Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
A Purpuric Patch on the Flank Ohara Aivaz, MD; Mamina M. Turegano, MD; Arash Radfar, MD, PhD
A
B
C
Figure. A, Photograph of a purpuric patch on the left flank. B, Biopsy specimen 1 (hematoxylin-eosin, original magnification ×40) showing needle-shaped clefts within the lumen of a blood vessel with minimal perivascular inflammation.
C, Biopsy specimen 2 (hematoxylin-eosin, original magnification ×40). Eccrine ducts show cellular dyshesion and necrosis.
A man in his 60s presented to the emergency department for left flank pain of 1 week’s duration. His medical history included severe peripheral arterial disease and a remote history of ruptured abdominal aortic aneurysm. Three months before presentation, he underwent percutaneous endovascular stenting of a left popliteal artery aneurysm. Physical examination of the left flank showed a well-defined 5 × 12-cm purpuric patch with a darker stellate patch within it (Figure, A). Two punch biopsy specimens were obtained (Figure, B and C).
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Warfarin necrosis B. Calciphylaxis C. Cutaneous cholesterol embolism D. Intravascular B-cell lymphoma
JAMA Dermatology January 2015 Volume 151, Number 1
Copyright 2014 American Medical Association. All rights reserved.
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Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis C. Cutaneous cholesterol embolism
Microscopic Findings and Clinical Course Histopathologic examination of both biopsies revealed intravascular needle-shaped clefts within the lumina of blood vessels (Figure, B). Eccrine coil and duct necrosis were seen within the dermis (Figure, C). The clinical presentation and histologic findings confirmed the diagnosis of spontaneous cholesterol embolism (CE). The patient denied warfarin or enoxaparin use. Computed tomography (CT) of the abdomen and pelvis showed no intraperitoneal or retroperitoneal hemorrhages. Results of CT angiography revealed occluded bilateral common, internal, and external iliac arteries and patent renal arteries. Arterial Doppler studies of the left groin showed that an aorto-bifemoral stent and other lower extremity vessels were patent. Magnetic resonance imaging of the pelvis and thighs showed no evidence of muscle or bone infarction. Laboratory studies were notable for a C-reactive protein level of 57.50 mg/L (reference range, 0.08-3.1 mg/L). Peripheral eosinophil count, creatinine level, and urinalysis results were within normal limits. Urine toxicological screen results were negative. The patient was discharged with instructions to apply warm compresses for pain relief. He had a history of severe allergy to statins; thus, no lipid-modifying agents were initiated. Given the absence of visceral involvement, systemic medications were not started.
Discussion Cholesterol embolism syndrome (CES) occurs when cholesterol crystals break off from unstable atherosclerotic plaques in major arteries and occlude downstream arterioles, causing tissue ischemia.1,2 Usually, CES is seen in men 50 years or older; common comorbidities include diabetes mellitus, hyperlipidemia, hypertension, history of tobacco abuse, and peripheral vascular disease.3 PrecipitatingeventsforCE,includingendovascularproceduresand coronary artery stent placement, mechanically disrupt atherosclerotic plaques and shower downstream vessels with emboli.1 The use of chronic anticoagulation or acute thrombolytics can also predispose to atheroembolization by dissolving a clot that overlies and stabilizes an ulcerated atherosclerotic plaque.4 About 20% of emboli occur spontaneously with no known inciting event.2 High shearing forces as seen in hypertension, spontaneous hemorrhage within a plaque, and aneurysm formation are thought to contribute to plaque instability. ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Dermatology, Georgetown University Hospital–Washington Hospital Center, Washington, DC.
1. Avci G, Akoz T, Gul AE. Cutaneous cholesterol embolization. J Dermatol Case Rep. 2009;3(2):27.
Corresponding Author: Ohara Aivaz, MD, Department of Dermatology, Georgetown University Hospital–Washington Hospital Center, 110 Irving St NW, Ste 2B-44, Washington, DC 20010 ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: November 5, 2014. doi:10.1001/jamadermatol.2014.2721. Conflict of Interest Disclosures: None reported.
