Diagnostic significance of an elevated ferritin in adult onset Stills disease

Diagnostic significance of an elevated ferritin in adult onset Stills disease

An extremely elevated serum ferritin (>1000 ng/mL) in the proper clinical setting is suggestive of Still’s disease and seen in up to 70% patients.

Values over 4000 ng/mL are seen in <50% cases.

In addition to AOSD, the differential diagnosis of fever with hyperferritinemia includes infections (HIV, TB, cytomegalovirus [CMV]), malignancies (colon, prostate, breast, lung, liver, and metastatic melanoma), lymphomas, liver metastasis, septic shock, catastrophic antiphospholipid antibody syndrome, MAS/RHL, and systemic lupus erythematosus (SLE). However, unlike these other causes, the elevated ferritin in AOSD is mostly nonglycosylated (H-ferritin), with the glycosylated form (L-ferritin) being <20% of total ferritin. This pattern of ferritin (ferritin >1000 ng/mL, <20% glycosylated) has a 70% to 80% sensitivity and 84% to 93% specificity for the diagnosis of AOSD. The etiology of the elevated ferritin is postulated to be from proinflammatory cytokines (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-18, others) inducing the heme-degrading enzyme, heme oxygenase-1, on macrophages and endothelial cells causing the release of iron from heme, which stimulates ferritin synthesis. Interestingly, ferritin can then provide positive feedback by activating the nuclear factor-κB signaling pathway, leading to more proinflammatory cytokine production. Some experts recommend following ferritin levels for response to therapy.


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