What is the treatment for macrophage activation syndrome?

Treatment of Macrophage Activation Syndrome

High-dose intravenous methylprednisolone at 15-30 mg/kg/day (maximum 1g/infusion) for 3-5 consecutive days is the first-line treatment for MAS, with immediate addition of cyclosporine A (2-7 mg/kg/day) for severe cases or inadequate response within 24-48 hours. 1, 2

First-Line Treatment Approach

• Initiate high-dose pulse methylprednisolone immediately upon diagnosis, administered as 1g/day intravenously for 3-5 consecutive days in adults, or 15-30 mg/kg/day (maximum 1g/infusion) in pediatric patients 3, 1
• Switch to dexamethasone when central nervous system involvement is present, as it crosses the blood-brain barrier more effectively than methylprednisolone 1
• Early treatment initiation is critical to prevent irreversible organ damage and reduce mortality, which remains high at approximately 42.5% in adult MAS patients 4

Second-Line and Combination Therapies

For patients showing inadequate response to corticosteroids or presenting with severe MAS and rapid clinical deterioration, add cyclosporine A immediately rather than waiting for treatment failure. 1, 2

• Cyclosporine A should be administered at 2-7 mg/kg/day, either orally or intravenously in critical care settings 3, 1, 2
• Cyclosporine achieves rapid fever resolution within 36 hours of initiation and should be considered first-line therapy alongside corticosteroids in severe cases 5
• Anakinra (IL-1 receptor antagonist) at 2-10 mg/kg/day subcutaneously in divided doses is an effective alternative or addition to cyclosporine, particularly in Still's disease-related MAS 3, 1, 2
• Tocilizumab (IL-6 blockade) has increasing evidence for efficacy in MAS-HLH, particularly when associated with systemic rheumatic conditions 3, 1

Treatment Algorithm for Severe or Refractory Cases

In severe MAS with multi-organ failure or shock, initiate combination therapy with corticosteroids plus cyclosporine A plus anakinra simultaneously rather than sequentially. 1, 2

• Emapalumab (anti-IFN-γ antibody) has demonstrated efficacy in clinical trials for Still's disease-related MAS refractory to standard therapy, achieving remission in the majority of patients 1
• JAK inhibitors (ruxolitinib or baricitinib) show efficacy in case reports of refractory MAS and represent emerging therapeutic options 1, 2
• Etoposide at reduced doses (50-100 mg/m² weekly) should be considered for patients not responding within 24-48 hours, though this is more commonly used in primary HLH than MAS-HLH 2

Subtype-Specific Considerations

Still's Disease-Related MAS

• First-line: high-dose corticosteroids plus cyclosporine A or anakinra 1, 2
• Alternative: tocilizumab for patients with inadequate response 1

Infection-Triggered MAS

• Simultaneously treat the underlying infection with appropriate antimicrobials while administering immunosuppressive therapy for MAS 1, 6
• Failure to adequately treat the infectious trigger is a common pitfall that significantly increases mortality 6

Malignancy-Associated MAS

• Treatment must target both the MAS and the underlying malignancy concurrently 1, 2

Critical Care Management

• Reassess clinical status at least every 12 hours to determine need for escalation of HLH-directed therapy 3, 2, 6
• Monitor ferritin levels, cytopenias, and coagulopathy as indicators of treatment response 6
• Provide aggressive supportive care including vasopressors, mechanical ventilation, renal replacement therapy, and transfusions as needed 2, 6
• Consider ICU admission for patients with shock, severe organ dysfunction, or grade 3 or higher neurotoxicity 6

Critical Pitfalls to Avoid

• Delayed diagnosis and treatment is the most significant factor increasing mortality—maintain high clinical suspicion in patients with persistent fever, cytopenias, and hyperferritinemia 6
• Do not wait for complete diagnostic workup before initiating treatment in clinically severe cases 2
• Avoid sequential monotherapy in severe MAS; use combination therapy upfront 1, 2
• Do not overlook infectious triggers—always initiate appropriate antimicrobial therapy alongside immunosuppression 1, 6
• Recognize that fever may be masked by antipyretics, continuous renal replacement therapy, or extracorporeal life support in critically ill patients 3

Prognostic Factors

• Older age, platelet count <30 g/L, shock at ICU admission, and markedly elevated ferritin levels at diagnosis are associated with higher mortality 2, 4
• Decreasing ferritin levels and improving cytopenias indicate positive treatment response 6