Definition of Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA)
Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA), now increasingly referred to as Still's disease in children, is defined as arthritis in one or more joints for at least 6 weeks' duration in a child under 16 years of age, with or preceded by quotidian (daily) fever of at least 2 weeks' duration documented for at least 3 days, accompanied by one or more of the following: evanescent erythematous rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, or serositis. 1
Core Diagnostic Features
The diagnosis of SOJIA is clinical and based on four cardinal manifestations 1, 2:
- Recurrent spiking fever: Quotidian fever pattern (daily fever spikes) that must be documented for at least 2 weeks, with fever present for at least 3 days 1, 2
- Characteristic skin rash: Evanescent, salmon-colored, maculopapular rash that typically accompanies fever spikes and is transient in nature 1, 2
- Arthritis or arthralgia: Joint involvement, though notably arthritis is not essential for diagnosis according to recent consensus 1, 2
- Systemic inflammation: Markedly elevated inflammatory markers including ESR, CRP, leukocytosis with neutrophil predominance, and hyperferritinemia (often exceeding 1000 ng/mL) 2
Additional Clinical Manifestations
Beyond the core features, SOJIA patients frequently present with 2:
- Organomegaly: Hepatosplenomegaly with elevated liver function tests 2
- Serositis: Pericarditis, pleuritis, or peritonitis 1, 2
- Lymphadenopathy: Generalized lymph node enlargement 1, 2
- Thrombocytosis: Elevated platelet count during active inflammation 2
Age and Classification Criteria
- Age requirement: Onset must occur before 16 years of age, distinguishing it from Adult-Onset Still's Disease (AOSD), which requires onset after 18 years 1, 3
- Duration requirement: Symptoms must persist for at least 6 weeks according to ILAR criteria 3
- Unified nomenclature: The 2024 EULAR/PReS guidelines now recognize SOJIA and AOSD as the same disease entity across all ages, termed "Still's disease," eliminating the arbitrary age-based distinction 1, 2
Pathophysiology
SOJIA is classified as an autoinflammatory disorder rather than a traditional autoimmune disease 4:
- Cytokine-driven: IL-1β and IL-6 are key cytokines driving the inflammatory process, distinguishing SOJIA from other JIA subtypes 5, 4
- Innate immune dysfunction: Defects in innate immune system pathways lead to significant systemic inflammation 4
Life-Threatening Complications
Two critical complications define the severity of SOJIA 2:
- Macrophage Activation Syndrome (MAS): Occurs in 11.9-36% of patients, representing the leading cause of mortality; presents with persistent high fever, hepatosplenomegaly, cytopenias, coagulopathy, and extreme hyperferritinemia 2, 6
- SOJIA-associated lung disease (SOJIA-LD): A severe evolving phenotype requiring specialized management 7
Differential Diagnosis Considerations
The diagnosis requires exclusion of 1, 3:
- Infectious causes: Viral syndromes (rubella, CMV, EBV), bacterial infections, fungal, mycobacterial infections 1, 3
- Malignancy: Leukemia, lymphoma, angioblastic lymphadenopathy 1, 3
- Other rheumatic diseases: SLE, vasculitis, reactive arthritis 1, 3
- Periodic fever syndromes: Familial Mediterranean fever, TRAPS 1
Clinical Course and Prognosis
- Variable outcomes: Up to 50% of severely affected children develop chronic, destructive polyarthritis 5-10 years after diagnosis 1
- Risk of disability: Children with SOJIA are at significant risk of lifelong disability, growth disturbances, and joint damage 1
- Treatment responsiveness: The condition may be less responsive to traditional DMARDs and even anti-TNF therapy compared to other JIA subtypes 1