Association of risk of incident acne and treatment with systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta-analysis.

INTRODUCTION: The therapeutic efficacy of systemic Janus kinase (JAK) inhibitors in moderate-to-severe atopic dermatitis (AD) is well established. However, the associated risk of incident acne, which is a prevalent adverse event in AD patients treated with systemic JAK inhibitors, has yet to be systematically analyzed. METHODOLOGY: To evaluate the risk of incident acne in AD patients treated with systemic JAK inhibitors, an extensive database search (clinicaltrials.gov, PubMed) was performed to identify publications eligible for inclusion from January 2020 to October 2022. Five randomized clinical trials (RCTs) of abrocitinib, four RCTs of upadacitinib, and one RCT of baricitinib, encompassing a total of 7901 participants, were included in the analysis. The risk difference for incident acne between systemic JAK inhibitors and controls was assessed using Review Manager, version 5.3, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Meta-analysis elucidated a significant difference in the risk of incident acne between AD participants receiving 200 mg abrocitinib (Mantel-Haenszel risk difference, 3.69; 95% CI 1.60-8.48; P < 0.01), 15 mg upadacitinib (Mantel-Haenszel risk difference, 4.61; 95% CI 2.79-7.62; P < 0.00001), and 30 mg upadacitinib (Mantel-Haenszel risk difference, 6.82; 95% CI 4.59-10.13; P < 0.00001) compared with controls receiving placebo or dupilumab. In contrast, no significant difference was found in the risk of incident acne between participants receiving 100 mg abrocitinib, 2 mg baricitinib, and 4 mg baricitinib, as compared with controls. CONCLUSIONS: Based on the current evidence, there is an increased risk of acne related to systemic JAK inhibitors, particularly with abrocitinib and upadacitinib. For patients predisposed to acne, the balance between the benefits of symptomatic relief from AD and the potential risk of acne may need to be carefully considered. This study contributes to a nuanced understanding of the risk profile of systemic JAK inhibitors and has the potential to guide personalized treatment decisions for AD patients.

Dupilumab-Associated Psoriasis and Psoriasiform Manifestations: A Scoping Review.

BACKGROUND: Dupilumab is the first approved IL-4Rα inhibitor for the treatment of atopic dermatitis at present with good efficacy and safety. However, there have been several reports of psoriasis and psoriasiform manifestations occurring after dupilumab therapy in recent years, showing a new paradoxical cutaneous reaction associated with biologics. SUMMARY: This is a scoping review in order to summarize the demographics and epidemiology, clinical manifestations, diagnosis, potential pathogenesis, and promising management of dupilumab-associated psoriasis and psoriasiform manifestations.

Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes.

Interleukin (IL)-13 plays a key role in the pathogenesis of atopic dermatitis (AD). Our preliminary study demonstrated that forced expression of miR-143 could block IL-13-induced down-regulation of epidermal barrier related proteins in epidermal keratinocytes. As previous studies suggested that miR-143 expression was regulated by mammalian target of rapamycin (mTOR) signaling pathway, we investigated the mechanism of mTOR signaling pathway in the epidermal barrier dysfunction of AD. The HaCaT cells were stimulated by IL-13 and subsequently treated with rapamycin. The expression levels of miR-143, IL-13 receptor α1 (IL-13Rα1), p-mTOR, p-S6K1, p-Akt, and epidermal barrier related proteins were analyzed through RT-qPCR and/or western blotting. The current study showed that IL-13 increased the expression levels of p-mTOR, p-S6K1, and p-Akt, and that rapamycin blocked IL-13-induced down-regulation of miR-143, suppressed the IL-13Rα1 expression and up-regulated the expressions of filaggrin, loricrin, and involucrin in HaCaT cells. This study proposed that IL-13 could activate the mTOR signaling pathway, and confirmed the vital role of mTOR-miR-143 signaling axis in the pathogenesis of AD. It provided solid evidences regarding rapamycin as a potential effective therapeutic option in the management of AD.

Index Case of Cutaneous Follicular Mycosis Fungoides With Central Nervous System Involvement and Review of Literature.

Central nervous system involvement by mycosis fungoides (MF) is rare and is usually seen in advanced stages of the disease. We describe a patient with early-stage follicular MF who presented with changes in mental status. Despite an initial diagnosis of vasculitis based on clinical and brain biopsy results, the postmortem examination revealed extensive infiltration of MF cells throughout the brain with leptomeningeal involvement. This case in addition to the accompanied review of literature illustrates the importance of the awareness of central nervous system involvement by MF and highlights the need for an urgent neurologic evaluation in patients with a history of MF now presenting with neurologic signs or symptoms.

