What are the possible causes of a markedly elevated C‑reactive protein level of 120 mg/L on routine laboratory testing?

Markedly Elevated CRP of 120 mg/L: Diagnostic Approach

Most Likely Cause

A CRP of 120 mg/L most strongly suggests acute bacterial infection, as bacterial infections show a median CRP of precisely 120 mg/L. 1, 2 This level demands urgent evaluation for sepsis, pneumonia, intra-abdominal abscess, urinary tract infection, soft tissue infection, or bloodstream infection. 2

Immediate Clinical Assessment Required

Check immediately for fever, hypothermia, hemodynamic instability, and signs of organ dysfunction requiring urgent intervention when CRP exceeds 50 mg/L. 1 The presence of any of these findings mandates:

• Blood cultures obtained immediately before antibiotics 1
• Assessment for respiratory, abdominal, urinary tract, soft tissue, and bloodstream infection sources 2
• Evaluation for septic complications or abscess formation, as persistent CRP >100 mg/L strongly suggests abscess or septic complication 2

Differential Diagnosis by CRP Level

While bacterial infection is most likely at 120 mg/L, other causes must be considered systematically:

Infectious Causes

• Bacterial infections: median CRP ~120 mg/L 1, 2
• Non-bacterial infections (viral, fungal): median CRP ~32 mg/L 1
• Tuberculosis should be considered in patients with recurrent fever, especially with immunosuppression or relevant exposure history, as TB can present with CRP around 125-148 mg/L 1

Non-Infectious Inflammatory Causes

• Inflammatory diseases (non-autoimmune): median CRP ~65 mg/L 1
• Giant cell arteritis requires urgent specialist referral within 24 hours if symptoms include new headache, jaw claudication, or visual disturbances with raised CRP/ESR 1
• Rheumatologic diseases account for only 5.6% of CRP levels above 250 mg/L 3

Malignancy

• Solid tumors: median CRP ~46 mg/L 1, 2
• Malignancy accounts for 5.1% of markedly elevated CRP cases and carries 37% mortality 3

Other Considerations

• Cardiovascular disease: median CRP ~6 mg/L (unlikely at this level) 1, 2
• Drug reactions: 1.7% of cases 3
• In one large series, 17.6% of markedly elevated CRP cases remained undiagnosed 3

Essential Laboratory Workup

Obtain the following tests immediately:

• Complete blood count to assess for leukocytosis, left-shift, neutropenia (associated with 20.7% mortality), or lymphopenia 1, 3
• Procalcitonin to differentiate bacterial from non-bacterial causes; PCT ≥1.5 ng/mL has 100% sensitivity and 72% specificity for sepsis 4
• Combined CRP ≥50 mg/L and PCT ≥1.5 ng/mL yields 98.5% sensitivity and 75% specificity for sepsis 4
• Liver enzymes (AST/ALT) to exclude fatty liver disease 1, 2
• Serum albumin and creatinine to evaluate chronic disease states 1

Imaging Studies

• Chest radiograph when respiratory symptoms are present to identify pulmonary sources 1
• Consider CT imaging for suspected intra-abdominal or pelvic abscess, as 88.9% of CRP levels >350 mg/L are due to infection 3

Critical Pitfalls to Avoid

• One-third of hospitalized patients with CRP >10 mg/L have non-infectious causes 4
• Single normal CRP does not rule out infection; serial measurements are more valuable than single values 1, 2
• Approximately 20% of smokers have CRP >10 mg/L from smoking alone, but a level of 120 mg/L is too high to attribute to lifestyle factors 2, 4
• CRP has poor specificity (40-67%) for bacterial infection and cannot reliably differentiate bacterial from non-infectious inflammation 4
• Confounding factors include neutropenia, immunodeficiency, and NSAID use 2

Temporal Considerations

CRP rises 4-6 hours after inflammatory insult, doubles every 8 hours, and peaks at 36-50 hours, making timing of measurement critical for interpretation. 4 In post-operative patients, CRP typically peaks on days 2-3 and returns to baseline by day 5 in uncomplicated cases. 2

When Tuberculosis Screening Is Indicated

Perform interferon-gamma release assay (IGRA) or tuberculin skin test if recurrent fever is present with markedly elevated CRP and normal complete blood count, especially with immunosuppression or relevant exposure history. 1 If pulmonary infiltrates are identified, proceed with bronchoscopy, bronchoalveolar lavage, and PCR testing for Mycobacterium tuberculosis. 1

Management Principles

• Treatment should address the identified pathology rather than attempting to lower CRP directly 1
• Serial CRP measurements should not be used to monitor therapeutic response; instead, focus on treating the underlying cause 1, 2
• Overall mortality with markedly elevated CRP is 8.6%, rising to 37% with malignancy and 21% with multiple diagnoses 3