Treatment Approach for Influenza A-Associated Hemophagocytic Lymphohistiocytosis (HLH)

Pathophysiological Connection

Influenza virus can trigger pathologic immune activation and hypercytokinemia leading to HLH development or reactivation, with viral infections being common triggers of HLH 2, 1

Suspect HLH in influenza patients with rapidly rising ferritin (>5000 ng/mL) with cytopenias and fever, liver dysfunction, renal dysfunction, or pulmonary edema 3, 1
Diagnostic workup should include ferritin levels, soluble CD25 levels, and complete blood counts 1

The American Society of Hematology recommends antiviral therapy combined with immunomodulatory agents to control hyperinflammation and prevent mortality 1
Corticosteroids, such as prednisolone 1-2 mg/kg or dexamethasone 5-10 mg/m², may be used to control hyperinflammation 2, 1
Intravenous Immunoglobulin (IVIG) 1.6 g/kg over 2-3 days may be considered for anti-inflammatory effects 2, 1
Etoposide-Based Therapy may be initiated according to HLH-94 protocol for rapidly deteriorating patients or those not responding to initial therapy 2, 1
Anakinra may reduce mortality in patients with MAS features and has shown benefit in refractory cases 2

Malignancy considerations: differentiate between "malignancy-triggered HLH" and "HLH during chemotherapy" as treatment approaches differ markedly 2, 1
Mortality in adult HLH ranges from 20% to 88%, primarily due to refractory HLH, secondary infections, and progression of underlying disease 2

Diagnostic challenges: HLH symptoms may overlap with severe sepsis or cytokine release syndrome, leading to delayed diagnosis 3
Treatment considerations: avoid delaying etoposide in rapidly deteriorating patients, and consider secondary infections as a major cause of fatality during HLH treatment 2