Treatment of Thromboangiitis Obliterans Using Smoking Cessation and Far-infrared Therapy: A Case Study
Abstract
Thromboangiitis obliterans (Buerger’s disease) is a rare, nonatherosclerotic segmental inflammatory vasculitis that commonly involves small- and medium-sized vessels. Ischemic tenderness impairs patient quality of life and places patients at high risk for amputation. The only definitive known treatment is smoking cessation. Far-infrared (FIR) therapy has shown promising effects on blood flow and healing, but its use in patients with Buerger’s disease has not been reported.
A 31-year-old man with a 15-pack-year history of smoking, no drug abuse, and no other significant medical history, trauma, or family history diagnosed with thromboangiitis obliterans presented for care at the authors’ clinic. Claudication with severe tenderness of both legs and an ischemic ulcer over the right big toe were noted. After surgical debridement of the devitalized tissue, the patient received FIR therapy (5–25 µm, peak at 8.2 µm) applied 25 cm above the surface of the ischemic wound for 40 minutes, 3 times per week. The patient also tapered his smoking. The wound started to heal; granulation tissue was evident and, after 8 weeks, the right lower extremities gradually rewarmed from 24˚ C to 28˚ C as measured on the dorsal foot. His pain level decreased from 8 to 5. FIR therapy was continued until the patient stopped smoking (8 months). At the 10-month follow-up visit, the wound had healed completely and resting pain had improved. The results of this case study suggest additional research to explore the potential effects of FIR on patients with thromboangiitis obliterans is warranted.
Thromboangiitis obliterans (TAO), also known as Buerger’s disease, is a nonatherosclerotic segmental inflammatory disease of the small- and medium-sized arteries and veins of the extremities. It typically occurs in young males and smokers, with onset of symptoms before the age of 40 to 45 years.1 The prevalence of this disease varies widely, ranging from as low as 0.5% to 5.6% in Western Europe to as high as 45% to 63% in India and 16% to 66% in Korea and Japan.2 TAO may present initially as episodic pain and coldness in the extremity. As the disease progresses, intermittent claudication, pain at rest, ischemic ulcerations, and gangrene of the critical limb can develop, which can lead to eventual amputation.3
Smoking cessation is the only known definitive therapy for the management of TAO.1 The effectiveness of other treatments including vasodilation or anti-clotting drugs, surgical revascularization, or sympathectomy in preventing amputation or treating pain remains to be determined.1,2
Far-infrared (FIR) therapy is an invisible electromagnetic wave with a longer wave length (3 to 1000 µm) than that of visible light.4 In a systemic review by Bashar et al4 which included 4 randomized, controlled trials (666 patients), FIR therapy improved endothelial function and hemodynamics in coronary arteries by upregulating endothelial nitric oxide synthase expression in the arterial endothelium, stimulating secretion of transforming growth factor-beta (TGF-beta)1 and activation of fibroblasts to improve wound healing independent of skin blood flow and skin temperature and improving the patency of arteriovenous fistula. In a randomized, controlled study by Lin et al5 (122 patients), FIR therapy improved the access flow, maturation, and patency of arteriovenous fistulae as measured by Doppler ultrasonography. In an animal study,6 FIR therapy promoted angiogenesis in ischemia-induced diabetic mice by enhancing endothelial progenitor cell function and the homing process. In the clinical evaluation and laboratory study by Li et al,7 a total of 32 patients affected by stage II and stage III lymphedema were treated with FIR therapy. A significant decrease in limb circumference was noted; microcirculation flow was promoted and collateral lymph circumfluence was improved without significant adverse events. Nevertheless, no report has been published about the use of adjunctive FIR therapy in a wound caused by TAO. This is a report of a patient with TAO with an ischemic ulcer over his right big toe and claudication of both legs successfully treated with smoking cessation and FIR therapy.
