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

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.

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Autoimmune lymphoproliferative syndrome mimicking chronic active Epstein–Barr virus infection

International Journal of Hematology ◽

10.1007/s12185-011-0877-9 ◽

2011 ◽

Vol 93 (6) ◽

pp. 760-764 ◽

Cited By ~ 11

Author(s):

Keiko Nomura ◽

Hirokazu Kanegane ◽

Keisuke Otsubo ◽

Hiroshi Wakiguchi ◽

Yukihiro Noda ◽

...

Keyword(s):

Virus Infection ◽

Epstein Barr Virus ◽

Epstein Barr Virus Infection ◽

Autoimmune Lymphoproliferative Syndrome ◽

Barr Virus ◽

Lymphoproliferative Syndrome ◽

Epstein Barr ◽

Barr Virus Infection

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Autoimmune Lymphoproliferative Syndrome and Epstein-Barr Virus-Associated Lymphoma: An Adjunctive Diagnostic Role for Monitoring EBV Viremia?

Case Reports in Immunology ◽

10.1155/2013/245893 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Romina Pace ◽

Donald C. Vinh

Keyword(s):

Epstein Barr Virus ◽

Genetic Disorder ◽

Autoimmune Lymphoproliferative Syndrome ◽

Barr Virus ◽

First Case ◽

Increased Risk ◽

Diagnostic Role ◽

Lymphoproliferative Syndrome ◽

Epstein Barr ◽

Ebv Viremia

Background. Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of lymphocyte homeostasis due to defects in FAS-mediated apoptosis. ALPS is characterized by childhood onset of chronic lymphadenopathy and splenomegaly, autoimmunity, an expanded population of double-negative T cells (DNTCs), and an increased risk of lymphoma. This propensity for lymphoma in ALPS is not well understood. It is possible that lymphomagenesis in some of these patients may result from Epstein-Barr virus (EBV) infection exploiting the defective T-cell surveillance resulting from impaired FAS-mediated apoptosis.Case Presentation. We report the first case, to our knowledge, of lymphoma in a patient with ALPS that was clinically heralded by progressively increasing EBV viremia. We discuss its practical implications and the possible immune pathways involved in the increased risk for EBV-associated lymphoproliferative disorders in ALPS patients.Conclusion. In patients with ALPS, distinguishing chronic lymphadenopathy from emerging lymphoma is difficult, with few practical recommendations available. This case illustrates that, at least for some patients, monitoring for progressively increasing EBV viremia may be useful.

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Interferon-gamma in a family with X-linked lymphoproliferative syndrome with acute Epstein-Barr virus infection

Journal of Clinical Immunology ◽

10.1007/bf00917127 ◽

1989 ◽

Vol 9 (1) ◽

pp. 48-54 ◽

Cited By ~ 23

Author(s):

Motohiko Okano ◽

Geoffrey M. Thiele ◽

Roger H. Kobayashi ◽

Jack R. Davis ◽

Mark S. Synovec ◽

...

Keyword(s):

Virus Infection ◽

Interferon Gamma ◽

Epstein Barr Virus ◽

Epstein Barr Virus Infection ◽

Barr Virus ◽

Lymphoproliferative Syndrome ◽

Epstein Barr ◽

Barr Virus Infection

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Epstein-Barr Virus Infection in an Elderly Nonimmunocompromised Adult Successfully Treated with Rituximab

Case Reports in Hematology ◽

10.1155/2014/641483 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4

Author(s):

Jacob P. Smeltzer ◽

Matthew T. Howard ◽

Wilson I. Gonsalves ◽

Thomas E. Witzig

Keyword(s):

Epstein Barr Virus ◽

The Elderly ◽

Lymph Node Biopsy ◽

Epstein Barr Virus Infection ◽

Diagnostic Challenge ◽

Barr Virus ◽

Age Related ◽

Epstein Barr ◽

Barr Virus Infection ◽

Systemic Symptoms

Epstein-Barr virus (EBV) is a ubiquitous virus that commonly affects children and adolescents. In addition to causing a viral illness, it is also associated with various malignancies in particular B cell lymphomas and lymphoproliferative disorders. Differentiating between the two processes can be a diagnostic challenge. Here, we present a case of an atypical EBV infection in an elderly patient with severe systemic symptoms, multiorgan involvement, lymphadenopathy, and negative EBV serology. Excisional lymph node biopsy demonstrated features of a lymphoproliferative process involving EBV. Despite supportive care, she experienced continued clinical deterioration and was successfully treated with rituximab. This case illustrates the diagnostic challenges of these cases particularly in the elderly who may have age related immunosenescence, the utility of EBV PCR testing, and the clinical efficacy of rituximab in clearing the infected cells.

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