Associations Between Elevated Plasma Total Homocysteine Level and Risk of Thromboangiitis Obliterans in a Chinese Population: A Matched Case-Control Study.

BACKGROUND: Elevated plasma total homocysteine level is a risk factor for various vascular diseases; however, an association with risk of thromboangiitis obliterans (TAO) has not been defined. This study aims to assess whether elevated plasma total homocysteine level is associated with risk of TAO. METHODS: We performed a matched case-control study including 64 patients with TAO and 256 controls. Multivariate logistic regression models were used to estimate the association between elevated plasma homocysteine level and the risk of TAO. Interaction and stratified analyses were conducted according to age, sex, smoking, alcohol consumption, and histories of chronic diseases. RESULTS: Patients with TAO versus controls had a higher mean plasma total homocysteine level (21.2 ± 12.8 µmol/L vs. 14.1 ± 4.9 µmol/L; P < 0.01). The risk of TAO was 3.68-fold increased in participants with plasma total homocysteine level >15 µmol/L (95% confidence interval [95% CI], 1.2-11.7). A 1 µmol/L increase in plasma total homocysteine level was associated with 20% higher risk of TAO (odds ratio, 1.2; 95% CI, 1.1-1.3). CONCLUSIONS: Our findings suggest that the risk of TAO was significantly associated with elevated plasma total homocysteine level independently of other factors analyzed, including smoking. Studies on the use of homocysteine-lowering therapy to prevent TAO would allow testing causality of the latter association.

Risk Factors, Mechanisms and Treatments of Thromboangiitis Obliterans: An Overview of Recent Research.

BACKGROUND: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive vasculitis that affects the vessels of the small and medium-sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed. OBJECTIVE: The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in figures to provide a comparatively complete reference. METHODS: We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature). RESULTS: After screening content of works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further study of relationship was required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role. CONCLUSION: 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons are needed.

Successful Fat Grafting in a Patient With Thromboangiitis Obliterans.

Thromboangiitis obliterans, or Buerger disease, is a rare nonatherosclerotic segmental inflammatory vasculitis that generally affects young tobacco smokers. Although no surgical treatment is available, the most effective way to halt the disease's progress is smoking cessation. In this case report, a 29-year-old smoker showed up to emergency department with gangrene of his fifth left toe and extensive plantar ulceration. After investigative angiography, he was diagnosed with Buerger disease. On November 2017, he underwent fifth left toe amputation and hyperbaric therapy. Five months after amputation, the patient was rehospitalized because of surgical wound dehiscence, wide ulceration, and pain. He was treated with lipofilling using the Coleman technique. Two weeks after the fat grafting procedure, the patient suspended pain control medication, and after 2 months, the surgical wound was almost healed. Fat grafting (lipofilling) is mostly used in plastic surgery; it offers regenerative effects, with minimal discomfort for the patient. This case report demonstrates a successful alternative use of lipofilling for this unique condition and opens up new options for use of this technique in other fields.

Photo Rounds: Painful blisters on fingertips and toes.

Our patient had visited the emergency department for painful blisters on her fingertips and toes. A follow-up visit to our clinic unearthed the cause.

Unilateral localized conjunctival amyloidosis in a patient with a history of contralateral orbit/eyelid lymphoma.

Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is much more sensitive in diagnosing amyloidosis and can determine the type of amyloid deposit. Here we reported a case of conjunctival amyloidosis in a 52 year-old male patient who was presented with left lower eyelid swelling to our medical center. He has a complicated past medical history of anti-phospholipid antibody syndrome, Buerger's disease (thromboangitis obliterans), and small cell lymphoma (SLL) of the right orbit/eyelid. The patient received radiation to the right orbit to treat SLL with therapy completed one and a half years prior to presentation. Physical examination revealed a firm, raised yellowish colored lesion in the left lower conjunctiva. The conjunctival lesion was biopsied, and tissue sections were examined with Congo red stains and LC-MS/MS analysis. The biopsy showed amyloid deposits without evidence of malignancy, and the type of proteins in the deposit was immunoglobulin light chain (AL) of kappa type. A complete work up was taken for possible systemic involvement of amyloidosis and results were all negative. To our knowledge, this is the first case of localized conjunctival amyloidosis with a history of contralateral orbit/eyelid SLL.

Endovascular Treatment of Thromboangiitis Obliterans (Buerger's Disease).

