Dedra Buchwald, MD; Paul R. Cheney, MD, PhD; Daniel L. Peterson, MD; Berch Henry, PhD; Susan B. Wormsley, BS; Ann Geiger, BA; Dharam V. Ablashi, DVM; S. Zaki Salahuddin, MS; Carl Saxinger, PhD; Royce Biddle, MD; Ron Kikinis, MD; Ferenc A. Jolesz, MD; Thomas Folks, PhD; N. Balachandran, PhD; James B. Peter, MD, PhD; Robert C. Gallo, MD; Anthony L. Komaroff, MD
Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A, et al. A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus Type 6 Infection. Ann Intern Med. 1992;116:103-113. doi: 10.7326/0003-4819-116-2-103
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Published: Ann Intern Med. 1992;116(2):103-113.
▪ Objective:To conduct neurologic, immunologic, and virologie 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.
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