What is the initial treatment for a pediatric patient with Systemic-Onset Juvenile Idiopathic Arthritis (SOJIA) who develops Hemophagocytic Lymphohistiocytosis (HLH)?

Treatment of HLH in SOJIA in Children

Initiate high-dose intravenous methylprednisolone at 1g/day for 3-5 consecutive days as first-line treatment, and if there is inadequate response within 24-48 hours, add cyclosporine A (2-7 mg/kg/day) or anakinra (2-10 mg/kg/day subcutaneously in divided doses). 1

First-Line Treatment Approach

High-dose corticosteroids are the cornerstone of initial therapy for MAS-HLH complicating SOJIA, specifically methylprednisolone 1g/day intravenously for 3-5 consecutive days. 2, 1 This differs from the standard HLH-94 protocol used in primary HLH, as MAS-HLH requires a distinct treatment approach due to the underlying autoinflammatory disease. 2

Critical Initial Management Steps:

• Simultaneously control the underlying SOJIA disease activity, as uncontrolled systemic inflammation perpetuates MAS. 1
• Provide intensive supportive care with frequent reassessment at least every 12 hours to determine if additional HLH-directed therapy is needed. 2, 1
• Monitor inflammatory parameters including ferritin, complete blood counts, liver function, coagulation studies, and organ function continuously. 1

Second-Line Treatment (Within 24-48 Hours if Inadequate Response)

Add cyclosporine A at 2-7 mg/kg/day to corticosteroids for patients showing insufficient immediate response. 2, 1 Alternatively, add anakinra at 2-10 mg/kg/day subcutaneously in divided doses (up to 10 mg/kg/day). 2, 1

Tocilizumab may be considered as an alternative, particularly if the patient was already receiving this medication for SOJIA management prior to developing MAS. 2, 1

SOJIA-Specific Medication Management

Biologic DMARDs:

• Continue or optimize IL-1 or IL-6 inhibitors if already in use, as these may help control both the underlying SOJIA and the MAS simultaneously. 1
• IL-1 and IL-6 inhibitors are extremely effective for SOJIA and have allowed marked reduction in glucocorticoid use. 2

Conventional DMARDs:

• Temporarily hold or reduce methotrexate during acute MAS due to bone marrow suppression risk. 1
• Conventional synthetic DMARDs are strongly recommended against as initial monotherapy for systemic JIA without MAS due to lack of efficacy at controlling systemic features. 2

Critical Monitoring Parameters

Watch for the following clinical indicators:

• Persistent fever, cytopenias, hepatosplenomegaly, and coagulopathy. 1
• Rising ferritin levels (hyperferritinemia is a cardinal feature). 2
• Multi-organ dysfunction including hepatic, renal, cardiac, and neurologic involvement. 1
• Development of disseminated intravascular coagulation (DIC), which is associated with high mortality. 3

Common Pitfalls to Avoid

Do not delay treatment initiation, as delayed treatment significantly increases mortality. 2 The mortality rate for children hospitalized with systemic JIA and MAS is estimated to be as high as 6%, but may be higher based on case series. 2

Do not use conventional synthetic DMARDs as initial monotherapy for active systemic features, as they lack efficacy for controlling systemic manifestations and lead to continued glucocorticoid dependence. 2

Do not apply standard HLH-94 protocols without modification, as MAS-HLH requires a different treatment approach focused on controlling the underlying autoinflammatory disease. 2

Prognostic Factors

Factors associated with worse outcomes include:

• Shock at presentation. 1
• Platelet count <30 g/L. 1
• Delayed treatment initiation. 1
• Development of multi-organ failure and DIC. 3, 4

Refractory Cases

For patients refractory to corticosteroids, cyclosporine A, and anakinra, consider plasma exchange therapy, which has shown success in case reports of severe HPS complicating SOJIA. 5 Etoposide-based regimens may be considered in truly refractory cases, though this is more commonly used in primary HLH. 6