Systemic JIA: new developments in the understanding of the pathophysiology and therapy

Vastert, Sebastiaan J.; Kuis, Wietse; Grom, Alexei A.

doi:10.1016/j.berh.2009.08.003

« Previous Next »Best Practice & Research Clinical Rheumatology
Volume 23, Issue 5 , Pages 655-664, October 2009

Systemic JIA: new developments in the understanding of the pathophysiology and therapy

Sebastiaan J. Vastert, MD (Paediatric Rheumatology Fellow)
- Department of Pediatric Immunology Wilhelmina Children´s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, the Netherlands
- Tel.: +31 887554339; Fax: +31 887555350.
Wietse Kuis, MD, PhD (Professor of Pediatrics and Head of the Department of Paediatric Rheumatology and Immunology)
- Department of Pediatric Immunology Wilhelmina Children´s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, the Netherlands
- Tel.: +31 887554339; Fax: +31 887555350.
Alexei A. Grom, MD (Associate Professor of Pediatrics and Attending Physician)
- Division of Rheumatology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA
- Corresponding author. Tel.: +1 513 636 3339; Fax: +1 513 636 3328.

Systemic juvenile idiopathic arthritis (sJIA) is a rare, systemic inflammatory disease classified as a subtype of JIA. Besides arthritis, it is characterised by systemic features such as spiking fever, skin rash, hepatosplenomegaly or serositis. It is becoming clear now that abnormalities in the innate immunity (cytokines such as interleukin (IL)-1, IL-6 and IL-18, and neutrophils and monocytes/macrophages rather than lymphocytes) play a major role in the pathogenesis of sJIA, distinguishing it from other JIA subtypes. Another distinctive feature of sJIA is its strong association with macrophage activation syndrome (MAS). Based on this, consensus is emerging that sJIA should be viewed as an autoinflammatory syndrome rather than a classic auto-immune disease.

As a consequence of the progression in understanding the underlying mechanisms of sJIA, major changes in the management are evolving.

So far, treatment has been based on glucocorticosteroids in combination with disease-modifying drugs such as methotrexate. Recently, remarkable improvement has been observed with IL-1 and IL-6 targeted therapies. These therapies might also change the long-term outcome of this disease. However, controlled trials set up in international collaboration are needed to determine the optimal treatment strategies for all sJIA patients.

Keywords: systemic juvenile idiopathic arthritis, innate immunity, myeloid related proteins (MRPs), IL-1, IL-6, macrophage activation syndrome (MAS)