Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome

Clin Infect Dis. 2015 Oct 1;61(7):1084-91. doi: 10.1093/cid/civ470. Epub 2015 Jun 16.


Background: A subset of patients reporting a diagnosis of Lyme disease can be described as having alternatively diagnosed chronic Lyme syndrome (ADCLS), in which diagnosis is based on laboratory results from a nonreference Lyme specialty laboratory using in-house criteria. Patients with ADCLS report symptoms similar to those reported by patients with chronic fatigue syndrome (CFS).

Methods: We performed a case-control study comparing patients with ADCLS and CFS to each other and to both healthy controls and controls with systemic lupus erythematosus (SLE). Subjects completed a history, physical exam, screening laboratory tests, 7 functional scales, reference serology for Lyme disease using Centers for Disease Control and Prevention criteria, reference serology for other tick-associated pathogens, and cytokine expression studies.

Results: The study enrolled 13 patients with ADCLS (12 of whom were diagnosed by 1 alternative US laboratory), 25 patients with CFS, 25 matched healthy controls, and 11 SLE controls. Baseline clinical data and functional scales indicate significant disability among ADCLS and CFS patients and many important differences between these groups and controls, but no significant differences between each other. No ADCLS patient was confirmed as having positive Lyme serology by reference laboratory testing, and there was no difference in distribution of positive serology for other tick-transmitted pathogens or cytokine expression across the groups.

Conclusions: In British Columbia, a setting with low Lyme disease incidence, ADCLS patients have a similar phenotype to that of CFS patients. Disagreement between alternative and reference laboratory Lyme testing results in this setting is most likely explained by false-positive results from the alternative laboratory.

Keywords: Lyme disease; case-control study; chronic fatigue syndrome; clinical assessment; laboratory methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • British Columbia / epidemiology
  • Case-Control Studies
  • Cytokines / blood
  • Diagnosis, Differential
  • Fatigue Syndrome, Chronic / diagnosis*
  • Fatigue Syndrome, Chronic / epidemiology*
  • Female
  • Humans
  • Lyme Disease / diagnosis*
  • Lyme Disease / epidemiology*
  • Male
  • Middle Aged
  • Phenotype
  • Young Adult


  • Cytokines