Hemofagositik lenfohistiositozda santral sinir sistemi komplikasyonları
Year 2015,
Volume: 12 Issue: 1, 154 - 164, 15.04.2015
Mervan Bekdaş
,
Sevil Bilir Göksügür
,
Fatih Demircioğlu
Abstract
Hemofagositik lenfohistiositoz, çok sayıda sistemi etkileyen, nadir görülen bir hastalıktır. Santral sinir
sistemi tutulumu, prognozu etkilemesi ve ciddi sekel oluşturma riski nedeniyle çok önemlidir.
Hemofagositik lenfohistiositozun santral sinir sistemi tutulumu ilişkili nörolojik bulgu ve
komplikasyonların sıklıkları, özellikleri, morbidite ve mortaliteye etkisini irdeleyen yayın sayısı azdır. Bu
yazıda, hemofagositik lenfohistiositozun santral sinir sistemi tutulumu ile ilişkili klinik tabloya dikkat
çekmek istedik.
References
- 1)Imashuku S, Teramura T, Morimoto A, et al. Recent
developments in the management of haemophagocytic
lymphohistiocytosis. Expert Opin Pharmacother
2001;2:1437-48
2)Imashuku S, Hibi S, Sako M, et al. Soluble interleukin2 receptor: a useful prognostic factor for patients with
hemophagocytic lymphohistiocytosis. Blood 1995,
86:4706-7 1)
3)Ravelli A: Macrophage activation syndrome. Curr
Opin Rheumatol 2002;14:548-52
4)Osugi Y, Hara J, Tagawa S, et al. Cytokine
production regulating Th1 and Th2 cytokines in
hemophagocytic lymphohistiocytosis. Blood 1997;
89: 4100-3
5)Teruya-Feldstein J, Setsuda J, Yao X, et al. MIP-1
expression in tissues from patients with
h emo p h a g o c y ti c s y n d r ome . La b I n v e st
1999;79:1583-90
6)Schneider EM, Lorenz I, Müller-Rosenberger M, et
al. Hemophagocytic lymphohistiocytosis is associated
with deficiencies of cellular cytolysis but normal
expression of transcripts relevant to killer-cellinducedapoptosis. Blood 2002;100:2891-8
7)Janka GE, Schneider EM. Modern management of
children with haemophagocytic lymphohistiocytosis.
Br J Haematol 2004;124:4-14
8)Janka GE: Hemophagocytic syndromes. Blood Rev
2007;21:245-53
9)Henter JI, Elinder G. Incidence in Sweden and clinical
f e a t u r e s o f f a m i l i a l h e m o p h a g o c y t i c
lymphohistiocytosis. Acta Paediatr Scand 1991;80:428-
35
10)Gurgey A, Gogus S, Ozyurek E et al. Primary
hemophagocytic lymphohistiocytosis in Turkish
children. Pediatr Hematol Oncol 2003;20:367–71
11)Behrens EM, Canna SW, Slade K, et al: Repeated
TLR9 stimulation results in macrophage activation
syndrome-like disease in mice. J Clin Invest
2011;121:2264-771)
12)De Saint Basile G, Fischer A. Defective cytotoxic
granule-mediated cell death pathway impairs T
lymphocyte homeostasis. Curr Opin Rheumatol
2003;15:436-45
13)Zhang K, Jordan MB, Marsh RA, et al:
Hypomorphic mutations in PRF1, MUNC13-4, and
STXBP2 are associated with adult-onset familial
hemophagocytic lymphohistiocytosis. Blood
2011;118:5794-98
14)Clementi R, Emmi L, Maccario R, et al. Adult onset
and atypical presentation of hemophagocytic
lymphohistiocytosis in siblings carrying PRF1
mutations. Blood 2002;100:2266-67
15)Ansuini V, Rigante D, Esposito S. Debate around
infection- dependent hemophagocytic syndrome in
paediatrics. BMC Infectious Diseases 2013;13:15-23
16)Henter JI, Ehrnst A, Andersson J, Elinder G. Familial
hemophagocytic lymphohistiocytosis and viral
infections. Acta Paediatr 1993;82:369- 72
17)Rajagopala S, Singh N. Diagnosing and treating
hemophagocytic lymphohistiocytosis in the tropics:
Systematic review from the indian subcontinent. Acta
Medica Academica 2012;41:161-174
18)De Saint Basile G, Menasche G, Fischer A. Molecular
mechanisms of biogenesis and exocytosis of cytotoxic
granules. Nat Rev Immunol 2010;10:568-79
19)Katano H, Cohen JI. Perforin and lymphohistiocytic
proliferative disorders. Br J Haematol 2005;128:739-50
1)
20)Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al.
