"Outside-to-inside, back to outside" paradigm in atopic dermatitis focuses on skin barrier

Pathogenesis of atopic dermatitis includes:

- Th1/Th2 cell dysregulation
- abnormalities in IgE production and dendritic cell signaling
- mast cell hyperactivity

Current therapy has been largely directed towards ameliorating Th2-mediated inflammation and pruritus.

There is emerging evidence that atopic dermatitis results from inherited and acquired insults to the skin barrier,

There is a strong association between mutations in filaggrin and atopic dermatitis, particularly in Northern Europeans.

Sustained hapten access through a defective skin barrier stimulates a Th1 to Th2 shift in immunophenotype, which in turn further aggravates the barrier.

Secondary Staphylococcus aureus colonization not amplifies inflammation and further stresses the barrier in atopic dermatitis.

There is a new 'outside-to-inside, back to outside' paradigm for the pathogenesis of atopic dermatitis. 'Barrier repair' therapies could be developed in the future.

References:
Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Elias, Peter M; Schmuth, Matthias. Current Opinion in Allergy and Clinical Immunology, 2009.
Image source: Skin layers. Wikipedia, public domain.