40.1 More than Skin Deep

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease. It often commences in infancy and can remain a life-long struggle for patients. About 20 to 30% of children and 7 to 10% of adults are affected by AD. Almost 50% of children with AD continue to have symptoms into adulthood. Adult onset AD is considered a distinct subtype of AD; these patients are at increased risk for systemic complications including inflammatory bowel disease and rheumatoid arthritis.

The etiology of AD is thought to be multifactorial; a combination of impaired barrier dysfunction, immune dysregulation, and environmental risk factors. The barrier defect can result in skin sensitization to allergens. It is debated as to whether this is an “outside-in” model or an “inside-out” model.

The outside-in hypothesis proposes that AD is the result of genetic mutations affecting the epidermal barrier. Mutations of the filaggrin (FLG) gene cause defective expression of filaggrin, a barrier protection protein, which is important for the structure of the epidermis. Filaggrin plays a key role in epidermal hydration and pH regulation. FLG mutations have been linked to more severe and persistent AD. The outside-in hypothesis maintains that epidermal barrier disruption and allergen/microbe penetration cause immune dysfunction.

Whereas the inside-out hypothesis proposes that AD is caused by an inflammatory process inhibiting epidermal differentiation. The skin barrier becomes compromised after elevated T_h2 and T_h22 cytokine expression (interleukin [IL]-4, IL-13, IL-31) lead to localized inflammation and activation of other immune cells. The inside-out hypothesis is supported by evidence of elevated T-cell numbers present in nonlesional skin of AD patients.

Just like asthma, AD is a heterogeneous disorder. There is more than one inflammatory pathway that is involved in its pathogenesis. It is important to remember that the epithelial, immune, and microbial abnormalities in AD extend well beyond the inflamed skin. Atopic dermatitis does have systemic aspects. It is definitely more than skin deep.

Further suggestion that AD is more than skin deep includes the fact that patients with AD have significantly higher immunoglobulin E (IgE) responses than any other allergic disease, including asthma, food allergy, allergic rhinitis, and allergic conjunctivitis. Penetration of allergens through a defective skin barrier containing high levels of thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 creates an ideal environment for increased IgE production.

Atopic dermatitis is often seen in conjunction with various atopic and allergic comorbidities, including food allergy, allergic rhinoconjunctivitis, and asthma. Atopic dermatitis can have significant effects on quality of life. These patients are often absent more frequently from work and school than their peers; disrupting not only their lives but their families’ lives as well. The patients with AD complain of a debilitating chronic itch and skin pain that can dramatically affect sleep and lead to an increase in depression and anxiety.