From atopic dermatitis to asthma: the atopic march.
OBJECTIVE
To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march.


METHODS
PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march.


METHODS
Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined.


RESULTS
The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases.


CONCLUSIONS
The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made.
Spergel
Jonathan M
JM
Division of Allergy and Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4399, USA. spergel@email.chop.edu
D017668:Age of Onset; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D015897:Comorbidity; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D018450:Disease Progression; D004781:Environmental Exposure / Q000009:adverse effects; D004817:Epidermis / Q000276:immunology / Q000378:metabolism*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012221:Rhinitis, Allergic, Perennial / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D014481:United States
D000485:Allergens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins