What are the possible causes of neutrophilia in a patient with hyperlipidemia, taking statin therapy, and presenting with left bicep pain, leukocytosis, and neutrophilia?

Causes of Neutrophilia in a Patient on Statin Therapy with Left Bicep Pain

In this clinical scenario, the most likely cause of neutrophilia is an infectious or inflammatory process affecting the left bicep, potentially pyomyositis or bacterial myositis, rather than a statin-related adverse effect. While statins can cause muscle injury, they do not typically cause neutrophilia or leukocytosis 1, 2.

Primary Differential Diagnosis for Neutrophilia

Infectious/Inflammatory Causes (Most Likely)

• Bacterial infection of the bicep muscle (pyomyositis, abscess, or cellulitis) is the most probable explanation for the combination of localized bicep pain, leukocytosis, and neutrophilia 3
• Acute inflammatory response to tissue injury or infection characteristically produces neutrophilia as neutrophils play a critical role in acute inflammatory responses and host defenses against bacterial infections 3
• The localized nature of the bicep pain strongly suggests a focal infectious or inflammatory process rather than a systemic drug reaction 3

Statin-Related Muscle Injury (Less Likely to Cause Neutrophilia)

• Statin-associated myopathy can cause muscle pain and elevated creatine kinase but does NOT typically cause leukocytosis or neutrophilia 1, 2
• Myopathy occurs in <0.1% of statin-treated patients and presents with diffuse myalgias, muscle tenderness, or weakness with CPK elevation >10 times upper limit of normal 2
• Immune-mediated necrotizing myopathy (IMNM) is a rare autoimmune myopathy associated with statins, characterized by proximal muscle weakness and elevated CK that persists despite statin discontinuation, but this also does not typically present with neutrophilia 2

Obesity-Related Leukocytosis (Chronic, Not Acute)

• Obesity can cause persistent mild neutrophilia due to chronic low-grade inflammation from adipose tissue producing inflammatory cytokines 4
• This presents as asymptomatic mild persistent neutrophilia with elevated acute-phase reactants, not acute leukocytosis with localized pain 4
• In a cross-sectional study, obese subjects with leukocytosis had higher BMI and CRP levels, but this was a chronic finding, not associated with acute symptoms 4

Clinical Approach Algorithm

Step 1: Assess for Infection

• Examine the left bicep for signs of infection: warmth, erythema, swelling, fluctuance, or tenderness 3
• Check vital signs for fever, tachycardia, or hypotension suggesting systemic infection 3
• Obtain blood cultures if febrile or systemically ill 3
• Consider imaging (ultrasound or MRI) of the left bicep to evaluate for abscess, pyomyositis, or deep tissue infection 3

Step 2: Evaluate for Statin-Associated Myopathy

• Measure creatine kinase (CK) levels to assess for muscle injury; statin myopathy typically shows CK >10× upper limit of normal 2
• Assess symptom pattern: statin myopathy presents with bilateral proximal muscle involvement (shoulders, hips, thighs), not unilateral bicep pain 5
• Review timing: statin-related myalgia typically occurs within weeks to months of starting therapy or dose increase 5

Step 3: Rule Out Other Causes

• Review complete blood count differential: neutrophilia with left shift (increased band forms) suggests acute bacterial infection 3
• Check inflammatory markers: elevated CRP and ESR support acute inflammation or infection 4
• Assess for other predisposing factors: uncontrolled hypothyroidism, renal impairment, or recent acute illness that could predispose to both infection and statin toxicity 2

Management Recommendations

If Infection is Suspected (Most Likely Scenario)

• Initiate empiric antibiotic therapy if clinical evidence of bacterial infection is present 3
• Continue statin therapy unless CK is markedly elevated (>10× ULN) or severe myopathy is diagnosed 2
• Monitor clinical response to antibiotics; resolution of neutrophilia with treatment confirms infectious etiology 3

If Statin Myopathy is Diagnosed

• Discontinue statin immediately if CK is markedly elevated or myopathy is diagnosed 2
• Temporarily withhold statin in any patient with acute serious condition predisposing to rhabdomyolysis (sepsis, hypotension, major surgery, trauma) 2
• Rechallenge with alternative statin at lower dose once symptoms resolve and CK normalizes 1

Common Pitfalls to Avoid

• Do not attribute neutrophilia to statin therapy alone: statins cause muscle injury but not leukocytosis; neutrophilia indicates infection or inflammation requiring separate evaluation 1, 2
• Do not routinely measure CK in asymptomatic patients: CK should only be checked in patients with severe muscle symptoms or objective weakness 1
• Do not overlook focal infection: unilateral limb pain with leukocytosis warrants imaging and infectious workup, not just statin discontinuation 3
• Do not confuse chronic obesity-related leukocytosis with acute neutrophilia: obesity causes mild persistent neutrophilia without acute symptoms, not acute leukocytosis with localized pain 4