The Journal of Allergy and Clinical Immunology
Volume 128, Issue 6 , Pages 1235-1241.e5, December 2011

Predictive value of food sensitization and filaggrin mutations in children with eczema

  • Birgit Filipiak-Pittroff, MSc

      Affiliations

    • Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    • Marien-Hospital, Wesel, Germany
    • These authors contributed equally to this work.
  • ,
  • Christina Schnopp, MD

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    • These authors contributed equally to this work.
  • ,
  • Dietrich Berdel, MD

      Affiliations

    • Marien-Hospital, Wesel, Germany
  • ,
  • Aline Naumann, MSc

      Affiliations

    • Department of Medical Biometry, Eberhard-Karls-University, Tübingen, Germany
  • ,
  • Simon Sedlmeier

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
  • ,
  • Anna Onken, MD

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
  • ,
  • Elke Rodriguez, MSc

      Affiliations

    • Department of Dermatology, Venereology and Allergy, Christian-Albrechts-Universität Kiel, Kiel, Germany
  • ,
  • Regina Fölster-Holst, MD

      Affiliations

    • Department of Dermatology, Venereology and Allergy, Christian-Albrechts-Universität Kiel, Kiel, Germany
  • ,
  • Hansjörg Baurecht, MSc

      Affiliations

    • Department of Dermatology, Venereology and Allergy, Christian-Albrechts-Universität Kiel, Kiel, Germany
    • Graduate School of Information Science in Health (GSISH), Technische Universität München, Munich, Germany
  • ,
  • Markus Ollert, MD

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
  • ,
  • Johannes Ring, MD, PhD

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
  • ,
  • Claudia Cramer, MSc

      Affiliations

    • IUF–Leibniz-Research Institute for Environmental Medicine at the Heinrich-Heine-University, Düsseldorf, Germany
  • ,
  • Andrea von Berg, MD

      Affiliations

    • Marien-Hospital, Wesel, Germany
  • ,
  • Carl Peter Bauer, MD

      Affiliations

    • Department of Pediatrics, Technische Universität München, Munich, Germany
  • ,
  • Olf Herbarth, PhD

      Affiliations

    • Faculty of Medicine, Environmental Medicine and Environmental Hygiene, University of Leipzig, Leipzig, Germany
  • ,
  • Irina Lehmann, PhD

      Affiliations

    • Department of Human Exposure Research and Epidemiology, UFZ-Centre for Environmental Research Leipzig, Leipzig, Germany
  • ,
  • Beate Schaaf, MD

      Affiliations

    • Praxis für Kinder- und Jugendmedizin, Bad Honnef, Germany
  • ,
  • Sibylle Koletzko, MD

      Affiliations

    • Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
  • ,
  • Heinz-Erich Wichmann, MD, PhD

      Affiliations

    • Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • ,
  • Joachim Heinrich, PhD

      Affiliations

    • Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    • Corresponding Author InformationCorresponding author: Joachim Heinrich, PhD, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • ,
  • Stephan Weidinger, MD

      Affiliations

    • Department of Dermatology, Venereology and Allergy, Christian-Albrechts-Universität Kiel, Kiel, Germany
    • These authors contributed equally to this work.
  • ,
  • GINIplus and LISAplus study groups

      Affiliations

    • The members of the GINIplus and LISAplus study groups are shown in Appendix 1.

Received 15 July 2011; received in revised form 13 September 2011; accepted 13 September 2011. published online 28 October 2011.

Background

It was reported that in infants with eczema and food sensitization, the presence of a filaggrin (FLG) null mutation predicts future asthma with a specificity and positive predictive value of 100%.

Objectives

We sought to evaluate the predictive value of food sensitization and food allergy, FLG haploinsufficiency, and their combination in infants with early-onset eczema for persistent eczema and childhood asthma.

Methods

The German Infant Nutritional Intervention (GINI) and Influence of Lifestyle-related Factors on the Immune System and the Development of Allergies in Childhood (LISA) birth cohorts, as well as a collection of 65 cases of early-onset eczema with and without food allergy were investigated.

Results

The risk for asthma was significantly increased by food sensitization (positive diagnostic likelihood ratios [PLRs] of 1.9 [95% CI, 1.1-3.4] in the GINI cohort and 5.5 [95% CI, 2.8-10.8] in the LISA cohort) and the presence of an FLG mutation (PLRs of 2.9 [95% CI, 1.2-6.6] in the GINI cohort and 2.8 [95% CI, 1.0-7.9] in the LISA cohort) with a rather high specificity (79.1% and 92.9% in the GINI cohort and 89.0% and 91.7% in the LISA cohort, respectively) but low sensitivity (40.0% and 39.3% in the GINI cohort and 31.6% and 23.5% in the LISA cohort, respectively). Likewise, the risk for persistent eczema was increased. In the clinical cases neither food allergy nor FLG mutations had a significant effect. The combination of both parameters did not improve prediction and reached positive predictive values of 52.3% (GINI cohort), 66.9% (LISA cohort), and 30.6% (clinical cases), assuming an asthma prevalence in children with early eczema of 30%.

Conclusion

Early food sensitization and the presence of an FLG mutation in infants with early eczema increase the risk for later asthma, but the combination of the 2 factors does not represent a clinically useful approach to reliably identify children at risk.

Key words: Eczema, atopic dermatitis, asthma, food sensitization, food allergy, filaggrin, prediction

Abbreviations used: DBPCFC, Double-blind, placebo-controlled food challenge, FLG, Filaggrin, GINI, German Infant Nutritional Intervention, LISA, Influence of Lifestyle-related Factors on the Immune System and the Development of Allergies in Childhood, MAS, Multicenter Allergy Study, NPV, Negative predictive value, PLR, Positive diagnostic likelihood ratio, PPV, Positive predictive value, RR, Relative risk, sIgE, Specific IgE

 

 Supported by a grant of the German Ministry of Education and Research (BMBF) as part of the National Genome Research Network (NGFN 01GS 0818) and the Christiane Kühne Center for Allergy Research and Education (http://www.ck-care.ch/). The German Infant Nutritional Intervention study was supported for the first 3 years by grants of the Federal Ministry for Education, Science, Research and Technology (grant no. 01 EE 9401-4). The 6-year follow-up was partly funded by the Federal Ministry for Environment (IUF, FKZ 20462296) and by the GSF National Research Centre for the Environment and Health. The LISA birth cohort was funded by grants of the Federal Ministry for Education, Science, Research and Technology (grant no. 01 EG 9705/2 and 01EG9732) and the Federal Ministry for Environment (IUF, FKZ 20462296). S.W. is supported by a Heisenberg professorship of the DFG (WE 2678/4-1).

 Disclosure of potential conflict of interest: M. Ollert has received honoraria from Phadia. J. Ring has received research support from ALK-Abelló, Allergopharma, Almirall-Hermal, Astellas, Bavarian Nordic, Bencard, Biogen-Idec, Galderma, GlaxoSmithKline-Stiefel, Leo, MSD, Novartis, Phadia, PLS Design, Procter & Gamble, Sanofi Aventis, and Stallergenes. C. P. Bauer has received honoraria from MSD and Nestlé. The rest of authors declare that they have no relevant conflicts of interest.

PII: S0091-6749(11)01485-0

doi:10.1016/j.jaci.2011.09.014

The Journal of Allergy and Clinical Immunology
Volume 128, Issue 6 , Pages 1235-1241.e5, December 2011