Can Still's Disease Present with Normal WBC Count?
Yes, Still's disease can absolutely be present with a normal white blood cell count, and a normal WBC should never exclude the diagnosis when other clinical features are suggestive. While neutrophilic leukocytosis is typical, it is not mandatory for diagnosis.
Understanding the Diagnostic Criteria
The 2024 EULAR/PReS guidelines emphasize that Still's disease diagnosis relies on a combination of clinical and laboratory findings, with no single feature being absolutely required 1:
- Fever ≥39°C (102.2°F) for at least 7 days with characteristic spiking pattern 1, 2
- Evanescent salmon-pink rash that often coincides with fever spikes 1, 3
- Musculoskeletal involvement (arthralgia/myalgia is sufficient; overt arthritis is NOT required for diagnosis) 1, 3
- High levels of inflammation are typically identified by neutrophilic leukocytosis, increased CRP, and ferritin 1
Why Normal WBC Doesn't Exclude Still's Disease
The guidelines specifically state that "high levels of inflammation are typically identified" by neutrophilic leukocytosis—the word "typically" is critical here 1. This indicates it's a common but not universal finding. The diagnostic approach is pattern-based, not checklist-based.
The most validated classification criteria (Yamaguchi criteria) do not require leukocytosis as a mandatory criterion 2, 3. While leukocytosis ≥10,000/μL with ≥80% granulocytes is one of the minor criteria in Yamaguchi, patients can meet diagnostic criteria without it.
What Matters More Than WBC Count
Critical Diagnostic Biomarkers to Obtain:
- Serum IL-18: Marked elevation strongly supports diagnosis (sensitivity 78-95%, specificity 83-99% depending on cutoff) 1
- S100 proteins (calprotectin): Highly elevated levels identify Still's disease with high sensitivity and specificity 1
- Ferritin: Typically markedly elevated (often >1000 ng/mL) 1
- CRP/ESR: Usually elevated even when WBC is normal 1
Clinical Pattern Recognition:
The diagnosis hinges on recognizing the constellation of features 1, 2:
- Quotidian or double-quotidian fever pattern
- Transient rash coinciding with fever spikes
- Arthralgia (arthritis may appear later, median 1 month after onset) 3
- Exclusion of alternative diagnoses (infections, malignancies, other autoimmune diseases) 1
Critical Pitfalls to Avoid
Do not delay diagnosis waiting for "classic" laboratory findings like leukocytosis 2, 4. This is explicitly warned against in the guidelines. Delaying diagnosis while waiting for laboratory abnormalities to develop can lead to:
- Progression to life-threatening complications like macrophage activation syndrome (MAS) 1, 3
- Missed therapeutic window of opportunity 1, 5
- Unnecessary diagnostic delays that worsen outcomes 2, 4
When to Strongly Consider Still's Disease Despite Normal WBC
Maintain high suspicion when you see:
- High spiking fevers (≥39°C) for ≥7 days with characteristic pattern 1
- Salmon-pink evanescent rash 1
- Markedly elevated ferritin (especially if >1000 ng/mL) 1
- Elevated IL-18 or S100 proteins if available 1
- Elevated CRP/ESR even with normal WBC 1
- Arthralgia or myalgia 1
Practical Approach
If clinical suspicion is high based on fever pattern, rash, and musculoskeletal symptoms:
- Measure IL-18 and/or S100 proteins (calprotectin) if available—these have superior diagnostic value compared to WBC count 1
- Check ferritin levels—often dramatically elevated even when WBC is normal 1
- Ensure CRP/ESR are measured—inflammation markers may be elevated despite normal WBC 1
- Systematically exclude alternative diagnoses (infections, malignancies, other autoimmune conditions) 1
- Do not wait for leukocytosis to develop before initiating treatment if other features strongly suggest Still's disease 2, 4
The absence of leukocytosis should prompt you to be more thorough in excluding mimics, but it should never be used as a reason to dismiss the diagnosis when the clinical picture is otherwise compelling 1, 2.