A Rare Autoimmune Triad: Coexistence of Systemic Lupus Erythematosus, Sjögren's Syndrome, and Ankylosing Spondylitis: A Case Report.

Systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and ankylosing spondylitis (AS) are distinct immune-mediated diseases with different classification frameworks and usual treatment approaches. Coexistence of all three disorders in a single patient is rare and creates diagnostic and therapeutic challenges. We report a 40-year-old woman with longstanding SLE, SS associated with SLE, and subsequently recognized axial spondyloarthritis (axSpA)/AS. The patient fulfilled the 2019 ACR/EULAR classification criteria for SLE (total score ≥ 10), the 2016 ACR/EULAR classification criteria for primary SS (total score ≥ 4), and the 2009 ASAS classification criteria for axSpA through both the imaging and clinical arms. Conventional treatment options were limited by prior gastrointestinal bleeding with NSAIDs and concern for drug-induced lupus-like syndromes with TNF inhibitors. The patient remained stable on hydroxychloroquine 200 mg daily and was enrolled in a Phase 2 SLE clinical trial evaluating a JAK inhibitor. Treatment assignment was unknown during the blinded period; during the unblinded continuation phase, she was confirmed to be receiving upadacitinib 15 mg daily. Over a 6-month duration of confirmed upadacitinib exposure, clinical improvement in lupus- and sicca-related symptoms were observed, and follow-up MRI showed resolution of previously documented sacroiliitis. Although causality cannot be established from a single uncontrolled observation, the clinical and imaging improvement during confirmed upadacitinib exposure is hypothesis-generating and suggests that shared inflammatory pathways may warrant further investigation in selected overlap cases.