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.