Cholesterol embolism

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Cholesterol embolism
Other namesCholesterol crystal embolism, atheroembolism, blue toe, purple toe syndrome, trash foot, warfarin blue toe syndrome [1] : 338 
Cholesterol embolus - intermed mag.jpg
Micrograph showing a cholesterol embolus in a medium sized artery of the kidney. Kidney biopsy. H&E stain.
Specialty Cardiology   OOjs UI icon edit-ltr-progressive.svg

Cholesterol embolism occurs when cholesterol is released, usually from an atherosclerotic plaque, and travels as an embolus in the bloodstream to lodge (as an embolism) causing an obstruction in blood vessels further away. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene of the extremities and sometimes kidney failure; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. [2] When the kidneys are involved, the disease is referred to as atheroembolic renal disease. [3] The diagnosis usually involves biopsy (removing a tissue sample) from an affected organ. Cholesterol embolism is treated by removing the cause and giving supportive therapy; statin drugs have been found to improve the prognosis. [2]

Contents

Signs and symptoms

The symptoms experienced in cholesterol embolism depend largely on the organ involved. Non-specific symptoms often described are fever, muscle ache and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toes, small infarcts and areas of gangrene due to tissue death that usually appear black, and areas of the skin that assume a marbled pattern known as livedo reticularis . [3] The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities. Very rarely the ulcerated plaque is below the aortic bifurcation and those cases the changes occur only in one lower extremity.[ citation needed ]

Kidney involvement leads to the symptoms of kidney failure, which are non-specific but usually cause nausea, reduced appetite (anorexia), raised blood pressure (hypertension), and occasionally the various symptoms of electrolyte disturbance such as an irregular heartbeat. Some patients report hematuria (bloody urine) but this may only be detectable on microscopic examination of the urine. Increased amounts of protein in the urine may cause edema (swelling) of the skin (a combination of symptoms known as nephrotic syndrome). [3]

If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal pain, gastrointestinal hemorrhage (vomiting blood, or admixture of blood in the stool), and occasionally acute pancreatitis (inflammation of the pancreas). [3]

Both the central nervous system (brain and spinal cord) and the peripheral nervous system may be involved. Emboli to the brain may cause stroke-like episodes, headache and episodes of loss of vision in one eye (known as amaurosis fugax). [3] Emboli to the eye can be seen by ophthalmoscopy and are known as plaques of Hollenhorst. [4] Emboli to the spinal cord may cause paraparesis (decreased power in the legs) or cauda equina syndrome, a group of symptoms due to loss of function of the distal part of the spinal cord – loss of control over the bladder, rectum and skin sensation around the anus. [3] If the blood supply to a single nerve is interrupted by an embolus, the result is loss of function in the muscles supplied by that nerve; this phenomenon is called a mononeuropathy . [3]

Causes

It is relatively unusual (25% of the total number of cases) for cholesterol emboli to occur spontaneously; this usually happens in people with severe atherosclerosis of the large arteries such as the aorta. In the other 75% it is a complication of medical procedures involving the blood vessels, such as vascular surgery or angiography. In coronary catheterization, for instance, the incidence is 1.4%. [5] Furthermore, cholesterol embolism may develop after the commencement of anticoagulants or thrombolytic medication that decrease blood clotting or dissolve blood clots, respectively. They probably lead to cholesterol emboli by removing blood clots that cover up a damaged atherosclerotic plaque; cholesterol-rich debris can then enter the bloodstream. [3]

Diagnosis

Micrograph of a cholesterol embolus showing the characteristic cholesterol clefts (biconvex white spaces) and a giant cell reaction. Kidney biopsy. H&E stain. Cholesterol embolus - high mag.jpg
Micrograph of a cholesterol embolus showing the characteristic cholesterol clefts (biconvex white spaces) and a giant cell reaction. Kidney biopsy. H&E stain.

