Evans syndrome: clinical perspectives, biological insights and treatment modalities

Abstract

Evans syndrome (ES) is a rare and chronic autoimmune disease characterized by autoimmune hemolytic anemia and immune thrombocytopenic purpura with a positive direct anti-human globulin test. It is classified as primary and secondary, with the frequency in patients with autoimmune hemolytic anemia being 37%–73%. It predominates in children, mainly due to primary immunodeficiencies or autoimmune lymphoproliferative syndrome. ES during pregnancy is associated with high fetal morbidity, including severe hemolysis and intracranial bleeding with neurological sequelae and death. The clinical presentation can include fatigue, pallor, jaundice and mucosal bleeding, with remissions and exacerbations during the person’s lifetime, and acute manifestations as catastrophic bleeding and massive hemolysis. Recent molecular theories explaining the physiopathology of ES include deficiencies of CTLA-4, LRBA, TPP2 and a decreased CD4/CD8 ratio. As in other autoimmune cytopenias, there is no established evidence-based treatment and steroids are the first-line therapy, with intravenous immunoglobulin administered as a life-saving resource in cases of severe immune thrombocytopenic purpura manifestations. Second-line treatment for refractory ES includes rituximab, mofetil mycophenolate, cyclosporine, vincristine, azathioprine, sirolimus and thrombopoietin receptor agonists. In cases unresponsive to immunosuppressive agents, hematopoietic stem cell transplantation has been successful, although it is necessary to consider its potential serious adverse effects. In conclusion, ES is a disease with a heterogeneous course that remains challenging to patients and physicians, with prospective clinical trials needed to explore potential targeted therapy to achieve an improved long-term response or even a cure.

Evans syndrome in children below 13 years of age – A nationwide population-based cohort study

“…Viral infections often precedes ES in young children [14], while adult patients may suffer from underlying haematological cancer (e.g. CLL [15]).…”

Evans syndrome in adults ‐ incidence, prevalence, and survival in a nationwide cohort

“…Hemolytic anemia and thrombocytopenia can lead to functional impairment, organ dysfunction, and bleeding complications. The incidence and prevalence of ES are unknown, although recent studies in children indicate that it may not be as rare as presumed . Although both AIHA and ITP were found to be associated with elevated risk of thrombosis and increased mortality, we know little about morbidity and mortality in patients with ES .…”

Evans’ syndrome in an old patient: case presentation

“…Second-line treatments include immunosuppressants (cyclosporin), monoclonal antibodies (rituximab), splenectomy. The third line includes cytostatics (cyclophosphamide), thrombopoietin receptor agonists (with ITP prevalence), allogenic or autologous stem cell transplantation 16,17 .…”