Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort.
Evans syndrome (ES) is a rare autoimmune disorder whose long-term outcome is not well known. In France, a collaborative pediatric network set up via the National Rare Disease Plan now provides comprehensive clinical data in children with this disease. Patients aged less than 18 years at the initial presentation of autoimmune cytopenia have been prospectively included into a national observational cohort since 2004. The definition of ES was restricted to the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Cases were deemed secondary if associated with a primitive immunodeficiency or systemic lupus erythematosus. In December 2014, we analyzed the data pertaining to 156 children from 26 centers with ES whose diagnosis was made between 1981 and 2014. Median age (range) at the onset of cytopenia was 5.4 years (0.2-17.2). In 85 sequential cases, the time lapse between the first episodes of AIHA and ITP was 2.4 years (0.1-16.3). The follow-up period as from ES diagnosis was 6.5 years (0.1-28.8). ES was secondary, revealing another underlying disease, in 10% of cases; various associated immune manifestations (mainly lymphoproliferation, other autoimmune diseases, and hypogammaglobulinemia) were observed in 60% of cases; and ES remained primary in 30% of cases. Five-year ITP and AIHA relapse-free survival were 25 and 61%, respectively. Overall, 69% of children required one or more second-line immune treatments, and 15 patients (10%) died at the age of 14.3 years (1.7-28.1). To our knowledge, this is the first consistent long-term clinical description of this rare syndrome. It underscores the high rate of associated immune manifestations and the burden of long-term complications and treatment toxicity. Future challenges include (1) the identification of the underlying genetic defects inducing immune dysregulation and (2) the need to better characterize patient subgroups and second-line treatment strategies.
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 0005, INSERM CICP, University Hospital of Bordeaux , Bordeaux , France.
Nathalie
N
Aladjidi
Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), University Hospital of Bordeaux , Bordeaux , France ; CIC 0005, INSERM CICP, University Hospital of Bordeaux , Bordeaux , France.
Helder
H
Fernandes
Department of Hematology, APHP - Hôpital Robert Debré , Paris , France ; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), APHP - Hôpital Robert Debré , Paris , France.
Thierry
T
Leblanc
Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), University Hospital of Bordeaux , Bordeaux , France.
Amélie
A
Vareliette
Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine, INSERM UMR_S1163, Université Paris Descartes , Paris , France.
Frédéric
F
Rieux-Laucat
Pediatric Immuno-Hematology Unit, University Hospital of Lyon - IHOP , Lyon , France.
Yves
Y
Bertrand
Department of Pediatric Hematology, University Hospital Timone Enfants , Marseille , France.
Hervé
H
Chambost
Hôpital des Enfants, University Hospital of Toulouse , Toulouse , France.
Marlène
M
Pasquet
Department of Pediatrics, Hôpital Jeanne de Flandre, University Hospital of Lille , Lille , France.
Françoise
F
Mazingue
Department of Pediatrics, APHP - Hôpital Bicêtre , Le Kremlin-Bicêtre , France.
Corinne
C
Guitton
Pediatric Hemato-Oncology Unit, University Hospital of Angers , Angers , France.
Isabelle
I
Pellier
Pediatric Hemato-Oncology Unit, University Hospital of Nice , Nice , France.
Françoise
F
Roqueplan-Bellmann
Department of Pediatrics, University Hospital of Grenoble , Grenoble , France.
Corinne
C
Armari-Alla
Pediatric Hemato-Oncology Unit, Hôpital Mère Enfant, University Hospital of Nantes , Nantes , France.
Caroline
C
Thomas
Pediatric Immuno-Hematology-Oncology Unit, University Hospital of Rouen , Rouen , France.
Aude
A
Marie-Cardine
Pediatric Hemato-Oncology Unit, Centre de Pédiatrie Gatien De Clocheville, University Hospital of Tours , Tours , France.
Odile
O
Lejars
Service de Médecine Infantile II, Hôpital d'Enfants, University Hospital of Nancy , Vandoeuvre-lès-Nancy , France.
Fanny
F
Fouyssac
Department of Pediatric Hematology, Hôpital Sud, University Hospital of Rennes , Rennes , France.
Sophie
S
Bayart
Pediatric Hemato-Oncology Unit, Hôpital de Hautepierre, University Hospital of Strasbourg , Strasbourg , France.
Patrick
P
Lutz
Pediatric Hemato-Oncology Unit, Hôpital Mère Enfants, University Hospital of Limoges , Limoges , France.
Christophe
C
Piguet
Department of Pediatric Hematology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier , Montpellier , France ; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), Hôpital Arnaud de Villeneuve, University Hospital of Montpellier , Montpellier , France.
Eric
E
Jeziorski
Pediatric Hemato-Oncology Unit 1, University Hospital of Besançon , Besançon , France.
Pierre
P
Rohrlich
Onco-Hematology Unit, Hôpital Morvan, University Hospital of Brest , Brest , France.
Philippe
P
Lemoine
Onco-Hematology Unit, University Hospital of Caen , Caen , France.
Damien
D
Bodet
Pediatric Hemato-Oncology Unit, Hôtel-Dieu, University Hospital of Clermont-Ferrand , Clermont-Ferrand , France.
Catherine
C
Paillard
Pediatric Hemato-Oncology Unit, Hôpital d'Enfants, University Hospital of Dijon , Dijon , France.
Gérard
G
Couillault
Pediatric Hemato-Oncology Unit, University Hospital of Poitiers , Poitiers , France.
Frédéric
F
Millot
Department of Immuno-Hematology, APHP - Hôpital Necker-Enfants Malades , Paris , France ; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), APHP - Hôpital Necker-Enfants Malades , Paris , France.
Alain
A
Fischer
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 0005, INSERM CICP, University Hospital of Bordeaux , Bordeaux , France.
Yves
Y
Pérel
Department of Onco-Hematologie, APHP - Hôpital Trousseau , Paris , France ; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), APHP - Hôpital Trousseau , Paris , France.
Guy
G
Leverger
Evans syndrome; autoimmune hemolytic anemia; child; immune thrombocytopenic purpura