Treatment recommendations for the systemic pharmacological treatment of systemic sclerosis digital ulcers: Results from the World Scleroderma Foundation Ad Hoc Committee

Nancy Maltez¹, Laura Ross², Murray Baron³, Alessia Alunno^{4

5}, Corrado Campochiaro⁶, Yossra A Suliman⁷, Jan W Schoones⁸, Yannick Allanore⁹, Francesco Del Galdo¹⁰, Christopher P Denton^{11

12}, Oliver Distler¹³, Tracy Frech¹⁴, Daniel E Furst¹⁵, Dilia Giuggioli¹⁶, Dinesh Khanna¹⁷, Thomas Krieg¹⁶, Masataka Kuwana¹⁸, Marco Matucci-Cerinic¹⁹, Pia Moinzadeh²⁰, Janet Pope²¹, Lorinda Chung²², Michael Hughes^{23

24}

Affiliations

¹ Division of Rheumatology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
² Department of Medicine and Rheumatology, University of Melbourne at St Vincent's Hospital, Melbourne, VIC, Australia.
³ Division of Rheumatology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
⁴ Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
⁵ Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L'Aquila, L'Aquila, Italy.
⁶ Department of Immunology, Rheumatology, Allergy and Rare Diseases, Raffaele Hospital, Vita-Salute San Raffaele Universita, Milan, Italy.
⁷ Department of Rheumatology and Rehabilitation, Assiut University Hospital, Assiut, Egypt.
⁸ Directorate of Research Policy (formerly Walaeus Library), Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Rheumatology, Cochin Hospital, AP-HP, Paris Descartes University, Paris, France.
¹⁰ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹¹ Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, London, UK.
¹² UCL Division of Medicine, University College London, London, UK.
¹³ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹⁴ Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Veterans Affairs Medical Center, Nashville, TN, USA.
¹⁵ Department of Rheumatology and Medicine, University of California, Los Angeles, CA, USA.
¹⁶ Division of Rheumatology, Department of Rheumatology, University of Modena and Reggio Emilia, Policlinico of Modena, Modena, Italy.
¹⁷ Department of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
¹⁸ Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan.
¹⁹ Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, Florence, Italy.
²⁰ Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany.
²¹ Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
²² Department of Rheumatology, Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, CA, USA.
²³ Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK.
²⁴ Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.

PMID: 40852405
PMCID: PMC12367710
DOI: 10.1177/23971983251340559

Treatment recommendations for the systemic pharmacological treatment of systemic sclerosis digital ulcers: Results from the World Scleroderma Foundation Ad Hoc Committee

Nancy Maltez et al. J Scleroderma Relat Disord. 2025.

. 2025 Aug 19:23971983251340559.

doi: 10.1177/23971983251340559. Online ahead of print.

Authors

Affiliations

¹ Division of Rheumatology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
² Department of Medicine and Rheumatology, University of Melbourne at St Vincent's Hospital, Melbourne, VIC, Australia.
³ Division of Rheumatology, Jewish General Hospital, McGill University, Montreal, QC, Canada.
⁴ Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
⁵ Internal Medicine and Nephrology Division, ASL1 Avezzano-Sulmona-L'Aquila, L'Aquila, Italy.
⁶ Department of Immunology, Rheumatology, Allergy and Rare Diseases, Raffaele Hospital, Vita-Salute San Raffaele Universita, Milan, Italy.
⁷ Department of Rheumatology and Rehabilitation, Assiut University Hospital, Assiut, Egypt.
⁸ Directorate of Research Policy (formerly Walaeus Library), Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Rheumatology, Cochin Hospital, AP-HP, Paris Descartes University, Paris, France.
¹⁰ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹¹ Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, London, UK.
¹² UCL Division of Medicine, University College London, London, UK.
¹³ Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹⁴ Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Veterans Affairs Medical Center, Nashville, TN, USA.
¹⁵ Department of Rheumatology and Medicine, University of California, Los Angeles, CA, USA.
¹⁶ Division of Rheumatology, Department of Rheumatology, University of Modena and Reggio Emilia, Policlinico of Modena, Modena, Italy.
¹⁷ Department of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
¹⁸ Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan.
¹⁹ Division of Rheumatology, Department of Experimental and Clinical Medicine, Careggi University Hospital, University of Florence, Florence, Italy.
²⁰ Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany.
²¹ Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
²² Department of Rheumatology, Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, CA, USA.
²³ Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK.
²⁴ Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.

