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 sea...
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E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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Enthalten in: Journal of clinical immunology - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981, 40(2020), 6 vom: 07. Juli, Seite 901-916 |
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| Übergeordnetes Werk: |
volume:40 ; year:2020 ; number:6 ; day:07 ; month:07 ; pages:901-916 |
| Links: |
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| DOI / URN: |
10.1007/s10875-020-00814-6 |
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| Katalog-ID: |
SPR040533271 |
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| 520 | |a 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. | ||
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| 650 | 4 | |a CNS disease |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CNS inflammation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a therapy |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Heeg, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Patrick K. |e verfasserin |4 aut | |
| 700 | 1 | |a Hines, Melissa |e verfasserin |4 aut | |
| 700 | 1 | |a Khojah, Amer |e verfasserin |4 aut | |
| 700 | 1 | |a Klein-Gitelman, Marisa |e verfasserin |4 aut | |
| 700 | 1 | |a Talano, Julie-An |e verfasserin |4 aut | |
| 700 | 1 | |a Speckmann, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Touzot, Fabien |e verfasserin |4 aut | |
| 700 | 1 | |a Lankester, Arjan |e verfasserin |4 aut | |
| 700 | 1 | |a Legger, Geertje E. |e verfasserin |4 aut | |
| 700 | 1 | |a Rivière, Jacques G. |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia-Prat, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Alonso, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Putti, Maria C. |e verfasserin |4 aut | |
| 700 | 1 | |a Lehmberg, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Maier, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a El Chazli, Yasmine |e verfasserin |4 aut | |
| 700 | 1 | |a Elmaksoud, Marwa Abd |e verfasserin |4 aut | |
| 700 | 1 | |a Astigarraga, Itziar |e verfasserin |4 aut | |
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| 700 | 1 | |a Worth, Austen |e verfasserin |4 aut | |
| 700 | 1 | |a Wassmer, Evangeline |e verfasserin |4 aut | |
| 700 | 1 | |a Schmitt, Erica G. |e verfasserin |4 aut | |
| 700 | 1 | |a Warren, Julia T. |e verfasserin |4 aut | |
| 700 | 1 | |a Bednarski, Jeffrey J. |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Salah |e verfasserin |4 aut | |
| 700 | 1 | |a Chiang, Kuang-Yueh |e verfasserin |4 aut | |
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| 700 | 1 | |a Henry, Michael M. |e verfasserin |4 aut | |
| 700 | 1 | |a Holland, Steven M. |e verfasserin |4 aut | |
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| 700 | 1 | |a Haddad, Elie |e verfasserin |4 aut | |
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10.1007/s10875-020-00814-6 doi (DE-627)SPR040533271 (SPR)s10875-020-00814-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Blincoe, Annaliesse verfasserin aut Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 Heeg, Maximilian verfasserin aut Campbell, Patrick K. verfasserin aut Hines, Melissa verfasserin aut Khojah, Amer verfasserin aut Klein-Gitelman, Marisa verfasserin aut Talano, Julie-An verfasserin aut Speckmann, Carsten verfasserin aut Touzot, Fabien verfasserin aut Lankester, Arjan verfasserin aut Legger, Geertje E. verfasserin aut Rivière, Jacques G. verfasserin aut Garcia-Prat, Marina verfasserin aut Alonso, Laura verfasserin aut Putti, Maria C. verfasserin aut Lehmberg, Kai verfasserin aut Maier, Sarah verfasserin aut El Chazli, Yasmine verfasserin aut Elmaksoud, Marwa Abd verfasserin aut