Development of a foundation for a case definition of post-treatment Lyme disease syndrome

Aucott, John N.; Crowder, Lauren A.; Kortte, Kathleen B.

doi:10.1016/j.ijid.2013.01.008

Cited by 87 publications

(99 citation statements)

References 41 publications

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“…There were no statistically significant differences between these two groups on any of the demographic variables examined. The PTLDS definition (25) was applied to our cohort of 76 Lyme disease participants. Eleven participants (14.47%) met the criteria for PTLDS at either 6 or 12 months, 29 (38.16%) met the criteria for the symptoms-only group, and 36 (47.37%) met the criteria for the return-to-health group.…”

Section: Resultsmentioning

confidence: 99%

“…Mediators with significant changes (q Ͻ 0.1%) are displayed as heat maps to visualize differences. All study time points are represented in panels A to F for healthy controls, those that returned to health, those that reported symptoms without functional impact, and those that met the criteria for PTLDS (25). (A) Mediators with significant changes (q Ͻ 0.1%) at the acute-phase, pretreatment visit; (B) mediators with significant changes (q Ͻ 0.1%) at the posttreatment follow-up visit 3 weeks later; (C) mediators with significant changes (q Ͻ 0.1%) at 1 month following treatment completion; (D) mediators with significant changes (q Ͻ 0.1%) at 3 months following treatment completion; (E) mediators with significant changes (q Ͻ 0.1%) at 6 months following treatment completion; (F) mediators with significant changes (q Ͻ 0.1%) at 1 year following treatment completion.…”

Section: Resultsmentioning

confidence: 99%

“…Sensitivity and specificity plots were generated (data not shown), and the inter- a Clinical outcome group status (PTLDS, symptoms only, and return to health) was defined using a previously published definition incorporating both persistent symptoms and functional impact (25). b For immune markers, a unit increase was set at 0.5 SD for the Lyme disease participant sample.…”

Section: Resultsmentioning

confidence: 99%

“…The expression of CCL19 is thought to be constitutive, but activated dendritic cells produce high levels of CCL19 in order to increase immune cell trafficking in secondary lymphoid organs during active immune responses. This is likely responsible for Lyme disease-exposed participants are divided into the PTLDS, symptoms-only, and return-to-health clinical outcome groups on the basis of self-reported symptoms and survey measurements at 6 months and 1 year posttreatment (25). The median control value (79.28 pg/ml; interquartile range, 62.60 to 114.85 pg/ml) is represented by a triangle in the graph.…”

Section: Discussionmentioning

confidence: 99%

“…This definition includes two components: (i) the presence of persistent symptoms, defined by either fatigue, musculoskeletal pain in at least three areas of the body, or cognitive complaints of difficulty finding words, focusing, concentrating, or memory impairment, and (ii) functional impact, defined by a composite T score of less than 45 (a half standard deviation below the normative mean) on four previously identified subscales of the Short Form (36) Health Survey (SF-36). This cutoff was chosen on the basis of prior research demonstrating its sensitivity for determination of the impact of symptoms on daily life functioning in this population (25). Three clinical outcome groups were defined on the basis of this definition.…”

Section: Methodsmentioning

confidence: 99%

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CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Aucott

Soloski

Crowder³

et al. 2016

Clin Vaccine Immunol

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d Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Aucott

Soloski

Crowder³

et al. 2016

Clin Vaccine Immunol

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Hyperbaric Oxygen Therapy and Chronic Lyme Disease: The Controversy and the Evidence

Fife

Eckert

2017

Textbook of Hyperbaric Medicine

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Expectancies as predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease

et al. 2021

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Introduction/Objective Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive. Methods A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health–related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone. At end-of-treatment (14 weeks after trial start) and follow-up (52 weeks), complete data of 231 and 170 (of initial 280) patients with persistent symptoms temporally related to a history of erythema migrans or otherwise confirmed symptomatic Lyme disease, or accompanied by B. burgdorferi IgG or IgM antibodies, were examined through hierarchical regression analyses. Results In addition to pre-treatment HRQoL, pre-treatment expectancies regarding symptom improvement were consistently associated with stronger physical and mental HRQoL improvements at both end-of-treatment and follow-up (95% CI range: .09;.54, p < .01 to .27;.92, p < .001). Post-treatment expectancies regarding having received antibiotics vs. placebo was associated with more HRQoL improvement at end-of-treatment, but not at follow-up (95% CI-range 1.00;4.75, p = .003 to −7.34; −2.22, p < .001). Conclusions The present study shows that, next to pre-treatment functioning, patients’ pre-treatment and post-treatment expectancies regarding improvement of persistent symptoms attributed to Lyme disease relate to a more beneficial symptom course. Expectancies of patients may be relevant to explain and potentially improve patient outcomes (e.g., by optimized communication about treatment success). Trial registration ClinicalTrials.gov, NCT01207739 (Registration date: 23–09-2010) Key Points• As there is currently no sufficient symptom resolution or symptomatic improvement for many patients with persistent symptoms attributed to Lyme disease, it is relevant to know which factors determine symptom progression and predict heterogeneity in treatment response.• Next to pre-treatment functioning, expectancies regarding symptom improvement and having received antimicrobial study medication are associated with a more beneficial symptom course after both shorter-term and longer-term antimicrobial treatment.• Expectancies are relevant to consider in treatment studies and may be useful in clinical settings to improve symptom course and treatment outcome (e.g., by optimized communication about treatment success).

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Development of a foundation for a case definition of post-treatment Lyme disease syndrome

Cited by 87 publications

References 41 publications

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

Hyperbaric Oxygen Therapy and Chronic Lyme Disease: The Controversy and the Evidence

Expectancies as predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease

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