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Cutaneous Manifestations of Cholesterol Embolism Treatment & Management

  • Author: Laura F McGevna, MD; Chief Editor: William D James, MD  more...
 
Updated: Jun 27, 2016
 

Medical Care

Cholesterol embolization has a serious prognosis; unfortunately, treatment options remain limited. However, both conservative medical care and surgical therapy are available. In 1999, Belenfant et al published a prospective study of 67 patients with cholesterol embolism using therapies targeted at the most common causes of death in cholesterol embolism.[2] This approach reduced the 1-year mortality rate to as low as 23%.

Remove precipitating factors. Discontinue all forms of anticoagulants and, if possible, planned invasive endovascular procedures.

Modify risk factors. Manage blood pressure (goal blood pressure <140/80 mm Hg) using vasodilators (eg, ACE inhibitors, calcium channel blockers, nitrates). Use statin lipid-lowering medications. Use prednisolone in patients with laboratory evidence of inflammation (ie, elevation of C-reactive protein and fibrinogen levels, increased erythrocyte sedimentation rate, a change in serum complement levels).

Institute supportive care. Use high-dose loop diuretics and/or ultrafiltration in patients with pulmonary edema. Provide enteral or parenteral nutritional support.

It must be emphasized that management principles for cholesterol embolism are often conflicting because therapeutic vascular procedures and/or dialysis may aggravate the condition, and these patients tend to be high risk for surgery. Further, there are reports of improvement with anticoagulation.[30, 31] This is likely because damage is not solely from cholesterol crystals, but the clinical picture of thrombosis and vessel obstruction that occur concomitantly and the cascade of inflammation resulting from endothelial damage.

Many published anecdotal reports describe other therapeutic approaches to cholesterol embolism. None has been studied critically; however, these methods may be of some value if surgical intervention cannot be performed or must be delayed.

Case reports exist of spontaneously healing cutaneous lesions.

Individual case reports show benefit from high-dose corticosteroids. Dahlberg et al,[32] Vacher-Coponat et al,[17] Belenfant et al,[2] and others detailed the potential use of steroid therapy for advanced disease, including those with acute renal failure or in those with pronounced cutaneous manifestations.[33] Steroids may limit the inflammatory effects of ischemia and resultant vascular occlusion. Further study is needed to clearly define the role of corticosteroids in the management of cholesterol embolism. Doses have included prednisone at 60 mg/d and methylprednisolone at 80 mg/d, with therapy lasting from 5 days to months, depending on the patient's response.

Multiple case reports have found that low-density lipoprotein (LDL) apheresis with the concomitant administration of other medications has produced favorable clinical outcomes. Simvastatin or alprostadil with LDL apheresis reportedly improves livedo reticularis.[34, 35] LDL apheresis with corticosteroids and/or an angiotensin receptor blocker has been found to decrease skin and brain manifestations, decrease eosinophilia, and improve kidney function.

The 2003 and 2007 studies by Scolari et al[9, 13] underscored the theory that statin therapy may be beneficial in patients with known atheroembolic renal disease. In these patients, statin therapy was associated with a better prognosis (P < .001), even when initiated well after diagnosis. The favorable outcomes associated with statin therapy may be secondary to both the anti-inflammatory and lipid-lowering properties of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, contributing to plaque stabilization and regression, perhaps initiating recanalization.

Successful pain relief and the improvement of purpura, livedo reticularis, and severe cyanosis on the lower extremities have been reported after treatment with intravenous iloprost in 4 cases.[36]

Success has been reported with oral pentoxifylline.[37]

Isolated case reports exist of successful management of cholesterol embolism with combination corticosteroid and cyclophosphamide therapy.[38] Yucel et al noted the treatment of a patient with corticosteroid and cyclophosphamide combination therapy, leading to improvement.[39] The outcome was appreciable improvement in skin lesions, but ultimately the patient was lost to follow up and succumbed to complications associated with infection.

