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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

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
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

Adult-onset Still's disease masquerading as acute coronary syndrome: a case report and review of the literature.
Milne I, Kanwar R, Martin W, Egert D, Leisgang A, Albano-Aluquin SA, Henao MP, Kreider C, Ssentongo P
J Med Case Rep 2024 Oct 10;18(1):489. doi: 10.1186/s13256-024-04799-3. PMID: 39385309Free PMC Article
Lamotrigine: A Safe and Effective Mood Stabilizer for Bipolar Disorder in Reproductive-Age Adults.
Cyrkler M, Drabik A, Czerwiak KZ, Soroka E
Med Sci Monit 2024 Oct 7;30:e945464. doi: 10.12659/MSM.945464. PMID: 39370636Free PMC Article
Too much of a good thing: a review of primary immune regulatory disorders.
Tsilifis C, Slatter MA, Gennery AR
Front Immunol 2023;14:1279201. Epub 2023 Oct 31 doi: 10.3389/fimmu.2023.1279201. PMID: 38022498Free PMC Article

Diagnosis

Adult-onset Still's disease masquerading as acute coronary syndrome: a case report and review of the literature.
Milne I, Kanwar R, Martin W, Egert D, Leisgang A, Albano-Aluquin SA, Henao MP, Kreider C, Ssentongo P
J Med Case Rep 2024 Oct 10;18(1):489. doi: 10.1186/s13256-024-04799-3. PMID: 39385309Free PMC Article
Lamotrigine: A Safe and Effective Mood Stabilizer for Bipolar Disorder in Reproductive-Age Adults.
Cyrkler M, Drabik A, Czerwiak KZ, Soroka E
Med Sci Monit 2024 Oct 7;30:e945464. doi: 10.12659/MSM.945464. PMID: 39370636Free PMC Article

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
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
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: 37486733Free PMC Article
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

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