Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

Psychiatric sequelae of thromboangiitis obliterans: a case report and review of the literature.

BACKGROUND: Peripheral manifestations secondary to progressive vascular occlusions are characteristic of the rare condition termed thromboangiitis obliternas (TAO) or Buerger's disease. The central manifestations of this disease are however poorly characterized, particularly those of psychiatric nature, and their prevalence is largely unknown. Speculations have been made around the polymorphic nature and triggers of observed psychopathology in TAO; much however remains to be unraveled in this area. CASE PRESENTATION: We present the case of a 33-year-old Caucasian male who developed first episode of psychosis at the age of 29 years. There was no history of previous mental illness either in the patient, or in any of his family members. He had been a long- term heavy smoker and was experiencing progressive lower limb claudication since the age of 22 years; however, all inflammatory, autoimmune and atherosclerotic markers were negative. His psychosis was characterized by retention of a warm affect, and despite some amelioration, was generally resistant to a fair trial of several anti-psychotic medications including Clozapine. CONCLUSION: The pathophysiology of psychosis secondary to Buerger's is not yet well characterized which adds to the complexity of managing these cases. Recognizing that cerebral manifestations of this disease may evolve several years after the onset of peripheral thromboangiitic features is important for following the natural history and considering measures that may reduce the burden of illness.

Chronic management of pulmonary embolism in thromboangiitis obliterans.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare small vessel vasculitis that is associated with an increased risk of arterial occlusion. Although venous thromboembolism has been described, the risk of its recurrence and the best long-term anticoagulation management is not known. Considering this, we would like to share our experience with two patients admitted to our hospital with recurrent pulmonary embolism and previous diagnosis of TAO, aiming to discuss the indication for indefinite anticoagulation in this population.

Milestones in thromboangiitis obliterans: a position paper of the VAS-European independent foundation in angiology/vascular medicine.

Even today thromboangiitis obliterans has disease features that remain misunderstood or underappreciated. The epidemiology, etiology and pathophysiology of the disease are still unclear. Biomarkers and disease activity markers are lacking, thus clinical assessment is difficult. We are still struggling to establish unique diagnostic, staging and treatment criteria. This is an academic-collaborative effort to describe the pathophysiology, the clinical manifestations, the diagnostic approach, and the challenges of management of patients with TAO. A systematic search for relevant studies dating from 1900 to the end of 2020 was performed on the PubMed, SCOPUS, and Science Direct databases. Given the intriguing nature of presentation of TAO, its management, to some extent is not only different in different regions of the world but also varies within the same region. Following this project, we discovered ambiguity, overlap and lack of clear-cut criteria for management of TAO. An international group of experts however came to one conclusion. They all agree that management of TAO needs a call for action for a renewed global look with multi-center studies, to update the geographical distribution of the disease and to establish a unique set of diagnostic criteria and a consensus-based guideline for best treatment based on current evidence.

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients.

ABSTRACT: Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.

Women and Pregnancy in Thromboangiitis Obliterans.

Data regarding women and thromboangiitis obliterans (TAO) are conflicted, and a few cases of pregnancy have been described. We aimed to describe the interplay between TAO and pregnancies. Among 224 TAO patients, 22.8% were women. Demographic data, clinical manifestations, and outcomes were similar between men and women. Twenty-one (41.2%) women had 48 pregnancies. Thirty-six (75%) pregnancies with on term and complication free delivery occurred. None of the patients experienced a disease flare of TAO during pregnancy. TAO does not seem to affect pregnancy complications, and pregnancy does not seem to interfere with the course of TAO.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

The Incidence and Prevalence of Thromboangiitis Obliterans in Taiwan: A Nationwide, Population-based Analysis of Data Collected from 2002 to 2011.

