What are the possible causes of elevated C-Reactive Protein (CRP) levels?

Causes of Elevated C-Reactive Protein (CRP) Levels

Bacterial infections are the most common cause of extreme CRP elevations (>40 mg/L), while chronic inflammatory conditions, cardiovascular disease, and lifestyle factors typically cause mild to moderate elevations. 1

Major Categories of CRP Elevation

Infectious Causes

• Bacterial infections (most common cause of extreme elevations):
  • Respiratory infections
  • Urinary tract infections
  • Septicemia
  • Meningitis
  • Skin/soft tissue infections 1
• Viral infections (typically cause lower elevations than bacterial)
• Fungal infections
• Parasitic infections

Inflammatory Conditions

• Autoimmune diseases:
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE) (though CRP may be only mildly elevated) 2
  • Inflammatory bowel disease (particularly Crohn's disease) 3
  • Vasculitis
• Tissue injury/damage:
  • Recent surgery
  • Trauma
  • Burns
  • Myocardial infarction 1

Chronic Diseases

• Cardiovascular disease:
  • Atherosclerosis
  • Coronary artery disease 1
• Malignancies:
  • Solid tumors
  • Hematologic malignancies 1, 4
• Chronic kidney disease 1
• Cachexia/chronic disease-related malnutrition (CRP typically 5-40 mg/L) 2

Lifestyle and Metabolic Factors

• Obesity
• Smoking
• Sedentary lifestyle
• Poor diet
• Chronic alcohol consumption 1

CRP Level Interpretation

Risk Stratification

• Low risk: <1.0 mg/L
• Average risk: 1.0-3.0 mg/L
• High risk: >3.0 mg/L 1

Inflammation Severity

• Normal range: 0.8-3.0 mg/L
• Mild inflammation: 10-40 mg/L
• Acute inflammation/bacterial infection: 40-200 mg/L
• Severe acute illness: >500 mg/L 1, 4

Clinical Pearls

• CRP levels in SLE are often lower than expected for the degree of inflammation, and a significant increase (>50 mg/L) should raise suspicion for superimposed infection 2

• In chronic disease-related malnutrition with inflammation (cachexia), CRP is typically >5 mg/L but rarely exceeds 40 mg/L 2

• Extremely elevated CRP (>500 mg/L) is most commonly associated with bacterial infections (88% of cases) and carries high mortality (36% overall, 61% in patients with active malignancies) 4

• CRP is more reliable as a marker of inflammation in Crohn's disease than in ulcerative colitis 3

• CRP should be interpreted in clinical context; a single elevated value should not be used to make a diagnosis 1

• Many non-pathological factors can influence CRP levels, including age, sex, socioeconomic status, race, body mass index, exercise, diet, sleep, and medication use 2

Pitfalls to Avoid

• Don't rely solely on the traditional 10 mg/L threshold to differentiate between normal and abnormal CRP levels, as this cutoff originated from older studies with less sensitive assays 2, 1

• Don't assume that elevated CRP always indicates infection; consider the full spectrum of inflammatory conditions 1

• Don't use CRP alone to differentiate between bacterial and viral infections 5

• Don't ignore persistently elevated CRP levels (>10 mg/L) after repeated testing, as these warrant evaluation for underlying causes 1