NEUROLOGICAL INVOLVEMENT IN EVANS SYNDROME AND CHRONIC HEMOLYTIC AUTOIMMUNE ANEMIA OF CHILDREN: DESCRIPTION, EVOLUTION AND GENETICS
Author(s): ,
Thomas Pincez
Affiliations:
Department of Onco-Hematology,APHP - Hôpital Trousseau,Paris,France
,
Nathalie Aladjidi
Affiliations:
Department of Pediatric Hematology,University Hospital of Bordeaux,Bordeaux,France;Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE),University Hospital of Bordeaux,Bordeaux,France;CIC 1401 - INSERM CICP,University Hospital of Bordeaux,Bordeaux,France
,
Helder Fernandes
Affiliations:
Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE),University Hospital of Bordeaux,Bordeaux,France
,
Hubert Ducou Le Pointe
Affiliations:
Pediatric Radiology department,APHP - Hôpital Trousseau,Paris,France
,
Bénédicte Neven
Affiliations:
Pediatric Hematology-Immunology Department,APHP- Hôpital Necker-Enfants Malades,Paris,France;Immunogenetics of Pediatric Autoimmune Diseases - INSERM UMR-S1163,Institut Imagine, Université Paris Descartes,Paris,France
,
Guy Leverger
Affiliations:
Department of Onco-Hematology,APHP - Hôpital Trousseau,Paris,France
,
Thierry Leblanc
Affiliations:
Department of Hematology,APHP - Hôpital Robert Debré,Paris,France
,
Gérard Michel
Affiliations:
Department of Pediatric Hematology,University Hospital Timone Enfants,Marseille,France
,
Marlène Pasquet
Affiliations:
Department of Pediatric Hematology,University Hospital of Toulouse,Toulouse,France
,
Olivier Hermine
Affiliations:
Department of Hematology,APHP- Hôpital Necker-Enfants Malades,Paris,France
,
Alexis Mathian
Affiliations:
Department of Internal Medicine,APHP - Hôpital de la Pitié-Salpétrière,Paris,France
,
Hélène Zéphir
Affiliations:
Clinique Neurologique, Pôle des Neurosciences et de l'Appareil Locomoteur,,Université de Lille,Lille,France
,
Mohamed Hamidou
Affiliations:
Department of Internal Medicine,University Hospital of Nantes,Nantes,France
,
Jean-Marc Durand
Affiliations:
Department of Internal Medicine,University Hospital Timone,Marseille,France
,
Yves Perel
Affiliations:
Department of Pediatric Hematology,University Hospital of Bordeaux,Bordeaux,France;Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE),University Hospital of Bordeaux,Bordeaux,France;CIC 1401 - INSERM CICP,University Hospital of Bordeaux,Bordeaux,France
,
Fréderic Rieux-Laucat
Affiliations:
Immunogenetics of Pediatric Autoimmune Diseases - INSERM UMR-S1163,Institut Imagine, Université Paris Descartes,Paris,France
Judith Landman-Parker
Affiliations:
Department of Onco-Hematology,APHP - Hôpital Trousseau,Paris,France
EHA Library. Pincez T. 06/24/17; 182003; P716
Dr. Thomas Pincez
Dr. Thomas Pincez
Contributions
Abstract

Abstract: P716

Type: Poster Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 17:30 - 19:00

Location: Poster area (Hall 7)

Background
Neurological involvement is poorly described in autoimmune cytopenias (AIC), containing immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). This association suggests an underlying primary immunodeficiency (PID).

Aims
To describe neurological involvement observed in autoimmune cytopenias, evolution under treatment and PID profiles in these patients.

Methods
OBS’CEREVANCE is a French nationwide prospective cohort including children with an AIC since 2004. Patients with a neurological involvement were analyzed excluding neurological symptoms related to a traumatism or isolated febrile seizures. Clinical, radiological and biological data were collected from primary centers. Centralized radiological review was performed. Genetic analyses were performed by Sanger gene sequencing or gene-panel based next generation sequencing.

