Disease trajectories in childhood atopic dermatitis: an update and practitioner's guide

A D Irvine, P Mina-Osorio, A D Irvine, P Mina-Osorio

Abstract

Background: Atopic dermatitis (AD) is a heterogeneous disease with a multifactorial aetiology and complex pathophysiology. This heterogeneity translates into different trajectories of disease progression with respect to severity, persistence and risk of development of atopic comorbidities. Determining which possible disease trajectories or comorbidities any individual child might develop is challenging in clinical practice. Tools that help identify paediatric patients at higher risk of disease progression would greatly aid clinicians.

Methods: We reviewed recent cohort studies to synthesize and simplify the epidemiological data to try to identify shared clinically relevant characteristics that may help physicians estimate the risk of disease progression in paediatric patients with AD.

Results: Despite the variability in data collection and methods of analysis and their limitations, there are common patterns of early-childhood AD that may aid in the estimation of risk for disease progression. Factors associated with risk of AD progression include younger age of onset, family history of atopy, greater AD severity, filaggrin mutations, urban environment and polysensitization and/or allergic multimorbidity. Based on these factors, we provide a practitioner's guide for identifying, counselling and/or referring infants and children with AD at potentially higher risk of developing persistent AD and atopic comorbidities. We also present clinical scenarios to illustrate how these data relate to real-life situations.

Conclusions: Useful insights are provided for physicians and patients to inform them better about the risk of AD progression and to help guide care pathways for the paediatric population with AD. What's already known about this topic? The complex pathophysiology of atopic dermatitis (AD) translates into a heterogeneous clinical presentation and trajectories of disease progression. Although the consensus is that most paediatric patients with AD will eventually 'outgrow' the disease or follow the longitudinal trajectory known as the 'atopic march', a significant proportion will develop persistent AD and/or other atopic conditions. No known factors conclusively predict the risk of progression or development of comorbidities. What does this study add? Recent analyses of data from large cohorts of paediatric patients with AD have suggested the existence of potentially discrete clusters of patients who present with relatively common AD phenotypes. These studies have shed some light onto the factors associated with risk of progression, which we review in this article. A practitioner's guide with clinical scenarios is provided to help identify patients at high risk of progression to determine whether a patient should be monitored and/or would require specialist referral.

© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Figures

Figure 1
Figure 1
Atopic dermatitis (AD) has a multifactorial pathophysiology involving genetic and environmental factors leading to immune dysregulation and skin barrier dysfunction. This complexity translates into heterogeneous clinical presentations (phenotypes). The term ‘endotype’ encompasses all these clinical, pathological and aetiological aspects of a disease and has been applied to asthma and other complex diseases to refer to the molecular mechanisms underlying observable disease characteristics (phenotypes).
Figure 2
Figure 2
The atopic march has been defined as the sequential progression from atopic dermatitis to asthma and allergic rhinitis. The common perception is that patients either follow this trajectory or outgrow the disease. This graph shows the percentage of patients with each of the indicated allergic conditions (y‐axis) at different age groups (x‐axis) in the subset of patients who follow what is traditionally known as the atopic march trajectory. This corresponds to the cross‐sectional analysis of the data described by Belgrave et al.41
Figure 3
Figure 3
Despite the different methodologies used in recent data‐driven analyses of cohort data, the characteristics of the patient clusters representing distinct trajectories of disease progression are remarkably similar among studies. We have consolidated the information from the table into four more or less overlapping subsets represented in different shades of red in the concentric circles. AD, atopic dermatitis; ALSPAC, Avon Longitudinal Study of Parents and Children; MAAS, Manchester Asthma and Allergy Study; MAS, Multicenter Allergy Study; MeDALL, Mechanisms of the Development of Allergy; PARIS, Pollution and Asthma Risk: an Infant Study; PASTURE, Protection Against Allergy: Study in Rural Environments; PIAMA, Prevention and Incidence of Asthma and Mite Allergy.
Figure 4
Figure 4
Paediatric patients with atopic dermatitis (AD) can follow multiple trajectories of disease progression. The atopic march represents one of multiple such possible trajectories. Analysing data cross‐sectionally at a population level at any of the indicated time points could result in either under‐ or overestimation of the co‐occurrence of any number of atopic comorbidities studied. The figure is based on the findings described by Belgrave et al.41
Figure 5
Figure 5
A practitioner's guide for identifying paediatric patients with atopic dermatitis who are at risk of disease progression and developing atopic comorbidities. This figure presents the relevant questions to ask in the clinic, which may aid in family counselling and the decision‐making process for the management and/or early referral of paediatric patients with atopic dermatitis. Based on data from the cohorts listed on the left, circled responses to these questions represent the highest risk. Referral to a specialist is recommended for patients with any of these characteristics. ALSPAC, Avon Longitudinal Study of Parents and Children; BAMSE, Children Allergy Milieu Stockholm Epidemiology; MAS, Multicenter Allergy Study; MeDALL, Mechanisms of the Development of Allergy; PASTURE, Protection Against Allergy: Study in Rural Environments; PEER, Pediatric Eczema Elective Registry; PIAMA, Prevention and Incidence of Asthma and Mite Allergy; TOACS, The Odense Adolescents Cohort Study; WISC, Wisconsin Birth Cohort Study.