Astigarraga, Itziar verfasserin aut Kurjane, Natalja verfasserin aut Bulina, Inita verfasserin aut Kenina, Viktorija verfasserin aut Bryceson, Yenan verfasserin aut Rascon, Jelena verfasserin aut Lortie, Anne verfasserin aut Goldstein, Gal verfasserin aut Booth, Claire verfasserin aut Worth, Austen verfasserin aut Wassmer, Evangeline verfasserin aut Schmitt, Erica G. verfasserin aut Warren, Julia T. verfasserin aut Bednarski, Jeffrey J. verfasserin aut Ali, Salah verfasserin aut Chiang, Kuang-Yueh verfasserin aut Krueger, Joerg verfasserin aut Henry, Michael M. verfasserin aut Holland, Steven M. verfasserin aut Marsh, Rebecca A. verfasserin aut Ehl, Stephan verfasserin aut Haddad, Elie verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 6 vom: 07. Juli, Seite 901-916 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:6 day:07 month:07 pages:901-916 https://dx.doi.org/10.1007/s10875-020-00814-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 6 07 07 901-916 |
| spelling |
10.1007/s10875-020-00814-6 doi (DE-627)SPR040533271 (SPR)s10875-020-00814-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Blincoe, Annaliesse verfasserin aut Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 Heeg, Maximilian verfasserin aut Campbell, Patrick K. verfasserin aut Hines, Melissa verfasserin aut Khojah, Amer verfasserin aut Klein-Gitelman, Marisa verfasserin aut Talano, Julie-An verfasserin aut Speckmann, Carsten verfasserin aut Touzot, Fabien verfasserin aut Lankester, Arjan verfasserin aut Legger, Geertje E. verfasserin aut Rivière, Jacques G. verfasserin aut Garcia-Prat, Marina verfasserin aut Alonso, Laura verfasserin aut Putti, Maria C. verfasserin aut Lehmberg, Kai verfasserin aut Maier, Sarah verfasserin aut El Chazli, Yasmine verfasserin aut Elmaksoud, Marwa Abd verfasserin aut Astigarraga, Itziar verfasserin aut Kurjane, Natalja verfasserin aut Bulina, Inita verfasserin aut Kenina, Viktorija verfasserin aut Bryceson, Yenan verfasserin aut Rascon, Jelena verfasserin aut Lortie, Anne verfasserin aut Goldstein, Gal verfasserin aut Booth, Claire verfasserin aut Worth, Austen verfasserin aut Wassmer, Evangeline verfasserin aut Schmitt, Erica G. verfasserin aut Warren, Julia T. verfasserin aut Bednarski, Jeffrey J. verfasserin aut Ali, Salah verfasserin aut Chiang, Kuang-Yueh verfasserin aut Krueger, Joerg verfasserin aut Henry, Michael M. verfasserin aut Holland, Steven M. verfasserin aut Marsh, Rebecca A. verfasserin aut Ehl, Stephan verfasserin aut Haddad, Elie verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 6 vom: 07. Juli, Seite 901-916 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:6 day:07 month:07 pages:901-916 https://dx.doi.org/10.1007/s10875-020-00814-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 6 07 07 901-916 |
| allfields_unstemmed |
10.1007/s10875-020-00814-6 doi (DE-627)SPR040533271 (SPR)s10875-020-00814-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Blincoe, Annaliesse verfasserin aut Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 Heeg, Maximilian verfasserin aut Campbell, Patrick K. verfasserin aut Hines, Melissa verfasserin aut Khojah, Amer verfasserin aut Klein-Gitelman, Marisa verfasserin aut Talano, Julie-An verfasserin aut Speckmann, Carsten verfasserin aut Touzot, Fabien verfasserin aut Lankester, Arjan verfasserin aut Legger, Geertje E. verfasserin aut Rivière, Jacques G. verfasserin aut Garcia-Prat, Marina verfasserin aut Alonso, Laura verfasserin aut Putti, Maria C. verfasserin aut Lehmberg, Kai verfasserin aut Maier, Sarah verfasserin aut El Chazli, Yasmine verfasserin aut Elmaksoud, Marwa Abd verfasserin aut Astigarraga, Itziar verfasserin aut Kurjane, Natalja verfasserin aut Bulina, Inita verfasserin aut Kenina, Viktorija verfasserin aut Bryceson, Yenan verfasserin aut Rascon, Jelena verfasserin aut Lortie, Anne