PeDRA

Pediatric Dermatology Research Alliance

Inflammatory Skin Disease

The Relationship between the Cutaneous Microbiome and Skin Barrier in Infantile Atopic Dermatitis

By

Principal Investigator:

Jennifer Schoch, MD – University of Florida

Co-Investigator:

Reesa Monir, MD – University of Florida

Overview:

Infantile atopic dermatitis (i.e. eczema) is a common pediatric skin condition leading to significant complications for patients and parents. Sleep disturbances, behavioral issues, and parental exhaustion are just a few of the negative ramifications. Though advances have been made in disease treatment, preventive interventions lag far behind.

Infancy is a unique, impressionable period of time during which the physical skin barrier, the cutaneous immune system, and the skin microbiome are developing in parallel. These closely intertwined factors are critical to the development of eczema. The skin barrier becomes “leaky” in kids with eczema, making it dry and prone to infection. The skin’s immune system becomes more reactive, leading to itching and inflammation. The collection of microbes that live in and on the skin (the skin microbiome) also changes in kids with eczema. The timeline of these changes and how they are related, however, is unclear.

In this study, we will begin exploration of the relationship between skin structure, cutaneous immunity, and the cutaneous microbiome. We will examine skin pH and the cutaneous microbiome in infants with newly-onset atopic dermatitis, compared to infants without eczema. Infants age three to nine months with newly-onset atopic dermatitis and without atopic dermatitis will be compared, with the goal of identifying how and when various aspects of skin development go awry. Understanding normal and pathologic skin changes is the first step in developing preventative interventions.

Status:

This study was funded through the 2019 PeDRA Research Hot Seat – A PeDRA Shark Tank.

Dermatitis and the Microbiome

By

Principal Investigator:

Pranab Mukherjee, PhD – Case Western Reserve University

Overview:

Atopic dermatitis (AD) is a complex disease that affects millions of people worldwide. It has many contributing factors, including genetics, environmental factors, and the microbiome.

A recent pilot study has suggested that Halomonas species were abundant on the skin of AD patients. This unexpected, saline-loving organism led to the speculation that increased skin salinity may allow proliferation of microbes that promote itch. The objective of this study is to further examine the relationship of itching after perspiration with changes in the microbiome. Itching with perspiration is a common symptom reported in some but not all AD patients. This may be a clue to identify patients where the microbiome provokes an immune response resulting in itch. We hypothesize that the abundance of Halomonas on the skin of AD patients who itch with perspiration is higher than that of AD patients who do not itch with perspiration.

The second objective of this study is to compare microbiome and mycobiome variations in AD patients versus controls, and how this differs in adults and children. Recent literature shows that the mycobiome of children’s skin changes during puberty to become more similar to adult skin, however the microbiome and mycobiome of children with and without AD are not well understood. In our study, we compare the microbiome and mycobiome of the skin of children compared to adults with AD, and compared to that of children without AD, to see if there are different organisms that drive AD in children.

Status:

This study was funded as a 2017 PeDRA Pilot Grant and has concluded with plans to pursue related research questions in future.

Quality of Life of Parents with Children with Alopecia Areata

By

Principal Investigator:

Leslie Castelo-Soccio, MD, PhD – Children’s Hospital of Philadelphia

Overview:

Alopecia areata (AA) is an autoimmune disease resulting in non-scarring hair loss of hair-bearing areas, most frequently the scalp with a lifetime incidence of 1-2%. There is no sex predominance and it occurs in all parts of the world.  In the united states it accounts for 2.4 million doctor visits per year.   The more severe variants alopecia totalis (AT) and alopecia universalis (AU) lead to more extensive hair loss .  Due to its visibility, lack of curative therapy, and chronic nature, alopecia areata can create a significant psychosocial burden on patients who suffer from the disease. Though many studies have been conducted to determine psychosocial impact from the patient perspective, caregiver-oriented research is lacking. When available, clinicians could use information from such quality of life (QoL) tools to guide management and tailor support and education for patients and their families.

This was a multi-center, prospective study examining the impact on QoL of parents with children affected by alopecia areata. The overall goal was to quantitatively evaluate impairment in QoL in parents of children with AA. Secondary objectives were to investigate the relationship between scores on QoL tools and severity of disease, child’s QoL, and time since diagnosis.

Status:

This study was funded as a 2017 PeDRA Pilot Grant and is complete, with one publication resulting in 2019 (see publications page).

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea

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Principal Investigator:

Dawn Eichenfield, MD, PhD – UCSD

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 (Figure 1A) or extremity (Figure 1B). 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.

Fecal Microbiome in Alopecia Areata

By

Principal Investigator:

Leslie Castelo-Soccio, MD, PhD – Children’s Hospital of Philadelphia

Overview:

Alopecia areata is an autoimmune disease that leads to hair loss. There is no approved therapy for this stigmatizing disease. Current off-label immune suppressive therapies can put children at short-term risk for infection and long-term risk for malignancy. In other similar autoimmune diseases, there has been increasing evidence that altering the bacteria of the gastrointestinal tract may mitigate disease. There is no specific data on the microbiome in individuals with alopecia areata. We propose to create a database of stool samples from children with and without alopecia areata. We will then analyze the genetics of the stool to classify the diversity and type of bacteria in the samples of children with alopecia and without alopecia. We expect to see differences between these populations. Longer term, we aim for this pilot to become the basis for novel interventional studies creating complementary therapeutics for pediatric alopecia areata.

Status:

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

Systemic Treatment of Atopic Dermatitis

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Principal Investigator:

Wynnis Tom, MD – UCSD

Overview:

This is a prospective, observational study of traditional systemic agents for severe, refractory atopic dermatitis in children. We are comparing the efficacy and safety of oral cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate, guided by consensus-derived dosing and administration protocols.

Status:

Enrollment 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 is in late stages of development and almost ready to be deployed.

Retrospective Review of Topical Immunotherapy for Alopecia Areata

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Principal Investigator:

Nanette Silverberg, MD – Mount Sinai Health System

Overview:

Alopecia areata (AA) is an autoimmune disease resulting in non-scarring hair loss of hair-bearing areas, most frequently the scalp with a lifetime incidence of 1-2%. This is a registry study intended to help us learn more about the use of topical immunotherapy for AA.

Status:

Enrolling patients.