Atopic dermatitis: Risk factors for disease development

Two risk factors appear to be consistently and strongly associated with the development of atopic dermatitis:  1) a family history of atopy and 2) loss of function mutations in the filaggrin (FLG) gene.  

Approximately 70% of AD patients have a positive family history of atopic diseases.109 The odds of developing AD are 2- to 3-fold higher in children with one atopic parent, and this increases to 3- to 5-fold if both parents are atopic.110,111 A maternal history of AD is possibly more predictive.112 The FLG gene encodes profilaggrin, which is degraded to filaggrin monomers, and these proteins play key roles in the terminal differentiation of the epidermis and formation of the skin barrier including the stratum corneum.  Filaggrin breakdown products are part of natural moisturizing factor, which contributes to epidermal hydration and barrier function.  FLG null mutations confer a risk for earlier-onset AD, and for more severe, persistent disease.113,114 They also lead to an increased tendency for eczema herpeticum. Different defects in FLG have been noted in different ethnic populations with AD, demonstrating its importance to pathogenesis. However, a significant number of patients with AD have no known FLG mutations, and conversely, approximately 40% of individuals with FLG null alleles do not develop AD.113

The type of delivery during childbirth (caesarean or vaginal) does not appear to alter AD risk.115 Elevated birth weights may be a risk factor for disease development, but the effect size is likely small as studies have been conflicting, with some showing a negative association.116-118

While patients with atopic dermatitis are often sensitized to certain foods, the timing of solid food introduction or withholding of allergenic foods does not appear to alter the risk for AD.119 Most studies of dietary modification of the maternal or infant diet do not show a protective effect, although recently published studies of hydrolyzed formula and probiotic supplementation suggest that these approaches could have a beneficial effect in preventing disease development in some high-risk infants who are not exclusively breast fed.120-125 But at present, there is insufficient evidence to recommend any specific dietary or other measures as being effective for the primary prevention of AD.  Breastfeeding for the first 6 months of life is encouraged for its other benefits for the infant and mother (e.g. bonding, passive immunity).

Navigate section 1 of the AD guideline: Diagnosis and assessment

Citation note 

When referencing this guideline in a publication, please use the following citation: Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51. 



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