Normoferritinemic Versus Hyperferritinemic Inflammation in Patients Admitted to the Department of Internal Medicine

Background: Screening patients admitted to internal medicine for hyperferritinemia might reveal a dichotomy between normoferritinemic inflammation and hyperferritinemic inflammation phenotypes, opening new research into innate immunity activation during acute inflammation. Methods: We identified 4514 consecutive patients screened for CRP and ferritin on admission. Patients with CRP ≤ 150 mg/L were excluded. We selected 100 patients with the lowest (normoferritinemic inflammation) and 100 with the highest (hyperferritinemic inflammation) ferritin concentrations. Sub-analysis of 39 CRP-matched pairs (±15 mg/L) and multivariable logistic regression-adjusting for age, sex, sepsis, malignancy, CRP, and comorbidities-were performed. Results: Groups did not differ significantly by age (p = 0.068) or sex (p = 0.319). Mortality was significantly higher in the hyperferritinemic inflammation group (41% vs. 7%, p < 0.001), a trend maintained in non-malignant (31.1% vs. 6.5%, p < 0.001) and CRP-matched (25.6% vs. 2.6%, p = 0.012) subgroups. Multivariable regression confirmed hyperferritinemic inflammation as a significant independent predictor of mortality (OR 3.726; 95% CI 1.304-10.647; p = 0.014), even after adjusting for the Charlson Comorbidity Index. Conclusions: Significant inflammation accompanied by hyperferritinemic inflammation is associated with elevated mortality compared to normoferritinemic inflammation, suggesting a dichotomous divergence of the inflammatory response.