Blue Toe Syndrome ( Cholesterol Embolization Syndrome)
Blue toe syndrome is characterised by tissue ischaemia secondary to cholesterol crystal or atherothrombotic embolisation. It leads to the occlusion of small vessels. Cyanosis of the digits may have several etiologies ranging from trauma to connective tissue disease, however the most common cause of blue toe syndrome is atheroembolic disease or aneurysm. Embolisation occurs typically following an ulcerated atherosclerotic plaque or aneurysms located in the aorto-iliac-femoral arterial system. Embolisation can occur spontaneously or due to a variety of causes. Most often, microembolisation appears in elderly men who have undergone an angiographic procedure or vascular surgery or even anticoagulant or thrombolytic treatment.
The following 6 key elements are required for the development of cholesterol embolization syndrome:
Presence of a plaque in a proximal, large-caliber artery (such as the internal carotid artery, the iliac arteries, or the aorta)
Plaque rupture (spontaneous, traumatic, or iatrogenic)
Embolization of plaque debris (containing cholesterol crystals, platelets, fibrin, and calcified detritus)
Lodging of the emboli in small to medium arteries with a diameter of 100 to 200 μm, leading to mechanical occlusion
Foreign-body inflammatory response to cholesterol emboli
End-organ damage due to a combined effect of mechanical plugging and inflammation.
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Clinically apparent atheroembolism is an uncommon complication of cardiac catheterization. In a prospective study of 1786 consecutive patients aged ≥40 years, who underwent left-heart catheterization in Japan, cholesterol embolization syndrome (defined as livedo reticularis, blue toe syndrome, digital gangrene, or renal failure) was found in 25 patients (incidence of 1.4%). There was no significant difference in the risk of atheroembolism between femoral and brachial approach, suggesting that the ascending aorta is the predominant source of cholesterol emboli. In another prospective study that examined renal failure as the only manifestation of cholesterol embolization syndrome after cardiac catheterization, the incidence was also relatively low. Among 263 study patients, renal failure was attributed to cholesterol emboli in 5 patients (incidence of 1.9%).
The syndrome of cholesterol embolism is often a multiorgan disorder. Clinical presentation can range from a cyanotic toe or livedo reticularis to a diffuse multiorgan systemic disease that can mimic other systemic illnesses. Mild forms of the disease have a good prognosis and subside without sequelae. However, diffuse multisystemic forms have a very poor prognosis. The kidney is the organ that is most often affected (in approximataly 50 % of cases). In the systemic form prognosis is poor, with a mortality rate of about 70 % .
Medical treatment is mostly symptomatic: rest, warm condition, appropriate dressing, hydration, and organ support when necessary, principally to ensure renal function. Treatment of pain that is usually disproportionate to the extension of tissue lesion is of utmost importance. Because these patients usually have advanced atherosclerotic disease, secondary prevention with elimination of risk factors of atherosclerosis is mandatory. Antiplatelet drugs represent one of the basic treatment options of blue toe syndrome . The complete relief of pain and restoration of circulation is also obtained by aspirin administration in ischaemic complications of polycythemia vera complete. Vasodilator drugs, including alpha-1 blocking agents that are usually used for the treatment of vasospastic disorders have no proven efficacy in blue toe syndrome. In diffuse and multi-visceral embolisation either colchicine or corticosteroids adjuvant therapy may be useful. According to our experience prostanoid drugs are also effective in treating ischaemic lesions caused by microembolisation. In the future large randomised studies will be needed to help predict embolisation and thus decide on the proper medical therapy.
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