PeDRA

Pediatric Dermatology Research Alliance

Active Studies

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.

Exploring the Cutaneous Microbiome in Premature Neonates: A Pilot Study

By

Principal Investigator:

Jennifer Schoch, MD – University of Florida

Overview:

The study sought to characterize the cutaneous microbiome in a cohort of premature infants, and explore the impact of early postnatal antibiotic exposure on the cutaneous microbiome. Bacterial colonization of both the infant gut and skin are likely critical in immune system development, though little is known about the parallel assembly of the microbiome across sites. This study built on the previous work on the impact of antibiotics on the intestinal microbiome, metabolome, and inflammatory responses in premature infants. The addition of cutaneous microbiome sampling to this existing cohort allowed for comparison between the development of the microbiome in both the skin and gut within the same subject. It also allowed the exploration the impact of antibiotic exposure on cutaneous microbial diversity and adverse outcomes including sepsis. Finally, in the event of adverse outcomes, cultured pathogenic organisms will be compared to microbial profiles of the skin and intestine to explore which site was likely breached. We hypothesized that antibiotic exposure was associated with a loss of microbial diversity across both the cutaneous and intestinal microbiome, and that these effects extend beyond the duration of the antibiotic exposure. We also suspected that the altered microbial ecology would be associated with a higher incidence of adverse outcomes, including late onset sepsis (LOS), which can be associated with a breach in the intestinal, mucosal, or cutaneous barrier.

Status:

This study was funded as a 2017 PeDRA Pilot Grant and is now complete. Final results were presented at the 2019 Annual Meeting of the Society for Pediatric Dermatology.

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).

Genomic and Non genomic Causes of Segmental Pigmentation Disorder

By

Principal Investigator:

Marcia Hogeling, MD – UCLA

Overview:

Segmental Pigmentation Disorder (SegPD) is an uncommon skin condition affecting young children. Segmental Pigmentation Disorder consists of white and brown pigmented birthmarks that appear as large patches on the body. The underlying cause of Segmental Pigmentation Disorder is not known, but it suspected to be due to genetic changes in these different areas of skin color, in the way that the skin cells produce pigment. The purpose of this study is to search for the cause of SegPD, by performing genetic testing of skin samples. Knowing the underlying cause of SegPD will allow us to better explain this skin problem to parents, and make informed recommendations on screening, monitoring and possibly treatments. Many birthmarks in children have the same mutations seen in cancer, and we think our study also might contribute to cancer research if SegPD has these mutations.

Status:

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

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea

By

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

By

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

By

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.