Case Report: Autoimmune Lymphoproliferative Syndrome vs. Chronic Active Epstein-Barr Virus Infection in Children: A Diagnostic Challenge

Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder characterized by a disruption of the lymphocyte apoptosis pathway, self-tolerance, and immune system homeostasis. Defects in genes within the first apoptosis signal (FAS)-mediated pathway cause an expansion of autoreactive double-negative T cells leading to non-malignant lymphoproliferation, autoimmune disorders, and an increased risk of lymphoma. The aim of the study was to show the diagnostic dilemmas and difficulties in the process of recognizing ALPS in the light of chronic active Epstein-Barr virus (CAEBV) infection. Clinical, immunological, flow cytometric, biomarkers, and molecular genetic approaches of a pediatric patient diagnosed with FAS-ALPS and CAEBV are presented. With the ever-expanding spectrum of molecular pathways associated with autoimmune lymphoproliferative disorders, multiple genetic defects of FAS-mediated apoptosis, primary immunodeficiencies with immune dysregulation, malignant and autoimmune disorders, and infections are included in the differential diagnosis. Further studies are needed to address the issue of the inflammatory and neoplastic role of CAEBV as a triggering and disease-modifying factor in ALPS.

Lymphoproliferation in Inborn Errors of Immunity: The Eye Does Not See What the Mind Does Not Know

“…Histopathological features in ALPS include marked proliferation of non-clonal CD4-/CD8-CD45RA+ CD57+TCRαβ+ cytotoxic (TIA+ and perforin+) double-negative T-cells (DNTs), involving peripheral blood, lymph nodes, liver, spleen, and extranodal sites, a few cases may show γδ-T-cell proliferation ( 36 , 46 ). Follicular and paracortical hyperplasia and PTGC have been frequently described ( 1 ).…”

“…Histopathological features of LP in ALPS may overlap with CAEBV, especially in those cases where classic ALPS morphology is not evident. In such cases, florid paracortical hyperplasia comprising plasma cells, immunoblasts, EBER+ lymphocytes, cytotoxic T-cells, and γδ-T-cells is the predominant finding ( 46 ). CTLA-4 deficient patients have an increased risk of solid and lymphoid malignancies including lymphomas and multiple myeloma.…”