A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus Type 6 Infection

Ann Intern Med. 1992 Jan 15;116(2):103-13. doi: 10.7326/0003-4819-116-2-103.

Abstract

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 less than 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 less than 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 less than 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Brain / pathology
  • CD4-CD8 Ratio
  • Cluster Analysis
  • Fatigue Syndrome, Chronic / microbiology*
  • Female
  • Herpesviridae Infections / cerebrospinal fluid
  • Herpesviridae Infections / complications*
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / physiopathology
  • Herpesvirus 6, Human* / immunology
  • Herpesvirus 6, Human* / physiology
  • Human T-lymphotropic virus 1 / immunology
  • Humans
  • Immunophenotyping
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Virus Replication

Substances

  • Antibodies, Viral