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Original Investigation | Epidemiology

Association Between Atopy and Herpetic Eye Disease Results From the Pacific Ocular Inflammation Study FREE

Durga S. Borkar, MD1; John A. Gonzales, MD1; Vivien M. Tham, MD2; Elizabeth Esterberg, MS1; Aleli C. Vinoya, BS3; John V. Parker, BS3; Aileen Uchida, MPH3; Nisha R. Acharya, MD, MS1,4
[+] Author Affiliations
1F. I. Proctor Foundation, University of California, San Francisco
2Department of Ophthalmology, Kaiser Permanente Hawaii, Honolulu
3Center for Health Research, Kaiser Permanente Hawaii, Honolulu
4Department of Ophthalmology, University of California, San Francisco
JAMA Ophthalmol. 2014;132(3):326-331. doi:10.1001/jamaophthalmol.2013.6277.
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Published online

Importance  Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited.

Objective  To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO).

Design, Setting, and Participants  Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217 061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period.

Main Outcomes and Measures  Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship–trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases.

Results  One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO.

Conclusions and Relevance  The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

Figures in this Article

Herpetic eye disease is a significant cause of sight-threatening infection worldwide.13 Cell-mediated immunity, including the helper T cell, subtype 1 (TH1) response, is crucial in combating herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO).48 Several studies912 have shown that atopic diseases, such as asthma, allergic rhinitis, and atopic dermatitis, heighten the TH2 response and can weaken the TH1 response through a complex interplay of regulatory cytokines.

Patients who develop eczema herpeticum or have bilateral HSV ocular disease frequently have a history of atopic disease.1216 In addition, patients with atopy may develop resistant infection or require longer and higher dosages of antiviral therapy to prevent recurrences.1619 The largest population-based case-control study20 published on this subject to date found an association between atopy and HSV ocular disease; however, an older study21 did not. It is unknown if there is an association between HZO and atopy.

The Pacific Ocular Inflammation project is an epidemiologic study of ocular inflammatory disease in the Hawaiian Islands. Kaiser Permanente Hawaii provides an ideal setting for this because it serves more than 15% of the general Hawaiian population and has a racially diverse membership that has not been studied extensively. The objective of this specific population–based case-control study was to assess whether there is an association between atopy and herpetic eye disease, including HSV ocular disease and HZO.

Institutional review board and ethics committee approval was obtained at the University of California, San Francisco, and Kaiser Permanente Hawaii. All work was Health Insurance Portability and Accountability Act compliant and adhered to the tenets of the Declaration of Helsinki. Informed consent was not obtained because this was a study using previously collected information for standard patient care. However, all members of the Kaiser system are informed that their deidentified data may be used for research purposes. As a result, waiver of informed consent was granted by the Kaiser Permanente Hawaii Institutional Review Board and the University of California, San Francisco, Ethics Committee.

Patient encounters in the Kaiser Permanente Hawaii electronic medical record between January 1, 2006, and December 31, 2007, were queried for International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes corresponding to herpes zoster or herpes simplex with ophthalmic complications (Table 1). All diagnoses of HSV ocular disease and HZO were individually verified through electronic medical record review by a cornea and uveitis fellowship–trained ophthalmologist (N.R.A.). In addition, patients were classified as having blepharitis, conjunctivitis, dermatitis, keratitis, or uveitis based on clinical examination information. All patients with a confirmed diagnosis of HSV ocular disease or HZO who were 18 years or older as of the midpoint of the study period (January 1, 2007) were included in the study.

Table Graphic Jump LocationTable 1.  International Classification of Diseases, Ninth Revision (ICD-9) Diagnosis Codes Used to Identify Herpetic Eye Disease and Atopic Disease

Two control groups were each randomly selected at a 4:1 ratio of controls to HSV ocular disease cases and to HZO cases. An ophthalmology clinic control group was selected from the population of Kaiser Permanente Hawaii patients who were 18 years or older as of January 1, 2007, and had at least 1 visit to the Kaiser ophthalmology clinic during the study period. An age- and sex-matched control group was selected from the general Kaiser Permanente Hawaii population having at least 1 physician visit during the study period. Age was matched within 5 years.

