Key Points
- Systemic juvenile idiopathic arthritis accounts for approximately 4-15% of juvenile idiopathic arthritis (JIA) and is defined as arthritis in ≥1 joint for ≥6 weeks in a child age <16 years with or preceded by fever of ≥2 weeks that is documented to be daily (“quotidian”) for ≥3 days and accompanied by one or more of the following: evanescent erythematous rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, and serositis.
- The goal of therapy for systemic JIA is similar to that of the other categories of JIA, and focuses on the prompt control of active inflammation and symptoms and the prevention of a number of disease- and/or treatment-related morbidities such as growth disturbances, joint damage, and functional limitations.
- Many children with systemic JIA have a particularly refractory course, with persistent disease associated with a high risk of joint damage and severe growth impairment.
- The inflammatory process underlying systemic JIA appears to be distinct from other categories of JIA, with a central role for both interleukin-1 (IL-1) and IL-6.
- Approximately 10% of children with systemic JIA develop overt clinical features of macrophage activation syndrome (MAS), a life-threatening condition characterized by fever, organomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and coagulopathy, among other findings.
- The mortality rate for children hospitalized with systemic JIA and MAS is estimated to be as high as 6% but may be even higher based on estimates from case series.
Treatment
Systemic JIA With Active Systemic Features and Varying Degrees of Synovitis
Systemic JIA Without Active Systemic Features and Varying Degrees of Synovitis
Systemic JIA with Features Concerning for MAS
Note: These treatment options are not meant to be mutually exclusive, and there may be certain clinical situations for which the simultaneous initiation of more than one of these medications is appropriate. Combination therapy with anakinra, a calcineurin inhibitor, and systemic GCs was not specifically addressed.
Table 1. Initial Therapy for Systemic JIA with Features Concerning for MAS
| Treatment | Quality of Evidence |
|---|---|
| Anakinra | C |
| Calcineurin inhibitor | C |
| Systemic GC monotherapy (IV or PO) | C With the exception of continuing GC monotherapy for >2 weeks in patients with continued features concerning for MAS, in which case it was inappropriate (D). Specific tapering strategies for GCs were not specifically addressed by the ACR. |
Table 2. Uncertain or Inappropriate Options for Continued MAS Activity
| Treatment | Quality of Evidence |
|---|---|
| Canakinumab | Uncertain With the exception of patients with an MD global <5 who had received no prior therapy, GC monotherapy, or calcineurin monotherapy, in which case it was inappropriate (D) |
| Rilonacept | Uncertain |
| Tocilizumab | Uncertain |
| Abatacept | D Inappropriate |
| IVIG | D Inappropriate With the exception of patients who had tried a calcineurin inhibitor in combination with anakinra, in which case it was uncertain. |
| MTX or leflunomide | D Inappropriate |
| Rituximab | D Inappropriate |
| TNF-α | D Inappropriate With the exception of patients who had tried a calcineurin inhibitor in combination with anakinra, in which case it was uncertain. |
Table 3. Repeat Testing for Latent TB in Children with All Categories of JIA
| Test | Quality of Evidence |
|---|---|
| Annual screening of children at low risk of TB with an initial negative TB test | D Inappropriate |
| Repeat TB screening of patients with an initial negative TB test prior to starting a biologic agent at any point if their risk of TB changed to moderate or high, as determined by regional infectious disease guidelines | D |
