AB0903 LYME ARTHRITIS IN HIGH LYME DISEASE ENDEMIC EUROPE ZONE

The diagnosis of Lyme disease, caused by Borrelia burgdorferi, is clinical but frequently supported by laboratory tests. Lyme arthritis is now less frequently seen than at the time of its discovery. However, it still occurs, and it is important to recognize this, the differential diagnoses, and how laboratory tests can be useful and their limitations. The most frequently used diagnostic tests are antibody based. However, antibody testing still suffers from many drawbacks and is only an indirect measure of exposure. In contrast, evolving direct diagnostic methods can indicate active infection.

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Regulatory T Cells Contribute to Resistance against Lyme Arthritis

Infection and Immunity ◽

10.1128/iai.00160-20 ◽

2020 ◽

Vol 88 (11) ◽

Author(s):

Emily M. Siebers ◽

Elizabeth S. Liedhegner ◽

Michael W. Lawlor ◽

Ronald F. Schell ◽

Dean T. Nardelli

Keyword(s):

T Cells ◽

T Cell ◽

Lyme Disease ◽

Regulatory T Cells ◽

Regulatory T Cell ◽

Interleukin 10 ◽

Lyme Arthritis ◽

Interleukin 17 ◽

Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

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Postoperative Lyme Arthritis in the Orthopaedic Patient

Sports Health A Multidisciplinary Approach ◽

10.1177/1941738119845671 ◽

2019 ◽

Vol 11 (4) ◽

pp. 350-354

Author(s):

Matthew C. Hess ◽

Zachary Devilbiss ◽

Garry Wai Keung Ho ◽

Raymond Thal

Keyword(s):

United States ◽

Lyme Disease ◽

Postoperative Complication ◽

Joint Pain ◽

English Language ◽

The United States ◽

Lyme Arthritis ◽

Level Of Evidence ◽

Pubmed Database ◽

Level 3

Context:Lyme disease is the most common tick-borne illness in North America and Europe, and Lyme arthritis is a frequent late-stage manifestation in the United States. However, Lyme arthritis has rarely been reported as a postoperative complication.Evidence Acquisition:The PubMed database was queried through June 2018, and restricted to the English language, in search of relevant articles.Study Design:Clinical review.Level of Evidence:Level 3.Results:A total of 5 cases of Lyme arthritis as a postoperative complication have been reported in the literature.Conclusion:These cases highlight the importance for providers practicing in Lyme-endemic regions to keep such an infection in mind when evaluating postoperative joint pain and swelling. We propose herein an algorithm for the workup of potential postoperative Lyme arthritis.Strength of Recommendation Taxonomy (SORT):C

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Lyme Arthritis in Children on the Uptick in Western New York Area

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.1177/1179544119890851 ◽

2019 ◽

Vol 12 ◽

pp. 117954411989085

Author(s):

Lauren N Lucente ◽

Aseel Abu-Dayya ◽

Teresa Hennon ◽

Shamim Islam ◽

Brian H Wrotniak ◽

...

Keyword(s):

Health Care ◽

New York ◽

Lyme Disease ◽

Clinical Features ◽

Health Care Providers ◽

Pediatric Population ◽

Geographic Area ◽

Rapid Onset ◽

Lyme Arthritis ◽

Care Providers

Objective: This study explores a suspected increasing incidence of Lyme arthritis in the Western New York pediatric population. In addition, we aim to describe a clinical picture of Lyme arthritis and the clinical features that distinguish it from other forms of arthritis. Methods: Patients diagnosed with Lyme arthritis between January 2014 and September 2018 were identified using International Classification of Diseases—10th Revision (ICD 10) codes for Lyme disease and Lyme arthritis. Patients were included in the study if they (1) exhibited arthritis, (2) tested positive for Lyme antibodies, and (3) exhibited a positive Western blot. Results: A total of 22 patients were included in the study. There was a general trend toward an increasing number of cases of Lyme arthritis over the 45-month observation period. We identified 1 case in each 2014 and 2015, 4 cases in 2016, 7 in 2017, and 9 in the first 9 months of 2018. In total, 17 patients had arthritis as their only symptom at the time of diagnosis and 10 patients had a rash or a history that prompted suspicion of Lyme disease. The knee was the most frequent joint (86.4% of patients), and patients typically had 2 or fewer joints affected (86.4% of patients). Conclusions: A significant increase ( P = .02) in Lyme arthritis cases was observed at Oishei Children’s Hospital of Buffalo. Lyme arthritis may clinically present similarly to other forms of arthritis, such as oligoarticular juvenile idiopathic arthritis, so health care providers should be aware of distinguishing clinical features, which include rapid onset of swelling and patient age. Because the geographic area of endemic Lyme disease is expanding, all health care providers need to be aware of Lyme arthritis as a possible diagnosis.

