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Difficulty: HardFormulating a Differential Diagnosis

A 65-year-old man is evaluated in the clinic for a 2-week history of low-grade fever, diffuse myalgias, and a newly developed, painful rash on his legs. His past medical history is significant for hypertension, hyperlipidemia, and ischemic heart disease. Three weeks ago, he underwent left heart catheterization with coronary angiography for worsening angina, which revealed non-obstructive coronary artery disease. His medications include aspirin, metoprolol, atorvastatin, and lisinopril, all of which he has taken for several years without recent dose changes. Temperature is 37.8°C (100.0°F), blood pressure is 152/90 mm Hg, and pulse is 88/min. Physical examination reveals a violaceous, net-like reticular pattern on the skin of bilateral lower extremities. His toes are cyanotic and tender to palpation, but bilateral dorsalis pedis and posterior tibial pulses are palpable and bounding.

Laboratory studies are notable for:
Leukocytes: 11,000/mm³ (Eosinophils 14%)
Erythrocyte sedimentation rate: 75 mm/hr
Blood urea nitrogen: 42 mg/dL
Serum creatinine: 2.6 mg/dL (baseline 1.1 mg/dL)

Urinalysis shows 5-10 white blood cells/hpf, 1-2 red blood cells/hpf, and the presence of urine eosinophils.

Which of the following is the most likely diagnosis?

  1. A
    Acute interstitial nephritis
  2. Cholesterol embolization syndromeAnswer
  3. C
    Contrast-induced nephropathy
  4. D
    Infective endocarditis
  5. E
    Polyarteritis nodosa

Answer

Cholesterol embolization syndrome
The patient's clinical picture is highly characteristic of cholesterol embolization syndrome (CES). CES occurs when atherosclerotic plaques in large arteries are mechanically disrupted, typically during endovascular procedures like cardiac catheterization. This disruption showers cholesterol crystals downstream into the microcirculation of various organs. The emboli trigger a systemic inflammatory response, leading to low-grade fever, myalgias, and an elevated erythrocyte sedimentation rate. The intense foreign-body reaction to the crystals classically results in eosinophilia and eosinophiluria. Skin involvement is the most common physical finding, presenting as livedo reticularis (due to sluggish flow in subpapillary venous plexuses) and 'blue toe syndrome' (microvascular occlusion leading to digital ischemia despite intact, palpable pedal pulses). Renal involvement typically manifests as a subacute, progressive acute kidney injury occurring days to weeks after the procedure, perfectly matching this patient's timeline and presentation.

Step-by-Step Solution

1
Analyze the patient's timeline and recent exposures.
The patient had an invasive endovascular procedure (coronary angiography) three weeks prior to symptom onset, which is a major risk factor for mechanical disruption of atherosclerotic plaques.
Identifying recent triggers is essential for formulating a prioritized differential diagnosis in acute presentations.
2
Synthesize the physical examination findings.
The patient exhibits livedo reticularis (violaceous, net-like rash) and 'blue toe syndrome' (cyanotic, tender toes) despite having palpable, intact peripheral pedal pulses.
Intact peripheral pulses combined with distal ischemia indicate microvascular rather than macrovascular occlusion, characteristic of micro-emboli.
3
Evaluate the laboratory data in the context of the clinical presentation.
The patient has subacute acute kidney injury, systemic inflammation (elevated ESR, fever), and prominent eosinophilia/eosinophiluria.
While many conditions cause acute kidney injury, the specific combination of eosinophilia, livedo reticularis, and a recent catheterization is the classic triad for atheroembolic disease.

Key Concept

Cholesterol embolization syndrome should be strongly suspected in patients who develop subacute acute kidney injury, systemic inflammation, eosinophilia, and microvascular skin changes (livedo reticularis, blue toes) days to weeks following an endovascular procedure.
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Topics

Formulating a Differential Diagnosis

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