Abstract
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors are effective treatments for autoimmune diseases but may cause paradoxical adverse events (PAEs), including sarcoid-like granulomatosis. Etanercept, a soluble TNF receptor fusion protein, has been more frequently associated with this phenomenon compared to monoclonal antibodies. CASE PRESENTATION: We describe a 61-year-old man with chronic plaque psoriasis on long-term etanercept therapy who developed bilateral visual symptoms. Ophthalmologic evaluation revealed granulomatous panuveitis with retinal vasculitis and macular edema. Imaging and lung biopsy confirmed pulmonary sarcoidosis with non-caseating granulomas. Etanercept was discontinued, and systemic corticosteroids were started. Because of steroid dependence, secukinumab (an IL-17A inhibitor) was introduced, together with an intravitreal dexamethasone implant for refractory macular edema. Over a 4-year follow-up, the patient achieved complete and sustained resolution of ocular inflammation with stable systemic control, without the need for further corticosteroids. DISCUSSION: This case illustrates a rare but clinically significant presentation of etanercept-induced sarcoidosis with primary ocular involvement. Unlike typical psoriatic uveitis, the bilateral granulomatous pattern prompted further systemic work-up, which revealed otherwise silent pulmonary disease. To our knowledge, this is the first long-term report of etanercept-induced ocular sarcoidosis successfully managed with secukinumab, which allowed steroid withdrawal. While IL-17A inhibitors are not yet approved for uveitis, available data and our observation suggest a potential role in selected cases. CONCLUSION: Etanercept-induced ocular sarcoidosis is a rare but clinically significant PAE. Prompt recognition and multidisciplinary management are crucial to prevent vision loss. IL-17A inhibition may represent a promising steroid-sparing therapeutic option when TNF-α inhibitors are contraindicated or cause paradoxical reactions.