The innovative topical or systemic drugs, targeting single specific itch mediators (anti-cytokine monoclonal antibodies as anti-IL-31, anti-IL-33 and anti-TSLP) or inhibiting multiple pruritogenic cytokines by blocking common signal transduction pathways (anti-JAKS) actually already used or under investigation in atopic dermatitis seem plausible candidates for difficult to treat patients. This evidence concerns the gene IL33 and atopic eczema.