Evaluation of the causes of extreme hyperferritinemia in rheumatology and hematology clinics

Ajder, M. Evaluation of the Causes of Extreme Hyperferritinemia in Rheumatology and Hematology Clinics. Eskişehir Osmangazi University Faculty of Medicine, Department of Internal Medicine, Specialization Thesis in Medicine, Eskişehir, 2025. Extreme hyperferritinemia is a condition that must be carefully evaluated, considering a broad differential diagnosis. This study aimed to investigate the frequency and causes of extreme hyperferritinemia in rheumatology and hematology practice, to determine the demographic, laboratory, clinical characteristics and outcomes of the patients, and to evaluate the impact of the obtained data on mortality by comparing it with the existing literature. In our study, patients followed in the rheumatology and hematology clinics with ferritin levels ≥5,000 ng/mL were retrospectively reviewed for etiology. Over a 13-year period, extreme hyperferritinemia was detected in 0.76% of the 43,110 ferritin tests performed. Of the 139 patients, 74.8% were from the hematology unit, and 25.2% were from the rheumatology unit. Of all patients, 56.1% were female; this rate was 71.4% among rheumatology cases and 50.9% among hematology cases. The mean age of the patients was 51.69±17.12 (18–83) years. The median ferritin level was 7,768 ng/mL, and the mean was 13,022±17,141 (5,017–100,000) ng/mL. Regarding the etiology of extreme hyperferritinemia, 42.4% of patients had iron overload, 23.0% had infections, and 14.4% had Still's disease. The most common cause among rheumatology patients was Still's disease (54.3%), while the most common cause among hematology patients was iron overload (55.8%). By the end of the first month, 25 (18.0%) patients had died, with a mean time to death of 15.84±9.05 (0–30) days. We identified a ferritin cutoff value of >34,311 ng/mL for predicting 1-month mortality in rheumatology patients with extreme hyperferritinemia [%100 sensitivity and %96,77 specificity (p<0.0001, AUC: 0.976)]. In conclusion, encountering extreme hyperferritinemia in both rheumatology and hematology practice is possible. Although Still's disease is the most common cause in rheumatology patients and iron overload in hematology patients, infections, Macrophage activation syndrome (MAS), and chronic kidney disease should also be considered as potential causes. Key Words: Hyperferritinemia, Etiology, Rheumatology, Hematology, Mortality