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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

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
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
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

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
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
Henderson LA, Cron RQ
Paediatr Drugs 2020 Feb;22(1):29-44. doi: 10.1007/s40272-019-00367-1. PMID: 31732958Free PMC Article
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
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

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
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
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
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
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

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
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
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
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
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

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
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
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
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
Fisman DN
Emerg Infect Dis 2000 Nov-Dec;6(6):601-8. doi: 10.3201/eid0606.000608. PMID: 11076718Free PMC Article

Clinical prediction guides

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
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
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
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
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

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
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
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
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
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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