Perforin gene defects in familial hemophagocytic
lymphohistiocytosis. Science 1999; 286:1957-9
21)Menasche G, Feldmann J, Fischer A, et al. Primary
hemophagocytic syndromes point to a direct link
between lymphocyte cytotoxicity and homeostasis.
Immunol Rev 2005;203:165-79
22)Zur Stadt U, Schmidt S, Kasper B, et al. Linkage of
familial hemophagocytic lymphohistiocytosis (FHL)
type-4 to chromosome 6q24 and identification of
mutations in syntaxin 11. Hum Mol Genet 2005;14:827-
34
23)Brochetta C, Vita F, Tiwari N, et al. Involvement of
Munc18 isoforms in the regulation of granule
exocytosis in neutrophils. Biochim. Biophys. Acta.
2008;1783:1781-91
24)Zur Stadt U, Rohr J, Seifert W, et al. Familial
hemophagocytic lymphohistiocytosis type 5 (FHL-5)
is caused by mutations in Munc18-2 and impaired
binding to syntaxin 11. Am J Hum Genet 2009;85:482-
92
Meeths M,
25)Entesarian M, Al-Herz W, et al. Spectrum of
clinical presentations in familial hemophagocytic
lymphohistiocytosis type 5 patients with mutations in
STXBP2. Blood. 2010;116:2635-43
26)Janka G: Hemophagocytic lymphohistiocytosis:
when the immune system runs amok. Klin Pediatr
2009;221:278-285
27)Machaczka M, Vaktnas J, Klimkowska M, et al.
Ma lignancy- a ssoc i a t ed hemophagocyti c
lymphohistiocytosis in adults: a retrospective
population- based analysis from a single center. Leuk
Lymphoma 2011;52:613-191)
28)Bryceson YT, Pende D, Maul-Pavicic A, et al. A
prospective evaluation of degranulation assays in the
rapid diagnosis of familial hemophagocytic syndromes.
Blood 2012;119:2754-63
29)Lartigue A, Courville P, Auquit I, et al. Role of
TLR9 in anti- nucleosome and anti-DNA antibody
production in lpr mutation-induced murine lupus. J
Immunol 2006;177:1349-54
30)Fisman DN. Hemophagocytic syndromes and
infection. Emerg Infect Dis 2000;6:601-8
31)Rigante D, De Rosa G, Bertoni B, et al. Large
pericardial effusion requiring pericardiocentesis as
cardinal sign of macrophage activation syndrome in
systemic onset juvenile idiopathic arthritis.
Rheumatol Int 2007;27:767-70
32)Janka G, Imashuku S, Elinder G, et al. Infection
and malignancy associated hemophagocytic
s y n d r ome s. Se c o n d a r y h emo p h a g o c y ti c
lymphohistiocytosis. Hematol Oncol Clin North Am
1998;12:435-44
33)Wong K, Chan JK. Reactive hemophagocytic
syndrome-a clinicopathologic study of 40 patients in
an oriental population. Am J Med 1992;93:177-80
34)Henter JI, Nennesmo I. Neuropathologic findings
and neurologic symptoms in twenty-three children
with hemophagocytic lymphohistiocytosis. J Pediatr
1997;130:358-65
35)Haddad E, Sulis ML, Jabado N, et al. Frequency
and severity of central nervous system lesions in
hemophagocytic lymphohistiocytosis. Blood
1997;89:794-8001)
3 6 )Gu rg e y A, Ay t a c S, Ba lt a G, e t a l.