verfasserin aut Goldstein, Gal verfasserin aut Booth, Claire verfasserin aut Worth, Austen verfasserin aut Wassmer, Evangeline verfasserin aut Schmitt, Erica G. verfasserin aut Warren, Julia T. verfasserin aut Bednarski, Jeffrey J. verfasserin aut Ali, Salah verfasserin aut Chiang, Kuang-Yueh verfasserin aut Krueger, Joerg verfasserin aut Henry, Michael M. verfasserin aut Holland, Steven M. verfasserin aut Marsh, Rebecca A. verfasserin aut Ehl, Stephan verfasserin aut Haddad, Elie verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 6 vom: 07. Juli, Seite 901-916 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:6 day:07 month:07 pages:901-916 https://dx.doi.org/10.1007/s10875-020-00814-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 6 07 07 901-916 |
| allfieldsGer |
10.1007/s10875-020-00814-6 doi (DE-627)SPR040533271 (SPR)s10875-020-00814-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Blincoe, Annaliesse verfasserin aut Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 Heeg, Maximilian verfasserin aut Campbell, Patrick K. verfasserin aut Hines, Melissa verfasserin aut Khojah, Amer verfasserin aut Klein-Gitelman, Marisa verfasserin aut Talano, Julie-An verfasserin aut Speckmann, Carsten verfasserin aut Touzot, Fabien verfasserin aut Lankester, Arjan verfasserin aut Legger, Geertje E. verfasserin aut Rivière, Jacques G. verfasserin aut Garcia-Prat, Marina verfasserin aut Alonso, Laura verfasserin aut Putti, Maria C. verfasserin aut Lehmberg, Kai verfasserin aut Maier, Sarah verfasserin aut El Chazli, Yasmine verfasserin aut Elmaksoud, Marwa Abd verfasserin aut Astigarraga, Itziar verfasserin aut Kurjane, Natalja verfasserin aut Bulina, Inita verfasserin aut Kenina, Viktorija verfasserin aut Bryceson, Yenan verfasserin aut Rascon, Jelena verfasserin aut Lortie, Anne verfasserin aut Goldstein, Gal verfasserin aut Booth, Claire verfasserin aut Worth, Austen verfasserin aut Wassmer, Evangeline verfasserin aut Schmitt, Erica G. verfasserin aut Warren, Julia T. verfasserin aut Bednarski, Jeffrey J. verfasserin aut Ali, Salah verfasserin aut Chiang, Kuang-Yueh verfasserin aut Krueger, Joerg verfasserin aut Henry, Michael M. verfasserin aut Holland, Steven M. verfasserin aut Marsh, Rebecca A. verfasserin aut Ehl, Stephan verfasserin aut Haddad, Elie verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 6 vom: 07. Juli, Seite 901-916 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:6 day:07 month:07 pages:901-916 https://dx.doi.org/10.1007/s10875-020-00814-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 6 07 07 901-916 |
| allfieldsSound |
10.1007/s10875-020-00814-6 doi (DE-627)SPR040533271 (SPR)s10875-020-00814-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.45 bkl Blincoe, Annaliesse verfasserin aut Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 Heeg, Maximilian verfasserin aut Campbell, Patrick K. verfasserin aut Hines, Melissa verfasserin aut Khojah, Amer verfasserin aut Klein-Gitelman, Marisa verfasserin aut Talano, Julie-An verfasserin aut Speckmann, Carsten verfasserin aut Touzot, Fabien verfasserin aut Lankester, Arjan verfasserin aut Legger, Geertje E. verfasserin aut Rivière, Jacques G. verfasserin aut Garcia-Prat, Marina verfasserin aut Alonso, Laura verfasserin aut Putti, Maria C. verfasserin aut Lehmberg, Kai verfasserin aut Maier, Sarah verfasserin aut El Chazli, Yasmine verfasserin aut Elmaksoud, Marwa Abd verfasserin aut Astigarraga, Itziar verfasserin aut Kurjane, Natalja verfasserin aut Bulina, Inita verfasserin aut Kenina, Viktorija verfasserin aut Bryceson, Yenan verfasserin aut Rascon, Jelena verfasserin aut Lortie, Anne verfasserin aut Goldstein, Gal verfasserin aut Booth, Claire verfasserin aut Worth, Austen verfasserin aut Wassmer, Evangeline verfasserin aut Schmitt, Erica G. verfasserin aut Warren, Julia