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Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis

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Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis. / Blincoe, Annaliesse; Heeg, Maximilian; Campbell, Patrick K; Hines, Melissa; Khojah, Amer; Klein-Gitelman, Marisa; Talano, Julie-An; Speckmann, Carsten; Touzot, Fabien; Lankester, Arjan; Legger, Geertje E; Rivière, Jacques G; Garcia-Prat, Marina; Alonso, Laura; Putti, Maria C; Lehmberg, Kai; Maier, Sarah; El Chazli, Yasmine; Elmaksoud, Marwa Abd; Astigarraga, Itziar; Kurjane, Natalja; Bulina, Inita; Kenina, Viktorija; Bryceson, Yenan; Rascon, Jelena; Lortie, Anne; Goldstein, Gal; Booth, Claire; Worth, Austen; Wassmer, Evangeline; Schmitt, Erica G; Warren, Julia T; Bednarski, Jeffrey J; Ali, Salah; Chiang, Kuang-Yueh; Krueger, Joerg; Henry, Michael M; Holland, Steven M; Marsh, Rebecca A; Ehl, Stephan; Haddad, Elie.

In: J CLIN IMMUNOL, Vol. 40, No. 6, 08.2020, p. 901-916.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Blincoe, A, Heeg, M, Campbell, PK, Hines, M, Khojah, A, Klein-Gitelman, M, Talano, J-A, Speckmann, C, Touzot, F, Lankester, A, Legger, GE, Rivière, JG, Garcia-Prat, M, Alonso, L, Putti, MC, Lehmberg, K, Maier, S, El Chazli, Y, Elmaksoud, MA, Astigarraga, I, Kurjane, N, Bulina, I, Kenina, V, Bryceson, Y, Rascon, J, Lortie, A, Goldstein, G, Booth, C, Worth, A, Wassmer, E, Schmitt, EG, Warren, JT, Bednarski, JJ, Ali, S, Chiang, K-Y, Krueger, J, Henry, MM, Holland, SM, Marsh, RA, Ehl, S & Haddad, E 2020, 'Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis', J CLIN IMMUNOL, vol. 40, no. 6, pp. 901-916. https://doi.org/10.1007/s10875-020-00814-6

APA

Blincoe, A., Heeg, M., Campbell, P. K., Hines, M., Khojah, A., Klein-Gitelman, M., Talano, J-A., Speckmann, C., Touzot, F., Lankester, A., Legger, G. E., Rivière, J. G., Garcia-Prat, M., Alonso, L., Putti, M. C., Lehmberg, K., Maier, S., El Chazli, Y., Elmaksoud, M. A., ... Haddad, E. (2020). Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis. J CLIN IMMUNOL, 40(6), 901-916. https://doi.org/10.1007/s10875-020-00814-6

Vancouver

Blincoe A, Heeg M, Campbell PK, Hines M, Khojah A, Klein-Gitelman M et al. Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis. J CLIN IMMUNOL. 2020 Aug;40(6):901-916. https://doi.org/10.1007/s10875-020-00814-6