Lymphohistiocytosis Central Nervous System
Involvement in Turkish Children With Primary
Hemophagocytic. J Child Neurol 2008;23:1293-99
37)Janabi N, Chabrier S, Tardieu M. Endogenous
nitric oxide activates prostaglandin F2a production in
human microglial cells but not in astrocytes. J
Immunol 1996;157:2129
38)Ören H. Hemofagositik Sendrom. Türk Çocuk
Hematoloji Dergisi 2007;1:7-13
39)Horne A, Trottestam H, Aricò M, et al. Frequency
and spectrum of central nervous system involvement in
1 9 3 c h i l d r e n w i t h h a e m o p h a g o c y t i c
lymphohistiocytosis. Br J Haematol 2008;140:327-35
40)Yang S, Zhang L, Jia C, et al. Frequency and
development of CNS involvement in Chinese children
with hemophagocytic lymphohistiocytosis. Pediatr
Blood Cancer 2010;54:408-15
41)J anka GE. Famili a l ha emophagocyti c
lymphohistiocytosis. Eur tion of graft failure by a
monoclonal antibody (anti-LFA-1-CD11a). J Pediatr
1983;140:221
Tardieu M,
42)Lacroix C, Neven B, et al. Progressive neurologic
dysfunctions 20 years after allogeneic bone marrow
transplantation for Chediak- Higashi syndrome. Blood
2005;106:40-42
43)Rostasy K, Kolb R, Pohl D, et al. CNS disease as the
ma i n ma n if e st a t i o n o f h emo p h a g o c y t i c
lymphohistiocytosis in two children. Neuropediatrics
2004;35:45-91)
44)Deiva K, Mahlaoui N, Beaudonnet F, et al. CNS
involvement at the onset of primary hemophagocytic
lymphohistiocytosis. Neurology 2012;78:1150-56
Kim MM
45)Yum MS, Choi HW, et al. Central nervous system
(CNS) involvement is a critical prognostic factor for
hemophagocytic lymphohistiocytosis. Korean J
Hematol 2012;47:273-80
46)Hirst WJ, Layton DM, Singh S, et al.
Haemophagocytic lymphohistiocytosis: experience at
two U.K. centres. Br J Haematol 1994;88:731-39
Ramachandran B,
47)Balasubramanian S, Abhishek N, et al. Profile of
hemophagocytic lymphohistiocytosis in children in a
tertiary care hospital in India. Indian Pediatr
2011;48:31-5
48)Kieslich M, Vecchi M, Driever PH, et al. Acute
encephalopathy as a primary manifestation of
hemophagocytic lymphohistiocytosis. Dev Med Child
Neurol 2001;43:555-58
49)Thompson PA, Allen CE, Horton T, et al. Severe
neurologic sideeffects in patients being treated for
hemophagocytic lymphohistiocytosis. Pediatr Blood
Cancer 2009;52:621-5
5 0 ) F i l i p o v i c h A H . H e m o p h a g o c y t i c
lymphohistiocytosis (HLH) and related disorders.
Hematology Am Soc Hematol Educ Program.
2009:127-31
51)Palazzi DL, McClain KL, Kaplan SL.
Hemophagocytic syndrome in children: an important
diagnostic consideration in fever of unknown origin.
Clin Infect Dis 2003;36:306-121)
52)Arico M, Janka G, Fischer A, et al. Hemophagocytic
lymphohistiocytosis: report of 122 children from the
International Registry. FHL Study Group of the
Histiocyte Society. Leukemia 1996;10:197-203
53)Niece JA, Rogers ZR, Ahmad N, et al.
Hemophagocytic lymphohistiocytosis in Texas:
observations on ethnicity and race. Pediatr Blood Cancer
2010;54:424-28
54)Ost A, Nilsson-Ardnor S, Henter JI. Autopsy findings
i n 2 7 c h i l d r e n w i t h h a e m o p h a g o c y t i c
lymphohistiocytosis. Histopathology 1998;32:310-16
55)Stapp J, Wilkerson S, Stewart D, et al. Fulminant
neonatal liver failure in siblings: probable congenital
hemophagocytic lymphohistiocytosis. Pediatr Dev Pathol
2006;9:239-44
56)Ouachee-Chardin M, Elie C, De Saint BG, et al.
Hematopoietic stem cell transplantation in
hemophagocytic lymphohistiocytosis: a single-center
report of 48 patients. Pediatrics. 2006;117:e743-e750
57)Fitzgerald N, McClain KL. Imaging characteristics of
hemophagocytic lymphohistiocytosis. Pediatr Radiol
2003;33:392-401
58)Pa l a z z i DL, McCl a in KL, Kapl an SL.
