Case report
Guillain-Barré syndrome and hemophagocytic lymphohistiocytosis in a patient with severe chronic active Epstein–Barr virus infection syndrome

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Abstract

Epstein–Barr virus (EBV) infection causes a wide range of neurologic and hematologic manifestations. We report a 72-year-old Japanese male patient with severe chronic active EBV infection syndrome (SCAEBV) who presented with Guillain-Barré syndrome (GBS) and developed hemophagocytic lymphohistiocytosis (HLH) several months after the onset of GBS. He showed acute onset of distal muscle weakness, ophthalmoplegia and bulbar palsy. Results of nerve conduction study revealed acute motor-sensory axonal neuropathy (AMSAN). His serum was positive for anti-LM1 IgG and anti-GM1b IgM. Titers of antibodies to EBV-related antigens indicated chronic reactivated EBV infection. Treatment with IVIg resolved the acute ophthalmoplegia, but there was no notable improvement in the AMSAN and bulbar palsy despite repeated. Finally, he developed refractory HLH resulting in a fatal outcome. In the present patient, it seems that SCAEBV was associated with the development of GBS and fatal HLH via parainfectious autoimmunity and direct infectious immune mechanisms, respectively.

Introduction

Epstein–Barr virus (EBV) causes a wide range of immunological disorders, such as infectious mononucleosis, nasopharlyngeal carcinoma and lymphoma, and occasionally produces chronic active infection [1]. Chronic EBV infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms. Severe chronic active EBV infection syndrome (SCAEBV) is a serious form of this infection that shows more severe clinical and hematological features associated with extremely high antibody titers to EBV-related antigens [2]. SCAEBV has high rates of mortality and morbidity because of life-threatening complications, such as hemophagocytic lymphohistiocytosis (HLH) [2], [3]. On the other hand, EBV infection is occasionally associated with the development of various neurologic disorders. EBV is one of the infectious agents causing onset of Guillain-Barré syndrome (GBS) [4], [5], [6]. We report a patient with SCAEBV who presented with GBS and developed fatal HLH several months after the onset of GBS.

Section snippets

Case report

A 72-year-old Japanese man suffered from upper respiratory tract infection, which improved on October 15, 2001. On October 22, blepharoptosis, diplopia and distal muscle weakness occurred. He was admitted to Tokushima University Hospital because he developed dysphagia and muscle weakness resulting in him becoming chair-bound on November 16, 2001.

As shown in Fig. 1, he had pancytopenia and pneumonia in November 1999 at the age of 70 years. Serum titers of antibodies to EBV-related antigens

Discussion

The present patient harbored persistently high titers of antibodies to EBV-VCA (IgG), EA-DR (IgG) and EBNA, indicating chronic reactivated EBV infection. He also had intermittent fever, pancytopenia and polyclonal gammopathy. These findings fulfilled the diagnostic criteria for SCAEBV [2]. Increased CD16 and CD56 positive cells suggested active natural killer cell subpopulations, which was compatible for active EBV infection. EBV ubiquitously infects humans and persists for the life time of the

Acknowledgement

We would like to thank Dr. Keiko Tanaka, Department of Neurology, Brain Research Institute, Niigata University, for an extensive analysis of anti-neuronal antibodies.

References (15)

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