98
Depending on the case series, skin findings are seen in 35% to 88% of patients with CES.5,6 In a study of 26 patients with histologically proven CE, 23% of patients had solely cutaneous involvement.6 Livedo reticularis is the most common skin finding (49%), followed by gangrene (35%), cyanosis (28%), ulceration (17%), nodules (10%), and purpura (9%).5 The toes are the most common site for CE to deposit; truncal involvement can also occur. There are reports of CE presenting with necrotic and purpuric plaques of the sacrum, superolateral thighs, and suprapubic skin1,7 and case reports of men with facial livedo racemosa secondary to spontaneous atheroembolism from the external carotid artery.8 The symptomology of CES depends on the embolus’s site of origin. As the descending aorta and iliofemoral arteries are major sites of atherosclerosis, the kidneys, gastrointestinal tract, and lower extremities are the most common sites of CE.1 Renal emboli occur in about 50% of reported CE cases4,5; these can lead to a rapid rise in blood pressure and creatinine level, and roughly 35% of such patients require hemodialysis. Gastrointestinal tract involvement occurs in 15% to 20% of patients with systemic atheroemboli and presents as abdominal pain or gastrointestinal bleeding. Atheroemboli from the ascending aorta can travel to the eye, affecting vision, and to the brain, leading to altered mentation or transient ischemic attacks.3-5 When CES is limited to the skin, the disease course is relatively benign. Constitutional symptoms commonly associated with CES include weight loss, myalgias, headache, and fevers.3 Common laboratory abnormalities include leukocytosis, mild anemia, and elevated erythrocyte sedimentation rate.2 Peripheral eosinophilia is found in 80% of cases.7 The nonspecific signs and symptoms and multiorgan involvement of CES can mimic systemic vasculitis, autoimmune connective tissue disease, or infective endocarditis. Biopsy of the many cutaneous morphologies seen in CES is diagnostic in 92% of cases and prevents the increased morbidity of visceral biopsy.2 Characteristic findings are needle-shaped clefts in the arterial lumen, which correspond to cholesterol crystals dissolved during tissue processing.2,4 There are no universally accepted drug treatments for CES. Anticoagulant therapy should be discontinued if it seems to have precipitated the condition. While most studies support it, corticosteroid treatment of CE is controversial. Successful treatment of skin necrosis with iloprost, a prostacyclin analogue, as well as hyperbaric oxygen and pentoxifylline, has been reported.7,9,10
2. Patro N, George R, Singh P, Joseph G. Cutaneous cholesterol embolization syndrome. Dermatol Online J. 2012;18(7):10. 3. Chandrashekariah R, Fresko O, Lynfield YL. Cholesterol embolism. Cutis. 2001;68(4):263-267.
7. Erdim M, Tezel E, Biskin N. A case of skin necrosis as a result of cholesterol crystal embolisation. J Plast Reconstr Aesthet Surg. 2006; 59(4):429-432. 8. Eberl M, Fink AM, Jurecka W. Facial livedo racemosa as a warning sign of cholesterol embolism from atherosclerotic plaques of the carotid artery. J Am Acad Dermatol. 2011;64(6):1203-1205.
4. Hirschmann JV, Raugi GJ. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009;60(1):1-20.
9. Elinav E, Chajek-Shaul T, Stern M. Improvement in cholesterol emboli syndrome after iloprost therapy. BMJ. 2002;324(7332):268-269.
5. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol. 1986;122(10):1194-1198.
10. Gurgo A, Valenti V, Paneni F, et al. Hyperbaric oxygen therapy in a case of cholesterol crystal embolization. Am J Emerg Med. 2011;29(6):e3-e6.