Results
On October 2016, among the 1,167 patients of the cohort (371 AHAI, 615 ITP, 181 ES), a significant neurological involvement was observed in 8 patients from 7 centers. With a median (range) follow-up of 12 years (6-26.5), 7 children had ES (including autoimmune neutropenia in 5) and 1 child had isolated AIHA. Median age at initial cytopenia was 11.5 years (1.6-15.8). At the last follow-up point, AIC were in partial or complete remission for all patients. Neurological symptoms appeared with a mean delay of 6 years (2.5-18) after AIC onset. The symptomatology was: seizures (n=4), cranial nerve palsy (n=2), Brown-Sequard syndrome (n=2) and / or sensory neuronopathy (n=1). No infectious pathogens were identified. MRI showed multiple (n=6) or unique (n=2) inflammatory lesions with hyperintense T2 signal in all patients, gadolinium-enhancing lesions in 7 and perilesional edema in 5. Five patients had a total of 8 biopsies, which confirmed the inflammatory process with macrophagic (n=3) or lymphoplasmocytic (n=5) infiltrates. In 4 cases, a lymphocytic meningitis was associated. Non-neurological organ involvement was present in all patients, mainly pulmonary nodules (n=6) and lymphoproliferation (n=4). All patients had an abnormal immunophenotype, with T-cell (n=7) or B-cell (n=3) deficiency and hypogammaglobulinemia was present in 7 of the 8 cases. Patients have been given steroids (n=6), intravenous immunoglobulins (n=2) or immunosuppressive treatment (n=3, Ciclosporin, Mycophenolate Mofetil and Methotrexate), improving symptomatology and MRI for all. Five patients relapsed and 3 patients had an asymptomatic radiological progression. At the last follow up point, all patients had neurological sequels and 7 persisting radiological abnormalities. Four out of the 6 patients analyzed had a PID: 22q11.2 microdeletion (n=1), heterozygous CTLA mutation (n=2) or homozygous LRBA mutation (n=1).

Conclusion
Neurological involvement is a rare and severe late event in the course of childhood ES, or exceptionally AHAI, that may reveal various underlying PID. Complete imaging and pathology examination highlight a causative immune dysregulation and could guide specific therapeutic strategies.

Session topic: 31. Other Non-malignant hematopoietic disorders

Keyword(s): Immune thrombocytopenia (ITP), Immune deficiency, Childhood, Autoimmune hemolytic anemia (AIHA)

Abstract: P716

Type: Poster Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 17:30 - 19:00

Location: Poster area (Hall 7)

Background
Neurological involvement is poorly described in autoimmune cytopenias (AIC), containing immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). This association suggests an underlying primary immunodeficiency (PID).

Aims
To describe neurological involvement observed in autoimmune cytopenias, evolution under treatment and PID profiles in these patients.

Methods
OBS’CEREVANCE is a French nationwide prospective cohort including children with an AIC since 2004. Patients with a neurological involvement were analyzed excluding neurological symptoms related to a traumatism or isolated febrile seizures. Clinical, radiological and biological data were collected from primary centers. Centralized radiological review was performed. Genetic analyses were performed by Sanger gene sequencing or gene-panel based next generation sequencing.

Results
On October 2016, among the 1,167 patients of the cohort (371 AHAI, 615 ITP, 181 ES), a significant neurological involvement was observed in 8 patients from 7 centers. With a median (range) follow-up of 12 years (6-26.5), 7 children had ES (including autoimmune neutropenia in 5) and 1 child had isolated AIHA. Median age at initial cytopenia was 11.5 years (1.6-15.8). At the last follow-up point, AIC were in partial or complete remission for all patients. Neurological symptoms appeared with a mean delay of 6 years (2.5-18) after AIC onset. The symptomatology was: seizures (n=4), cranial nerve palsy (n=2), Brown-Sequard syndrome (n=2) and / or sensory neuronopathy (n=1). No infectious pathogens were identified. MRI showed multiple (n=6) or unique (n=2) inflammatory lesions with hyperintense T2 signal in all patients, gadolinium-enhancing lesions in 7 and perilesional edema in 5. Five patients had a total of 8 biopsies, which confirmed the inflammatory process with macrophagic (n=3) or lymphoplasmocytic (n=5) infiltrates. In 4 cases, a lymphocytic meningitis was associated. Non-neurological organ involvement was present in all patients, mainly pulmonary nodules (n=6) and lymphoproliferation (n=4). All patients had an abnormal immunophenotype, with T-cell (n=7) or B-cell (n=3) deficiency and hypogammaglobulinemia was present in 7 of the 8 cases. Patients have been given steroids (n=6), intravenous immunoglobulins (n=2) or immunosuppressive treatment (n=3, Ciclosporin, Mycophenolate Mofetil and Methotrexate), improving symptomatology and MRI for all. Five patients relapsed and 3 patients had an asymptomatic radiological progression. At the last follow up point, all patients had neurological sequels and 7 persisting radiological abnormalities. Four out of the 6 patients analyzed had a PID: 22q11.2 microdeletion (n=1), heterozygous CTLA mutation (n=2) or homozygous LRBA mutation (n=1).

Conclusion
Neurological involvement is a rare and severe late event in the course of childhood ES, or exceptionally AHAI, that may reveal various underlying PID. Complete imaging and pathology examination highlight a causative immune dysregulation and could guide specific therapeutic strategies.

Session topic: 31. Other Non-malignant hematopoietic disorders

Keyword(s): Immune thrombocytopenia (ITP), Immune deficiency, Childhood, Autoimmune hemolytic anemia (AIHA)

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