aspects of this connection. This review analyzes research trends over the past decade, highlighting trends and hotspots in the study of AD, particularly in infants, and the role of microbiota. This review serves as a valuable reference for future investigations, aiming to provide deeper insights into this burgeoning field and suggests directions for future research.

Reducing Radiation Dermatitis for PBS Proton Therapy Breast Cancer Patients Using SpotDelete.

Purpose: The purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak. Patients and Methods: Our center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visit data from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/ß of 10 was assumed for the skin. Results: In the MinDepth cohort (n = 28), grade 1, 2, and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n = 27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0 instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5 cm skin rind between the cohorts. Conclusion: Despite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/ß for skin and RBE models based on skin cell lines could provide insight into the efficacy of the SpotDelete technique.

Real-World Efficacy and Safety of Oral Tofacitinib in Patients with Refractory Moderate to Severe Atopic Dermatitis: A Multicenter Retrospective Study.

Background: Atopic dermatitis (AD) has a complex etiology that includes Th2 polarization, which is accompanied by the cytokines IL4, IL-5, IL-13, and IL-31, as well as Th17 and Th22, and in chronic lesions, Th1 cells. Tofacitinib inhibits Th1-, Th2-, and Th17-associated cytokines by selectively blocking JAK1 and JAK3 receptors. We conducted a multicentric, retrospective chart analysis to study the efficacy and safety of tofacitinib in patients with moderate to severe refractory AD. Materials and Methods: We included 16 adult patients (aged >18 years) with moderate to severe AD who had previously undergone systemic therapy with inadequate response. In the baseline, demographic data, previous treatment history, severity scores (eczema area and severity index [EASI] and SCORing Atopic Dermatitis [SCORAD]), and quality of life score (Dermatology Life Quality Index [DLQI]) were noted. Baseline blood investigations, including complete blood count, liver function test, renal function test, lipid profile, and interferon gamma release assay for tuberculosis, were done. Patients were followed up every month for 6 months that included documentation of severity scores, blood investigations, and DLQI. Any adverse events, if reported, were noted. Result: All 16 patients completed the 6-month trial. Our patients were previously treated with cyclosporine (n = 10), methotrexate (n = 3), or both (n = 3). The mean EASI scores improved from 23.38 ± 9.56 at baseline to 8.50 ± 7.57 at the end of 6 months. The mean SCORAD score improved from 41.25 ± 8.69 at baseline to 14.93 ± 7.82 at the end of 6 months. Quality of life also improved as the mean DLQI improved from 15.18 ± 2.73 at baseline to 5.31 ± 4.11 at the end of the study period. No severe adverse reactions were noted, but 3 patients experienced dyslipidemia and 2 patients had altered bleeding time. Conclusion: Tofacitinib is a safe and effective treatment option for recalcitrant moderate to severe adult AD.

Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

[Translated article] Patient-reported outcome measures for assessing atopic dermatitis in clinical practice.

Atopic dermatitis is a chronic skin condition that affects up to 20% of children and 10% of adults worldwide. Due to the high burden of dermatological signs and symptoms, atopic dermatitis has a significant impact on the quality of life of patients and their families. In the absence of objective measures to accurately assess severity and symptom burden, patient-reported outcome measures are essential to monitor the impact and progression of the disease, as well as the efficacy of treatments. Although there are currently no standardised guidelines for their use in clinical practice, there are some initiatives, such as the Harmonise Outcome Measures for Eczema and Vivir con Dermatitis Atópica, that can provide guidance. As healthcare systems move toward value-based healthcare models, patient-reported measures are becoming increasingly important for incorporating the patient perspective and improving the quality of healthcare services. The use of these measures can help monitor disease activity and guide treatment decisions. This article discusses the impact of atopic dermatitis and describes the patient-reported outcome measures commonly used in atopic dermatitis and the recommendations of the initiatives that have selected a core set of measures to best assess atopic dermatitis in clinical practice. Considering the recommendations of these initiatives and based on our experience in clinical practice, we propose the use of the Dermatology Life Quality Index to assess the impact of the disease on quality of life, the Patient-Oriented Eczema Measure to assess symptom severity, and the Numerical Rating Scale or the Visual Analogue Scale to measure itch intensity. To systematise the administration of these measures and to integrate them into hospital information systems and medical records, we emphasise the importance of telemedicine platforms that allow the electronic administration of these instruments.

Ferrostatin-1 alleviates skin inflammation and inhibits ferroptosis of neutrophils and CD8+ T cells in allergic contact dermatitis.

BACKGROUND: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown. OBJECTIVE: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD. METHODS: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD. RESULTS: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8+ T cells both of which contribute to development of ACD. CONCLUSION: Ferroptosis was activated in immune cells, especially neutrophils and CD8+ T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8+ T cells and relieved skin damage in ACD mice.

