Will a patient with lymphedema have elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)?

Inflammatory Markers in Lymphedema

Patients with lymphedema typically have normal ESR and CRP levels unless there is an active inflammatory complication such as cellulitis, which would cause elevation of these inflammatory markers. 1

Understanding Inflammatory Markers in Lymphedema

Lymphedema itself is not primarily an inflammatory condition but rather a disorder of lymphatic drainage. Therefore, in uncomplicated lymphedema:

• ESR (Erythrocyte Sedimentation Rate) is typically normal
• CRP (C-Reactive Protein) is typically normal

When Inflammatory Markers Become Elevated in Lymphedema

Inflammatory markers may become elevated in lymphedema patients in the following scenarios:

1. Cellulitis/Infection: The most common complication of lymphedema that causes elevated inflammatory markers

   • In a study of lymphedema patients with cellulitis, abnormal CRP levels were found in 76.1% of cases 1
   • Increased limb circumference plus elevated CRP were the strongest indicators of cellulitis in lymphedema patients 1

2. Secondary inflammatory conditions: Patients with lymphedema may have underlying conditions that can cause elevated inflammatory markers

Characteristics of Inflammatory Markers

CRP (C-Reactive Protein)

• Rises quickly (within 4-6 hours) after onset of inflammation
• Returns to normal levels more rapidly (half-life of 19 hours)
• Higher sensitivity (73%) and specificity (78%) for detecting acute inflammation 2
• Better predictor of disease activity in most acute conditions

ESR (Erythrocyte Sedimentation Rate)

• Rises more slowly after onset of inflammation
• Remains elevated longer
• Lower sensitivity (54-78%) and variable specificity (46-95%) 2
• More suitable for monitoring chronic inflammatory diseases

Clinical Implications

Monitoring for Complications

• Regular monitoring of inflammatory markers is not necessary in stable, uncomplicated lymphedema
• Elevation of CRP and ESR should prompt evaluation for:
  • Cellulitis (most common)
  • Other infections
  • Underlying inflammatory conditions

Diagnostic Approach When Inflammatory Markers Are Elevated

1. Assess for cellulitis signs:

   • Increased limb circumference (present in 96.9% of lymphedema cellulitis cases) 1
   • Erythema, warmth, tenderness
   • Fever or systemic symptoms

2. Laboratory workup:

   • Complete blood count with differential
   • Blood cultures if fever is present
   • Consider imaging if deep infection suspected

Important Considerations

Discordance Between ESR and CRP

• Discordance between ESR and CRP occurs in approximately 28% of cases 2, 3
• Elevated ESR with normal CRP may indicate:
  • Chronic inflammation
  • Non-inflammatory factors affecting ESR (anemia, renal insufficiency)
• Elevated CRP with normal ESR may indicate:
  • Early acute inflammation
  • Factors suppressing ESR

Pitfalls to Avoid

• Don't attribute elevated inflammatory markers to lymphedema itself
• Don't miss cellulitis, which can be subtle in lymphedema patients
• Remember that lymphedema patients have a high recurrence rate of cellulitis (56.6%) 1
• Consider that factors like renal insufficiency and low albumin can cause falsely elevated ESR 3

In summary, uncomplicated lymphedema should not cause elevation of inflammatory markers. If ESR and CRP are elevated in a patient with lymphedema, a thorough evaluation for complications (particularly cellulitis) or other inflammatory conditions is warranted.