A diagnosis of atopic disease was determined based on an ICD-9 diagnosis code related to atopy before or during the study period (Table 1). Patients with atopic disease were classified as having asthma, atopic dermatitis, or allergic rhinitis based on specific ICD-9 diagnosis codes. Additional demographic data were collected electronically for cases and controls. Smoking status for cases and controls was determined based on electronic data obtained at physician office visits. A patient’s smoking status closest to the midpoint of the study period was used for cases and controls.

Demographic data were compared between cases and controls using Fisher exact test and t test for categorical and continuous variables, respectively. The association between atopy and herpetic eye disease was assessed using a logistic regression with herpetic eye disease (herpes simplex or herpes zoster) as the outcome. A conditional logistic regression was used when comparing cases with the age- and sex-matched controls. Age and sex were included as covariates for analyses using the ophthalmology clinic controls. Additional analyses were performed to assess the effect of race and smoking status on the association.

P < .05 was considered statistically significant. All analyses were performed using statistical software (STATA 11.0; StataCorp LP).

The midpoint population of Kaiser Permanente Hawaii on January 1, 2007, was 217 061 patients. Of this population, 114 adult patients had a confirmed diagnosis of HSV ocular disease, and 137 adult patients had a confirmed diagnosis of HZO. Ocular manifestations for each type of herpetic eye disease are shown in the Figure. For the ophthalmology clinic controls, 456 patients and 548 patients were randomly selected for comparison with the patients having HSV ocular disease and the patients having HZO, respectively. When selecting the age- and sex-matched controls, there were 4 patients with HSV ocular disease and 7 patients with HZO for whom only 3 controls could be matched. As a result, 452 patients and 541 patients comprised the HSV ocular disease and HZO age- and sex-matched controls, respectively.

Place holder to copy figure label and caption
Figure.
Ocular Manifestations of Patients With Herpetic Eye Disease

Patients with more than 1 ocular manifestation were counted in each category. HSV indicates herpes simplex virus; HZO, herpes zoster ophthalmicus.

Graphic Jump Location

Demographic data, atopic disease, and smoking status were compared between patients with HSV ocular disease and both control groups (Table 2). Using the ophthalmology clinic controls, patients who had atopic dermatitis had a 3.9-fold (95% CI, 1.8-8.5; P = .001) higher odds of having HSV ocular disease compared with patients who did not have atopic dermatitis (Table 3). Similarly, patients who had asthma had a 1.8-fold (95% CI, 1.1-3.1; P = .03) higher odds of having HSV ocular disease compared with patients who did not have asthma. This association was strengthened for both conditions using the age- and sex-matched controls. Furthermore, patients who had a diagnosis of any atopic disease had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopic disease. An association was also found between allergic rhinitis and HSV ocular disease (odds ratio, 2.2; 95% CI, 1.1-4.6; P = .04) using this control group. If allergic rhinitis was omitted as an atopic diagnosis to allow for comparison with a prior case-control study20 investigating the association between atopy and HSV ocular disease, patients who had atopic disease had a 3.5-fold (95% CI, 2.1-5.8; P < .001) increased odds of having HSV ocular disease compared with patients who did not have atopic disease using the age- and sex-matched controls.

Table Graphic Jump LocationTable 2.  Demographic Data for Patients With HSV Ocular Disease and Controls
Table Graphic Jump LocationTable 3.  Logistic Regression Models Predicting HSV Ocular Diseasea

Similarly, HZO cases were compared with both control groups (Table 4). Using the age- and sex-matched controls, patients who had any type of atopic disease had a 1.8-fold (95% CI, 1.2-2.8; P = .01) higher odds of having HZO compared with patients who had no atopic disease (Table 5). A significant association was also found specifically in patients with asthma for this control group. Patients who had asthma had a 1.9-fold (95% CI, 1.1-3.2; P = .02) higher odds of having HZO compared with patients who did not have asthma. Controlling for race or smoking status did not affect the results for HSV ocular disease or HZO.

