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Hemophagocytic lymphohistiocytosis

MedGen UID:
6158
•Concept ID:
C0024291
•
Disease or Syndrome
Synonyms: Hemophagocytic Lymphohistiocytoses; Hemophagocytic Lymphohistiocytosis; Lymphohistiocytoses, Hemophagocytic; Lymphohistiocytosis, Hemophagocytic
SNOMED CT: Hemophagocytic lymphohistiocytosis (234437005); Hemophagocytic syndrome (234437005); Hyperinflammatory lymphohistiocytosis (234437005)

Definition

A rare but potentially life-threatening disorder characterized by the proliferation of histiocytes and macrophages and phagocytosis of red blood cells, white blood cells, and platelets. It may be inherited or secondary, due to infections, autoimmune disorders, or underlying malignancies. Signs and symptoms include fever, lymphadenopathy, hepatomegaly, splenomegaly, and pancytopenia. [from NCI]

Professional guidelines

PubMed

Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management.
Brudno JN, Kochenderfer JN
Blood Rev 2019 Mar;34:45-55. Epub 2018 Nov 14 doi: 10.1016/j.blre.2018.11.002. PMID: 30528964Free PMC Article
Capillary leak syndrome: etiologies, pathophysiology, and management.
Siddall E, Khatri M, Radhakrishnan J
Kidney Int 2017 Jul;92(1):37-46. Epub 2017 Mar 17 doi: 10.1016/j.kint.2016.11.029. PMID: 28318633
HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis.
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G
Pediatr Blood Cancer 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039. PMID: 16937360

Recent clinical studies

Etiology

Virus-triggered secondary hemophagocytic lymphohistiocytosis.
Imashuku S, Morimoto A, Ishii E
Acta Paediatr 2021 Oct;110(10):2729-2736. Epub 2021 Jun 22 doi: 10.1111/apa.15973. PMID: 34096649
Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.
Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C
N Engl J Med 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326. PMID: 32374962
Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management.
Henderson LA, Cron RQ
Paediatr Drugs 2020 Feb;22(1):29-44. doi: 10.1007/s40272-019-00367-1. PMID: 31732958Free PMC Article
Hemophagocytic Lymphohistiocytosis.
Skinner J, Yankey B, Shelton BK
AACN Adv Crit Care 2019 Summer;30(2):151-164. doi: 10.4037/aacnacc2019463. PMID: 31151946
How I treat hemophagocytic lymphohistiocytosis.
Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL
Blood 2011 Oct 13;118(15):4041-52. Epub 2011 Aug 9 doi: 10.1182/blood-2011-03-278127. PMID: 21828139Free PMC Article

Diagnosis

Cytokine Storm Syndrome.
Cron RQ, Goyal G, Chatham WW
Annu Rev Med 2023 Jan 27;74:321-337. Epub 2022 Oct 13 doi: 10.1146/annurev-med-042921-112837. PMID: 36228171
Hemophagocytic Lymphohistiocytosis.
Ponnatt TS, Lilley CM, Mirza KM
Arch Pathol Lab Med 2022 Apr 1;146(4):507-519. doi: 10.5858/arpa.2020-0802-RA. PMID: 34347856
Hemophagocytic lymphohistiocytosis: An update on pathogenesis, diagnosis, and therapy.
Griffin G, Shenoi S, Hughes GC
Best Pract Res Clin Rheumatol 2020 Aug;34(4):101515. Epub 2020 May 7 doi: 10.1016/j.berh.2020.101515. PMID: 32387063
How I treat hemophagocytic lymphohistiocytosis.
Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL
Blood 2011 Oct 13;118(15):4041-52. Epub 2011 Aug 9 doi: 10.1182/blood-2011-03-278127. PMID: 21828139Free PMC Article
HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis.
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G
Pediatr Blood Cancer 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039. PMID: 16937360

Therapy

Use of the JAK Inhibitor Ruxolitinib in the Treatment of Hemophagocytic Lymphohistiocytosis.
Keenan C, Nichols KE, Albeituni S
Front Immunol 2021;12:614704. Epub 2021 Feb 16 doi: 10.3389/fimmu.2021.614704. PMID: 33664745Free PMC Article
Immunopathogenesis and treatment of cytokine storm in COVID-19.
Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, Kronbichler A, Shin JI
Theranostics 2021;11(1):316-329. Epub 2021 Jan 1 doi: 10.7150/thno.49713. PMID: 33391477Free PMC Article
Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.
Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C
N Engl J Med 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326. PMID: 32374962
Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO).
Jordan MB, Allen CE, Greenberg J, Henry M, Hermiston ML, Kumar A, Hines M, Eckstein O, Ladisch S, Nichols KE, Rodriguez-Galindo C, Wistinghausen B, McClain KL
Pediatr Blood Cancer 2019 Nov;66(11):e27929. Epub 2019 Jul 24 doi: 10.1002/pbc.27929. PMID: 31339233Free PMC Article
Hemophagocytic lymphohistiocytosis in adults.
Bhatt NS, Oshrine B, An Talano J
Leuk Lymphoma 2019 Jan;60(1):19-28. Epub 2018 Jul 3 doi: 10.1080/10428194.2018.1482543. PMID: 29966474

