Diagnosis and management of autoimmune cytopenias in childhood

Abstract

The diagnosis and management of children with autoimmune cytopenias can be challenging. Children can present with immune-mediated destruction of a single-cell lineage or multiple cell lineages, including platelets (immune thrombocytopenia [ITP]), erythrocytes (autoimmune hemolytic anemia), and neutrophils (autoimmune neutropenia). Immune-mediated destruction can be primary or secondary to a comorbid immunodeficiency, malignancy, rheumatologic condition, or lymphoproliferative disorder. Treatment options generally consist of nonspecific immune suppression or modulation. This nonspecific approach is changing as recent insights into disease biology have led to targeted therapies, including the use of thrombopoietin mimetics in ITP and sirolimus for cytopenias associated with autoimmune lymphoproliferative syndrome.

Keywords: Autoimmune hemolytic anemia; Autoimmune lymphoproliferative syndrome; Autoimmune neutropenia; Evans syndrome; Immune thrombocytopenia.

Figure 1. Fas apoptotic pathway

Normally, as part of the down-regulation of the immune response, activated B and T lymphocytes up-regulate FAS and activated T lymphocytes up-regulate FAS-ligand. These interact and trigger the caspase cascade leading to proteolysis, DNA degradation, and apoptosis. This FAS-mediated pathway is part of the extrinsic apoptotic pathway. In contrast, mitochondrial-induced apoptosis after cellular stress is part of the intrinsic apoptotic pathway. Patients with ALPS have a defect in the FAS-apoptotic pathway, leading to abnormal lymphocyte survival. Courtesy of © Sue Seif.