Haemophagocytic Lymphohistiocytosis Secondary to Severe Falciparum Malaria: A Case Series from a UK Tertiary Centre.

Abstract

Background: Haemophagocyticlymphohistiocytosis (HLH) is a rare but often fatal hyperinflammatory syndrome that can be triggered by infections, including Plasmodium falciparum. Although HLH secondary to malaria is documented, it remains under-recognised in clinical practice. We describe two cases of HLH complicating severe falciparum malaria, aiming to highlight diagnostic challenges and therapeutic considerations.

Methodology: This is a retrospective case series of two adult female patients admitted to a tertiary intensive care unit (ICU) in London, UK. Clinical data were extracted from the electronic health record (Epic Hyperspace). HLH was diagnosed using HLH-2004 criteria and the HScore (calculated with MDCalc). Both patients were treated with anti-malarials and HLH-directed immunomodulation, including corticosteroids, IVIG, and anakinra.

Results: Both patients fulfilled ≥5 of the HLH-2004 criteria and had elevated ferritin (>21,000 and 48,000 µg/L, respectively) with HScore probabilities of 98–99%. One case was confirmed by bone marrow haemophagocytosis. Both required renal replacement therapy and invasive ventilation. Ferritin and organ function improved following combined immunosuppressive therapy, with complete clinical recovery and discharge by days 31 and 32 of illness.

Conclusion: Malaria-associated HLH, though rare, should be suspected in adults with severe P. falciparum infection and extreme hyperferritinaemia. Early recognition and immunomodulatory therapy guided by HScore and HLH-2004 criteria can be lifesaving. Clinicians in endemic regions and among returning travellers should maintain vigilance for HLH in cases of severe malaria unresponsive to standard treatment.