Hemophagocytic syndrome in children: an important
diagnostic consideration in fever of unknown origin. Clin
Infect Dis 2003;36:306-12
59)Feldmann J, Menasche G, Callebaut I, et al. Severe
and progressive encephalitis as a presenting
manifestation of a novel missense perforin mutation and
impaired cytolytic activity. Blood 2005;105:2658-
631)
60)Gholam C, Grigoriadou S, Gilmour KC, et al. Familial
haemophagocytic lymphohistiocytosis: advances in the
genetic basis, diagnosis and management. Clin Exper
Immunol 2011;163: 271-83
61)Gupta A, Weitzman S, Abdelhaleem M. The role of
hemophagocytosis in bone marrow aspirates in the
diagnosis of hemophagocytic lymphohistiocytosis.
Pediatr Blood Cancer 2008;50:192-94
62)Kuwata K, Yamada S, Kinuwaki E, et al. Peripheral
hemophagocytosis: an early indicator of advanced
systemic inflammatory response syndrome/
hemophagocytic syndrome. Shock 2006;25:344-50
63)Gauvin F, Toledano B, Champagne J, et al. Reactive
hemophagocytic syndrome presenting as a component of
multiple organ dysfunction syndrome. Crit Care Med
2000;28:3341-45
64)Turtzo LC, Lin DDM, Hartung H, et al. A Neurologic
Pr e s ent a tion of Famili a l Hemophagocyti c
Lymphohistiocytosis Which Mimicked Septic Emboli to
the Brain. J Child Neurol 2007;22:863-64
65)Schaer DJ, Schleiffenbaum B, Kurrer M, et al. Soluble
hemoglobin- haptoglobin scavenger receptor CD163 as a
lineagespecific marker in the reactive hemophagocytic
syndrome. Eur J Haematol 2005;74:6-10
66) Bleesing J, Prada A, Siegel DM, et al. The diagnostic
significance of soluble CD163 and soluble interleukin-2
receptor a-chain in macrophage activation syndrome and
unrelated new-onset systemic juvenile idiopathic
arthritis. Arthritis Rheum 2007;56:965-711)
67)Rooms L, Fitzgerald N, McClain KL. Hemophagocytic
lymphohistiocytosis masquerading as child abuse:
presentation of three cases and review of central nervous
system findings in hemophagocytic lymphohistiocytosis.
Pediatrics 2003;111:636-40
68)Chung TW. CNS Involvement in hemophagocytic
lymphohistiocytosis: CT and MR findings. Korean J Radiol 2007;8:78-81
69)Goo HW, Weon YC. A spectrum of
neuroradiological findings in children with
haemophagocytic lymphohistiocytosis. Pediatr
Radiol 2007;37:1110-17
70)Tang YM, Xu XJ. Advances in Hemophagocytic
Lymphohistiocytosis: Pathogenesis, Early
Diagnosis/Differential Diagnosis, and Treatment. The
Scientific World J 2011;11:697-708
71)Munoz Ruano MM, Castillo M. Brain CT and MR
i m a g i n g i n f a m i l i a l h e m o p h a g o c y t i c
lymphohistiocytosis. AJR Am J Roentgenol
1998;170:802-5
72)Jordan MB, Allen CE, Weitzman S, et al. How I treat
hemophagocytic lymphohistiocytosis. Blood
2011;118:4041-52
73)Bör Ö. Çocukluk Çağında Hemofagositik
Sendromlar. Güncel Pediatri 2006;4:100-1
74)Bode SFN, Lehmberg K, Maul-Pavicic A, et al.
