This case is notable for two reasons. First, a 43-year-old man with AIDS initially suspected to have lymphoma due to his clinical features at presentation, was subsequently diagnosed with MCD. Second, within three weeks he presented with EBV myelitis.
With respect to the former condition, this case brings to light the importance of obtaining definitive histological diagnoses in HIV-infected patients who present with lymphadenopathy and systemic symptoms. MCD is relatively uncommon cause for such a presentation. Though clinically similar to lymphoma, MCD is an entity that is distinct from malignant lymphoproliferative disorders in both histology and prognosis. It is characterized by significant peripheral lymphadenopathy and hepatosplenomegaly, as well as by frequent fevers, night sweats, fatigue and weight loss . Abnormal laboratory findings include pancytopenia, elevated liver function tests, raised C-reactive protein and interleukin-6 (IL-6), and hypergammaglobulinemia [3, 8]. The condition typically presents in patients between the ages of 50 and 65 years, but HIV-infected patients tend to be younger at presentation, as in our case, and can be at an increased risk for MCD [4, 9]. This disease often arises concurrently with KS. It has been reported that, among HIV-positive patients with MCD who are infected with HHV-8, up to 70 percent will develop KS at some time during their clinical course. MCD may present at any CD4 count in these patients .
Although no standard treatment has been established, MCD often is treated systemically  with such aggressive remission-induction chemotherapy regimens as cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) and doxorubicin-bleomycin-vincristine; immunomodulatory agents like thalidomide and interferon alpha; and monoclonal antibodies, like those directed against the IL-6 receptor (atlizumab) and CD20 (rituximab) [10, 11]. The contribution of aggressive anti-retroviral treatment to the treatment of MCD remains controversial. Novel treatments targeted at HHV-8 have yielded promising results. Our patient was enrolled in an NIH clinical trial of high-dose oral zidovudine and valganciclovir for MCD ClinicalTrials.gov identifier: NCT00099073.
EBV is a γ-herpes virus that is detectable in over 90 percent of the general population. Even though most infections with EBV go unnoticed, in some cases it can be associated with the development of serious conditions, including infectious mononucleosis. EBV has been associated with CNS diseases, including meningitis and encephalitis [1, 2]. EBV myelitis is uncommon, but is important in the differential diagnosis of acute myelopathy. Acute EBV myelitis can present as neurologic dysfunction due to involvement of the white matter. When EBV infection affects only part of the transverse expanse of the spinal cord, it manifests as asymmetric motor and sensory symptoms. The pathogenesis of EBV-associated CNS disorders is not completely understood, but may be due to direct viral invasion of the CNS. Alternatively, damage may be immunologically-mediated via the infiltration of cytotoxic CD8+ lymphocytes into neural tissue, or the deposition of antibody-antigen complexes . EBV infection may cause mild symptoms of mononucleosis, like pharyngitis, prior to the onset of acute myelitis .
Patients with AIDS have 10 to 20 times as many circulating EBV-infected B-cells as those who are healthy. T-cells from patients with AIDS suppress EBV-infected B-cells less effectively than do cells from normal controls . A decline in EBV-specific cytotoxic T-cells and an elevated EBV viral load precedes the development of EBV-associated non-Hodgkin's lymphomas in HIV-infected patients; however, these changes are not seen in patients with HIV before the development of opportunistic infections. HIV viral load and the progression of HIV disease do not appear to be affected by primary infection with EBV .
In our patient, both the clinical and radiological findings were characteristic of myeloradiculopathy. The CSF abnormalities further indicated that the disease was inflammatory. Extensive virological analysis of serum and CSF revealed the presence of EBV DNA in the CSF, as well as the absence of CMV, HSV, VZV and HHV-8. The clinical features of myelitis, and the increased signal in the cervical and thoracic spinal cord in this patient on MRI, were similar to those described in previously reported EBV myelitis cases [2, 15–17].
The International Herpes Management Forum recommends that the diagnosis of EBV infections of the CNS can include evidence of EBV DNA in CSF by PCR. Unfortunately, there is no definitive treatment for EBV infection of the nervous system. Steroids and immunoglobulin have been used empirically, but their effects on disease progression are unknown. Anti-viral therapy has not demonstrated clinical efficacy in the treatment of EBV-related CNS disorders .