U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from Gene

Hemophagocytic lymphohistiocytosis, familial, 6(FHL6, FORMERLY; IMDYSHI)

MedGen UID:
1736944
•Concept ID:
C5436563
•
Disease or Syndrome
Synonym: IMMUNE DYSREGULATION AND SYSTEMIC HYPERINFLAMMATION SYNDROME
 
Gene (location): RC3H1 (1q25.1)
 
Monarch Initiative: MONDO:0033557
OMIM®: 618998

Definition

Immune dysregulation and systemic hyperinflammation syndrome (IMDYSHI) is an autosomal recessive immunologic disorder characterized by systemic hyperinflammation in the absence of an infectious agent or autoimmune trigger. Features include lymphadenopathy, hepatosplenomegaly, recurrent fever, and laboratory evidence of immune dysregulation with abnormal immune cell populations and increased serum levels of inflammatory cytokines. The phenotype is reminiscent of relapsing hemophagocytic lymphohistiocytosis (HLH; see FHL1, 267700) (summary by Tavernier et al., 2019). [from OMIM]

Professional guidelines

PubMed

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
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
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

Recent clinical studies

Etiology

The changing landscape of pediatric histiocytoses: Birth, life, and transdifferentiation of pediatric histiocytes.
Auerbach A, Aguilera NS
Semin Diagn Pathol 2023 Nov;40(6):420-428. Epub 2023 May 20 doi: 10.1053/j.semdp.2023.05.003. PMID: 37258365
Malignancy-associated haemophagocytic lymphohistiocytosis.
Setiadi A, Zoref-Lorenz A, Lee CY, Jordan MB, Chen LYC
Lancet Haematol 2022 Mar;9(3):e217-e227. Epub 2022 Jan 31 doi: 10.1016/S2352-3026(21)00366-5. PMID: 35101205
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
Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages.
Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, Requena-Caballero L, Jordan MB, Abdel-Wahab O, Allen CE, Charlotte F, Diamond EL, Egeler RM, Fischer A, Herrera JG, Henter JI, Janku F, Merad M, Picarsic J, Rodriguez-Galindo C, Rollins BJ, Tazi A, Vassallo R, Weiss LM; Histiocyte Society
Blood 2016 Jun 2;127(22):2672-81. Epub 2016 Mar 10 doi: 10.1182/blood-2016-01-690636. PMID: 26966089Free PMC Article
The haemophagocytic syndrome.
Dierickx D, Cortoos A, Vanderschueren S
Acta Clin Belg 2011 Nov-Dec;66(6):448-52. doi: 10.2143/ACB.66.6.2062613. PMID: 22338310

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
A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis.
Zhang Q, Zhao YZ, Ma HH, Wang D, Cui L, Li WJ, Wei A, Wang CJ, Wang TY, Li ZG, Zhang R
Blood 2022 Jun 16;139(24):3493-3504. doi: 10.1182/blood.2021014860. PMID: 35344583
Malignancy-associated haemophagocytic lymphohistiocytosis.
Setiadi A, Zoref-Lorenz A, Lee CY, Jordan MB, Chen LYC
Lancet Haematol 2022 Mar;9(3):e217-e227. Epub 2022 Jan 31 doi: 10.1016/S2352-3026(21)00366-5. PMID: 35101205
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
Macrophage activation syndrome in the era of biologic therapy.
Grom AA, Horne A, De Benedetti F
Nat Rev Rheumatol 2016 May;12(5):259-68. Epub 2016 Mar 24 doi: 10.1038/nrrheum.2015.179. PMID: 27009539Free PMC Article

Therapy

Recent advances and evolving concepts in Still's disease.
Ruscitti P, Cantarini L, Nigrovic PA, McGonagle D, Giacomelli R
Nat Rev Rheumatol 2024 Feb;20(2):116-132. Epub 2024 Jan 11 doi: 10.1038/s41584-023-01065-6. PMID: 38212542
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
Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.
Knaak C, Schuster FS, Spies C, Vorderwülbecke G, Nyvlt P, Schenk T, Balzer F, La Rosée P, Janka G, Brunkhorst FM, Keh D, Lachmann G
Shock 2020 Jun;53(6):701-709. doi: 10.1097/SHK.0000000000001454. PMID: 31626037
Macrophage activation syndrome in the era of biologic therapy.
Grom AA, Horne A, De Benedetti F
Nat Rev Rheumatol 2016 May;12(5):259-68. Epub 2016 Mar 24 doi: 10.1038/nrrheum.2015.179. PMID: 27009539Free PMC Article
The haemophagocytic syndrome.
Dierickx D, Cortoos A, Vanderschueren S
Acta Clin Belg 2011 Nov-Dec;66(6):448-52. doi: 10.2143/ACB.66.6.2062613. PMID: 22338310

Prognosis

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
Hematologic manifestations of babesiosis.
Akel T, Mobarakai N
Ann Clin Microbiol Antimicrob 2017 Feb 15;16(1):6. doi: 10.1186/s12941-017-0179-z. PMID: 28202022Free 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
The haemophagocytic syndrome.
Dierickx D, Cortoos A, Vanderschueren S
Acta Clin Belg 2011 Nov-Dec;66(6):448-52. doi: 10.2143/ACB.66.6.2062613. PMID: 22338310
Hemophagocytic syndromes and infection.
Fisman DN
Emerg Infect Dis 2000 Nov-Dec;6(6):601-8. doi: 10.3201/eid0606.000608. PMID: 11076718Free PMC Article

Clinical prediction guides

Chronic active Epstein-Barr virus disease originates from infected hematopoietic stem cells.
Wang J, Su M, Wei N, Yan H, Zhang J, Gong Y, Wu L, Suolitiken D, Pi Y, Song D, Chen L, Liu H, Yang S, Wang X, Wang Z
Blood 2024 Jan 4;143(1):32-41. doi: 10.1182/blood.2023021074. PMID: 37824804
Hyperinflammatory syndrome resembling haemophagocytic lymphohistiocytosis following axicabtagene ciloleucel and brexucabtagene autoleucel.
Porter TJ, Lazarevic A, Ziggas JE, Fuchs E, Kim K, Byrnes H, Luznik L, Bolaños-Meade J, Ali SA, Shah NN, Wagner-Johnston N, Jain T
Br J Haematol 2022 Dec;199(5):720-727. Epub 2022 Sep 16 doi: 10.1111/bjh.18454. PMID: 36111395Free PMC Article
Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases?
Opoka-Winiarska V, Grywalska E, Roliński J
BMC Med 2020 Jul 15;18(1):214. doi: 10.1186/s12916-020-01682-y. PMID: 32664932Free PMC Article
Macrophage activation syndrome in the era of biologic therapy.
Grom AA, Horne A, De Benedetti F
Nat Rev Rheumatol 2016 May;12(5):259-68. Epub 2016 Mar 24 doi: 10.1038/nrrheum.2015.179. PMID: 27009539Free PMC Article
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

A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy.
Cordas Dos Santos DM, Tix T, Shouval R, Gafter-Gvili A, Alberge JB, Cliff ERS, Theurich S, von Bergwelt-Baildon M, Ghobrial IM, Subklewe M, Perales MA, Rejeski K
Nat Med 2024 Sep;30(9):2667-2678. Epub 2024 Jul 8 doi: 10.1038/s41591-024-03084-6. PMID: 38977912
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
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

    Clinical resources

    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.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      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...