OBJECTIVE: To estimate the incidence and prevalence of thromboangiitis obliterans in Taiwan in the period spanning from 2002 to 2011. METHODS: We identified all incident and prevalent cases with a diagnosis of thromboangiitis obliterans (International Classification of Diseases, Ninth Revision code 443.1) in the period spanning from 2002 to 2011 using Taiwan's National Health Insurance Research Database. We calculated the age- and sex-specific incidence and prevalence rates of thromboangiitis obliterans during the study period. RESULTS: From 2002 to 2011, 158 patients were diagnosed with thromboangiitis obliterans; of these, 76% were men. Most (63%) of the patients were <50 years old when they were first diagnosed. After reaching 20 years of age, the incidence rate increased with age and peaked among those aged ≥60 years. The average incidence rate of thromboangiitis obliterans during the 2002-2011 period was 0.068 per 105 years. The incidence of thromboangiitis obliterans decreased with time, from 0.10 per 105 years in 2002 to 0.04 per 105 years in 2011. The prevalence increased from 0.26 × 10-5 in 2002 to 0.65 × 10-5 in 2011. CONCLUSION: This is the first epidemiologic study of thromboangiitis obliterans using claims data from a general population in Taiwan. This nationwide, population-based study found that the incidence and prevalence of thromboangiitis obliterans in Taiwan in the 2002-2011 period were lower than those in other countries before 2000. This study also revealed a trend of decreasing incidence with simultaneous increasing prevalence of thromboangiitis obliterans in Taiwan from 2002 to 2011.

The Incidence and Prevalence of Thromboangiitis Obliterans in Taiwan: A Nationwide, Population-based Analysis of Data Collected from 2002 to 2011

OBJECTIVE: To estimate the incidence and prevalence of thromboangiitis obliterans in Taiwan in the period spanning from 2002 to 2011. METHODS: We identified all incident and prevalent cases with a diagnosis of thromboangiitis obliterans (International Classification of Diseases, Ninth Revision code 443.1) in the period spanning from 2002 to 2011 using Taiwan’s National Health Insurance Research Database. We calculated the age- and sex-specific incidence and prevalence rates of thromboangiitis obliterans during the study period. RESULTS: From 2002 to 2011, 158 patients were diagnosed with thromboangiitis obliterans; of these, 76% were men. Most (63%) of the patients were <50 years old when they were first diagnosed. After reaching 20 years of age, the incidence rate increased with age and peaked among those aged ≥60 years. The average incidence rate of thromboangiitis obliterans during the 2002–2011 period was 0.068 per 105 years. The incidence of thromboangiitis obliterans decreased with time, from 0.10 per 105 years in 2002 to 0.04 per 105 years in 2011. The prevalence increased from 0.26 × 10−5 in 2002 to 0.65 × 10−5 in 2011. CONCLUSION: This is the first epidemiologic study of thromboangiitis obliterans using claims data from a general population in Taiwan. This nationwide, population-based study found that the incidence and prevalence of thromboangiitis obliterans in Taiwan in the 2002–2011 period were lower than those in other countries before 2000. This study also revealed a trend of decreasing incidence with simultaneous increasing prevalence of thromboangiitis obliterans in Taiwan from 2002 to 2011.

Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results.

OBJECTIVE: To investigate the efficiency of autologous peripheral blood stem cell transplantation (APBSCT) to treat severe the lower limbs ischemia caused by thromboangiitis obliterans (TAO). PATIENTS AND METHODS: From April 2007 to December 2014, a total of 64 patients with TAO (80 affected limbs) received APBSCT at our hospital. The treatment effect was evaluated by subjective indicators including pains and cold sensation of the affected limbs, combined with objective indicators including claudication distance, ankle brachial index (ABI), transcutaneous oxygen pressure (TcPO2) and skin temperature. RESULTS: Five patients (with 5 affected limbs) suffered from necrosis below the middle of the leg 4 weeks after transplantation and received amputation. For the remaining 59 patients (75 affected limbs), pain and cold sensation of the affected limbs were improved with varying extent 3 months after transplantation; there were statistically significant differences in pain score and cold sensation score of the affected limbs before and after APBSCT (p<0.05). Claudication distance, ABI, TcPO2 and skin temperature were also improved. Claudication distance increased from 85.69 m ± 43.48 m to 36.5 ± 9.88 mmHg, and the skin temperature of the lower limbs increased from 27.70 °C ± 0.53 °C to 33.49 °C ± 0.60 °C. All four indicators were considerably improved after APBSCT (p<0.05). Arteriography was performed for 75 affected limbs in 59 patients 6 months after transplantation and found that new collateral vessels were formed in the affected limbs. No patients were complicated by retinal hyperplasia, malignant tumors, myocardial infarction and cerebral infarction during the follow-up examinations; no patients underwent symptom aggravation during 9-48 month follow-up (average, 28.5 months). CONCLUSIONS: APBSCT is an easy, safe and reliable treatment for ischemia of lower limbs, especially for those with poor distal arterial outflow tract in the lower limbs that do not permit bridging.