Filip and Dillon reported successful therapy for cholesterol embolism using circulator boot therapy.[40] A circulator boot is a compression boot designed to restore blood flow to areas of ischemia. In the study, 41 legs were treated. Of these, 81% healed completely, 15% improved, and only 2 required amputation. Levels of evidence were not reported. The circulator boot is thought to function by expelling venous and lymphatic columns from the leg, thereby increasing the arterial-to-venous pressure ratio and providing force substantial enough to reperfuse areas of ischemia.

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Surgical Care

The principal goal of surgical treatment of cholesterol embolism is to promptly identify and eradicate the embolic source and to restore arterial flow. Carefully weigh the risks versus benefits of the surgical intervention and/or preoperative arteriography. In select cases, procedural intervention may be a favorable option.

Amputation or resection of infarcted or symptomatic tissues is often required in severe cases. Blue toe syndrome is usually an indication for limb salvage surgery.

Identification of the embolic source and removal of the atheromatous lesions by endarterectomy, a bypass graft, stent grafting, or excision and replacement of the involved segment of aorta may be important in preventing recurrent showers of emboli. In one study of endovascular stent-graft repair of an abdominal aortic aneurysm, resolution of cholesterol embolism was noted in only 2 of 19 patients at 30-day postoperative follow-up. At 1 year, 8 of 9 patients had complete resolution of their ischemic symptoms.[41]

For small uncomplicated aneurysms, intraluminal grafts inserted on a balloon catheter via the transfemoral route may offer an alternative to open surgery.

The role of lumbar sympathectomy to relieve symptoms from ischemic lower extremities in selected patients with blue toe syndrome remains controversial.

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Prevention

Carefully weigh the risks versus benefits of surgical therapies, and apply the results individually to patients with cholesterol embolism syndrome.

Prevention of recurrent cholesterol embolism may be achieved by discontinuing all forms of anticoagulants.

Identification of the embolic source and removal of atheromatous lesions by endarterectomy, bypass graft surgery, or excision and replacement of the involved segment of aorta may be important in preventing recurrent showers of emboli.

One study of 7621 patients by Eggebrecht et al indicates that use of catheters smaller than 8 French in angiographic procedures may prevent some cases of cholesterol embolism.[42]

Use of distal filters in endovascular procedures is being studied to explore feasibility for procedural effectiveness and prevention of distal embolization. Although these procedures have shown favorable results with the immediate release of cholesterol emboli, it is unlikely that they will prove useful in delayed events. In one study by Holden and Hill,[43] 46 ischemic nephropathic renal arteries underwent renal artery angioplasty and stenting with distal main renal artery protection. In 95% of patients, renal function was stabilized or improved at follow-up. In the control group without distal protection, 25% of patients experienced either unchanged decline or acute deterioration in renal function after the procedure.

Whitlow et al described 75 patients with severe internal carotid artery stenosis who were treated with stents deployed with a distal system protection system. All 75 patients (100%) had grossly visible particulate material aspirated from the filter, and all were without major or minor stroke or death at 30 days.[44]

Siablis et al described 16 patients who underwent lower limb recanalization for both acute and subacute occlusions with distal filter devices. The recanalization rate was 16 (100%) of 16, without any clinical or angiographic evidence of periprocedural distal embolization.[45]

Cardaioli et al reported successful use of filter-assisted stenting in a 70-year-old man.

New strategies for minimizing cholesterol emboli as a result of cardiopulmonary bypass are emerging. One possible preventive measure is off-pump bypass surgery. Lund et al studied cerebral microembolization in 52 patients during cardiopulmonary bypass (29 off-pump). While a greater reduction of cerebral microemboli was noted during off-pump compared with on-pump surgery, clinical outcomes were not significant.

