Case Presentation: A 36 year old male with no past medical history presented to the ER with a 3 day history of fevers, nausea, vomiting, and diarrhea. Labs demonstrated hyponatremia to 126 and acute renal injury (1.7 up from 0.6). He was admitted for presumed viral gastroenteritis and treated supportively. Two days later his symptoms persisted and so he was started in ciprofloxacin and metronidazole. Symptoms continued and on hospital day 6 he developed elevated liver associated enzymes and pancytopenia. Ferritin was elevated at 4450 ng/ml. He then developed multiple pulmonary embolisms, proteinuria (4.36 grams/24 hours), lower extremity edema, new onset ascites. Blood and urine cultures were negative. He underwent a bone marrow biopsy which showed hemophagocytosis, a renal biopsy which showed FSGS and his IL-2 soluble receptor was elevated at 2710 µg/mL. He was started on prednisone 1 mg/kg then transitioned to tocilizumab.
Discussion: The pathogenesis of HLH is excessive activation and proliferation of T lymphocytes and macrophages. Downstream, this leads to phagocytosis of hematopoietic cells in the bone marrow and hypersecretion of proinflammatory cytokines. The diagnosis of HLH can be challenging because there are no pathognomonic features. Fardet et al developed the Hscore, which is a scoring system to help predict the probability of HLH. HLH was considered early in the hospital course due to an initial ferritin level greater than 4000 ng/ml. Our patient’s Hscore was 209, which equated to an 88-93% probability of hemophagocytic syndrome. Early consideration of HLH is critical due to the systemic damage involved with this disease state and high mortality rates. A study by Cetica et al showed that primary HLH has significantly higher mortality rates (50%) compared to secondary HLH (10%). The lower probability of death in secondary HLH prompts caution in treatment of the disease.
Conclusions: Hemophagocytic Lymphohistiocytosis (HLH) is a rare disorder resulting from an uncontrolled and hyperinflammatory immune activation by aberrant histiocytes and T lymphocytes. It can present as an inherited disease or as an acquired syndrome associated with various triggers such as infection, malignancy, or rheumatologic disorders. Prompt recognition of HLH can be challenging as most of the diagnostic criteria are non-specific and based on pediatric protocols. Cardinal features of HLH are fever, cytopenias, and hepatosplenomegaly. Elevated ferritin, triglycerides, liver associated enzymes, and soluble IL2-receptor are common findings. Delayed diagnosis of HLH can culminate in multi-organ dysfunction.