Recent advances in the diagnosis and treatment of
hemophagocytic lymphohistiocytosis. Arthritis
Research&Therapy 2012;14:213-16
75)Gupta S, Weitzman S. Primary and secondary
hemophagocytic lymphohistiocytosis: clinical
features, pathogenesis and therapy. Expert Rev Clin
Immunol 2010;6:137 541)
76)Janka GE. Familial and acquired hemophagocytic
lymphohistiocytosis. Eur J Pediatr 2007;166:95-109
77)Trottestam H, Berglof E, Horne A, et al. Risk factors
for early death in children with haemophagocytic
lymphohistiocytosis. Acta Paediatr 2011;101:313- 18
78)Sung L, King SM, Carcao M, et al. Adverse outcomes
in primary hemophagocytic lymphohistiocytosis. J
Pediatr Hematol Oncol 2002;24:550-54
Central nervous system complications in hemophagocytic lymphohistiocytosis
Year 2015,
Volume: 12 Issue: 1, 154 - 164, 15.04.2015
Mervan Bekdaş
,
Sevil Bilir Göksügür
,
Fatih Demircioğlu
Abstract
Hemophagocytic lymphohistiocytosis is a rare disease, affecting multiple systems. Central nervous system
involvement is very important because of the effect on the prognosis. Arising neurological symptoms as a
result of this involvement are included in some publications, but the number of publications related to their
frequency, characteristics, and relations with morbidity and mortality is rare. In this article, we wanted to
attract attention to the picture of the central nervous system involvement as a result of hemophagocytic
lymphohistiocytosis.
References
- 1)Imashuku S, Teramura T, Morimoto A, et al. Recent
developments in the management of haemophagocytic
lymphohistiocytosis. Expert Opin Pharmacother
2001;2:1437-48
2)Imashuku S, Hibi S, Sako M, et al. Soluble interleukin2 receptor: a useful prognostic factor for patients with
hemophagocytic lymphohistiocytosis. Blood 1995,
86:4706-7 1)
3)Ravelli A: Macrophage activation syndrome. Curr
Opin Rheumatol 2002;14:548-52
4)Osugi Y, Hara J, Tagawa S, et al. Cytokine
production regulating Th1 and Th2 cytokines in
hemophagocytic lymphohistiocytosis. Blood 1997;
89: 4100-3
5)Teruya-Feldstein J, Setsuda J, Yao X, et al. MIP-1
expression in tissues from patients with
h emo p h a g o c y ti c s y n d r ome . La b I n v e st
1999;79:1583-90
6)Schneider EM, Lorenz I, Müller-Rosenberger M, et
al. Hemophagocytic lymphohistiocytosis is associated
with deficiencies of cellular cytolysis but normal
expression of transcripts relevant to killer-cellinducedapoptosis. Blood 2002;100:2891-8
7)Janka GE, Schneider EM. Modern management of
children with haemophagocytic lymphohistiocytosis.
Br J Haematol 2004;124:4-14
8)Janka GE: Hemophagocytic syndromes. Blood Rev
2007;21:245-53
9)Henter JI, Elinder G. Incidence in Sweden and clinical
f e a t u r e s o f f a m i l i a l h e m o p h a g o c y t i c
lymphohistiocytosis. Acta Paediatr Scand 1991;80:428-
35
10)Gurgey A, Gogus S, Ozyurek E et al. Primary
hemophagocytic lymphohistiocytosis in Turkish
children. Pediatr Hematol Oncol 2003;20:367–71
11)Behrens EM, Canna SW, Slade K, et al: Repeated
TLR9 stimulation results in macrophage activation
syndrome-like disease in mice. J Clin Invest
2011;121:2264-771)
12)De Saint Basile G, Fischer A. Defective cytotoxic
granule-mediated cell death pathway impairs T
lymphocyte homeostasis. Curr Opin Rheumatol
2003;15:436-45
13)Zhang K, Jordan MB, Marsh RA, et al:
Hypomorphic mutations in PRF1, MUNC13-4, and
STXBP2 are associated with adult-onset familial
hemophagocytic lymphohistiocytosis. Blood
2011;118:5794-98
14)Clementi R, Emmi L, Maccario R, et al. Adult onset
and atypical presentation of hemophagocytic
lymphohistiocytosis in siblings carrying PRF1
mutations. Blood 2002;100:2266-67
15)Ansuini V, Rigante D, Esposito S. Debate around
infection- dependent hemophagocytic syndrome in
paediatrics. BMC Infectious Diseases 2013;13:15-23
16)Henter JI, Ehrnst A, Andersson J, Elinder G. Familial
hemophagocytic lymphohistiocytosis and viral
infections. Acta Paediatr 1993;82:369- 72
17)Rajagopala S, Singh N. Diagnosing and treating
hemophagocytic lymphohistiocytosis in the tropics:
Systematic review from the indian subcontinent. Acta
Medica Academica 2012;41:161-174
18)De Saint Basile G, Menasche G, Fischer A. Molecular
mechanisms of biogenesis and exocytosis of cytotoxic
granules. Nat Rev Immunol 2010;10:568-79
19)Katano H, Cohen JI. Perforin and lymphohistiocytic
proliferative disorders. Br J Haematol 2005;128:739-50
1)
20)Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al.