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Contributor Information and Disclosures
Author

Laura F McGevna, MD Assistant Professor of Medicine, Dermatology Division, University of Vermont College of Medicine

Laura F McGevna, MD is a member of the following medical societies: American Academy of Dermatology, Dermatology Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Samreen R Raza, MD Resident Physician, Department of Internal Medicine, University of Vermont College of Medicine

Samreen R Raza, MD is a member of the following medical societies: American College of Physicians, Royal Society of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Catharine Lisa Kauffman, MD, FACP Georgetown Dermatology and Georgetown Dermpath

Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, Royal Society of Medicine, Women's Dermatologic Society, American Medical Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Edwin Rhim, MD, and Heather D. Rogers, MD, to the development and writing of this article.

References
  1. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology. 1987 Oct. 38(10):769-84. [Medline].

  2. Belenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999 May. 33(5):840-50. [Medline].

  3. Brown NJ, Morgan HJ. Spontaneous cholesterol emboli presenting as livedo reticularis. J Tenn Med Assoc. 1992 Feb. 85(2):64. [Medline].

  4. Enomae M, Takeda S, Yoshimoto K, Takagawa K. Chronic cholesterol crystal embolism with a spontaneous onset. Intern Med. 2007. 46(14):1123-6. [Medline].

  5. Gore I, Collins DP. Spontaneous atheromatous embolization. Review of the literature and a report of 16 additional cases. Am J Clin Pathol. 1960 May. 33:416-26. [Medline].

  6. Klein R, Klein BE, Moss SE, Meuer SM. Retinal emboli and cardiovascular disease: the Beaver Dam Eye Study. Arch Ophthalmol. 2003 Oct. 121(10):1446-51. [Medline].

  7. Moolenaar W, Lamers CB. Cholesterol crystal embolization in the Netherlands. Arch Intern Med. 1996 Mar 25. 156(6):653-7. [Medline].

  8. Jucgla A, Moreso F, Muniesa C, Moreno A, Vidaller A. Cholesterol embolism: still an unrecognized entity with a high mortality rate. J Am Acad Dermatol. 2006 Nov. 55(5):786-93. [Medline].

  9. Scolari F, Ravani P, Pola A, et al. Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study. J Am Soc Nephrol. 2003 Jun. 14(6):1584-90. [Medline].

  10. Manganoni AM, Venturini M, Scolari F, et al. The importance of skin biopsy in the diverse clinical manifestations of cholesterol embolism. Br J Dermatol. 2004 Jun. 150(6):1230-1. [Medline].

  11. Karmody AM, Powers SR, Monaco VJ, Leather RP. "Blue toe" syndrome. An indication for limb salvage surgery. Arch Surg. 1976 Nov. 111(11):1263-8. [Medline].

  12. Panuncialman J, Falanga V. Unusual causes of cutaneous ulceration. Surg Clin North Am. 2010 Dec. 90(6):1161-80. [Medline]. [Full Text].

  13. Scolari F, Ravani P, Gaggi R, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007 Jul 17. 116(3):298-304. [Medline].

  14. Tappenden J, Suvarna SK, Ackroyd R. Cholesterol crystal embolization leading to perforation of the gallbladder. Hepatobiliary Pancreat Dis Int. 2007. 6:653-655.

  15. Sarwar S, Al-Absi A, Wall BM. Catastrophic cholesterol crystal embolization after endovascular stent placement for peripheral vascular disease. Am J Med Sci. 2008 May. 335(5):403-6. [Medline].

  16. Takahashi K, Iijima K, Nagasaki M, Torii I, Yamaguchi S, Kobayashi S. Deterioration of vascular dementia caused by recurrent multiple small emboli from thoracic aortic atheroma. Intern Med. 2004 Jul. 43(7):607-11. [Medline].

  17. Vacher-Coponat H, Pache X, Dussol B, Berland Y. Pulmonary-renal syndrome responding to corticosteroids: consider cholesterol embolization. Nephrol Dial Transplant. 1997 Sep. 12(9):1977-9. [Medline].

