Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review

Corrado Campochiaro¹, Yossra A Suliman², Michael Hughes³, Jan W Schoones⁴, Dilia Giuggioli⁵, Pia Moinzadeh⁶, Murray Baron⁷, Lorinda Chung⁸, Laura Ross⁹, Nancy Maltez¹⁰, Yannick Allanore¹¹, Christopher P Denton¹², Oliver Distler¹³, Tracy Frech¹⁴, Daniel E Furst¹⁵, Dinesh Khanna¹⁶, Thomas Krieg¹⁷, Masataka Kuwana¹⁸, Marco Matucci-Cerinic¹⁹, Janet Pope²⁰, Alessia Alunno²¹

Affiliations

¹ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University. Electronic address: campochiaro.corrado@hsr.it.
² Assiut University Hospital, Egypt.
³ Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester.
⁴ Directorate of Research Policy (formerly Walaeus Library), Leiden University Medical Center, Leiden, The Netherlands.
⁵ University of Modena, Italy.
⁶ University Hospital of Cologne, Germany.
⁷ Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
⁸ Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, CA, USA.
⁹ The University of Melbourne, Melbourne, VIC, Australia; St Vincent's Hospital, Melbourne, Australia.
¹⁰ University of Ottawa, Ottawa, ON, Canada.
¹¹ Paris Descartes University, Paris, France.
¹² University College London, London, United Kingdom.
¹³ University of Zurich, Zurich, Switzerland.
¹⁴ University of Utah, Veterans Affairs Medical Center, Salt Lake City, UT, USA.
¹⁵ University of California, Los Angeles, CA, USA.
¹⁶ University of Michigan, Ann Arbor, MI, USA.
¹⁷ Department of Dermatology and Venereology, University Hospital of Cologne, Cologne, Germany.
¹⁸ Nippon Medical School, Tokyo, Japan.
¹⁹ University of Florence, Florence, Italy.
²⁰ Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
²¹ Department of Life, Health & Environmental Sciences, University of L'Aquila and Internal Medicine and Nephrology Unit and Department of Medicine, ASL Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy.

PMID: 37778090
DOI: 10.1016/j.semarthrit.2023.152267

Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review

Corrado Campochiaro et al. Semin Arthritis Rheum. 2023 Dec.

. 2023 Dec:63:152267.

doi: 10.1016/j.semarthrit.2023.152267. Epub 2023 Sep 26.

Authors

Affiliations

¹ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University. Electronic address: campochiaro.corrado@hsr.it.
² Assiut University Hospital, Egypt.
³ Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester.
⁴ Directorate of Research Policy (formerly Walaeus Library), Leiden University Medical Center, Leiden, The Netherlands.
⁵ University of Modena, Italy.
⁶ University Hospital of Cologne, Germany.
⁷ Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
⁸ Stanford University School of Medicine and Palo Alto VA Health Care System, Palo Alto, CA, USA.
⁹ The University of Melbourne, Melbourne, VIC, Australia; St Vincent's Hospital, Melbourne, Australia.
¹⁰ University of Ottawa, Ottawa, ON, Canada.
¹¹ Paris Descartes University, Paris, France.
¹² University College London, London, United Kingdom.
¹³ University of Zurich, Zurich, Switzerland.
¹⁴ University of Utah, Veterans Affairs Medical Center, Salt Lake City, UT, USA.
¹⁵ University of California, Los Angeles, CA, USA.
¹⁶ University of Michigan, Ann Arbor, MI, USA.
¹⁷ Department of Dermatology and Venereology, University Hospital of Cologne, Cologne, Germany.
¹⁸ Nippon Medical School, Tokyo, Japan.
¹⁹ University of Florence, Florence, Italy.
²⁰ Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
²¹ Department of Life, Health & Environmental Sciences, University of L'Aquila and Internal Medicine and Nephrology Unit and Department of Medicine, ASL Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy.

PMID: 37778090
DOI: 10.1016/j.semarthrit.2023.152267

Abstract

Introduction: Digital ulcers (DUs) are difficult to treat in patients with systemic sclerosis (SSc) and systemic (i.e., pharmacological) therapy is currently considered the 'standard of care'. Our aim was to examine the safety and efficacy of local, non-surgical treatment for SSc-DUs.