Perforin gene defects in familial hemophagocytic
lymphohistiocytosis. Science 1999; 286:1957-9
21)Menasche G, Feldmann J, Fischer A, et al. Primary
hemophagocytic syndromes point to a direct link
between lymphocyte cytotoxicity and homeostasis.
Immunol Rev 2005;203:165-79
22)Zur Stadt U, Schmidt S, Kasper B, et al. Linkage of
familial hemophagocytic lymphohistiocytosis (FHL)
type-4 to chromosome 6q24 and identification of
mutations in syntaxin 11. Hum Mol Genet 2005;14:827-
34
23)Brochetta C, Vita F, Tiwari N, et al. Involvement of
Munc18 isoforms in the regulation of granule
exocytosis in neutrophils. Biochim. Biophys. Acta.
2008;1783:1781-91
24)Zur Stadt U, Rohr J, Seifert W, et al. Familial
hemophagocytic lymphohistiocytosis type 5 (FHL-5)
is caused by mutations in Munc18-2 and impaired
binding to syntaxin 11. Am J Hum Genet 2009;85:482-
92
Meeths M,
25)Entesarian M, Al-Herz W, et al. Spectrum of
clinical presentations in familial hemophagocytic
lymphohistiocytosis type 5 patients with mutations in
STXBP2. Blood. 2010;116:2635-43
26)Janka G: Hemophagocytic lymphohistiocytosis:
when the immune system runs amok. Klin Pediatr
2009;221:278-285
27)Machaczka M, Vaktnas J, Klimkowska M, et al.
Ma lignancy- a ssoc i a t ed hemophagocyti c
lymphohistiocytosis in adults: a retrospective
population- based analysis from a single center. Leuk
Lymphoma 2011;52:613-191)
28)Bryceson YT, Pende D, Maul-Pavicic A, et al. A
prospective evaluation of degranulation assays in the
rapid diagnosis of familial hemophagocytic syndromes.
Blood 2012;119:2754-63
29)Lartigue A, Courville P, Auquit I, et al. Role of
TLR9 in anti- nucleosome and anti-DNA antibody
production in lpr mutation-induced murine lupus. J
Immunol 2006;177:1349-54
30)Fisman DN. Hemophagocytic syndromes and
infection. Emerg Infect Dis 2000;6:601-8
31)Rigante D, De Rosa G, Bertoni B, et al. Large
pericardial effusion requiring pericardiocentesis as
cardinal sign of macrophage activation syndrome in
systemic onset juvenile idiopathic arthritis.
Rheumatol Int 2007;27:767-70
32)Janka G, Imashuku S, Elinder G, et al. Infection
and malignancy associated hemophagocytic
s y n d r ome s. Se c o n d a r y h emo p h a g o c y ti c
lymphohistiocytosis. Hematol Oncol Clin North Am
1998;12:435-44
33)Wong K, Chan JK. Reactive hemophagocytic
syndrome-a clinicopathologic study of 40 patients in
an oriental population. Am J Med 1992;93:177-80
34)Henter JI, Nennesmo I. Neuropathologic findings
and neurologic symptoms in twenty-three children
with hemophagocytic lymphohistiocytosis. J Pediatr
1997;130:358-65
35)Haddad E, Sulis ML, Jabado N, et al. Frequency
and severity of central nervous system lesions in
hemophagocytic lymphohistiocytosis. Blood
1997;89:794-8001)
3 6 )Gu rg e y A, Ay t a c S, Ba lt a G, e t a l.