  18. Reuter MD, Chor PJ, Dehlendorf A, Alpert MA. Spontaneous cholesterol crystal embolization to bone marrow. South Med J. 2007 May. 100(5):533-6. [Medline].

  19. Pierce JR Jr, Wren MV, Cousar JB Jr. Cholesterol embolism: diagnosis antemortem by bone marrow biopsy. Ann Intern Med. 1978 Dec. 89(6):937-8. [Medline].

  20. Muretto P, Carnevali A, Ansini AL. Cholesterol embolism of bone marrow clinically masquerading as systemic or metastatic tumor. Haematologica. 1991 May-Jun. 76(3):248-50. [Medline].

  21. Glassock RJ, Ritz E, Bommer J, Andrassy K, Waldherr R. Acute renal failure, hypertension and skin necrosis in a patient with streptokinase therapy. Am J Nephrol. 1984. 4(3):193-200. [Medline].

  22. Ridker PM, Michel T. Streptokinase therapy and cholesterol embolization. Am J Med. 1989 Sep. 87(3):357-8. [Medline].

  23. Schwartz MW, McDonald GB. Cholesterol embolization syndrome. Occurrence after intravenous streptokinase therapy for myocardial infarction. JAMA. 1987 Oct 9. 258(14):1934-5. [Medline].

  24. Dubel GJ, Murphy TP. Distal embolic protection for renal arterial interventions. Cardiovasc Intervent Radiol. 2008 Jan-Feb. 31(1):14-22. [Medline].

  25. Fukumoto Y, Tsutsui H, Tsuchihashi M, Masumoto A, Takeshita A. The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study. J Am Coll Cardiol. 2003 Jul 16. 42(2):211-6. [Medline].

  26. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol. 1986 Oct. 122(10):1194-8. [Medline].

  27. Nakashima Y, Fujii H, Sumiyoshi S, Wight TN, Sueishi K. Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler Thromb Vasc Biol. 2007 May. 27(5):1159-65. [Medline].

  28. Sklar JL, Taira JW. Cholesterol emboli syndrome. Int J Dermatol. 1993 Aug. 32(8):607-9. [Medline].

  29. Grau R. Pseudovasculitis: mechanisms of vascular injury and clinical spectrum. Curr Rheumatol Rep. 2002 Feb. 4 (1):83-9. [Medline].

  30. Wakabayashi T, Yoshizawa Y, Kawana S. Successful use of heparin and warfarin in the treatment of cholesterol crystal embolization. J Dermatol. 2008 Feb. 35(2):111-4. [Medline].

  31. Funabiki K, Masuoka H, Shimizu H, et al. Cholesterol crystal embolization (CCE) after cardiac catheterization: a case report and a review of 36 cases in the Japanese literature. Jpn Heart J. 2003 Sep. 44(5):767-74. [Medline].

  32. Dahlberg PJ, Frecentese DF, Cogbill TH. Cholesterol embolism: experience with 22 histologically proven cases. Surgery. 1989 Jun. 105(6):737-46. [Medline].

  33. Desai M, Ram R, Prayaga A, Dakshinamurty KV. Cholesterol crystal embolization (CCE): Improvement of renal function with high-dose corticosteroid treatment. Saudi J Kidney Dis Transpl. 2011 Mar. 22(2):327-30. [Medline].

  34. Finch TM, Ryatt KS. Livedo reticularis caused by cholesterol embolization may improve with simvastatin. Br J Dermatol. 2000 Dec. 143(6):1319-20. [Medline].

  35. Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998 May 2. 351(9112):1331-2. [Medline].

  36. Elinav E, Chajek-Shaul T, Stern M. Improvement in cholesterol emboli syndrome after iloprost therapy. BMJ. 2002 Feb 2. 324(7332):268-9. [Medline]. [Full Text].

  37. Carr ME Jr, Sanders K, Todd WM. Pain relief and clinical improvement temporally related to the use of pentoxifylline in a patient with documented cholesterol emboli--a case report. Angiology. 1994 Jan. 45(1):65-9. [Medline].