PMID: 40852405
PMCID: PMC12367710
DOI: 10.1177/23971983251340559

Abstract

Introduction: Digital ulcers are an important disease manifestation of systemic sclerosis and are associated with significant morbidity. As such, there is an urgent need for the development of evidence-based recommendations to guide clinicians in the treatment of digital ulcers.

Methods: A steering committee of international experts was established. A systematic review of the literature pertaining to the use of pharmacologic treatments in the management of digital ulcers was performed to inform the development of treatment recommendations for systemic sclerosis digital ulcers. Consensus methodology was used to develop the final treatment recommendations.

Results: The World Scleroderma Foundation committee agreed on 8 overarching treatment principles and 10 pharmacologic treatment recommendations for the management of systemic sclerosis digital ulcers. Phosphodiesterase 5 inhibitors and intravenous iloprost were recommended for the management of acute digital ulcers. Bosentan was recommended for prevention of digital ulcers.

Conclusion: This study has yielded pragmatic treatment recommendations to direct treatment decisions for the management of systemic sclerosis digital ulcers. In addition, results have highlighted areas in need of future research in order to improve patient outcomes.

Keywords: Systemic sclerosis; consensus; digital ulcer; recommendations; treatment.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: M.H. reports research funding and speaker fees from Janssen, outside of the submitted work. Chair of a Data Safety Monitoring Board: SHED SSc – SHarp dEbridement of Digital ulcers in Systemic Sclerosis: a multi-centre Randomised Controlled Trial feasibility study (REC reference: 21/YH/0278). M.K. has received consulting fees, speaking fees and/or research grants from Argenx, Asahi Kasei Parma, AstraZeneca, Boehringer Ingelheim, Chugai, GSK, Janssen, Kissei, MBL, Mochida, Ono Pharmaceuticals and Tanabe-Mitsubishi. L.C. has received consulting fees from Mitsubishi Tanabe, Genentech, Kyverna, IgM Biosciences, Lilly and Janssen. D.G. has received speaking fees from Boehringer Ingelheim and Janssen. O.D. has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Prometheus, Redxpharma, Roivant, EMD Serono, Topadur and UCB. Patent issued ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). Co-founder of CITUS AG. None of the other authors report any relevant conflicts of interest.

References

1. Hughes M, Herrick AL. Systemic sclerosis. Br J Hosp Med 2019; 80(9): 530–536. - PubMed
1. Matucci-Cerinic M, Krieg T, Guillevin L, et al. Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry. Ann Rheum Dis 2016; 75(10): 1770–1776. - PMC - PubMed
1. Hughes M, Allanore Y, Chung L, et al. Raynaud phenomenon and digital ulcers in systemic sclerosis. Nat Rev Rheumatol 2020; 16(4): 208–221. - PubMed
1. Mihai C, Landewé R, van der Heijde D, et al. Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis 2016; 75(4): 681–686. - PubMed
1. Morrisroe K, Stevens W, Sahhar J, et al. Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden. Arthritis Res Ther 2019; 21(1): 299. - PMC - PubMed

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Treatment recommendations for the systemic pharmacological treatment of systemic sclerosis digital ulcers: Results from the World Scleroderma Foundation Ad Hoc Committee

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Treatment recommendations for the systemic pharmacological treatment of systemic sclerosis digital ulcers: Results from the World Scleroderma Foundation Ad Hoc Committee

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