Case Report: Upadacitinib and apremilast combination therapy for guselkumab-induced paradoxical eczema in psoriasis

Psoriasis is an immune-mediated inflammatory skin disease. Although biologics have markedly improved psoriasis symptoms, they may occasionally trigger paradoxical inflammatory reactions, particularly with IL-17A or TNF-α inhibitors. However, paradoxical inflammatory reactions associated with the IL-23 inhibitor guselkumab is exceptionally rare. We describe the case of a 70-year-old male with a 5-year history of psoriasis who had previously received tofacitinib for one year without achieving complete clearance. Following the initiation of guselkumab, the patient developed paradoxical eczema. Subsequent treatment with cyclosporine and the TYK2 inhibitor deucravacitinib proved ineffective. Ultimately, combination therapy with the JAK1 inhibitor upadacitinib and the PDE4 inhibitor apremilast achieved satisfactory control of both the paradoxical eczema and the underlying psoriatic lesions. This case highlights that upadacitinib used in combination with apremilast can effectively reverse paradoxical inflammatory reactions while sustaining psoriasis control. This dual-targeting strategy offers a novel therapeutic option for biologic-induced paradoxical reactions, and its broad-spectrum anti-inflammatory properties and potential synergistic effects warrant further clinical investigation.