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.

Keywords: Evans syndrome; HSCT; IVIG; autoimmune cytopenias; low-dose rituximab; mofetil mycophenolate; sirolimus; systemic lupus erythematosus.

Figure 1

Diagnostic approach for Evans syndrome. Abbreviations: aCL, anticardiolipin; ALPS, autoimmune lymphoproliferative syndrome; ANA, antinuclear antibodies; anti-CCP, anti-cyclic citrullinated peptide; anti-LC1, anti-liver cytosol antibody; anti-MCV, anti-mutated citrullinated vimetin; anti-Sm, anti-Smith antibody; APS, antiphospholipid syndrome; CVID, common variable immunodeficiency; LA, lupus anticoagulant; LKM-1, liver kidney microsomal type 1 antibodies; PA-IgG, platelet-associated IgG; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SMA, smooth muscle antibody; TSI, thyroid stimulating immunoglobulin; VEGF, vascular endothelial growth factor.