Table Graphic Jump LocationTable 4.  Demographic Data for Patients With HZO and Controls
Table Graphic Jump LocationTable 5.  Logistic Regression Models Predicting HZOa

For HSV ocular disease and HZO, having 2 or more atopic conditions had an even stronger association with herpetic eye disease compared with having fewer than 2 atopic conditions. Specifically, patients who had 2 or more atopic conditions had a 2.9-fold (95% CI, 1.4-6.1; P = .01) higher odds of having HSV ocular disease and a 1.7-fold (95% CI, 0.7-4.2; P = .25) higher odds of having HZO compared with patients who had fewer than 2 atopic conditions using the ophthalmology clinic controls and adjusting for age and sex. Using the age- and sex-matched controls, patients who had multiple atopic diseases had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO compared with patients who had one or no atopic disease.

Before this study, evidence suggested that patients with atopy are more likely to develop eczema herpeticum, have bilateral HSV ocular disease, and require antiviral therapy for longer durations.1218 A previous study20 showed an association between atopy and HSV ocular disease. Similarly, this study found that patients with atopic disease were more than twice as likely to have HSV ocular disease. An association between atopic disease and HZO has not been previously described to our knowledge. We found that patients with atopy were almost twice as likely to have HZO. Furthermore, having more than 1 atopic condition increased the odds of having herpetic eye disease for HSV ocular disease and for HZO.

Like an earlier population-based case-control study20 researching this question, we observed an association between HSV ocular disease and atopic disease. In our study, we found a 2.6-fold increased odds of having HSV ocular disease for patients with atopy using the age- and sex-matched controls. This is similar to the 1.9-fold higher odds of having HSV ocular disease for patients with atopy that was found in the earlier study. We also included patients with allergic rhinitis in our analyses, while the prior study did not because it may be a nonspecific diagnosis. In a sensitivity analysis, we excluded allergic rhinitis as an atopic condition, and our association became even stronger.

In our study, atopic dermatitis had the strongest association with HSV ocular disease, followed by asthma. Of the prior smaller investigations on this topic, studies12,13,17,22 have also reported an association with atopic dermatitis, in particular, and with ocular disease. In addition, studies12,23 in the systemic literature have noted that patients with atopic dermatitis may have a predisposition to more severe HSV infection. There may be some explanation for this specific association at the cellular level. For example, it is well known that mutations in several genes associated with skin barrier dysfunction are found in patients with atopic dermatitis.24,25 As a result, colonization of several pathogens, including HSV, is facilitated in these patients.26

While an association between HSV ocular disease and atopy has been described, information on HZO and atopy is lacking. In this study, we found that patients who had atopic disease had an almost 2.0-fold increased odds of having HZO compared with patients who did not have atopic disease using age- and sex-matched controls. A prior study27 has shown a protective effect of primary varicella zoster virus infection on the subsequent development and severity of atopic dermatitis in children. Further study is needed to determine if children with primary varicella zoster virus infection who eventually manifest atopic conditions are more likely to develop herpes zoster compared with those who do not manifest atopic conditions. In addition, patients who had asthma had an almost 2.0-fold increased odds of having HZO compared with patients who did not have asthma in our study. It is possible that the association between asthma and HZO could in part be due to the immunosuppressant medications that are used to treat asthma, such as corticosteroids. However, a prior study28 has shown no association between inhaled corticosteroid use, one of the most common immunosuppressant treatments for asthma, and the development of herpes zoster.

The association between atopy and both HSV ocular disease and HZO can potentially be explained by the immune system dysregulation observed in patients with atopy. Specifically, these patients have been shown to have a predominance of TH2 cells, leading to increased levels of interleukin 4 and IgE.29 These immune system modulators can prevent differentiation of TH1 cells that stimulate production of key cytokines, including interferon-γ, for combating viral infections.30,31 In this study, we found that having more than 1 atopic condition significantly increased the odds of having herpetic eye disease. Prior studies3234 have shown a positive association between severity of atopic conditions and serum IgE levels. Therefore, it is possible that multiple atopic conditions could correlate with increased immune dysregulation, explaining the stronger association with HSV ocular disease and HZO that we found in patients with at least 2 atopic conditions.

