Discussion:
These cases highlight the intricacies of the management of m-HLH in
pediatric patients with the spectrum of disease severity and complex
diagnostic evaluations one must consider at presentation. Careful
consideration must be taken with suspicion of HLH to carry out a
thorough workup that will prevent delays in diagnosis for possible
underlying malignancy.
The treatment of m-HLH is a delicate balance due to the myriad
toxicities that arise from HLH and malignancy protocols. Although they
are the backbone of HLH treatment, dexamethasone and etoposide may be
inappropriate for some of the most unstable patients. This also
highlights the importance of recognizing a lack of response to standard
treatment to explore the use of investigational therapeutics for
refractory cases in a timely manner. There is much to explore and learn
from the use of novel therapeutics as with our patients who received
emapalumab for their refractory HLH. Although they both demonstrated
response to the addition of emapalumab, one of our patients may have
succumbed to fulminant candidiasis as result of emapalumab. We theorize
that as emapalumab blocks IFNγ, subsequently blocking neutrophil
activation and IL-6 modulation, it led to our patient being more
susceptible to systemic candidiasis, resulting in fungal emboli that led
to her intraparenchymal hemorrhage. [8]
Due to the toxicity of treatment options required for concurrent
processes of malignancy, infection, and HLH, novel therapeutics such as
emapalumab and ruxolitinib are required and should be evaluated in
larger studies. Considerations for the diagnostic approach of m-HLH
should account for significant correlations like those seen in
lymphoma-associated HLH and the sIL-2 to ferritin ratio. [9]
Furthermore, guidelines for the management of pediatric m-HLH are
required with inclusion of adjustments to standard therapy based on
toxicity, inciting factors, concurrent infections, and the incorporation
of novel therapeutics to lead to improved outcomes.
Conflict of interest statement:We have no conflicts of interests to disclose.