The Convergence of Fibrosis and Granulomatous Inflammation: A Case Series on the Diagnostic and Therapeutic Challenges of Systemic Sclerosis and Sarcoidosis Overlap Syndrome

The coexistence of systemic sclerosis and sarcoidosis is very rare. Both are systemic autoimmune diseases with lung involvement but different pathogenesis. In contrast to findings of mid- to upper-lobe interstitial lung disease (ILD) that may occur with hilar lymphadenopathy in sarcoidosis, the most common lung manifestation of systemic sclerosis is lower-lobe ILD, which is typically characterized by a non-specific interstitial pneumonia pattern. This distinction in lung involvement between the two diseases is crucial due to the need for different therapeutic approaches. We present a series of three overlap cases: two with sarcoidosis onset before the diagnosis of systemic sclerosis and another with systemic sclerosis onset before the diagnosis of sarcoidosis. Three cases of concomitant sarcoidosis and systemic sclerosis are reviewed, including the pathophysiology of each disease and the shared pathways leading to the development of both conditions. Systemic sclerosis–sarcoidosis overlap is a high-risk phenotype. Early recognition and a personalized, aggressive therapeutic approach are essential to alter the natural course of these two converging fibrotic and granulomatous processes.