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Review
. 2011 Dec;41(3):282-95.
doi: 10.1007/s12016-010-8231-1.

Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis

Peter M Elias  1 , Joan S Wakefield
Affiliations
Review

Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis

Peter M Elias et al. Clin Rev Allergy Immunol. 2011 Dec.

Abstract

Excessive Th2 cell signaling and IgE production play key roles in the pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the inflammation in AD instead is initiated by inherited insults to the barrier, including a strong association between mutations in FILAGGRIN and SPINK5 in Netherton syndrome, the latter of which provides an important clue that AD is provoked by excess serine protease activity. But acquired stressors to the barrier may also be required to initiate inflammation in AD, and in addition, microbial colonization by Staphylococcus aureus both amplifies inflammation, but also further stresses the barrier in AD. Therapeutic implications of these insights are as follows: While current therapy has been largely directed toward ameliorating Th2-mediated inflammation and/or pruritus, these therapies are fraught with short-term and potential long-term risks. In contrast, "barrier repair" therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum lipids, is more logical, of proven efficacy, and it provides a far-improved safety profile.

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Conflict of interest statement

Conflict of Interest Statement Dr. Elias is a co-inventor of the optimal ratio, triple-lipid therapy for atopic dermatitis. He also is a consultant for Promius Pharma, LLC and Pediapharm, Inc., which market EpiCeram® in the USA and Canada, respectively

Figures

Fig. 1
Fig. 1. Lamellar body secretion delivers key components of both permeability and antimicrobial barriers (modified from Elias [11])
Fig. 2
Fig. 2. Relationship of ichthyosis vulgaris and Netherton syndrome to atopic dermatitis
Fig. 3
Fig. 3. Mechanisms whereby filaggrin (FLG) deficiency in IV could predispose to the development of atopic dermatitis
Fig. 4
Fig. 4. Filaggrin proteolytic pathway impacts multiple SC functions: potential implications for pathogenesis of AD (modified from Elias et al. [70])
Fig. 5
Fig. 5. Pathogenesis of Netherton syndrome
Fig. 6
Fig. 6. Secondary infections further aggravate barrier abnormality in AD (modified from Elias et al. [70])
Fig. 7
Fig. 7. Tacrolimus blood levels in adults and children (6–12 year) following application of 0.1% ointment
Fig. 8
Fig. 8. Percent changes in mean SCORAD scores—EpiCeram® vs. Cutivate (Fluticasone) cream 0.05% in moderate-to-severe AD
See this image and copyright information in PMC

References

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