What is your approach to treatment of infection-triggered HLH that does not respond to treatment of the underlying infection?

The algorithm our center follows is to

1. Recognize hyperinflammation (see answer to question above -- in addition to baseline labs, we obtain an infectious disease consult)
2. Look for and treat the trigger. A concern, if the patient is responding, is that we are missing a trigger (HLH does not occur spontaneously in the animal models of disease). We send a thorough evaluation for infection including evaluating for viral reactivation or infection (CMV, EBV, adenovirus, HHV6, HIV), bacterial cultures...

Patients with infection-triggered HLH often require HLH therapy alongside treatment of the underlying infection, especially herpesvirus infections. Patients with infection-related HLH who are extremely ill with organ failure and severe symptoms usually require upfront HLH treatment along with treatment of the underlying infection. The one reassuring aspect of this is that, with the exception of EBV, most viral-associated HLH, even if patients require HLH treatment, resolves without anticipation ...