PeDRA

Pediatric Dermatology Research Alliance

Atopic Derm & Psoriasis

Investigating the Role of Age, Race and Ethnicity in Response to Immunomodulating Agents in Children with Moderate to Severe Atopic Dermatitis

By

Fellow

Angel Pagan
Ponce Health Sciences University

Mentor

Emma Guttman-Yassky, MD, PhD
Ichan School of Medicine at Mount Sinai

Overview

Up to 11% of United States children are affected by atopic dermatitis (AD) and one-third of these suffer from moderate-to-severe disease. The negative impact of AD in children include feelings of isolation from peers due to disease-related lifestyle restrictions, embarrassment, and bullying. There’s also a large burden of disease on families, with parents of children with AD reporting lower total sleep time and higher frequency of missed workdays. Despite a worldwide increase in the incidence of pediatric AD, the development of effective long-term treatments has been slow.

Our objective is to investigate the role of age, race and ethnicity in response to immunomodulating agents in children with moderate to severe atopic dermatitis. Our central hypothesis is formulated on the basis that TH17-cell–generated products such as IL-17A and IL-17F, important for skin antimicrobial and barrier functions, recently showed the greatest upregulations in infant (0-5 years old) AD, which could show a different frequency of adverse events such as Staphylococcus aureus skin infections and ocular manifestations, compared to children (6-11 years old). If this hypothesis is correct, efforts can be directed towards maximing effectiveness during infancy and applying strategies proven successful in the older age group to directly address dupilumab adverse events in pediatric AD. Our long-term is to disseminate knowledge at the clinical level that reduce the burden of AD in affected families. By pursuing the following specific aims, we will gather data essential to help direct future interventions.

Aim 1: Compare differences in the incidence of skin infections and injection-site reactions in multiple dose treatment with dupilumab in infants compared to children.

Aim 2: Compare differences in the incidence of treatment‐emergent adverse events such as nasopharyngitis, conjunctivitis, and anaphylactic reactions in multiple dose treatment with dupilumab in infants compared to children.

Aim 3: Compare differences in the incidence of adverse events between African American, Hispanic, Asian, and European American children in multiple dose treatment with dupilumab.

Status

This project was funded through a 2021 PeDRA Research Fellowship Grant.

The Impact of Topical Prescription Drug Delivery Devices in the Adherence and Ease of Use of Corticosteroids in Pediatric Patients with Atopic Dermatitis

By

Fellow

Wenelia Baghoomian
Oregon Health & Science University

Mentor

Eric Simpson, MD
Oregon Health & Science University

Overview

Atopic dermatitis (AD) is the most common pediatric inflammatory skin disease affecting 15-30% of children worldwide. Topical corticosteroids remain the mainstay of treatment in AD and when used as directed, are highly effective. However, upwards of 50% to 88% of children and adolescents are non-adherent with their prescribed regimen. Current studies exploring the barriers and interventions in adherence place the blame and responsibility on patients and clinicians to improve outcomes. Yet, no effort has been made to improve the application and delivery of topical medication to help promote adherence and alleviate the burden on patients. Since the patent of the collapsible metal tube in 1841, there have been very little changes, improvements, or alterations made to the packaging of topically prescribed treatments. In addition, the tube packaging of topical medications does not provide a mechanism for accurate dosing. Patients are required to apply arbitrary amounts like “pea-sized” or “palm of hand”, which often leads to underutilization and subpar therapeutic results. Thus, rather than placing the responsibility of adherence on pediatric patients and their caregivers, our efforts will be to optimize a drug delivery device that would encourage adherence, reduce dose discrepancies, and improve treatment outcomes.

To solve this problem, we will investigate topical prescription drug delivery devices and their impact on adherence and ease of use in the pediatric population suffering from AD. This process will include identifying the needs and barriers in the application process of topical medication and utilizing these findings to discover and design a drug delivery device that addresses these issues. We will also be focusing on using a topical drug delivery device that would deliver medication in a dose-dependent manner, reducing the responsibility on patients to guess the amount that is needed and improve adherence. The rationale of our proposed model is supported by the fact that several studies in the elderly population demonstrating changes in packaging design increases the adherence of medication, and thus improving treatment outcomes. Therefore, our central hypothesis is that redesigning the method of drug delivery of topically prescribed medication can improve adherence and reduce dose discrepancies for pediatric patients suffering from AD.

Aim 1: Determine the specific barriers in the tube packaging of topical medication in pediatric patients and their caregivers.

Aim 2: Investigate and compare alternative models of topical drug delivery devices that would increase ease of use and adherence in the pediatric population.

