Correct!
5. Possibly all the above
HLH is a highly fatal disease caused by dysregulation of the immune system, severe hypercytokinemia and resultant multiorgan failure. Primary HLH is a genetic disorder of impaired NK cell function presenting early in childhood, but most cases of HLH in adults do not undergo testing for genetic abnormalities and are presumed to be secondary, although in some cases, adults with HLH have been found to have inborn errors. The patient presented above was later tested for known genetic abnormalities associated with primary HLH and none were found. Secondary HLH can be triggered by a wide variety of infections (particularly EBV and herpes virus infections), malignancies and rheumatological diseases (particularly Still’s disease) (2). Some authors believe that HLH secondary to Still’s is a distinct syndrome and have used the term “macrophage activation syndrome” to describe it. But MAS and secondary HLH share many clinical features, diagnostic criteria and treatment options.
The patient meets all eight “HLH 2004” diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) – but only five are required to confirm the diagnosis (Table 1) (1).
Table 1. HLH 2004 diagnostic criteria for HLH
Histological evidence of HLH on tissue biospy is neither necessary or sufficient to make the diagnosis (3). Hyperferritinemia is also non-specific for HLH, but is present in nearly all cases.
Secondary HLH is likely underdiagnosed in the adult ICU. We have previously shown that HLH can present as sepsis/septic shock refractory to antibiotic therapy (4). In an autopsy study, Straus et al. (5) identified HLH in the bone marrow of 35 of 107 patients who died from sepsis. HLH was identified in 9/25 (36%) of critically ill patients with confirmed influenza A (H1N1) infection (6). We have personally diagnosed 27 patients with secondary HLH in our ICU, and have observed that it is most often originally misdiagnosed as typical sepsis or septic shock. The diagnosis of HLH is usually suspected only when the patient continues to deteriorate despite broad spectrum antibiotics and progressive multisystem organ failure and bone marrow failure appear to be imminently life-threatening. In many cases the development of pancytopenia triggered suspicion of the diagnosis, which was then supported by finding hyperferritinemia. Treatment has almost always been started before sIL-2r and NK cell activity testing is resulted. The mortality of this syndrome presenting in the adult ICU exceeds 50% even when the diagnosis is recognized and rapidly treated.
Which of the following have been used to treat HLH? (Click on the correct answer to be directed to the sixth and final page)