What are the clinical features of Still's disease?

Clinical Features of Still's Disease

Still's disease presents with four cardinal features: high spiking fever (≥39°C for ≥7 days), transient salmon-pink rash coinciding with fever spikes, musculoskeletal involvement (arthralgia/myalgia with or without arthritis), and marked systemic inflammation with neutrophilic leukocytosis, elevated CRP, and hyperferritinaemia. 1

Core Clinical Manifestations

Fever Pattern

• Spiking fever ≥39°C (102.2°F) lasting at least 7 days is the hallmark feature, occurring in approximately 95.7% of patients 1, 2
• The fever pattern is characteristically quotidian (daily spikes) with return to baseline or below between episodes 3

Cutaneous Manifestations

• Salmon-pink, evanescent rash occurs in 51-87% of patients and is pathognomonic when present 2, 3
• The rash is transient, often coinciding with fever spikes, and preferentially involves the trunk 1
• May be difficult to visualize on darker skin tones, requiring careful examination 1
• Other rash patterns (urticarial, persistent papules/plaques) may occur but are less typical 1, 4
• Histologically shows variable patterns: predominantly lymphocytic, mixed, or neutrophilic infiltrates with possible vacuolar interface changes 4

Musculoskeletal Features

• Arthralgia/myalgia is nearly universal, with myalgia occurring in 56-84% of patients 2, 5
• Overt arthritis is NOT required for diagnosis and typically appears later (median delay of 1 month after disease onset, range 0 to several months) 1
• This represents a critical diagnostic update: requiring arthritis causes unnecessary and potentially deleterious diagnostic delays 1

Systemic Features

• Sore throat/pharyngitis occurs in 35-92% of patients and is a distinctive early feature 2, 3, 5
• Lymphadenopathy is present in 32-74% of patients 2
• Splenomegaly occurs in 14-65% of patients (average ~32%) 2
• Hepatomegaly and elevated liver enzymes are common 6, 5

Laboratory Hallmarks

Inflammatory Markers

• Neutrophilic leukocytosis with striking elevation (often >15,000/μL) 1, 5
• Markedly elevated serum ferritin (often >1000 ng/mL, frequently >5000 ng/mL) 1, 2
• Elevated CRP and ESR are consistently present 1
• Elevated platelet count, fibrinogen, and D-dimers are typical 1

Supportive Biomarkers

• Marked elevation of serum IL-18 and/or S100 proteins (calprotectin) strongly supports the diagnosis and should be measured when available 1, 2
• These biomarkers are among the most promising diagnostic tools currently under validation 1

Serious Complications Requiring Vigilance

Macrophage Activation Syndrome (MAS)

• MAS is the most life-threatening complication, more frequent in children under age 2 but can occur at any age 1
• Can present at disease onset, during treatment, or even when disease is in remission, especially with concurrent infection 1
• Clinical clues include: persistent fever, splenomegaly, elevated or rising ferritin, inappropriately low cell counts (cytopenias), abnormal liver function tests, intravascular coagulation, elevated triglycerides 1

Cardiovascular Manifestations

• Pericarditis occurs in 10-37% of patients and represents a significant cardiac complication 2
• Cardiac tamponade can occur and requires urgent intervention 2

Pulmonary Involvement

• Pleuritis occurs in 12-53% of patients 2
• Still's lung disease requires active screening with clinical symptoms (clubbing, persistent cough, dyspnea), pulmonary function tests, and high-resolution CT when symptomatic 1

Hematologic Complications

• Disseminated intravascular coagulation (DIC) is a rare but potentially fatal complication that can develop during disease course 6

Clinical Patterns and Heterogeneity

No single symptom or laboratory finding is specific for Still's disease, making it a diagnosis of exclusion 1. The clinical expression is heterogeneous, and alternative diagnoses including malignancies, infections, other immune-mediated inflammatory diseases, and monogenic autoinflammatory disorders must be carefully excluded 1.

The disease typically follows one of three patterns (each affecting approximately one-third of patients): self-limited/monocyclic, intermittent/polycyclic, or chronic articular pattern 2.

Diagnostic Approach

The Yamaguchi criteria remain the most validated classification system, tested in both pediatric (sJIA) and adult (AOSD) populations with high sensitivity 1. Critically, these criteria do not require arthritis for diagnosis, aligning with current understanding that arthritis is supportive but not mandatory 1.