PeDRA

Pediatric Dermatology Research Alliance

Atopic Derm & Psoriasis

T regulatory cell dysfunction and Staphylococcus aureus infection enable atopic dermatitis onset and progression

By

Principal Investigator:

Hazel Wilkie, PhD
Boston Children’s Hospital

Overview:

Atopic dermatitis (AD, also called allergic eczema) affects 20% of children and 10% of adults. The dry, red, itchy skin lesions are often infected with bacteria. Intriguingly, skin bacterial burden increases prior to the development of eczema lesions in infant children but how or if the bacteria is causing the disease is not clear.

AD often occurs in children whose parents also suffer from allergies. This heritable link is associated with mutations in numerous genes. Patients with mutations in the DOCK8 gene universally suffer from severe AD and bacterial infections. Mice with the same DOCK8 mutations as the patients are an excellent model to investigate the pathways underlying the development of AD. We will test novel treatment strategies that target these pathways in order to reduce allergic skin inflammation.

This work will illuminate novel therapies for eczema patients targeted towards preventing disease and restoring suppression of allergic skin inflammation.

Status:

This project was funded by a 2022 PeDRA Research Grant.

Childhood Atopic Dermatitis: The Role of Outdoor Air Pollution on Disease Burden and Racial and Ethnic Disparities

By

Principal Investigator:

Emily Croce, PhD, MSN, ADPRN, NPNP-CP
The University of Texas at Austin

Overview:

Atopic dermatitis (AD) is the most common chronic childhood skin disease and there are significant and persistent racial and ethnic disparities in atopic dermatitis (AD) among children in the United States (US). A variety of contextual factors such as allergen exposure, psychosocial stress, decreased access to healthcare, and others, have been implicated as causes or exacerbators of AD. Several lines of evidence suggest that outdoor air pollution (OAP) may play a significant role in AD risk and AD disparities. Many of children with AD will develop asthma, the most common
chronic non-skin related disease in childhood, which is also linked to OAP exposure. Both of these conditions lead to substantial negative impacts on quality of life and place children at risk for other medical and psychological complications. However, they are rarely studied together in spite of their common co-occurrence and shared risk factors.

This study aims to understand the impact of outdoor airborne pollution on AD prevalence, severity, and persistence and comorbid AD+asthma. Further, the study will advance our understanding of the contribution of outdoor air pollution to racial and ethnic AD disparities and AD+asthma disparities. It has significant implications for 3 of the 4 NEA research priorities: eczema heterogeneity, understanding & alleviating disease burden, and eczema prevention – while simultaneously supporting NEA’s and PeDRA’s commitment to advancing equity. Results will lead to interventions directly aimed at reducing AD burden and racial and ethnic AD disparities.

Status:

This study was funded through the 2022 Childhood Eczema Challenge Grant.

Post-Market Surveillance of the Safety of Systemic JAK Inhibitors for Dermatologic Diseases in Children

By

Principal Investigator:

Jeff Yu, MD
Massachusetts General Hospital

Overview:

Oral Janus Kinase inhibitors (JAKi) are novel therapeutic options for patients with various inflammatory skin conditions, such as alopecia areata, atopic dermatitis, and psoriasis. Currently, most of the data that exists on the long-term side effects of JAKis comes from the rheumatology literature, where JAKis are used to treat highly inflammatory systemic diseases (i.e. rheumatoid arthritis). There is scant literature on the side effect profile or recommended laboratory monitoring during the use of JAKis in dermatologic conditions. Thus, the purpose of this database will be to provide pediatric dermatologists with accurate safety information and appropriate lab monitoring during the use of JAKis in the treatment of cutaneous inflammatory diseases, such as those listed above.

Status:

This project is new and needs additional sites. If you are interested in joining this study, please contact Hadley Johnson.

Evaluation of the Efficacy of Popular Over the Counter Ointments in Atopic Dermatitis: A Double Blinded Randomized Controlled Trial

By


Principal Investigator:

JiaDe Yu, MD
Massachusetts General Hospital

Overview:

Atopic dermatitis (AD) or eczema is a common skin disease seen in 20% or more of children in the United States. There are many potential causes of AD but disorders in the skin barrier leads to increased water loss from the skin thereby drying out the skin making it more prone to AD. Over the counter moisturizers such as Aquaphor, Cerave Ointment, Vaseline Ointment, and Vanicream Ointment are frequently recommended by dermatologists for the treatment and prevention of AD. While these products differ in their ingredients, there is currently no published evidence that one is superior to the other. The goal of this study is to evaluate the four moisturizing ointments in children with AD to see if we can determine which ointment is more efficacious in prevent dry skin and water loss.

Status:

This project was funded by a 2021 PeDRA Research Grant.

Neonatal Cutaneous Microbiome Predictors of Infantile Eczema

By

Principal Investigator:

Jennifer Schoch, MD
University of Florida

Overview:

Though the cause of eczema is yet unknown, animal studies suggest importance of the early interaction between bacteria present on the skin and the immune system. If bacteria are present on the skin of mice shortly after birth, then the immune system learns to “tolerate” the bacteria, and doesn’t create inflammation (i.e. eczema) when later exposed to the bacteria. To explore the possibility of a similar human mechanism, we will collect skin microbiome samples (including bacterial genetic material) from infants weekly for the first 4 weeks of life. The bacteria found on the skin in infants who later develop infantile eczema will be compared to infants who do not develop eczema. We hypothesize that specific bacteria (e.g. Staphylococcus) will be more abundant in the early skin microbiome of infants who do not develop eczema, compared to infants who do develop eczema. Successful completion will guide strategies to prevent eczema.

Status:

This study was funded through the 2021 Childhood Eczema Challenge Grant.

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.