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. 2025 Jul;44(7):2849-2860.
doi: 10.1007/s10067-025-07449-1. Epub 2025 May 15.

Prevalence and clinical relevance of digital ulcers in systemic sclerosis patients from the real-life: the experience of the SPRING Registry of the Italian Society for Rheumatology

Martina Orlandi  1 , Giacomo De Luca  2 , Clodoveo Ferri  3   4 , Amelia Spinella  3 , Federica Lumetti  3 , Riccardo Cuoghi Costantini  3 , Rossella De Angelis  5 , Valeria Riccieri  6 , Silvia Laura Bosello  7 , Fabio Cacciapaglia  8   9 , Veronica Codullo  10   11 , Gianluigi Bajocchi  12 , Corrado Campochiaro  2 , Giovanni Zanframundo  10   11 , Rosario Foti  13 , Giovanna Cuomo  14 , Alarico Ariani  15 , Edoardo Rosato  16 , Francesco Girelli  17 , Elisabetta Zanatta  18 , Ilaria Cavazzana  19 , Francesca Ingegnoli  20 , Maria De Santis  21 , Giuseppe Murdaca  22 , Giuseppina Abignano  23 , Pettiti Giorgio  24 , Alessandra Della Rossa  25 , Maurizio Caminiti  26 , Anna Maria Iuliano  27 , Giovanni Ciano  28 , Lorenzo Beretta  29 , Gianluca Bagnato  30 , Ennio Lubrano  31 , Ilenia De Andres  32 , Alessandro Giollo  33 , Marta Saracco  34 , Cecilia Agnes  35 , Edoardo Cipolletta  5 , Luca Magnani  9 , Elisa Visalli  12 , Carlo Iandoli  13 , Antonietta Gigante  15 , Greta Pellegrino  36   37 , Erika Pigatto  38 , Maria Grazia Lazzaroni  19 , Franco Franceschini  19 , Elena Generali  21 , Gianna Mennillo  23 , Simone Barsotti  25 , Giuseppa Pagano Mariano  26 , Federica Furini  39 , Licia Vultaggio  39 , Simone Parisi  40 , Clara Lisa Peroni  40 , Gerolamo Bianchi  41 , Enrico Fusaro  40 , Gian Domenico Sebastiani  27 , Marcello Govoni  39 , Salvatore D'Angelo  23 , Franco Cozzi  42 , Serena Guiducci  43 , Andrea Doria  36 , Carlo Salvarani  10   11 , Florenzo Iannone  8 , Lorenzo Dagna  2   44 , Marco Matucci-Cerinic  2   44 , Silvia Bellando-Randone  43 , Dilia Giuggioli  3 ; SPRING-SIR (Systemic Sclerosis PRogression INvestiGation group of the Italian Society of Rheumatology) coworkers
Collaborators, Affiliations

Prevalence and clinical relevance of digital ulcers in systemic sclerosis patients from the real-life: the experience of the SPRING Registry of the Italian Society for Rheumatology

Martina Orlandi et al. Clin Rheumatol. 2025 Jul.

Abstract

Introduction: Digital ulcers (DU) are one of the most frequent manifestations in systemic sclerosis (SSc). The presence of DU seems to be a sentinel sign of internal organ involvement and is related to a poor prognosis of the disease. The aim of this study was to evaluate the prevalence and the relationship of DU with clinical manifestations/variants in a large SSc cohort from the SPRING registry.

Methods: SSc patients fulfilling the ACR/EULAR 2013 classification criteria without missing data on digital ulcers were enrolled in a cross-sectional study. Logistic regression models were built to test the association between the presence of DU and SSc-related features.

