Skip to main content

Advertisement

SpringerLink
Log in

Genetic predisposition and environmental factors associated with the development of atopic dermatitis in infancy: a prospective birth cohort study

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The influence of environmental factors on atopic dermatitis (AD) has been investigated in many cross-sectional studies. It remains however unclear if they could influence AD development early in life. This prospective birth cohort study aimed to monitor aspects of family lifestyle and child’s nutrition within a Caucasian population and to assess its association with AD development over the first 2 years of life. Genetic predisposition was evaluated based on family history and profilaggrin genotyping. Of 149 included children, 36 developed AD. Infants with a family history of atopy developed AD 2.6 times more frequently (30 of 97) than infants without atopic predisposition (6 of 52). Genotyping was carried out on 50% of the children included. Profilaggrin mutations (R501X, 2282del4, R2447X, and S3247X) were infrequent in our population. Lower incidence of AD was observed in infants exposed to a damp housing environment, lower household income, and smoking mothers with a higher but not with a lower education level.

Conclusion: Family history of atopy was a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. Humidity at home and passive smoking seem associated with AD development in infancy.

What is Known:

• Atopic dermatitis (AD) is associated with mutations in various genes of the immune system and the epidermal barrier complex in particular filaggrin (FLG) mutation.

• Inherited factors alone cannot explain the rising AD; environmental factors are therefore likely to play a decisive role in this rise but the exact role that these factors may play in increasing AD risk in infancy remains unclear. Moreover, the relationship between environmental factors and AD has been the focus of mostly cross-sectional studies and not prospective studies.

What is New:

• This prospective birth cohort study demonstrates that family history of atopy is a significant risk factor for AD regardless of the most common, currently defined, FLG mutations.

• A lower incidence of AD was observed in infants exposed to a moist housing environment, lower household income, and smoking of mothers with a higher but not with a lower education level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AB:

Antibiotic

AD:

Atopic dermatitis

CI:

Confidence interval

FLG :

Filaggrin

HR:

Hazard ratio

References

  1. Wadonda-Kabondo N, Sterne JAC, Golding J, Kennedy CTC, Archer CB, Dunnill MGS, ALSPAC Study Team (2004) Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study. Arch Dis Child 89(10):917–921

    PubMed  PubMed Central  CAS  Google Scholar 

  2. Parazzini F, Cipriani S, Zinetti C, Chatenoud L, Frigerio L, Amuso G, Ciammella M, Di Landro A, Naldi L (2014) Perinatal factors and the risk of atopic dermatitis: a cohort study. Pediatr Allergy Immunol 25(1):43–50

    PubMed  Google Scholar 

  3. Draaisma E, Garcia-Marcos L, Mallol J, Solé D, Pérez-Fernández V, Brand PLP, EISL Study Group (2015) A multinational study to compare prevalence of atopic dermatitis in the first year of life. Pediatr Allergy Immunol 26(4):359–366

    PubMed  Google Scholar 

  4. Liang Y, Chang C, Lu Q (2016) The genetics and epigenetics of atopic dermatitis-filaggrin and other polymorphisms. Clin Rev Allergy Immunol 51(3):315–328

    PubMed  CAS  Google Scholar 

  5. Schultz LF (1993) Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample. J Am Acad Dermatol 28(5 Pt 1):719–723

    Google Scholar 

  6. McPherson T (2016) Current understanding in pathogenesis of atopic dermatitis. Indian J Dermatol 61(6):649–655

    PubMed  PubMed Central  Google Scholar 

  7. Diepgen TL (2001) Atopic dermatitis: the role of environmental and social factors, the European experience. J Am Acad Dermatol 45(1):S44–S48

    PubMed  CAS  Google Scholar 

  8. Harris JM, Cullinan P, Williams HC, Mills P, Moffat S, White C, Newman Taylor AJ (2001) Environmental associations with eczema in early life. Br J Dermatol 144(4):795–802