MicroRNA-143 inhibits IL-13-induced dysregulation of the epidermal barrier-related proteins in skin keratinocytes via targeting to IL-13Rα1.

Atopic dermatitis is a chronic inflammatory skin disease characterized by the dysregulation of the epidermal barrier and the immune system. Interleukin (IL)-13, a key T helper 2 cytokine, has been shown to impair the epidermal barrier function via downregulating epidermal barrier proteins. MicroRNAs are small noncoding RNAs of approximately 22 nucleotides that act as negative regulators of gene expression at posttranscriptional levels. MicroRNA-143 is known to be a tumor suppressor in various tumors; however, its role in the regulation of allergic diseases including atopic dermatitis remains elusive. In this study, we investigated whether IL-13Rα1 was a microRNA-143 target to regulate the effects of IL-13 on epidermal barrier function. After the stimulation of IL-13 in human epidermal keratinocytes, the level of microRNA-143 was decreased. The luciferase activity of the vector containing 3'UTR of IL-13Rα1 was decreased in keratinocytes transfected with microRNA-143 mimic compared to those of the corresponding controls. The forced expression of microRNA-143 mimic blocked the IL-13-induced downregulation of filaggrin, loricrin, and involucrin in epidermal keratinocytes. Collectively, these data suggest that microRNA-143 suppresses IL-13 activity and inflammation through targeting of IL-13Rα1 in epidermal keratinocytes. MicroRNA-143 may serve as a potential preventive and therapeutic target in atopic dermatitis.

Research interest in the usage of dupilumab for atopic dermatitis: a bibliometric analysis.

BACKGROUND: Recently, dupilumab has been used for the treatment of atopic dermatitis (AD), and growing interest in the subject has resulted in an increasing number of publications. OBJECTIVES: Our study aimed to evaluate the rapid progress, identify hot topics, and explore scientific advances and future trends in this field. MATERIALS & METHODS: The global distribution of publications was estimated with no time restrictions. Dupilumab as a treatment for AD was scanned in the Web of Science core collection using the topic terms "dupilumab" and "atopic Dermatitis". VOSviewer was applied for visualization of bibliometric analysis. Analysis of country and region distribution, impact of journal, authors, population, economic estimation among countries and regions, key words, as well as the top 20 cited articles were performed. RESULTS: In total, 910 publications were yielded from the Web of Science core collection database. Most studies were published in the USA (46.15%), Germany (17.91%), and France (14.07%); other countries included Denmark, the Netherlands, and Canada based on normalization of article numbers according to population and economic evaluation. Studies were most frequently reported in the British Journal of Dermatology and the Journal of the American Academy of Dermatology. Pirozzi, G. from France was the top-cited author. The most frequent key words were concepts in dermatology, allergy, and immunology. Remarkable landmark clinical trials were noted in the top 20 cited publications. CONCLUSION: The research of dupilumab for AD is rapidly developing. Countries in North America and Europe have remarkably contributed to researches of dupilumab as a treatment for AD. The bibliometric analysis also presents hallmark publications reporting scientific advances in therapy progress, which may provide a foundation for further research.

Scientific landscape and trend analysis of chronic urticaria: a two-decade bibliometric review.

BACKGROUND: In the past 20 years, an increasing number of studies have advanced our understanding of the pathogenic mechanism of chronic urticaria (CU), providing new treatment options. OBJECTIVES: This bibliometric study aimed to evaluate published reports of CU-related studies from a number of different angles, review the research trends of the studies, and provide future perspectives of CU. MATERIALS & METHODS: Publications related to CU from 2001-2022 were searched in the Web of Science Core Collection. The database file was imported to Excel and analysed using bibliometric software, including VOSviewer and BiblioShiny. RESULTS: A total of 4,452 publications of CU were included. The number of publications related to CU has increased steadily over time. The journal with the most published articles was Allergy, and the countries with the most publications were the United States, Germany, and Italy. The most productive author was Maurer Marcus from Germany. There was close co-authorship between authors and countries (and regions) across the world. Recent studies have focused more on the pathogenesis and treatment of CU. Future hotspots may include emerging biologics for treatment. CONCLUSION: This study shows the research development of CU over the past two decades, which may provide beneficial reference for publication and future trends in CU research.

Skin diseases of the nipple and areola complex: A case series study from China.