Case Report
History and presentation. Mr. U, a 31-year-old man with a 15-pack-year history of smoking, no drug abuse, and no other significant medical history, trauma, or family history, presented to the authors’ department with intermittent claudication, marked tenderness, numbness of the toes of the right foot, cyanotic changes, and an ischemic ulcer of 2 months’ duration over his right big toe (see Figure 1a). He rated his pain as 8 out of 10 on a visual analog scale. He received an analgesic agent and local wound care for more than 1 month, but the symptoms persisted and impaired his quality of life. Physical examination revealed coldness of the right foot (24˚ C on the dorsal foot measured by thermograph) and decreased distal pulsation; his ankle/brachial index was 0.5. Magnetic resonance angiography and an angiogram of the lower legs demonstrated occlusion of the arterial segment at the right popliteal artery with collaterals (see Figure 1b). However, no atherosclerosis was found. Laboratory test results, including a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, fasting blood sugar, lipid levels, hepatitis screening, renal function, urinalysis, and plasma homocystine concentrations, were all normal. Screening for hypercoagulability, such as anticardiolipin antibodies, proteins C and S, antithrombin III, and factor V Leiden, was negative. The toxicology panel also was negative. Immunological tests, including antinuclear antibody, rheumatic factor, complement, cryoglobulinemia, and anti-SCL-70 and anticentromere antibodies, were unremarkable. Ultrasound scans showed no embolic source in the heart or abdominal aorta. 
Diagnosis. The authors made a clinical diagnosis of Buerger’s disease based on Olin’s review1: 1) Mr. U was <45 years old; 2) he had a current or recent history of tobacco use; 3) he exhibited the presence of distal extremity ischemia indicated by claudication, pain at rest, ischemic ulcers, or gangrene, documented by noninvasive vascular testing; 4) autoimmune diseases, hypercoagulable states, and diabetes mellitus were excluded; 5) a proximal source of emboli was excluded by echocardiography or arteriography; and 6) arteriography findings were consistent in the clinically involved and noninvolved limbs.1
Treatment. Mr. U underwent surgical debridement of the devitalized tissue (shown in Figure 2). The WS TY101 FIR emitter (WS Far Infrared Medical Technology Co, Ltd, Taipei, Taiwan), which generates electromagnetic waves with wavelengths in the range of 5–25 µm (peak at 8.2 µm), was applied to the patient postoperatively. The top radiator was set to a height of 25 cm above the surface of the ischemic wound, and the treatment time was set at 40 minutes. Treatment was provided 3 times per week. The wound was treated with normal saline irrigation and covered with gauze after FIR therapy. 
Mr. U’s wound started to heal; granulation tissue was evident and the right lower extremities had gradually rewarmed to a temperature of 28˚ C on the dorsal foot by ~8 weeks postoperatively. After 8 weeks, Mr. U’s pain decreased from 8 initially to 5. Mr. U heeded physician advice so he could alleviate the discomfort of his right lower leg and tapered his smoking, quitting over 8 months and continuing FIR therapy throughout until he stopped smoking.
The wound healed completely and Mr. U was pain-free at 10 months (see Figure 3a,b). The ankle/brachial index at that time was 0.8. After more than 2 years of follow-up evaluations, Mr. U resumed his regular activities with no recurrence of right foot ulceration. Furthermore, claudication and tenderness of the lower legs also resolved, and Mr. U no longer required analgesic medicine. 
Discussion
TAO is a rare, nonatherosclerotic segmental inflammatory vasculitis that commonly involves small- and medium-sized vessels and nerves of the extremities. TAO is associated with a high risk of limb amputation. As reported in a study by Cooper et al8 utilizing a follow-up survey and chart review of 111 patients with TAO, 25% of patients experience their first amputation at 5 years after diagnosis, 38% at 10 years, and 46% at 20 years. Reviews1,9,10 reported several risk factors, such as tobacco and marijuana use and chronic anaerobic periodontal infection. Pathological characteristics show TAO is a highly cellular, inflammatory intraluminal thrombus with relative sparing of the internal elastic lamina.11 Nonetheless, its pathogenesis remains unclear. It has been postulated that smoking may induce a delayed type of hypersensitivity or toxic angiitis, increasing production of cytokines and contributing to the inflammatory response.12,13 In addition, endothelial dysfunction with impairment of endothelium-dependent vasodilation and mutation of the prothrombin gene also may be involved.14,15 Cessation of tobacco use is the only known effective method of halting the progression of TAO; according to a review by Olin,1 94% of persons who quit smoking avoided amputation, whereas 43% of those who continued smoking required 1 or more amputations. Unfortunately, according to retrospective analysis by Ohta et al16 of 110 patients with TAO, less than half of patients were able to quit smoking.