    PubMed  CAS  Google Scholar 

  9. Taylor-Robinson DC, Williams H, Pearce A, Law C, Hope S (2016) Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. millennium cohort study. Br J Dermatol 174(3):569–578

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Williams HC, Strachan DP, Hay RJ (1994) Childhood eczema: disease of the advantaged? BMJ. 308(6937):1132–1135

    PubMed  PubMed Central  CAS  Google Scholar 

  11. Flohr C, Pascoe D, Williams HC (2005) Atopic dermatitis and the “hygiene hypothesis”: too clean to be true? Br J Dermatol 152(2):202–216

    PubMed  CAS  Google Scholar 

  12. Flohr C, Mann J (2014) New insights into the epidemiology of childhood atopic dermatitis. Allergy. 69(1):3–16

    PubMed  CAS  Google Scholar 

  13. Kantor R, Silverberg JI (2016) Environmental risk factors and their role in the management of atopic dermatitis. Expert Rev Clin Immunol 28:1–12

    Google Scholar 

  14. Tamburini S, Shen N, Wu HC, Clemente JC (2016) The microbiome in early life: implications for health outcomes. Nat Med 22(7):713–722

    PubMed  CAS  Google Scholar 

  15. Carson CG (2009) Risk factors for developing atopic dermatitis. J Allergy Clin Immunol 123(6):1355–1360

    Google Scholar 

  16. Ludvigsson JF, Mostrom M, Ludvigsson J, Duchen K (2005) Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants. Pediatr Allergy Immunol 16(3):201–208

    PubMed  Google Scholar 

  17. Yang YW, Tsai CL, Lu CY (2009) Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies. Br J Dermatol 161(2):373–383

    PubMed  CAS  Google Scholar 

  18. Giwercman C, Halkjaer LB, Jensen SM, Bønnelykke K, Lauritzen L, Bisgaard H (2010) Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants. J Allergy Clin Immunol 125(4):866–871

    PubMed  Google Scholar 

  19. Silverberg NB, Lee-Wong M, Yosipovitch G (2016) Diet and atopic dermatitis. Cutis. 97(3):227–232

    PubMed  Google Scholar 

  20. Roduit C, Frei R, Loss G, Büchele G, Weber J, Depner M, Loeliger S, Dalphin M-L, Roponen M, Hyvärinen A, Riedler J, Dalphin J-C, Pekkanen J, von Mutius E, Braun-Fahrländer C, Lauener R (2012) Development of atopic dermatitis according to age of onset and association with early-life exposures. J Allergy Clin Immunol 130(1):130–136.e5

    PubMed  Google Scholar 

  21. Meylan P, Lang C, Mermoud S, Johannsen A, Norrenberg S, Hohl D, Vial Y, Prod’hom G, Greub G, Kypriotou M, Christen-Zaech S (2017) Skin colonization by Staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy. J Invest Dermatol 137(12):2497–2504

    PubMed  CAS  Google Scholar 

  22. Hanifin JM, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol Stockh 92:44–47

    Google Scholar 

  23. R Development Core Team (2008) R: A language and environment for statistical computing [Internet]. R Foundation for Statistical Computing, Vienna. Available from: http://www.R-project.org

  24. Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model. Springer, New York

    Google Scholar 

  25. Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1(1):43–46

    PubMed  CAS  Google Scholar 

  26. Sandilands A, Terron-Kwiatkowski A, Hull PR, O’Regan GM, Clayton TH, Watson RM, Carrick T, Evans AT, Liao H, Zhao Y, Campbell LE, Schmuth M, Gruber R, Janecke AR, Elias PM, van Steensel MAM, Nagtzaam I, van Geel M, Steijlen PM, Munro CS, Bradley DG, Palmer CNA, Smith FJD, McLean WHI, Irvine AD (2007) Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 39(5):650–654

