Immediate hypersensitivity reactions to systemic steroids are reported rarely in the literature. The authors present a case of Behçet's disease-associated panuveitis in a patient with skin test confirmed immunoglobulin E-mediated allergy to methylprednisolone and reported allergic reaction to prednisone. The patient tolerated prednisolone eyedrops for his anterior segment disease, as well as oral prednisolone for systemic therapy. This case demonstrates a challenge to conventional treatment, as it involves a hypersensitivity that is rarely reported. It also highlights class differences in corticosteroids with regard to immune reactivity. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:447-449.].