IgG4-related Disease: Current Principles and Approaches in Diagnosis and Treatment

IgG4-related disease (IgG4-RD) has evolved from a series of organ-specific clusters into a recognized systemic fibroinflammatory disorder defined by a unique B-T cell axis. This review provides a comprehensive analysis of current diagnostic and therapeutic paradigms, emphasizing the pathogenic roles of CD4+ cytotoxic T lymphocytes and follicular helper T cells in driving storiform fibrosis. Despite the utility of the 2019 ACR/EULAR classification criteria, diagnostic challenges persist; notably, serum IgG4 remains a fallible biomarker, with a significant amount of patients maintaining normal concentrations during active disease. While glucocorticoids are the traditional first-line treatment, their long-term toxicity and high relapse rates have catalyzed a shift toward targeted B-cell depletion. Emerging evidence suggests that early intervention with biological agents can arrest and even reverse established fibrotic lesions, highlighting the dynamic nature of the immune-fibroblast interface. However, the current reliance on retrospective data and the lack of sensitive biomarkers for diagnosis and monitoring disease activity remain significant hurdles. This review underscores the necessity for precision-driven management and large-scale randomized trials to optimize long-term outcomes and minimize organ damage in this complex multi-organ condition.