Treatment of Hemophagocytic Lymphohistiocytosis (HLH) Triggered by Malaria
For malaria-triggered HLH, treatment should include antimalarial therapy combined with corticosteroids, with etoposide reserved for severe cases with rapid deterioration or organ failure. 1, 2
Diagnostic Considerations
- Suspect HLH in malaria patients with persistent fever despite antimalarials, unexplained cytopenias, organomegaly, and disproportionate inflammatory response 3, 4
- Diagnostic workup should include ferritin levels (often markedly elevated), soluble CD25 levels, and complete blood counts 5, 4
- HLH diagnosis may be confirmed by the presence of 5 of 8 HLH-2004 criteria 1
Treatment Algorithm for Malaria-Associated HLH
First-Line Treatment
- Administer appropriate antimalarial therapy based on Plasmodium species and resistance patterns 2, 6
- Add corticosteroids (prednisolone 1-2 mg/kg or dexamethasone 5-10 mg/m²) to control hyperinflammation 1, 2
- Consider IV immunoglobulin (IVIG) up to 1.6 g/kg in split doses over 2-3 days for anti-inflammatory effects 1
For Severe or Refractory Cases
- Initiate etoposide according to modified HLH-94 protocol (dexamethasone 10 mg/m² with/without etoposide) for patients with severe HLH presenting with imminent organ failure 1
- Etoposide dose should be reduced if renal function is impaired, but no dose reduction is needed for isolated hyperbilirubinemia or elevated transaminases 1
- Weekly reevaluation of the need for continued etoposide therapy is recommended 1
Monitoring and Follow-up
- Regularly monitor ferritin, soluble CD25, cell counts, and liver function tests to assess treatment response 1, 5
- Vigilantly monitor for secondary infections, which are a major cause of mortality in HLH patients 1
- Consider antimicrobial prophylaxis against Pneumocystis jirovecii and fungi for patients requiring immunosuppressive treatment 1
Prognosis and Special Considerations
- Malaria-associated HLH appears to have a better prognosis (5% mortality) compared to other infection-triggered HLH (e.g., 25% in EBV-HLH) 4
- Resolution of HLH without HLH-specific treatment has been observed in some cases of infection-associated HLH, including malaria 1, 4
- In patients with refractory HLH, consider consultation with an HLH reference center 1, 7
Common Pitfalls and Caveats
- Delayed diagnosis is a major reason for progression from mild to severe disease; maintain high suspicion for HLH in malaria patients not responding to antimalarials 6, 8
- Avoid delaying etoposide in rapidly deteriorating patients with severe disease 1, 5
- HLH symptoms may overlap with severe sepsis or cytokine release syndrome, leading to diagnostic challenges 5, 8
- Secondary infections during treatment are a major cause of mortality and require vigilant monitoring 1