Are systemic sclerosis and localized scleroderma (morphea) part of a common disease spectrum? A systematic review on their coexistence

Scleroderma encompasses systemic sclerosis (SSc), which may be divided into limited cutaneous and diffuse cutaneous forms, as well as localized scleroderma (LoS), also known as morphea, each with distinct yet overlapping features. Although SSc affects internal organs, LoS (morphea) is typically confined to skin and the underlying tissues. We reviewed the records from 23 studies of 57 patients for coexistence of SSc and LoS (morphea). The majority of patients were women (84%) with a mean disease onset age of 44 years. Limited cutaneous SSc (46%) and nodular morphea (25%) were the most frequent subtypes. Raynaud phenomenon (63%) and sclerodactyly (53%) were common systemic manifestations, with severe complications, such as interstitial lung disease (25%) and esophageal dysmotility (18%), observed in 35% of the patients. Autoantibodies were detected in 67% of the patients, with anti-centromere (28%) and anti-nuclear (23%) antibodies as the most frequent markers. Disease sequencing showed SSc preceding LoS (morphea) in 47% of cases (mean latency: five years), LoS (morphea) preceding SSc in 26% (latency: seven years), and concurrent onset in 26%, often with generalized morphea. The coexistence suggests shared pathogenic mechanisms involving autoimmunity and TGF-β-mediated fibrosis. Treatment data were limited but indicated partial to complete improvement with systemic steroids, immunosuppressants, and other modalities. These findings highlight the importance of monitoring LoS (morphea) patients, particularly those with Raynaud phenomenon or autoantibody positivity, for potential progression to SSc. The overlap supports considering SSc and LoS (morphea) as a continuum rather than distinct entities.