References

    1. Garg N, Silverberg JI. Epidemiology of childhood atopic dermatitis. Clin Dermatol 2015; 33:281–8.
    1. Spergel JM. Epidemiology of atopic dermatitis and atopic march in children. Immunol Allergy Clin North Am 2010; 30:269–80.
    1. Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387:1109–22.
    1. Bin L, Leung DY. Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol 2016; 12:52.
    1. Guttman‐Yassky E, Waldman A, Ahluwalia J et al Atopic dermatitis: pathogenesis. Semin Cutan Med Surg 2017; 36:100–3.
    1. Weidinger S, Beck LA, Bieber T et al Atopic dermatitis. Nat Rev Dis Primers 2018; 4:1.
    1. Garmhaussen D, Hagemann T, Bieber T et al Characterization of different courses of atopic dermatitis in adolescent and adult patients. Allergy 2013; 68:498–506.
    1. Bieber T, D'Erme AM, Akdis CA et al Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 2017; 139(4 Suppl.):S58–64.
    1. Nissen SP, Kjær HF, Høst A et al The natural course of sensitization and allergic diseases from childhood to adulthood. Pediatr Allergy Immunol 2013; 24:549–55.
    1. Bousquet J, Anto J, Auffray C et al MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy 2011; 66:596–604.
    1. Wan J, Mitra N, Hoffstad OJ et al Variations in risk of asthma and seasonal allergies between early‐ and late‐onset pediatric atopic dermatitis: a cohort study. J Am Acad Dermatol 2017; 77:634–40.
    1. Margolis DJ, Gupta J, Apter AJ et al Filaggrin‐2 variation is associated with more persistent atopic dermatitis in African American subjects. J Allergy Clin Immunol 2014; 133:784–9.
    1. Bergmann RL, Bergmann KE, Lau‐Schadensdorf S et al Atopic diseases in infancy. The German multicenter atopy study (MAS‐90). Pediatr Allergy Immunol 1994; 5 (6 Suppl.):19–25.
    1. Bisgaard H. The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study. Ann Allergy Asthma Immunol 2004; 93:381–9.
    1. Böhme M, Svensson A, Kull I et al Clinical features of atopic dermatitis at two years of age: a prospective, population‐based case–control study. Acta Derm Venereol 2001; 81:193–7.
    1. Boyd A, Golding J, Macleod J et al Cohort profile: the ‘children of the 90s’ – the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 2013; 42:111–27.
    1. Halkjaer LB, Loland L, Buchvald FF et al Development of atopic dermatitis during the first 3 years of life: the Copenhagen prospective study on asthma in childhood cohort study in high‐risk children. Arch Dermatol 2006; 142:561–6.
    1. Pinart M, Benet M, Annesi‐Maesano I et al Comorbidity of eczema, rhinitis, and asthma in IgE‐sensitised and non‐IgE‐sensitised children in MeDALL: a population‐based cohort study. Lancet Respir Med 2014; 2:131–40.
    1. Roduit C, Frei R, Depner M et al Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood. JAMA Pediatr 2017; 171:655–62.
    1. Simpson BM, Hallam CL, Marolia H et al Manchester Asthma and Allergy Study (MAAS): recruitment of infant cohort. J Allergy Clin Immunol 2000; 105 (1 Part 2):S4.
    1. Simpson BM, Custovic A, Simpson A et al NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults. Clin Exp Allergy 2001; 31:391–9.
    1. von Mutius E, Schmid S. The PASTURE project: EU support for the improvement of knowledge about risk factors and preventive factors for atopy in Europe. Allergy 2006; 61:407–13.
    1. Wahidi M, Vrtis RF, Fujimura KE et al Evaluation of indoor microbiota in Wisconsin farm vs. non‐farm homes using electrostatic dust collectors. J Allergy Clin Immunol 2017; 139 (2 Suppl.):AB116 (Abstr. 364).
