Hemophagocytic Lymphohistiocytosis

被引:318
作者
Al-Samkari, Hanny [1 ]
Berliner, Nancy [2 ]
机构
[1] Massachusetts Gen Hosp, Boston, MA 02114 USA
[2] Brigham & Womens Hosp, Boston, MA 02115 USA
来源
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 13 | 2018年 / 13卷
关键词
hemophagocytic lymphohistiocytosis; hemophagocytosis; macrophage activation syndrome; immune activation; reactive hemophagocytic syndrome; MACROPHAGE ACTIVATION SYNDROME; JUVENILE RHEUMATOID-ARTHRITIS; STEM-CELL TRANSPLANTATION; CLINICAL-FEATURES; ERYTHROPHAGOCYTIC LYMPHOHISTIOCYTOSIS; CUTANEOUS MANIFESTATIONS; SCAVENGER RECEPTOR; ADULT PATIENTS; PERFORIN GENE; DEP REGIMEN;
D O I
10.1146/annurev-pathol-020117-043625
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immune-mediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger). Clinical and laboratory manifestations include fever, splenomegaly, neurologic dysfunction, coagulopathy, liver dysfunction, cytopenias, hypertriglyceridemia, hyperferritinemia, hemophagocytosis, and diminished NK cell activity. It is treated with immune suppressants, etoposide, and allogeneic hematopoietic stem cell transplantation; more than 50% of children who undergo transplant survive, but adults have quite poor outcomes even with aggressive management. Newer agents directed at subduing the uncontrolled immune response in a targeted fashion offer promise in this highly morbid disease.
引用
收藏
页码:27 / 49
页数:23
相关论文
共 105 条
  • [21] Debaugnies F, 2016, AM J CLIN PATHOL, V145, P862, DOI [10.1093/AJCP/AQW076, 10.1093/ajcp/aqw076]
  • [22] Hemophagocytic lymphohistiocytosis due to acute primary herpes simplex virus 1 infection
    Drori, Ariel
    Ribak, Yaarit
    van Heerden, P. Vernon
    Meir, Karen
    Wolf, Dana
    Safadi, Rifaat
    [J]. JOURNAL OF CLINICAL VIROLOGY, 2015, 68 : 6 - 10
  • [23] Emile JF, 2016, BLOOD, V127, P2672, DOI [10.1182/blood-2016-01-690636, 10.1182/blood-2016-01690636]
  • [24] Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis
    Ericson, KG
    Fadeel, B
    Nilsson-Ardnor, S
    Söderhäll, C
    Samuelsson, A
    Janka, G
    Schneider, M
    Gürgey, A
    Yalman, N
    Révész, T
    Egeler, RM
    Jahnukainen, K
    Storm-Mathiesen, I
    Haraldsson, A
    Poole, J
    de Saint Basile, G
    Nordenskjöld, M
    Henter, JI
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (03) : 590 - 597
  • [25] Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome
    Fardet, L.
    Galicier, L.
    Vignon-Pennamen, M. -D.
    Regnier, S.
    Noguera, M. E.
    de Labarthe, A.
    Raffoux, E.
    Martinez, V.
    Buyse, S.
    Viguier, M.
    Osio, A.
    Lebbe, C.
    Morel, P.
    Dupuy, A.
    Rybojad, M.
    [J]. BRITISH JOURNAL OF DERMATOLOGY, 2010, 162 (03) : 547 - 553
  • [26] Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome
    Fardet, Laurence
    Galicier, Lionel
    Lambotte, Olivier
    Marzac, Christophe
    Aumont, Cedric
    Chahwan, Doumit
    Coppo, Paul
    Hejblum, Gilles
    [J]. ARTHRITIS & RHEUMATOLOGY, 2014, 66 (09) : 2613 - 2620
  • [27] FAMILIAL HAEMOPHAGOCYTIC RETICULOSIS
    FARQUHAR, JW
    CLAIREAUX, AE
    [J]. ARCHIVES OF DISEASE IN CHILDHOOD, 1952, 27 (136) : 519 - 525
  • [28] Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3)
    Feldmann, J
    Callebaut, I
    Raposo, G
    Certain, S
    Bacq, D
    Dumont, C
    Lambert, N
    Ouachée-Chardin, M
    Chedeville, G
    Tamary, H
    Minard-Colin, V
    Vilmer, E
    Blanche, S
    Le Deist, F
    Fischer, A
    Saint Basile, GD
    [J]. CELL, 2003, 115 (04) : 461 - 473
  • [29] Functional consequences of perforin gene mutations in 22 patients with familial haemophagocytic lymphohistiocytosis
    Feldmann, J
    Le Deist, F
    Ouachée-Chardin, M
    Certain, S
    Alexander, S
    Quartier, P
    Haddad, E
    Wulffraat, N
    Casanova, JL
    Blanche, S
    Fischer, A
    de Saint Basile, G
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2002, 117 (04) : 965 - 972
  • [30] The expanding spectrum of hemophagocytic lymphohistiocytosis
    Filipovich, Alexandra H.
    [J]. CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2011, 11 (06) : 512 - 516