Pre-scleroderma and new opportunities for preventive medicine – Authors’ reply

We thank Devis Benfaremo and colleagues for their interest in our Viewpoint 1 Lescoat A Bellando-Randone S Campochiaro C et al. Beyond very early systemic sclerosis: deciphering prescleroderma and its trajectories to open new avenues for preventive medicine. Lancet Rheumatol. 2023; 5: e683-e694 Summary Full Text Full Text PDF Scopus (1) Google Scholar and for reporting their stimulating data supporting the concept that the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) and the clinical conditions preceding it are of paramount importance in understanding the natural history of systemic sclerosis. 1 Lescoat A Bellando-Randone S Campochiaro C et al. Beyond very early systemic sclerosis: deciphering prescleroderma and its trajectories to open new avenues for preventive medicine. Lancet Rheumatol. 2023; 5: e683-e694 Summary Full Text Full Text PDF Scopus (1) Google Scholar They proposed a definition of pre-scleroderma, based on the association of Raynaud's phenomenon, antinuclear antibodies, and systemic sclerosis-specific autoantibodies or scleroderma pattern on nailfold capillaroscopy but without puffy fingers. Applying this pre-scleroderma definition in consecutive patients with Raynaud's phenomenon, they showed that pre-scleroderma represented 16% of the patients, while VEDOSS only represented 3%. The authors did not specify what percentage of pre-scleroderma was based on Raynaud's phenomenon and anti-nuclear antibody positivity versus Raynaud's phenomenon and systemic sclerosis-specific autoantibodies, as the previous group might be associated with other connective tissue diseases. Also, as acknowledged by Benfaremo and colleagues, there is absence of longitudinal data to show the proportion of patients developing definite systemic sclerosis, per the American College of Rheumatology-European League against Rheumatisms criteria in this population without puffy fingers. Therefore, if Benfaremo and colleagues could hereafter provide longitudinal data on the evolution of these patients, this would be of paramount importance to expand the knowledge and discuss whether the definitions of VEDOSS and pre-scleroderma should be revisited. In the VEDOSS study, 2 Bellando-Randone S Del Galdo F Lepri G et al. Progression of patients with Raynaud's phenomenon to systemic sclerosis: a five-year analysis of the European Scleroderma Trial and Research group multicentre, longitudinal registry study for Very Early Diagnosis of Systemic Sclerosis (VEDOSS). Lancet Rheumatol. 2021; 3: e834-e843 Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar 19·8% of the patients had puffy fingers and Raynaud's phenomenon at baseline and among these 70·8% progressed to definite systemic sclerosis within 5 years, making puffy fingers the symptom with one of the highest positive predicted values but with expected low negative predictive value, since 47·9% of the patients without puffy fingers nonetheless progressed to definite systemic sclerosis. Pre-scleroderma and new opportunities for preventive medicineWe read with great interest the Viewpoint by Alain Lescoat and colleagues1 in The Lancet Rheumatology, in which the authors highlighted the importance of deciphering the differential trajectories of individuals with pre-scleroderma. In our opinion, two points raised in this Viewpoint are essential. First, the absence of reliable data on the prevalence of pre-scleroderma (also due to the lack of consensus on its definition), and second, the absence of biomarkers of disease progression at early stages. Full-Text PDF Beyond very early systemic sclerosis: deciphering pre‑scleroderma and its trajectories to open new avenues for preventive medicineThe identification of individuals with systemic sclerosis in an oligosymptomatic phase preceding the very early manifestations of the disease represents a challenge in the search for a new window of opportunity in systemic sclerosis. This phase could be identified in a clinical scenario as the pre-scleroderma phase, in which the disease would still be far from systemic sclerosis-related fibrotic or irreversible manifestations in skin or organs. In this Personal View, we discuss parameters and candidate definitions for a conceptual framework of pre-scleroderma, from the identification of populations at risk to autoantibodies and their potential functional activities. Full-Text PDF