Cutaneous Neuroanatomical and Cellular Response to Dupilumab Treatment in Atopic Dermatitis

Itch is the dominant symptom in atopic dermatitis. Cutaneous neuronal alterations underlying this symptom are still poorly understood. Therefore, we aimed at deciphering cutaneous neuronal alterations during atopic dermatitis treatment with dupilumab. Skin biopsies and blood from 49 adult patients with severe atopic dermatitis receiving 300 mg dupilumab subcutaneously every 2 weeks over a period of 16 weeks were analyzed at initial assessment and at follow-up for intraepidermal nerve fiber density, alloknesis, and biomarkers. Decreased intraepidermal nerve fiber density and increased alloknesis in pruritic lesional and nonpruritic nonlesional skin at initial assessment improved after dupilumab treatment. Formation of tight junctions (claudin-1 staining) was correlated with the epidermal level of intraepidermal nerve fiber growth. Expressions of targeted IL receptors (IL4R, IL13RA1, IL13RA2) and mediators related to innervation density (NGF, SEMA3A) were increased in pruritic lesion skin at initial assessment compared with those in nonpruritic nonlesional skin at initial assessment and former pruritic lesional skin/healed at follow-up. Blood CD8+ central memory T cells and CD4+ CD25+ CD127- cells, including regulatory T cells, increased at follow-up; CD8 T-effector cells and CLA+ activated CD4+ cells decreased. In conclusion, treatment with an IL4Rα antibody is paralleled by an improvement of neuroanatomy and a reduction of neuronal sensitization, paralleled by relevant biomarker improvement.