Acquired Hemophagocytic Lymphohistiocytosis Among Adults: A Single Center Experience

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life threatening syndrome characterized by an uncontrolled inflammatory reaction and is often associated with poor outcomes. The current study was conducted to characterize clinical features and outcomes of acquired HLH among adults.

Thirteen consecutive patients with HLH presenting to Indiana University Medical Center (IU) between January 2010 and June 2013 were analyzed retrospectively. The criteria described by Henter et al (Pediatr Blood Cancer 2007; 48:124-131) were used for diagnosis.

Median age was 45 years (range 30-73), 8 patients were female and 12 patients were Caucasians. Four patients had a malignancy (one in remission), 2 had history of a solid organ transplant, 6 had an underlying infection (3 viral, 1 bacterial, 2 fungal), 2 had an underlying autoimmune illness and 3 patients had idiopathic HLH. Four patients were on immunosuppressants for their history of organ transplant (n=2), autoimmunity (n=1) or as part of their chemotherapy for a malignancy (n=1). All patients had fevers and 2 or more cytopenias. Multi-organ failure was frequent with liver failure (bilirubin >2.0; 11 patients), renal failure (Cr >2.0; 11 patients), respiratory failure requiring mechanical ventilation (10 patients), hemodynamic instability requiring vasopressor support (8 patients) and encephalopthy or generalized weakness (all patients). Other commonly seen clinical features included rash (6 patients), hyponatremia (Na <135; 11 patients), steatosis (5 patients), hepatomegaly (2 patients) and venous thromboembolism (5 patients). Seven of 12 patients had elevated triglycerides (≥265 mg/dL). Of 11 patients for whom fibrinogen was checked, 7 had a low fibrinogen (≤ 150mg/dL); two had undetectable fibrinogen in the absence of coagulopathy. All patients had markedly elevated ferritin levels (median 16500 ng/mL; range 2002-138705). Twelve of 13 patients had histopathological evidence of HLH on biopsy or autopsy. Soluble IL-2 receptor level was elevated (>2400 U/mL) in 9 patients (available for 11 patients) and all 6 patients (available for 6 patients) had decreased or absent natural killer cell activity. All patients received steroids as part of treatment (modified HLH 2004 protocol); 4 patients were too unstable to receive standard treatment and received only steroids. Eight patients died of HLH (6 at initial hospitalization; 2 later) at a median of 27 days (range 4-131). Multi-organ failure was the cause of death in 7 patients. Time to establishment of diagnosis was similar for patients who died at initial admission vs. those discharged alive (median 7 vs. 10 days).

Acquired HLH among adults is a systemic syndrome with diverse and sometimes unknown etiology. Most clinical features are nonspecific; incorporation of markedly high ferritin (≥2000 ng/mL), high soluble IL-2 receptor level, decreased/absent natural killer cell activity and histopathological evidence of HLH as major criteria for diagnosis may enhance specificity. Rash, steatosis/hepatomegaly, hyponatremia, thromboembolism and hypofibrinoginemia in the absence of coagulopathy can also be seen. Mortality is high due to multi-organ failure. Time to diagnosis does not seem to be a predictor of in-hospital mortality suggesting that the biology of underlying disease might be a more important factor.

No relevant conflicts of interest to declare.