Aim 3: Evaluate the adherence and ease of use of a topical corticosteroid dose-dependent drug delivery device in an open label pilot study in pediatric patients with AD.

Status

This project was funded through a 2021 PeDRA Research Fellowship Grant.

Characterization of Non-Alcoholic Fatty Liver in Pediatric Psoriasis

By

Fellow

Jennifer Gionah Laborada
University of California Riverside School of Medicine

Mentor

Wynnis Tom, MD
University of California San Diego

Overview

Psoriasis is a chronic inflammatory skin disease associated with overweight/obesity and increased cardiometabolic risk. One particularly pertinent metabolic comorbidity is non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in the developed world. Several studies of adults with psoriasis have demonstrated not only an increased prevalence of NAFLD, but also increased severity of fatty liver disease compared to matched controls without psoriasis.1 Furthermore, presence of NAFLD was associated with psoriasis severity as assessed by the Psoriasis Area and Severity Index.

We propose a multi-center retrospective study examining the clinical, imaging, and histologic findings of NAFLD in children and young adults with concomitant psoriasis, compared to those with NAFLD but without psoriasis. Our inclusion criteria are psoriasis patients up to 21 years of age diagnosed with psoriasis at age ≤18 years who underwent workup for NAFLD at Rady Children’s Hospital San Diego and collaborative centers (Baylor/Texas Children’s, Mayo Clinic, Northwestern, University of Wisconsin, and Seattle Children’s have expressed interest) between January 1, 1990 and March 30, 2021. We will utilize controls from the NIDDK NAFLD Pediatric Database. We hypothesize that psoriasis is associated with increased severity of NAFLD in children, as measured by steatosis and fibrosis.

Specific Aim 1: To better characterize NAFLD disease patterns, symptoms, signs, and severity in the setting of pediatric psoriasis.

Specific Aim 2: To examine if NAFLD severity is related to characteristics of psoriasis, such as duration and severity of skin disease, and the effect of systemic therapies administered for psoriasis.

Status

This project was funded through a 2021 PeDRA Research Fellowship Grant.

Effects of poverty and environmental exposures across race and ethnicity in children with atopic dermatitis

By

Fellow

Emily Croce, MSN, APRN, CPNP-PC
The University of Texas at Austin School of Nursing

Mentor

Moise Levy, MD
Dell Medical School at The University of Texas at Austin

Overview

The purpose of this study is to understand the effects of living in a poor neighborhood on AD prevalence and severity. We will examine these relationships using data from a sample of children with persistent asthma, among whom an estimated 50% are expected to have AD. We will use data from TexHALE (P.I. Elizabeth Matsui), a cross-sectional study of 350 children, ages 5-17 years with persistent asthma in Travis County (Austin, Texas). Participants are recruited from high poverty/high minority, low poverty/high minority, high poverty/low minority, and low poverty/low minority census tracts. Therefore, we will have an ethnically diverse study population and be strongly positioned to explore associations between race/ethnicity and AD prevalence/severity, and whether/to what extent these are explained by neighborhood poverty. The specific aims (SA) of this study are:

1. To compare the prevalence and severity of AD between children with persistent asthma living in high poverty neighborhoods with those living in low poverty neighborhoods, adjusting for individual-level socioeconomic status.

2. To examine associations between poverty-associated factors (indoor and outdoor air pollution, indoor allergen exposure, and psychosocial stress) and AD prevalence and severity, adjusting for individual-level socioeconomic status.

By examining these aims within a sample with robust demographic, neighborhood, and indoor/outdoor environmental exposure data, we may begin to understand how neighborhood poverty contributes to AD prevalence and severity and will have a rich source for secondary analyses. Should neighborhood poverty be implicated in excess burden of AD (independent of individual factors such as income), this would be among the first evidence that discriminatory forces that have led to environmental injustices may be responsible, at least in part, for racial and ethnic disparities in AD prevalence and/or severity. Reducing these forces would shrink AD disparities and potential interventions include expansion of housing mobility programs coupled with policies to directly address neighborhood poverty. For example, if housing related exposures seem to be the most important contributors, then housing regulation that increases housing quality would be an important intervention. If differences are found across neighborhoods, we will also determine whether indoor and outdoor air pollution, indoor allergen exposure, and/or psychosocial stress, mediate the effect of poverty on AD prevalence and severity.

Status

This project was funded through a 2021 PeDRA Research Fellowship Grant.

