Locoregional Treatments for Digital Ulcers in Systemic Sclerosis: A Systematic Review
DOI:
https://doi.org/10.2340/00015555-3839Keywords:
systemic sclerosis, digital ulcers, systematic review, botulinum toxin, fat-derived cellsAbstract
The management of digital ulcers in systemic sclerosis is difficult. While the 2017 European League Against Rheumatism (EULAR) guidelines clearly defined the use of systemic therapies for digital ulcers, little is known about the efficacy of locoregional treatments. The aim of this review is to systematically assess the spectrum of published locoregional therapies for digital ulcers. A total of 58 studies were included. Among the different locoregional treatment strategies described, injections of fat-derived cells and botulinum toxin showed promising results in the reduction of pain and the number of digital ulcers. By contrast, this review found that sympathectomy yielded disappointing results, with low rates of effectiveness and frequent recurrence. For other treatments, such as hyperbaric oxygen therapy, phototherapy (ultraviolet A), low-level light therapy, intermittent compression, Waon therapy, extracorporeal shockwave, vitamin E gel, and topical dimethyl sulphoxide, the conflicting results or limited published data reflected the low level of evidence. Larger randomized clinical trials are required to confirm the validity of promising techniques.
Downloads
References
Denton CP, Khanna D. Systemic sclerosis. Lancet 2017; 390: 1685-1699.
DOI: https://doi.org/10.1016/S0140-6736(17)30933-9
Meunier P, Dequidt L, Barnetche T, Lazaro E, Duffau P, Richez C, et al. Increased risk of mortality in systemic sclerosis-associated digital ulcers: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2019; 33: 405-409.
DOI: https://doi.org/10.1111/jdv.15114
Hughes M, Herrick AL. Digital ulcers in systemic sclerosis. Rheumatol Oxf Engl 2017; 56: 14-25.
DOI: https://doi.org/10.1093/rheumatology/kew047
Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati I, Czirjak L, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 2009; 68: 620-628.
DOI: https://doi.org/10.1136/ard.2008.096677
Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76: 1327-1339.
DOI: https://doi.org/10.1136/annrheumdis-2016-209909
Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 2004; 50: 3985-3993.
DOI: https://doi.org/10.1002/art.20676
Matucci-Cerinic M, Denton CP, Furst DE, Mayes MD, Hsu VM, Carpentier P, 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: 32-38.
DOI: https://doi.org/10.1136/ard.2010.130658
Del Papa N, Di Luca G, Andracco R, Zaccara E, Maglione W, Pignataro F, 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: 7.
DOI: https://doi.org/10.1186/s13075-018-1792-8
Bello RJ, Cooney CM, Melamed E, Follmar K, Yenokyan G, Leatherman G, et al. The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud's phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol 2017; 69: 1661-1669.
DOI: https://doi.org/10.1002/art.40123
Motegi S-I, Uehara A, Yamada K, Sekiguchi A, Fujiwara C, Toki S, et al. Efficacy of botulinum toxin B injection for Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis. Acta Derm Venereol 2017; 97: 843-850.
DOI: https://doi.org/10.2340/00015555-2665
Hassanien M, Rashad S, Mohamed N, Elawamy A, Ghaly MS. Non-invasive oxygen-ozone therapy in treating digital ulcers of patients with systemic sclerosis. Acta Reumatol Port 2018; 43: 210-216.
Williams HJ, Furst DE, Dahl SL, Steen VD, Marks C, Alpert EJ, et al. Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis. Arthritis Rheum 1985; 28: 308-314.
DOI: https://doi.org/10.1002/art.1780280311
Ishii T, Kawaguchi Y, Ishikawa O, Takasaawa N, Kodera T, Yasuoka H, et al. Non-randomized controlled trial to evaluate the effect of extracorporeal shock wave therapy on digital ulcers in systemic sclerosis. Available from: https://acrabstracts.org/abstract/non-randomized-controlled-trial-to-evaluate-the-effect-of-extracorporeal-shock-wave-therapy-on-digital-ulcers-in-systemic-sclerosis/.