    1. Wijga AH, Kerkhof M, Gehring U et al Cohort profile: the prevention and incidence of asthma and mite allergy (PIAMA) birth cohort. Int J Epidemiol 2014; 43:527–35.
    1. Tran MM, Lefebvre DL, Dharma C et al Predicting the atopic march: results from the Canadian Healthy Infant Longitudinal Development Study. J Allergy Clin Immunol 2018; 141:601–7.
    1. Mortz CG, Andersen KE, Dellgren C et al Atopic dermatitis from adolescence to adulthood in the TOACS cohort: prevalence, persistence and comorbidities. Allergy 2015; 70:836–45.
    1. Strachan DP, Aït‐Khaled N, Foliaki S et al Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood. Clin Exp Allergy 2015; 45:126–36.
    1. Sargen MR, Hoffstad O, Margolis DJ. Warm, humid, and high sun exposure climates are associated with poorly controlled eczema: PEER (Pediatric Eczema Elective Registry) cohort, 2004–2012. J Invest Dermatol 2014; 134:51–7.
    1. Margolis JS, Abuabara K, Bilker W et al Persistence of mild to moderate atopic dermatitis. JAMA Dermatol 2014; 150:593–600.
    1. Clarisse B, Nikasinovic L, Poinsard R et al The Paris prospective birth cohort study: which design and who participates? Eur J Epidemiol 2007; 22:203–10.
    1. Ziyab AH, Raza A, Karmaus W et al Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study. Clin Exp Allergy 2010; 40:1776–84.
    1. Martinez FD, Wright AL, Taussig LM et al Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995; 332:133–8.
    1. Christiansen ES, Kjaer HF, Eller E et al The prevalence of atopic diseases and the patterns of sensitization in adolescence. Pediatr Allergy Immunol 2016; 27:847–53.
    1. Grabenhenrich LB, Keil T, Reich A et al Prediction and prevention of allergic rhinitis: a birth cohort study of 20 years. J Allergy Clin Immunol 2015; 136:932–40.
    1. Gabet S, Just J, Couderc R et al Early polysensitization is associated with allergic multimorbidity in PARIS birth cohort infants. Pediatr Allergy Immunol 2016; 27:831–7.
    1. University of Bristol . Avon Longitudinal Study of Parents and Children. Cohort profile. Available at (last accessed 10 April 2019).
    1. Custovic A, Simpson A, Woodcock A. Manchester cohort. Pediatr Pulmonol Suppl 2004; 26:12–13.
    1. Garcia‐Aymerich J, Benet M, Saeys Y et al Phenotyping asthma, rhinitis and eczema in MeDALL population‐based birth cohorts: an allergic comorbidity cluster. Allergy 2015; 70:973–84.
    1. Schoos AM, Chawes BL, Melén E et al Sensitization trajectories in childhood revealed by using a cluster analysis. J Allergy Clin Immunol 2017; 140:1693–9.
    1. Lau S, Matricardi PM, Wahn U et al Allergy and atopy from infancy to adulthood: messages from the German birth cohort MAS. Ann Allergy Asthma Immunol 2019; 122:25–32.
    1. Belgrave DCM, Granell R, Simpson A et al Developmental profiles of eczema, wheeze, and rhinitis: two population‐based birth cohort studies. PLOS Med 2014; 11:e1001748.
    1. Vrbova M, Dorociakova P, Vyskovsky R et al Dynamics of allergy development during the first 5 years of life. Eur J Pediatr 2018; 177:1317–25.
    1. Ballardini N, Kull I, Söderhäll C et al Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort. Br J Dermatol 2013; 168:588–94.
    1. Hose AJ, Depner M, Illi S et al Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts. J Allergy Clin Immunol 2017; 139:1935–45.
