What is Pediatric Still's Disease?
Pediatric Still's disease, now officially termed "Still's disease" (formerly systemic juvenile idiopathic arthritis or sJIA), is an acquired autoinflammatory condition characterized by spiking fevers ≥39°C, transient salmon-pink rash, musculoskeletal involvement, and marked systemic inflammation—representing the same disease entity as adult-onset Still's disease, differing only by age of onset before 16 years. 1
Core Clinical Features
The 2024 EULAR/PReS guidelines establish operational definitions for rapid diagnosis 1:
Cardinal manifestations include:
- Fever: Spiking pattern with temperature ≥39°C (102.2°F) for at least 7 days
- Rash: Transient, erythematous (salmon pink), coinciding with fever spikes, predominantly on trunk (though urticarial variants may occur)
- Musculoskeletal involvement: Arthralgia/myalgia is typical; overt arthritis is NOT required for diagnosis and often appears later (median 1 month delay, range 0 to several months)
- Systemic inflammation: Neutrophilic leukocytosis, elevated ESR, CRP, and markedly elevated ferritin 1
Critical point: The requirement for arthritis to diagnose Still's disease leads to unnecessary and potentially deleterious diagnostic delays. The underlying immunological mechanisms are similar whether arthritis is present or not 1.
Diagnostic Approach
Laboratory hallmarks:
- High neutrophil count
- Elevated platelet count, fibrinogen, D-dimers
- Markedly elevated serum ferritin
- Marked elevation of IL-18 and/or S100 proteins (e.g., calprotectin) strongly supports diagnosis and should be measured if available 1
Essential exclusions: Malignancies, infectious diseases, other immune-mediated inflammatory diseases, and monogenic autoinflammatory disorders must be carefully ruled out 1.
Disease Nomenclature and Continuum
The 2024 EULAR/PReS consensus achieved 100% expert agreement that sJIA and adult-onset Still's disease (AOSD) are the same disease and should be designated by the single name "Still's disease" 1, 2. The arbitrary age cutoff of 16 years was historically based on healthcare system organization in the UK, not biological differences 1.
Life-Threatening Complications
Macrophage Activation Syndrome (MAS)
MAS is the main life-threatening complication, particularly in children under age 2, with approximately 10% mortality 1. This can occur:
- At disease onset
- During treatment
- Even during remission (especially with concurrent infection)
Screen for MAS with:
- Persistent fever
- Splenomegaly
- Elevated or rising ferritin
- Inappropriately low cell counts
- Abnormal liver function tests
- Intravascular coagulation activation
- Elevated or rising triglycerides 1
MAS treatment requires immediate high-dose glucocorticoids PLUS anakinra, ciclosporin, and/or interferon-γ inhibitors as part of initial therapy 1.
Lung Disease
Active screening is mandatory through:
- Clinical symptoms (clubbing, persistent cough, shortness of breath)
- Pulmonary function tests (pulse oximetry, DLCO measurement)
- High-resolution CT scan for symptomatic patients 1
Important: The presence of lung disease risk factors or active lung disease should NOT be considered a contraindication to IL-1 or IL-6 inhibitors 1.
Disease Heterogeneity
Still's disease manifests with distinct phenotypes 2, 3:
- Systemic inflammatory phenotype: Predominant autoinflammation driven by innate immune dysregulation
- Chronic articular phenotype: With or without residual systemic features, involving adaptive immunity
Recent recognition of a particularly severe form associated with MAS, very high IL-18 levels, and adverse reactions to typically effective biologics (anti-IL-1 or anti-IL-6) requires specialized management 4, 3.
Pathophysiology
Still's disease represents a complex, polygenic autoinflammatory syndrome with overexpression of inflammatory cytokines (IL-1, IL-6, IL-18) and calcium-binding proteins 2, 5. The innate immune system plays the predominant role, particularly early in disease, with potential progression to adaptive immune-mediated chronic arthritis 5.
Management Principles
Treatment-to-target approach with the ultimate goal of drug-free remission 1. IL-1 and IL-6 inhibitors should be prioritized and initiated as early as possible when diagnosis is established to avoid prolonged glucocorticoid use 1.
Difficult-to-treat patients, those with severe MAS, and those with lung disease should be managed in collaboration with Still's disease expert centers 1.