The Epidemiologic and Clinical Findings of Patients with Buerger Disease.

BACKGROUND: Buerger disease is a nonatherosclerotic peripheral arterial disease, which is mostly observed in young male smokers. Buerger disease is characterized by the observation of peripheral arterial occlusion by angiography. The condition may be caused by microembolization in the small-sized arteries of the distal extremities. Buerger disease is diagnosed based on the Shionoya's clinical diagnostic criteria, which include: (1) a history of smoking, (2) onset before the age of 50 years, (3) the presence of infrapopliteal arterial occlusions, (4) either upper limb involvement or phlebitis migrans, and (5) the absence of atherosclerotic risk factors other than smoking. Several studies have reported that oral bacterial infections (periodontitis) could activate the onset of Buerger disease. In this study, we report the epidemiologic and clinical manifestations of patients with Buerger disease. METHODS: Fifty-eight patients who were surgically treated between July 1989 and June 2014 at Tokyo Medical and Dental University Hospital were enrolled in this study. All of the patients clinically diagnosed with Buerger disease based on Shionoya's clinical diagnostic criteria. Fifty-five male and 3 female patients were treated. The mean age of the patients was 48 years (range, 21-73 years). RESULTS: All of the patients were either smokers or had a history of smoking. The mean Brinkman index score was 780 (range, 150-1,640). Their mean age at the onset of Buerger disease was 38 years (range, 21-50). The arterial lesions extended to the femoral arteries in 25% of cases, to the iliac arteries in 8% and to the abdominal aorta and/or visceral arteries in 6% of cases. Upper limb involvement, including cyanosis, paleness, and gangrene, was obvious in 84% of patients, and phlebitis migrans was recognized in 34%. The lower extremities symptoms involved intermittent claudication in 23% of the patients, rest pain in 13% of the patients, and ulceration or gangrene in 64% of the patients. Fifteen patients had undergone surgical arterial reconstruction, 4 patients had received endovascular therapy, 33 patients had undergone lumbar sympathectomy and 8 patients had undergone thoracic sympathectomy. Twenty percent of the patients needed minor limb amputations, and 4% required major limb amputations. In the patients who were examined for their oral conditions, periodontitis corresponding to grades B (moderate periodontitis), C (severe periodontitis), and D (edentulous patients) was revealed in 31%, 56%, and 13% of the patients, respectively. CONCLUSIONS: More than half of the Buerger disease patients in this study were suffering from severe periodontitis. It is possible that not only the cessation of smoking, but also the improvement of periodontal care could improve the clinical symptoms related to Buerger disease.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

BACKGROUND: The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. MATERIALS AND METHODS: In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. RESULTS: A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. CONCLUSIONS: The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.

The Pathogenesis and Diagnosis of Thromboangiitis obliterans: Is It Still a Mystery?

Thromboangiitis obliterans (TAO) is a rare disease of unknown etiology that results in the occlusion of limb arteries located distally to the elbow and knee. Despite the fact that more than one hundred years have passed since its first description, knowledge on the pathogenesis of TAO and precipitating factors is still limited. Due to a lack of decisive noninvasive diagnostic methods and geographical differences in the prevalence of this condition, data on TAO epidemiology also remains sparse. This review presents important evidence on the pathogenesis and the course of the condition, as well as diagnostic modalities, with a focus on differential diagnosis. Theories on the pathogenesis of TAO include the theory of an infectious disease, coagulation disorders and injury to vascular endothelium resulting in activation of the inflammatory response. Differential diagnosis should exclude thoracic outlet syndrome, blue toe syndrome, infectious endocarditis, popliteal entrapment syndrome, Takayasu disease, primary and secondary systemic vasculitis, antiphospholipid syndrome, infection with the anaerobic Clostridium sp. bacilli and some less common conditions.