T. verfasserin aut Bednarski, Jeffrey J. verfasserin aut Ali, Salah verfasserin aut Chiang, Kuang-Yueh verfasserin aut Krueger, Joerg verfasserin aut Henry, Michael M. verfasserin aut Holland, Steven M. verfasserin aut Marsh, Rebecca A. verfasserin aut Ehl, Stephan verfasserin aut Haddad, Elie verfasserin aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 40(2020), 6 vom: 07. Juli, Seite 901-916 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:40 year:2020 number:6 day:07 month:07 pages:901-916 https://dx.doi.org/10.1007/s10875-020-00814-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.45 ASE AR 40 2020 6 07 07 901-916 |
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Enthalten in Journal of clinical immunology 40(2020), 6 vom: 07. Juli, Seite 901-916 volume:40 year:2020 number:6 day:07 month:07 pages:901-916 |
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Enthalten in Journal of clinical immunology 40(2020), 6 vom: 07. Juli, Seite 901-916 volume:40 year:2020 number:6 day:07 month:07 pages:901-916 |
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Familial hemophagocytic lymphohistiocytosis CNS disease CNS inflammation therapy |
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Blincoe, Annaliesse @@aut@@ Heeg, Maximilian @@aut@@ Campbell, Patrick K. @@aut@@ Hines, Melissa @@aut@@ Khojah, Amer @@aut@@ Klein-Gitelman, Marisa @@aut@@ Talano, Julie-An @@aut@@ Speckmann, Carsten @@aut@@ Touzot, Fabien @@aut@@ Lankester, Arjan @@aut@@ Legger, Geertje E. @@aut@@ Rivière, Jacques G. @@aut@@ Garcia-Prat, Marina @@aut@@ Alonso, Laura @@aut@@ Putti, Maria C. @@aut@@ Lehmberg, Kai @@aut@@ Maier, Sarah @@aut@@ El Chazli, Yasmine @@aut@@ Elmaksoud, Marwa Abd @@aut@@ Astigarraga, Itziar @@aut@@ Kurjane, Natalja @@aut@@ Bulina, Inita @@aut@@ Kenina, Viktorija @@aut@@ Bryceson, Yenan @@aut@@ Rascon, Jelena @@aut@@ Lortie, Anne @@aut@@ Goldstein, Gal @@aut@@ Booth, Claire @@aut@@ Worth, Austen @@aut@@ Wassmer, Evangeline @@aut@@ Schmitt, Erica G. @@aut@@ Warren, Julia T. @@aut@@ Bednarski, Jeffrey J. @@aut@@ Ali, Salah @@aut@@ Chiang, Kuang-Yueh @@aut@@ Krueger, Joerg @@aut@@ Henry, Michael M. @@aut@@ Holland, Steven M. @@aut@@ Marsh, Rebecca A. @@aut@@ Ehl, Stephan @@aut@@ Haddad, Elie @@aut@@ |
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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. 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Blincoe, Annaliesse |
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Blincoe, Annaliesse ddc 610 bkl 44.45 misc Familial hemophagocytic lymphohistiocytosis misc CNS disease misc CNS inflammation misc therapy Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis |
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610 ASE 44.45 bkl Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis Familial hemophagocytic lymphohistiocytosis (dpeaa)DE-He213 CNS disease (dpeaa)DE-He213 CNS inflammation (dpeaa)DE-He213 therapy (dpeaa)DE-He213 |
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Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis |
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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 |
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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 |
| abstract |
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. |
| abstractGer |
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. |
| abstract_unstemmed |
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. |
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| doi_str |
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| up_date |
2024-07-03T16:37:32.483Z |
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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. 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| score |
7.400529 |