Differential diagnosis

Findings on general investigations (such as blood tests) are not specific for cholesterol embolism, which makes diagnosis difficult. The main problem is the distinction between cholesterol embolism and vasculitis (inflammation of the small blood vessels), which may cause very similar symptoms - especially the skin findings and the kidney dysfunction. [3] Worsening kidney function after an angiogram may also be attributed to kidney damage by substances used during the procedure (contrast nephropathy). Other causes that may lead to similar symptoms include ischemic kidney failure (kidney dysfunction due to an interrupted blood supply), a group of diseases known as thrombotic microangiopathies and endocarditis (infection of the heart valves with small clumps of infected tissue embolizing through the body). [3]

Blood and urine

Tests for inflammation (C-reactive protein and the erythrocyte sedimentation rate) are typically elevated, and abnormal liver enzymes may be seen. [3] If the kidneys are involved, tests of kidney function (such as urea and creatinine) are elevated. [3] The complete blood count may show particularly high numbers of a type of white blood cell known as eosinophils (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. [3] [5] Examination of the urine may show red blood cells (occasionally in casts as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. [3] If vasculitis is suspected, complement levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism. [6]

Tissue diagnosis

The microscopic examination of tissue (histology) gives the definitive diagnosis. The diagnostic histopathologic finding is intravascular cholesterol crystals, which are seen as cholesterol clefts in routinely processed tissue (embedded in paraffin wax). [7] The cholesterol crystals may be associated with macrophages, including giant cells, and eosinophils.[ citation needed ]

The sensitivity of small core biopsies is modest, due to sampling error, as the process is often patchy. Affected organs show the characteristic histologic changes in 50-75% of the clinically diagnosed cases. [3] [5] Non-specific tissue findings suggestive of a cholesterol embolization include ischemic changes, necrosis and unstable-appearing complex atherosclerotic plaques (that are cholesterol-laden and have a thin fibrous cap). While biopsy findings may not be diagnostic, they have significant value, as they help exclude alternate diagnoses, e.g. vasculitis, that often cannot be made confidently based on clinical criteria.[ citation needed ]

Treatment

Treatment of an episode of cholesterol emboli is generally symptomatic, i.e. it deals with the symptoms and complications but cannot reverse the phenomenon itself. [5] In kidney failure resulting from cholesterol crystal emboli, statins (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis. [2]

History

The phenomenon of embolisation of cholesterol was first recognized by the Danish pathologist Dr. Peter Ludvig Panum and published in 1862. [8] Further evidence that eroded atheroma was the source of emboli came from American pathologist Dr. Curtis M. Flory, who in 1945 reported the phenomenon in 3.4% of a large autopsy series of older individuals with severe atherosclerosis of the aorta. [3] [9]

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Eosinophilia Blood condition

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 x 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.

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Ischemia Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to any tissues, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also means local hypoxia in a given part of a body sometimes resulting from constriction. Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes. Ischemia can be partial or total blockage. The inadequate delivery of oxygenated blood to the organs must be resolved either by treating the cause of the inadequate delivery or reducing the oxygen demand of the system that needs it. For example, patients with myocardial ischemia have a decreased blood flow to the heart and are prescribed with medications that reduce chronotrophy and ionotrophy to meet the new level of blood delivery supplied by the stenosed so that it is adequate.

Vasculitis Medical disorders that destroy blood vessels by inflammation

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.

Henoch–Schönlein purpura Medical condition

Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura, often with joint pain and abdominal pain. With kidney involvement, there may be a loss of small amounts of blood and protein in the urine, but this usually goes unnoticed; in a small proportion of cases, the kidney involvement proceeds to chronic kidney disease. HSP is often preceded by an infection, such as a throat infection.

A vulnerable plaque is a kind of atheromatous plaque – a collection of white blood cells and lipids in the wall of an artery – that is particularly unstable and prone to produce sudden major problems such as a heart attack or stroke.

Eosinophilic granulomatosis with polyangiitis Medical condition

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Polyarteritis nodosa Medical condition

Polyarteritis nodosa (PAN) is a systemic necrotizing inflammation of blood vessels (vasculitis) affecting medium-sized muscular arteries, typically involving the arteries of the kidneys and other internal organs but generally sparing the lungs' circulation. Small aneurysms are strung like the beads of a rosary, therefore making this "rosary sign" an important diagnostic feature of the vasculitis. PAN is sometimes associated with infection by the hepatitis B or hepatitis C virus. The condition may be present in infants.

Minimal change disease Medical condition

Minimal change disease is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.

Livedo reticularis Medical condition

Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by reduction in blood flow through the arterioles that supply the cutaneous capillaries, resulting in deoxygenated blood showing as blue discoloration. This can be a secondary effect of a condition that increases a person's risk of forming blood clots, including a wide array of pathological and nonpathological conditions. Examples include hyperlipidemia, microvascular hematological or anemia states, nutritional deficiencies, hyper- and autoimmune diseases, and drugs/toxins.