Medications such as iloprost, bosentan, phosphodiesterase type-5 inhibitors, and calcium channel blockers have been used to treat TAO. Surgical modalities include thrombolytic therapy, arterial reconstruction, lumbar sympathectomy, spinal cord stimulation, microvascular flap transfer, pedicled omental graft, distraction osteogenesis, and, when required, amputation.17-21 However, the treatment of TAO is still being studied. Based on the results of a variety of studies4-7,22 of FIR therapy applied to arteriovenous fistulas and wound healing, the current authors applied FIR therapy to treat this patient.
The meta-analysis by Bashar et al4 that included 4 randomized, controlled trials showed FIR therapy may positively influence the patency rate of arteriovenous fistulas. Unassisted patency, assessed in 610 patients, was significantly better among those who received FIR therapy (228/311) compared to controls (185/299) (pooled risk ratio of 1.23 [1.12-1.35], P = .00001). Based on Lin et al’s5 randomized controlled study (N = 122), patients were randomly allocated to the intervention (n = 60) and control (n = 62) groups. FIR therapy improved the access flow and facilitated a higher rate of maturation along with patency of newly created arteriovenous fistulas in patients with stage 4 and stage 5 chronic kidney disease in comparison to controls. Animal studies by Huang6 revealed FIR therapy promotes collateral flow recovery and new vessel formation in diabetic mice. In a clinical study by Li et al7 and an animal study by Toyokawa et al,22 FIR therapy enhanced microcirculation flow and significantly decreased limb circumference in extremities with lymphedema and promoted wound healing in a rat model in comparison to controls.
Based on the meta-analysis and systematic review of FIR therapy in dialysis, arteriovenous fistula maturation and survival by Bashar et al4; Doppler perfusion imaging and immunofluorescence staining study in diabetic mice by Huang et al6; a randomized, controlled trial of FIR therapy on arteriovenous fistula by Lin et al,5 in comparison to control, the thermal effects of FIR increased the skin temperature up to only 38˚ C to 39˚ C after treatment for <60 minutes at a distance of 20 cm above the skin, inducing vasodilation and increasing blood flow without burning the skin. The nonthermal effects of FIR therapy improve endothelial dysfunction, augment angiogenesis, decrease oxidative stress, inhibit platelet aggregation, and suppress inflammation by enhancing the activity of endothelial nitric oxide synthase, thereby improving endothelial progenitor cell function and stimulation of heme oygenase (HO-1) expression. According to the etiology of TAO and mechanisms of FIR therapy, it is reasonable to consider the use of FIR therapy in TAO.
In this study case, the wound began to heal and Mr. U’s pain decreased when FIR therapy and tapered smoking were combined over 8 months. The wound healed completely and Mr. U experienced no pain 2 months after he stopped smoking. With the implementation of FIR therapy, the affected leg showed evidence of vasodilation and enhanced blood flow along with an improved ankle/brachial index. Although it is uncertain whether smoking cessation alone would have affected healing, this case represents a successful clinical outcome when TAO was used as a adjuvant treatment along with cessation of smoking.
Conclusion
The gold standard for treatment of TAO is smoking cessation. In the case study presented, FIR therapy, a convenient and noninvasive technology, was found to be an effective adjuvant therapeutic modality in wound healing in a patient with TAO. Further larger studies needed are warranted.
References
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Potential Conflicts of Interest: none disclosed
Dr. Chiang is a resident in plastic surgery; Dr. Chen is a vice-president, professor, and attending physician in plastic surgery; and Dr. Tzeng is an assistant professor and attending physician in plastic surgery, Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. Please address correspondence to: Yuan-Sheng Tzeng, MD, Division of Plastic Surgery, Department of Surgery, Tri-Service General Hospital, No. 325, Sec. 2, Cheng-Kung Road, Nei-Hu 114, Taipei, Taiwan, Republic of China; email: m6246kimo@yahoo.com.tw.