What autoimmune diseases can cause markedly elevated ferritin, low iron saturation, high‑normal total iron‑binding capacity, normal hemoglobin and hematocrit, and an elevated white blood cell count with neutrophilia?

Adult-Onset Still's Disease (AOSD) is the Primary Autoimmune Condition Matching This Profile

The constellation of markedly elevated ferritin, low iron saturation, high-normal TIBC, normal hemoglobin/hematocrit, and neutrophilic leukocytosis is highly characteristic of Adult-Onset Still's Disease (AOSD), which represents the adult form of Still's disease—a hyperferritinemic inflammatory syndrome. 1, 2

Why AOSD Fits This Clinical Picture

The laboratory pattern you describe is pathognomonic for AOSD:

• Markedly elevated ferritin (often >1000 ng/mL, frequently >5000 ng/mL): AOSD is one of four conditions comprising the "hyperferritinemic syndrome" where ferritin levels reach extreme elevations 3, 4. Studies show ferritin cutoffs of 1120-2500 ng/mL have sensitivities of 74-96% and specificities of 50-94% for AOSD diagnosis 1

• Low iron saturation with high-normal TIBC: This reflects the "anemia of chronic inflammation" pattern where iron is sequestered in storage (hence high ferritin) but not available for erythropoiesis. However, in your case, the hemoglobin remains normal, which is consistent with early or well-compensated AOSD 4, 5

• Normal hemoglobin/hematocrit: While many AOSD patients develop anemia, it's not universal, particularly in early disease or less severe cases. The inflammatory state causes iron sequestration without necessarily causing anemia initially 6

• Elevated WBC with neutrophilia: Neutrophilic leukocytosis is a cardinal feature of AOSD, reflecting the acute inflammatory state. The 2024 EULAR/PRES guidelines specifically identify "neutrophilic leucocytosis" as one of the key laboratory features for Still's disease diagnosis 2

Diagnostic Approach for AOSD

According to the 2024 EULAR/PRES guidelines 2, the operational definition requires:

1. Fever: Spiking pattern ≥39°C (102.2°F) for ≥7 days
2. Rash: Transient, salmon-pink, erythematous, often coinciding with fever spikes
3. Musculoskeletal involvement: Arthralgia/myalgia (arthritis is supportive but NOT required for diagnosis)
4. High inflammation markers: Neutrophilic leukocytosis, elevated CRP, ESR, and ferritin

Critical point: The guidelines emphasize that arthritis is NOT mandatory for diagnosis, as it often appears later (median 1 month delay, range 0 to several months) 2. Requiring arthritis causes dangerous diagnostic delays.

Enhanced Diagnostic Specificity

Glycosylated ferritin (GF) ≤20% combined with elevated total ferritin significantly improves diagnostic accuracy for AOSD, with sensitivity of 79.5% and specificity of 66.4% 1. When using the combination of ferritin >5× normal + GF ≤20%, specificity increases to 92.9% 1.

Other Conditions in the Hyperferritinemic Syndrome

Three other conditions share this extreme ferritin elevation pattern 3, 4:

1. Macrophage Activation Syndrome (MAS): Often complicates AOSD itself; characterized by cytopenias (which you don't have), hepatosplenomegaly, and coagulopathy
2. Catastrophic Antiphospholipid Syndrome: Requires antiphospholipid antibodies and thrombotic events
3. Septic shock/severe sepsis: Clinical context would be obvious

Why Other Autoimmune Diseases Are Less Likely

• Systemic Lupus Erythematosus (SLE): While ferritin can be elevated in SLE, it correlates with anemia of chronic disease 6. Your normal hemoglobin makes this less likely. SLE typically shows lymphopenia rather than neutrophilia.

• Rheumatoid Arthritis: May show elevated ferritin but rarely to the extreme levels seen in AOSD (typically <1000 ng/mL) 7

• Other inflammatory conditions: Malignancy and iron overload syndromes are actually more common causes of marked hyperferritinemia than autoimmune diseases 7, but these wouldn't explain the low iron saturation with high-normal TIBC pattern

Critical Clinical Caveat

Monitor vigilantly for Macrophage Activation Syndrome (MAS), which is the most life-threatening complication of AOSD 2. MAS can occur at disease onset, during treatment, or even during remission (especially with concurrent infection). The 2024 guidelines emphasize that physicians must "always be aware of this specific risk" and "rapidly adjust treatment" 2.

Red Flags for MAS Development:

• Falling blood counts (especially platelets, WBC)
• Worsening ferritin (often >10,000 ng/mL)
• Elevated triglycerides, low fibrinogen
• Hepatosplenomegaly, liver dysfunction
• Neurological changes

Practical Algorithm

1. Confirm AOSD diagnosis: Apply Yamaguchi criteria (validated for both children and adults with high sensitivity) 2
2. Measure glycosylated ferritin: If ≤20% with total ferritin >5× normal, strongly supports AOSD 1
3. Rule out infection and malignancy: These are more common causes of hyperferritinemia overall 7
4. Monitor for MAS: Serial CBC, ferritin, liver function, coagulation studies
5. Initiate treatment: Per EULAR/PRES guidelines, treat-to-target approach with goal of drug-free remission 2