Can Dexamethasone Be Used in HLH?
Yes, dexamethasone is a cornerstone of HLH treatment and should be used as first-line therapy for most patients with hemophagocytic lymphohistiocytosis. 1, 2, 3
Treatment Approach Based on Disease Severity
Mild-to-Moderate HLH
- Start with dexamethasone 5-10 mg/m² daily or prednisolone 1-2 mg/kg/day as initial immunosuppression. 2, 3
- This approach is sufficient for patients who are clinically stable without imminent organ failure. 1, 3
- Alternatively, high-dose pulse methylprednisolone 1 g/day IV for 3-5 consecutive days can be used for MAS-HLH presentations. 3
Severe HLH with Imminent Organ Failure
- Dexamethasone 10 mg/m² should be combined with etoposide as part of the modified HLH-94 protocol. 1, 2, 3
- The HLH-94 protocol, which includes dexamethasone as a core component, improved long-term survival to >50% in pediatric HLH and remains the standard of care. 1
- This intensive regimen typically lasts 8 weeks with weekly reevaluation of the need for continued therapy. 1, 3
Dosing Modifications and Duration
For adults, particularly elderly patients, consider reduced etoposide frequency (once weekly instead of twice weekly) while maintaining standard dexamethasone dosing. 1
- Etoposide requires dose reduction for renal impairment but not for isolated liver dysfunction. 1, 3
- Clinical response should be reevaluated at least every 12 hours in critically ill patients to determine if escalation is needed. 2, 3
When to Escalate Beyond Dexamethasone Alone
Add cyclosporine A (2-7 mg/kg/day) if there is inadequate immediate response to pulse steroids. 3
Consider IL-1 blockade with anakinra (2-10 mg/kg/day subcutaneously) for steroid-refractory cases. 3, 4
Recent evidence suggests anakinra combined with dexamethasone may allow avoidance of etoposide in some secondary HLH cases, particularly infection-triggered HLH. 4 However, this approach requires careful monitoring and early initiation when HLH is suspected. 4
Maintenance Therapy
After the initial 8-week intensive phase, continue maintenance therapy with corticosteroids (along with cyclosporine) for patients requiring allogeneic stem cell transplantation. 1, 3
Critical Supportive Care Requirements
All patients receiving dexamethasone-based HLH therapy require prophylaxis against Pneumocystis jirovecii, fungi, and viruses due to severe T-cell depletion. 1, 2, 3
- Hospitalization in units with HEPA-filtered air should be considered for patients on intensive immunosuppression. 1
- Secondary infections are a major cause of fatality during HLH treatment. 1, 2
Important Caveats
The evidence shows that dexamethasone is effective across different HLH triggers—whether infection-associated, malignancy-associated, or rheumatologic (MAS). 1, 2 However, treating the underlying trigger aggressively is equally important: antimicrobials for infection-associated HLH, disease-specific therapy for malignancy-associated HLH, and optimizing rheumatologic disease control for MAS-HLH. 2
A common pitfall is delaying dexamethasone initiation while searching for an underlying trigger. In patients who are deteriorating or unstable, start corticosteroids immediately while investigating the cause. 1
Recent studies have explored alternatives like ruxolitinib combined with dexamethasone, showing promising results with an 85.7% 2-month overall survival rate in newly diagnosed adult HLH. 5 This may be particularly useful when etoposide is contraindicated due to renal failure. 6