    1. Paternoster L, Savenije OEM, Heron J et al Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts. J Allergy Clin Immunol 2018; 141:964–71.
    1. Coca AF, Cooke RA. On the classification of the phenomenon of hypersensitiveness. J Immunol 1923; 8:163–82.
    1. Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003; 112:S118–27.
    1. Hahn EL, Bacharier LB. The atopic march: the pattern of allergic disease development in childhood. Immunol Allergy Clin North Am 2005; 25:231–46.
    1. Burgess JA, Lowe AJ, Matheson MC et al Does eczema lead to asthma? J Asthma 2009; 46:429–36.
    1. Hill DA, Spergel JM. The atopic march: critical evidence and clinical relevance. Ann Allergy Asthma Immunol 2018; 120:131–7.
    1. Busse WW. The atopic march: fact or folklore? Ann Allergy Asthma Immunol 2018; 120:115–19.
    1. Ferreira MA, Vonk JM, Baurecht H et al Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 2017; 49:1752–7.
    1. Khan SJ, Dharmage SC, Matheson MC, Gurrin LC. The atopic march related to confounding by genetics and early‐life environment? A systematic review of sibship and twin data. Allergy 2018; 73:17–28.
    1. Bousquet J, Anto JM, Wickman M et al Are allergic multimorbidities and IgE polysensitization associated with the persistence or re‐occurrence of foetal type 2 signalling? The MeDALL hypothesis. Allergy 2015; 70:1062–78.
    1. Mortz CG, Andersen KE, Bindslev‐Jensen C. Recall bias in childhood atopic diseases among adults in the Odense Adolescence Cohort Study. Acta Derm Venereol 2015; 95:968–72.
    1. Gustafsson D, Sjöberg O, Foucard T. Development of allergies and asthma in infants and young children with atopic dermatitis – a prospective follow‐up to 7 years of age. Allergy 2000; 55:240–5.
    1. Ricci G, Patrizi A, Baldi E et al Long‐term follow‐up of atopic dermatitis: retrospective analysis of related risk factors and association with concomitant allergic diseases. J Am Acad Dermatol 2006; 55:765–71.
    1. Pinart M, Albang R, Maier D et al Systematic review on the definition of allergic diseases in children: the MeDALL study. Int Arch Allergy Immunol 2015; 168:110–21.
    1. Dharmage SC, Lowe AJ, Matheson MC et al Atopic dermatitis and the atopic march revisited. Allergy 2014; 69:17–27.
    1. Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): a systematic review and meta‐analysis. J Am Acad Dermatol 2016; 75:681–7.
    1. Abuabara K, Langan SM, Yu AM. Conclusions about atopic dermatitis persistence might be premature. J Am Acad Dermatol 2017; 76:e177–8.
    1. Silverberg JI, Simpson EL. Reply to: ‘Conclusions about atopic dermatitis persistence might be premature’. J Am Acad Dermatol 2017; 76:e179.
    1. Williams HC, Wüthrich W. The natural history of atopic dermatitis In: Atopic Dermatitis: the Epidemiology, Causes and Prevention of Atopic Eczema. (Williams HC, ed), Cambridge: Cambridge University Press, 2000; 41–59.
    1. Smith JA, Drake R, Simpson A et al Dimensions of respiratory symptoms in preschool children: population‐based birth cohort study. Am J Respir Crit Care Med 2008; 177:1358–63.
    1. Simpson A, Tan VY, Winn J et al Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study. Am J Respir Crit Care Med 2010; 181:1200–6.
    1. Lazic N, Roberts G, Custovic A et al Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts. Allergy 2013; 68:764–70.
    1. Burgess JA, Walters EH, Byrnes GB et al Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol 2007; 120:863–9.