  38. Maeshima E, Yamada Y, Mune M, Yukawa S. A case of cholesterol embolism with ANCA treated with corticosteroid and cyclophosphamide. Ann Rheum Dis. 2001 Jul. 60(7):726. [Medline].

  39. Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998 May 2. 351(9112):1331-2. [Medline].

  40. Filip JR, Dillon RS. Treatment of end-stage "trash feet" with the end-diastolic pneumatic boot. Angiology. 2008 Apr-May. 59(2):214-9. [Medline].

  41. Carroccio A, Olin JW, Ellozy SH, et al. The role of aortic stent grafting in the treatment of atheromatous embolization syndrome: results after a mean of 15 months follow-up. J Vasc Surg. 2004 Sep. 40(3):424-9. [Medline].

  42. Eggebrecht H, Oldenburg O, Dirsch O, et al. Potential embolization by atherosclerotic debris dislodged from aortic wall during cardiac catheterization:: histological and clinical findings in 7,621 patients. Catheter Cardiovasc Interv. 2000 Apr. 49(4):389-94. [Medline].

  43. Holden A, Hill A. Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience. J Vasc Surg. 2003 Nov. 38(5):962-8. [Medline].

  44. Whitlow PL, Lylyk P, Londero H, et al. Carotid artery stenting protected with an emboli containment system. Stroke. 2002 May. 33(5):1308-14. [Medline].

  45. Siablis D, Karnabatidis D, Katsanos K, Ravazoula P, Kraniotis P, Kagadis GC. Outflow protection filters during percutaneous recanalization of lower extremities' arterial occlusions: a pilot study. Eur J Radiol. 2005 Aug. 55(2):243-9. [Medline].

 
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A 76-year-old man with a history of aortobifemoral bypass graft developed this eruption after an angiographic procedure. This image shows the plantar surface of the right foot with some of the discoloration resulting from petechiae arranged in a reticulated pattern. This is not livedo reticularis. Petechiae do not blanch on diascopy, but the lesions of livedo reticularis do blanch.
Aorta with an ulcerated plaque (black arrowhead) on the luminal side photographed under water to enhance reflection of cholesterol crystals (white arrowhead).
Low-power view of a skin biopsy specimen demonstrating an arteriole within the subcutaneous fat occluded with thrombus material that contains (black arrowhead) needle-shaped cholesterol clefts (hematoxylin and eosin stain, original magnification X40).
High-power view of occluded vessel (hematoxylin and eosin stain, original magnification X100).
Symmetric involvement of the feet with livedo reticularis on the plantar surface of the forefoot and cyanosis of the left fifth toe. The painful cyanotic toe is typical of blue toe syndrome.
Dorsal surface of the toes of the right foot of a patient with discoloration resulting from petechiae. This image shows cyanosis of the fourth toe. The dominant eruption is petechial. Note the pallor of the tip of the great toe and the second toe. This finding indicates acute loss of perfusion.
Plantar surface of the right foot. The distal half of the great toe is gangrenous, with a sharp demarcation between the necrotic tissue and the normal proximal skin. Livedo reticularis is present on the distal plantar forefoot, and petechiae are present on the distal pad of the second and fourth toes.
The lower extremities show well-developed livedo reticularis and focal areas of erosion and ulceration.
Photomicrographs of histologic sections of an aorta with van Gieson stain. (Left) An atherosclerotic plaque with the fibrous cap (black arrowhead) overlying a necrotic core of cellular debris, extracellular lipids, and cholesterol clefts (white arrowhead). Underneath the plaque is the elastic media (arrow). (Right) A ruptured atherosclerotic plaque exposing the atheromatous debris containing cholesterol crystals to the bloodstream on the luminal side of the aorta.
CT scan of an infrarenal abdominal aortic aneurysm showing the mural thrombosis (white arrowhead) and the bright atherosclerotic calcifications (black arrowhead).
 
 
 
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