Antineutrophil cytoplasmic antibody positivity in systemic lupus erythematosus: Diagnostic dilemma and therapeutic implications

Objectives Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in up to 25% of systemic lupus erythematosus (SLE) patients, but differentiating incidental ANCA from ANCA-associated vasculitis (AAV) in SLE nephritis remains a diagnostic and therapeutic challenge. Case A 14-year-old female presented with a 3-month history of undiagnosed autoimmune manifestations and chronic kidney disease. Based on autoimmune workup and kidney biopsy, she was diagnosed with SLE nephritis with incidental ANCA positivity. Despite appropriate SLE nephritis-directed treatment as per guidelines, an inflammatory flare and superimposed acute kidney injury (AKI) prompted a diagnosis revision to SLE-AAV overlap syndrome. Broadening treatment to target concomitant AAV led to autoimmune remission and AKI resolution. Conclusions This case underscores the importance of early suspicion of autoimmune disorders by primary care providers for a timely referral and the critical role of specialists in recognizing the limitations of conventional tools, including renal histology, when distinguishing incidental ANCA positivity from SLE-AAV overlap to guide appropriate treatment.