Buerger's disease medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]
Overview
There is no treatment for Buerger's disease. In order to prevent progression and control symptoms smoking cessation is crucial. Smoking cessation does not reverse damage already caused. Pharmacologic medical therapies for Buerger's disease include smoking cessation, palliative treatments, prostaglandin analogs and phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor anatagonists, compression therapy and some experimental therapies. It should be noted, however, that these therapies are purely palliative and do not reverse previous damage caused.
Medical Therapy
Pharmacologic medical therapies for Buerger's disease include smoking cessation, palliative treatments, prostaglandin analogs and phosphodiesterase inhibitors, calcium channel blockers, endothelin receptor anatagonists, compression therapy and some experimental therapies. It should be noted, however, that these therapies are purely palliative and do not reverse previous damage caused.
Smoking cessation
- Smoking cessation is crucial to the management of Buerger's disease. Not only does smoking cessation halt progression but also controls pain symptoms and decreases the risk of amputation.
- The patient may, however, still suffer from intermittent cluadication or Reynaud's phenomenon.
- Complete abstinence from smoking is a must as Buerger's disease in susceptible individuals can be triggered by a single cigarette.
- Any anti-smoking aid containing nicotine such as transdermal patches or gum must be avoided as they may also trigger the disease.
- Anti-smoking aids such as bupropion or varenicline may be of use and do not contribute to disease progression.
- A patient that claims to have stopped smoking but continues to suffer symptoms of active disease should be tested for urinary nicotine and cotinine.
- Previous studies have demonstrated that only 50% of patients with Buerger's disease are able to quit smoking. In these patients, nicotine dependence treatment may be sought.
Iloprost
- Iloprost is a prostaglandin analog and is available in an IV and oral form.
- Iloprost is especially effective in the intravenous form at reducing pain symptoms, better than low dose aspirin or lumbar sympathectomy.
- Iloprost can facilitate smoking cessation and may be used to manage resting pain symptoms in those patients with critical limb ischemia.
- Iloprost may also hasten ulcer healing.
Calcium channel blockers
Calcium channel blockers are frequently used to manage vasospasm associated with the Raynaud phenomenon. When significant vasospasm is present in patients with thromboangiitis obliterans, calcium channel blocking agents such as nifedipine, nicardipine or amlodipine may similarly be used [4] (See "Initial treatment of the Raynaud phenomenon", section on 'Calcium channel blockers'.)
Intermittent pneumatic compression
Application of intermittent pneumatic compression (IPC) to the foot and calf augments popliteal artery flow through a sharp decrease in peripheral arterial resistance manifested by increases in peak systolic and end diastolic flow velocities on Doppler ultrasound [73].
Intermittent pneumatic compression enhances calf inflow in patients with intermittent claudication or critical limb ischemia. In one study, complete healing of ischemic ulcers was demonstrated in patients with small vessel occlusive diseases such as scleroderma, CREST and thromboangiitis obliterans [74]. We utilize this therapy in patients with painful ulcerations when there is no viable revascularization option. It is useful in decreasing pain even before complete ulcer healing occurs. While there are limited studies, specifically in thromboangiitis obliterans, studies have demonstrated efficacy in small vessel occlusive disease of many etiologies. (See 'Revascularization' below.)
Experimental therapies
A number of additional therapies have been studied or are under active clinical investigation [46]. Some of these are highlighted below:
●Therapeutic angiogenesis has been evaluated for treatment of peripheral artery disease and this therapy may improve the ischemic manifestations of thromboangiitis obliterans. Short-term results of therapeutic angiogenesis using growth factors or autologous bone marrow have been promising, but longer term studies are needed.
•In one trial of six patients with nonhealing wounds (>1 month), intramuscular vascular endothelial growth factor (VEGF) 165 was injected into seven affected limbs [75]. Ulcers completely healed in three of five limbs. In the other two patients, nocturnal rest pain was relieved, although both continued to have claudication. In all seven limbs, perfusion was improved on magnetic resonance imaging and newly visible collateral vessels were seen on contrast angiography.
•A second phase one trial tested the safety of intramuscular gene transfer by using naked plasmid DNA encoding the gene for VEGF in seven patients with thromboangiitis obliterans [76]. Ischemic pain in the affected limb was relieved or improved markedly in six of seven patients, and ischemic ulcers healed or improved in four of six patients.
●Cell-based therapy with autologous bone marrow mononuclear cell implantation has also been used with some degree of success [77]. A meta-analysis indicates that intramuscular autologous bone marrow cell therapy is a feasible, relatively safe and potentially effective therapeutic strategy for patients with severe peripheral artery disease who are not candidates for traditional revascularization [78]. The therapeutic angiogenesis by cell transplantation (TACT) trial, which included patients with thromboangiitis obliterans, randomly assigned patients to autologous bone marrow mononuclear cell injection versus placebo [79]. Significant improvements were seen in leg pain scale, ulcer size and pain-free walking distance that were maintained at two years after therapy. Other available small nonrandomized studies have shown similar short-term improvements [80-83]. A confounding factor for many of these studies is the fact that, in addition to receiving therapy, many of the patients stopped smoking.
●Immunoabsorption therapy was tested in a pilot study of 10 patients. The treatment was tolerated without side effects. Pain intensity decreased rapidly from a mean of 7.7/10.0 before treatment to 2.0/10.0 at the second day of five consecutive days of therapy [84]. One month after immunoabsorption, all patients were without pain, an effect that persisted over the follow-up period of six months. Healing of ischemic ulcerations was observed in all patients during follow-up. Six of the ten patients were studies were active smokers and smoking habits were reported not to change throughout the course of the study. Although the results are encouraging, the sample size of this observational study was quite small; a randomized trial would be needed to prove efficacy.
●Another method of stimulating angiogenesis using a Kirschner wire placed in the medullary canal of the tibia was used in six patients with thromboangiitis obliterans [85]. At a mean follow-up of 19 months, significant improvements were seen in symptoms with reduced rest pain, increased pain-free walking distance and ulcer healing. Most studies have not reported significant adverse events to angiogenic therapy; however, in one study, four of eight patients suffered significant clinical events underscoring the need for long-term monitoring [86].
●Bosentan, which is an endothelin receptor antagonist, was used to treat 12 patients with thromboangiitis obliterans and ischemic ulceration or rest pain [87]. An increase in distal flow was observed in 10 out of the 12 patients on magnetic resonance and digital subtraction arteriography and clinical improvement was observed in 12 of the 13 extremities; however, 2 extremities subsequently required amputation. In a separate series of 26 patients, a complete therapeutic response was achieved in 80 percent of patients, whereas a partial response was observed in 12 percent [88]. No significant differences were found for bosentan efficacy when comparing patients who gave up smoking with those who were unable to completely abstain from smoking during follow-up.
●Cilostazol is a phosphodiesterase inhibitor that suppresses platelet aggregation and is a direct arterial vasodilator [89]. It is often used in the treatment of peripheral artery disease. In one small study, flow improvements measured in response to reactive hyperemia were significantly increased after two weeks of cilostazol therapy [90]. Case reports treating patients with digital ischemia with cilostazol have reported improvements in digit pain and ulceration [91].
Management of ulcers
Digit ulcerations are managed as with other ischemic wounds, debridement and moist dressing. Negative pressure wound therapy is becoming popular for the management of open wounds and has been used in the management of open wounds associated with thromboangiitis obliterans [64]. General considerations for the clinical assessment and management of open wounds are discussed in elsewhere. (See "Clinical assessment of wounds" and "Negative pressure wound therapy".)