Objective:

To report a case of IgG4-related disease (IgG4-RD) following dual immune checkpoint inhibitor therapy and discuss its management.

Approach:

• Case Presentation: A 65-year-old man with metastatic clear cell renal carcinoma was treated with nivolumab and ipilimumab. Follow-up imaging revealed mass-like lesions in the remaining kidney, initially suspected as metastatic progression.
• Histopathological Examination: CT-guided biopsy showed subacute pyelonephritis, acute tubular injury, and dense IgG4-positive plasma cell infiltration, confirming IgG4-RD.
• Treatment Strategy: Rituximab was chosen as a steroid-sparing first-line therapy to avoid compromising antitumor immunity. Two infusions led to stabilization/regression of renal lesions.

Key Findings:

• IgG4-RD can mimic malignant progression in patients receiving immune checkpoint inhibitors.
• Histologic confirmation is essential for accurate diagnosis.
• Rituximab may be an effective treatment for IgG4-RD while preserving antitumor immunity.

Interpretation:

This case illustrates IgG4-RD as an immune-related adverse event from dual ICI therapy, highlighting the need for careful histological evaluation.

Limitations:

• The rarity of IgG4-RD following ICI therapy limits generalizability.
• Further studies are needed to establish treatment protocols for similar cases.

Conclusion:

This case highlights the recognition of IgG4-RD as a complication of ICI therapy and the role of rituximab in its management.