What is the next step to determine the source of inflammation in a patient with elevated high-sensitivity C-reactive protein (hs CRP)?

Determining the Source of Inflammation in Patients with Elevated hs-CRP

When a patient has an elevated high-sensitivity C-reactive protein (hs-CRP), a systematic clinical evaluation should be performed to identify the underlying source of inflammation, beginning with a thorough history and physical examination focused on common inflammatory conditions, followed by targeted laboratory and imaging studies based on clinical suspicion. 1

Initial Approach to Elevated hs-CRP

• Confirm the elevated hs-CRP with repeat testing, ideally two measurements taken 2 weeks apart, to establish a stable estimate and rule out transient elevations 1
• For markedly elevated hs-CRP levels (≥10 mg/L), a thorough search for non-cardiovascular causes of inflammation or infection should be initiated 1
• Interpret hs-CRP levels in the clinical context; no single value can be used to rule in or rule out a specific diagnosis 2

Clinical Evaluation

• Perform a complete physical examination focusing on:
  • Vascular access sites for signs of phlebitis or cellulitis 1
  • Surgical and traumatic wounds for signs of infection 1
  • Pressure areas or injection sites for evidence of soft tissue infection 1
  • Signs of sinusitis or endophthalmitis (through fundoscopy) 1
  • Urinary catheter for evidence of purulent urine 1
  • Presence of diarrhea that may indicate C. difficile colitis 1

Laboratory Investigations

• Consider the following laboratory tests based on clinical suspicion:
  • Complete blood count with differential to assess for neutrophilia, neutropenia, or left-shift 1
  • Blood cultures if fever, chills, hypothermia, leukocytosis, neutropenia, or signs of hemodynamic compromise are present 1
  • Urinalysis and urine culture if urinary tract infection is suspected 1
  • Fecal calprotectin or lactoferrin if inflammatory bowel disease is suspected 1
  • Tests for specific infectious agents based on clinical presentation 1, 3

Specific Considerations for Different Patient Populations

• For patients with cardiovascular risk:

  • Assess traditional cardiovascular risk factors and calculate an absolute risk score 1
  • Consider that elevated hs-CRP may indicate increased cardiovascular risk, especially in those with intermediate risk (10-20% risk of CHD over 10 years) 1

• For dialysis patients:

  • Evaluate for clotted access grafts and persistent infections 4
  • Consider dialysis-related factors such as bioincompatible membranes or impure dialysate 4
  • Assess for failed kidney grafts in transplant patients returning to dialysis 4

• For patients with gastrointestinal symptoms:

  • Consider Helicobacter pylori infection, which can cause elevated hs-CRP in peptic ulcer disease 5
  • For inflammatory bowel disease, consider endoscopic assessment if elevated biomarkers persist 1

Imaging Studies

• Select imaging studies based on clinical suspicion:
  • Chest X-ray if respiratory symptoms are present 1
  • Abdominal imaging if intra-abdominal source is suspected 1
  • Endoscopic assessment for patients with gastrointestinal symptoms and persistently elevated inflammatory markers 1

Common Pitfalls and Caveats

• Single determinations of inflammatory markers may be problematic since they vary with time 4
• Normal CRP does not rule out inflammation, particularly in early stages of infection 2
• Elevated hs-CRP should not be used alone to guide treatment decisions without identifying the underlying cause 1
• In patients with known cardiovascular disease, elevated hs-CRP should not drive early management of acute coronary syndromes 1
• There is no consensus on the optimal "cut-off" point of CRP to define inflammation in chronic kidney disease patients 4

By following this systematic approach, clinicians can effectively identify the source of inflammation in patients with elevated hs-CRP, leading to appropriate management strategies and improved patient outcomes.