More significant associations were found between atopy and both HSV ocular disease and HZO using the age- and sex-matched control group. This may in part be explained by differences between the 2 control groups. Patients in the ophthalmology clinic control group may have been more likely to have diseases diagnosed because of increased interaction with physicians for existing comorbidities, such as diabetes mellitus. In contrast, the age- and sex-matched controls needed only one physician visit during the study period to be included. A similar difference in results using a clinic-based control group and a population-based control group was noted in the prior study20 that investigated the association between atopy and HSV ocular disease.

There are some limitations of the study. Demographic differences may affect the applicability of our results to the Hawaiian population. Based on the most recent census data, the age and sex distribution of Kaiser Permanente Hawaii is comparable to that of the general Hawaiian population; however, Kaiser Permanente Hawaii has a larger percentage of Pacific Islanders.35 Similarly, differences in demographic factors, such as racial distribution, may affect the generalizability of this study to other populations outside of Hawaii. However, an association between HSV ocular disease and atopy has been found in a different population,20 suggesting that the findings in our study may not be unique to the present study population. It is also possible that certain cases or controls may have been diagnosed as having an atopic condition by a physician outside of the Kaiser system, but only approximately 5% of the Kaiser Permanente Hawaii membership has dual insurance that would facilitate receiving health care outside of the Kaiser system.

In addition, there are some diagnostic considerations. While misdiagnosis of herpetic eye disease is possible, all patients were seen by a Kaiser Permanente Hawaii ophthalmologist, and cases of herpetic eye disease were individually verified through medical record review by a uveitis and cornea fellowship–trained ophthalmologist (N.R.A.), decreasing the likelihood of misdiagnosis. A diagnosis of atopic disease was determined based on ICD-9 diagnosis codes alone. Although this could potentially lead to misdiagnosis, the same method was used to determine an atopic diagnosis for both cases and controls. The temporal association of atopic disease and a herpetic eye disease diagnosis should also be considered. It is possible that some patients were diagnosed as having atopic disease after their initial diagnosis of herpetic eye disease. However, this would be unlikely because atopic diseases are generally more chronic and diagnosed at a young age. The mean age of the patients with herpetic eye disease in this study is older than 50 years for HSV ocular disease and for HZO, and more than 80% of these patients were incident cases. Theoretically, it is possible that ophthalmologists were diagnosing patients having HSV ocular disease with atopic conditions because of their knowledge of an association that was published during the study period.20 However, our medical record review demonstrated that this was not the case. In addition, no association was known between HZO and atopy before the present study, so it would be unlikely for a diagnostic bias to exist.

In conclusion, we found an almost 2.0-fold increased odds of having HZO and a more than 2.0-fold increased odds of having HSV ocular disease for patients who had atopic disease compared with patients who had no atopic disease. Specific diagnoses, such as atopic dermatitis, as well as the presence of more than 1 atopic condition increased the odds of having herpetic eye disease. While an association between atopy and HSV ocular disease has been shown in a prior study,20 no association between atopy and HZO has been described. The results of this study are novel and should be validated in other populations. Knowledge of this association could help support the diagnosis of herpetic eye disease in patients with atopy. These findings also raise questions about whether there are common pathophysiological mechanisms behind both of these conditions.

Section Editor: Leslie Hyman, PhD.

Submitted for Publication: May 6, 2013; final revision received July 25, 2013; accepted July 26, 2013.

Corresponding Author: Nisha R. Acharya, MD, MS, F. I. Proctor Foundation, University of California, San Francisco, 513 Parnassus Ave, Room S309, San Francisco, CA 94143-0412 (nisha.acharya@ucsf.edu).

Published Online: December 26, 2013. doi:10.1001/jamaophthalmol.2013.6277.

Author Contributions: Dr Acharya had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Borkar and Gonzales contributed equally to the manuscript.

Study concept and design: Borkar, Gonzales, Acharya.