Lymphohistiocytosis Central Nervous System
Involvement in Turkish Children With Primary
Hemophagocytic. J Child Neurol 2008;23:1293-99
37)Janabi N, Chabrier S, Tardieu M. Endogenous
nitric oxide activates prostaglandin F2a production in
human microglial cells but not in astrocytes. J
Immunol 1996;157:2129
38)Ören H. Hemofagositik Sendrom. Türk Çocuk
Hematoloji Dergisi 2007;1:7-13
39)Horne A, Trottestam H, Aricò M, et al. Frequency
and spectrum of central nervous system involvement in
1 9 3 c h i l d r e n w i t h h a e m o p h a g o c y t i c
lymphohistiocytosis. Br J Haematol 2008;140:327-35
40)Yang S, Zhang L, Jia C, et al. Frequency and
development of CNS involvement in Chinese children
with hemophagocytic lymphohistiocytosis. Pediatr
Blood Cancer 2010;54:408-15
41)J anka GE. Famili a l ha emophagocyti c
lymphohistiocytosis. Eur tion of graft failure by a
monoclonal antibody (anti-LFA-1-CD11a). J Pediatr
1983;140:221
Tardieu M,
42)Lacroix C, Neven B, et al. Progressive neurologic
dysfunctions 20 years after allogeneic bone marrow
transplantation for Chediak- Higashi syndrome. Blood
2005;106:40-42
43)Rostasy K, Kolb R, Pohl D, et al. CNS disease as the
ma i n ma n if e st a t i o n o f h emo p h a g o c y t i c
lymphohistiocytosis in two children. Neuropediatrics
2004;35:45-91)
44)Deiva K, Mahlaoui N, Beaudonnet F, et al. CNS
involvement at the onset of primary hemophagocytic
lymphohistiocytosis. Neurology 2012;78:1150-56
Kim MM
45)Yum MS, Choi HW, et al. Central nervous system
(CNS) involvement is a critical prognostic factor for
hemophagocytic lymphohistiocytosis. Korean J
Hematol 2012;47:273-80
46)Hirst WJ, Layton DM, Singh S, et al.
Haemophagocytic lymphohistiocytosis: experience at
two U.K. centres. Br J Haematol 1994;88:731-39
Ramachandran B,
47)Balasubramanian S, Abhishek N, et al. Profile of
hemophagocytic lymphohistiocytosis in children in a
tertiary care hospital in India. Indian Pediatr
2011;48:31-5
48)Kieslich M, Vecchi M, Driever PH, et al. Acute
encephalopathy as a primary manifestation of
hemophagocytic lymphohistiocytosis. Dev Med Child
Neurol 2001;43:555-58
49)Thompson PA, Allen CE, Horton T, et al. Severe
neurologic sideeffects in patients being treated for
hemophagocytic lymphohistiocytosis. Pediatr Blood
Cancer 2009;52:621-5
5 0 ) F i l i p o v i c h A H . H e m o p h a g o c y t i c
lymphohistiocytosis (HLH) and related disorders.
Hematology Am Soc Hematol Educ Program.
2009:127-31
51)Palazzi DL, McClain KL, Kaplan SL.
Hemophagocytic syndrome in children: an important
diagnostic consideration in fever of unknown origin.
Clin Infect Dis 2003;36:306-121)
52)Arico M, Janka G, Fischer A, et al. Hemophagocytic
lymphohistiocytosis: report of 122 children from the
International Registry. FHL Study Group of the
Histiocyte Society. Leukemia 1996;10:197-203
53)Niece JA, Rogers ZR, Ahmad N, et al.
Hemophagocytic lymphohistiocytosis in Texas:
observations on ethnicity and race. Pediatr Blood Cancer
2010;54:424-28
54)Ost A, Nilsson-Ardnor S, Henter JI. Autopsy findings
i n 2 7 c h i l d r e n w i t h h a e m o p h a g o c y t i c
lymphohistiocytosis. Histopathology 1998;32:310-16
55)Stapp J, Wilkerson S, Stewart D, et al. Fulminant
neonatal liver failure in siblings: probable congenital
hemophagocytic lymphohistiocytosis. Pediatr Dev Pathol
2006;9:239-44
56)Ouachee-Chardin M, Elie C, De Saint BG, et al.
Hematopoietic stem cell transplantation in
hemophagocytic lymphohistiocytosis: a single-center
report of 48 patients. Pediatrics. 2006;117:e743-e750
57)Fitzgerald N, McClain KL. Imaging characteristics of
hemophagocytic lymphohistiocytosis. Pediatr Radiol
2003;33:392-401
58)Pa l a z z i DL, McCl a in KL, Kapl an SL.
