What is the treatment for macrophage activation syndrome (MAS) in dengue fever?

Treatment of Macrophage Activation Syndrome in Dengue Fever

High-dose corticosteroids are the first-line treatment for macrophage activation syndrome (MAS) in dengue fever, with methylprednisolone 1g/day for 3-5 consecutive days recommended as the initial therapy, followed by second-line options including cyclosporine A and anakinra for inadequate response. 1, 2

Diagnosis and Recognition

• MAS should be suspected in dengue patients with prolonged or recurrent fever (>7 days), persistent cytopenias, hepatosplenomegaly, and laboratory abnormalities including markedly elevated ferritin (>10,000 ng/mL) 1, 3
• Diagnosis is based on fulfilling at least 5 of the 8 HLH-2004 criteria, including fever, splenomegaly, cytopenias, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low NK cell activity, elevated ferritin, and elevated soluble CD25 4
• While bone marrow examination showing hemophagocytosis is strongly supportive of the diagnosis, it is not essential for initiating treatment 5

Treatment Algorithm

First-Line Therapy

• High-dose intravenous corticosteroids are the cornerstone of initial treatment 6, 1, 2
  • Methylprednisolone 1g/day for 3-5 consecutive days 2
  • Alternatively, dexamethasone 10 mg/m² for 3-4 days 3

Second-Line Options (for inadequate response to corticosteroids)

• Cyclosporine A (2-7 mg/kg/day) 6, 1, 2
• Anakinra (IL-1 receptor antagonist, 2-10 mg/kg/day subcutaneously) 6, 1, 2
• Intravenous immunoglobulin (IVIG) at 2 gm/kg 1, 7

Severe/Refractory Cases

• Etoposide (VP-16) may be considered in severe cases that do not respond to the above therapies 1
• Emapalumab (anti-IFNγ antibody) has shown high rates of complete response (>90%) in high-risk populations with MAS 6
• JAK inhibitors have been proposed for chronic-relapsing MAS that is not responsive to other therapies 6

Critical Care Management

• Patients with grade 3 or higher neurotoxicity or severe MAS should receive ICU care 6
• Supportive care includes ventilation, vasopressors, renal replacement therapy, and transfusions as needed 2
• Serial laboratory monitoring is essential, including ferritin levels, complete blood count, coagulation parameters, and liver function tests 1

Special Considerations in Dengue-Associated MAS

• Treatment should simultaneously address both the MAS and the underlying dengue infection 2, 3
• Short courses of high-dose steroids (3-4 days) have shown favorable outcomes in dengue-associated MAS/HLH 3
• Outcomes can be favorable with steroid therapy alone in many cases of dengue-associated MAS 3
• Early recognition and prompt treatment are crucial to prevent irreversible organ damage and improve survival 4, 7

Monitoring Response to Therapy

• Frequent clinical reassessment (at least every 12 hours) and monitoring of inflammatory parameters and organ function 2
• Decreasing ferritin levels, improving cytopenias, and resolving coagulopathy indicate response to therapy 1
• Consider repeating neuroimaging every 2-3 days if persistent neurotoxicity is grade 3 or higher 6

Pitfalls to Avoid

• Delayed diagnosis and treatment significantly increases mortality 2
• Failure to recognize MAS as a complication of dengue fever, especially in cases with prolonged fever and worsening cytopenias 3, 7
• Inadequate use of antimicrobials when infection is the primary trigger 2
• Direct application of pediatric protocols without adjustments for adults 2