What is the initial workup for systemic inflammation?

Initial Workup for Systemic Inflammation

The clinical workup of systemic inflammation should include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count (CBC) with differential; if available, serum amyloid A (SAA) and S100 proteins may also be assessed. 1

Basic Laboratory Evaluation

First-Line Tests

• Complete Blood Count (CBC) with differential

  • Evaluate for leukocytosis pattern
  • Check for neutrophilia (suggestive of acute inflammation)
  • Assess for anemia (may be present in chronic inflammation)
  • Look for thrombocytosis (common in inflammatory conditions)

• Inflammatory Markers

  • CRP (more sensitive for acute inflammation)
  • ESR (may reflect chronic inflammation)
  • Consider SAA when available (more sensitive than CRP for some conditions)
  • S100 proteins (when available)

• Comprehensive Metabolic Panel

  • Assess renal function (BUN, creatinine)
  • Evaluate hepatic function (ALT, AST, alkaline phosphatase)
  • Check albumin (often decreased in chronic inflammation)

Interpretation of Inflammatory Markers

CRP	ESR	Clinical Interpretation
Elevated	Normal	Acute inflammation (early infection, early flare)
Normal	Elevated	Chronic inflammation, autoimmune diseases
Elevated	Elevated	Active inflammation (both acute and chronic processes)
Normal	Normal	Low likelihood of significant inflammation

Additional Testing Based on Clinical Presentation

Rheumatologic/Autoimmune Evaluation

• Antinuclear antibody (ANA)
• Rheumatoid factor (RF)
• Anti-cyclic citrullinated peptide (anti-CCP)
• Complement levels (C3, C4)

Infectious Disease Workup

• Blood cultures (if fever present)
• Procalcitonin (helps distinguish bacterial from non-bacterial causes)
• Specific testing based on symptoms:
  • Respiratory: Sputum culture, respiratory pathogen panel
  • Gastrointestinal: Stool cultures, C. difficile testing, fecal calprotectin
  • Urinary: Urinalysis and culture

Specific Inflammatory Markers

• Ferritin (often elevated in inflammatory conditions, typically 500-2,000 ng/dL in systemic inflammation) 1
• D-dimer (elevated in inflammatory states) 2
• Lactate dehydrogenase (LDH) 1
• Consider cytokine panels if available (IL-6, TNF-α, IL-10) 1, 2

Imaging Studies

• Selection based on clinical presentation:
  • Chest X-ray or CT chest for respiratory symptoms
  • CT abdomen/pelvis or MR enterography for abdominal symptoms
  • Joint imaging for articular symptoms
  • MRI for suspected osteomyelitis or spine involvement 3

Specialized Testing

• Genetic testing using next-generation sequencing (NGS) platforms should be considered for suspected autoinflammatory syndromes 1
• Tissue biopsy may be necessary in certain cases (e.g., vasculitis, sarcoidosis, myositis) 1
• Peripheral blood smear to identify microangiopathic changes 1

Clinical Evaluation for Specific Syndromes

• For suspected autoinflammatory syndromes:
  • Evaluate for urticaria-like rash, cold/stress-triggered episodes, sensorineural hearing loss (CAPS)
  • Check for long-lasting fever episodes, migratory rash, periorbital edema (TRAPS)
  • Look for early onset (<1 year), GI symptoms, painful lymph nodes (MKD) 1

Common Pitfalls to Avoid

• Do not dismiss elevated ESR when CRP is normal, as this pattern can occur in several serious conditions 3
• Do not initiate empiric antimicrobial therapy without appropriate cultures 3
• Avoid treating the inflammatory marker itself rather than the underlying cause 3
• Do not assume that normal inflammatory markers rule out all significant disease 4
• Remember that discordance between ESR and CRP occurs in approximately 28% of cases 3, 4

Follow-up Recommendations

• Serial monitoring of inflammatory markers every 4-6 weeks after treatment initiation 3
• Adjust frequency based on clinical response and suspected underlying condition
• Screen for complications of longstanding inflammation (e.g., amyloidosis) by monitoring proteinuria and microalbuminuria 1

The workup should be tailored based on the clinical presentation, and patients with unexplained systemic inflammation should be referred to specialty centers for further evaluation if initial workup is inconclusive 1.