    1. Leynaert B, Neukirch C, Kony S et al Association between asthma and rhinitis according to atopic sensitization in a population‐based study. J Allergy Clin Immunol 2004; 113:86–93.
    1. Shaaban R, Zureik M, Soussan D et al Rhinitis and onset of asthma: a longitudinal population‐based study. Lancet 2008; 372:1049–57.
    1. Anto JM, Bousquet J, Akdis M et al Mechanisms of the Development of Allergy (MeDALL): introducing novel concepts in allergy phenotypes. J Allergy Clin Immunol 2017; 139:388–99.
    1. van der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: a systematic review. J Allergy Clin Immunol 2007; 120:565–9.
    1. Domínguez‐Hüttinger E, Christodoulides P, Miyauchi K et al Mathematical modeling of atopic dermatitis reveals ‘double‐switch’ mechanisms underlying 4 common disease phenotypes. J Allergy Clin Immunol 2017; 139:1861–72.
    1. Herr M, Just J, Nikasinovic L et al Risk factors and characteristics of respiratory and allergic phenotypes in early childhood. J Allergy Immunol 2012; 130:389–96.
    1. Abuabara K, Yu AM, Okhovat JP et al The prevalence of atopic dermatitis beyond childhood: a systematic review and meta‐analysis of longitudinal studies. Allergy 2018; 73:696–704.
    1. Rystedt I. Prognostic factors in atopic dermatitis. Acta Derm Venereol 1985; 65:206–13.
    1. Lammintausta K, Kalimo K, Raitala R, Forsten Y. Prognosis of atopic dermatitis. A prospective study in early adulthood. Int J Dermatol 1991; 30:563–8.
    1. Sandström MH, Faergemann J. Prognosis and prognostic factors in adult patients with atopic dermatitis: a long‐term follow‐up questionnaire study. Br J Dermatol 2004; 150:103–10.
    1. Illi S, von Mutius E, Lau S et al The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol 2004; 113:925–31.
    1. Kulig M, Bergmann R, Edenharter G, Wahn U. Does allergy in parents depend on allergy in their children? Recall bias in parental questioning of atopic diseases. Multicenter Allergy Study Group. J Allergy Clin Immunol 2000; 105:274–8.
    1. Abuabara K, Hoffstad O, Troxel AB et al Patterns and predictors of atopic dermatitis disease control past childhood: an observational cohort study. J Allergy Clin Immunol 2018; 141:778–80.
    1. Bousquet J, Anto JM, Akdis M et al Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; project no: 261357; 2010–2015. Allergy 2016; 71:1513–25.
    1. Brown SJ, Kroboth K, Sandilands A et al Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose‐dependent effect. J Invest Dermatol 2012; 132:98–104.
    1. Rystedt I. Long term follow‐up in atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1985; 114:117–20.
    1. Somanunt S, Chinratanapisit S, Pacharn P et al The natural history of atopic dermatitis and its association with atopic march. Asian Pac J Allergy Immunol 2017; 35:137–43.
    1. Wüthrich B. Clinical aspects, epidemiology, and prognosis of atopic dermatitis. Ann Allergy Asthma Immunol 1999; 83:464–70.
    1. Williams HC, Burney PG, Hay RJ et al The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol 1994; 131:383–96.
    1. Vaughn AR, Sivamani RK, Lio PA, Shi VY. Paternal vs. maternal factors in childhood atopic dermatitis. Dermatitis 2017; 28:241–5.
    1. Depner M, Fuchs O, Genuneit J et al Clinical and epidemiologic phenotypes of childhood asthma. Am J Respir Crit Care Med 2014; 189:129–38.
    1. Grabenhenrich LB, Gough H, Reich A et al Early‐life determinants of asthma from birth to age 20 years: a German birth cohort study. J Allergy Clin Immunol 2014; 133:979–88.
