Conflicts — skin-barrier-dysfunction

Conflict: [Elias & Wakefield, Clin Rev Allergy Immunol, 2011] says up to 60% of Europeans with AD carry FLG mutations. [Furue, Int J Mol Sci, 2020] says rates range from 10% to 50% depending on ethnicity. Unresolved — add to open_questions.

Conflict: [Elias & Wakefield, 2011] says the barrier defect is the primary “driver” of AD (outside-in) and filaggrin deficiency initiates disease via raised pH/proteases. [Agrawal & Woodfolk, Curr Allergy Asthma Rep, 2014] cites data that filaggrin knock-down alone does not raise SC permeability and that FLG status did not change sensitisation through healthy skin. Unresolved — add to open_questions.

Conflict: [Elias & Wakefield, 2011] argue Th2 inflammation is mostly secondary to barrier failure, so barrier repair should come before immunosuppression. [Furue, 2020] presents IL-4/IL-13 as potent primary suppressors of barrier proteins, and the success of IL-4Rα blockade as evidence of their central role. Unresolved — add to open_questions.