Browsing by Subject "Atopic dermatitis"
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Item A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis(Wiley, 2022) Rao, Megana; Grove, Daniel; Haggstrom, Anita; Medicine, School of MedicineA 4‐year‐old female with a history of atopic dermatitis developed herpes simplex virus (HSV) encephalitis while being treated with dupilumab and concomitant topical steroids. There was no prior history of HSV infections or immunodeficiency. To our knowledge, this is the first case of HSV encephalitis in a patient receiving dupilumab.Item Effectiveness of atopic dermatitis patient education programs - a systematic review and meta-analysis(Springer, 2024-04-25) Andrade, Luis F.; Abdi, Parsa; Mashoudy, Kayla D.; Kooner, Amritpal; Egler, Ashley; Urbonas, Rebecca; Smith, Aaron; Yosipovitch, Gil; Pathology and Laboratory Medicine, School of MedicinePatient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens. In addition to improving patient education, past investigations of educational interventions have demonstrated profound reductions in disease severity for patients living with AD. However, prior meta-analytical work has focused mostly on comparing in-person interventions, and thus the need to determine the effectiveness of virtual methodologies in the current post-COVID era remains. In this study, we conducted a systematic review of the literature to determine the effectiveness of online programming in AD education compared to in-person interventions. A comprehensive search was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 2019. Studies were retrieved based on articles published up to 04 April 2023. Adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement guided the reportage process for this systematic review and meta-analysis. The primary outcome of our meta-analysis was the effect of various educational modalities on atopic dermatitis severity as measured by multiple scales across the studies, the most common including SCORAD, Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Eczema Area and Severity Index (EASI). Most studies were randomized controlled trials, primarily from North America and Western Europe and focused on patient and/or caregiver education about disease management, self-care techniques, avoidance of triggers, and comprehensive understanding of the disease process. Our pooled analyses showed that targeted educational programs in understudied adult populations can be as impactful as those in pediatric groups. Moreover, virtual interventions can be employed as constructive tools for reducing barriers of access to patient education. Future research on educational interventions should utilize various methodologies to encourage individual learning preferences with a focus on adult cohorts.Item IL-4 impairs wound healing potential in the skin by repressing fibronectin expression(Elsevier, 2017-01) Serezani, Ana PM; Bozdogan, Gunseli; Sehra, Sarita; Walsh, Daniel; Krishnamurthy, Purna; Potchanant, Elizabeth A Sierra; Nalepa, Grzegorz; Goenka, Shreevrat; Turner, Matthew J.; Spandau, Dan F.; Kaplan, Mark H.; Pediatrics, School of MedicineBACKGROUND: Atopic dermatitis (AD) is characterized by intense pruritis and is a common childhood inflammatory disease. Many factors are known to affect AD development, including the pleiotropic cytokine IL-4. Yet little is known regarding the direct effects of IL-4 on keratinocyte function. OBJECTIVE AND METHODS: In this report RNA sequencing and functional assays were used to define the effect of the allergic environment on primary keratinocyte function and wound repair in mice. RESULTS: Acute or chronic stimulation by IL-4 modified expression of more than 1000 genes expressed in human keratinocytes that are involved in a broad spectrum of nonoverlapping functions. Among the IL-4-induced changes, repression of fibronectin critically impaired the human keratinocyte wound response. Moreover, in mouse models of spontaneous and induced AD-like lesions, there was delayed re-epithelialization. Importantly, topical treatment with fibronectin restored the epidermal repair response. CONCLUSION: Keratinocyte gene expression is critically shaped by IL-4, altering cell fate decisions, which are likely important for the clinical manifestations and pathology of allergic skin disease.Item Increased Th2 activity and diminished skin barrier function cooperate in allergic skin inflammation(Wiley, 2016-11) Sehra, Sarita; Krishnamurthy, Purna; Koh, Byunghee; Zhou, Hong-Ming; Seymour, Lee; Akhtar, Nahid; Travers, Jeffrey