Sleep and quality of life in adults with atopic dermatitis: cross sectional study.

Summary: Background.Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that causes sleep disturbances and worsens quality of life. However, few studies have been conducted on sleep in adults with atopic dermatitis. This study aimed to evaluate sleep and quality of life in adults with AD. Methods. A cross-sectional study was conducted with 36 adults diagnosed with AD and 21 healthy volunteers (controls), who completed questionnaires on sleep, itching, and quality of life. Disease severity was estimated using SCORing Atopic Dermatitis (SCORAD). All participants wore actigraphy watches for one week to objectively assess sleep quality. Results. Adults with AD slept worse than controls as measured by self-report (Global Pittsburgh Sleep Quality Index, mean ± SD, 9.33 ± 3.59 vs 5.00 ± 2.30, p < 0.001) and by actigraphy (sleep efficiency, SE), mean ± SD, 74.48 ± 11.63 vs 85.6 ± 6.53, p < 0.001). Actigraphy showed that adults with AD slept, on average, almost one hour less (p = 0.010), stayed awake during sleep for almost 44 minutes more (p < 0.001), and woke up 25% more than the controls (p = 0.047). In the AD group, SE and total sleep time were significantly inversely correlated with SCORAD (rs = -0.601, p < 0.001 and rs = -0.604, p < 0.001, respectively), but no significant correlation was found between itch and SE. A decreased quality of life was observed in adults with AD (DLQI, mean ± SD, 8.75 ± 6.7). Conclusions. Adults with AD slept worse than the controls and had a diminished quality of life. Actigraphy is a useful tool to objectively measure sleep quality in adults with AD especially those with moderate to severe disease.

Validation of the Skin Symptom Assessment (SSA) questionnaire for the evaluation of radiation dermatitis in breast cancer patients.

PURPOSE: Radiation dermatitis (RD) is a painful side effect of radiation therapy (RT). The objective of this analysis was to investigate the validity and reliability of the Skin Symptom Assessment (SSA) questionnaire in evaluating the severity of patient- and clinician-reported outcomes for RD in breast cancer patients by comparing it to a validated assessment tool, the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) questionnaire. METHODS: This study compared patient and clinician-reported outcomes for RD from previous clinical trials conducted in a Canadian cancer centre. The analysis included 376 and 38 patients in the two trials using Mepitel Film (doi.org/10.1200) and StrataXRT (clinicaltrials.gov identifier: NCT05594498), respectively. Patients in both studies completed the SSA and RISRAS questionnaires at baseline, 2-weeks post-RT, and 3 months after completion of RT. Clinician SSA and RISRAS assessments were collected at baseline and 2-weeks post-RT. These time points were analyzed longitudinally to investigate the SSA's validity in RD symptom assessment. RESULTS: The majority of patient-reported items on the SSA and RISRAS assessments demonstrated positive significant associations between symptoms of itchiness, between pain/soreness and pain/discomfort, and between blistering or erythema with burning sensation items. All items in the clinician-reported SSA and clinician component of RISRAS showed positive statistical significance between items measuring erythema, pigmentation or edema with dry desquamation, and blistering/peeling with moist desquamation. CONCLUSIONS: The SSA has been validated for assessing patient- and clinician-reported symptoms of RD accurately as outcomes correlate well with the previously validated RISRAS assessment.

Protease-Activated Receptor 2 in inflammatory skin disease: current evidence and future perspectives.

Protease-activated receptor-2 (PAR2) is a class-A G protein-coupled receptor (GPCR) activated by serine proteases and is expressed by multiple tissues, including the skin. PAR2 is involved in the skin inflammatory response, promoting Th2 inflammation, delaying skin barrier repair, and affecting the differentiation of keratinocytes. It also participates in the transmission of itch and pain sensations in the skin. Increasing evidence indicates that PAR2 plays an important role in the pathogenesis of inflammatory skin diseases such as acne vulgaris, rosacea, psoriasis, and atopic dermatitis. Additional focus will be placed on potential targeted therapies based on PAR2. The Goal of this review is to outline the emerging effects of PAR2 activation in inflammatory skin disease and highlight the promise of PAR2 modulators.

Effect of Staphylococcus aureus colonization and immune defects on the pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.

Atopy and asthma in children born to mothers at risk of gestational diabetes mellitus: a follow-up study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring's risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring. METHODS: The follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother-child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children's serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0). RESULTS: According to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08-20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03-9.63, p = 0.045). Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04-7.31, p = 0.041). CONCLUSION: Among pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases.

Analysis of patient experiences regarding JAK inhibitors for atopic dermatitis, psoriasis, alopecia areata, and vitiligo.