Takahashi M, Izawa A, Ishigatsubo Y, Fujimoto K, Miyamoto M, Horie T, et al. Therapeutic neovascularization by the implantation of autologous mononuclear cells in patients with connective tissue diseases. Curr Pharm Des 2009; 15: 2778-2783.
DOI: https://doi.org/10.2174/138161209788923813
Takagi G, Miyamoto M, Tara S, Kirinoki-Ichikawa S, Kubota Y, Hada T, et al. Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study. Rheumatology 2014; 53: 854-859.
DOI: https://doi.org/10.1093/rheumatology/ket432
Nevskaya T, Ananieva L, Bykovskaia S, Eremin I, Karandashov E, Khrennikov J, et al. Autologous progenitor cell implantation as a novel therapeutic intervention for ischaemic digits in systemic sclerosis. Rheumatol Oxf Engl 2009; 48: 61-64.
DOI: https://doi.org/10.1093/rheumatology/ken407
Ishigatsubo Y, Ihata A, Kobayashi H, Hama M, Kirino Y, Ueda A, et al. Therapeutic angiogenesis in patients with systemic sclerosis by autologous transplantation of bone-marrow-derived cells. Mod Rheumatol 2010; 20: 263-272.
DOI: https://doi.org/10.3109/s10165-010-0274-x
Kamata Y, Takahashi Y, Iwamoto M, Matsui K, Murakami Y, Muroi K, et al. Local implantation of autologous mononuclear cells from bone marrow and peripheral blood for treatment of ischaemic digits in patients with connective tissue diseases. Rheumatology (Oxford) 2007; 46: 882-884.
DOI: https://doi.org/10.1093/rheumatology/kel436
Van Rhijn-Brouwer FCC, Gremmels H, Fledderus JO, Schuurman AH, Bonte-Mineur F, Vonk MC, et al. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol. BMJ Open 2018; 8: e020479.
DOI: https://doi.org/10.1136/bmjopen-2017-020479
Granel B, Daumas A, Jouve E, Harlé J-R, Nguyen P-S, Chabannon C, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis 2015; 74: 2175-2182.
DOI: https://doi.org/10.1136/annrheumdis-2014-205681
Daumas A, Magalon J, Jouve E, Truillet R, Casanova D, Giraudo L, et al. Long-term follow-up after autologous adipose-derived stromal vascular fraction injection into fingers in systemic sclerosis patients. Fundam Clin Pharmacol 2017; 31: 65.
DOI: https://doi.org/10.1016/j.retram.2016.10.006
Del Papa N, Di Luca G, Sambataro D, Zaccara E, Maglione W, Gabrielli A, 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: 2297-2305.
DOI: https://doi.org/10.3727/096368914X685636
Bank J, Fuller SM, Henry GI, Zachary LS. Fat grafting to the hand in patients with Raynaud phenomenon: a novel therapeutic modality. Plast Reconstr Surg 2014; 133: 1109-1118.
DOI: https://doi.org/10.1097/PRS.0000000000000104
Faggioli P, Saporiti E, Falaschi M, Mazzone A, Moscatelli A. Autologous fat grafting as treatment of scleroderma-induced digital ulcers and perioral sclerosis. Experience of a single center. Ann Rheum Dis 2015; 74: 1139.
DOI: https://doi.org/10.1136/annrheumdis-2015-eular.5786
Bene MD, Pozzi MR, Rovati L, Mazzola I, Erba G, Bonomi S. Autologous fat grafting for scleroderma-induced digital ulcers. An effective technique in patients with systemic sclerosis. Handchir Mikrochir Plast Chir 2014; 46: 242-247.
DOI: https://doi.org/10.1055/s-0034-1376970
Serri J, Legré R, Veit V, Guardia C, Gay A-M. Intérêt de la toxine botulinique de type A dans le traitement des syndromes de Raynaud sévères secondaires à la sclérodermie systémique. Ann Chir Plast Esthét 2013; 58: 658-662.
DOI: https://doi.org/10.1016/j.anplas.2011.11.001
Uppal L, Dhaliwal K, Butler PE. A prospective study of the use of botulinum toxin injections in the treatment of Raynaud's syndrome associated with scleroderma. J Hand Surg Eur Vol 2014; 39: 876-880.
DOI: https://doi.org/10.1177/1753193413516242
Medina S, Gómez-Zubiaur A, Valdeolivas-Casillas N, Polo-Rodríguez I, Ruíz L, Izquierdo C, et al. Botulinum toxin type A in the treatment of Raynaud's phenomenon: a three-year follow-up study. Eur J Rheumatol 2018; 5: 224-229.
DOI: https://doi.org/10.5152/eurjrheum.2018.18013
Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud's phenomenon. J Hand Surg 2009; 34: 446-452.
DOI: https://doi.org/10.1016/j.jhsa.2008.11.026
Motegi S, Yamada K, Toki S, Uchiyama A, Kubota Y, Nakamura T, 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: 56-62.
DOI: https://doi.org/10.1111/1346-8138.13030
Van Beek AL, Lim PK, Gear AJL, Pritzker MR. Management of vasospastic disorders with botulinum toxin A. Plast Reconstr Surg 2007; 119: 217-226.
DOI: https://doi.org/10.1097/01.prs.0000244860.00674.57
Motegi S-I, Sekiguchi A, Saito S, Ishibuchi H, Kishi C, Yasuda M, et al. Successful treatment of Raynaud's phenomenon and digital ulcers in systemic sclerosis patients with botulinum toxin B injection: assessment of peripheral vascular disorder by angiography and dermoscopic image of nail fold capillary. J Dermatol 2018; 45: 349-352.
DOI: https://doi.org/10.1111/1346-8138.14140
Souk J-W, Kim H-S. Effects of botulinum toxin injection on systemic sclerosis-related digital ulcers. Korean J Intern Med 2019; 34: 1169-1170.
DOI: https://doi.org/10.3904/kjim.2018.199
Berk-Krauss J, Christman MP, Franks A, Sicco KL, Liebman TN. Botulinum toxin for treatment of Raynaud phenomenon in CREST syndrome. Dermatol Online J 2018; 24: 13030/qt9zr1318w.
DOI: https://doi.org/10.5070/D32412042444
Blaise S, Roustit M, Forli A, Imbert B, Cracowski J-L. Non-healing ischaemic digital ulcer in a systemic sclerosis patient: a challenging clinical case. Int Wound J 2017; 14: 978-981.
DOI: https://doi.org/10.1111/iwj.12742
Mirasoglu B, Bagli BS, Aktas S. Hyperbaric oxygen therapy for chronic ulcers in systemic sclerosis - case series. Int J Dermatol 2017; 56: 636-640.
DOI: https://doi.org/10.1111/ijd.13570
Poirier E, Wind H, Cordel N. Efficacité de l'oxygénothérapie hyperbare dans le traitement d'un ulcère nécrotique d'orteil au cours d'une sclérodermie systémique. Ann Dermatol Vénéréologie 2017; 144: 55-59.
DOI: https://doi.org/10.1016/j.annder.2016.06.007
Ueno T, Omi T, Uchida E, Yokota H, Kawana S. Evaluation of hyperbaric oxygen therapy for chronic wounds. J Nippon Med Sch 2014; 81: 4-11.
DOI: https://doi.org/10.1272/jnms.81.4
Gerodimos C, Stefanidou S, Kotsiou M, Melekos T, Mesimeris T. Hyperbaric oxygen treatment of intractable ulcers in a systemic sclerosis patient. Aristotle University Med 2013; 40: 4.
Markus YM, Bell MJ, Evans AW. Ischemic scleroderma wounds successfully treated with hyperbaric oxygen therapy. J Rheumatol 2006; 33: 1694-1696.
Dowling GB, Copeman PW, Ashfield R. Raynaud's phenomenon in scleroderma treated with hyperbaric oxygen. Proc R Soc Med 1967; 60: 1268-1269.
DOI: https://doi.org/10.1177/003591576706001211
Greengrass RA, Feinglass NG, Murray PM, Trigg SD. Continuous regional anesthesia before surgical peripheral sympathectomy in a patient with severe digital necrosis associated with Raynaud's phenomenon and scleroderma. Reg Anesth Pain Med 2003; 28: 354-358.
DOI: https://doi.org/10.1016/S1098-7339(03)00186-X
Volchok J, Santamarina R, Sadighi P. Transaxillary thoracoscopically assisted sympathectomy for nonhealing ulcers in scleroderma: a case report of successful treatment. Curr Surg 2005; 62: 348-350.
DOI: https://doi.org/10.1016/j.cursur.2004.09.010
Gahhos F, Ariyan S, Frazier WH, Cuono CB. Management of sclerodermal finger ulcers. J Hand Surg Am 1984; 9: 320-327.
DOI: https://doi.org/10.1016/S0363-5023(84)80216-6
Ruch DS, Holden M, Smith BP, Smith TL, Koman LA. Periarterial sympathectomy in scleroderma patients: intermediate-term follow-up. J Hand Surg Am 2002; 27: 258-264.
DOI: https://doi.org/10.1053/jhsu.2002.29483
Hartzell TL, Makhni EC, Sampson C. Long-term results of periarterial sympathectomy. J Hand Surg Am 2009; 34: 1454-1460.
DOI: https://doi.org/10.1016/j.jhsa.2009.05.003
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: 441-446.
DOI: https://doi.org/10.1002/micr.22379
Stratton R, Howell K, Goddard N, Black C. Digital sympathectomy for ischaemia in scleroderma. Br J Rheumatol 1997; 36: 1338-1339.
DOI: https://doi.org/10.1093/rheumatology/36.12.1338
Tomaino MM, Goitz RJ, Medsger TA. Surgery for ischemic pain and Raynaud's' phenomenon in scleroderma: a description of treatment protocol and evaluation of results. Microsurgery 2001; 21: 75-79.
DOI: https://doi.org/10.1002/micr.1013
Ward WA, Van Moore A. Management of finger ulcers in scleroderma. J Hand Surg Am 1995; 20: 868-872.
DOI: https://doi.org/10.1016/S0363-5023(05)80446-0
O'Brien BM, Kumar PA, Mellow CG, Oliver TV. Radical microarteriolysis in the treatment of vasospastic disorders of the hand, especially scleroderma. J Hand Surg Br 1992; 17: 447-452.
DOI: https://doi.org/10.1016/S0266-7681(05)80272-4
Tham S, Grossman JA. Limited microsurgical arteriolysis for complications of digital vasospasm. J Hand Surg Br 1997; 22: 359-361.
DOI: https://doi.org/10.1016/S0266-7681(97)80402-0
Jones NF, Imbriglia JE, Steen VD, Medsger TA. Surgery for scleroderma of the hand. J Hand Surg Am 1987; 12: 391-400.
DOI: https://doi.org/10.1016/S0363-5023(87)80012-6
McCall TE, Petersen DP, Wong LB. The use of digital artery sympathectomy as a salvage procedure for severe ischemia of Raynaud's disease and phenomenon. J Hand Surg Am 1999; 24: 173-177.
DOI: https://doi.org/10.1053/jhsu.1999.jhsu24a0173
Flatt AE. Digital artery sympathectomy. J Hand Surg Am 1980; 5: 550-556.
DOI: https://doi.org/10.1016/S0363-5023(80)80104-3
Van den Broeck D, Coessens BC, Peretz A. On surgical microarteriolysis for treatment of Raynaud's phenomenon in scleroderma. Br J Rheumatol 1997; 36: 706-707.
DOI: https://doi.org/10.1093/rheumatology/36.6.706
Wasserman A, Brahn E. Systemic sclerosis: bilateral improvement of Raynaud's phenomenon with unilateral digital sympathectomy. Semin Arthritis Rheum 2010; 40: 137-146.
DOI: https://doi.org/10.1016/j.semarthrit.2009.08.002
Hafner J, Santa DD, Zuber C, Christen Y, Bounameaux H. Digital sympathectomy (mictoarteriolysis) in the treatment of severe Raynaud's phenomenon secondary to systemic sclerosis. Br J Dermatol 1997; 137: 1019-1020.
DOI: https://doi.org/10.1111/j.1365-2133.1997.tb01576.x
Agarwal J, Zachary L. Digital sympathectomy of the lower extremity: a novel approach to toe salvage. Plast Reconstr Surg 2005; 116: 1098-1102.
DOI: https://doi.org/10.1097/01.prs.0000178795.21651.cc
El-Gammal TA, Blair WF. Digital periarterial sympathectomy for ischaemic digital pain and ulcers. J Hand Surg 1991; 16: 382-385.
DOI: https://doi.org/10.1016/0266-7681(91)90007-B
Koman LA, Smith BP, Pollock FE, Smith TL, Pollock D, Russell GB. The microcirculatory effects of peripheral sympathectomy. J Hand Surg Am 1995; 20: 709-717.
DOI: https://doi.org/10.1016/S0363-5023(05)80419-8
Tomaino MM, King J, Medsger T. Rationale for and efficacy of digital arterial reconstruction in scleroderma: report of two cases. J Reconstr Microsurg 2002; 18: 263-268.
DOI: https://doi.org/10.1055/s-2002-30181
Comte C, Bessis D, Picot E, Peyron J-L, Guillot B, Dereure O. Traitement des acrosyndromes des connectivites par photothérapie UVA-1. Etude ouverte de 11 cas. Ann Dermatol Venereol 2009; 136: 323-329.
DOI: https://doi.org/10.1016/j.annder.2008.12.022
Inoue T, Yamaoka T, Murota H, Yokomi A, Tanemura A, Igawa K, et al. Effective oral psoralen plus ultraviolet a therapy for digital ulcers with revascularization in systemic sclerosis. Acta Derm Venereol 2014; 94: 250-251.
DOI: https://doi.org/10.2340/00015555-1678
Saito S, Ishii T, Kamogawa Y, Watanabe R, Shirai T, Fujita Y, et al. Extracorporeal shock wave therapy for digital ulcers of systemic sclerosis: a phase 2 pilot study. Tohoku J Exp Med 2016; 238: 39-47.
DOI: https://doi.org/10.1620/tjem.238.39
Hughes M, Moore T, Manning J, Wilkinson J, Watson S, Samraj P, et al. A feasibility study of a novel low-level light therapy for digital ulcers in systemic sclerosis. J Dermatolog Treat 2019; 30: 251-257.
DOI: https://doi.org/10.1080/09546634.2018.1484875
Fiori G, Galluccio F, Braschi F, Amanzi L, Miniati I, Conforti ML, et al. Vitamin E gel reduces time of healing of digital ulcers in systemic sclerosis. Clin Exp Rheumatol 2009; 27: 51-54.
Nishijima C, Inaoki M. Digital ulcer in systemic sclerosis successfully treated with Waon therapy. Int J Rheum Dis 2013; 16: 102-104.