Fate of ischemic limbs in patients with Buerger's disease based on our 30-year experience: does smoking have a definitive impact on the late loss of limbs?

PURPOSE: We herein review the long-term results of our series of critical ischemic limbs caused by Buerger's disease. METHODS: A retrospective review of 103 patients with critical limb ischemia who were diagnosed with Buerger's disease by Shionoya's criteria between 1980 and 2010. RESULTS: The age of onset was 38.0 ± 9.7 years (mean ± SD). The median follow-up was 97 months. Thirty-three patients had pain at rest, and 65 patients presented with ischemic ulcers in their toes and/or fingers. Gangrene was present in five patients. Sixteen patients achieved remission with medical therapy and smoking cessation. Sixty-six patients underwent sympathectomy. Bypass to the crural arteries was performed in 23 limbs, with assisted primary patency rates of 67.0 and 45.6 % at five and 10 years. Graft failure caused major amputation in two out of 10 smokers, but no limbs were lost among the 12 ex-smokers. Therapeutic angiogenesis using cell transplantation led to improvement in three ex-smokers; however, amputation was unavoidable in the one smoker who was treated. The limb salvage rate at 20 years was 90 % in ex-smokers and 69 % in smokers, which was not significantly different. CONCLUSIONS: This study demonstrated no significant difference in the limb salvage rate between ex-smokers and smokers. Our results do not support any advantageous effect of smoking cessation on the long-term remission in patients with Buerger's disease.

Thromboangiitis obliterans (Buerger's disease).

Thromboangiitis obliterans (TAO, Buerger's disease) is an inflammatory vascular disease affecting small and medium sized arteries and veins. It is characterized by segmental thrombotic occlusions by highly mononuclear cellular thrombi. Its occurrence and re-occurrence is closely related to tobacco use. Immunohistological examinations and the detections of various autoantibodies led to the new paradigm of an immunopathogenesis of TAO. Clinically it is characterized by distal ischemia syndromes in young people and high amputation rates. This article summarizes the disease characteristics, clinical features, and diagnostic and therapeutic approaches and focuses on new therapeutic options, i.e. stem cell derived therapies, immunoadsorption, and the endothelin-receptor-blocking agent bosentan.

Smoking and Thromboangitis Obliterans- Are they related ?

INTRODUCTION: In 1908 Leo Buerger first gave the world the clinical picture of this dreadful disease which he called Thromboangitis Obliterans. Virtually all investigators believe that smoking or tobacco use in some form is a requirement for the diagnosis of Thromboangitis Obliterans. We studied the demographic profile and smoking pattern of patients with Thromboangiitis Obliterans. METHODS: Retrospective study carried out in a tertiary level hospital of South India from 1st January 1997 to 31st December 2003. Patients fulfilling Shionoya's criteria form the study group. Incidence of Thromboangitis Obliterans, relation to smoking habits, type and nature of manifestation were analyzed. RESULTS: A total of 105 cases were studied and found to have declining pattern of incidence from 0.9%-0.3%. All patients were males, smokers at the time admission and 76% out of them were from low socioeconomic background. Patients smoking 5-15 cigarettes per day, for 5-10 years duration constituted 45% of the study group. The most frequent reasons for being referred to hospital were ischemic ulcers (83.80%), claudication (78.0%) and rest pain (26.66%). CONCLUSIONS: In those who present early with the disease the number of cigarettes and duration of smoking shows no direct correlation to the severity. Most patients continue to smoke inspite of counseling and awareness that the disease progresses due to smoking. Ulcer, intermittent claudication and rest pain are the three common presenting symptoms of Thromboangitis Obliterans.

Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

BACKGROUND: This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups. METHODS AND RESULTS: This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI). CONCLUSIONS: According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.

Imaging appearances of Buerger's disease complications in the upper and lower limbs.

Thromboangiitis obliterans (Buerger's disease) is a rare, non-atherosclerotic, segmental, inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities and affects tobacco smokers between the ages of 25 and 45 years. The manifestations of Buerger's disease can be extremely variable and, therefore, awareness of the condition is important for both general and musculoskeletal radiologists. This paper presents the radiological appearance of the sequelae of Buerger's disease involving the upper and lower limbs.