FDG PET/CT, C-reactive protein, and Charlson Comorbidity Index in fever of unknown origin: A retrospective two-center cohort study

Gonenli M. G., Muslu B., Bayramlar O. F., Demirel A., Tor Y. B., Saglam B., ...More

International Journal of Infectious Diseases, vol.165, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 165
  • Publication Date: 2026
  • Doi Number: 10.1016/j.ijid.2026.108474
  • Journal Name: International Journal of Infectious Diseases
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: 18F-FDG PET/CT, C-reactive protein, Charlson Comorbidity Index, Diagnostic delay, Fever of unknown origin
  • Istanbul University Affiliated: Yes

Abstract

Objectives To describe etiologies of classic fever of unknown origin (FUO) and evaluate associations of FDG PET/CT, C-reactive protein (CRP), age, and Charlson Comorbidity Index (CCI) with biopsy performance, diagnostic yield, and time to diagnosis. Methods Retrospective cohort of 179 adults with classic FUO. In the PET/CT subgroup ( n = 106), logistic regression assessed predictors of biopsy and final diagnosis; CRP discrimination was evaluated by ROC analysis; and time to diagnosis by Kaplan–Meier analysis (CCI=0 vs CCI≥3). Results Autoimmune/autoinflammatory diseases (31.3%), infections (30.7%), and malignancy (19.0%) predominated; 16.8% remained undiagnosed. PET/CT positivity predicted biopsy (aOR 4.85, 95% CI: 1.45-16.19) but not diagnostic yield. Higher log-CRP increased odds of diagnosis (OR 2.11, 95% CI: 1.28-3.48), whereas age decreased odds (OR 0.95 per year, 95% CI: 0.90-0.99). CRP AUC 0.68 (cut-off 30.3 mg/L). CCI≥3 was associated with longer time to diagnosis (log-rank P = 0.034). Conclusion PET/CT mainly facilitated biopsy, while diagnostic yield was more closely related to CRP and age. High comorbidity burden may contribute to diagnostic delay.