The use of medications which target the JAK-STAT signaling pathway, also known as janus kinase (JAK) inhibitors, has rapidly increased in recent years. Patient perceptions, opinions, and concerns regarding the use of JAK inhibitors are largely uninvestigated. Our objective is to better understand patient concerns, reported side effects, and sentiments regarding the use of JAK inhibitors for dermatologic disease. The authors performed a cross-sectional analysis of the most frequented subreddits for dermatologic disease in which JAK inhibitors have obtained FDA approval (r/atopic dermatitis, r/psoriasis, r/alopecia areata, r/vitiligo, and r/eczeJAKS). The sentiment, central theme, and engagement level of each post was evaluated using previously utilized methods. Nine hundred twenty-three posts were analyzed, with the majority focusing on efficacy (433, 47%) and medication-related side effects (150, 16%). Other themes of interest to patients were Payment/Insurance (84, 9%), Study Results/News (69, 7%), Administration/Dosage (33, 4%), and Medication Interactions (31, 3%). The most frequently reported side effects were acne/folliculitis (24, 22%), nausea/gastrointestinal disturbance (11,10%), and fatigue/muscle aches (10, 9%). At the same time, the medication interactions garnering the most concern were sunscreens/facial moisturizers (5, 16%), topical calcineurin inhibitors (4, 13%), and Marijuana/THC (3, 9.%). This analysis highlights that patients are most concerned about the efficacy and side effects of JAK inhibitors in addition to issues regarding access to JAK inhibitors. Providers can use the insights gained from this study to address hesitancy better and guide comprehensive, patient-centered discussions with patients regarding JAK inhibitor use.

Toxic epidermal necrolysis following heart transplantation may caused by cefoperazone sodium and sulbactam sodium.

BACKGROUND: The outcome of heart transplantation is significantly affected by perioperative infections. Individualised immunosuppression strategies are essential to reduce the risk of such infections. CASE PRESENTATION: We report the successful management of a 56-year-old male patient diagnosed with dilated cardiomyopathy who underwent heart transplantation. During the perioperative period, the patient was prescribed cefoperazone sodium and sulbactam sodium, which induced a severe skin reaction: toxic epidermal necrolysis (TEN). The patient was treated with prednisone, immunoglobulins, etanercept, and other active immunomodulatory measures, together with an individualised anti-rejection regimen and physical therapy. The systemic rash resolved within a month, and the patient was successfully discharged after surgery. CONCLUSION: Effective management of heart transplantation necessitates balancing immunosuppression and infection prevention. Individualised immunosuppressive strategies are critical for optimal clinical outcomes.

Hypericum sampsonii ameliorates radiodermatitis by inhibiting NLRP3 inflammasome activation.

BACKGROUND: Radiodermatitis (RD) is an inflammatory lesion of skin mucosa caused by radiation, which causes itching and pain in patients' skin. Hypericum sampsonii has an anti-inflammatory effect. This study aims to explore the potential effect and mechanism of H. sampsonii on RD. MATERIALS AND METHODS: The RD model was established using X-ray irradiation of mice and the pain response of mice under different treatment methods. Serum levels of IL-1ß, IL-6, and TNF-α were measured by ELSA. The RD cell model was constructed by RAW264.7 cell, H. sampsonii intervention was conducted, and the changes of the NLRP3 inflammasome in the cells were detected by qRT-PCR. The cells were stimulated with LPS and the protein changes of TLR4/NF-κB were investigated by Western Blotting. RESULTS: H. sampsonii can better improve the skin status of RD mice, relieve pain, and reduce the secretion of serum inflammatory factors IL-1ß, IL-6, and TNF-α. H. sampsonii significantly down-regulated the expression of NLRP3, Caspase-1, pro IL-1ß, and IL-1ß. Lps-induced activation of the TLR4/NF-κB pathway promotes the expression of NLRP3 and pro-IL-1ß, and H. sampsonii can inhibit this promotion. CONCLUSION: H. sampsonii may inhibit NLRP3 inflammatory vesicle activation via interfering with TLR4/NF-κB signaling to reduce the inflammatory response in macrophages and thus play a role in the treatment of RD.

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis.

BACKGROUND: Abrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated. CASE PRESENTATION: A 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship. CONCLUSIONS: The present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

Superficial Conjunctival Cells from Dupilumab-treated Atopic Dermatitis Patients with Ocular Adverse Events Display a Transcriptomic Psoriasis Signature.

Dupilumab has demonstrated efficacy in the treatment of atopic dermatitis (AD). However, a subset of patients experiences ocular adverse events (OAE), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of AD patient conjunctival cells collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in two groups according to their ophthalmological status at M4: 12 with OAE (OAE+) and 24 without (OAE-). The analysis revealed 52 differentially expressed genes (DEG) between OAE+ and OAE- patients at M0, and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. Additionally, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 DEG selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ vs OAE- patients, validating the psoriasis signature, while MUC-7 was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some AD patients to develop OAE upon dupilumab treatment.