Etiologic spectrum and early mortality predictors in extreme hyperferritinemia: insights from rheumatology and hematology clinics.

objectivesThis study aimed to determine the frequency, causes, mortality rates, and predictors of mortality in patients with extreme hyperferritinemia (≥ 5000 ng/mL) followed in rheumatology and hematology clinics.

methodPatients with a ferritin level of ≥ 5000 ng/mL were retrospectively screened using the electronic data recording system.

resultsExtreme hyperferritinemia was detected in 0.76% of 43,110 ferritin tests performed over 13 years. The data of 139 patients, including 35 patients from the rheumatology clinic and 104 patients from the hematology clinic, were analyzed. In the study, 71.4% of rheumatology cases and 50.9% of hematology cases were female. The median ferritin value for the overall group was 7768 ng/mL, and the mean value was 13,022 ± 17,141 (5017-100,000) ng/mL. Regarding the etiology of extreme hyperferritinemia, iron overload was detected in 42.4% of all patients, infection in 23.0%, and Still's disease in 14.4%. The most common cause was Still's disease (54.3%) in rheumatology patients and iron overload (55.8%) in hematology patients. Within the first month, 25 (18.0%) patients died. The most common cause of mortality was macrophage activation syndrome (MAS) in rheumatology patients and infection in the hematology group. In rheumatology patients, the risk factors for mortality in univariate analysis were the presence of MAS [HR = 13.257 (95% CI = 1.374-127.934, p = 0.025)]. Ferritin level can predict first month mortality in rheumatology patients with extreme hyperferritinemia (cutoff > 36,137.5 ng/mL; sensitivity 100%, specificity 96.77%, p < 0.0001, AUC = 0.976, 95% CI = 0.915-1.000) but not in hematology patients.

conclusionsIn conclusion, severe hyperferritinemia may be encountered in rheumatology and hematology practice. Ferritin level may be a good marker for predicting mortality, especially in rheumatology patients. Key points • In patients with extreme hyperferritinemia, the most common etiologies were Still's disease among rheumatology patients and iron overload among hematology patients. • The 1-month mortality rate was 11.4% in the rheumatology group and 20.2% in the hematology group. The leading cause of death was macrophage activation syndrome (MAS) in the rheumatology cohort and infection in the hematology cohort. • Among rheumatology patients, serum ferritin levels were a strong predictor of 1-month mortality, with a cutoff value of >36,137.5 ng/mL yielding a sensitivity of 100%, specificity of 96.77%, and an AUC of 0.976 (95% CI,: 0.915-1.000;, p < 0.0001). However, ferritin levels did not demonstrate predictive value for 1-month mortality in hematology patients.