While anakinra has been successfully utilized in MAS, it has not been formally studied in HLH associated with bonafide mutations. In our patient with two identified UNC13D mutations, anakinra was utilized as an immunomodulator while the diagnosis was evolving. Although the progression of our patient's disease was not florid while receiving anakinra, there were decreased platelet and neutrophil counts during therapy. However, when anakinra was stopped, there was a clear surge in ferritin levels. It is unclear from our experience if anakinra magnifies certain abnormalities found in primary HLH while moderately quelling others. A more likely explanation is that the anakinra functioned in partially blocking the HLH-associated inflammation in our patient thus allowing for the masking of certain phenotypic associations of HLH such as ferritin, but not others (i.e., platelet counts). While we were not situated to immunologically prove the partial blockade of inflammation in our patient while receiving anakinra, our experience suggests that its use be reserved for the more mild secondary forms of Figure 3 Comparison of CD163 immunohistochemical stain of bone marrow one month before trial of anakinra trial (3a), and the day after discontinuation (3b). Shown at 40x magnification. CD163 is an immunohistochemical stain that is specific for monocytes and macrophages and the positive cells show brown surface staining. Prior to anakinra, there are slit-like macrophages and some with a few ingested cells (blue arrow). On repeat biopsy and stain done after anakinra, there is an increase in the number of macrophages and the CD163 stain demonstrates numerous hemophagocytic macrophages containing multiple ingested cells (blue arrows).