Unraveling complex autoimmunity: a case series of rheumatologic overlap syndromes

Abstract

Overlap syndromes represent a complex interplay of multiple connective tissue diseases coexisting within a single patient, posing significant diagnostic and therapeutic challenges due to overlapping clinical, serologic, and immunologic features that defy classification into a single disease entity. We report a case series of ten patients evaluated at a tertiary care rheumatology unit in Northeast India, illustrating the heterogeneity of this clinical entity. The cohort included overlaps of systemic sclerosis with rheumatoid arthritis, Sjögren's syndrome with polymyositis, systemic lupus erythematosus with rheumatoid arthritis, systemic lupus erythematosus with Sjögren's syndrome, and systemic sclerosis with polymyositis, with organ involvement ranging from interstitial lung disease and pulmonary arterial hypertension to lupus nephritis, neuropsychiatric lupus, and lupus enteritis. Nine of the ten patients were female, and diagnosis relied on comprehensive autoantibody profiling alongside clinical evaluation. Management with corticosteroids, mycophenolate mofetil, cyclophosphamide, and hydroxychloroquine, guided by dominant organ involvement, achieved favourable outcomes in most patients; two patients with treatment non-adherence progressed to fatal complications. These cases emphasize the importance of maintaining a high index of suspicion for overlap syndromes in patients with multisystem autoimmune manifestations. Early recognition, detailed immunologic profiling, and multidisciplinary management are essential to prevent irreversible organ damage, guide personalized therapy, and optimize long-term outcomes in this challenging and increasingly recognized domain of clinical rheumatology.