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17 Lyme Disease in Eastern Ontario - A Paediatric Centre’s Experience from 2009-2018

Paediatrics & Child Health ◽

10.1093/pch/pxaa068.016 ◽

2020 ◽

Vol 25 (Supplement_2) ◽

pp. e6-e7

Author(s):

Stephanie Zahradnik ◽

Nick Barrowman ◽

Anne Tsampalieros ◽

Mary-Ann Harrison ◽

Jennifer Bowes ◽

...

Keyword(s):

Lyme Disease ◽

Laboratory Data ◽

Geographic Location ◽

Retrospective Chart Review ◽

Lyme Arthritis ◽

Annual Number ◽

Eastern Region ◽

Local Public Health ◽

Inpatient Ward ◽

Lyme Carditis

Abstract Background Lyme disease (LD) is caused by the tick-borne bacterium Borrelia burgdorferi. Over the past ten years, robust local public health data indicates that the incidence of LD has increased significantly in the eastern region of Ontario due to the spread of its vector, the blacklegged tick. As a result, we have seen an increase in the number of cases of LD in children at our tertiary paediatric centre, at all stages of infection. Familiarity with Lyme disease is important as incidence increases. We sought to characterize the cases at our centre. Objectives To describe the epidemiology of LD in children at our centre from 2009-2018, as well as the variety of clinical presentations of paediatric LD. Design/Methods We completed a retrospective chart review from 2009-2018 of all cases admitted or seen in the Infectious Disease (ID) clinic or the Emergency Department (ED) with a diagnosis of LD. Demographic, clinical and laboratory data were collected, including geographic location where infection occurred and resource utilization. We used descriptive statistics to describe cases and comparative statistics to determine changes in number of cases over time. Results There were 171 LD cases managed at our centre during this period. Mean age was 7.4 (SD 4.5) years, 89 (52.0%) were male. The annual number of cases from 2009 - 2018 increased from 1 to 44 and peaked in 2017 (47 cases). The highest number of cases occurred among children <6, the lowest in children ≥11. Most cases occurred in summer (60%), with the fewest in winter months (4%). Stage of LD was not documented in 1 case. Of the remainder, 98 (57.6%) cases were early localized, 41 (25.7%) early disseminated and 31 (19.7%) late disseminated LD. Early and late disseminated cases occurred more commonly in the summer and accounted for the majority of admissions. These included neurologic Lyme (lymphocytic meningitis [2, 1.2%], polyneuropathy [1, 0.6%], cranial nerve palsy [13, 7.6%]), Lyme carditis (5, 2.9%), and Lyme arthritis (29, 17.0%). There were 133 (77.8%) patients managed in ED, 66 (38.6%) in the ID clinic and 17 (9.9%) in the inpatient ward; median length of stay was 6 (IQR 5, 9) days, with a range of 1 to 30 days. The most common geographic locations of infection acquisition were Ottawa (120 cases, 71.0%) and Kingston (26, 15.4%). Conclusion Cases of LD managed at our paediatric centre have increased in keeping with population trends, with all LD stages experienced. Severe cases of meningitis, carditis, and arthritis resulted in hospitalization, with increasing numbers over the study period.

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Macrophage Polarization during Murine Lyme Borreliosis

Infection and Immunity ◽

10.1128/iai.00369-15 ◽

2015 ◽

Vol 83 (7) ◽

pp. 2627-2635 ◽

Cited By ~ 16

Author(s):

Carrie E. Lasky ◽

Rachel M. Olson ◽

Charles R. Brown

Keyword(s):

Lyme Disease ◽

Time Course ◽

Macrophage Polarization ◽

Lyme Arthritis ◽

Macrophage Phenotype ◽

Content Type ◽

C3h Mice ◽

Inflammatory Site ◽

Macrophage Subset ◽

Inflammatory Infiltrates

Infection of C3H mice withBorrelia burgdorferi, the causative agent of Lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. During Lyme disease it is clear that macrophages are capable of clearingBorreliaspirochetes and exhausted neutrophils; however, the role of macrophage phenotype in disease development or resolution has not been studied. Using classical (NOS2) and alternative (CD206) macrophage subset-specific markers, we determined the phenotype of F4/80+macrophages within the joints and heart throughout the infection time course. Within the joint, CD206+macrophages dominated throughout the course of infection, and NOS2+macrophage numbers became elevated only during the peak of inflammation. We also found dual NOS2+CD206+macrophages which increased during resolution. In contrast to findings for the ankle joints, numbers of NOS2+and CD206+macrophages in the heart were similar at the peak of inflammation. 5-Lipoxygenase-deficient (5-LOX−/−) mice, which display a failure of Lyme arthritis resolution, recruited fewer F4/80+cells to the infected joints and heart, but macrophage subset populations were unchanged. These results highlight differences in the inflammatory infiltrates during Lyme arthritis and carditis and demonstrate the coexistence of multiple macrophage subsets within a single inflammatory site.

