Treatment of bullous pemphigoid with dupilumab: Dupilumab exerts its effect by primarily suppressing T-helper 2 cytokines.

We report a patient with bullous pemphigoid (BP) who was successfully treated with dupilumab monotherapy. To clarify the underlying mechanism of this effective treatment, we investigated the dynamics of a variety of cytokine-producing T cells before and after treatment in the circulation and in blister fluid using flow cytometry. The patient was a 72-year-old woman who had a pruritic eruption consisting of erythema and tense blisters on the whole body. The skin biopsy and direct immunofluorescence of the skin were typical for BP. The serum level of anti-BP180NC16a antibodies was 111 U/ml. Flow cytometric analyses revealed that the proportions of circulating interleukin (IL)-4-, IL-13-, and IL-31-producing CD4 and CD8 T cells were substantially higher in our BP patient than in healthy subjects. Moreover, IL-4- and IL-13-producing CD4 and CD8 T cells were much higher in the blister fluids than in the circulation, whereas IL-31-producing CD4 and CD8 T cells were only slightly higher in the blister fluids. The proportions of circulating interferon (IFN)-γ-producing CD4 and CD8 T cells in the circulation were slightly lower in the patient than in healthy subjects. There was no significant difference in the circulating IL-17-producing CD4 and CD8 T cells between the patient and healthy subjects, although IL-17-producing CD4 and CD8 T cells were slightly higher in the blister fluids. Treatment with dupilumab promptly improved the pruritus and skin lesions, and anti-BP180 antibodies became negative. After treatment with dupilumab, the proportions of circulating IL-4- and IL-13-producing CD4 T cells mainly decreased and IL-17- and IL-31-producing CD4 T cells slightly decreased. There were no significant differences in the proportions of circulating IFN-γ-producing CD4 and CD8 T cells between before and after treatment. These results suggest that T-helper (Th)2 cells are involved in the pathogenesis of BP, and dupilumab exerts its effect mainly by suppressing Th2 cytokines.