Symptom heterogeneity and patient subgroup classification among US patients with post-treatment Lyme disease: an observational study

Abstract

Objectives: To identify underlying subgroups with distinct symptom profiles, and to characterise and compare these subgroups across a range of demographic, clinical and psychosocial factors, within a heterogeneous group of patients with well-defined post-treatment Lyme disease (PTLD).

Design: A clinical case series of patents.

Setting: Participants were recruited from a single-site, Lyme disease referral clinic patient population and were evaluated by physical exam, clinical laboratory testing and standardised questionnaires.

Participants: Two hundred and twelve participants met study criteria for PTLD, with medical record-confirmed prior Lyme disease as well as current symptoms and functional impact.

Results: Exploratory factor analysis classified 30 self-reported symptoms into 6 factors: 'Fatigue Cognitive', 'Ocular Disequilibrium', 'Infection-Type', 'Mood-Related', 'Musculoskeletal Pain' and 'Neurologic'. A final latent profile analysis was conducted using 'Fatigue Cognitive', 'Musculoskeletal Pain' and 'Mood-Related' factor-based scores, which produced three emergent symptom profiles, and participants were classified into corresponding subgroups with 59.0%, 18.9% and 22.2% of the sample, respectively. Compared with the other two groups, subgroup 1 had similarly low levels across all factors relative to the sample as a whole, and reported lower rates of disability (1.6% vs 10.0%, 12.8%; q=0.126, 0.035) and higher self-efficacy (median: 7.5 vs 6.0, 5.3; q=0.068,<0.001). Subgroup 2 had the highest 'Musculoskeletal Pain' factor-based scores (q≤0.001). Subgroup 3 was characterised overall by higher symptom factor-based scores, and reported higher depression (q≤0.001).

Conclusions: This analysis identified six symptom factors and three potentially clinically relevant subgroups among patients with well-characterised PTLD. We found that these subgroups were differentiated not only by symptom phenotype, but also by a range of other factors. This may serve as an initial step towards engaging with the symptom heterogeneity that has long been observed among patients with this condition.

Keywords: infectious diseases; internal medicine; primary care.

Figure 1

Exploratory factor analysis of 30 common post-treatment Lyme disease syndrome symptoms suggests a six-factor model. Three of the symptoms either did not load or loaded weakly and had close cross-loading, and they were not included in the final model.

Figure 2

Three subgroups of participants identified based on latent profile analysis (A, B).

Figure 3

Participant subgroup differences in median standardised symptom factor-based scores, depicted as a heat map. The higher the score, the higher the severity of reported symptoms within each factor.

Figure 4

Short-Form Health Survey-36 (SF-36) health-related quality-of-life physical and mental component scores for the three patient subgroups. ns=not significant; *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001.