A century has passed since thromboangiitis obliterans (TAO), or Buerger's disease, was first described, but the etiology remains unclear. It is still uncertain as to whether thrombosis or vascular inflammation is the first event. TAO is an episodic inflammatory and thrombotic-occlusive vascular disease of unknown origin. The involvement of the distal vessels and nerves within the neuro-vascular bundles occurs almost always in legs and occasionally in arms. The cumulative data demonstrate that at the cellular and molecular levels, at least four main components of inflammatory reactions, including endothelial cells, platelets, leukocytes and sensory neurons, might be involved in TAO pathogenesis. The interactions among these cells in an altered microenvironment of small- and medium-sized vessels may also orchestrate the onset of TAO events. In this review, the factors that may promote thrombosis and angiitis are reconsidered at three levels: (1) host characteristics such as male gender and genetic background; (2) probable triggers including cigarette smoking and infectious agents; and (3) environmental factors such as chronic anxiety and mental stress as a consequence of low socioeconomic status. At each level, the interactions among vascular endothelium, platelets, leukocytes and sensory neurons are discussed.

Thromboangiitis obliterans (TAO) or Buerger’s disease is a segmental inflammatory, thrombotic occlusive peripheral vascular disease with unknown aetiology that usually involves the medium and small-sized vessels of young male smokers. Due to its unknown aetiology and similarities with atherosclerosis and vasculitis, TAO diagnosis is still challenging. We aimed to review the status of biomolecular and laboratory para-clinical markers in TAO compared to atherosclerosis and vasculitis. We reported that, although some biomarkers might be common in TAO, atherosclerosis, and vasculitis, each disease occurs through a different pathway and, to our knowledge, there is no specific and definitive marker for differentiating TAO from atherosclerosis or vasculitis. Our review highlighted that pro-inflammatory and cell-mediated immunity cytokines, IL-33, HMGB1, neopterin, MMPs, ICAM1, complement components, fibrinogen, oxidative stress, NO levels, eNOS polymorphism, adrenalin and noradrenalin, lead, cadmium, and homocysteine are common markers. Nitric oxide, MPV, TLRs, MDA, ox-LDL, sST2, antioxidant system, autoantibodies, and type of infection are differential markers, whereas platelet and leukocyte count, haemoglobin, lipid profile, CRP, ESR, FBS, creatinine, d-dimer, hypercoagulation activity, as well as protein C and S are controversial markers. Finally, our study proposed diagnostic panels for laboratory differential diagnosis to be considered at first and in more advanced stages.

Venous leg ulcers (VLUs) are the most severe complication caused by the progression of chronic venous insufficiency. They account for approximately 70–90% of all chronic leg ulcers (CLUs). A total of 1% of the Western population will suffer at some time in their lives from a VLU. Furthermore, most CLUs are VLUs, defined as chronic leg wounds that show no tendency to heal after three months of appropriate treatment or are still not fully healed at 12 months. The essential feature of VLUs is their recurrence. VLUs also significantly impact quality of life and could cause social isolation and depression. They also have a significant avoidable economic burden. It is estimated that the treatment of venous ulceration accounts for around 3% of the total expenditure on healthcare. A VLU-free world is a highly desirable aim but could be challenging to achieve with the current knowledge of the pathophysiology and diagnostic and therapeutical protocols. To decrease the incidence of VLUs, the long-term goal must be to identify high-risk patients at an early stage of chronic venous disease and initiate appropriate preventive measures. This review discusses the epidemiology, socioeconomic burden, pathophysiology, diagnosis, modes of conservative and invasive treatment, and prevention of VLUs.