Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry ‘SPRING’ of the Italian Society for Rheumatology
Authors: De Angelis Rossella , Ferri Clodoveo , Giuggioli Dilia , Bajocchi Gianluigi , Dagna Lorenzo , Bellando-Randone Silvia , Zanframundo Giovanni , Foti Rosario , Cacciapaglia Fabio , Cuomo Giovanna , Ariani Alarico , Rosato Edoardo , Lepri Gemma , Girelli Francesco , Riccieri Valeria , Zanatta Elisabetta , Bosello Silvia Laura , Cavazzana Ilaria , Ingegnoli Francesca , De Santis Maria , Murdaca Giuseppe , Abignano Giuseppina , Romeo Nicoletta , Della Rossa Alessandra , Caminiti Maurizio , Iuliano Anna Maria , Ciano Giovanni , Beretta Lorenzo , Bagnato Gianluca , Lubrano Ennio , De Andres Ilenia , Giollo Alessandro , Saracco Marta , Agnes Cecilia , Cipolletta Edoardo , Lumetti Federica , Spinella Amelia , Magnani Luca , Campochiaro Corrado , De Luca Giacomo , Codullo Veronica , Visalli Elisa , Di Vico Claudio , Gigante Antonietta , Pellegrino Greta , Pigatto Erika , Lazzaroni Maria-Grazia , Franceschini Franco , Generali Elena , Mennillo Gianna , Barsotti Simone , Mariano Giuseppa Pagano , Furini Federica , Vultaggio Licia , Parisi Simone , Peroni Clara Lisa , Rozza Davide , Zanetti Anna , Carrara Greta , Landolfi Gianpiero , Scirè Carlo Alberto , Bianchi Gerolamo , Fusaro Enrico , Sebastiani Gian Domenico , Govoni Marcello , D'Angelo Salvatore , Cozzi Franco , Guiducci Serena , Doria Andrea , Salvarani Carlo , Iannone Florenzo , Matucci-Cerinic Marco 
Published: March 2023

Objective

To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.

Methods

Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.

Results

Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001).

Conclusion

The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.