Primary HLH: Associated with immune deficiency syndromes, such as X-linked lymphoproliferative disease, Griscelli type 2, & Chediak Higashi
Acquired/secondary HLH
Environmental or acquired mechanisms, such as infection, malignancy, autoimmune conditions, immunocompromise
IMAGING
General Features
Radiographic Findings
CT Findings
MR Findings
Ultrasonographic Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
Staging, Grading, & Classification
CLINICAL ISSUES
Presentation
Demographics
Natural History & Prognosis
Treatment
Selected References
Bergsten E et al: Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study. Blood Adv. 4(15):3754-66, 2020
Canna SW et al: Pediatric hemophagocytic lymphohistiocytosis. Blood. 135(16):1332-43, 2020
Shieh AC et al: Hemophagocytic lymphohistiocytosis: a primer for radiologists. AJR Am J Roentgenol. 214(1):W11-9, 2020
Benson LA et al: Pediatric CNS-isolated hemophagocytic lymphohistiocytosis. Neurol Neuroimmunol Neuroinflamm. 6(3):e560, 2019
Al-Samkari H et al: Hemophagocytic lymphohistiocytosis. Annu Rev Pathol. 13:27-49, 2018
Bergsten E et al: Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 130(25):2728-38, 2017
Emile JF et al: Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 127(22):2672-81, 2016
Allen CE et al: Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematology Am Soc Hematol Educ Program. 2015:177-82, 2015
Lehmberg K et al: Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol. 170(4):539-49, 2015
George MR: Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 5:69-86, 2014
Guandalini M et al: Spectrum of imaging appearances in Australian children with central nervous system hemophagocytic lymphohistiocytosis. J Clin Neurosci. 21(2):305-10, 2014
Rosado FG et al: Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol. 139(6):713-27, 2013
Zhang K et al: Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 118(22):5794-8, 2011
Niece JA et al: Hemophagocytic lymphohistiocytosis in Texas: observations on ethnicity and race. Pediatr Blood Cancer. 54(3):424-8, 2010
Janka G: Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr. 221(5):278-85, 2009
Henter JI et al: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48(2):124-31, 2007
Histiocyte Society: HLH-2004 Study Group. Published January, 2004. Accessed November 20, 2020. https://www.skion.nl/workspace/uploads/HLH-2004-protocol1.pdf
Fitzgerald NE et al: Imaging characteristics of hemophagocytic lymphohistiocytosis. Pediatr Radiol. 33(6):392-401, 2003
Rooms L et al: Hemophagocytic lymphohistiocytosis masquerading as child abuse: presentation of three cases and review of central nervous system findings in hemophagocytic lymphohistiocytosis. Pediatrics. 111(5 Pt 1):e636-40, 2003
Related Anatomy
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Related Differential Diagnoses
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References
Tables
Tables
KEY FACTS
Terminology
Imaging
Clinical Issues
TERMINOLOGY
Abbreviations
Hemophagocytic lymphohistiocytosis (HLH)
Synonyms
Hyperferritinemic inflammation
Macrophage activation syndrome (MAS) when occurring in those with underlying rheumatologic or autoimmune syndrome
Cytokine release syndrome (CRS) if related to iatrogenic immunosuppression therapy
Definitions
Rare, life-threatening disorder of pathological immune activation resulting in extreme systemic hyperinflammation
Despite name, hemophagocytosis is not required for diagnosis
Likely to represent wide spectrum, divided into 2 types
Primary HLH: Associated with immune deficiency syndromes, such as X-linked lymphoproliferative disease, Griscelli type 2, & Chediak Higashi
Acquired/secondary HLH
Environmental or acquired mechanisms, such as infection, malignancy, autoimmune conditions, immunocompromise
IMAGING
General Features
Radiographic Findings
CT Findings
MR Findings
Ultrasonographic Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
Staging, Grading, & Classification
CLINICAL ISSUES
Presentation
Demographics
Natural History & Prognosis
Treatment
Selected References
Bergsten E et al: Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study. Blood Adv. 4(15):3754-66, 2020
Canna SW et al: Pediatric hemophagocytic lymphohistiocytosis. Blood. 135(16):1332-43, 2020
Shieh AC et al: Hemophagocytic lymphohistiocytosis: a primer for radiologists. AJR Am J Roentgenol. 214(1):W11-9, 2020
Benson LA et al: Pediatric CNS-isolated hemophagocytic lymphohistiocytosis. Neurol Neuroimmunol Neuroinflamm. 6(3):e560, 2019
Al-Samkari H et al: Hemophagocytic lymphohistiocytosis. Annu Rev Pathol. 13:27-49, 2018
Bergsten E et al: Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 130(25):2728-38, 2017
Emile JF et al: Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 127(22):2672-81, 2016
Allen CE et al: Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis. Hematology Am Soc Hematol Educ Program. 2015:177-82, 2015
Lehmberg K et al: Malignancy-associated haemophagocytic lymphohistiocytosis in children and adolescents. Br J Haematol. 170(4):539-49, 2015
George MR: Hemophagocytic lymphohistiocytosis: review of etiologies and management. J Blood Med. 5:69-86, 2014
Guandalini M et al: Spectrum of imaging appearances in Australian children with central nervous system hemophagocytic lymphohistiocytosis. J Clin Neurosci. 21(2):305-10, 2014
Rosado FG et al: Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol. 139(6):713-27, 2013
Zhang K et al: Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 118(22):5794-8, 2011
Niece JA et al: Hemophagocytic lymphohistiocytosis in Texas: observations on ethnicity and race. Pediatr Blood Cancer. 54(3):424-8, 2010
Janka G: Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr. 221(5):278-85, 2009
Henter JI et al: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48(2):124-31, 2007
Histiocyte Society: HLH-2004 Study Group. Published January, 2004. Accessed November 20, 2020. https://www.skion.nl/workspace/uploads/HLH-2004-protocol1.pdf
Fitzgerald NE et al: Imaging characteristics of hemophagocytic lymphohistiocytosis. Pediatr Radiol. 33(6):392-401, 2003
Rooms L et al: Hemophagocytic lymphohistiocytosis masquerading as child abuse: presentation of three cases and review of central nervous system findings in hemophagocytic lymphohistiocytosis. Pediatrics. 111(5 Pt 1):e636-40, 2003
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