What is Still's disease?

Still's Disease: A Systemic Inflammatory Disorder

Still's disease is a rare systemic inflammatory disorder characterized by high spiking fevers, evanescent salmon-pink rash, musculoskeletal involvement, and elevated inflammatory markers, which encompasses both systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) as part of the same disease continuum across different age groups. 1, 2

Clinical Presentation

Still's disease presents with four cardinal features:

• Fever: Typically spiking with temperature ≥39°C (102.2°F) for at least 7 days, often with a quotidian (daily) or double-quotidian pattern 1, 2
• Rash: Transient, salmon-pink, maculopapular rash that often coincides with fever spikes and predominantly affects the trunk 1, 2
• Musculoskeletal involvement: Arthralgia/myalgia is common; overt arthritis may appear later (median delay of 1 month) but is not necessary for diagnosis 1
• Inflammatory markers: High levels of inflammation marked by neutrophilic leukocytosis, elevated ESR, CRP, and markedly elevated serum ferritin 1, 2

Additional common manifestations include:

• Sore throat (38-92% of patients)
• Lymphadenopathy and splenomegaly (32-74%)
• Liver dysfunction (50-75%)
• Cardiac involvement including pericarditis (23-37%) 2

Diagnostic Approach

No single diagnostic test exists for Still's disease. Diagnosis relies on:

1. Clinical criteria: The Yamaguchi criteria are commonly used, requiring ≥5 criteria with at least 2 major criteria (fever, arthralgia, typical rash, and leukocytosis) 2

2. Laboratory findings:

   • Neutrophilic leukocytosis
   • Elevated acute phase reactants (ESR, CRP)
   • Markedly elevated serum ferritin
   • Glycosylated ferritin <20% (highly specific)
   • Negative RF and ANA
   • Liver enzyme abnormalities (usually mild) 2

3. Supportive biomarkers (if available):

   • Elevated serum IL-18
   • Elevated S100 proteins (e.g., calprotectin) 1, 2

4. Exclusion of alternative diagnoses:

   • Infections
   • Malignancies
   • Other autoimmune disorders
   • Monogenic autoinflammatory disorders 1

Disease Course and Patterns

Still's disease typically follows one of three patterns:

1. Monocyclic: Single episode with complete resolution (30%)
2. Polycyclic/intermittent: Recurrent episodes with periods of remission (30%)
3. Chronic articular: Persistent arthritis with potential joint destruction (40%) 2

Prognosis is generally more favorable when systemic symptoms predominate rather than articular manifestations 2, 3.

Treatment Approach

The 2024 EULAR/PReS recommendations provide a clear treatment algorithm:

1. First-line therapy:

   • IL-1 or IL-6 inhibitors should be initiated as early as possible when diagnosis is established 1, 2
   • NSAIDs may be effective as monotherapy in 7-15% of patients 2

2. Second-line therapy:

   • Corticosteroids (required in 76-95% of patients) 2

3. Third-line therapy (for refractory cases):

   • Conventional DMARDs (e.g., methotrexate)
   • Biological agents targeting IL-1 or IL-6 2

Treatment Targets and Monitoring

Treatment follows a treat-to-target (T2T) approach with sequential goals:

• Day 7: Resolution of fever and reduction of CRP by >50%
• Week 4: No fever, reduction of active joint count by >50%, normal CRP, and physician/patient global assessment <20/100
• Month 3: Clinically inactive disease with glucocorticoids <0.1-0.2 mg/kg/day
• Month 6: Clinically inactive disease without glucocorticoids
• Ultimate goal: Drug-free remission (defined as ≥6 months without symptoms and normal ESR/CRP) 1, 2

Complications and Warning Signs

The most serious complication is Macrophage Activation Syndrome (MAS), a life-threatening condition requiring prompt detection and treatment. Warning signs include:

• Persistent fever
• Splenomegaly
• Elevated/rising serum ferritin
• Inappropriately low cell counts
• Abnormal liver function tests
• Intravascular activation of coagulation
• Elevated/rising serum triglycerides 1, 2

Other potential complications include:

• Cardiac involvement
• Respiratory failure (Still's lung disease)
• Amyloidosis 2

Key Pitfalls to Avoid

1. Diagnostic delay: Do not require arthritis for diagnosis as it may appear later, leading to unnecessary delays 1

2. Inadequate monitoring: Regular assessment of disease activity and adjustment of therapy is crucial 1

3. Failure to recognize MAS: This complication can occur at disease onset, during treatment, or even when the disease appears to be in remission, particularly in the context of infection 1

4. Overlooking Still's lung disease: Screen for clinical symptoms and perform pulmonary function tests, with high-resolution CT scan for patients with symptoms 2

By understanding these key aspects of Still's disease, clinicians can achieve earlier diagnosis and more effective management of this challenging condition.