Results: Among 1873 eligible SSc patients, the presence of DU was significantly associated with gastrointestinal involvement (OR 1.88, 2.04 and 1.74; p < 0.001) and serum ATA positivity (OR 2.15; p < 0.001), as well as with telangiectasias, sclerodactyly, digital pitting scar, and calcinosis (OR 1.40, p = 0.005; OR 3.43, p < 0.001, OR 9.12, p < 0.001 and OR 2.77, p < 0.001; respectively). In the multivariable regression models, even after adjustment for covariates, ATA positivity (OR 1.76, p = 0.039), puffy fingers (OR 2.82, p < 0.001), and a higher revEUSTAR-AI (OR 6.63, p < 0.001) emerged as risk factors for the presence of DU. Moreover, a low presence of DU was recorded in SSc patients with a history of previous immunosuppressive treatments (OR 0.53, p = 0.032).

Conclusion: In our Italian SSc cohort, DUs were significantly associated with the presence of puffy fingers, high revEUSTR-AI, and ATA seropositivity. Noteworthy, immunosuppressive treatments were associated with a low rate of DU, suggesting that they might contribute to the prevention of these harmful manifestations. Key Points • Digital ulcers were significantly associated with the presence of puffy fingers, high disease activity, and anti-Scl70 seropositivity. • Immunosuppressive treatments were associated with a low rate of digital ulcers, suggesting that they might contribute to the prevention of these harmful manifestations.

Keywords: Digital ulcers; Immunosuppressive therapy; Systemic sclerosis; Vascular disease.

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Conflict of interest statement

Declarations. Conflicts of interest: Orlandi M, Giuggioli D, Bellando-Randone S, Lubrano E, Lumetti F, Ferri C, Generali E, Rosato E, Bianchi G, Sebastiani GD, Pellegrino G, Murdaca G, Foti R, Visalli E, Zanframundo G, Codullo V, De Angelis R, Riccieri V, Parisi S, Peroni CL, D’Angelo S, Pigatto E, Spinella A, Govoni M, Bagnato G, Agnes C, Cuomo G, Franceschini F, Cavazzana I, Campochiaro C, De Luca G, Bajocchi G, Lazzaroni MG, Iannone F, Cacciapaglia F, Scirè CA, Magnani L, Ariani A,, Dagna L, Girelli F, Zanatta F, Ingegnoli F, De Santis M, Abignano G, Della Rossa A, Caminiti M, Iuliano AM, Ciano G, Beretta L, De Andres I, Giollo A, Saracco A, Di Vico C, Gigante A, Mennillo G, Barsotti S, Pagano Mariano G, Furini F, Vultaggio L, Landolfi G, Fusaro E, Cozzi F, Doria A, Salvarani C and Guiducci S have no conflict of interest to declare. Silvia Laura Bosello received consulting fees and/or honoraria from GSK, Abbvie, Boehringer Ingelheim, Research grants from Gruppo Italiano Lotta alla Sclerodermia (GILS). Edoardo Cipolletta received consulting fees and/or honoraria from Novartis and Horizon Therapeutics; research grants from the Foundation for Research in Rheumatology (FOREUM), congress supports from Eli-Lilly, educational grants from the European Alliance of Associations for Rheumatology (EULAR). Matucci-Cerinic M received fees from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche.

Figures

Fig. 1
Fig. 1
Differences in disease burden between SSc phenotypes. This spider plot illustrates the comparison of SSc phenotypes based on clinical features identified as significant in multivariate analysis. These features include mRSS, puffy fingers, ATA positivity, calcinosis, revEUSTAR-AI, and previous immunosuppressive treatment. Phenotypes and key insights: 1. Clinical features + DU (yellow area): This phenotype shows the highest intensity across most features, such as calcinosis, revEUSTAR-AI, and mRSS. Represents the most severe clinical phenotype, combining DU with systemic involvement. 2. Clinical features without DU (orange area): Moderate intensity in features like ATA positivity and puffy fingers. Indicates a milder systemic phenotype without DU. 3. No clinical features + DU (red area): Low intensity across all features but retains some involvement in features like revEUSTAR-AI. Suggests isolated vascular complications leading to DU without significant systemic manifestations. 4. No clinical features without DU (pink area): Minimal involvement in all features, representing the mildest phenotype with neither DU nor significant systemic disease
See this image and copyright information in PMC

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Supplementary concepts