The Association Between Psoriasis and Bacterial Infection

By

Principal Investigator:

Esteban Fernandez Faith, MD
Nationwide Children’s Hospital

Overview:

Gut dysbiosis has been implicated in the onset and course of psoriasis, and the gut-skin axis highlights the relationship between the two organs. The association of streptococcal infections and psoriasis has been well documented in the setting of streptococcal respiratory infections, mainly pharyngitis. The relationship between perianal and genital bacterial dermatitis and psoriasis is less well characterized in the literature. We seek to describe the clinical features, treatment regimen, and outcomes of psoriasis associated with pharyngeal or anogenital bacterial infection, with the ultimate goal of enhancing the care of patients affected by psoriasis with this association.

Status:

This study is ongoing and actively seeking collaborators. If you are interested in joining this study as a site, please contact Manisha Ravi or Esteban Fernandez Faith, MD.

CACHES-US: Child and Adolescent Chronic Hand Eczema Study – United States

By

Principal Investigator:

Larry Eichenfield, MD
University of California, San Diego

Overview:

Chronic hand eczema (CHE) has been poorly investigated in children and adolescents. Prior epidemiologic studies are very limited to a few studies in Scandinavia, with few studies of pediatric CHE in the United States. This is concerning as CHE has significant signs and symptoms, impact on school, sports and other activities, psychosocial effects, and measurable impacts on quality of life. Potential associations with atopic dermatitis, active or by history, and allergic contact dermatitis are suspected. We plan to query providers from the Society of Pediatric Dermatology and Pediatric Dermatology Research Alliance regarding the diagnosis, testing, and treatments they utilize for pediatric CHE through a survey designed as a series of questions and vignettes. We will execute a ‘selective response’ survey method where we send out a message to all PeDRA and SPD members requesting their willingness to take part in the survey. Then we will distribute the survey to those that have said they are interested in participating. Methodology of the survey development included development of case vignettes, reviewed by experts in CHE and atopic dermatitis. After survey collection, the data will be analyzed to understand the variation in clinical experience with, diagnosis, categorization, and treatment of chronic hand eczema among physicians. Given the significant influence CHE has on individual quality of life this investigation can serve as the foundation for determining best practices of management of this disorder to prevent high morbidity in adulthood and will impact the design of a planned prospective epidemiologic study of pediatric CHE.

Status:

This project is underway and the survey will be open for responses soon.

TNF inhibitor-induced psoriasiform dermatitis in children: Clinical and mechanistic analyses

By

Principal Investigators:

Amy Paller, MD
Northwestern University

Jennifer Boles-Scott, MD
Northwestern University

Overview:

Injectable medications that inhibit tumor necrosis factor (TNF) block inflammation in arthritis, inflammatory bowel disease, and psoriasis. However, there are reports of psoriasis or a psoriasis-like skin disease developing, particularly in adults, during treatment with TNF inhibitors. Diagnosis can be challenging and the mechanism of disease, particularly in children, has not been explored.

We plan to study the clinical patterns of TNF-induced versus classic psoriasis in children, with the expectation that their patterns of distribution, appearance, and types of immune markers expressed in the skin will differ. We will use tape strips (a painless, non-invasive technique) to collect superficial skin cells, and will identify markers of their immune system response in skin. We predict that the degree of altered immune expression will correlate with disease severity. Our goal is to better understand TNFi psoriasiform disease and develop a tape strip panel to distinguish TNFi-induced psoriasis from classic psoriasis.

Status:

This project was funded by a 2020 PeDRA Research Grant.

Characterization of Lipoprotein Composition and Function in Pediatric Psoriasis Before and After Treatment

By

Principal Investigator:

Amy Paller, MD
Northwestern University

Overview:

Psoriasis is a chronic inflammatory skin disease associated with early onset cardiovascular disease. Despite studies demonstrating high cholesterol, increased diabetes and higher rate of obesity in psoriasis, these traditional risk factors only explain a fraction of total cardiovascular risk in psoriasis. One-third of the psoriasis patients start developing psoriatic plaques during childhood and studies have shown that the children with psoriasis have similar or higher risk for obesity and future problems with high cholesterol and diabetes. In fact, children have been shown to have abnormal cholesterol as early as age 13 years in psoriasis. However, little is known about how pediatric psoriasis severity affects cholesterol function, including its relationship with proteins involved in inflammation. Importantly, whether treatment of pediatric psoriasis early in the life leads to improvement in cholesterol function and overall lipoprotein composition is unknown. Therefore, the goal of this proposal is to understand the effect of disease activity and psoriasis treatment on cholesterol and metabolic markers in pediatric psoriasis.

Status:

This project was funded as a 2018 PeDRA and NPF Pediatric Psoriasis Challenge Grant and is currently underway.