There are two alternative hypotheses to explain the etiology of AD, the inside-out theory and the outside-in theory.

The traditional inside-out theory postulates that a genetic defect causes an abnormal immune system, which leads to the inflammation and symptoms of AD. Advances in the understanding of the skin barrier have led to the development of the outside-in theory. The outside-in theory proposes that a genetic defect causes a dysfunctional skin barrier leading to the signs and symptoms of AD.