    PubMed  CAS  Google Scholar 

  27. Esparza-Gordillo J, Matanovic A, Marenholz I, Bauerfeind A, Rohde K, Nemat K, Lee-Kirsch M-A, Nordenskjöld M, Winge MCG, Keil T, Krüger R, Lau S, Beyer K, Kalb B, Niggemann B, Hübner N, Cordell HJ, Bradley M, Lee Y-A (2015) Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance. PLoS Genet 11(3):e1005076

    PubMed  PubMed Central  Google Scholar 

  28. Bin L, Leung DYM (2016) Genetic and epigenetic studies of atopic dermatitis. Allergy, Asthma Clin Immunol 12:52

    Google Scholar 

  29. Palmer CNA, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJD, O’Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WHI (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4):441–446

    PubMed  CAS  Google Scholar 

  30. Chiesa Fuxench ZC (2017) Atopic dermatitis: disease background and risk factors. Adv Exp Med Biol 1027:11–19

    PubMed  Google Scholar 

  31. Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ, Tazi-Ahnini R (2006) New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. J Allergy Clin Immunol 118(1):3–21 -23

    PubMed  CAS  Google Scholar 

  32. Linneberg A, Simonsen J, Petersen J, Stensballe L, Benn C (2006) Differential effects of risk factors on infant wheeze and atopic dermatitis emphasize a different etiology. J Allergy Clin Immunol 117(1):184–189

    PubMed  Google Scholar 

  33. Yang H-J (2016) Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases. Korean J Pediatr 59(8):319–327

    PubMed  PubMed Central  Google Scholar 

  34. Saulyte J, Regueira C, Montes-Martínez A, Khudyakov P, Takkouche B (2014) Active or passive exposure to tobacco smoking and allergic rhinitis, allergic dermatitis, and food allergy in adults and children: a systematic review and meta-analysis. PLoS Med 11(3):e1001611

    PubMed  PubMed Central  Google Scholar 

  35. Linneberg A, Nielsen NH, Madsen F, Frølund L, Dirksen A, Jørgensen T (2001) Smoking and the development of allergic sensitization to aeroallergens in adults: a prospective population-based study. The Copenhagen Allergy Study. Allergy 56(4):328–332

    PubMed  CAS  Google Scholar 

  36. Hjern A, Hedberg A, Haglund B, Rosén M (2001) Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents. Clin Exp Allergy 31(6):908–914

    PubMed  CAS  Google Scholar 

  37. Holt PG (1987) Immune and inflammatory function in cigarette smokers. Thorax. 42(4):241–249

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Logan J, Chen L, Gangell C, Sly PD, Fantino E, Liu K (2014) Brief exposure to cigarette smoke impairs airway epithelial cell innate anti-viral defence. Toxicol in Vitro 28(8):1430–1435

    PubMed  CAS  Google Scholar 

  39. Ni I, Ji C, Vij N (2015) Second-hand cigarette smoke impairs bacterial phagocytosis in macrophages by modulating CFTR dependent lipid-rafts. PLoS One 10(3):e0121200

    PubMed  PubMed Central  Google Scholar 

  40. Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez-Martinez S, Breidenassel C, Gonzalez-Gross M, Tsatsakis AM, Saris WH, Moreno LA, Kafatos AG, HELENA Heraklion Study Group (2010) Passive smoking alters circulating naïve/memory lymphocyte T-cell subpopulations in children. Pediatr Allergy Immunol 21(8):1171–1178

    PubMed  Google Scholar 

  41. Baron JA (1996) Beneficial effects of nicotine and cigarette smoking: the real, the possible and the spurious. Br Med Bull 52(1):58–73

    PubMed  CAS  Google Scholar 

  42. Sato J, Denda M, Chang S, Elias PM, Feingold KR (2002) Abrupt decreases in environmental humidity induce abnormalities in permeability barrier homeostasis. J Invest Dermatol 119(4):900–904

    PubMed  CAS  Google Scholar 

  43. Sunwoo Y, Chou C, Takeshita J, Murakami M, Tochihara Y (2006) Physiological and subjective responses to low relative humidity in young and elderly men. J Physiol Anthropol 25(3):229–238

