Dupilumab as Immunomodulatory Rescue for Severe Recalcitrant Pemphigus Vulgaris: A Case Report and Literature Review.

Abstract

Standard treatment of pemphigus vulgaris (PV) includes corticosteroid, immunosuppressants, and biologics such as rituximab, a monoclonal antibody targeting CD20⁺ B cells. However, some patients develop resistance to rituximab, requiring alternative therapeutic approaches. We report a 15-year-old female with severe PV who developed rituximab refractoriness after an initially effective response. Despite treatment with a combination of intravenous immunoglobulin, corticosteroid, and immunosuppressants, the patient failed to achieve disease control. Consequently, dupilumab, an interleukin-4 receptor α antagonist, was initiated on a biweekly regimen. Her lesions showed dramatic improvement, with the pemphigus disease area index (PDAI) reaching 0. Her anti-desmoglein 1 antibody level became negative, and T helper (Th)-2 inflammatory markers, including eosinophil count and immunoglobulin E (IgE) level, was normalized, allowing corticosteroid tapering after the 8th dose (last dose) of dupilumab. She has maintained complete remission for at least 28 weeks with regular follow-ups. We additionally propose possible mechanisms underlying rituximab refractoriness and how dupilumab modulates this treatment response. Our case highlights dupilumab's potential in modulating Th-2-driven autoantibody production for PV patients with high peripheral eosinophils and IgE levels who have severe disease resistant to corticosteroids or rituximab.