PURPOSE: When critical limb ischemia (CLI) occurs in patients with thromboangiitis obliterans (TAO) or Buerger's disease, smoking cessation alone may be insufficient to relieve rest pain and promote wound healing. Accordingly, adjunctive measures are warranted to restore adequate blood flow required for limb salvage. This study aimed to evaluate the feasibility and efficacy of percutaneous transluminal angioplasty (PTA) for the treatment of patients with TAO and CLI. In addition, a review of the literature on endovascular management of TAO is included. METHODS: Between April 2012 and June 2017, all patients with TAO and CLI who underwent PTA were studied retrospectively. Patient demographics, presentation, procedural details, and clinical response were recorded. Patients were monitored at 1 week, 1, 2, 3, and 6 months after revascularization and at least every 6 months thereafter. RESULTS: Thirteen patients with TAO and CLI, who presented with rest pain only (n = 1), ischemic ulcer (n = 4), or gangrene (n = 8) underwent endovascular interventions with primary and assisted primary technical success of 85% and 92%, respectively. A below-knee amputation was eventually done in the only patient with technical failure (limb salvage rate: 92%). Following the procedures, 11 patients had clinical response, one of whom also received intra-arterial vasodilator to achieve complete symptom relief. The other patient who failed PTA underwent a successful lumbar sympathectomy. In addition, all ulcers healed and eight minor amputations were performed due to already established gangrene. During follow-up (mean: 19.4 months), four patients needed reintervention. Patients who continued to smoke experienced more severe ischemia ( P = .017) and were more likely to require reintervention ( P = .009). CONCLUSION: Percutaneous transluminal angioplasty can be considered as a technically feasible and potentially effective treatment for patients with TAO and CLI, as well as a last resort for limb salvage when other options have failed. However, reintervention may be required, especially in patients who continue smoking.

[Thromboangiitis obliterans: notions for practice]. / Thromboangéite oblitérante :notions pour la pratique.

Thromboangiitis obliterans is an occlusive vasculopathy affecting small- and medium-size arteries. It can result in severe ischemic status. Thrombophlebitis can be associated. The exact etiology has still to be elucidated. Smoking is the main contributing factor. Diagnosis is based on clinic and paraclinic context, as well as exclusion of other vascular pathologies. Its management consists in complete smoking cessation and instauration of vasodilator treatment. Revascularization is an option that has to be evaluated on a case by case basis. New promising therapeutic approaches are emerging.

La thromboangéite oblitérante se caractérise principalement par une atteinte occlusive des artères de petit et moyen calibres, pouvant mener à un tableau clinique ischémique grave. Une thrombophlébite peut y être associée. L'étiologie exacte n'est pas encore connue. Le tabagisme est le facteur de risque prépondérant. Le diagnostic se base sur les contextes clinique et paraclinique, ainsi que l'exclusion d'autres pathologies vasculaires. La prise en charge consiste en l'arrêt définitif du tabagisme et l'introduction de traitements vasodilatateurs. Les options de revascularisation sont à discuter de cas en cas. De nouvelles modalités thérapeutiques semblent prometteuses.

Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia.

BACKGROUND: Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited. PATIENTS AND METHODS: Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up. RESULTS: Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %). CONCLUSIONS: Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

Very distal vein bypass in patients with thromboangiitis obliterans.

BACKGROUND: Surgical revascularization for chronic critical limb ischaemia in patients with thromboangiitis obliterans (TAO) still remains controversial. Generally, besides cessation of smoking, conservative treatment supported by intravenous administration of vasoactive agents is regarded as the treatment of choice, in combination with local wound therapy or minor amputation. PATIENTS AND METHODS: In four male patients (42-47 years) surgical revascularization was chosen as therapy for established gangrene or non-healing ulceration after unsuccessful conservative treatment and cessation of smoking. Angiography was able to identify a suitable distal arterial segment for the bypass which was revascularized by means of an autologous vein graft. Grafts were followed with repetitive duplex ultrasound. Revision of the bypass graft was initiated if indicated by pathological duplex findings. RESULTS: In all cases a bypass could be constructed with either the ipsilateral greater saphenous vein or arm veins. A distal origin configuration was possible in three cases with popliteo-pedal or cruro-pedal bypasses. In the fourth case the distal superficial femoral artery was used for inflow. Two early graft thromboses underwent successful revision. During follow-up, duplex ultrasound identified graft stenoses in three bypasses which were successfully treated with endovascular techniques. All grafts are patent with complete resolution of ischaemic symptoms after 46, 42, 32, and 29 months. The patients remained non-smokers and returned to a professional life. CONCLUSIONS: Surgical therapy with distal vein bypass for persistent ischaemic symptoms after definitive cessation of smoking seems feasible in selected cases with TAO and a suitable distal artery. Close follow-ups of the patients with duplex ultrasound are necessary to identify developing vein graft stenoses. Angioplasty seems to be an important part of the long-term therapeutic concept.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

Pathogenesis and Management of Buerger's Disease.

Buerger's disease or thromboangiitis obliterans causes pain, ulceration, or gangrene in the lower or upper extremity. It is associated with chronic cigarette smoking and is believed to be an immune mediated vasculitis. The pathogenesis is still unknown but recent postulate of its association with odontal bacteria has generated much renewed interest. Despite its recognition more than a century ago, little progress has been made in its treatment. Until the pathogenesis is elucidated, abstinence from cigarette is the only effective therapy.

