Can CRP Be Normal in MS Flare?
Yes, CRP can be completely normal during a Multiple Sclerosis flare, and this is actually a well-recognized limitation of using CRP as a biomarker in MS.
Evidence from MS-Specific Research
The current literature consistently demonstrates that CRP is an unreliable marker for MS disease activity:
CRP levels do not correlate with MS disease activity or severity. Multiple studies examining CRP in MS patients during relapses have found inconsistent or absent elevations, indicating that CRP lacks utility as a diagnostic or prognostic biomarker in MS 1, 2.
Even during acute MS exacerbations, CRP may remain normal. A 2001 study found no correlation between CRP levels and fatigue scores in MS patients, and only a minority of patients showed elevated CRP even during symptomatic periods 3.
Historical data from 1976 showed that while some acute phase reactants could be elevated during MS flares, this was not universal. Only 12 of 13 patients with clinically active MS showed elevation of one or more inflammatory markers, suggesting that normal inflammatory markers do not exclude active disease 4.
A 2024 study definitively concluded that CRP has no role as a marker for disease severity or prognosis in relapsing-remitting MS patients. The study found that while CRP was significantly increased during relapse phases compared to controls, it did not correlate with disability scores or predict disease progression 2.
Why CRP Behaves Differently in MS
MS is primarily a central nervous system inflammatory disease with limited systemic inflammatory spillover:
The inflammatory process in MS is largely compartmentalized within the CNS, behind the blood-brain barrier 1.
Unlike inflammatory bowel disease or rheumatoid arthritis where systemic inflammation drives CRP elevation, MS pathophysiology involves localized CNS immune activation that may not trigger sufficient hepatic IL-6 production to elevate CRP 1.
Clinical Implications
Do not rely on CRP to rule out or confirm MS disease activity:
A normal CRP does not exclude an active MS flare and should not delay appropriate clinical assessment or treatment decisions 1, 2.
Clinical evaluation, MRI findings, and neurological examination remain the gold standard for assessing MS disease activity, not serum inflammatory markers 1.
If you suspect an MS flare based on clinical presentation, proceed with appropriate neurological assessment and imaging regardless of CRP values 2.
Important Caveat
If a patient with known MS presents with an elevated CRP, consider alternative explanations such as concurrent infection, other inflammatory conditions, or comorbidities rather than attributing it solely to MS activity 3, 2.