Longitudinal Immunophenotypic Changes in Refractory Lupus Nephritis After B-cell Depletion: A 25-year Case Study

Background/Aim: Long-term management of systemic lupus erythematosus (SLE) requires a persistent balance between intensive immunosuppression and the prevention of opportunistic infections. This is particularly challenging in patients with a multi-decade disease history and evolving renal pathology. Case Report: We report a female patient diagnosed with SLE in 2001 (Age 25). Following biopsy-proven class IV lupus nephritis (LN) in 2003, she achieved a remarkable 20-year clinical remission after receiving a 12-cycle induction regimen of intravenous cyclophosphamide (IV-CYC). In December 2025, the patient presented with a severe refractory flare-up; a repeat renal biopsy revealed progression to mixed Class IV+V LN. Management included steroid pulse therapy and rituximab (RTX) infusion. The post-RTX clinical course was complicated by Salmonella bacteremia and cytomegalovirus (CMV) viremia with associated acute kidney injury. A multidisciplinary approach utilizing targeted antibiotics (Meropenem/Ciprofloxacin) and antivirals (Valganciclovir) successfully resolved the infections while maintaining control of the underlying LN. Conclusion: This case highlights the long-term efficacy of IV-CYC induction and the complexities of managing refractory LN flares. It underscores the critical necessity of vigilant monitoring and prompt intervention for multi-microbial opportunistic infections following intensive B-cell depletion therapy in long-standing SLE patients.