B.; Turner, Matthew J.; Kaplan, Mark H.; Pediatrics, School of MedicineAtopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T-cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function. Our results demonstrate that over 90% of the Stat6VT transgenic mice carrying the Ft alleles (Stat6VTxFt−/−) develop severe atopic dermatitis lesions by 3-5 months of age, compared with only 40% of Stat6VT mice that develop disease by 6-7 months of age. Further, histopathological analysis of skin tissues from Stat6VTxFt−/− mice revealed extensive thickening of the dermis with increased inflammatory infiltrates as compared with Stat6VT mice. Our study suggests that skin barrier defects and altered Th2 responses independently cooperate in the pathogenesis of allergic skin inflammation, similar to effects observed in patients with AD.Item The IUPUI Signature Center for Atopic Dermatitis(Office of the Vice Chancellor for Research, 2010-04-09) Travers, Jeffrey B.; Kaplan, Mark; Holbreich, Mark; Leickly, FrederickAtopic dermatitis is a chronic inflammatory skin disease characterized by dry skin, hypersensitivity to irritants and allergens, and significant pruritus. Atopic dermatitis is commonly associated with other atopic diseases including asthma, allergic rhinitis, and gastrointestinal disorders including eosinophilic esophagitis. Though a very common disease, there exists much misinformation and controversy/conflict in both the lay and medical communities about its pathogenesis and treatment, resulting in suboptimal care for the atopic dermatitis patient. Thus, education of both clinicians and lay public is needed. Inasmuch as atopic dermatitis is considered a systemic disorder, the optimal management should entail a multidisciplinary approach. Finally, research into the mechanisms by which atopic dermatitis occurs is needed to improve treatment of this common and quite debilitating disorder. The objective of the IUPUI Signature Center for Atopic Dermatitis is to provide optimal patient care, education and research in atopic dermatitis for the citizens of the state of Indiana. The Atopic Dermatitis has three separate components. First, we have developed an Atopic Dermatitis Working Group (ADWG) consisting of clinicians and scientists who meet on a monthly basis to disseminate information about research ideas/trials, and discuss topics and present difficult patients. Second, we have developed a monthly multidisciplinary AD clinic which has attracted the most challenging AD patients. Finally, we have developed infrastructure to assist in clinical and basic science research projects involving AD. Altogether, the IUPUI Signature Center for AD has been very successful as measured by the numbers of clinicians, researchers and patients who have been impacted by its presence.Item Periostin activates distinct modules of inflammation and itching downstream of the type 2 inflammation pathway(Elsevier, 2023) Nunomura, Satoshi; Uta, Daisuke; Kitajima, Isao; Nanri, Yasuhiro; Matsuda, Kosuke; Ejiri, Naoko; Kitajima, Midori; Ikemitsu, Hitoshi; Koga, Misaki; Yamamoto, Sayaka; Honda, Yuko; Takedomi, Hironobu; Andoh, Tsugunobu; Conway, Simon J.; Izuhara, Kenji; Pediatrics, School of MedicineAtopic dermatitis (AD) is a chronic relapsing skin disease accompanied by recurrent itching. Although type 2 inflammation is dominant in allergic skin inflammation, it is not fully understood how non-type 2 inflammation co-exists with type 2 inflammation or how type 2 inflammation causes itching. We have recently established the FADS mouse, a mouse model of AD. In FADS mice, either genetic disruption or pharmacological inhibition of periostin, a downstream molecule of type 2 inflammation, inhibits NF-κB activation in keratinocytes, leading to downregulating eczema, epidermal hyperplasia, and infiltration of neutrophils, without regulating the enhanced type 2 inflammation. Moreover, inhibition of periostin blocks spontaneous firing of superficial dorsal horn neurons followed by a decrease in scratching behaviors due to itching. Taken together, periostin links NF-κB-mediated inflammation with type 2 inflammation and promotes itching in allergic skin inflammation, suggesting that periostin is a promising therapeutic target for AD.Item Predictive biomarker modeling of pediatric atopic dermatitis severity based on longitudinal serum collection(Oxford University Press, 2021) Engle, Sarah M.; Chang, Ching-Yun; Ulrich, Benjamin