What is the role of procalcitonin (PCT) in differentiating between bacterial infections and inflammatory manifestations in patients with Adult-Onset Still's Disease (AOSD)?

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Last updated: January 3, 2026 • View editorial policy

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Procalcitonin in Adult-Onset Still's Disease

Procalcitonin (PCT) has limited utility in AOSD because it is frequently elevated during disease flares even without bacterial infection, creating false positives that can mislead clinicians into unnecessary antibiotic use. 1

Key Diagnostic Challenge

The fundamental problem with PCT in AOSD is its paradoxical elevation during inflammatory flares:

  • PCT levels are markedly elevated in AOSD patients without infection, making it unreliable as a standalone marker for differentiating bacterial infection from disease activity 1
  • In a prospective study of 44 febrile patients with systemic autoimmune diseases, AOSD was specifically identified as a "false positive subgroup" showing elevated PCT levels (median 0.24 ng/mL in non-infected AOSD patients) despite absence of infection 1
  • When AOSD patients were excluded from analysis, PCT specificity for bacterial infection improved dramatically from 75% to 89.4%, and the area under the ROC curve increased from 0.801 to 0.904 1

Performance Characteristics in Mixed Autoimmune Populations

When AOSD patients are included in the analysis:

  • Sensitivity: 75% for detecting bacterial infection 1
  • Specificity: 75% for detecting bacterial infection 1
  • Positive predictive value: 71.4% 1
  • Negative predictive value: 78.2% 1

These modest performance characteristics make PCT unreliable in the AOSD population specifically.

Superior Alternative Biomarkers for AOSD

Instead of relying on PCT, use IL-18 and ferritin in combination to differentiate bacterial infection from AOSD inflammatory activity:

IL-18 and Ferritin Combination

  • A decision tree combining plasma IL-18 and ferritin achieves 97.67% diagnostic accuracy, 96.15% sensitivity, and 100% specificity for distinguishing bloodstream infection from AOSD 2
  • IL-18 levels are significantly higher in AOSD than in bacterial infections, showing the opposite pattern from PCT 2
  • IL-18 correlates positively with ferritin and decreases after successful treatment in both conditions, making it useful for monitoring 2

Individual Biomarker Patterns

  • Ferritin: Extremely elevated in AOSD (4,000-250,000 ng/mL), higher than in bacterial infections 3, 4
  • IL-18: Elevated in AOSD and correlates with disease activity 5, 4
  • S100 proteins (S100A8/A9 and A12): Show diagnostic value in AOSD 5, 4
  • Procalcitonin: Significantly higher in bacterial infection (median 1.11 ng/mL) versus AOSD flare (median 0.24 ng/mL), but overlap exists 1

Clinical Algorithm for Differentiating Infection from AOSD Flare

When evaluating a febrile AOSD patient for possible bacterial infection:

  1. Measure IL-18 and ferritin levels simultaneously 2

    • Very high IL-18 + very high ferritin → favors AOSD flare
    • Lower IL-18 + moderately elevated ferritin → favors bacterial infection

  2. Assess clinical features that favor AOSD over infection 2:

    • Evanescent salmon-pink rash (not petechial) 3
    • Arthralgia/arthritis pattern (knees, wrists, ankles) 3
    • Myalgia with fever exacerbations 3
    • Sore throat 3
    • Lymphadenopathy 3

  3. Perform thorough microbiologic screening regardless of biomarker results 1:

    • Blood cultures
    • Urinalysis and culture
    • Chest imaging
    • Site-specific cultures based on clinical suspicion

  4. Do not rely on PCT alone - if PCT is elevated, interpret in context of IL-18, ferritin, and clinical picture 1

Critical Pitfall to Avoid

The most dangerous error is assuming elevated PCT in an AOSD patient automatically indicates bacterial infection and delaying appropriate immunosuppressive therapy. 1 Conversely, dismissing all PCT elevations as "just AOSD" without proper microbiologic workup can miss true bacterial infections that require antibiotics.

Monitoring Treatment Response

  • IL-18 levels decrease after successful treatment in both bacterial infection and AOSD, making serial measurements useful for assessing therapeutic response 2
  • Ferritin also correlates with AOSD disease activity and normalizes with remission 3

References

3
Guideline

Adult-Onset Still's Disease: Clinical Manifestations and Diagnostic Considerations

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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