Exostosin 1/exostosin 2-associated membranous nephropathy in undifferentiated connective tissue disease: a case report and literature review.

BACKGROUND: Renal involvement in undifferentiated connective tissue disease (UCTD) is rare and not well characterized, with membranous nephropathy (MN) representing an uncommon but clinically significant manifestation. While exostosin 1/exostosin 2 (EXT 1/EXT 2)-associated MN has been increasingly recognized in systemic autoimmune diseases such as lupus and Sjögren’s syndrome, its association with UCTD has not been previously reported. CASE PRESENTATION: We present the case of a 32-year-old male with UCTD who developed nephrotic syndrome and was found to have exostosin 1/exostosin 2 (EXT 1/EXT 2)-associated membranous nephropathy (MN) on renal biopsy. The patient exhibited serological markers including ANA, anti-SSA/Ro, and anti-ribosomal P protein antibodies, alongside characteristic pathological features of secondary MN with IgG1-dominant deposits and negative PLA2R/THSD7A staining. He was successfully treated with prednisone, tacrolimus, and hydroxychloroquine, achieving significant reduction in proteinuria within two months. CONCLUSIONS: This case underscores the diagnostic utility of EXT 1/EXT 2 immunohistochemistry in identifying autoimmune-mediated MN in UCTD and supports the use of combined immunosuppressive therapy. To our knowledge, this is the first reported case of EXT 1/EXT 2-associated MN in a patient with UCTD, thereby expanding the spectrum of renal pathology in this condition and underscoring the importance of precise histological classification to guide targeted treatment.