ABSTRACT: Cholesterol crystal embolization is a rare but recognized complication of cardiac catheterization. While management has traditionally been supportive only, we demonstrate the successful use of corticosteroids in treatment of a patient with cholesterol crystal embolization to the distal extremity. J INVAS CARDIOL 2004;16:222–223 Key words: atheroembolism, angiography, corticosteroid Cholesterol crystal embolization (CCE) is a known, albeit uncommon, complication of all angiography, including cardiac catheterization and percutaneous transluminal angioplasty (PTCA). Its clinical presentation is diverse, ranging from relatively benign with involvement limited to the lower limbs, to life-threatening with multi-organ dysfunction including renal failure, heart failure, gastrointestinal ischemia, pancreatitis, encephalopathy, muscle ischemia, and skin necrosis.1 Medical treatment is mostly supportive and optimal therapy is yet to be established. However, several anecdotal reports have pointed to the possible benefit of corticosteroids in the management of CCE.1–4 In this report, we describe a patient diagnosed with cholesterol crystal embolization to the distal lower limb after PTCA who improved with corticosteroid therapy. Case Report. A 47-year-old Caucasian male with a history of angina pectoris, hypertension, and dyslipidemia underwent coronary angiography and was found to have a 70% stenosis of the right coronary artery. He subsequently underwent a successful PTCA and stenting procedure with access obtained through a 6 Fr sheath placed in the right femoral artery. He received abciximab and heparin during the procedure. The patient was discharged after 10 hours. However, 18 hours after the procedure, he complained of pain in his right great toe and was noted to have swelling, tenderness, and a 2 cm by 2 cm ecchymoses on the plantar aspect of the right great toe (Figure 1), and a 2 cm by 1 cm ecchymoses on the right heel. No femoral bruits were heard and the patient had 2+ femoral, popliteal, dorsalis pedis, and tibialis posterior artery pulses. Following readmission, CT scan of the abdomen and pelvis did not reveal the presence of aneurysm or unstable atherosclerotic plaque in the aorta, and Doppler ultrasound studies showed normal blood flow to the lower extremities. The patient was diagnosed as having microembolic disease of the distal right lower extremity secondary to cholesterol crystal embolization caused by his recent angiography and PTCA. He was given methylprednisolone 100 mg IV and subsequently placed on methylprednisolone PO starting at 24 mg then tapered off over 1 week. Twenty-four hours after initiation of corticosteroid therapy, the patient reported a marked decrease in intensity of tenderness, and on follow-up after 1 week, there was complete resolution of the swelling, tenderness, and ecchymoses. Discussion. Cholesterol crystal embolization (CCE) is defined as the occlusion of arterioles by cholesterol crystals after their dislodgement from eroded atheromatous plaques. The cholesterol crystals can spread to almost any organ, thereby giving rise to a varied clinical picture. However, a study of 833 histologically proven cases of CCE in the Netherlands showed that the most common presentations were renal failure (17.5%), gastrointestinal ischemia (14.8%), and skin lesions (14.4%).5 In the same study, Moolenar et al. noted common predisposing factors were aortic aneurysm surgery, angiography, and PTCA. CCE is a relatively rare complication of angiography. In a paper by Drost et al., CCE was diagnosed in only 7 out of 4587 catheterizations.6 However, the incidence may actually be higher as shown by a study that reported a finding of cholesterol embolism on autopsy in 25.5% of patients who underwent recent cardiac catheterization and coronary angiography.7 This suggests a significant number of asymptomatic cases. The underlying mechanism of CCE is believed to be destabilization of cholesterol plaques, resulting into release of cholesterol crystals into the circulation. These lodge into smaller vessels and cause infarction of distal tissues.1,8 Additionally, it has been proposed that the cholesterol crystals aggravate the initial injury by inciting a foreign body reaction involving an inflammatory cascade of leukocyte aggregation, release of leukocytic enzymes and oxidants, endothelial injury, and intravascular coagulation that eventually leads to fibrosis of the involved vessels.4,8 Biopsy of arteries affected by CCE has shown arteritis and periarteritis, with eosinophils, polymorphs, leukocytes, and macrophages around intraluminal cholesterol materials, supporting the inflammatory nature of CCE.9 To date, no definitive treatment for CCE has been established. Management is still mostly supportive. A review of recent literature revealed that 3 classes of medications — HMG-CoA reductase inhibitors, prostanoids, and corticosteroids — have been used to treat CCE with some success. HMG-CoA reductase inhibitors have previously been used to treat patients with CCE, with subsequent improvement of renal and dermatologic symptoms.11–13 It has been proposed that the mechanism behind this is the stabilization of cholesterol-rich atherosclerotic plaques that had been showering the distal circulations with emboli.12 Prostanoids, which are potent vasodilators and antiplatelet aggregants, have also been looked at. In a series of four case reports, iloprost, a prostacyclin analogue, was used in patients with cholesterol emboli syndrome, with associated improvement in ischemic skin lesions and renal function.14 Corticosteroids may decrease the inflammation and foreign body reaction associated with cholesterol embolization. Corticosteroids have been described in the successful treatment of renal failure due to CCE after renal arteriography and angioplasty, with note of rapid and sustained improvement in renal function.2 Prednisolone, in conjunction with plasma exchange, was associated with improvement in 3 patients with renal artery cholesterol embolism.3 Dahlberg et al. reported the use of high-dose corticosteroids in 2 patients with peripheral CCE who responded with dramatic improvement.4 Belenfant et al. described the use of prednisolone at a dose of 0.3 mg/kg in a 18 patients, with subsequent relief of lower limb and/or gastrointestinal pain due to CCE. Other authors observed lack of improvement in patients with CCE after being treated with steroids.6 However, the steroid dose and duration of treatment was not mentioned in their report. In this case report, the corticosteroid methylprednisolone was used in a patient who presented with microembolic disease to the distal lower limb after angiography and PTCA, with note of dramatic and complete resolution of pain, swelling, and skin changes. This is in sharp contrast to patients with distal embolic disease due to CCE who were managed supportively, in whom symptoms lasted for several months and in some cases, even led to toe amputation.6,13 In cholesterol crystal embolization, use of high-dose corticosteroids may decrease the amount of inflammatory reaction to the cholesterol crystals, thus limiting the extent and duration of the disease.
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