Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. Systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that SJIA is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of SJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation, continue to be a major issue in SJIA patients’ care. Translational research leading to a profound understanding of the cytokine crosstalk in SJIA and the identification of risk factors for SJIA complications will help to improve long-term outcome.

Keywords:

• anakinra
• biological agents
• canakinumab
• macrophage activation syndrome
• risk factors
• systemic juvenile idiopathic arthritis
• tocilizumab

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition presenting with spiking fevers, evanescent rash, hepatosplenomegaly, serositis, lymphadenopathy and arthritis.

• SJIA is considered an autoinflammatory disease, with key players of innate immunity involved in pathophysiology.

• Major therapeutic improvements have been seen with biological agents such as IL-1 or IL-6 inhibitors, making inactive disease and clinical remission an achievable goal in the treatment of SJIA.

• Complications of SJIA include macrophage activation syndrome, damage from severe erosive arthritis occurring during the disease course, osteoporosis, growth retardation, cardiovascular events such as pulmonary hypertension and amyloidosis.

• As macrophage activation syndrome is a relatively common SJIA complication and may carry a high mortality rate, early diagnosis is crucial to prevent fatal clinical course.

• Complications due to SJIA treatment caused by immunosuppressive drugs may be severe and need thorough evaluation for the best benefit–risk ratio.

• Future management concepts for SJIA may include early introduction of IL-1 inhibitors or IL-6 inhibitors, in order to minimize or refrain from corticosteroid use. Further studies are needed to validate this therapeutic approach.

Notes

PFAPA: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis; TRAPS: Tumor necrosis factor receptor-associated periodic syndrome.

^†The diagnosis of macrophage activation syndrome requires the presence of any two or more laboratory criteria or of any two or three or more clinical and/or laboratory criteria. A bone marrow aspirate for the demonstration of hemophagocytosis may be required only in doubtful cases.

^‡Addition of the ferritin criterion showed a sensitivity of 86% and a specificity of 95% in discriminating systemic juvenile idiopathic arthritis with macrophage activation syndrome versus systemic infection.