Background: Skin diseases of the nipple and areola complex (NAC) are numerous and difficult to diagnose, which is a great challenge for clinicians. A better understanding of the clinical features of NAC skin diseases is of great value for the correct diagnosis. Methods: To investigate the clinical characteristics of skin diseases of the NAC, we retrospectively analyzed the demographic data, disease constitution, rash characteristics, inconsistency between the clinical and pathological diagnosis from 260 patients with NAC lesions that were confirmed by histopathology at Peking Union Medical College Hospital, China from 2012 to 2022. Results: The patients' average age was 43.6 (8 to 82) years, and the ratio of females to males was 13.4:1. Out of the 260 patients biopsied, the most common diseases were eczema, Paget's disease (PD), adenoma of the nipple (AN), seborrheic keratosis (SK), cutaneous metastasis of breast cancer, wart, soft fibroma, and hyperkeratosis of the nipple and areola. There were 77 (29.6%) patients with inconsistency between the clinical impressions and pathological diagnoses. AN was the most clinically misdiagnosed condition, most commonly presumed to be PD or eczema. Conclusion: Eczema and PD are the most common biopsied NAC skin diseases. Late onset, unilateral involvement, and predilection for the nipple are several characteristics of PD, which are different from eczema. NAC skin diseases are easily misdiagnosed clinically, especially AN.

Clinical epidemiology and disease burden of bronchiolitis in hospitalized children in China: a national cross-sectional study.

BACKGROUND: Bronchiolitis is a common acute lower respiratory tract infection (ALRTI) and the most frequent cause of hospitalization of infants and young children with ALRTI. Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis. The disease burden is relatively high. To date, few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available. This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China. METHODS: This study included the face sheet of discharge medical records collected from 27 tertiary children's hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords (FUTURE) database. The sociodemographic variables, length of stay (LOS) and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests. RESULTS: In total, 42,928 children aged 0-3 years were hospitalized due to bronchiolitis from January 2016 to December 2020, accounting for 1.5% of the total number of hospitalized children of the same age in the database during the period and 5.31% of the hospitalizations for ALRTI. The male to female ratio was 2.01:1. Meanwhile, more boys than girls were observed in different regions, age groups, years, and residences. The 1-2 year age group had the greatest number of hospitalizations for bronchiolitis, while the 29 days-6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group. In terms of region, the hospitalization rate of bronchiolitis was the highest in East China. Overall, the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016. Seasonally, the peak hospitalizations for bronchiolitis occurred in winter. Hospitalization rates in North China in autumn and winter were higher than those in South China, while hospitalization rates in South China were higher in spring and summer. Approximately, half of the patients with bronchiolitis had no complications. Among the complications, myocardial injury, abnormal liver function and diarrhea were more common. The median LOS was 6 days [interquartile range (IQR) = 5-8], and the median hospitalization cost was 758 United States dollars (IQR = 601.96-1029.53). CONCLUSIONS: Bronchiolitis is a common respiratory disease in infants and young children in China, and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children. Among them, children aged 29 days-2 years are the main hospitalized population, and the hospitalization rate of boys is significantly higher than that of girls. The peak season for bronchiolitis is winter. Bronchiolitis causes few complications and has a low mortality rate, but the burden of this disease is heavy.

Ocular Adverse Effects in Atopic Dermatitis Patients Treated With Dupilumab: A Bibliometric Analysis.

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders. Dupilumab, the first targeted biological drug approved for the treatment of AD, has been widely used, along with increasing ocular adverse effects (AEs). Objective: To perform a bibliometric analysis of all the qualified literature involving ocular AEs during the treatment of AD with dupilumab. Methods: Relevant studies were extracted from the Web of Science database and screened by researchers. The bibliographic analysis was performed using the VOSviewer. Results: A total of 138 articles were enrolled in this study. The first study was published in 2016 by Oregon Health and Science University from the United States. The majority of publications were published in the past 3 years. British Journal of Dermatology published the highest number of articles. The United States was the country with the most publications. Sanofi (France) and Regeneron Pharmaceuticals (USA) were the leading organizations with the most contributions. Conjunctivitis was the most common ocular AE. The management of AD will continue to be the research hotspot and development trend in this area. The milestone research is the first article "Two Phase 3 Trials of Dupilumab vs. Placebo in Atopic Dermatitis" published in the New England Journal of Medicine. Most of the top 10 papers were mainly randomized, placebo-controlled phase 2 and phase 3 clinical trials and real-life large cohort studies. Conclusions: This study may help better understand ocular AEs in the dupilumab treatment of AD, and grasp the research trends and most influential topics in this field.