Bibtex

@article{2424fe8ddbc249aca77af0a44a8b7cf2,
title = "Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis",
abstract = "Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.",
keywords = "Adolescent, Adult, Age of Onset, Alleles, Biomarkers, Biopsy, Child, Child, Preschool, Disease Progression, Female, Genetic Predisposition to Disease, Genotype, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Infant, Lymphohistiocytosis, Hemophagocytic/diagnosis, Magnetic Resonance Imaging, Male, Mutation, Neuroimaging, Phenotype, Symptom Assessment, Young Adult",
author = "Annaliesse Blincoe and Maximilian Heeg and Campbell, {Patrick K} and Melissa Hines and Amer Khojah and Marisa Klein-Gitelman and Julie-An Talano and Carsten Speckmann and Fabien Touzot and Arjan Lankester and Legger, {Geertje E} and Rivi{\`e}re, {Jacques G} and Marina Garcia-Prat and Laura Alonso and Putti, {Maria C} and Kai Lehmberg and Sarah Maier and {El Chazli}, Yasmine and Elmaksoud, {Marwa Abd} and Itziar Astigarraga and Natalja Kurjane and Inita Bulina and Viktorija Kenina and Yenan Bryceson and Jelena Rascon and Anne Lortie and Gal Goldstein and Claire Booth and Austen Worth and Evangeline Wassmer and Schmitt, {Erica G} and Warren, {Julia T} and Bednarski, {Jeffrey J} and Salah Ali and Kuang-Yueh Chiang and Joerg Krueger and Henry, {Michael M} and Holland, {Steven M} and Marsh, {Rebecca A} and Stephan Ehl and Elie Haddad",
year = "2020",
month = aug,
doi = "10.1007/s10875-020-00814-6",
language = "English",
volume = "40",
pages = "901--916",
journal = "J CLIN IMMUNOL",
issn = "0271-9142",
publisher = "Springer New York",
number = "6",

}

RIS

TY - JOUR

T1 - Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis

AU - Blincoe, Annaliesse

AU - Heeg, Maximilian

AU - Campbell, Patrick K

AU - Hines, Melissa

AU - Khojah, Amer

AU - Klein-Gitelman, Marisa

AU - Talano, Julie-An

AU - Speckmann, Carsten

AU - Touzot, Fabien

AU - Lankester, Arjan

AU - Legger, Geertje E

AU - Rivière, Jacques G

AU - Garcia-Prat, Marina

AU - Alonso, Laura

AU - Putti, Maria C

AU - Lehmberg, Kai

AU - Maier, Sarah

AU - El Chazli, Yasmine

AU - Elmaksoud, Marwa Abd

AU - Astigarraga, Itziar

AU - Kurjane, Natalja

AU - Bulina, Inita

AU - Kenina, Viktorija

AU - Bryceson, Yenan

AU - Rascon, Jelena

AU - Lortie, Anne

AU - Goldstein, Gal

AU - Booth, Claire

AU - Worth, Austen

AU - Wassmer, Evangeline

AU - Schmitt, Erica G

AU - Warren, Julia T

AU - Bednarski, Jeffrey J

AU - Ali, Salah

AU - Chiang, Kuang-Yueh

AU - Krueger, Joerg

AU - Henry, Michael M

AU - Holland, Steven M

AU - Marsh, Rebecca A

AU - Ehl, Stephan

AU - Haddad, Elie

PY - 2020/8

Y1 - 2020/8

N2 - Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

AB - Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly with ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory disease fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected in PRF1 in 23 patients (61%), RAB27A in 10 (26%), UNC13D in 3 (8%), LYST in 1 (3%), and STXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3 months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 non-transplanted patients, only 3 improved or had stable disease, one relapsed, and 10 died. Isolated CNS-HLH is a rare and often overlooked cause of inflammatory brain disease. HLH-directed therapy followed by HSCT seems to improve survival and outcome.

KW - Adolescent

KW - Adult

KW - Age of Onset

KW - Alleles

KW - Biomarkers

KW - Biopsy

KW - Child

KW - Child, Preschool

KW - Disease Progression

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Humans

KW - Infant

KW - Lymphohistiocytosis, Hemophagocytic/diagnosis

KW - Magnetic Resonance Imaging

KW - Male

KW - Mutation

KW - Neuroimaging

KW - Phenotype

KW - Symptom Assessment

KW - Young Adult

U2 - 10.1007/s10875-020-00814-6

DO - 10.1007/s10875-020-00814-6

M3 - SCORING: Journal article

C2 - 32638196

VL - 40

SP - 901

EP - 916

JO - J CLIN IMMUNOL

JF - J CLIN IMMUNOL

SN - 0271-9142

IS - 6

ER -