Renal vein thrombosis Medical condition

Renal vein thrombosis (RVT) is the formation of a clot in the vein that drains blood from the kidneys, ultimately leading to a reduction in the drainage of one or both kidneys and the possible migration of the clot to other parts of the body. First described by German pathologist Friedrich Daniel von Recklinghausen in 1861, RVT most commonly affects two subpopulations: newly born infants with blood clotting abnormalities or dehydration and adults with nephrotic syndrome.

Interstitial nephritis Medical condition

Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules. In addition to providing a scaffolding support for the tubular architecture, the interstitium has been shown to participate in the fluid and electrolyte exchange as well as endocrine functions of the kidney.

Fat embolism syndrome Medical condition

Fat embolism syndrome occurs when fat enters the blood stream and results in symptoms. Symptoms generally begin within a day. This may include a petechial rash, decreased level of consciousness, and shortness of breath. Other symptoms may include fever and decreased urine output. The risk of death is about 10%.

Cerebral vasculitis is vasculitis involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels (capillaries), medium-size blood vessels, or large blood vessels. If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die. It may produce a wide range of neurological symptoms, such as headache, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to coma and herniation. Some of its signs and symptoms may resemble multiple sclerosis. 10% have associated bleeding in the brain.

Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis.

Cutaneous small-vessel vasculitis Medical condition

Cutaneous small-vessel vasculitis (CSVV), also known as hypersensitivity vasculitis, cutaneous leukocytoclastic vasculitis, hypersensitivity angiitis, cutaneous leukocytoclastic angiitis, cutaneous necrotizing vasculitis and cutaneous necrotizing venulitis, is inflammation of small blood vessels, characterized by palpable purpura. It is the most common vasculitis seen in clinical practice.

Renal biopsy

Renal biopsy is a medical procedure in which a small piece of kidney is removed from the body for examination, usually under a microscope. Microscopic examination of the tissue can provide information needed to diagnose, monitor or treat problems of the kidney.

Arterial embolism Interruption of blood flow to an organ

Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmonary embolism is classified as arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins. Arterial embolism is the major cause of infarction.

Arterial occlusion

Arterial occlusion is a condition involving partial or complete blockage of blood flow through an artery. Arteries are blood vessels that carry oxygenated blood to body tissues. An occlusion of arteries disrupts oxygen and blood supply to tissues, leading to ischemia. Depending on the extent of ischemia, symptoms of arterial occlusion range from simple soreness and pain that can be relieved with rest, to a lack of sensation or paralysis that could require amputation.

References

  1. ↑ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN   978-1-4160-2999-1.
  2. 1 2 3 Scolari F, Ravani P, Gaggi R, et al. (July 2007). "The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors". Circulation. 116 (3): 298–304. doi: 10.1161/CIRCULATIONAHA.106.680991 . PMID   17606842.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Modi KS, Rao VK (August 2001). "Atheroembolic renal disease". J. Am. Soc. Nephrol. 12 (8): 1781–7. doi:10.1681/ASN.V1281781. PMID   11461954.
  4. ↑ Schwarcz TH; Eton D; Ellenby MI; Stelmack T; McMahon TT; Mulder S; Meyer JP; Eldrup-Jorgensen J; Durham JR (May 1990). "Hollenhorst plaques: retinal manifestations and the role of carotid endarterectomy". J Vasc Surg. 11 (5): 635–641. doi:10.1016/0741-5214(90)90208-R. PMID   2335833.
  5. 1 2 3 4 Fukumoto Y, Tsutsui H, Tsuchihashi M, Masumoto A, Takeshita A (July 2003). "The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study". J. Am. Coll. Cardiol. 42 (2): 211–6. doi: 10.1016/S0735-1097(03)00579-5 . PMID   12875753.
  6. ↑ Cosio FG, Zager RA, Sharma HM (July 1985). "Atheroembolic renal disease causes hypocomplementaemia". Lancet. 2 (8447): 118–21. doi:10.1016/S0140-6736(85)90225-9. PMID   2862317. S2CID   30580788.
  7. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 1735–6. ISBN   978-0-7817-7942-5.
  8. ↑ Panum PL (1862). "Experimentelle Beitrage zur Lehre von der Embolie". Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (in German). 25 (5–6): 308–310. doi:10.1007/BF01879803. S2CID   29504624.
  9. ↑ Flory CM (1945). "Arterial occlusions produced by emboli from eroded aortic atheromatous plaques". Am J Pathol. 21 (3): 549–565. PMC   1934118 . PMID   19970827.
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