Síndrome auto-inflamatório adquirido
Disease spectrum
- Systemic-onset juvenile idiopathic arthritis: onset before 16 years old
- Adult onset Still disease: onset at or after 16 years old
Juvenile Idiopathic Arthritis classified in 7 major types
- Systemic-onset (Still disease)
- Rheumatoid factor positive polyarticular
- RF negative polyarticular
- Oligoarticular
Epidemiology
- Juvenile Idiopathic Arthritis is the most common rheumatic disease in childhood
- 0,2-1 per 1000 children
- Systemic-onset represents 15-20% of all JIA
Mechanism: autoinflammatory disease (not autoimmune)
- Activation of innate immune system
- Dysregulated IL1 (hence response to IL1 antagonists)
- IL1 → stimulates granulopoiesis in bone marrow
- IL1 → activates thermoregulatory functions of the hypothalamus
- IL-6 → stimulates osteoclastogenesis, production of C reactive protein
Clinical presentation
- Skin → evanescent exanthem
- Evanescent, erythematous eruption
- Coincides with fevers
- Transient, disappears within a few hours (<24h) without scar
- Accompanied by arthralgias, but in 1/4 of patients rash may precede arthritis
- Predilection for axillae and waist
- May have persistent plaques, which may be linear
- Periorbital erythematous edema
- May have linear lesions due to Koebner
- May have dermographism
- Daily high fevers (usually >38,9ºC)
Complications
- Macrophage activation syndrome
- Fever, cytopenias, liver dysfunction, coagulopathy, hypofibrinogenimia, hypertriglyceridemia, high levels of ferritin
- Severe interstitial lung disease due to alveolar proteinosis and/or endogenous lipoid pneumonia
- Acute clubbing
Histology of evanescent exanthem
- Perivascular and interstitial neutrophil-dominant mixed infiltrate ~neutrophilic urticarial dermatosis
DDx - “Still disease remains a diagnosis of exclusion after other causes, particularly infectious ones have been ruled out”
- Transient exanthem associated with fever
- Rheumatic fever - erythema marginatum
- Hypocomplementemic urticarial vasculitis
- Serum-sickness like reaction
- Hereditary periodic fever syndromes
- Leukemia, lymphoma
- Parvovirus B19
- Malaria
- Chronic miningococcemia
- Rat bite fever
- Cystic fibrosis associated episodic arthritis
Treatment
- NSAIDs
- IL-1/IL-1R antagonists
- Anakinra
- Canakinumab
- IL-6R antagonists
- Tocilizumab
- TNF inhibitors less effective
- Conventional steroid sparing immunomodulators
- MTX
- Abatacept
- Azathioprine
- Leflunomide
- Thalidomide
- Hematopoietic stem cell transplantation