    PubMed  Google Scholar 

  44. Engebretsen KA, Johansen JD, Kezic S, Linneberg A, Thyssen JP (2016) The effect of environmental humidity and temperature on skin barrier function and dermatitis. J Eur Acad Dermatol Venereol 30(2):223–249

    PubMed  CAS  Google Scholar 

  45. Bisgaard H, Halkjaer LB, Hinge R, Giwercman C, Palmer C, Silveira L, Strand M (2009) Risk analysis of early childhood eczema. J Allergy Clin Immunol 123(6):1355–1360.e5

    PubMed  Google Scholar 

  46. Suárez-Varela MM, García-Marcos Alvarez L, Kogan MD, González AL, Gimeno AM, Aguinaga Ontoso I, Díaz CG, Pena AA, Aurrecoechea BD, Monge RMB, Quiros AB, Garrido JB, Canflanca IM, Varela AL-S (2008) Climate and prevalence of atopic eczema in 6- to 7-year-old school children in Spain. ISAAC phase III. Int J Biometeorol 52(8):833–840

    PubMed  Google Scholar 

  47. Tsakok T, Marrs T, Mohsin M, Baron S, du Toit G, Till S, Flohr C (2016) Does atopic dermatitis cause food allergy? A systematic review. J Allergy Clin Immunol 137(4):1071–1078

    PubMed  Google Scholar 

  48. Flohr C, Perkin M, Logan K, Marrs T, Radulovic S, Campbell LE, Maccallum SF, McLean WHI, Lack G (2014) Atopic dermatitis and disease severity are the main risk factors for food sensitization in exclusively breastfed infants. J Invest Dermatol 134(2):345–350

    PubMed  CAS  Google Scholar 

  49. Werfel T, Breuer K (2004) Role of food allergy in atopic dermatitis. Curr Opin Allergy Clin Immunol 4(5):379–385

    PubMed  Google Scholar 

  50. Newland K, Warren L, Gold M (2013) Food allergy testing in infantile eczema: a clinical approach and algorithm. Australas J Dermatol 54(2):79–84

    PubMed  Google Scholar 

Download references

Funding

Swiss National Science Foundation (grant 3203B_133088 to SCZ and 31003A_176097 to CR).

Author information

Author notes

  1. Caroline Gallay and Patrick Meylan contributed equally to this work.

Authors and Affiliations

  1. Pediatric Dermatology Unit, Departments of Dermatology & Venereology, and Pediatrics, University Hospital Lausanne, University of Lausanne, Chemin de Montétan 16, 1004, Lausanne, Switzerland

    Caroline Gallay, Patrick Meylan, Sophie Mermoud, Alexandre Johannsen, Caroline Lang & Stephanie Christen-Zaech

  2. Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne, Switzerland

    Carlo Rivolta

  3. Department of Genetics and Genome Biology, University of Leicester, Leicester, UK

    Carlo Rivolta

Authors
  1. Caroline Gallay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Meylan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie Mermoud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandre Johannsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Caroline Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlo Rivolta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephanie Christen-Zaech
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SCZ conceived and designed the study and participated in the collection data. SM and CL collected the data. CG, PM, and SCZ analyzed the data. CG, PM, and SCZ wrote the first manuscript draft. All authors provided intellectual input, had access to the complete dataset, contributed to manuscript revisions, and approved of the final version. SCZ is the guarantor.

Corresponding author

Correspondence to Stephanie Christen-Zaech.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This prospective birth cohort study was approved by the Research Ethics Committee of the University of Lausanne and was conducted according to the Declaration of Helsinki principles.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study

Additional information

Communicated by Nicole Ritz

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 602 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gallay, C., Meylan, P., Mermoud, S. et al. Genetic predisposition and environmental factors associated with the development of atopic dermatitis in infancy: a prospective birth cohort study. Eur J Pediatr 179, 1367–1377 (2020). https://doi.org/10.1007/s00431-020-03616-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-020-03616-5

Keywords

Search

Navigation