Hemophagocytic Lymphohistiocytosis in the Emergency Department: Recognizing and Evaluating a Hidden Threat

Abstract

Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder resulting from an ineffective and pathologic activation of the immune response system that may mimic common emergency department presentations, including sepsis, acute liver failure, disseminated intravascular coagulation, and flu-like illnesses such as coronavirus disease 2019 (COVID-19). Objective This narrative review provides a summary of the disease and recommendations for the recognition and diagnostic evaluation of HLH with a focus on the emergency clinician. Discussion Though the condition is rare, mortality rates are high, ranging from 20% to 80% and increasing with delays in treatment. Importantly, HLH has been recognized as a severe variation of the cytokine storm associated with COVID-19. Common features include a history of infection or malignancy, fever, splenomegaly or hepatomegaly, hyperferritinemia, cytopenias, coagulopathies, abnormal liver enzymes, and hypertriglyceridemia. Using specific features of the history, physical examination, laboratory studies, and tools such as the HScore, HLH-2004/2009, and hyperferritinemia thresholds, the emergency clinician can risk-stratify patients and admit for definitive testing. Once diagnosed, disease specific treatment can be initiated. Conclusion This review describes the relevant pathophysiology, common presentation findings, and a framework for risk stratification in the emergency department.

Facial Natural Killer/T-Cell Lymphoma: A Deadly Sinusitis Mimic

“…Despite treatment, the prognosis for nasal NKTL remains poor with a five-year mortality rate of 10%-45% [ 4 , 10 ]. Additionally, NKTL is a frequent cause of HLH; the development of this macrocyte hyperactivation immediately following or during treatment for NKTL further increases mortality up to 96.4% [ 14 - 15 ].…”

Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature

“…[4][5][6] This syndromic disease (also named "Hemophagocytic Syndrome") may clinically resemble sepsis, disseminated intravascular coagulation, and/or acute liver failure, highlighting the need of early diagnosis and treatment. 7,8 Common findings include unremitting fever, splenomegaly, cytopenia, coagulopathy, liver dysfunction, hemophagocytosis, hyperferritinemia, and, in many cases, neurologic abnormalities. 8 Considering this complex picture of nonspecific signs and symptoms, the Histiocyte Society published the revised HLH-2004 protocol guidelines (originally described as guidelines in 1991), in which 5 out of 8 diagnostic criteria must be fulfilled TA B L E 1 HLH-2004 and modified 2009 diagnostic criteria for HLH Traditional HLH-2004 Criteria 11 Modified HLH-2009 Criteria 12 1.…”

“…7,8 Common findings include unremitting fever, splenomegaly, cytopenia, coagulopathy, liver dysfunction, hemophagocytosis, hyperferritinemia, and, in many cases, neurologic abnormalities. 8 Considering this complex picture of nonspecific signs and symptoms, the Histiocyte Society published the revised HLH-2004 protocol guidelines (originally described as guidelines in 1991), in which 5 out of 8 diagnostic criteria must be fulfilled TA B L E 1 HLH-2004 and modified 2009 diagnostic criteria for HLH Traditional HLH-2004 Criteria 11 Modified HLH-2009 Criteria 12 1. A molecular diagnosis consistent with HLH # : 1.…”

“…It is a life‐threatening immune disorder characterized by systemic lymphocyte and macrophage activation, together with increased levels of cytokines, which lead to an uncontrolled hyperinflammation state and progressive multiorgan damage 4–6 . This syndromic disease (also named “Hemophagocytic Syndrome”) may clinically resemble sepsis, disseminated intravascular coagulation, and/or acute liver failure, highlighting the need of early diagnosis and treatment 7,8 . Common findings include unremitting fever, splenomegaly, cytopenia, coagulopathy, liver dysfunction, hemophagocytosis, hyperferritinemia, and, in many cases, neurologic abnormalities 8 .…”

Priorities in the Evaluation of Hemophagocytic Lymphohistiocytosis Syndrome in the Emergency Department

“…Given the fact that mycobacterial infection is one of the most eminently treatable underlying causes of hemophagocytic lymphohistiocytosis (HLH) syndrome in both immunocompetent and immunocompromised subjects, priority should be given to evaluation for disseminated tuberculosis in the workup of patients with HLH, even if that work-up does not include lumbar puncture ( 1 , 2 , 3 ).…”