Dataset Information

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

ABSTRACT:

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections.

Objective

We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections.

Methods

Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled. Vaccinia virus (VV) expression was measured by means of PCR and immunofluorescent staining in skin biopsy specimens from each study group after incubation with VV. Transgenic mice with a constitutively active signal transducer and activator of transcription 6 gene (STAT6) were characterized for response to VV skin inoculation. Genotyping for 10 STAT6 single nucleotide polymorphisms (SNPs) was performed in a white patient sample (n = 444).

Results

VV gene and protein expression were significantly increased in the skin of patients with EH compared with other subject groups after incubation with VV in vitro. Antibody neutralization of IL-4 and IL-13 resulted in lower VV replication in patients with a history of EH. Mice that expressed a constitutively active STAT6 gene compared with wild-type mice had increased mortality and satellite lesion formation after VV skin inoculation. Significant associations were observed between STAT6 SNPs and EH (rs3024975, rs841718, rs167769, and rs703817) and IFN-? production. The strongest association was observed for a 2-SNP haplotype (patients with AD with a history of EH vs patients with AD without a history of EH, 24.9% vs 9.2%; P = 5.17 × 10(-6)).

Conclusion

The STAT6 gene increases viral replication in the skin of patients with AD with a history of EH. Further genetic association studies and functional investigations are warranted.

SUBMITTER: Howell MD

PROVIDER: S-EPMC3205328 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

Howell Michael D MD Gao Peisong P Kim Byung Eui BE Lesley Leighann J LJ Streib Joanne E JE Taylor Patricia A PA Zaccaro Daniel J DJ Boguniewicz Mark M Beck Lisa A LA Hanifin Jon M JM Schneider Lynda C LC Hata Tissa R TR Gallo Richard L RL Kaplan Mark H MH Barnes Kathleen C KC Leung Donald Y M DY

The Journal of allergy and clinical immunology 20110718 5

<h4>Background</h4>Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections.<h4>Objective</h4>We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections.<h4>Methods</h4>Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled. Vaccinia virus (VV) expression was measured by means of PCR and immunofluorescent staining i ...[more]

PMID: 21762972

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Project description:BACKGROUND:Atopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain. OBJECTIVE:To characterize the patient burden of skin pain in AD. METHODS:We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist. RESULTS:Overall, 305 patients (age range, 13-97 years) were included in the study, with 564 encounters. The cohort included 195 females (63.9%) and 193 whites (63.7%). The mean (SD) age at enrollment was 42.3 (18.1) years, and the mean (SD) age of patient-reported AD onset was 29.6 (31.9) years. At baseline, 144 patients (42.7%) reported skin pain in the past week, with 42 (13.8%) reporting severe or very severe pain. Twenty-four (16.8%) thought the skin pain was part of their itch, 16 (11.2%) from scratching, and 77 (72.0%) from both. Patients with skin pain were more likely to describe their itch using terms that resembled neuropathic pain. Prevalence of skin pain was increased in patients with vs without excoriations (72.6% vs 57.6%; ?2 test P?=?.02) but not other morphologic characteristics. Skin pain severity was most strongly correlated with the Patient-Oriented Eczema Measure (Spearman ??=?0.54), followed by ItchyQOL (??=?0.52), 5-dimensions of itch scale (??=?0.47), Dermatology Life Quality Index (??=?0.45), numeric rating scale for itch (??=?0.43) and sleep (??=?0.36), Patient Health Questionnaire 9 (??=?0.36), patient-reported global AD severity (??=?0.34), Eczema Area and Severity Index (??=?0.23), and objective Scoring AD index (??=?0.20) (P?<?.001 for all). Patients with both severe itch and pain vs those with only one or neither symptom being severe had significant increases in all these measures. CONCLUSION:Skin pain is a common and burdensome symptom in AD. Skin pain severity should be assessed with itch severity in AD patients and may be an important end point for monitoring treatment response.

Dataset Information

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

Background

Objective

Methods

Results

Conclusion

Publications

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

Similar Datasets

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