6. Jucgla A, Moreso F, Muniesa C, Moreno A, Vidaller A. Cholesterol embolism. J Am Acad Dermatol. 2006;55(5):786-793.
JAMA Dermatology January 2015 Volume 151, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
A Purpuric Patch on the Flank Ohara Aivaz, MD; Mamina M. Turegano, MD; Arash Radfar, MD, PhD
A
B
C
Figure. A, Photograph of a purpuric patch on the left flank. B, Biopsy specimen 1 (hematoxylin-eosin, original magnification ×40) showing needle-shaped clefts within the lumen of a blood vessel with minimal perivascular inflammation.
C, Biopsy specimen 2 (hematoxylin-eosin, original magnification ×40). Eccrine ducts show cellular dyshesion and necrosis.
A man in his 60s presented to the emergency department for left flank pain of 1 week’s duration. His medical history included severe peripheral arterial disease and a remote history of ruptured abdominal aortic aneurysm. Three months before presentation, he underwent percutaneous endovascular stenting of a left popliteal artery aneurysm. Physical examination of the left flank showed a well-defined 5 × 12-cm purpuric patch with a darker stellate patch within it (Figure, A). Two punch biopsy specimens were obtained (Figure, B and C).
jamadermatology.com
WHAT IS THE DIAGNOSIS?
A. Warfarin necrosis B. Calciphylaxis C. Cutaneous cholesterol embolism D. Intravascular B-cell lymphoma
JAMA Dermatology January 2015 Volume 151, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
97
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis C. Cutaneous cholesterol embolism
Microscopic Findings and Clinical Course Histopathologic examination of both biopsies revealed intravascular needle-shaped clefts within the lumina of blood vessels (Figure, B). Eccrine coil and duct necrosis were seen within the dermis (Figure, C). The clinical presentation and histologic findings confirmed the diagnosis of spontaneous cholesterol embolism (CE). The patient denied warfarin or enoxaparin use. Computed tomography (CT) of the abdomen and pelvis showed no intraperitoneal or retroperitoneal hemorrhages. Results of CT angiography revealed occluded bilateral common, internal, and external iliac arteries and patent renal arteries. Arterial Doppler studies of the left groin showed that an aorto-bifemoral stent and other lower extremity vessels were patent. Magnetic resonance imaging of the pelvis and thighs showed no evidence of muscle or bone infarction. Laboratory studies were notable for a C-reactive protein level of 57.50 mg/L (reference range, 0.08-3.1 mg/L). Peripheral eosinophil count, creatinine level, and urinalysis results were within normal limits. Urine toxicological screen results were negative. The patient was discharged with instructions to apply warm compresses for pain relief. He had a history of severe allergy to statins; thus, no lipid-modifying agents were initiated. Given the absence of visceral involvement, systemic medications were not started.
Discussion Cholesterol embolism syndrome (CES) occurs when cholesterol crystals break off from unstable atherosclerotic plaques in major arteries and occlude downstream arterioles, causing tissue ischemia.1,2 Usually, CES is seen in men 50 years or older; common comorbidities include diabetes mellitus, hyperlipidemia, hypertension, history of tobacco abuse, and peripheral vascular disease.3 PrecipitatingeventsforCE,includingendovascularproceduresand coronary artery stent placement, mechanically disrupt atherosclerotic plaques and shower downstream vessels with emboli.1 The use of chronic anticoagulation or acute thrombolytics can also predispose to atheroembolization by dissolving a clot that overlies and stabilizes an ulcerated atherosclerotic plaque.4 About 20% of emboli occur spontaneously with no known inciting event.2 High shearing forces as seen in hypertension, spontaneous hemorrhage within a plaque, and aneurysm formation are thought to contribute to plaque instability. ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Dermatology, Georgetown University Hospital–Washington Hospital Center, Washington, DC.
1. Avci G, Akoz T, Gul AE. Cutaneous cholesterol embolization. J Dermatol Case Rep. 2009;3(2):27.
Corresponding Author: Ohara Aivaz, MD, Department of Dermatology, Georgetown University Hospital–Washington Hospital Center, 110 Irving St NW, Ste 2B-44, Washington, DC 20010 ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: November 5, 2014. doi:10.1001/jamadermatol.2014.2721. Conflict of Interest Disclosures: None reported.