Acquisition of data: Tham, Esterberg, Vinoya, Parker, Uchida.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: Borkar, Gonzales, Acharya.

Critical revision of the manuscript for important intellectual content: All authors.

Conflict of Interest Disclosures: None reported.

Funding/Support: The University of California, San Francisco, Department of Ophthalmology is supported by grant EY06190 from the National Eye Institute, by That Man May See Foundation, and by an unrestricted grant from Research to Prevent Blindness. Dr Acharya is supported by grant K23EY017897 from the National Eye Institute, by a Research to Prevent Blindness Career Development Award, and by a University of California, San Francisco, Research Evaluation and Allocation Committee Award.

Role of the Sponsor: The sponsors or funding organization had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: The results of this study were presented in part at the 2012 Association for Research in Vision and Ophthalmology Annual Meeting; May 10, 2012; Fort Lauderdale, Florida.

Ragozzino  MW, Melton  LJ  III, Kurland  LT, Chu  CP, Perry  HO.  Population-based study of herpes zoster and its sequelae. Medicine (Baltimore). 1982;61(5):310-316.
PubMed   |  Link to Article
Liesegang  TJ.  Epidemiology of ocular herpes simplex: natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165.
PubMed   |  Link to Article
Borkar  DS, Tham  VM, Esterberg  E,  et al.  Incidence of herpes zoster ophthalmicus: results from the Pacific Ocular Inflammation Study. Ophthalmology. 2013;120(3):451-456.
PubMed
Zhang  Y, Cosyns  M, Levin  MJ, Hayward  AR.  Cytokine production in varicella zoster virus–stimulated limiting dilution lymphocyte cultures. Clin Exp Immunol. 1994;98(1):128-133.
PubMed   |  Link to Article
Wilson  A, Sharp  M, Koropchak  CM, Ting  SF, Arvin  AM.  Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation. J Infect Dis. 1992;165(1):119-126.
PubMed   |  Link to Article
Manickan  E, Rouse  BT.  Roles of different T-cell subsets in control of herpes simplex virus infection determined by using T-cell–deficient mouse-models. J Virol. 1995;69(12):8178-8179.
PubMed
Daheshia  M, Feldman  LT, Rouse  BT.  Herpes simplex virus latency and the immune response. Curr Opin Microbiol. 1998;1(4):430-435.
PubMed   |  Link to Article
Schmid  DS, Rouse  BT.  The role of T cell immunity in control of herpes simplex virus. Curr Top Microbiol Immunol. 1992;179:57-74.
PubMed
Larché  M, Akdis  CA, Valenta  R.  Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6(10):761-771.
PubMed   |  Link to Article
Romagnani  S.  Regulation of the T cell response. Clin Exp Allergy. 2006;36(11):1357-1366.
PubMed   |  Link to Article
Akkoc  T, de Koning  PJ, Ruckert  B, Barlan  I, Akdis  M, Akdis  CA.  Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases. J Allergy Clin Immunol. 2008;121(3):652-658.e1.
PubMed   |  Link to Article
Wollenberg  A, Wetzel  S, Burgdorf  WH, Haas  J.  Viral infections in atopic dermatitis: pathogenic aspects and clinical management. J Allergy Clin Immunol. 2003;112(4):667-674.
PubMed   |  Link to Article
David  TJ, Longson  M.  Herpes simplex infections in atopic eczema. Arch Dis Child. 1985;60(4):338-343.
PubMed   |  Link to Article
Souza  PM, Holland  EJ, Huang  AJ.  Bilateral herpetic keratoconjunctivitis. Ophthalmology. 2003;110(3):493-496.
PubMed   |  Link to Article
Wilhelmus  KR, Falcon  MG, Jones  BR.  Bilateral herpetic keratitis. Br J Ophthalmol. 1981;65(6):385-387.
PubMed   |  Link to Article
