TY - JOUR
T1 - Phenotype of atopic dermatitis subjects with a history of eczema herpeticum
AU - Beck, Lisa A.
AU - Boguniewicz, Mark
AU - Hata, Tissa
AU - Schneider, Lynda C.
AU - Hanifin, Jon
AU - Gallo, Rich
AU - Paller, Amy S.
AU - Lieff, Susi
AU - Reese, Jamie
AU - Zaccaro, Daniel
AU - Milgrom, Henry
AU - Barnes, Kathleen C.
AU - Leung, Donald Y.M.
N1 - Funding Information:
The ADVN is composed of 3 distinct groups supported by 3 separate National Institutes of Health contracts: the Clinical Study Consortium (CSC; contract NO1 AI 40029), the Statistical and Data Coordinating Center (SDCC; contract NO1 AI 40033), and the Animal Study Consortium (ASC; contract NO1 AI 40030). These groups work closely together to achieve the common goal of the ADVN, which is to investigate the mechanism or mechanisms responsible for the susceptibility of subjects with AD to viral infections. The central hypothesis of the CSC studies is that subjects with AD who are susceptible to generalized cutaneous infections with HSV or who have complications after smallpox (or possibly other live-attenuated vaccinations [yellow fever vaccine]) might have common immunologic defects that could be reflected in serum biomarkers or phenotypes identified by means of an extensive history and physical examination. The role of the ASC is to characterize mouse models of EV and define cellular and molecular immune mechanisms that give rise to EV. The SDCC is managed by Rho, Inc, under the leadership of Drs Susan Lieff and Gloria David and helps with development of clinical protocols; coordination of local institutional review board and Division of Allergy, Immunology, and Transplantation at the NIAID branch (DAIT) protocol and consent form approval; coordination of study activities; study-specific training; data collection; maintenance of a clinical database; sample tracking; statistical data analysis; and coordination of activities of both the ASC and CSC. For example, regulatory documents (informed consents and advertisements) were submitted to the SDCC followed by the DAIT division of the NIAID for review before local institutional review board submission. Institutional review board approvals were forwarded to the SDCC for central tracking of all regulatory documentation. Each site had a site-initiation visit before enrolling a subject, as well as an interim monitoring visit shortly after the start of enrollment and at least once a year thereafter to ensure data quality assurance and quality control.
Funding Information:
Supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis and Vaccinia Network contract N01 AI40029 and NO1 AI40033. Partial funding also provided by Mary Beryl Patch Turnbull Scholar Program.
Funding Information:
Disclosure of potential conflict of interest: L. A. Beck owns stock in Wyeth; receives grant support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, Centocor, and the National Institutes of Health/Clinical and Transitional Science Institute/University of Rochester Medical Center; is a consultant for Glycomimetics, Anacor, and Magen; and is on the scientific advisory board for the National Eczema Association. M. Boguniewicz received grant support from Novartis, serves as a consultant for Graceway and Unilever; and is a member of and speaker at the annual meeting of the American College of Allergy, Asthma & Immunology. L. C. Schneider received grant support from Novartis and the National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Vaccinia Network. A. S. Paller received grant support from the National Institutes of Health. S. Lieff is employed by Rho, Inc. J. Reese is employed by Rho, Inc. D. Zaccaro is employed by Rho, Inc. D. Y. M. Leung received grant support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases.
PY - 2009/8
Y1 - 2009/8
N2 - Background: A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum. Objective: This National Institute of Allergy and Infectious Diseases-funded multicenter study was performed to establish a database of clinical information and biologic samples on subjects with AD with and without a history of eczema herpeticum (ADEH+ and ADEH- subjects, respectively) and healthy control subjects. Careful phenotyping of AD subsets might suggest mechanisms responsible for disseminated viral infections and help identify at-risk individuals. Methods: We analyzed the data from 901 subjects (ADEH+ subjects, n = 134; ADEH- subjects, n = 419; healthy control subjects, n = 348) enrolled between May 11, 2006, and September 16, 2008, at 7 US medical centers. Results: ADEH+ subjects had more severe disease based on scoring systems (Eczema Area and Severity Index and Rajka-Langeland score), body surface area affected, and biomarkers (circulating eosinophil counts and serum IgE, thymus and activation-regulated chemokine, and cutaneous T cell-attracting chemokine) than ADEH- subjects (P < .001). ADEH+ subjects were also more likely to have a history of food allergy (69% vs 40%, P < .001) or asthma (64% vs 44%, P < .001) and were more commonly sensitized to many common allergens (P < .001). Cutaneous infections with Staphylococcus aureus or molluscum contagiosum virus were more common in ADEH+ subjects (78% and 8%, respectively) than in ADEH- subjects (29% and 2%, respectively; P < .001). Conclusion: Subjects with AD in whom eczema herpeticum develops have more severe TH2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. They are also much more likely to experience cutaneous infections with S aureus or molluscum contagiosum.
AB - Background: A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum. Objective: This National Institute of Allergy and Infectious Diseases-funded multicenter study was performed to establish a database of clinical information and biologic samples on subjects with AD with and without a history of eczema herpeticum (ADEH+ and ADEH- subjects, respectively) and healthy control subjects. Careful phenotyping of AD subsets might suggest mechanisms responsible for disseminated viral infections and help identify at-risk individuals. Methods: We analyzed the data from 901 subjects (ADEH+ subjects, n = 134; ADEH- subjects, n = 419; healthy control subjects, n = 348) enrolled between May 11, 2006, and September 16, 2008, at 7 US medical centers. Results: ADEH+ subjects had more severe disease based on scoring systems (Eczema Area and Severity Index and Rajka-Langeland score), body surface area affected, and biomarkers (circulating eosinophil counts and serum IgE, thymus and activation-regulated chemokine, and cutaneous T cell-attracting chemokine) than ADEH- subjects (P < .001). ADEH+ subjects were also more likely to have a history of food allergy (69% vs 40%, P < .001) or asthma (64% vs 44%, P < .001) and were more commonly sensitized to many common allergens (P < .001). Cutaneous infections with Staphylococcus aureus or molluscum contagiosum virus were more common in ADEH+ subjects (78% and 8%, respectively) than in ADEH- subjects (29% and 2%, respectively; P < .001). Conclusion: Subjects with AD in whom eczema herpeticum develops have more severe TH2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. They are also much more likely to experience cutaneous infections with S aureus or molluscum contagiosum.
KW - Atopic dermatitis
KW - Staphylococcus aureus
KW - biomarkers
KW - eczema herpeticum
KW - eczema vaccinatum
KW - herpes simplex virus
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U2 - 10.1016/j.jaci.2009.05.020
DO - 10.1016/j.jaci.2009.05.020
M3 - Article
C2 - 19541356
AN - SCOPUS:67651211687
SN - 0091-6749
VL - 124
SP - 260-269.e7
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -
