Gene transfer
Intramuscular injections of vascular endothelial growth factor have had some encouraging preliminary results at improving collateral vessel formation.[52]Isner JM, Baumgartner I, Rauh G, et al. Treatment of thromboangiitis obliterans (Buerger's disease) by intramuscular gene transfer of vascular endothelial growth factor: preliminary clinical results. J Vasc Surg. 1998 Dec;28(6):964-73.
http://www.ncbi.nlm.nih.gov/pubmed/9845647?tool=bestpractice.com
One study of patients with critical limb ischemia (including 10 patients with Buerger disease) found a sustained decrease in ischemic ulcer size in the hepatocyte growth factor gene therapy group after 12 weeks.[53]Morishita R, Shimamura M, Takeya Y, et al. Combined analysis of clinical data on HGF gene therapy to treat critical limb ischemia in Japan. Curr Gene Ther. 2020;20(1):25-35.
https://www.doi.org/10.2174/1566523220666200516171447
http://www.ncbi.nlm.nih.gov/pubmed/32416690?tool=bestpractice.com
However, resting pain on a visual analog scale was not significantly improved compared with placebo.
Autologous bone marrow cell transplantation
Implantation of autologous bone marrow cells by multiple injections into the gastrocnemius muscle may increase collateral vessel formation. Improved ankle-brachial index, transcutaneous oxygen concentration, rest pain, pain-free walking distance, ulcer healing, and limb salvage has been reported.[54]Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomized controlled trial. Lancet. 2002 Aug 10;360(9331):427-35.
http://www.ncbi.nlm.nih.gov/pubmed/12241713?tool=bestpractice.com
[55]Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease: meta-analysis and systematic review of the literature. Atherosclerosis. 2010 Mar;209(1):10-7.
http://www.ncbi.nlm.nih.gov/pubmed/19740466?tool=bestpractice.com
Autologous bone marrow mononuclear cell (BM-MNC) implantation has been shown to reduce amputation rates in those unsuitable for angioplasty or surgical revascularization. In a nonrandomized trial, patients with Buerger disease who had rest pain and nonhealing ulcers had a 4-year amputation-free rate of 95% with BM-MNC (n=26) compared with 6% in those who did not receive BM-MNC (n=16).[56]Idei N, Soga J, Hata T, et al. Autologous bone-marrow mononuclear cell implantation reduces long-term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease. Circ Cardiovasc Interv. 2011 Feb 1;4(1):15-5.
http://circinterventions.ahajournals.org/content/4/1/15.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/21205941?tool=bestpractice.com
High-quality trials are needed to confirm the safety and efficacy of this treatment.[57]Cacione DG, do Carmo Novaes F, Moreno DH. Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease). Cochrane Database Syst Rev. 2018 Oct 31;10:CD012794.
https://www.doi.org/10.1002/14651858.CD012794.pub2
http://www.ncbi.nlm.nih.gov/pubmed/30378681?tool=bestpractice.com
Bosentan
An endothelin receptor antagonist reported to improve digital necrosis.[58]Todoli Parra JA, Hernández MM, Arrébola López MA. Efficacy of bosentan in digital ischemic ulcers. Ann Vasc Surg. 2010 Jul;24(5):690.e1-4.
http://www.ncbi.nlm.nih.gov/pubmed/20579585?tool=bestpractice.com
In one meta-analysis of patients with Buerger disease refractory to conventional treatment, a complete therapeutic response was achieved in 80% of patients treated with bosentan; 12% achieved a partial response.[59]Narváez J, García-Gómez C, Álvarez L, et al. Efficacy of bosentan in patients with refractory thromboangiitis obliterans (Buerger disease): a case series and review of the literature. Medicine (Baltimore). 2016 Nov;95(48):e5511.
https://www.doi.org/10.1097/MD.0000000000005511
http://www.ncbi.nlm.nih.gov/pubmed/27902617?tool=bestpractice.com
Guanethidine
Reduces catecholamine release by acting on the Na+-ATPase-dependent pump. Reduction of rest pain and ulceration healing have been reported with guanethidine injections into the affected limb, sometimes with the additional use of a Bier block (intravenous regional sympathetic blockade).[60]Stümpflen A, Ahmadi A, Attender M, et al. Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia. Angiology. 2000;51:115-122.
http://www.ncbi.nlm.nih.gov/pubmed/10701719?tool=bestpractice.com
[61]Paraskevas KI, Trigka AA, Samara M. Successful intravenous regional sympathetic blockade (Bier's Block) with guanethidine and lidocaine in a patient with advanced Buerger's Disease (thromboangiitis obliterans) - a case report. Angiology. 2005;56:493-496.
http://www.ncbi.nlm.nih.gov/pubmed/16079935?tool=bestpractice.com
Injections can be easily repeated if beneficial effects are seen. Data on the effectiveness of guanethidine are limited, and it is not available in many countries, including the US.