Prevalence of persistent symptoms after treatment for lyme borreliosis: A prospective observational cohort study

Lancet Reg Health Eur. 2021 May 27;6:100142. doi: 10.1016/j.lanepe.2021.100142. eCollection 2021 Jul.


Background: Concerns about long-lasting symptoms attributed to Lyme borreliosis (LB) are widespread in the Western world, while such symptoms are highly prevalent in the general population.

Methods: In the largest prospective study to date, adults with physician-confirmed LB were included at the start of antibiotic treatment. Primary outcomes, prevalence of persistent symptoms and symptom severity, were assessed using three-monthly standardised questionnaires during one year. Persistent symptoms were defined as impaired scores for fatigue (CIS, subscale fatigue), cognitive impairment (CFQ) or pain (SF-36, subscale bodily pain) ≥6 months, with onset <6 months. Outcomes were compared with a longitudinal general population and a tick-bite cohort without LB as a reference.

Findings: Of 1135 LB patients (94•8% erythema migrans, 5•2% disseminated LB), 1084 fulfilled primary analysis criteria, as well as 1942 population and 1887 tick-bite controls. Overall prevalence of persistent symptoms in LB patients was 27•2% (95%CI, 24•7%-29•7%); 6•0% and 3•9% higher than in population (21•2%, 95%CI, 19•3%-23•1%; p < 0•0001) and tick-bite (23•3%, 95%CI 21•3%-25•3%; p = 0•016) cohorts, respectively. At 12 months, fatigue, cognitive impairment, and pain were significantly more severe in erythema migrans patients than in reference cohorts, while in disseminated LB patients, only pain was more severe.

Interpretation: In treated LB patients, persistent symptoms were significantly more prevalent and symptoms were more severe than in individuals without LB, although the background prevalence was substantial. This suggests an association, either direct or indirect, between persistent symptoms and LB in a relatively small subset of patients.

Funding: ZonMw; Dutch Ministry of Health, Welfare and Sport.

Keywords: ACA, Acrodermatitis chronica atrophicans; CFQ, Cognitive Failure Questionnaire; CIS, Checklist Individual Strength; EM, Erythema migrans; LB, Lyme borreliosis; PCR, Polymerase Chain Reaction; PHQ-15, Patient Health Questionnaire; PTLDS, Post-treatment Lyme Disease Syndrome; SF-36, SF-36 item Health Survey; TiC-P, Treatment Inventory of Costs in Patients with psychiatric disorders; s.l., sensu lato.