Quadruple Autoimmune Syndrome: Sjögren's Syndrome, Systemic Lupus Erythematosus, Systemic Sclerosis, and Celiac Disease

Multiple autoimmune syndrome (MAS) is characterized by the coexistence of three or more autoimmune diseases in a single patient and reflects a profound breakdown of immune tolerance. Although overlap syndromes are relatively common in rheumatology, the occurrence of four distinct autoimmune diseases remains exceptionally rare. We report the case of a 40-year-old woman who sequentially developed primary Sjögren’s syndrome, systemic lupus erythematosus, systemic sclerosis, and celiac disease over a prolonged follow-up period. The initial presentation was marked by cytopenias, positive antinuclear antibodies, anti-Ro/SSA positivity, and glandular dysfunction, leading to the diagnosis of Sjögren’s syndrome. Subsequently, the patient evolved with cutaneous involvement, hypocomplementemia, and systemic features fulfilling classification criteria for systemic lupus erythematosus despite persistently negative anti-dsDNA antibodies. Years later, she developed Raynaud’s phenomenon, esophageal dysmotility, interstitial lung disease, and skin fibrosis, consistent with systemic sclerosis. Concomitantly, gastrointestinal manifestations led to the diagnosis of celiac disease confirmed by histopathology. The patient required multiple immunosuppressive therapies, including methotrexate, azathioprine, and mycophenolate mofetil, achieving clinical stabilization after a severe episode of pericardial effusion. This case highlights the dynamic evolution of autoimmunity, the heterogeneity of serological profiles, and the importance of long-term surveillance in patients with autoimmune diseases. It also reinforces the role of shared genetic and immunological mechanisms underlying multiple autoimmune conditions.