98
Depending on the case series, skin findings are seen in 35% to 88% of patients with CES.5,6 In a study of 26 patients with histologically proven CE, 23% of patients had solely cutaneous involvement.6 Livedo reticularis is the most common skin finding (49%), followed by gangrene (35%), cyanosis (28%), ulceration (17%), nodules (10%), and purpura (9%).5 The toes are the most common site for CE to deposit; truncal involvement can also occur. There are reports of CE presenting with necrotic and purpuric plaques of the sacrum, superolateral thighs, and suprapubic skin1,7 and case reports of men with facial livedo racemosa secondary to spontaneous atheroembolism from the external carotid artery.8 The symptomology of CES depends on the embolus’s site of origin. As the descending aorta and iliofemoral arteries are major sites of atherosclerosis, the kidneys, gastrointestinal tract, and lower extremities are the most common sites of CE.1 Renal emboli occur in about 50% of reported CE cases4,5; these can lead to a rapid rise in blood pressure and creatinine level, and roughly 35% of such patients require hemodialysis. Gastrointestinal tract involvement occurs in 15% to 20% of patients with systemic atheroemboli and presents as abdominal pain or gastrointestinal bleeding. Atheroemboli from the ascending aorta can travel to the eye, affecting vision, and to the brain, leading to altered mentation or transient ischemic attacks.3-5 When CES is limited to the skin, the disease course is relatively benign. Constitutional symptoms commonly associated with CES include weight loss, myalgias, headache, and fevers.3 Common laboratory abnormalities include leukocytosis, mild anemia, and elevated erythrocyte sedimentation rate.2 Peripheral eosinophilia is found in 80% of cases.7 The nonspecific signs and symptoms and multiorgan involvement of CES can mimic systemic vasculitis, autoimmune connective tissue disease, or infective endocarditis. Biopsy of the many cutaneous morphologies seen in CES is diagnostic in 92% of cases and prevents the increased morbidity of visceral biopsy.2 Characteristic findings are needle-shaped clefts in the arterial lumen, which correspond to cholesterol crystals dissolved during tissue processing.2,4 There are no universally accepted drug treatments for CES. Anticoagulant therapy should be discontinued if it seems to have precipitated the condition. While most studies support it, corticosteroid treatment of CE is controversial. Successful treatment of skin necrosis with iloprost, a prostacyclin analogue, as well as hyperbaric oxygen and pentoxifylline, has been reported.7,9,10
2. Patro N, George R, Singh P, Joseph G. Cutaneous cholesterol embolization syndrome. Dermatol Online J. 2012;18(7):10. 3. Chandrashekariah R, Fresko O, Lynfield YL. Cholesterol embolism. Cutis. 2001;68(4):263-267.
7. Erdim M, Tezel E, Biskin N. A case of skin necrosis as a result of cholesterol crystal embolisation. J Plast Reconstr Aesthet Surg. 2006; 59(4):429-432. 8. Eberl M, Fink AM, Jurecka W. Facial livedo racemosa as a warning sign of cholesterol embolism from atherosclerotic plaques of the carotid artery. J Am Acad Dermatol. 2011;64(6):1203-1205.
4. Hirschmann JV, Raugi GJ. Blue (or purple) toe syndrome. J Am Acad Dermatol. 2009;60(1):1-20.
9. Elinav E, Chajek-Shaul T, Stern M. Improvement in cholesterol emboli syndrome after iloprost therapy. BMJ. 2002;324(7332):268-269.
5. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol. 1986;122(10):1194-1198.
10. Gurgo A, Valenti V, Paneni F, et al. Hyperbaric oxygen therapy in a case of cholesterol crystal embolization. Am J Emerg Med. 2011;29(6):e3-e6.
6. Jucgla A, Moreso F, Muniesa C, Moreno A, Vidaller A. Cholesterol embolism. J Am Acad Dermatol. 2006;55(5):786-793.
JAMA Dermatology January 2015 Volume 151, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/22/2015
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