"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. S. aureus (enterotoxins), M sympodialis, and allergens are trigger factors of atopic dermatitis - they stimulate dendritic cells (JACI, 2012).

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.



Atopic Dermatitis Treatment - Illustrated (click here for full size image).

References:

Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Elias, Peter M; Schmuth, Matthias. Current Opinion in Allergy and Clinical Immunology, 2009.
Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation http://goo.gl/Evqr
Loss-of-function mutations in filaggrin gene are associated with atopic dermatitis, and now with peanut allergy too. JACI, 2011.
Early food sensitization and FLG mutation in infants with early eczema increase the risk for later asthma (JACI, 2011).
Staphylococcus aureus biofilm and and superantigens are associated with chronic sinusitis, cause T-helper 2 skewing http://bit.ly/ngnxBe
Image source: Skin layers. Wikipedia, public domain.

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