Introduction
Atopic dermatitis (AD) is a chronic relapsing disease, which most often debuts in early childhood and remits later in childhood. It is characterized by defects in the barrier function due to an abnormal stratum corneum in both affected and nonaffected skin1,2. Several lines of evidence indicate that an epidermal barrier impairment in the skin of children with AD is involved in the development of allergic sensitization3,4. Recently, it has been proposed that early exposure to foods via the skin in children with AD may allow penetration of food allergens through the skin leading to development of sensitization and subsequent food allergy5,6. This is in contrast to an early, continuous oral exposure to some allergenic foods such as peanuts and egg, which may lead to development of immune tolerance and reduced risk of food allergy in young children6–8.
The development of specific IgE (sIgE) to environmental allergens has also been associated with a defective skin barrier function4; e.g. one study showed association between increasing total epidermal water loss and prevalence of sensitization to aeroallergens4. Another study used a chemical sensitizer to show that sensitization through the skin in AD induced a persistent skewing towards antigen-specific Th2 responses regardless of Filaggrin (FLG ) mutation status3. FLG is a key protein that assists in the final differentiation of the epidermis and formation of the skin barrier2. FLGmutation status leads to functional loss of barrier function in the skin and other mucosal surfaces2,9. A previous literature review described that up to 2/3 of patients with AD will develop allergic rhinitis10, and particularly earlier debut of AD seemed to impose a higher risk. To our knowledge, no previous studies have investigated the association between AD severity and later development of aeroallergen sensitization and allergic rhinitis, and none included FLG mutation status.
We hypothesized that the epidermal barrier defect in early-onset, more severe AD in infancy compared to late-onset AD may facilitate penetration of aeroallergens via the skin and increase the risk of developing aeroallergen sensitization and allergic rhinitis in childhood. To test this hypothesis, we used data from the Copenhagen Prospective Studies on Asthma in Childhood2000(COPSAC2000) at-risk mother-child cohort to determine whether early-onset vs. late-onset AD and severity of AD are associated with development of aeroallergen sensitization and allergic rhinitis at 6-7 and 12 years of age.