Easty  D, Entwistle  C, Funk  A, Witcher  J.  Herpes simplex keratitis and keratoconus in the atopic patient: a clinical and immunological study. Trans Ophthalmol Soc U K. 1975;95(2):267-276.
PubMed
Margolis  TP, Ostler  HB.  Treatment of ocular disease in eczema herpeticum. Am J Ophthalmol. 1990;110(3):274-279.
PubMed
Yao  YF, Inoue  Y, Kase  T, Uchihori  Y, Mori  Y, Ohashi  Y.  Clinical characteristics of acyclovir-resistant herpetic keratitis and experimental studies of isolates. Graefes Arch Clin Exp Ophthalmol. 1996;234(suppl 1):S126-S132.
PubMed   |  Link to Article
Rezende  RA, Hammersmith  K, Bisol  T,  et al.  Comparative study of ocular herpes simplex virus in patients with and without self-reported atopy. Am J Ophthalmol. 2006;141(6):1120-1125.
PubMed   |  Link to Article
Prabriputaloong  T, Margolis  TP, Lietman  TM, Wong  IG, Mather  R, Gritz  DC.  Atopic disease and herpes simplex eye disease: a population-based case-control study. Am J Ophthalmol. 2006;142(5):745-749.
PubMed   |  Link to Article
Brandt  BM, Mandleblatt  J, Asbell  PA.  Risk factors for herpes simplex–induced keratitis: a case-control study. Ann Ophthalmol. 1994;26(1):12-16.
PubMed
Garrity  JA, Liesegang  TJ.  Ocular complications of atopic dermatitis. Can J Ophthalmol. 1984;19(1):21-24.
PubMed
Peng  WM, Jenneck  C, Bussmann  C,  et al.  Risk factors of atopic dermatitis patients for eczema herpeticum. J Invest Dermatol. 2007;127(5):1261-1263.
PubMed   |  Link to Article
Guttman-Yassky  E, Suárez-Fariñas  M, Chiricozzi  A,  et al.  Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Clin Immunol. 2009;124(6):1235-1244.e1258.
PubMed   |  Link to Article
Palmer  CN, Irvine  AD, Terron-Kwiatkowski  A,  et al.  Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441-446.
PubMed   |  Link to Article
Boguniewicz  M, Leung  DY.  Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-246.
PubMed   |  Link to Article
Silverberg  JI, Norowitz  KB, Kleiman  E,  et al.  Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: a case-control study. J Allergy Clin Immunol. 2010;126(2):300-305.
PubMed   |  Link to Article
Ernst  P, Dell’Aniello  S, Mikaeloff  Y, Suissa  S.  Risk of herpes zoster in patients prescribed inhaled corticosteroids: a cohort study. BMC Pulm Med. 2011;11:e59.
PubMed   |  Link to Article
Jutel  M, Akdis  CA.  T-cell subset regulation in atopy. Curr Allergy Asthma Rep. 2011;11(2):139-145.
PubMed   |  Link to Article
Cunningham  AL, Diefenbach  RJ, Miranda-Saksena  M,  et al.  The cycle of human herpes simplex virus infection: virus transport and immune control. J Infect Dis. 2006;194(suppl 1):S11-S18.
PubMed   |  Link to Article
Asanuma  H, Sharp  M, Maecker  HT, Maino  VC, Arvin  AM.  Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression. J Infect Dis. 2000;181(3):859-866.
PubMed   |  Link to Article
Borish  L, Chipps  B, Deniz  Y, Gujrathi  S, Zheng  B, Dolan  CM; TENOR Study Group.  Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol. 2005;95(3):247-253.
PubMed   |  Link to Article
Limb  SL, Brown  KC, Wood  RA,  et al.  Adult asthma severity in individuals with a history of childhood asthma. J Allergy Clin Immunol. 2005;115(1):61-66.
PubMed   |  Link to Article
Laske  N, Bunikowski  R, Niggemann  B.  Extraordinarily high serum IgE levels and consequences for atopic phenotypes. Ann Allergy Asthma Immunol. 2003;91(2):202-204.
PubMed   |  Link to Article
Humes  KR,Jones  NA,Ramirez  RR. Overview of Race and Hispanic Origin: 2010. March 2011. 2010 Census Briefs. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed November 5, 2013.
PubMed

