Cascade of opportunistic infections in focal segmental glomerulosclerosis under dual immunosuppressive therapy: a case report.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a heterogeneous glomerular disease frequently treated with high-dose glucocorticoids and calcineurin inhibitors, which can markedly increase susceptibility to opportunistic infections. CASE PRESENTATION: A 53-year-old previously healthy male presented with nephrotic syndrome and was diagnosed with FSGS on renal biopsy, for which he received high-dose prednisolone followed by cyclosporine. During dual immunosuppressive therapy, he developed sequential opportunistic infections, beginning with Listeria monocytogenes bacteremia and pneumonia, followed by probable Cytomegalovirus pneumonitis with high serum and bronchoalveolar viral loads, herpesvirus reactivation compatible with VZV, Pneumocystis jirovecii pneumonia, oral and intra-abdominal candidiasis, and onychomycosis. His course was further complicated by severe anemia and radiologic evidence of pneumoperitoneum; laparotomy revealed diverticulitis with microperforation but no overt bowel perforation. Management required intensive care unit admission, mechanical ventilation, broad-spectrum antibacterial and antifungal therapy, ganciclovir/valganciclovir, high-dose trimethoprim-sulfamethoxazole, and subsequent de-escalation of immunosuppression from prednisolone plus cyclosporine to lower-dose prednisolone plus mycophenolate mofetil. Targeted gene panel sequencing excluded common monogenic FSGS mutations, and anti-interferon-γ autoantibodies were absent. Absolute lymphocyte count, CD4 count, and immunoglobulin levels were not profoundly suppressed, supporting iatrogenic immunosuppression as the main driver of infection susceptibility. After optimization of immunosuppressive and anti-infective therapy, he stabilized without further opportunistic infections over nine months of follow-up, despite persistent nephrotic-range proteinuria and hypoalbuminemia. CONCLUSIONS: This case illustrates how prolonged combined corticosteroid and calcineurin inhibitor therapy in FSGS can precipitate a cascade of severe opportunistic infections, emphasizing the need for early pathogen-specific prophylaxis, vaccination, systematic infection surveillance, and dynamic reassessment of cumulative immunosuppression.