A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection

D. Buchwald, P. R. Cheney, D. L. Peterson, B. Henry, S. B. Wormsley, A. Geiger, D. V. Ablashi, S. Z. Salahuddin, C. Saxinger, R. Biddle, R. Kikinis, F. A. Jolesz, T. Folks, N. Balachandran, J. B. Peter, R. C. Gallo, A. L. Komaroff

    Research output: Contribution to journalArticlepeer-review

    305 Scopus citations


    Objective: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset. Design: Cohort study with comparison to matched, healthy control subjects. Patients: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in. Main Outcome Measures: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6). Main Results: Patients had a higher mean (± SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 ± 1.5 compared with 2.3 ± 1.0, respectively; P < 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P < 10-9). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P < 10-8), a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA. Conclusions: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.

    Original languageEnglish (US)
    Pages (from-to)103-113
    Number of pages11
    JournalAnnals of internal medicine
    Issue numberSUPPL.1
    StatePublished - 1992


    • Fatigue
    • Fatigue syndrome, chronic
    • Herpesvirus-6, human
    • Immunologic diseases
    • Neurologic manifestations

    ASJC Scopus subject areas

    • Internal Medicine


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