    1. Alford SH, Zoratti E, Peterson EL et al Parental history of atopic disease: disease pattern and risk of pediatric atopy in offspring. J Allergy Clin Immunol 2004; 114:1046–50.
    1. Wahn U, von Mutius E. Childhood risk factors for atopy and the importance of early intervention. J Allergy Clin Immunol 2001; 107:567–74.
    1. Paternoster L, Standl M, Waage J et al Multi‐ancestry genome‐wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 2015; 47:1449–56.
    1. Henderson J, Northstone K, Lee SP et al The burden of disease associated with filaggrin mutations: a population‐based, longitudinal birth cohort study. J Allergy Clin Immunol 2008; 121:872–7.
    1. Irvine A. Fleshing out filaggrin phenotypes. J Invest Dermatol 2007; 127:504–7.
    1. Weidinger S, O'Sullivan M, Illig T et al Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol 2008; 121:1203–9.
    1. Rodríguez E, Baurecht H, Herberich E et al Meta‐analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol 2009; 123:1361–70.
    1. Li X, Ampleford EJ, Howard TD et al The C11orf30‐LRRC32 region is associated with total serum IgE levels in asthmatic patients. J Allergy Clin Immunol 2011; 129:575–8.
    1. Ramasamy A, Curjuric I, Coin LJ et al A genome‐wide meta‐analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J Allergy Clin Immunol 2011; 128:996–1005.
    1. Manz J, Rodríguez E, ElSharawy A et al Targeted resequencing and functional testing identifies low‐frequency missense variants in the gene encoding GARP as significant contributors to atopic dermatitis risk. J Invest Dermatol 2016; 136:2380–6.
    1. Nousbeck J, Irvine AD. Atopic dermatitis according to GARP: new mechanistic insights in disease pathogenesis. J Invest Dermatol 2016; 136:2340–1.
    1. Wickman M, Asarnoj A, Tillander H et al Childhood‐to‐adolescence evolution of IgE antibodies to pollens and plant foods in the BAMSE cohort. J Allergy Clin Immunol 2014; 133:580–2.
    1. Bieber T. How to define atopic dermatitis? Dermatol Clin 2017; 35:275–81.
    1. Ziyab AH, Karmaus W, Zhang H et al Association of filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier? Int Arch Allergy Immunol 2014; 164:308–18.
    1. Simpson EL, Chalmers JR, Hanifin JM et al Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol 2014; 134:818–23.
    1. Horimukai K, Morita K, Narita M et al Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol 2014; 134:824–30.
    1. Boguniewicz M, Nicol N, Kelsay K, Leung DY. A multidisciplinary approach to evaluation and treatment of atopic dermatitis. Semin Cutan Med Surg 2008; 27:115–27.
    1. Bieber T, Cork M, Reitamo S. Atopic dermatitis: a candidate for disease‐modifying strategy. Allergy 2012; 67:969–75.
    1. Esparza‐Gordillo J, Schaarschmidt H, Liang L et al A functional IL‐6 receptor (IL6R) variant is a risk factor for persistent atopic dermatitis. J Allergy Clin Immunol 2013; 132:371–7.
    1. du Toit G, Sayre PH, Roberts G et al Allergen specificity of early peanut consumption and effect on development of allergic disease in the Learning Early About Peanut Allergy study cohort. J Allergy Clin Immunol 2018; 141:1343–53.
    1. Eichenfield LF, Tom WL, Berger TG et al Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014; 71:116–32.
    1. Eichenfield LF, Boguniewicz M, Simpson EL et al Translating atopic dermatitis management guidelines into practice for primary care providers. Pediatrics 2015; 136:554–65.

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