J.; Satterwhite, Allyson; Hayes, Tristan; Robling, Kim; Sissons, Sean E.; Schmitz, Jochen; Tepper, Robert S.; Kaplan, Mark H.; Sims, Jonathan T.; Microbiology and Immunology, School of MedicineThe pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on atopic dermatitis diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at one and four years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (rmcorr=0.47) and TARC/CCL17 (rmcorr=0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T cell involvement in type 2 immune responses were enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD four years later. We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease.Item Role of the Microbiome in Allergic Disease Development(Springer, 2020-06-16) Aguilera, Andrea C.; Dagher, Isabelle A.; Kloepfer, Kirsten M.; Medicine, School of MedicinePURPOSE OF REVIEW: Evidence suggests that the microbiome of the skin, gastrointestinal tract, and airway contribute to health and disease. As we learn more about the role that the microbiota plays in allergic disease development, we can develop therapeutics to alter this pathway. RECENT FINDINGS: Epidemiologic studies reveal that an association exists between environmental exposures, which alter the microbiota, and developing atopic dermatitis, food allergy, and/or asthma. In fact, samples from the skin, gastrointestinal tract, and respiratory tract reveal distinct microbiotas compared with healthy controls, with microbial changes (dysbiosis) often preceding the development of allergic disease. Mechanistic studies have confirmed that microbes can either promote skin, gut, and airway health by strengthening barrier integrity, or they can alter skin integrity and damage gut and airway epithelium. In this review, we will discuss recent studies that reveal the link between the microbiota and immune development, and we will discuss ways to influence these changes.Item Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)(Wiley, 2021) Wollenberg, A.; Blauvelt, A.; Guttman-Yassky, E.; Worm, M.; Lynde, C.; Lacour, J.-P.; Spelman, L.; Katoh, N.; Saeki, H.; Poulin, Y.; Lesiak, A.; Kircik, L.; Cho, S. H.; Herranz, P.; Cork, M. J.; Peris, K.; Steffensen, L. A.; Bang, B.; Kuznetsova, A.; Jensen, T. N.; Østerdal, M. L.; Simpson, E. L.; ECZTRA 1 and ECZTRA 2 study investigators; Dermatology, School of MedicineBackground: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.Item Transcriptomic Analysis of Healthy and Atopic Dermatitis Samples Reveals the Role of IL-37 in Human Skin(American Association of Immunologists, 2021-10-26) Zhou, Jiajun; Gemperline, David C.; Turner, Matthew J.; Oldach, Jonathan; Molignano, Jennifer; Sims, Jonathan T.; Stayrook, Keith R.; Dermatology, School of MedicineAtopic dermatitis (AD) is a chronic inflammatory skin disease that affects up to one in five children and millions of adults in developed countries. Clinically, AD skin lesions manifest as subacute and/or chronic lichenified eczematous plaques, which are often intensely pruritic and prone to secondary bacterial and viral infections. Despite the emergence of novel therapeutic agents, treatment options and outcomes for AD remain suboptimal. An improved understanding of AD pathogenesis may help improve patient outcomes. Dysregulated Th2-polarized skin inflammation and impaired skin barrier function interact to drive AD pathogenesis; however, much remains to be understood about the molecular mechanisms underlying this interplay. The current study used published clinical trial datasets to define a skin-related AD gene signature. This meta-analysis revealed significant reductions in IL1F7 transcripts (encodes IL-37) in AD patient samples. Reduced IL1F7 correlated with lower transcripts for key skin barrier function genes in the epidermal differentiation complex. Immunohistochemical analysis of normal (healthy) human skin specimens and an in vitro three-dimensional human skin model localized IL-37 protein to the epidermis. In comparison with normal human skin, IL-37 levels were decreased in AD patient skin. Addition of Th2 cytokines to the aforementioned in vitro three-dimensional skin model recapitulates key aspects of AD skin and was sufficient to reduce epidermal IL-37 levels. Image analysis also indicated close relationship between epidermal IL-37 and skin epidermal differentiation complex proteins. These findings suggest IL-37 is intimately linked to normal keratinocyte differentiation and barrier function and implicates IL-37 as a potential biomarker and therapeutic target for AD.