Glucocorticoid resistance in immune thrombocytopenia: A therapeutic challenge or a window for precision medicine?

Immune thrombocytopenia (ITP) is a common acquired autoimmune hemorrhagic disorder characterized by both accelerated platelet destruction and defective thrombopoiesis. Glucocorticoids (GCs) remain the cornerstone of first-line therapy; however, approximately 10-20 % of patients exhibit GC resistance, which has traditionally been regarded as a hallmark of treatment failure and poor prognosis. Emerging evidence, however, suggests that GC resistance may not necessarily indicate therapeutic futility. Rather, it may reflect distinct immunopathological endotypes with limited responsiveness to GC signaling but potential sensitivity to targeted or steroid-sparing regimens. From this perspective, GC resistance represents not only a therapeutic challenge but also an opportunity for precision medicine. It promotes timely transition to targeted therapies, such as thrombopoietin receptor agonists, Syk/BTK inhibitors, or B-cell-modulating therapies, thereby reducing cumulative GC-related toxicity. This review critically summarizes current mechanistic insights into GC resistance in ITP, examines its potential clinical implications, and proposes a conceptual framework to redefine GC resistance as a biological marker guiding individualized management rather than a simple indicator of treatment failure.