Is the mild eosinophilia (absolute eosinophil count 697 cells per microliter, approximately 7% of the white‑blood‑cell differential) in a 60‑year‑old Black female on atorvastatin 40 mg daily for two years likely related to the statin?

Atorvastatin-Related Eosinophilia Assessment

The eosinophil count of 697 cells/µL (mild eosinophilia) in this patient on atorvastatin for two years is unlikely to represent a drug-induced hypersensitivity reaction, but statin-induced eosinophilia remains a documented possibility that warrants systematic evaluation for alternative causes before attributing it to the medication. 1

Understanding the Clinical Context

This patient presents with mild eosinophilia (absolute eosinophil count 697 cells/µL, approximately 7%), which falls into the 500–1,500 cells/µL range. 1 In this range, the most common causes in non-travelers are:

• Allergic/atopic disorders account for 50–80% of cases in adults with mild eosinophilia, including allergic rhinitis, atopic dermatitis, and asthma 1
• Medication reactions are a frequent trigger, requiring systematic medication review 1
• Helminth infections explain 19–80% of cases in travelers or migrants from endemic areas 1

Statin-Induced Eosinophilia: What the Evidence Shows

Documented Cases

Atorvastatin can cause drug reaction with eosinophilia and systemic symptoms (DRESS), a severe hypersensitivity syndrome characterized by:

• Febrile skin rash and facial edema
• Hypereosinophilia (up to 11,540/mm³ in reported cases)
• Systemic involvement (fever, abdominal pain, diarrhea, polyarthralgia, adenomegaly)
• Onset typically 6 weeks after starting therapy 2

Atorvastatin has also been associated with hypersensitivity reactions presenting as:

• Marked hypotension and shock
• Facial edema and angioedema
• Eosinophilia
• Onset can occur several months after commencing therapy 3

Critical Timing Issue

The key distinguishing feature is that documented statin hypersensitivity reactions typically occur within weeks to months of initiation, not after two years of stable therapy. 2, 3 Your patient has been on atorvastatin 40 mg daily for two years, making acute drug hypersensitivity less likely but not impossible.

Systematic Diagnostic Approach

Step 1: Assess for DRESS/Hypersensitivity Features

Look specifically for:

• Skin manifestations: rash, facial edema, urticaria 2
• Systemic symptoms: fever, abdominal pain, diarrhea, polyarthralgia, lymphadenopathy 2
• Hepatic involvement: check liver enzymes for cholestasis or cytolysis 2
• Cardiovascular symptoms: hypotension, angioedema 3

If any of these features are present, discontinue atorvastatin immediately and consider DRESS syndrome. 2

Step 2: Evaluate for Atopic/Allergic Causes (Most Likely)

Because 50–80% of adults with mild eosinophilia have concurrent atopic conditions, assess for: 1

• Allergic rhinitis (seasonal or perennial)
• Atopic dermatitis/eczema
• Asthma
• Consider aeroallergen sensitivity testing (skin-prick or specific IgE) to identify trigger allergens 1
• Account for seasonal pollen exposure, which can elevate eosinophil counts during peak periods 1

Step 3: Screen for Parasitic Infections

Even without travel history, obtain: 1

• Three separate concentrated stool specimens for ova and parasites
• Strongyloides serology (can persist lifelong and cause fatal hyperinfection in immunocompromised hosts) 1
• Schistosomiasis serology if any history of freshwater exposure in endemic areas 1

Critical caveat: Many helminth-infected patients do not have eosinophilia, so normal counts do not exclude infection. 1

Step 4: Evaluate for Eosinophilic Gastrointestinal Disease

If the patient has dysphagia or food impaction, perform upper endoscopy with ≥6 biopsies (2–3 proximal, 2–3 distal esophagus) to evaluate for eosinophilic esophagitis. 1

Important: Peripheral eosinophilia occurs in only 10–50% of adults with eosinophilic esophagitis, so tissue diagnosis is essential if symptoms are present. 1

Step 5: Review All Medications

Beyond atorvastatin, systematically review all medications for known eosinophilia-inducing agents, including:

• Nitrofurantoin (specifically implicated) 1
• Other antibiotics, NSAIDs, anticonvulsants 1

Management Algorithm

If Asymptomatic with Mild Eosinophilia (This Patient)

1. Continue atorvastatin while completing the diagnostic workup above 1
2. Optimize control of any identified atopic conditions (asthma, allergic rhinitis, eczema), as this can stabilize eosinophil counts 1
3. Monitor eosinophil count every 3–6 months 1
4. Reassess if counts rise or symptoms develop, including re-evaluation of atopic disease control, recent allergen exposure, and seasonal factors 1

If Symptomatic or Counts Rise

1. Discontinue atorvastatin if DRESS features develop 2
2. Refer to hematology if eosinophilia persists >3 months after infectious causes are excluded or treated 1
3. Urgent evaluation if any end-organ symptoms develop (cardiac, pulmonary, neurologic) 1

Common Pitfalls to Avoid

• Do not assume eosinophilia alone proves drug causation—atopic disorders are far more common in this range 1
• Do not overlook Strongyloides even in non-travelers, as it can persist lifelong and reactivate 1
• Do not rely on peripheral eosinophil counts to exclude eosinophilic esophagitis if GI symptoms are present 1
• Do not wait for symptoms before investigating persistent eosinophilia, as end-organ damage can be subclinical 1

Bottom Line for This Patient

The most likely explanation for mild eosinophilia (697 cells/µL) after two years of stable atorvastatin therapy is an undiagnosed atopic condition or seasonal allergen exposure, not the statin itself. 1 However, complete the systematic workup above to exclude parasitic infections and other secondary causes before definitively attributing the finding to allergy. 1 If the patient remains asymptomatic and the workup is negative, continue atorvastatin with periodic monitoring. 1