Buerger's disease - Emerging treatments

Intra-arterial thrombolysis

Revascularisation of crural vessels has been reported using intra-arterial thrombolysis, although it is not a commonly performed treatment modality in Buerger's disease.[57]

Gene transfer

Intramuscular injections of vascular endothelial growth factor have had some encouraging preliminary results at improving collateral vessel formation.[58] One study of patients with critical limb ischaemia (including 10 patients with Buerger’s disease) found a sustained decrease in ischaemic ulcer size in the hepatocyte growth factor gene therapy group after 12 weeks.[59] However, resting pain on a visual analogue 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.[60][61] Autologous bone marrow mononuclear cell (BM-MNC) implantation has been shown to reduce amputation rates in those unsuitable for angioplasty or surgical revascularisation. In a non-randomised trial, patients with Buerger's disease who had rest pain and non-healing 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).[62] High-quality trials are needed to confirm the safety and efficacy of this treatment.[63]

Bosentan

An endothelin receptor antagonist reported to improve digital necrosis.[64] In one meta-analysis of patients with Buerger’s disease refractory to conventional treatment, a complete therapeutic response was achieved in 80% of patients treated with bosentan; 12% achieved a partial response.[65]

Endovascular treatment

Technical advances including distal puncture and re-entry devices have proved beneficial in atherosclerotic peripheral arterial disease. However, their role in treating Buerger’s disease is unclear; a systematic review is in progress.[66] Buerger’s disease is thought to be a consequence of oxidative stress, immunity, and inflammatory factors, and whether this affects the endovascular outcomes seen in peripheral arterial disease (thought to be a different pathology) remains unknown.[67]

CLBS12

The US Food and Drug Administration (FDA) has granted orphan drug designation to CLBS12, an autologous CD34+ cell therapy, for the treatment of Buerger's disease. Preliminary evidence suggests that CD34+ cell therapy promotes vascular regeneration and improves outcomes in patients with critical limb ischaemia. This designation recognises the potential of CLBS12 to address unmet needs in Buerger’s disease.

Pulsed ultrasound

Low intensity pulsed ultrasound has been shown to reduce pain intensity scores in Buerger’s disease.[68]