DOI: https://doi.org/10.1111/1756-185X.12001
Hughes M, Moore T, Manning J, Wilkinson J, Dinsdale G, Roberts C, 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: https://doi.org/10.1016/j.mvr.2016.12.008
Murray AK, Moore TL, King TA, Herrick AL. Vasodilator iontophoresis a possible new therapy for digital ischaemia in systemic sclerosis? Rheumatology 2008; 47: 76-79.
DOI: https://doi.org/10.1093/rheumatology/kem314
Chung L, Fiorentino D. A pilot trial of treprostinil for the treatment and prevention of digital ulcers in patients with systemic sclerosis. J Am Acad Dermatol 2006; 54: 880-882.
DOI: https://doi.org/10.1016/j.jaad.2006.02.004
Roustit M, Gaillard-Bigot F, Blaise S, Stanke-Labesque F, Cracowski C, Seinturier C, et al. Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept study. Clin Pharmacol Ther 2014; 95: 439-445.
DOI: https://doi.org/10.1038/clpt.2013.255
Generali JA, Cada DJ. Off-label drug uses: nitroglycerin (transdermal): Raynaud phenomenon. Hosp Pharm 2012; 47: 924-926.
DOI: https://doi.org/10.1310/hpj4712-924
Coleman SR. Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 2006; 118: 108S-120S.
DOI: https://doi.org/10.1097/01.prs.0000234610.81672.e7
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13: 4279-4295.
DOI: https://doi.org/10.1091/mbc.e02-02-0105
Nguyen A, Guo J, Banyard DA, Fadavi D, Toranto JD, Wirth GA, et al. Stromal vascular fraction: a regenerative reality? Part 1: Current concepts and review of the literature. J Plast Reconstr Aesthet Surg 2016; 69: 170-179.
DOI: https://doi.org/10.1016/j.bjps.2015.10.015
Griffin M, Ryan CM, Pathan O, Abraham D, Denton CP, Butler PEM. Characteristics of human adipose derived stem cells in scleroderma in comparison to sex and age matched normal controls: implications for regenerative medicine. Stem Cell Res Ther 2017; 8: 23.
DOI: https://doi.org/10.1186/s13287-016-0444-7
Daumas A, Eraud J, Hautier A, Sabatier F, Magalon G, Granel B. Potentialités et intérêt du tissu adipeux dans la sclérodermie. Rev Med Interne 2013; 34: 763-769.
DOI: https://doi.org/10.1016/j.revmed.2013.08.007
Magalon G, Daumas A, Sautereau N, Magalon J, Sabatier F, Granel B. Regenerative approach to scleroderma with fat grafting. Clin Plast Surg 2015; 42: 353-364.
DOI: https://doi.org/10.1016/j.cps.2015.03.009
Magalon J, Daumas A, Veran J, Magalon G, Rossi P, Granel B, et al. Autologous adipose tissue-derived cells: are we talking about adipose derived stem cells, stromal vascular fraction, or Coleman fat grafting? Cell Transplant 2015; 24: 2667-2668.
DOI: https://doi.org/10.3727/096368915X687552
Del Papa N, Di Luca G, Sambataro D, Zaccara E, Maglione W, Gabrielli A, et al. Reply to J. Magalon et al. Cell Transplant 2015; 24: 2669-2670.
DOI: https://doi.org/10.3727/096368915X688218
Stone AV, Koman LA, Callahan MF, Eckman DM, Smith BP, Plate JF, et al. The effect of botulinum neurotoxin-A on blood flow in rats: a potential mechanism for treatment of Raynaud phenomenon. J Hand Surg Am 2012; 37: 795-802.
DOI: https://doi.org/10.1016/j.jhsa.2012.01.021
Schweizer DF, Schweizer R, Zhang S, Kamat P, Contaldo C, Rieben R, et al. Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps. J Surg Res 2013; 184: 1205-1213.
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 Ingrid Costedoat, Maeva Masson, Thomas Barnetche, Pierre Duffau, Estibaliz Lazaro, Christophe Richez, Julien Seneschal, Marie-Elise Truchetet
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.