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
The mainstay of treatment for Buerger's disease is smoking cessation. Smoking cessation prevents disease progression but not not reverse damage already caused.
Medical Therapy
- Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
- Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
- Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
- Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Disease Name
- 1 Stage 1 - Name of stage
- 1.1 Specific Organ system involved 1
- 1.1.1 Adult
- Preferred regimen (1): drug name 100 mg PO q12h for 10-21 days (Contraindications/specific instructions)
- Preferred regimen (2): drug name 500 mg PO q8h for 14-21 days
- Preferred regimen (3): drug name 500 mg q12h for 14-21 days
- Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
- Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
- Alternative regimen (3): drug name 500 mg PO q6h for 14–21 days
- 1.1.2 Pediatric
- 1.1.2.1 (Specific population e.g. children < 8 years of age)
- Preferred regimen (1): drug name 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
- Preferred regimen (2): drug name 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
- Alternative regimen (1): drug name10 mg/kg PO q6h (maximum, 500 mg per day)
- Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
- Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
- 1.1.2.2 (Specific population e.g. 'children < 8 years of age')
- Preferred regimen (1): drug name 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
- Alternative regimen (1): drug name 10 mg/kg PO q6h (maximum, 500 mg per day)
- Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
- Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
- 1.1.2.1 (Specific population e.g. children < 8 years of age)
- 1.1.1 Adult
- 1.2 Specific Organ system involved 2
- 1.1 Specific Organ system involved 1
- 2 Stage 2 - Name of stage
- 2.1 Specific Organ system involved 1
- Note (1):
- Note (2):
- Note (3):
- 2.1.1 Adult
- Parenteral regimen
- Oral regimen
- Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
- Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
- Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
- Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
- Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
- Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
- 2.1.2 Pediatric
- Parenteral regimen
- Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
- Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
- Alternative regimen (2): drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '(Contraindications/specific instructions)'
- Oral regimen
- Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
- Preferred regimen (2): drug name (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
- Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
- Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
- Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
- Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
- Parenteral regimen
- 2.2 'Other Organ system involved 2'
- Note (1):
- Note (2):
- Note (3):
- 2.2.1 Adult
- Parenteral regimen
- Oral regimen
- Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
- Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
- Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
- Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
- Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
- Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
- 2.2.2 Pediatric
- Parenteral regimen
- Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
- Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
- Alternative regimen (2): drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
- Oral regimen
- Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
- Preferred regimen (2): drug name 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
- Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
- Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
- Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
- Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
- Parenteral regimen
- 2.1 Specific Organ system involved 1
Medical Therapy
Symptoms are treated as there is no treatment for the disease. Cessation of tobacco use may slow any further progression of the disease. The goal of treatment for Buerger's disease is to control symptoms.
- Quitting smoking
- Keep warm and do regular exercises may help increase circulation.
- Medications: The following medications have shown somewhat effective in improving distal blood flow and relieve symptoms.
- Iloprost, a prostaglandin analogue
- Stem cell injection
- Streptokinase
MEDICAL MANAGEMENT — Smoking cessation is the only definitive therapy for patients diagnosed with thromboangiitis obliterans. Although a number of other therapies have been investigated, these should be considered palliative.
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".)
Smoking cessation — We recommend that patients discontinue cigarette smoking or the use of tobacco in any form because it is the only effective strategy for managing thromboangiitis obliterans. Complete abstinence from tobacco products is the only way to halt the progression of thromboangiitis obliterans and to avoid future amputations [4]. The disease may be activated by smoking as little as one or two cigarettes a day. Transdermal nicotine patches and nicotine chewing gum should be avoided because they may also keep the disease active, but bupropion or varenicline can be used as smoking cessation aids. The correlation between smoking and disease activity is so strong that measurement of urinary nicotine and cotinine (a byproduct of nicotine) should be performed if the disease is active despite patient claims of tobacco cessation [65]. (See "Overview of smoking cessation management in adults".)
Patients can be reassured that if they are able to discontinue tobacco use, the disease will remit and the need for amputation is low provided critical limb ischemia (gangrene and tissue loss) has not already occurred. However, the patient may continue to experience intermittent claudication or Raynaud's phenomenon. (See 'Outcomes' below.)
Unfortunately, only approximately one-half of patients are able to maintain smoking cessation long term [12,66]. In one series of 110 patients, only 41 (37 percent) were able to discontinue smoking [66]. Inpatient nicotine dependence treatment is an alternative for recidivist smokers [67].
Iloprost — Iloprost is a prostaglandin analog used to manage pain associated with thromboangiitis obliterans. Intravenous iloprost is more effective than the oral formulation [68-71]. The major benefit of iloprost may be in helping patients with critical limb ischemia get through the period of initial smoking cessation. Two randomized trials have evaluated its effectiveness.
In one trial, 152 patients were randomly assigned to a six-hour daily intravenous infusion of the drug versus low-dose aspirin [69]. Total relief of pain at rest and complete healing of all trophic changes were the primary outcome measures. At 28 days and at six months there was a significant improvement in the iloprost-treated group compared with the aspirin group, with 6 percent of patients in the iloprost group requiring amputation compared with 18 percent of those receiving aspirin.
In another trial, 200 patients were randomly assigned to lumbar sympathectomy or intravenous iloprost [70]. Rates of ulcer healing were significantly higher in the iloprost group compared with the lumbar sympathectomy group (62 versus 41 percent). Analgesic requirements were less and pain scores lower with iloprost treatment. A prospective study in 158 patients also noted benefits with respect to ulcer healing in patients with thromboangiitis obliterans [71].
A systematic review that included five trials (602 participants) found moderate-quality evidence that iloprost was more effective compared with aspirin for improving rest pain and healing ischemic ulcers intravenously [72]. Oral iloprost was not more effective than placebo.
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].