An Unusual Case of Overlapping Immunoglobulin G4-Related Disease and Systemic Lupus Erythematosus

Immunoglobulin G4-related disease (IgG4-RD) and systemic lupus erythematosus (SLE) are multisystemic autoimmune disorders that can present with renal manifestations. Overlapping cases of these diseases are extremely rare and present both diagnostic and therapeutic challenges. We report the case of a 70-year-old male with a history of autoimmune pancreatitis, who was admitted with fatigue, weight loss, and worsening kidney function. Laboratory tests revealed anemia with a positive Coombs test, leucopenia, elevated IgG4, hypocomplementemia, and positive results for ANA, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-RP11 antibodies, and rheumatoid factor. A spot urine sample showed subnephrotic proteinuria without hematuria. The patient met the criteria for both SLE and possible IgG4-RD, but the cause of the worsening renal function remained unclear, prompting a kidney biopsy. The biopsy revealed a lymphoplasmacytic infiltrate, storiform fibrosis, and IgG4-positive staining, consistent with IgG4-related tubulointerstitial nephritis, but without evidence of lupus nephritis. The patient was treated with prednisolone, resulting in improvement of both his symptoms and kidney function. However, significant leukopenia, anemia, and elevated anti-dsDNA titers persisted, which were presumed to be secondary to the overlapping SLE. Hydroxychloroquine and azathioprine were added to the treatment regimen, leading to improvement in cytopenias at the three-month follow-up. This case underscores the importance of kidney biopsy in suspected overlapping autoimmune diseases for identifying kidney involvement and guiding treatment, although evidence regarding optimal therapy remains limited.