Registry for the Atopic Dermatitis Research Network

Study Overview
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Brief Summary
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The purpose of this multi-center, clinical registry study is to determine genetic markers associated with susceptibility of AD patients to infections and to also serve as a potential participant database for future studies.

Detailed Description
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People with atopic dermatitis (AD), also known as eczema, experience hot, dry, scaly skin with severe itching. In addition, people with AD are prone to skin infections and inflammation. Little is known about the causes of AD or why people with AD are more prone to infections. The purpose of this multi-center, clinical registry study is to determine genetic markers associated with susceptibility of AD patients to infections and to also serve as a potential participant database for future studies. Study procedures will usually be completed in one visit to the clinic; however, participants may need to return for one or more additional visits to provide blood and skin swabs if they do not meet sampling criteria at the initial Screening Visit. A subset of participants from National Jewish Health may be asked to return to clinic for 2 additional visits approximately 7 and 14 days after the original sample collection for collection of skin swabs for assessment of antimicrobial activity. All participants may also be asked to return for an Unscheduled Visit to provide additional blood and/or skin swabs. Atopic Dermatitis with previous or current Eczema Herpeticum (ADEH+), Atopic Dermatitis with previous or current Eczema Vaccinatum (ADEV+) and Methicillin-Resistant S. Aureus (MRSA+) participants will be contacted every 6 months for the duration of the study. Recruitment emphasis will include Non-Hispanic Caucasian, Non-Hispanic African American, and Mexican American since these constitute the three largest racial/ethnic populations according to the U.S. Census Bureau 2009 data; however, no racial/ethnic groups will be excluded. Our scientific rationale for targeting these three racial/ethnic groups is to ensure that we are able to recruit sufficient numbers of participants in each group to perform meaningful tests for genetic association.

Official Title
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Registry for the Atopic Dermatitis Research Network (ADRN-02)

Conditions
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Atopic Dermatitis, Eczema Herpeticum

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who meet all of the following criteria are eligible for enrollment. Participants may be reassessed if not initially eligible. ADEH+ and Non-atopic males and females ages 8 months to 80 years, inclusive, at the time of Enrollment, and ADEH- males and females ages 3 years to 80 years, inclusive, at the time of Enrollment. Who are willing to sign the informed consent form or whose parent or legal guardian is willing to sign the informed consent form (age appropriate) prior to initiation of any study procedures. Who are willing to sign the assent form, if age appropriate. Who meet criteria for one of the diagnostic groups (ADEH-Staph+, ADEH-Staph-, ADEH+, ADEV+, Non-atopic) as defined in the ADRN Standard Diagnostic Criteria and the Staphylococcus aureus Colonization Criteria. Exclusion Criteria: Participants who meet any of the following criteria are not eligible for enrollment. Who have an active systemic malignancy; uncomplicated non-melanoma skin cancer and melanoma in situ with documentation of complete excision are not exclusionary. Who have any skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous diseases, psoriasis, cutaneous T cell lymphoma [also called Mycosis Fungoides or Sezary syndrome], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease). Who have a history of systemic immunological illness (e.g., immunodeficiency disorders such as human immunodeficiency virus [HIV] or lupus erythematosus) other than the condition being studied. Who have a first degree relative already enrolled in the study. Who are determined not to be eligible in the opinion of the Investigator.

Ages Eligible for Study
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Minimum Age: 8 Months
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ADEH-Staph+<br>Atopic Dermatitis without a history of Eczema Herpeticum and with S. aureus skin colonization. A minimum of 1100 participants will be enrolled; we will target 500 Non-Hispanic Caucasian, 300 Non-Hispanic African American, and 300 Mexican American Caucasian ADEH-Staph+ participants. Although we will target these three groups, no racial/ethnic groups will be excluded. | |
| ADEH-Staph-<br>Atopic Dermatitis without a history of Eczema Herpeticum and without S. aureus skin colonization. A minimum of 1100 participants will be enrolled; we will target 500 Non-Hispanic Caucasian, 300 Non-Hispanic African American, and 300 Mexican American Caucasian ADEH-Staph- participants. Although we will target these three groups, no racial/ethnic groups will be excluded. | |
| ADEH+<br>Atopic Dermatitis with previous or current Eczema Herpeticum.We will try to include a minimum of 150 Non-Hispanic Caucasian ADEH+ participants. ADEH+ participants of other racial/ethnic groups will not be excluded | |
| ADEV+<br>Atopic Dermatitis with previous or current Eczema Vaccinatum. ADEV+ sub-phenotype is very rare so all eligible participants will be enrolled. | |
| Non-atopic<br>Non-atopic healthy participants. A minimum of 250 non-atopic participants will be enrolled. Non-atopic participants will serve as a control group for the genetic, biomarker, Staph characterization, and microbiome studies. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genotype and sequence data from ADEH+ and ADEH- participants. |  | Day 1 | 
| Genotype and sequence data from ADEH- participants with and without bacterial colonization with S. aureus. |  | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Nucleotide Polymorphism (SNP) and Copy Number Variant (CNV) genotype data for candidate genes, including but not limited to Claudin-1 (CLDN1) and Filaggrin (FLG). |  | Day 1 | 
| SNP genotype data for candidate genes, including but not limited to CLDN1 and FLG, validated in samples from an independent AD population. |  | Day 1 | 
| Targeted deep resequencing of candidate genes, including but not limited to CLDN1. |  | Day 1 | 
| Analysis of S. aureus isolates for antibiotic sensitivity |  | Day 1 | 
| Analysis of S. aureus isolates for staphylococcal cassette chromosome (SCC) mec DNA elements. |  | Day 1 | 
| Analysis of S. aureus isolates for expression of virulence or other factors. |  | Day 1 | 
| Expression of biomarkers, including but not limited to serum biomarkers, among AD sub-phenotypes. |  | Day 1 | 
| Analysis of microbial composition by 16S ribosomal Deoxyribonucleic Acid (rDNA) amplicon sequencing. |  | Day 1 | 
| Analysis of DNA methylation profiles |  | Day 1 | 
| Analysis of messenger Ribonucleic Acid (mRNA) expression profiles in whole blood samples. |  | Day 1 | 
| Frequency of commensal Staphylococcus species producing antimicrobial activity |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Registry, Atopic Dermatitis, Eczema Herpeticum, GWAS, Staphylococcus aureus