PeDRA

Pediatric Dermatology Research Alliance

Connective Tissue & Autoimmune

Clinical and Genetic Characterization of Recurrent Reactive Infectious Mucocutaneous Eruption

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Principal Investigators:

Yvonne Chiu, MD
Medical College of Wisconsin

Michele Ramien, MD
University of Calgary

Beth Drolet, MD
University of Wisconsin, Madison

Overview:

Reactive infectious mucocutaneous eruption (RIME) is a condition activated by an infection, resulting in blisters on the skin and widespread sores on mucous membranes. RIME is rare but most commonly affects children and adolescents. Recurrent RIME, where people have multiple episodes of RIME, is even more rare.

Recent research studies have shown that genetic differences can affect how children respond to common viral infections. We hypothesize that people who have RIME have genetic differences that cause an abnormal hyper-inflammatory response to common infections, and that people with recurrent RIME have even stronger genetic susceptibility.

The medical community does not know much about RIME or how to treat it. We would like to characterize RIME and recurrent RIME, describing the clinical features, the immunologic profile, and discovering genetic variants. We hope that if we can understand what makes children have RIME, we will be able to treat the disease more effectively.

Status:

This project was funded by a 2020 PeDRA Research Grant.

Optimizing Clinical Application of Lymphocyte Activation Tests for the Detection of Causative Medications in severe cutaneous Adverse Reactions

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Principal Investigator:

Reid Oldenburg, MD, PhD
University of California, San Diego

Overview:

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are catastrophic drug reactions that destroy the skin, surface of the eyes and lining of the mouth and genitals. Antibiotics, ibuprofen and anti-seizures medications can cause SJS and TEN. When these severe cutaneous adverse reactions occur, the causative medication must be stopped immediately. However, identifying a causative medication can be difficult, especially when children are taking multiple medications.

There is no available blood test that can identify drugs that cause SJS and TEN, making it difficult for doctors to continue prescribing important medications, or use similar medications. Our long term interest is to develop diagnostic blood tests that can safely be used to identify causative medications for SJS and TEN patients. Our current project will stimulate blood from SJS and TEN patients with known causative medications to identify inflammatory molecules that can be later be used to develop diagnostic tests.

Status:

This project was funded by a 2020 PeDRA Research Grant.

Characterization of the presenting cutaneous manifestations of juvenile dermatomyositis

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Principal Investigator:

Sonia Kamath, MD
Children’s Hospital Los Angeles
Keck School of Medicine of the University of Southern California (USC)

Overview:

Juvenile dermatomyositis (JDM) is a rare autoimmune disease, causing muscle weakness and rash. The skin findings are variable and are crucial to establishing the diagnosis, as they often occur months or years prior to muscle weakness. Some children have a classic rash affecting the eyelids and knuckles, while others have less common findings, such as scalp rash. To better understand the skin disease in JDM, we propose to evaluate the spectrum of initial skin findings. We will conduct a multi-center, retrospective review of children diagnosed with JDM to determine the prevalence of skin findings at initial presentation, whether the presenting skin findings can help identify patients who develop muscle disease, and whether skin findings vary by race/ethnicity. Our findings will inform future prospective studies to define distinct presentations of JDM, characterize long-term disease outcomes, and improve treatment approaches for JDM.

Status:

This project was funded by a 2020 PeDRA Research Grant.

Investigating Constitutive and Cell-Driven Fibroblast Activation in Pediatric Morphea

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Fellow

Laila Abbas
UT Southwestern Medical Center

Mentor

Heidi Jacobe, MD, MSCS
UT Southwestern Medical Center

Overview

Morphea, or localized scleroderma, is a neglected autoimmune disease of the skin and underlying tissue that produces permanent disability due to joint contracture and soft tissue loss. Approximately half of patients have disease onset in childhood, and pediatric morphea is associated with significant morbidity, with reported complications including loss of range of motion, joint deformity, facial disfigurement, and neurologic manifestations. Morphea has remitting and relapsing activity, marked by inflammation and fibrosis, and damage which produces atrophy. The overarching hypothesis of this project is that fibroblasts are constitutively activated in morphea and that both T cells and macrophages will promote activation of fibroblasts.