Methods: A systematic literature review (SLR) of original research articles up to August, 29 2022 was performed according to the PICO framework. References were independently screened by two reviewers and risk of bias was assed using validated tools. Due to study heterogeneity narrative summaries are used to present data.

Results: Among 899 retrieved references, 14 articles were included (2 randomised trials (RTs), and 12 observational (OBS) studies). The most frequently studied procedure (5 studies) was botulin A toxin (hand or single finger) injection with a reported healing rate (HR) of 71%-100%. Amniotic and hydrocolloid membranes were examined in one study each and associated with a good HR. Tadalafil 2% cream was studied in a single study with a reduction in the number of DUs. Vitamin E gel was associated with a reduction in ulcer healing time. Low-level light therapy, hydrodissection and corticosteroid injection, extracorporeal shock wave (ESW) and photobiomodulation were evaluated in a single study each and showed a positive trend. Dimethyl sulfoxide was associated with significant local toxicity.

Conclusions: A range of non-surgical, local treatments for SSc-DUs have been explored and showed efficacy to some extent. We have identified methodological flaws that should be avoided in the design of future studies to explore locally-acting treatments for SSc-DUs.

Keywords: Digital ulcers: Management: Non-surgical; Scleroderma; Systemic sclerosis; Topical treatment.

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Conflict of interest statement

Declaration of Competing Interest CC: No conflict of interest to declare YAS: No conflict of interest to declare MH: Speaking fees from Actelion Pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work. Member of a Data and Safety Monitoring Board for Certa Therapeutics. JWS: No conflict of interest to declare DG: No conflict of interest to declare PM: Speaking fees from Actelion Pharmaceuticals and Boehringer Ingelheim. MB: No conflict of interest to declare LC: Has served as an Advisor and Steering Committee member for Eicos Sciences. Has received consulting fees from Mitsubishi Tanabe, Genentech, Kyverna, and Jasper. LR: No conflict of interest to declare NM: No conflict of interest to declare YA: Consulting fees from Boehringer Ingelheim and Sanofi, payment, or honoraria from Boehringer Ingelheim and participation in Data Safety or Advisory Board for Boehringer Ingelheim, Menarini, Chemomab, Curzion, Medseni, Sanofi. CPD: Received grants from GlaxoSmithKline, Inventiva, CSL Behring, Servier, Arxx Therapeutics. Consulting fees from GlaxoSmithKline, Janssen, Bayer, Sanofi, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Corbus, Acceleron. OD: 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: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL, Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). TF: Held a paid leadership role with the Scleroderma Clinical Trials Consortium. DEF: Grants or contracts from Amgen, Corbus, CSL Behring, Galapagos, Gilead, GSK, Horizon, Kadmon, Novartis, Pfizer, Roche / Genentech, Talaris. Consulting fees from Amgen, Corbus, Galapagos, Horizon, Kadmon, Pfizer, Talaris. Payment or honoraria from CME. DK: Consulting fees from Actelion Pharmaceuticals, Acceleron, Amgen, Bayer, Boehringer Ingelheim, Chemomab, CSL Behring, Genentech / Roche, Horizon, Paracrine Cell Therapy, Mitsubishi Tanabe, Prometheus. Stock or stock options in Eicos Sciences Inc. TK: World Scleroderma Foundation Board Member, Edith Busch Foundation Advisory Board Member, German Scleroderma Foundation Board Member. MK: Speakers fees from Abbvie, Asahi-Kasei, Astellas, Boehringer-Ingelheim, Chugai, Eisai, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi; Consultant fees from AstraZeneca, Boehringer-Ingelheim, Chugai, Corbus, GSK, Horizon, Mochida, Kissei; Grant/research support from Boehringer-Ingelheim, MBL, Ono Pharmaceuticals. MMC: Grants from Actelion Pharmaceuticals, consulting fees from Actelion Pharmaceuticals, Biogen, Bayer, Boehringer Ingelheim, CSL Behring, Eli Lilly. JP: No conflict of interest to declare AA: No conflict of interest to declare

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Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review

Affiliations

Non-surgical local treatments of digital ulcers in systemic sclerosis: a systematic literature review

Authors

Affiliations

Abstract

Conflict of interest statement

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MeSH terms

Supplementary concepts

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Medical