Elevated Ferritin in Sjögren's Syndrome
In Sjögren's syndrome, elevated ferritin is a marker of chronic inflammation and immune activation—not iron overload—and should be interpreted alongside transferrin saturation to avoid misdiagnosis and inappropriate iron-directed therapy. 1, 2
Understanding Ferritin Elevation in Sjögren's Syndrome
Ferritin functions as an acute-phase reactant that rises during inflammatory states independent of actual iron stores. 1, 2 In Sjögren's syndrome specifically:
Chronic inflammation drives ferritin elevation through the systemic inflammatory response characteristic of this autoimmune disease, similar to other rheumatologic conditions. 1, 2
Type I interferon overexpression in Sjögren's syndrome activates the immune system and contributes to the inflammatory milieu that elevates ferritin levels. 3
Cytokine dysregulation with overexpression of pro-inflammatory cytokines (TNF-alpha, IL-17, IL-12/IL-23) perpetuates the inflammatory state reflected in elevated ferritin. 4
Critical Diagnostic Algorithm
Step 1: Measure transferrin saturation (TS) simultaneously with ferritin to distinguish inflammatory hyperferritinemia from true iron overload. 1, 2
If TS <45%: The elevated ferritin reflects inflammation from Sjögren's syndrome, not iron overload—no iron-directed therapy is indicated. 1, 5
If TS ≥45%: Proceed to HFE genetic testing (C282Y and H63D mutations) to evaluate for coexistent hereditary hemochromatosis. 1, 2
Step 2: Assess for iron deficiency paradoxically coexisting with elevated ferritin:
In Sjögren's syndrome patients, iron deficiency is actually common (51% prevalence) despite the inflammatory state that elevates ferritin. 6
Functional iron deficiency can occur when hepcidin (elevated by inflammation) blocks iron release from storage sites, creating a pattern of elevated ferritin with low TS and true iron deficiency. 2
Check complete iron panel: serum iron, total iron binding capacity (TIBC), and transferrin saturation—not just ferritin alone. 1, 5
Clinical Significance and Management
The ferritin level correlates with disease activity in inflammatory conditions and may fluctuate with Sjögren's syndrome flares. 2
Management priorities:
Treat the underlying Sjögren's syndrome inflammation, not the ferritin number itself. 1, 5
Screen for coexistent deficiencies: Iron deficiency (51%), vitamin B12 deficiency (25%), and folate deficiency (9%) are highly prevalent in Sjögren's syndrome and require active surveillance. 6
Monitor thyroid function: Autoimmune thyroiditis occurs in 30% of Sjögren's syndrome patients and can contribute to metabolic dysfunction affecting ferritin levels. 6
Avoid iron supplementation if TS is normal or elevated, as this indicates adequate iron stores despite elevated ferritin. 1
Risk Stratification by Ferritin Level
Ferritin <1,000 μg/L: Low risk of organ damage; typical range for inflammatory hyperferritinemia in rheumatologic disease. 1, 2
Ferritin 1,000-10,000 μg/L: Warrants evaluation for other causes beyond Sjögren's syndrome alone, including malignancy (most common cause at this level), infection, or liver disease. 2, 7
Ferritin >10,000 μg/L: Rarely represents simple inflammatory disease—requires urgent specialist referral to evaluate for life-threatening conditions such as hemophagocytic lymphohistiocytosis, macrophage activation syndrome, or adult-onset Still's disease. 1, 2, 7
Common Pitfalls to Avoid
Never use ferritin alone without transferrin saturation to assess iron status in inflammatory conditions like Sjögren's syndrome. 1, 2
Do not assume elevated ferritin means iron overload in the context of known autoimmune disease—over 90% of hyperferritinemia cases reflect inflammation, not iron accumulation. 2, 5
Do not overlook true iron deficiency in Sjögren's syndrome patients with elevated ferritin—check TS and consider functional iron deficiency if TS is low despite elevated ferritin. 2, 6
Do not initiate phlebotomy or iron chelation based on elevated ferritin alone in Sjögren's syndrome patients without confirming true iron overload via TS ≥45% and genetic testing. 1, 2