Cutaneous Cholesterol Emboli Differential Diagnoses

Updated: Apr 12, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Diagnostic Considerations

Also consider the following:

  • Polymyositis
  • Mononeuritis multiplex
  • Giant cell arteritis
  • Heparin necrosis
  • Wegener granulomatosis or an allergic vasculitis
  • Buerger disease
  • Subacute bacterial endocarditis
  • Symmetric peripheral gangrene from sepsis
  • Diabetic vasculitis or neuropathy
  • Other collagen vascular diseases
  • Cryoglobulinemia
  • Immune complex disease
  • Macroglobulinemia
  • Dysproteinemias
  • Raynaud phenomenon
  • Obliterative arteriosclerosis
  • Thrombophlebitis
  • Polycythemia vera
  • Vasculitis [32]

CE may be classified as a cyanotic-infarctive pseudovasculitis due vaso-occlusion by emboli, thrombi, or fibrointimal hyperplasia (endarteritis obliterans). [33] Thus, the differential diagnosis of CE includes purpura fulminans, warfarin (Coumadin) necrosis, antiphospholipid antibody syndrome, cardiac myxoma, calciphylaxis, and radiation arteritis.

CE has been called the great masquerader because of the variety of clinical manifestations. One of the more common clinical pictures simulates a vasculitis. In a study of 73 cases of CCE, 12 (16%) were mistaken for vasculitis, 9 (12%) specifically for polyarteritis nodosa (PAN). Patients with CCE have also been mistakenly diagnosed with polymyositis, mononeuritis multiplex, giant cell arteritis, and heparin necrosis.

In cases simulating PAN, patients often report an abrupt onset of lower extremity pain followed by the appearance of tender nodules and LR in the presence of normal pulses. Systemic symptoms may involve the gastrointestinal and nervous systems. Laboratory findings include hypertension, neutrophilic leukocytosis, eosinophilia, elevation of the sedimentation rate, melena, hematuria, albuminuria, and azotemia.

Helpful in distinguishing between the two is a history of hypersensitivity in patients with PAN or a history of intra-arterial manipulation in patients with CCE. Clinically, PAN has a more generalized distribution than CE, which favors the lower half of the body because of the severity of abdominal aortic disease. Ischemic neuropathy and joint involvement are also common in patients with PAN but are rare in persons with CE.

Histologically, PAN may involve larger arteries or veins, while in CE, adventitial fibrosis is insignificant, vascular lumina and fibrinoid necrosis are eccentric, and necrosis usually involves only a portion of the wall. The principal cellular reaction is endothelial and mononuclear with few acute inflammatory cells. Most importantly, close inspection should reveal cholesterol clefts. Finally, a response to steroids may also help differentiate PAN from CE.

Two patients with presentations similar to polymyositis have been described who experienced the sudden onset of leg pain, cool legs with normal peripheral pulses, petechiae, LR, and elevated tender nodules that represented muscle necrosis (after biopsy). Laboratory abnormalities included elevation of the sedimentation rate, serum aspartate aminotransferase level, lactate dehydrogenase level, and creatine kinase and aldolase values and a myopathic pattern on electromyography.

Cholesterol embolism should be distinguished from cutaneous reactive angiomatosis, a proposed term to describe a group of reactive cutaneous vascular proliferation caused by various diseases. [34]

Cholesterol emboli were described in one patient in whom the emboli were so widespread as to account for an erythroderma and concern about the presence of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. [35]

Differential Diagnoses