Clinical trial NCT00515047: Identifying Genetic Determinants of Eczema Herpeticum and Other Viral Infections in Individuals With Atopic Dermatitis
Official title: Genetics of Atopic Dermatitis - Eczema Herpeticum
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
Eczema
Eczema Herpeticum
Molluscum Contagiousum
Herpes Simplex
Vaccinia
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2007-08-13
Enrollment: 900
Sex: ALL
Minimum age (years): 8
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: African-American, Caucasian, and Non-Hispanic people ages 8 months to 80 years

Brief summary: People with atopic dermatitis (AD), or eczema, are susceptible to skin infections and inflammations. Some individuals with AD develop a condition known as eczema herpeticum (EH) following exposure to the herpes simplex virus (HSV). The purpose of this study is to identify the genetic determinants that lead people with AD to develop EH and similar conditions caused by other viruses.

Detailed description: AD is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. However, people with AD do not all develop the same infections. For example, some people with AD who receive the smallpox vaccine develop a life-threatening condition known as eczema vaccinatum (EV). This study focuses on individuals with AD who also have a history of eczema herpeticum (ADEH+), a condition similar to EV. It is unlikely that the differences in the development of skin infections are due to differences in viral exposure, and instead due to differences in each individual's response to viruses. The purpose of this study is to determine the genetic pathways which are responsible for the development of viral skin infections in people with AD.

Participants in this study will also be enrolled in the ADVN Biomarker Registry Study. There will be only one clinical visit for this study at which blood and/or skin samples may be collected. The samples will then have high-throughput genotyping to define genetic markers in individuals susceptible to viral infections.

Eligibility criteria: Inclusion Criteria:

* Enrollment in ADVN Biomarker Registry Study
* Non-Hispanic and only African American or only Caucasian race
* Parent or guardian willing to provide informed consent, if necessary

Exclusion Criteria:

* History of any systemic illness, excluding AD
* Participation of a first degree relative already enrolled in the genotyping study unless the subject in question fulfills the diagnostic criteria for ADEH+. More information on this criterion can be found in the protocol.

Primary outcomes:
measure: Identification of variants/haplotypes in EH-associated genes and characterization of frequencies of variants in priority candidate genes for EH
timeFrame: Throughout Study
Secondary outcomes:
measure: Identification and prioritization of novel genes induced in response to viral infection (HSV/Vaccinia and MCV) in AD participants and relevant control groups
timeFrame: Throughout Study
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
Study officials:
affiliation: University of Rochester
name: Lisa Beck, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Allergy and Asthma Center
name: Kathleen Barnes, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baker BS. The role of microorganisms in atopic dermatitis. Clin Exp Immunol. 2006 Apr;144(1):1-9. doi: 10.1111/j.1365-2249.2005.02980.x.
citation: Kim BE, Leung DY, Streib JE, Kisich K, Boguniewicz M, Hamid QA, Howell MD. Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus. J Allergy Clin Immunol. 2007 Feb;119(2):457-63. doi: 10.1016/j.jaci.2006.10.005. Epub 2006 Dec 4.
citation: Porter CD, Muhlemann MF, Cream JJ, Archard LC. Molluscum contagiosum: characterization of viral DNA and clinical features. Epidemiol Infect. 1987 Oct;99(2):563-6. doi: 10.1017/s0950268800068072.
citation: Umene K, Yoshida M, Sakaoka H. Comparison of the association with eczema herpeticum in the two predominant genotypes of herpes simplex virus type 1. J Med Virol. 1996 Aug;49(4):329-32. doi: 10.1002/(SICI)1096-9071(199608)49:43.0.CO;2-5.
citation: Gao PS, Leung DY, Rafaels NM, Boguniewicz M, Hand T, Gao L, Hata TR, Schneider LC, Hanifin JM, Beaty TH, Beck LA, Weinberg A, Barnes KC. Genetic variants in interferon regulatory factor 2 (IRF2) are associated with atopic dermatitis and eczema herpeticum. J Invest Dermatol. 2012 Mar;132(3 Pt 1):650-7. doi: 10.1038/jid.2011.374. Epub 2011 Nov 24.
citation: Gao PS, Rafaels NM, Mu D, Hand T, Murray T, Boguniewicz M, Hata T, Schneider L, Hanifin JM, Gallo RL, Gao L, Beaty TH, Beck LA, Leung DY, Barnes KC. Genetic variants in thymic stromal lymphopoietin are associated with atopic dermatitis and eczema herpeticum. J Allergy Clin Immunol. 2010 Jun;125(6):1403-1407.e4. doi: 10.1016/j.jaci.2010.03.016. Epub 2010 May 13. No abstract available.