Evaluation of hyperferritinemia causes in rheumatology practice: a retrospective, single-center experience

Abstract

Hyperferritinemia may develop due to various reasons such as inflammation, infection, or malignancy. The purpose of the study to explore the prevalence and to figure out the causes of general hyperferritinemia and extreme hyperferritinemia as detected through the ferritin measurements requested by the rheumatology department. Adult patients at the age of 18 years and older with at least one serum ferritin level measurement at or above 500 ng/mL as requested by the rheumatology department between January 2010 and December 2019 were evaluated retrospectively. Hyperferritinemia was detected in 4.7% of 11,498 serum ferritin tests. The mean age of 242 patients found to have hyperferritinemia was 53.7 ± 17.1 years; of the patients, 63.2% were female, and the mean serum ferritin value was 2820 ± 5080 ng/mL. The most common cause of hyperferritinemia was rheumatological diseases with a ratio of 59.1%, which was followed by infections, iron overload, and solid malignancy. Among the rheumatologic diseases, adult-onset Still's disease (AOSD), rheumatoid arthritis, and vasculitis were the cause accounting for hyperferritinemia. Ferritin levels were significantly higher in the AOSD group compared to the other rheumatologic disease groups (p < 0.0001). While extreme hyperferritinemia (ferritin ≥ 10,000 ng/mL) rate in our cohort was 0.2%, the most common cause was AOSD (15/17). In patients with hyperferritinemia, 3 month mortality was found to be 8.7%. CRP level was identified as the only independent predictor for the 3 month mortality in all patients [OR 1.088 (95% CI 1.004-1.178), p = 0.039]. Although rheumatologic disease activation and infections are the most common causes, the other causes should also be considered for the differential diagnosis.

Causes of hyperferritinemia: what has changed with the pandemic?

“…Ferritin is a cellular iron storage protein that plays an essential role in iron metabolism. Ferritin synthesis increases in response to inflammation and oxidative stress 16,17 . Serum ferritin is one of the most commonly requested laboratory tests in day-to-day patient management.…”

“…Liver injury was defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels greater than 500 U/L 1 . Iron overload was defined as patients receiving monthly erythrocyte suspension transfusions for at least six months, requiring chelation therapy, or iron overload as determined by a hematologist 16,17 .…”

Iron metabolism and arthritis: Exploring connections and therapeutic avenues

“…[21] 3) Fe 2+ absorbed by enterocytes can enter mitochondria, be stored in ferritin, or be released into the systemic circulation via FPN1 on the membrane. (4,5) The released Fe 2+ is first oxidized to Fe 3+ by CP or HP, and then combined with TF to enter the bloodstream for circulation. ( 6) Most of the circulating TF is absorbed by erythroid precursors in the bone marrow for erythrocyte production, and the rest is distributed to other tissues or organs that require iron.…”

“…(2) Fe 2+ enters the enterocytes via DMT1. (3) Fe 2+ absorbed by enterocytes can enter mitochondria, be stored in ferritin, or be released into the systemic circulation via FPN1 on the membrane (4,5). The released Fe 2+ is first oxidized to Fe 3+ by CP or HP, and then combined with TF to enter the bloodstream for circulation.…”

A Streamlined Diagnostic Process Improved the Outcomes of Patients with Adult-Onset Still’s Disease: A Single-Center Retrospective Observational Study

“…Hyperferritinemia, a significant feature of several autoinflammatory diseases, has long been considered a disease marker and an activity indicator of AOSD [ 9 – 11 ]. Fautrel et al proposed a five-fold increase of serum ferritin levels as a specific marker for diagnosing AOSD [ 12 ].…”