Long-Term Sequelae and Health-Related Quality of Life Associated with Lyme disease: A Systematic Review
Objective: The long-term health burden of Lyme disease (LD) remains poorly characterized. Our objective was to systematically review the long-term sequelae and health-related quality of life (HRQoL) associated with LD. Methods: We performed systematic literature searches in Medline, Embase, Scopus, CINAHL, PsycInfo and Environment Complete up to July 2017 following PRISMA guidelines. The protocol describing study eligibility criteria was published on PROSPERO (CRD42017068765). We included North American and European observational studies measuring attributable health burden: long-term sequelae, HRQoL, and prognostic factors. We excluded studies with unclear LD diagnosis criteria, co-infected patients, or did not have a non-LD control group. Two reviewers independently completed screening, data extraction and quality appraisal. Results: We screened 8,698 articles and included 35 primary studies conducted between 1994 and 2016. Most studies were conducted in the United States (74%), used retrospective cohorts (54%), and used LD diagnosis based on, or adapted from, the CDC case definition (66%). Studies investigated patients with varying LD stages (1 early localized, 9 early disseminated, 2 late disseminated, 11 post-treatment LD syndrome, and 9 mixed). Studies reported sequelae (79%), HRQoL (42%) and prognostic factors (11%). Mortality was not reported. Arthralgia (8.3%), memory impairment (3.3%), facial nerve palsy (2.9%), and sleep difficulty (4.3%) were the most commonly reported physical, cognitive, neurologic, and functional sequelae, respectively. Most HRQoL studies used Short Form-36 (67%) and reported physical and mental component scores. Mean follow-up duration (range, 2.1–15.4 years) and HRQoL varied with LD stage. Approximately half (52%) of the included studies met 80% of their respective quality appraisal criteria. Conclusions: Our review highlights the presence of long-term sequelae and reduced quality of life associated with certain stages of Lyme disease. Outcomes reported can support clinical management and will be useful for future clinical and economic evaluations of interventions targeting LD treatment and prevention.