Figures

Place holder to copy figure label and caption
Figure.
Ocular Manifestations of Patients With Herpetic Eye Disease

Patients with more than 1 ocular manifestation were counted in each category. HSV indicates herpes simplex virus; HZO, herpes zoster ophthalmicus.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1.  International Classification of Diseases, Ninth Revision (ICD-9) Diagnosis Codes Used to Identify Herpetic Eye Disease and Atopic Disease
Table Graphic Jump LocationTable 2.  Demographic Data for Patients With HSV Ocular Disease and Controls
Table Graphic Jump LocationTable 3.  Logistic Regression Models Predicting HSV Ocular Diseasea
Table Graphic Jump LocationTable 4.  Demographic Data for Patients With HZO and Controls
Table Graphic Jump LocationTable 5.  Logistic Regression Models Predicting HZOa

References

Ragozzino  MW, Melton  LJ  III, Kurland  LT, Chu  CP, Perry  HO.  Population-based study of herpes zoster and its sequelae. Medicine (Baltimore). 1982;61(5):310-316.
PubMed   |  Link to Article
Liesegang  TJ.  Epidemiology of ocular herpes simplex: natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1160-1165.
PubMed   |  Link to Article
Borkar  DS, Tham  VM, Esterberg  E,  et al.  Incidence of herpes zoster ophthalmicus: results from the Pacific Ocular Inflammation Study. Ophthalmology. 2013;120(3):451-456.
PubMed
Zhang  Y, Cosyns  M, Levin  MJ, Hayward  AR.  Cytokine production in varicella zoster virus–stimulated limiting dilution lymphocyte cultures. Clin Exp Immunol. 1994;98(1):128-133.
PubMed   |  Link to Article
Wilson  A, Sharp  M, Koropchak  CM, Ting  SF, Arvin  AM.  Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation. J Infect Dis. 1992;165(1):119-126.
PubMed   |  Link to Article
Manickan  E, Rouse  BT.  Roles of different T-cell subsets in control of herpes simplex virus infection determined by using T-cell–deficient mouse-models. J Virol. 1995;69(12):8178-8179.
PubMed
Daheshia  M, Feldman  LT, Rouse  BT.  Herpes simplex virus latency and the immune response. Curr Opin Microbiol. 1998;1(4):430-435.
PubMed   |  Link to Article
Schmid  DS, Rouse  BT.  The role of T cell immunity in control of herpes simplex virus. Curr Top Microbiol Immunol. 1992;179:57-74.
PubMed
Larché  M, Akdis  CA, Valenta  R.  Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6(10):761-771.
PubMed   |  Link to Article
Romagnani  S.  Regulation of the T cell response. Clin Exp Allergy. 2006;36(11):1357-1366.
PubMed   |  Link to Article
Akkoc  T, de Koning  PJ, Ruckert  B, Barlan  I, Akdis  M, Akdis  CA.  Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases. J Allergy Clin Immunol. 2008;121(3):652-658.e1.
PubMed   |  Link to Article
Wollenberg  A, Wetzel  S, Burgdorf  WH, Haas  J.  Viral infections in atopic dermatitis: pathogenic aspects and clinical management. J Allergy Clin Immunol. 2003;112(4):667-674.
PubMed   |  Link to Article
David  TJ, Longson  M.  Herpes simplex infections in atopic eczema. Arch Dis Child. 1985;60(4):338-343.
PubMed   |  Link to Article
Souza  PM, Holland  EJ, Huang  AJ.  Bilateral herpetic keratoconjunctivitis. Ophthalmology. 2003;110(3):493-496.
PubMed   |  Link to Article
Wilhelmus  KR, Falcon  MG, Jones  BR.  Bilateral herpetic keratitis. Br J Ophthalmol. 1981;65(6):385-387.
PubMed   |  Link to Article
Easty  D, Entwistle  C, Funk  A, Witcher  J.  Herpes simplex keratitis and keratoconus in the atopic patient: a clinical and immunological study. Trans Ophthalmol Soc U K. 1975;95(2):267-276.
