In:
Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 746.2-747
Abstract:
Management of digital ulcers (DUs) in systemic sclerosis (SSc) is a major clinical challenge. To date, systemic therapy is generally considered as the ‘standard of care’ for significant SSc-DUs. However, there is a strong rationale to develop local approaches to DUs, to avoid side effects from systemic therapies. World Scleroderma Foundation DU Working Group intends to develop practical, evidence-based recommendations for DU management including local, Surgical Treatment (L-ST). Objectives To summarize the literature on the safety and efficacy of L-ST for SSc-DUs. Methods A systematic literature review (SLR) was conducted up to May 2021. According to the PICO framework, eligibility criteria were defined and original research articles about surgical treatment of SSc DUs in adult patients were included. References were independently screened by 2 reviewers who assessed the full text of eligible articles and extracted data. Results Thirteen eligible articles out of 790 total publications were identified (Table 1). Due to the paucity of randomized controlled trials of surgical treatments for SSc-DU, we included retrospective studies and case series with at least 4 patients. Autologous fat (adipose tissue AT) grafting was the surgical modality mostly identified (7 studies of which 1 RCT and 6 prospective open label single arm). The healing rate (HR) with autologous fat grafting (4 studies) ranged from 66-100 %. In the RCT, two age and sex matched groups were included, adipose tissue (AT)group (n=25 pts) and sham procedure (SP) group (n=13), DU healing was reported in 23/25 in AT group versus 1/13 in the SP group in 8 wks, (p 〈 0.0001), 12 pts in the SP group, received rescue AT injection, all of them healed after 8 wks. Three studies reported autologous adipose-derived stromal vascular fraction(SVF) grafting and the HR ranged from 32-60%, followed up to 12 months. Transient edema and paresthesia were reported in 2 studies, and amputation in 2 ulcers in 1 study, and no complications were reported in other studies. Surgical sympathectomy was reported in 3 studies, with a median healing rate of 81%. Bone marrow derived cell transplantation in a single study showed 87% healing rate over (4-24 wks). Two surgical studies (of direct microsurgical revascularization N=4, and microsurgical arteriolysis, N=6), showed 100% healing of ulcers, no complications reported. Table 1. Characteristics of the extracted studies. Studydesign Patients (n) Baseline DU (n) Background therapy (%) Follow-up OutcomeHealed ulcers(%) Adipose tissue graft Autologous fat graft p 9 .15 PG, CCB—100ETA 26PDE-5i 13 8-12 wks 66 Adipose tissue grafting RCT 25 case13- Ctr 25-case13- Ctr PG- 100CCB 100 8 wks 92-case7-Ctr Adipose tissue implant p 15 15 no therapy 7 wks 100 Adipose tissue graft p 12 9 PG,CCB-100ETA 6 month 88 adipose derived SVF p 12 15 PDE-5i, ccb, PG allowed 22m 6 Adipose derived SVF p 12 15 CCB 50ETA16 6 m 63 Adipose derived SVF p 18 19 CCB 50PG 27ETA 5IS 71 24 wks 32 Sympathectomy Sympathectomy R 6 11 CCB-100 20 m 81 Sympathectomy R 13 35 PGCCBAPA 35 Sympathectomy, vascular bypass ( + vein graft R 17 26 Ccb 35APA 47PDE-i5 58 9 m 100 Bone marrow derived cells transplantation ) p 8 8 PG-62 36 m 87 Direct microsurgical revascularization R 4 4m 100 Limited microsurgical arteriolysis R 6 17 12 m 100 SVF =stromal vascular fraction P = prospective. R = retrospective. RCT= double blind randomized-controlled trial. ETA = endothelin antagonist. CCB= calcium channel blockers. APA= anti-platelet agents. PG= prostaglandins. ARB= angiotensin receptor antagonist. ACEi= ACE inhibitors. PDE-5i= PDE-5 inhibitors. IS= immunosuppression. M=median. SoC= standard of care. HR= healing rate Conclusion Our SLR has identified several surgical modalities for SSc-DUs. L-STseemed generally effective and safe for DU healing, thus Significant methodological issues emerged including small numbers of pts, lack of comparator, failure to report confounders such as background therapies and variable follow up. Future research is warranted to rigorously investigate surgical interventions for Dus. Disclosure of Interests Yossra A. Suliman: None declared, Corrado Campochiaro: None declared, Michael Hughes Speakers bureau: speaking fees from Actelion pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work, Jan Schoones: None declared, Dilia Giuggioli: None declared, Nancy Maltez: None declared, Pia Moinzadeh Speakers bureau:: speaking fees from Actelion pharmaceuticals and Boehringer Ingelheim, Laura Ross: None declared, Lorinda Chung: None declared, Yannick Allanore: None declared, Murray Baron: None declared, Christopher P Denton: None declared, Oliver Distler Shareholder of: 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)., Speakers bureau: 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)., Consultant of: 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)., Grant/research support from: 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)., Tracy Frech: None declared, Daniel Furst: None declared, Dinesh Khanna Speakers bureau: Janssen and Eicos Sciences, Inc., Paid instructor for: Janssen and Eicos Sciences, Inc., Consultant of: Janssen and Eicos Sciences, Inc., Thomas Krieg: None declared, Masataka KUWANA Speakers bureau: Speakers fees from AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, and Consultant fees from AstraZeneca, Boehringer Ingelheim, Corbus, Kissei, Mochida, outside of the submitted work., Paid instructor for: Speakers fees from AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, and Consultant fees from AstraZeneca, Boehringer Ingelheim, Corbus, Kissei, Mochida, outside of the submitted work., Consultant of: Speakers fees from AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, and Consultant fees from AstraZeneca, Boehringer Ingelheim, Corbus, Kissei, Mochida, outside of the submitted work., Marco Matucci-Cerinic: None declared, Janet Pope: None declared, Alessia Alunno: None declared
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2022-eular.3442
Language:
English
Publisher:
BMJ
Publication Date:
2022
detail.hit.zdb_id:
1481557-6
