Dichotomous pathogenesis drives therapeutic choice: A case report and review of literature differentiating glucocorticoid-induced from disease activity-associated central serous chorioretinopathy in lupus nephritis

Objective Central serous chorioretinopathy (CSC) complicating lupus nephritis (LN) may arise from two distinct pathways: uncontrolled systemic inflammation (activity-associated CSC) or as an iatrogenic complication of therapy (glucocorticoid-induced CSC). This study aims to propose a clinically actionable framework for differentiating these entities and guide trigger-specific treatment selection. Methods We present a novel case of glucocorticoid (GC)-induced CSC successfully treated with a GC-free belimumab-tacrolimus regimen. A case report integrated with a review of the literature (PubMed, Embase, Web of Science, until May 2024) was conducted to identify all reported cases of concurrent LN and CSC. Cases were stratified by presumed CSC trigger, and treatment outcomes were analyzed. Results Four cases, including our index case, were analyzed. Two cases of activity-associated CSC (no recent GC exposure) achieved dual remission with aggressive GC-based immunosuppression. Two cases of GC-induced CSC (onset post-GC initiation) only achieved CSC remission after implementing GC-sparing strategies (GC taper to ≤5 mg/d or cessation). A treatment-trigger mismatch (using high-dose GC for GC-induced CSC) was associated with worsened ophthalmological outcomes. Conclusion These findings support a dichotomous pathogenesis model for CSC in LN. Correctly classifying CSC as activity-associated or glucocorticoid-induced is the critical first step in management. This distinction informs opposing therapeutic strategies: standard GC-based immunosuppression is appropriate for the former, while prompt initiation of GC-sparing therapy is imperative for the latter. This proposed framework offers a path to resolve the longstanding therapeutic paradox in this complex clinical scenario.