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.