Beyond the Usual: A Rare Triad of Sjögren Syndrome, ANCA-Associated Glomerulonephritis, and Cutaneous Lupus

Introduction: Overlap syndromes involve the co- occurrence of multiple autoimmune diseases, creating diagnostic and therapeutic challenges. This report describes a case of Sjögren’s syndrome with chronic liver disease , subacute cutaneous lupus erythematosus (SCLE) with negative dsDNA, ANA, and ANCA-associated RPGN Case Description: A 33-year-old female with a history of annular pancreas, presented with worsening renal function. She experienced one year of joint pain with morning stiffness, a forehead and post-auricular rash, 20 lbs weight loss, night sweats. Family history was significant for autoimmune diseases (SLE in two sisters, psoriasis in her father). She had previously tested positive for SSA, SSB, and anti-Smith antibodies, with negative dsDNA, ANA, CCP. Complement levels (C3, C4) were low, and ANCA serology revealed MPO positivity with a titer >8 and negative PR3. Initial labs showed creatinine 3.55 mg/dL, rising to 9.2 mg/dL. Urinalysis showed hematuria (RBC >50), dysmorphic RBCs, proteinuria (UPCR 1.5 g/g), and UACR 0.5 g/g. Renal biopsy revealed pauci-immune crescentic glomerulonephritis, and skin biopsy confirmed SCLE. Despite treatment with steroids and rituximab, her renal function deteriorated, started on hemodialysis. Cyclophosphamide was contraindicated due to hepatic impairment. Discussion: Cases of coexisting Sjogren and ANCA-associated vasculitis have been documented, although they remain rare.The Co-occurrence between Sjogren's syndrome and ANCA associated glomerulonephritis is a very rare finding adding diagnosis of cutaneous lupus erythematosus in which brings a higher-level of complexity to clinical presentation and management. In this case, the additional overlap with Sjögren’s syndrome contributed to a delayed recognition and treatment of vasculitis features, correlating with worse renal outcomes when diagnostic uncertainty postponed definitive therapy. The patient's renal pathology and clinical course strongly suggested ANCA-associated vasculitis as the primary driver of disease severity. Cyclophosphamide (CYC) combined with glucocorticoids is a commonly proposed induction regimen, especially when lupus nephritis (LN) is also present. However, due to the patient’s coexisting hepatic comorbidities , therapy was tailored by substituting rituximab for CYC promptly to optimize nephroprotection