U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Management of Dengue: An Updated Review.
Tayal A, Kabra SK, Lodha R
Indian J Pediatr 2023 Feb;90(2):168-177. Epub 2022 Dec 27 doi: 10.1007/s12098-022-04394-8. PMID: 36574088Free PMC Article
Recommendations for the management of hemophagocytic lymphohistiocytosis in adults.
La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JAM, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI
Blood 2019 Jun 6;133(23):2465-2477. Epub 2019 Apr 16 doi: 10.1182/blood.2018894618. PMID: 30992265
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
Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore.
Knaak C, Nyvlt P, Schuster FS, Spies C, Heeren P, Schenk T, Balzer F, La Rosée P, Janka G, Brunkhorst FM, Keh D, Lachmann G
Crit Care 2020 May 24;24(1):244. doi: 10.1186/s13054-020-02941-3. PMID: 32448380Free PMC Article
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

A Review of Current and Emerging Therapeutic Options for Hemophagocytic Lymphohistiocytosis.
Summerlin J, Wells DA, Anderson MK, Halford Z
Ann Pharmacother 2023 Jul;57(7):867-879. Epub 2022 Nov 9 doi: 10.1177/10600280221134719. PMID: 36349896
Recent advances in the treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome.
Jesudas R, Nichols KE
Curr Opin Allergy Clin Immunol 2022 Dec 1;22(6):364-370. Epub 2022 Sep 28 doi: 10.1097/ACI.0000000000000865. PMID: 36206094
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
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

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
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
Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation.
Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society
Blood 2002 Oct 1;100(7):2367-73. doi: 10.1182/blood-2002-01-0172. PMID: 12239144

Clinical prediction guides

Recognizing, defining, and managing CAR-T hematologic toxicities.
Rejeski K, Subklewe M, Locke FL
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):198-208. doi: 10.1182/hematology.2023000472. PMID: 38066881Free 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

The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, Piskin D, Ravelli A, Sinha R, Aletaha D, Allen C, Bassiri H, Behrens EM, Carcillo J, Carl L, Chatham W, Cohen JI, Cron RQ, Drewniak E, Grom AA, Henderson LA, Horne A, Jordan MB, Nichols KE, Schulert G, Vastert S, Demirkaya E, Goldbach-Mansky R, de Benedetti F, Marsh RA, Canna SW; HLH/MAS task force
Ann Rheum Dis 2023 Oct;82(10):1271-1285. Epub 2023 Jul 24 doi: 10.1136/ard-2023-224123. PMID: 37487610Free PMC Article
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, Piskin D, Ravelli A, Sinha R, Aletaha D, Allen C, Bassiri H, Behrens EM, Carcillo J, Carl L, Chatham W, Cohen JI, Cron RQ, Drewniak E, Grom AA, Henderson LA, Horne A, Jordan MB, Nichols KE, Schulert G, Vastert S, Demirkaya E, Goldbach-Mansky R, de Benedetti F, Marsh RA, Canna SW
Arthritis Rheumatol 2023 Oct;75(10):1714-1732. Epub 2023 Jul 24 doi: 10.1002/art.42636. PMID: 37486733
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
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

Supplemental Content

Table of contents

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Related information

    • MeSH
      Related Medical Subject Headings
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...