Thromboangiitis obliterans - case report.

Thromboangiitis obliterans (Buerger'€™s disease) represents an inflammatory disease of limbs'€™ small arteries and veins causing vascular thrombosis, and partial or total obstruction. It affects mostly male gender aged 40 years old. The peculiarity of our case is underlined by presenting a 62 years, chronic tobacco user and not compliant female patient known with thromb oangiitisobliterans for almost 15 years. The arteriographic and clinical features with concomitant and sever affected upper and lower limbs are highly suggestive, emphasizing the possibility of Buerger'€™s disease development even in female patients.

[THROMBOANGIITIS OBLITERANS (BUERGER'S DISEASE)]. / Maladie de Buerger.

To day there appears to be a consensus to recognize thromboangiftis obliterans (Buerger's disease) as a distinct clinical and pathological entity, characterized by an inflammatory occlusive vasculitis of the small and medium-sized arteries and veins that affects young adult smokers. The strong link with smoking is one of the unique features of thromboangiitis obliterans. Once the disease has became established stepping smoking is the only effective way to prevent evolution of the disease and to reduce the risk of major amputations. Ischaemia of the lower and upper limbs and superficial thrombophlabitis are the essential features of the clinical presentation. However the diagnosis of thromboangiitis is rendered difficult by the lack of specific clinical, radiological, biological and histapathological features. Thus the diagnosis is funded on a probabilistic approach. Discontinuation of tobacco use and to day cannabis are the cornerstone of therapeutic management of patients with thromboangiitis. In patients with ischaemic lesions local care is the other main component of therapeutic management, infusion of iloprost had demonstrated some efficacy.

Effectiveness of intravenous ilomedin infusion and smoking cessation in the treatment of acutely symptomatic Buerger disease.

We assessed the effectiveness of iloprost treatment in the management of symptomatic Buerger disease (BD) and assessed smoking cessation compliance, based on a single-center experience. Thirteen patients with BD were treated with sessions of intravenous (IV) Ilomedin infusion. At 1-year follow-up, pain status alteration, number of analgesics required, ankle-brachial index (ABI) change, compliance with supervised smoking cessation, and amputation-free rate were recorded. The pain status improved considerably according to a visual analog scale, the number of analgesics required was significantly reduced, and all patients improved their pain-free walking distance, the ABI, and their self-reported quality of life. Only 2 patients required minor amputations. Combination of IV Ilomedin infusion, supervised smoking cessation, and a specific follow-up protocol may lead to improvement in pain-free walking distance, pain status, quality of life, and substantial reduction in amputation risk.

Endarteritis obliterans in the pathogenesis of Buerger's disease from the pathological and immunohistochemical points of view.

Buerger's disease (thromboangiitis obliterans) is considered to be a nonatherosclerotic, inflammatory, and vaso-occlusive disease, although the details of the mechanisms of pathogenesis remain unknown. The occurrence of the disease is strongly related to tobacco abuse and its progression is closely linked to continued smoking. The purpose of this review article is to demonstrate the pathological characteristics of arteries affected with Buerger's disease from a possible immunoreactive point of view. In addition, we present the mechanisms for preserving the architecture of the arterial wall in affected vasculatures. Thereafter, we discuss the possibility that the pathogenesis of Buerger's disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides.

Investigation of the expression of mediators of neovascularization from mononuclear leukocytes in thromboangiitis obliterans.

The aim of this study was to investigate the expression of the cytokines, chemokines and effective molecules of peripheral blood mononuclear cells (PBMCs) that play a role in neovascularization in thromboangiitis obliterans (TAO). Lymphocytes from TAO patients (n = 20) and control subjects (healthy smokers [n = 16] and non-smokers [n = 17]) were evaluated using realtime polymerase chain reaction in order to examine the mRNA expression of CXCL1 and interleukin 8 (IL-8; inducers of collateral development by recruitment of circulating progenitor cells [CPCs]), endothelial cell growth factor A (VEGF-A) and inducible nitric oxide synthase (iNOS; inducers of angiogenesis) and interferon gamma (IFN-γ) and vascular endothelial growth factor receptor 1 (VEGFR-1; inhibitors of angiogenesis). CXCL1 expression was significantly higher in the TAO patients than control subjects. The expressions of IL-8, VEGFR-1 and IFN-γ were significantly higher in the TAO patients and smokers than in non-smokers. However, no differences in iNOS and VEGF-A expression were noted. In conclusion, PBMCs from TAO patients expressed cytokines that potentially recruit CPCs and promote arteriogenesis. However, TAO patients typically have low CPC levels, perhaps due to high oxidative stress. Further studies are recommended in order to investigate the efficacy of antioxidant therapy on the outcome of TAO before administration of angiogenic factors.