Introduction:
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune
dysregulation leading to a hyperinflammatory state. HLH is categorized
into primary and secondary forms. Primary, or familial HLH, is
associated with known genetic mutations related to T and NK cell
defects. Secondary HLH is an acquired form most often triggered by
infection or malignancy in the pediatric population.
In the context of m-HLH in pediatric patients, the initial presentation
presents a diagnostic conundrum. The HLH-2004 diagnostic criteria
include clinical features of fever, splenomegaly, and cytopenia that
overlap with infections and common malignancies of leukemia and
lymphoma. [1] There are also similarities in treatment guidelines
with the use of dexamethasone and etoposide. Patients are often
critically ill upon presentation, which may prevent opportunities to
carry out thorough diagnostic processes prior to treatment. This may
lead to delays in diagnosis and treatment of an underlying malignancy.
It also complicates the treatment of the malignancy with sub-optimal use
of dexamethasone and etoposide that may allow for selection of
chemotherapy-resistant cells. The histiocyte society recommends
consideration of evaluation for malignancy for any patient suspected
with HLH, but there are currently no established guidelines in pediatric
patients to address the initial diagnostic workup, the primary treatment
focus (HLH or malignancy), and the considerations for alterations of
treatment regimens with respect to the toxicities of chemotherapeutic
agents. [2]
We now discuss 3 patients with varying presentations of m-HLH with
respect to severity, response, treatment considerations, and overall
outcomes to demonstrate the spectrum of this hyperinflammatory syndrome.