Evans syndrome in children: the results of a retrospective study of 54 patients

Abstract

Evans syndrome (ES) is a rare disorder accompanied by autoimmune hemolytic anemia and immune thrombocytopenia. ES in children is often associated with the defect of immune system regulation. This article presents an analysis of the results of investigation of 54 children with ES admitted to the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology during the period 2012–2019. The male-to-female ratio was 1.07:1 and the median age of the disease onset was 4 years (0 months – 16 years). Based on the results of molecular genetic testing, the diagnosis was changed in three patients to congenital TTP. Thus, for further analysis 51 patients were available. Thirty-nine out of 51 children (76.5%) had secondary ES, the median age of the disease onset was 4 years (2 months – 12 years), the male-to-female ratio was 1.05:1. PID was genetically confimed in 25 out of 39 patients, in the remaining 14 cases the diagnosis of PID was based on clinical and laboratory fidings only. Twelve patients (22.2%) had idiopathic (primary) ES, the median age of the disease onset was 8 years (7 months – 16 years) and the male-to-female ratio was 1:1. The disease onset in ES was more often accompanied by isolated cytopenia: ITP – 22 (43.1%) patients, AIHA – 15 (29.4%) patients, immune neutropenia – 1 (2%) patient, simultaneously with AIHA and ITP – 8 (15.7%) patients, pancytopenia – 5 (9.8%) patients. The second cytopenia developed on average after 2 years (1 month – 9 years). Neutropenia was observed only in secondary ES. The mortality rate for ES was 9.8%. First-line therapy (IVIG, glucocorticoids) for ES showed low effctiveness and sustained remission was observed only in 5.9% of patients. Thirty-four (87%) patients with secondary ES and 9 (75%) patients with idiopathic ES required other lines of therapy. The next-line drugs that showed good effctiveness were rituximab (76.5%), MMF (94%), and sirolimus (83%). Combinations of rituximab and MMF, rituximab and sirolimus were also effctive and induced sustained remission without other therapy in 83.3% and 75% of patients respectively. Children with ES need thorough examination, including genetic testing, for the early diagnosis of PID and the exclusion of congenital TTP. The combination of rituximab and MMF proved to be the most effctive treatment for ES.