Prognosis

An improved index for diagnosis and mortality prediction in malignancy-associated hemophagocytic lymphohistiocytosis.
Zoref-Lorenz A, Murakami J, Hofstetter L, Iyer S, Alotaibi AS, Mohamed SF, Miller PG, Guber E, Weinstein S, Yacobovich J, Nikiforow S, Ebert BL, Lane A, Pasvolsky O, Raanani P, Nagler A, Berliner N, Daver N, Ellis M, Jordan MB
Blood 2022 Feb 17;139(7):1098-1110. doi: 10.1182/blood.2021012764. PMID: 34780598Free PMC Article
The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.
Bami S, Vagrecha A, Soberman D, Badawi M, Cannone D, Lipton JM, Cron RQ, Levy CF
Pediatr Blood Cancer 2020 Nov;67(11):e28581. Epub 2020 Jul 29 doi: 10.1002/pbc.28581. PMID: 32725881
Neonatal Hemophagocytic Lymphohistiocytosis.
McLean J, Katebian R, Suh E, Mirza K, Amin S
Neoreviews 2019 Jun;20(6):e316-e325. doi: 10.1542/neo.20-6-e316. PMID: 31261095
Familial Hemophagocytic Lymphohistiocytosis.
Degar B
Hematol Oncol Clin North Am 2015 Oct;29(5):903-13. Epub 2015 Aug 25 doi: 10.1016/j.hoc.2015.06.008. PMID: 26461150
Adult haemophagocytic syndrome.
Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X
Lancet 2014 Apr 26;383(9927):1503-1516. Epub 2013 Nov 27 doi: 10.1016/S0140-6736(13)61048-X. PMID: 24290661

Clinical prediction guides

T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis.
Chaturvedi V, Marsh RA, Zoref-Lorenz A, Owsley E, Chaturvedi V, Nguyen TC, Goldman JR, Henry MM, Greenberg JN, Ladisch S, Hermiston ML, Jeng M, Naqvi A, Allen CE, Wong HR, Jordan MB
Blood 2021 Apr 29;137(17):2337-2346. doi: 10.1182/blood.2020009499. PMID: 33512385Free PMC Article
Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis.
Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C
N Engl J Med 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326. PMID: 32374962
Hyperferritinemia and inflammation.
Kernan KF, Carcillo JA
Int Immunol 2017 Nov 1;29(9):401-409. doi: 10.1093/intimm/dxx031. PMID: 28541437Free PMC Article
Capillary leak syndrome: etiologies, pathophysiology, and management.
Siddall E, Khatri M, Radhakrishnan J
Kidney Int 2017 Jul;92(1):37-46. Epub 2017 Mar 17 doi: 10.1016/j.kint.2016.11.029. PMID: 28318633
Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome.
Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G
Arthritis Rheumatol 2014 Sep;66(9):2613-20. doi: 10.1002/art.38690. PMID: 24782338

Recent systematic reviews

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature.
Liu LL, Skribek M, Harmenberg U, Gerling M
J Immunother Cancer 2023 Mar;11(3) doi: 10.1136/jitc-2022-005841. PMID: 36878533Free PMC Article
Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study.
Dolladille C, Ederhy S, Ezine E, Choquet S, Nguyen LS, Alexandre J, Moslehi JJ, Dechartres A, Salem JE
Am J Hematol 2021 Sep 1;96(9):1101-1111. Epub 2021 Jun 23 doi: 10.1002/ajh.26259. PMID: 34057232
Autoimmune and Rheumatic Manifestations Associated With COVID-19 in Adults: An Updated Systematic Review.
Tang KT, Hsu BC, Chen DY
Front Immunol 2021;12:645013. Epub 2021 Mar 12 doi: 10.3389/fimmu.2021.645013. PMID: 33777042Free PMC Article
Clinical characteristics of severe neonatal enterovirus infection: a systematic review.
Zhang M, Wang H, Tang J, He Y, Xiong T, Li W, Qu Y, Mu D
BMC Pediatr 2021 Mar 15;21(1):127. doi: 10.1186/s12887-021-02599-y. PMID: 33722228Free PMC Article
Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review.
Hayden A, Park S, Giustini D, Lee AY, Chen LY
Blood Rev 2016 Nov;30(6):411-420. Epub 2016 May 20 doi: 10.1016/j.blre.2016.05.001. PMID: 27238576

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