Case Presentation: A 40 year old female with a medical history of pancreatitis and gastroesophageal reflux initially presented with cough and viral cold symptoms. She was initially febrile to 102 F, with labs significant for WBC 3,900 (normal 4,500-11,000 WBC/uL), hemoglobin 9.1 (12.0-15.5 g/dL), and platelet count 35,000 (150,000-450,000 /uL). She quickly deteriorated with new onset seizures, worsening mental status, lactic acidosis, and required immediate intubation and transfer to our intensive care unit four days after admission. Initial repeat labs were significant for elevated lactate of 18.0 (0.67-2.47 mmol/L), AST >10,000 (190 mg/dL) with hypofibrinogenemia <70 (180-460 mg/dL), elevated ferritin 32,052 (8-252 nl/mL), and elevated interleukin-2-receptor (IL-2R) 4,059 (223-710 U/mL). The predictive H-score was 253, which translated to a 99.5% probability of reactive hemophagocytic lymphohistiocytosis (HLH) [2]. Patient was treated with broad-spectrum vancomycin, piperacillin-tazobactam, acyclovir, and micafungin for possible infection triggering HLH. Hematology was emergently consulted and HLH-94 protocol (dexamethasone and etoposide) was started. EBV PCR was mildly high 179 copies/mL and thus intravenous immunoglobulin with rituximab was also started for this viral trigger. Patient's overall respiratory status improved along with decreasing transaminitis (AST to as low as 594 units/L) in the subsequent week with chemotherapy. However this was coupled with worsening mental status. She developed fixed pupils on exam and brain imaging showed severe diffuse swelling of brain with transforaminal herniation, and the family decided on palliative extubation 14 days after initial admission.
Discussion: Adult cases of HLH are rare, although increasing in prevalence. HLH, although usually observed in children, is an excessive immune activation and inflammation that is theorized to be from macrophage/monocyte activation in addition to natural killer (NK) cell activation. In combination, these elements combine to phagocytize the body’s own blood cells and create cytokine storms that lead to massively deleterious effects on different organ systems including renal dysfunction and acute liver failure (ALF). HLH can be genetic (mutations homozygous or heterozygous) or acquired from at least 5/8 diagnostic criteria from the HLH-2004 study [1]. In secondary associated illnesses, the most common in adults include infections (Epstein-Barr virus EBV, cytomegalovirus, parvovirus, and herpes simplex virus), malignancy (lymphoma and leukemia), rheumatologic triggers (arthritis, autoimmune diseases on drug therapy), and immunodeficiency. The manifestation of ALF in adult HLH is much more rare, and most patients in this subset become critically ill with high mortality. This report here elucidates one of those cases, and emphasizes the importance of early diagnosis and prompt treatment.
Conclusions: This patient suffered severe multiorgan failure during her progression of HLH, including ALF, renal failure, and disseminated intravascular coagulopathy. A final MRI of her brain showed extensive cortical edema that likely resulted from the worsening toxic hepatic encephalopathy due to her ALF. Although liver transplantation is an option for children with HLH, there have been none successful done in the adult population [3]. This however, is not a case of futility or treatment failure; on the contrary, it should encourage continued multidisciplinary efforts for researching this disease.