Hemophagocytic lymphohistiocytosis is an aggressive condition characterized by ineffective, excessive immune activation leading to a hyper-inflammatory response, ultimately with high morbidity and mortality--and often under-recognized due to the relatively non-specific nature of the clinical signs and overlap with other diseases.
HLH is usually a secondary process in adults, often triggered by an infection (~30% viral, 20% other), but can also be due a malignancy (can be the presenting manifestation; ~30% of cases), or a rheumatologic condition (<10%). There are also familial forms with genetic defects in natural killer cells and cytotoxic T-cells, known as primary HLH.
Diagnosis: Either molecular diagnosis consistent with HLH -OR- 5 out of the following 8 clinical criteria:
- Fever >38 C (due to high interleukin levels)
- Splenomegaly (due to infiltration by lymphocytes and macrophages)
- Cytopenias (affecting at least 2 cell lineages; due to high levels of TNF and interferon)
- Hypertriglyceridemia (usually > 265; due to decreased lipoprotein lipase levels2/2 high TNF levels) or hypofibrinogenemia <150 (as macrophages may secrete activators leading to degrading fibrinogen)
- Elevated ferritin (often >5000; >10000 is 90% sensitive and 96% specific for HLH--believed to increase during the anti-inflammatory process of macrophages scavenging heme)
- Hemophagocytosis in bone marrow/spleen/lymph nodes (on bone marrow biopsy)
- Low or absent NK cell activity
- Elevated soluble CD25 (IL-2 receptor)
Patients may also have elevated LDH, transaminases, and bilirubin--thought to be due to organ infiltration by lymphocytes and histiocytes. Lymphadenopathy, neurologic symptoms, and rash are not uncommon.
Treatment: urgent referral to hematology/oncology specialist and treatment of the underlying condition if stable. Acutely deteriorating patient may need HLH-specific treatment (etoposide, dexamethasone, etc).