Mistaken Identity: Many Diagnoses are Frequently Misattributed to Lyme Disease

Am J Med. 2022 Apr;135(4):503-511.e5. doi: 10.1016/j.amjmed.2021.10.040. Epub 2021 Nov 30.


Background: Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

Methods: This retrospective observational cohort study evaluated patients who lacked evidence for Borrelia burgdorferi infection referred for Lyme disease to a Mid-Atlantic academic center from 2000-2013. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Results: Of 1261 referred patients, 1061 (84%) had no findings of active Lyme disease, with 690 (65%) receiving other diagnoses; resulting in 405 (59%) having newly diagnosed medical conditions, 134 (19%) attributed to pre-existing medical issues, and 151 (22%) with both new and pre-existing conditions. Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%. Leading diagnoses were anxiety/depression 222 (21%), fibromyalgia 120 (11%), chronic fatigue syndrome 77 (7%), migraine disorder 74 (7%), osteoarthritis 62 (6%), and sleep disorder/apnea 48 (5%). Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis (n = 11), malignancy (n = 8), Parkinson's disease (n = 8), sarcoidosis (n = 4), or amyotrophic lateral sclerosis (n = 4).

Conclusions: Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

Keywords: Chronic Lyme disease; Fatigue; Long-term symptoms; Lyme disease; Misdiagnosis; Pain; Post-treatment Lyme syndrome; Tick-borne infections.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Borrelia burgdorferi*
  • Depression / epidemiology
  • Humans
  • Lyme Disease* / complications
  • Lyme Disease* / diagnosis
  • Migraine Disorders* / complications
  • Retrospective Studies