What happens to Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) in amyloidosis?

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ESR and CRP in Amyloidosis

In amyloidosis, ESR is typically elevated while CRP may be normal or only mildly elevated, creating a characteristic dissociation between these two inflammatory markers that can be a diagnostic clue.

Characteristic Pattern of Inflammatory Markers

ESR Behavior in Amyloidosis

  • ESR is usually elevated in amyloidosis, particularly in AA (secondary) amyloidosis where it reflects the underlying chronic inflammatory condition 1, 2, 3
  • In AA amyloidosis secondary to familial Mediterranean fever (FMF), baseline ESR values averaged 48.7 ± 31.0 mm/h before treatment 1
  • Even during attack-free periods in FMF patients with amyloidosis, ESR remains significantly elevated compared to those without amyloidosis, indicating persistent subclinical inflammation 2
  • The elevation of ESR in amyloidosis is related to increased fibrinogen and other acute phase proteins that accumulate as part of the disease process 4

CRP Behavior in Amyloidosis

  • CRP may be normal or only mildly elevated in AL (light chain) amyloidosis, despite significant disease burden 5
  • In AA amyloidosis, CRP is typically elevated, reflecting the underlying inflammatory condition, with baseline values averaging 18.1 ± 19.5 mg/L in FMF-associated cases 1
  • CRP levels are significantly higher in FMF patients with amyloidosis compared to those without amyloidosis during attack-free periods 2
  • In AA amyloidosis, both ESR and CRP remain elevated even with anti-IL-1 therapy, though they decrease significantly (CRP from 18.1 to 5.8 mg/L and ESR from 48.7 to 28.7 mm/h) 1

Critical Diagnostic Pitfall

Normal ESR Does NOT Exclude Amyloidosis

  • A normal ESR does not exclude the diagnosis of amyloidosis, particularly AL amyloidosis 5
  • A case report documented a 65-year-old woman with AL amyloidosis secondary to multiple myeloma who presented with normal ESR and normal urinalysis initially 5
  • When clinical features suggest amyloidosis (such as stiffness, recurrent carpal tunnel syndrome, or dysphagia), further workup including free light chain analysis should be performed even with normal ESR 5

Clinical Context by Amyloidosis Type

AA (Secondary) Amyloidosis

  • Both ESR and CRP are typically elevated, reflecting the underlying chronic inflammatory disease (such as FMF, rheumatoid arthritis, or chronic infections) 1, 2, 3
  • These markers remain elevated even during clinically quiescent periods, indicating ongoing subclinical inflammation 2
  • Treatment with IL-1 inhibitors significantly reduces but does not fully normalize these markers compared to healthy controls 2, 3

AL (Light Chain) Amyloidosis

  • ESR may be normal or elevated, and CRP is often normal or only mildly elevated 5
  • This dissociation between clinical severity and inflammatory markers is characteristic and can delay diagnosis 5
  • The lack of elevated acute phase reactants reflects the non-inflammatory nature of plasma cell dyscrasia-related amyloid deposition 5

Monitoring Treatment Response

  • ESR and CRP are useful for monitoring treatment response in AA amyloidosis 1, 3
  • Following IL-1 inhibitor therapy in FMF-associated AA amyloidosis, significant reductions occur: ESR decreases by approximately 40% and CRP normalizes in about 70% of patients 1, 3
  • CRP normalizes more rapidly than ESR during treatment, making it more useful for assessing acute treatment response 4
  • ESR has a longer half-life (reflecting fibrinogen levels) and is better suited for monitoring chronic inflammatory conditions over time 4

Practical Algorithm for Interpretation

When evaluating inflammatory markers in suspected amyloidosis:

  1. If ESR is elevated with normal or mildly elevated CRP, consider AL amyloidosis and check serum free light chains and immunofixation 5

  2. If both ESR and CRP are significantly elevated, consider AA amyloidosis and investigate underlying chronic inflammatory conditions 1, 2

  3. If ESR and CRP are both normal but clinical suspicion remains high (carpal tunnel syndrome, nephrotic syndrome, restrictive cardiomyopathy, peripheral neuropathy), proceed with tissue biopsy and free light chain analysis regardless 5

  4. In established AA amyloidosis on treatment, monitor both markers monthly, expecting CRP to normalize faster than ESR 1, 4

References

5
Research

[Amyloidosis despite normal ESR].

Nederlands tijdschrift voor geneeskunde, 2017

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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