Hemophagocytic syndrome in children: an important
diagnostic consideration in fever of unknown origin. Clin
Infect Dis 2003;36:306-12
59)Feldmann J, Menasche G, Callebaut I, et al. Severe
and progressive encephalitis as a presenting
manifestation of a novel missense perforin mutation and
impaired cytolytic activity. Blood 2005;105:2658-
631)
60)Gholam C, Grigoriadou S, Gilmour KC, et al. Familial
haemophagocytic lymphohistiocytosis: advances in the
genetic basis, diagnosis and management. Clin Exper
Immunol 2011;163: 271-83
61)Gupta A, Weitzman S, Abdelhaleem M. The role of
hemophagocytosis in bone marrow aspirates in the
diagnosis of hemophagocytic lymphohistiocytosis.
Pediatr Blood Cancer 2008;50:192-94
62)Kuwata K, Yamada S, Kinuwaki E, et al. Peripheral
hemophagocytosis: an early indicator of advanced
systemic inflammatory response syndrome/
hemophagocytic syndrome. Shock 2006;25:344-50
63)Gauvin F, Toledano B, Champagne J, et al. Reactive
hemophagocytic syndrome presenting as a component of
multiple organ dysfunction syndrome. Crit Care Med
2000;28:3341-45
64)Turtzo LC, Lin DDM, Hartung H, et al. A Neurologic
Pr e s ent a tion of Famili a l Hemophagocyti c
Lymphohistiocytosis Which Mimicked Septic Emboli to
the Brain. J Child Neurol 2007;22:863-64
65)Schaer DJ, Schleiffenbaum B, Kurrer M, et al. Soluble
hemoglobin- haptoglobin scavenger receptor CD163 as a
lineagespecific marker in the reactive hemophagocytic
syndrome. Eur J Haematol 2005;74:6-10
66) Bleesing J, Prada A, Siegel DM, et al. The diagnostic
significance of soluble CD163 and soluble interleukin-2
receptor a-chain in macrophage activation syndrome and
unrelated new-onset systemic juvenile idiopathic
arthritis. Arthritis Rheum 2007;56:965-711)
67)Rooms L, Fitzgerald N, McClain KL. Hemophagocytic
lymphohistiocytosis masquerading as child abuse:
presentation of three cases and review of central nervous
system findings in hemophagocytic lymphohistiocytosis.
Pediatrics 2003;111:636-40
68)Chung TW. CNS Involvement in hemophagocytic
lymphohistiocytosis: CT and MR findings. Korean J Radiol 2007;8:78-81
69)Goo HW, Weon YC. A spectrum of
neuroradiological findings in children with
haemophagocytic lymphohistiocytosis. Pediatr
Radiol 2007;37:1110-17
70)Tang YM, Xu XJ. Advances in Hemophagocytic
Lymphohistiocytosis: Pathogenesis, Early
Diagnosis/Differential Diagnosis, and Treatment. The
Scientific World J 2011;11:697-708
71)Munoz Ruano MM, Castillo M. Brain CT and MR
i m a g i n g i n f a m i l i a l h e m o p h a g o c y t i c
lymphohistiocytosis. AJR Am J Roentgenol
1998;170:802-5
72)Jordan MB, Allen CE, Weitzman S, et al. How I treat
hemophagocytic lymphohistiocytosis. Blood
2011;118:4041-52
73)Bör Ö. Çocukluk Çağında Hemofagositik
Sendromlar. Güncel Pediatri 2006;4:100-1
74)Bode SFN, Lehmberg K, Maul-Pavicic A, et al.
Recent advances in the diagnosis and treatment of
hemophagocytic lymphohistiocytosis. Arthritis
Research&Therapy 2012;14:213-16
75)Gupta S, Weitzman S. Primary and secondary
hemophagocytic lymphohistiocytosis: clinical
features, pathogenesis and therapy. Expert Rev Clin
Immunol 2010;6:137 541)
76)Janka GE. Familial and acquired hemophagocytic
lymphohistiocytosis. Eur J Pediatr 2007;166:95-109
77)Trottestam H, Berglof E, Horne A, et al. Risk factors
for early death in children with haemophagocytic
lymphohistiocytosis. Acta Paediatr 2011;101:313- 18
78)Sung L, King SM, Carcao M, et al. Adverse outcomes
in primary hemophagocytic lymphohistiocytosis. J
Pediatr Hematol Oncol 2002;24:550-54