PubMed
Margolis  TP, Ostler  HB.  Treatment of ocular disease in eczema herpeticum. Am J Ophthalmol. 1990;110(3):274-279.
PubMed
Yao  YF, Inoue  Y, Kase  T, Uchihori  Y, Mori  Y, Ohashi  Y.  Clinical characteristics of acyclovir-resistant herpetic keratitis and experimental studies of isolates. Graefes Arch Clin Exp Ophthalmol. 1996;234(suppl 1):S126-S132.
PubMed   |  Link to Article
Rezende  RA, Hammersmith  K, Bisol  T,  et al.  Comparative study of ocular herpes simplex virus in patients with and without self-reported atopy. Am J Ophthalmol. 2006;141(6):1120-1125.
PubMed   |  Link to Article
Prabriputaloong  T, Margolis  TP, Lietman  TM, Wong  IG, Mather  R, Gritz  DC.  Atopic disease and herpes simplex eye disease: a population-based case-control study. Am J Ophthalmol. 2006;142(5):745-749.
PubMed   |  Link to Article
Brandt  BM, Mandleblatt  J, Asbell  PA.  Risk factors for herpes simplex–induced keratitis: a case-control study. Ann Ophthalmol. 1994;26(1):12-16.
PubMed
Garrity  JA, Liesegang  TJ.  Ocular complications of atopic dermatitis. Can J Ophthalmol. 1984;19(1):21-24.
PubMed
Peng  WM, Jenneck  C, Bussmann  C,  et al.  Risk factors of atopic dermatitis patients for eczema herpeticum. J Invest Dermatol. 2007;127(5):1261-1263.
PubMed   |  Link to Article
Guttman-Yassky  E, Suárez-Fariñas  M, Chiricozzi  A,  et al.  Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Clin Immunol. 2009;124(6):1235-1244.e1258.
PubMed   |  Link to Article
Palmer  CN, Irvine  AD, Terron-Kwiatkowski  A,  et al.  Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441-446.
PubMed   |  Link to Article
Boguniewicz  M, Leung  DY.  Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-246.
PubMed   |  Link to Article
Silverberg  JI, Norowitz  KB, Kleiman  E,  et al.  Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: a case-control study. J Allergy Clin Immunol. 2010;126(2):300-305.
PubMed   |  Link to Article
Ernst  P, Dell’Aniello  S, Mikaeloff  Y, Suissa  S.  Risk of herpes zoster in patients prescribed inhaled corticosteroids: a cohort study. BMC Pulm Med. 2011;11:e59.
PubMed   |  Link to Article
Jutel  M, Akdis  CA.  T-cell subset regulation in atopy. Curr Allergy Asthma Rep. 2011;11(2):139-145.
PubMed   |  Link to Article
Cunningham  AL, Diefenbach  RJ, Miranda-Saksena  M,  et al.  The cycle of human herpes simplex virus infection: virus transport and immune control. J Infect Dis. 2006;194(suppl 1):S11-S18.
PubMed   |  Link to Article
Asanuma  H, Sharp  M, Maecker  HT, Maino  VC, Arvin  AM.  Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression. J Infect Dis. 2000;181(3):859-866.
PubMed   |  Link to Article
Borish  L, Chipps  B, Deniz  Y, Gujrathi  S, Zheng  B, Dolan  CM; TENOR Study Group.  Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol. 2005;95(3):247-253.
PubMed   |  Link to Article
Limb  SL, Brown  KC, Wood  RA,  et al.  Adult asthma severity in individuals with a history of childhood asthma. J Allergy Clin Immunol. 2005;115(1):61-66.
PubMed   |  Link to Article
Laske  N, Bunikowski  R, Niggemann  B.  Extraordinarily high serum IgE levels and consequences for atopic phenotypes. Ann Allergy Asthma Immunol. 2003;91(2):202-204.
PubMed   |  Link to Article
Humes  KR,Jones  NA,Ramirez  RR. Overview of Race and Hispanic Origin: 2010. March 2011. 2010 Census Briefs. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf. Accessed November 5, 2013.
PubMed

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