Aim 1: Determine constitutive expression of pro-fibrotic and inflammatory markers in fibroblasts derived from morphea lesions as compared to matched control specimens.

Aim 2: Co-cultures will be performed with combinations of healthy and morphea fibroblasts along with healthy and morphea derived T cells and macrophages to determine if these cells can potentiate fibroblast activation.

Status

This project was funded through a 2020 PeDRA Research Fellowship Grant.

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea

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Principal Investigator:

Dawn Eichenfield, MD, PhD
University of California, San Diego

Overview:

Morphea is an inflammatory skin condition leading to hardened, discolored, and ultimately, scarred skin. It has several different presentations. Linear morphea commonly appears in children as a depressed or bound-down line on the forehead or extremity. Exactly why morphea occurs is unknown; however, studies suggest it is caused by a combination of genetic and environmental factors. Our research aims to uncover the genetic causes of linear morphea. Where our study differs from prior studies is the focus on studying parts of the genome that do not code for proteins, but instead are involved in regulating when or how genes are active. It is only recently that we realized the importance and disease relevance of these “non-coding” portions and could feasibly study their effects. Our project will utilize the latest sequencing technologies to investigate genetic mutations in morphea that can lead to improved diagnosis and earlier treatment.

Status:

This study was funded as a 2018 PeDRA Pilot Grant and is currently underway.

Sun Protection for Pediatric Rheumatology Patients

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Principal Investigator:

Irene Lara-Corrales, MD
University of Toronto

Overview:

This is a survey study in collaboration with the Childhood Arthritis and Rheumatology Research Alliance (CARRA). Pediatric rheumatologists and pediatric rheumatology patients will be surveyed about the sun protection knowledge to identify practice gaps and target areas for education.

Status:

Survey instrument was deployed in March 2021.

North American Study of Pediatric Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Setting Diagnostic Criteria, Systematic Review and Retrospective Cohort Analysis Comparing Outcomes of Common Treatments

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Principal Investigator:

Michele Ramien, MD
University of Calgary

Overview:

A critical gap exists in our knowledge of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) in pediatrics. Little is known about how to accurately define the spectrum of disease or direct optimal treatment. Much of the literature we rely on to manage pediatric SJS and TEN (SJS/TEN) is extrapolated from adult studies, the applicability of which has been questioned in recent reviews. Discussion at the 2015 and 2016 PeDRA meetings with opinion leaders supports our proposal that diagnostic criteria are a critical first step to inform more detailed examination of pediatric SJS/TEN and advance clinical care.

We have three objectives:
1. Create consensus diagnostic criteria for the pediatric SJS/TEN spectrum using a combination of nominal group technique and the Delphi method;
2. Perform a systematic review of treatment responses in SJS/TEN;
3. Apply diagnostic criteria for a multicentre retrospective cohort analysis to determine optimal management and encourage standardized treatment.

Status:

This study was funded as a 2016 SPD-PeDRA Team Grant and is underway. The first of three anticipated publications is currently under review.

Participating Sites:

Mapping Morphea: Toward a Better Understanding

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Principal Investigator:

Yvonne Chiu, MD
Medical College of Wisconsin

Overview:

This is a retrospective chart and photograph review study conducted at seventeen collaborating sites. Using software initially developed for the Hemangioma Investigator Group, investigators have mapped morphea lesions on body diagrams, allowing better understanding of morphea distribution and correlation with other clinical features.

Status:

This study was funded as a 2015 PeDRA Pilot Grant. Data are currently being analyzed and manuscripts being prepared. Multiple publications are anticipated.

Participating Sites: