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A Practical Approach to the Management of Digital Ulcers in Patients With Systemic SclerosisA Narrative Review

Educational Objective
To describe the approach to assessing and managing digital ulcers in systemic sclerosis and highlight unmet needs and research priorities.
1 Credit CME

Importance  Digital ulcers (DUs) occurring on the fingers in patients with systemic sclerosis (SSc) are associated with substantial pain and disability and are often challenging to treat. However, careful clinical assessment and prompt intervention (wound bed management and systemic pharmacologic treatment) may modify the clinical course.

Objectives  To provide a practical approach to the assessment and management of SSc-DUs and highlight unmet needs and research priorities.

Evidence Review  A narrative review of the extant literature was undertaken to provide a broad overview of current knowledge and augmented by expert opinion.

Findings  Half of the patients with SSc have a history of DUs, and there is a point of prevalence of approximately 10%. Digital ulcers are often very painful and affect all aspects of physical, social, and family life as well as occupation. Digital ulcers are associated with a severe disease course. Systemic sclerosis DUs, particularly those occurring on the fingertips, represent a vascular ischemic complication, although other etiopathogenic factors play an important role. To guide management, a structured clinical approach is required, including DU definition, classification, and categorization. Digital ulcers require a multidisciplinary approach with close cooperation between physicians and specialist nursing and other allied health professionals to guarantee the appropriate treatment and provide patient education. Local wound bed management is necessary for all DUs and is combined with systemic (pharmacologic) treatments. When treating a DU, the clinician should actively review the therapeutic strategy to prevent further DUs, including the level of systemic disease control, and monitor closely for the development of DU complications, including infection and progression to gangrene. Despite a wide available therapeutic armory, a number of unmet needs and challenges remain that that require resolution to optimize DU management.

Conclusions and Relevance  A practical approach to DU management, including local wound bed management and systemic treatments, is useful. Digital ulcers are of interest to a broad range of dermatologists, rheumatologists, and other physicians providing care for patients with SSc. Careful clinical assessment and prompt intervention can substantially modify the clinical course of DUs in SSc.

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Article Information

Accepted for Publication: October 27, 2020.

Published Online: May 26, 2021. doi:10.1001/jamadermatol.2021.1463

Corresponding Author: Michael Hughes, PhD, Department of Rheumatology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2JF, United Kingdom (michael.hughes-6@postgrad.manchester.ac.uk).

Author Contributions: Dr Hughes had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Hughes, El Aoufy, Denton, Khanna, Krieg, Matucci-Cerinic.

Acquisition, analysis, or interpretation of data: Hughes, Allanore.

Drafting of the manuscript: Hughes, Denton, Matucci-Cerinic.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: Hughes.

Supervision: Allanore, Khanna, Krieg, Matucci-Cerinic.

Conflict of Interest Disclosures: Dr Hughes has received speaking fees from Actelion. Dr Allanore has had consultancy relationships and/or has received research funding from Actelion, Bayer, Boehringer Ingelheim, Genentech/Roche, Inventiva, Medsenic, and Sanofi in the area of potential treatments of scleroderma and its complications. Dr Denton has received grants from Servier; grants and personal fees from GSK, Arxx Therapeutics, Roche, and CSL Behring; and personal fees from Boehringer Ingelheim, Galapagos, and Horizon. Dr Khanna has received grants from National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study and grants from Immune Tolerance Network, BMS, and Pfizer; grants and personal fees from Bayer, Horizon, Boehringer Ingelheim, and Galapagos; personal fees from Acceleron, Actelion, Amgen, AstraZeneca, Blade Therapeutics, CSL Behring, Corbus, Cytori, Genentech/Roche, GSK, Merck, Mitsubishi Tanabe Pharma, Regeneron, Sanofi-Aventis, GlaxoSmithKline, and United Therapeutics; other support from Eicos Sciences Inc; and other support from CiviBioPharma/Eicos Sciences Inc outside the submitted work. Dr Krieg has received speaking fees from Actelion. Dr Matucci-Cerinic has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, and Roche. No other disclosures were reported.

Katsumoto  TR , Whitfield  ML , Connolly  MK .  The pathogenesis of systemic sclerosis.   Annu Rev Pathol. 2011;6:509-537. doi:10.1146/annurev-pathol-011110-130312 PubMedGoogle ScholarCrossref
Denton  CP , Khanna  D .  Systemic sclerosis.   Lancet. 2017;390(10103):1685-1699. doi:10.1016/S0140-6736(17)30933-9 PubMedGoogle ScholarCrossref
Meier  FMP , Frommer  KW , Dinser  R ,  et al; EUSTAR Co-authors.  Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database.   Ann Rheum Dis. 2012;71(8):1355-1360. doi:10.1136/annrheumdis-2011-200742 PubMedGoogle ScholarCrossref
Hughes  M , Allanore  Y , Chung  L , Pauling  JD , Denton  CP , Matucci-Cerinic  M .  Raynaud phenomenon and digital ulcers in systemic sclerosis.   Nat Rev Rheumatol. 2020;16(4):208-221. doi:10.1038/s41584-020-0386-4 PubMedGoogle ScholarCrossref
Hachulla  E , Clerson  P , Launay  D ,  et al.  Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study.   J Rheumatol. 2007;34(12):2423-2430.PubMedGoogle Scholar
Bruni  C , Guiducci  S , Bellando-Randone  S ,  et al.  Digital ulcers as a sentinel sign for early internal organ involvement in very early systemic sclerosis.   Rheumatology (Oxford). 2015;54(1):72-76. doi:10.1093/rheumatology/keu296 PubMedGoogle ScholarCrossref
Amanzi  L , Braschi  F , Fiori  G ,  et al.  Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions.   Rheumatology (Oxford). 2010;49(7):1374-1382. doi:10.1093/rheumatology/keq097 PubMedGoogle ScholarCrossref
Blagojevic  J , Bellando-Randone  S , Abignano  G ,  et al; EUSTAR co-workers.  Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey.   Arthritis Res Ther. 2019;21(1):35. doi:10.1186/s13075-019-1822-1 PubMedGoogle ScholarCrossref
Bérezné  A , Seror  R , Morell-Dubois  S ,  et al.  Impact of systemic sclerosis on occupational and professional activity with attention to patients with digital ulcers.   Arthritis Care Res (Hoboken). 2011;63(2):277-285. doi:10.1002/acr.20342 PubMedGoogle ScholarCrossref
Hughes  M , Pauling  JD , Jones  J ,  et al.  Multicenter qualitative study exploring the patient experience of digital ulcers in systemic sclerosis.   Arthritis Care Res (Hoboken). 2020;72(5):723-733. doi:10.1002/acr.24127 PubMedGoogle ScholarCrossref
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. doi:10.1186/s13075-019-2080-y PubMedGoogle ScholarCrossref
Jones  J , Hughes  M , Pauling  J , Gooberman-Hill  R , Moore  AJ .  What narrative devices do people with systemic sclerosis use to describe the experience of pain from digital ulcers: a multicentre focus group study at UK scleroderma centres.   BMJ Open. 2020;10(6):e037568. doi:10.1136/bmjopen-2020-037568 PubMedGoogle Scholar
Hughes  M , Pauling  JD , Jones  J ,  et al.  Patient experiences of digital ulcer development and evolution in systemic sclerosis.   Rheumatology (Oxford). 2020;59(8):2156-2158. doi:10.1093/rheumatology/keaa037 PubMedGoogle ScholarCrossref
Hughes  M , Herrick  AL .  Digital ulcers in systemic sclerosis.   Rheumatology (Oxford). 2017;56(1):14-25. doi:10.1093/rheumatology/kew047 PubMedGoogle ScholarCrossref
Smith  V , Decuman  S , Sulli  A ,  et al.  Do worsening scleroderma capillaroscopic patterns predict future severe organ involvement? a pilot study.   Ann Rheum Dis. 2012;71(10):1636-1639. doi:10.1136/annrheumdis-2011-200780 PubMedGoogle ScholarCrossref
Cutolo  M , Herrick  AL , Distler  O ,  et al; CAP Study Investigators.  Nailfold videocapillaroscopic features and other clinical risk factors for digital ulcers in systemic sclerosis: a multicenter, prospective cohort study.   Arthritis Rheumatol. 2016;68(10):2527-2539. doi:10.1002/art.39718 PubMedGoogle ScholarCrossref
Hughes  M , Moore  T , Manning  J , Dinsdale  G , Murray  A , Herrick  AL .  Digital ulcers in systemic sclerosis are associated with microangiopathic abnormalities of perilesional skin as assessed by capillaroscopy.   Scand J Rheumatol. 2017;46(1):81-82. doi:10.1080/03009742.2016.1178802 PubMedGoogle ScholarCrossref
Hughes  M , Murray  A , Denton  CP , Herrick  AL .  Should all digital ulcers be included in future clinical trials of systemic sclerosis-related digital vasculopathy?   Med Hypotheses. 2018;116:101-104. doi:10.1016/j.mehy.2018.04.024 PubMedGoogle ScholarCrossref
Tiev  KP , Diot  E , Clerson  P ,  et al.  Clinical features of scleroderma patients with or without prior or current ischemic digital ulcers: post-hoc analysis of a nationwide multicenter cohort (ItinérAIR-Sclérodermie).   J Rheumatol. 2009;36(7):1470-1476. doi:10.3899/jrheum.081044 PubMedGoogle ScholarCrossref
Khimdas  S , Harding  S , Bonner  A , Zummer  B , Baron  M , Pope  J ; Canadian Scleroderma Research Group.  Associations with digital ulcers in a large cohort of systemic sclerosis: results from the Canadian Scleroderma Research Group registry.   Arthritis Care Res (Hoboken). 2011;63(1):142-149. doi:10.1002/acr.20336 PubMedGoogle ScholarCrossref
Hughes  M , Moore  T , Manning  J , Dinsdale  G , Herrick  ALAL , Murray  A .  A pilot study using high-frequency ultrasound to measure digital ulcers: a possible outcome measure in systemic sclerosis clinical trials?   Clin Exp Rheumatol. 2017;35(4)(suppl 106):218-219.PubMedGoogle Scholar
Li  W , Frech  TM .  The critical need for accurately defining digital ulcers in scleroderma.   J Scleroderma Relat Disord. 2017;2(2):69-71. doi:10.5301/jsrd.5000238 PubMedGoogle ScholarCrossref
Suliman  YA , Bruni  C , Johnson  SR ,  et al.  Defining skin ulcers in systemic sclerosis: systematic literature review and proposed World Scleroderma Foundation (WSF) definition.   J Scleroderma Relat Disord. 2017;2(2):115-120. doi:10.5301/jsrd.5000236 PubMedGoogle ScholarCrossref
Hughes  M , Tracey  A , Bhushan  M ,  et al.  Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: a challenge for clinical trial design.   J Scleroderma Relat Disord. 2018;3(2):170-174. doi:10.1177/2397198318764796 PubMedGoogle ScholarCrossref
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. doi:10.1136/annrheumdis-2015-208121 PubMedGoogle ScholarCrossref
Schultz  GS , Sibbald  RG , Falanga  V ,  et al.  Wound bed preparation: a systematic approach to wound management.   Wound Repair Regen. 2003;11(s1)(suppl 1):S1-S28. doi:10.1046/j.1524-475X.11.s2.1.x PubMedGoogle ScholarCrossref
Ho  M , Veale  D , Eastmond  C , Nuki  G , Belch  J .  Macrovascular disease and systemic sclerosis.   Ann Rheum Dis. 2000;59(1):39-43. doi:10.1136/ard.59.1.39 PubMedGoogle ScholarCrossref
Dinsdale  G , Moore  TL , Manning  JB ,  et al.  Tracking digital ulcers in systemic sclerosis: a feasibility study assessing lesion area in patient-recorded smartphone photographs.   Ann Rheum Dis. 2018;77(9):1382-1384. doi:10.1136/annrheumdis-2017-212829 PubMedGoogle ScholarCrossref
Simpson  V , Hughes  M , Wilkinson  J , Herrick  AL , Dinsdale  G .  Quantifying digital ulcers in systemic sclerosis: reliability of computer-assisted planimetry in measuring lesion size.   Arthritis Care Res (Hoboken). 2018;70(3):486-490. doi:10.1002/acr.23300 PubMedGoogle ScholarCrossref
Suliman  YA , Kafaja  S , Fitzgerald  J ,  et al.  Ultrasound characterization of cutaneous ulcers in systemic sclerosis.   Clin Rheumatol. 2018;37(6):1555-1561. doi:10.1007/s10067-018-3986-5 PubMedGoogle ScholarCrossref
Hughes  M , Bruni  C , Cuomo  G ,  et al  The role of ultrasound in systemic sclerosis: on the cutting edge to foster clinical and research advancement.  Published online November 19, 2020.  J Scleroderma Relat Disord. doi:10.1177/2397198320970394Google Scholar
Ruaro  B , Sulli  A , Smith  V , Paolino  S , Pizzorni  C , Cutolo  M .  Short-term follow-up of digital ulcers by laser speckle contrast analysis in systemic sclerosis patients.   Microvasc Res. 2015;101:82-85. doi:10.1016/j.mvr.2015.06.009 PubMedGoogle ScholarCrossref
Ruaro  B , Paolino  S , Pizzorni  C , Cutolo  M , Sulli  A .  Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis.   Reumatismo. 2017;69(3):134-136. doi:10.4081/reumatismo.2017.986 PubMedGoogle ScholarCrossref
Hughes  M , Wilkinson  J , Moore  T ,  et al.  Thermographic abnormalities are associated with future digital ulcers and death in patients with systemic sclerosis.   J Rheumatol. 2016;43(8):1519-1522. doi:10.3899/jrheum.151412 PubMedGoogle ScholarCrossref
Bruni  C , Ngcozana  T , Braschi  F ,  et al.  Preliminary validation of the digital ulcer clinical assessment score in systemic sclerosis.   J Rheumatol. 2019;46(6):603-608. doi:10.3899/jrheum.171486 PubMedGoogle ScholarCrossref
Ngcozana  T , Ong  VH , Denton  CP .  Improving access to digital ulcer care through nurse-led clinic: a service evaluation.   Musculoskeletal Care. 2020;18(1):92-97. doi:10.1002/msc.1433 PubMedGoogle ScholarCrossref
Hughes  M , Ong  VH , Anderson  ME ,  et al.  Consensus best practice pathway of the UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis.   Rheumatology (Oxford). 2015;54(11):2015-2024. doi:10.1093/rheumatology/kev201 PubMedGoogle ScholarCrossref
Baron  M , Chung  L , Gyger  G ,  et al.  Consensus opinion of a North American working group regarding the classification of digital ulcers in systemic sclerosis.   Clin Rheumatol. 2014;33(2):207-214. doi:10.1007/s10067-013-2460-7 PubMedGoogle ScholarCrossref
Hughes  M , Alcacer-Pitarch  B , Allanore  Y ,  et al  Digital ulcers: should debridement be a standard of care in systemic sclerosis?   Lancet Rheumatol. 2020;2(5):e302-e307. doi:10.1016/S2665-9913(19)30164-XGoogle ScholarCrossref
Lebedoff  N , Frech  TM , Shanmugam  VK ,  et al.  Review of local wound management for scleroderma-associated digital ulcers.   J Scleroderma Relat Disord. 2018;3(1):66-70. doi:10.5301/jsrd.5000268 PubMedGoogle ScholarCrossref
Giuggioli  D , Manfredi  A , Vacchi  C , Sebastiani  M , Spinella  A , Ferri  C .  Procedural pain management in the treatment of scleroderma digital ulcers.   Clin Exp Rheumatol. 2015;33(1):5-10.PubMedGoogle Scholar
Hughes  M , Alcacer-Pitarch  B , Gheorghiu  AM ,  et al.  Digital ulcer debridement in systemic sclerosis: a systematic literature review.   Clin Rheumatol. 2020;39(3):805-811. doi:10.1007/s10067-019-04924-4 PubMedGoogle ScholarCrossref
Haque  A , Wyman  M , Dargan  D ,  et al.  Hand osteomyelitis in patients with secondary Raynaud phenomenon.   J Clin Rheumatol. Published online December 14, 2020. PubMedGoogle Scholar
Giuggioli  D , Manfredi  A , Colaci  M , Lumetti  F , Ferri  C .  Scleroderma digital ulcers complicated by infection with fecal pathogens.   Arthritis Care Res (Hoboken). 2012;64(2):295-297. doi:10.1002/acr.20673 PubMedGoogle ScholarCrossref
Rademaker  M , Cooke  ED , Almond  NE ,  et al.  Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud’s phenomenon in patients with systemic sclerosis: a double blind randomised study.   BMJ. 1989;298(6673):561-564. doi:10.1136/bmj.298.6673.561 PubMedGoogle ScholarCrossref
Tingey  T , Shu  J , Smuczek  J , Pope  J .  Meta-analysis of healing and prevention of digital ulcers in systemic sclerosis.   Arthritis Care Res (Hoboken). 2013;65(9):1460-1471. doi:10.1002/acr.22018 PubMedGoogle ScholarCrossref
Hachulla  E , Hatron  PY , Carpentier  P ,  et al; SEDUCE study group.  Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study.   Ann Rheum Dis. 2016;75(6):1009-1015. doi:10.1136/annrheumdis-2014-207001 PubMedGoogle ScholarCrossref
Wigley  FM , Wise  RA , Seibold  JR ,  et al.  Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.   Ann Intern Med. 1994;120(3):199-206. Accessed September 3, 2015. doi:10.7326/0003-4819-120-3-199402010-00004 PubMedGoogle ScholarCrossref
Negrini  S , Magnani  O , Matucci-Cerinic  M ,  et al.  Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.   Clin Exp Med. 2019;19(3):357-366. doi:10.1007/s10238-019-00553-y PubMedGoogle ScholarCrossref
Bellando-Randone  S , Bruni  C , Lepri  G ,  et al.  The safety of iloprost in systemic sclerosis in a real-life experience.   Clin Rheumatol. 2018;37(5):1249-1255. doi:10.1007/s10067-018-4043-0 PubMedGoogle ScholarCrossref
Denton  CP , Hachulla  É , Riemekasten  G ,  et al; Raynaud Study Investigators.  Efficacy and safety of selexipag in adults with Raynaud’s phenomenon secondary to systemic sclerosis: a randomized, placebo-controlled, phase ii study.   Arthritis Rheumatol. 2017;69(12):2370-2379. doi:10.1002/art.40242 PubMedGoogle ScholarCrossref
Seibold  JR , Wigley  FM , Schiopu  E ,  et al  Digital ulcers in SSc treated with oral treprostinil: a randomized, double-blind, placebo-controlled study with open-label follow-up.   J Scleroderma Relat Disord. 2017;2(1):42-49. doi:10.5301/jsrd.5000232Google ScholarCrossref
Korn  JH , Mayes  M , Matucci Cerinic  M ,  et al.  Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist.   Arthritis Rheum. 2004;50(12):3985-3993. doi:10.1002/art.20676 PubMedGoogle ScholarCrossref
Matucci-Cerinic  M , Denton  CP , Furst  DE ,  et al.  Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial.   Ann Rheum Dis. 2011;70(1):32-38. doi:10.1136/ard.2010.130658 PubMedGoogle ScholarCrossref
Khanna  D , Denton  CP , Merkel  PA ,  et al; DUAL-1 Investigators; DUAL-2 Investigators.  Effect of macitentan on the development of new ischemic digital ulcers in patients with systemic sclerosis: DUAL-1 and DUAL-2 randomized clinical trials.   JAMA. 2016;315(18):1975-1988. doi:10.1001/jama.2016.5258PubMedGoogle ScholarCrossref
Chung  L , Ball  K , Yaqub  A , Lingala  B , Fiorentino  D .  Effect of the endothelin type A-selective endothelin receptor antagonist ambrisentan on digital ulcers in patients with systemic sclerosis: results of a prospective pilot study.   J Am Acad Dermatol. 2014;71(2):400-401. doi:10.1016/j.jaad.2014.04.028 PubMedGoogle ScholarCrossref
Zachariae  H , Halkier-Sørensen  L , Heickendorff  L , Zachariae  E , Hansen  HE .  Cyclosporin A treatment of systemic sclerosis.   Br J Dermatol. 1990;122(5):677-681. doi:10.1111/j.1365-2133.1990.tb07290.x PubMedGoogle ScholarCrossref
Khor  C-G , Chen  XL-F , Lin  T-S , Lu  C-H , Hsieh  S-C .  Rituximab for refractory digital infarcts and ulcers in systemic sclerosis.   Clin Rheumatol. 2014;33(7):1019-1020. doi:10.1007/s10067-014-2579-1 PubMedGoogle ScholarCrossref
Fernandes das Neves  M , Oliveira  S , Amaral  MC , Delgado Alves  J .  Treatment of systemic sclerosis with tocilizumab.   Rheumatology (Oxford). 2015;54(2):371-372. doi:10.1093/rheumatology/keu435 PubMedGoogle ScholarCrossref
Inoue  T , Yamaoka  T , Murota  H ,  et al.  Effective oral psoralen plus ultraviolet a therapy for digital ulcers with revascularization in systemic sclerosis.   Acta Derm Venereol. 2014;94(2):250-251. doi:10.2340/00015555-1678 PubMedGoogle ScholarCrossref
Fiori  G , Galluccio  F , Braschi  F ,  et al.  Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis.   Clin Exp Rheumatol. 2009;27(3)(suppl 54):51-54.PubMedGoogle Scholar
Hughes  M , Moore  T , Manning  J ,  et al.  Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate.   Microvasc Res. 2017;111:32-36. doi:10.1016/j.mvr.2016.12.008 PubMedGoogle ScholarCrossref
Hughes  M , Moore  T , Manning  J ,  et al.  A feasibility study of a novel low-level light therapy for digital ulcers in systemic sclerosis.   J Dermatolog Treat. 2019;30(3):251-257. doi:10.1080/09546634.2018.1484875 PubMedGoogle ScholarCrossref
Del Papa  N , Di Luca  G , Sambataro  D ,  et al.  Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis.   Cell Transplant. 2015;24(11):2297-2305. doi:10.3727/096368914X685636 PubMedGoogle ScholarCrossref
Del Papa  N , Di Luca  G , Andracco  R ,  et al.  Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study.   Arthritis Res Ther. 2019;21(1):7. doi:10.1186/s13075-018-1792-8 PubMedGoogle ScholarCrossref
Ishigatsubo  Y , Ihata  A , Kobayashi  H ,  et al.  Therapeutic angiogenesis in patients with systemic sclerosis by autologous transplantation of bone-marrow–derived cells.   Mod Rheumatol. 2010;20(3):263-272. doi:10.3109/s10165-010-0274-x PubMedGoogle ScholarCrossref
Nevskaya  T , Ananieva  L , Bykovskaia  S ,  et al.  Autologous progenitor cell implantation as a novel therapeutic intervention for ischaemic digits in systemic sclerosis.   Rheumatology (Oxford). 2009;48(1):61-64. doi:10.1093/rheumatology/ken407 PubMedGoogle ScholarCrossref
Daumas  A , Magalon  J , Jouve  E ,  et al.  Long-term follow-up after autologous adipose-derived stromal vascular fraction injection into fingers in systemic sclerosis patients.   Curr Res Transl Med. 2017;65(1):40-43. doi:10.1016/j.retram.2016.10.006 PubMedGoogle ScholarCrossref
Guiducci  S , Porta  F , Saccardi  R ,  et al.  Autologous mesenchymal stem cells foster revascularization of ischemic limbs in systemic sclerosis: a case report.   Ann Intern Med. 2010;153(10):650-654. doi:10.7326/0003-4819-153-10-201011160-00007 PubMedGoogle ScholarCrossref
Giuggioli  D , Manfredi  A , Colaci  M , Lumetti  F , Ferri  C .  Osteomyelitis complicating scleroderma digital ulcers.   Clin Rheumatol. 2013;32(5):623-627. doi:10.1007/s10067-012-2161-7 PubMedGoogle ScholarCrossref
Haque  A , Cleveland  T , Powell  L , Stephenson  S , Hughes  M , Kilding  R .  Large vessel disease as a potentially treatable cause of devastating critical digital ischaemia in systemic sclerosis.   Clin Rheumatol. 2020;39(9):2823-2824. doi:10.1007/s10067-020-05128-x PubMedGoogle ScholarCrossref
Kowal-Bielecka  O , Fransen  J , Avouac  J ,  et al; EUSTAR Coauthors.  Update of EULAR recommendations for the treatment of systemic sclerosis.   Ann Rheum Dis. 2017;76(8):1327-1339. doi:10.1136/annrheumdis-2016-209909 PubMedGoogle ScholarCrossref
Denton  CP , Hughes  M , Gak  N ,  et al; BSR and BHPR Standards, Guidelines and Audit Working Group.  BSR and BHPR guideline for the treatment of systemic sclerosis.   Rheumatology (Oxford). 2016;55(10):1906-1910. doi:10.1093/rheumatology/kew224 PubMedGoogle ScholarCrossref
Ambach  A , Seo  W , Bonnekoh  B , Gollnick  H .  Low-dose combination therapy of severe digital ulcers in diffuse progressive systemic sclerosis with the endothelin-1 receptor antagonist bosentan and the phosphodiesterase V inhibitor sildenafil.   J Dtsch Dermatol Ges. 2009;7(10):888-891. doi:10.1111/j.1610-0387.2009.07057.x PubMedGoogle Scholar
Moinzadeh  P , Hunzelmann  N , Krieg  T .  Combination therapy with an endothelin-1 receptor antagonist (bosentan) and a phosphodiesterase V inhibitor (sildenafil) for the management of severe digital ulcerations in systemic sclerosis.   J Am Acad Dermatol. 2011;65(3):e102-e104. doi:10.1016/j.jaad.2011.04.029 PubMedGoogle ScholarCrossref
Ladak  K , Pope  JE .  A review of the effects of statins in systemic sclerosis.   Semin Arthritis Rheum. 2016;45(6):698-705. doi:10.1016/j.semarthrit.2015.10.013 PubMedGoogle ScholarCrossref
Abou-Raya  A , Abou-Raya  S , Helmii  M .  Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers.   J Rheumatol. 2008;35(9):1801-1808.PubMedGoogle Scholar
Beckett  VL , Conn  DL , Fuster  V ,  et al.  Trial of platelet-inhibiting drug in scleroderma: double-blind study with dipyridamole and aspirin.   Arthritis Rheum. 1984;27(10):1137-1143. doi:10.1002/art.1780271009 PubMedGoogle ScholarCrossref
Denton  CP , Howell  K , Stratton  RJ , Black  CM .  Long-term low molecular weight heparin therapy for severe Raynaud’s phenomenon: a pilot study.   Clin Exp Rheumatol. 2000;18(4):499-502.PubMedGoogle Scholar
Momeni  A , Sorice  SC , Valenzuela  A , Fiorentino  DF , Chung  L , Chang  J .  Surgical treatment of systemic sclerosis—is it justified to offer peripheral sympathectomy earlier in the disease process?   Microsurgery. 2015;35(6):441-446. doi:10.1002/micr.22379 PubMedGoogle ScholarCrossref
Chiou  G , Crowe  C , Suarez  P , Chung  L , Curtin  C , Chang  J .  Digital sympathectomy in patients with scleroderma: an overview of the practice and referral patterns and perceptions of rheumatologists.   Ann Plast Surg. 2015;75(6):637-643. doi:10.1097/SAP.0000000000000614 PubMedGoogle ScholarCrossref
Satteson  ES , Chung  MP , Chung  LS , Chang  J .  Microvascular hand surgery for digital ischemia in scleroderma.   J Scleroderma Relat Disord. 2020;5(2):130-136. doi:10.1177/2397198319863565Google ScholarCrossref
Żebryk  P , Puszczewicz  MJ .  Botulinum toxin A in the treatment of Raynaud’s phenomenon: a systematic review.   Arch Med Sci. 2016;12(4):864-870. doi:10.5114/aoms.2015.48152 PubMedGoogle Scholar
Motegi  S , Yamada  K , Toki  S ,  et al.  Beneficial effect of botulinum toxin A on Raynaud’s phenomenon in Japanese patients with systemic sclerosis: a prospective, case series study.   J Dermatol. 2016;43(1):56-62. doi:10.1111/1346-8138.13030 PubMedGoogle ScholarCrossref
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