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Familial hemophagocytic lymphohistiocytosis 4(FHL4)

MedGen UID:
350245
Concept ID:
C1863728
Disease or Syndrome
Synonym: FHL4
 
STX11 (6q24.2)
 
Monarch Initiative: MONDO:0011336
OMIM®: 603552

Definition

Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder clinically diagnosed based on the fulfillment of 5 of 8 criteria, including fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell activity, hyperferritinemia, and high soluble IL2 receptor levels (IL2R; 147730). The disorder typically presents in infancy or early childhood. Persistent remission is rarely achieved with chemo- or immunotherapy; hematopoietic stem cell transplantation is the only cure (summary by Muller et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL), see 267700. [from OMIM]

Clinical features

From HPO

Professional guidelines

PubMed

Liu B, Cheng L, Gao H, Zhang J, Dong Y, Gao W, Yuan S, Gong T, Huang W
Cancer Lett 2023 Jan 28;553:215996. Epub 2022 Nov 5 doi: 10.1016/j.canlet.2022.215996. PMID: 36343787
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
Liu P, Pan X, Chen C, Niu T, Shuai X, Wang J, Chen X, Liu J, Guo Y, Xie L, Wu Y, Liu Y, Liu T
Blood 2020 Mar 12;135(11):826-833. doi: 10.1182/blood.2019003886. PMID: 31914172

Recent clinical studies

Etiology

Zhang H, Zhao S, Cao Z
Front Immunol 2022;13:1001055. Epub 2022 Oct 28 doi: 10.3389/fimmu.2022.1001055. PMID: 36389673Free PMC Article
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
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
Karakike E, Giamarellos-Bourboulis EJ
Front Immunol 2019;10:55. Epub 2019 Jan 31 doi: 10.3389/fimmu.2019.00055. PMID: 30766533Free PMC Article
Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, Okada S, Yamashita M, Yeh TW, Nishikomori R, Takagi M, Imai K, Ochs HD, Morio T
Allergol Int 2018 Jan;67(1):43-54. Epub 2017 Jul 3 doi: 10.1016/j.alit.2017.06.003. PMID: 28684198

Diagnosis

Le Calvez B, Thomas C, Huault A, Cassagnau E, Béné MC, Eveillard M
Am J Hematol 2022 Apr;97(4):508-509. Epub 2021 Oct 5 doi: 10.1002/ajh.26364. PMID: 34591997
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
El-Mallawany NK, Curry CV, Allen CE
Br J Haematol 2022 Jan;196(1):31-44. Epub 2021 Jun 24 doi: 10.1111/bjh.17638. PMID: 34169507
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
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

Therapy

Iba T, Levy JH
Trends Cardiovasc Med 2022 Jul;32(5):249-256. Epub 2022 Feb 22 doi: 10.1016/j.tcm.2022.02.008. PMID: 35202800Free PMC Article
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
Karakike E, Giamarellos-Bourboulis EJ
Front Immunol 2019;10:55. Epub 2019 Jan 31 doi: 10.3389/fimmu.2019.00055. PMID: 30766533Free PMC Article
Kumar S, Ward BR, Irani AM
Immunol Allergy Clin North Am 2017 May;37(2):431-448. doi: 10.1016/j.iac.2017.01.013. PMID: 28366486
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

Prognosis

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
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
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
Karakike E, Giamarellos-Bourboulis EJ
Front Immunol 2019;10:55. Epub 2019 Jan 31 doi: 10.3389/fimmu.2019.00055. PMID: 30766533Free PMC Article
Malhotra AK, Bhaskar G, Nanda M, Kabra M, Singh MK, Ramam M
J Am Acad Dermatol 2006 Aug;55(2):337-40. doi: 10.1016/j.jaad.2005.11.1056. PMID: 16844525

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
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
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
Karakike E, Giamarellos-Bourboulis EJ
Front Immunol 2019;10:55. Epub 2019 Jan 31 doi: 10.3389/fimmu.2019.00055. PMID: 30766533Free 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

Recent systematic reviews

Meena DS, Kumar A, Kumar D, Bohra GK, Purohit A
Am J Trop Med Hyg 2024 Jun 5;110(6):1217-1222. Epub 2024 Apr 2 doi: 10.4269/ajtmh.23-0787. PMID: 38579699Free PMC Article
Tan CJ, Ng ZQ, Bhattacharyya R, Sultana R, Lee JH
Pediatr Blood Cancer 2023 Mar;70(3):e30122. Epub 2022 Dec 29 doi: 10.1002/pbc.30122. PMID: 36579732
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
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
Knaak C, Schuster FS, Nyvlt P, Spies C, Feinkohl I, Beutel G, Schenk T, La Rosée P, Janka G, Brunkhorst FM, Keh D, Lachmann G
Crit Care Med 2020 Nov;48(11):e1137-e1146. doi: 10.1097/CCM.0000000000004581. PMID: 32947471

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