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Serum epitope repertoire analysis enables early detection of Lyme disease with improved sensitivity in an expandable multiplex format

Journal of Clinical Microbiology ◽

10.1128/jcm.01836-20 ◽

2020 ◽

Author(s):

Jack Reifert ◽

Kathy Kamath ◽

Joel Bozekowski ◽

Ewa Lis ◽

Elizabeth J. Horn ◽

...

Keyword(s):

Lyme Disease ◽

Motif Discovery ◽

False Negative ◽

Serum Antibody ◽

High Sensitivity ◽

Bioinformatic Analysis ◽

Lyme Arthritis ◽

Igg Antibody ◽

Repertoire Analysis ◽

Validation Set

Widely employed diagnostic antibody serology for Lyme disease, known as standard two-tier testing (STTT), exhibits insufficient sensitivity in early Lyme disease yielding many thousands of false negative test results each year. Given this problem, we applied serum antibody repertoire analysis (SERA), or NGS-based serology, to discover IgG and IgM antibody epitope motifs capable of detecting Lyme disease specific antibodies with high sensitivity and specificity. Iterative motif discovery and bioinformatic analysis of epitope repertoires from subjects with Lyme disease (n = 264) and controls (n = 391) yielded a set of 28 epitope motifs representing 20 distinct IgG antibody epitopes, and set of 38 epitope motifs representing 21 distinct IgM epitopes which performed equivalently in a large validation cohort of STTT positive samples. In a second validation set from subjects with clinically-defined early Lyme disease (n=119) and controls (n = 257), the SERA Lyme IgG and IgM assay exhibited significantly improved sensitivity relative to STTT (77% vs. 62%, z-test, p = 0.013) and improved specificity (99% vs. 97%). Early Lyme disease subjects exhibited significantly fewer reactive epitopes (Mann-Whitney U-test, p < 0.0001), relative to subjects with Lyme arthritis. Thus, SERA Lyme IgG and M panels provided increased accuracy in early Lyme disease, in a readily expandable multiplex assay format.

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Seasonality of Acute Lyme Disease in Children

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6040196 ◽

2021 ◽

Vol 6 (4) ◽

pp. 196

Author(s):

Kathryn M. Sundheim ◽

Michael N. Levas ◽

Fran Balamuth ◽

Amy D. Thompson ◽

Desiree N. Neville ◽

...

Keyword(s):

Lyme Disease ◽

Regression Models ◽

Disease Incidence ◽

Erythema Migrans ◽

The United States ◽

Lyme Arthritis ◽

Cranial Neuropathy ◽

Acute Arthritis ◽

Presenting Symptoms ◽

Fourier Regression

Due to the life cycle of its vector, Lyme disease has known seasonal variation. However, investigations focused on children have been limited. Our objective was to evaluate the seasonality of pediatric Lyme disease in three endemic regions in the United States. We enrolled children presenting to one of eight Pedi Lyme Net participating emergency departments. Cases were classified based on presenting symptoms: early (single erythema migrans (EM) lesion), early-disseminated (multiple EM lesions, headache, cranial neuropathy, or carditis), or late (arthritis). We defined a case of Lyme disease by the presence of an EM lesion or a positive two-tier Lyme disease serology. To measure seasonal variability, we estimated Fourier regression models to capture cyclical patterns in Lyme disease incidence. While most children with early or early-disseminated Lyme disease presented during the summer months, children with Lyme arthritis presented throughout the year. Clinicians should consider Lyme disease when evaluating children with acute arthritis throughout the year.

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Lyme disease: New knowledge regarding its physiopathology, diagnosis, therapy and prevention

Medicinski pregled ◽

10.2298/mpns0206207v ◽

2002 ◽

Vol 55 (5-6) ◽

pp. 207-212

Author(s):

Jovan Vukadinov ◽

Sinisa Sevic ◽

Grozdana Canak ◽

Nadezda Madle-Samardzija ◽

Vesna Turkulov ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Antigenic Variation ◽

Clinical Symptoms ◽

Epidemiological Studies ◽

Lyme Arthritis ◽

Major Protein ◽

Selective Treatment ◽

Multisystem Disease ◽

New Guidelines

Introduction Lyme disease is a tick-borne disease caused by a spirochete Borrelia burgdorferi, which manifests as a multisystem disease of the skin nervous system, heart and joints. Recently it is the most common vector-borne disease in Yugoslavia. New epidemiological studies New epidemiological studies revealed that ticks can occasionally be infected not only by Borrelia burgdorferi, but also by some other microbes that can cause diseases in humans. Recently discovered the variable major protein-like sequence, antigenic variation of B. burgdorferi B 31 partly explains the ability of this organism to evade an active immune response. A key role in development of clinical symptoms associated with lyme disease belongs to the connection with ability of B. burgdorferi to induce and activate metallopeptidases and fibrinolytic enzymes, leading to extracellular matrix destruction. Diagnosis and treatment Diagnosis of Lyme borreliosis is made on the basis of clinical picture, exposure to ticks in endemic areas and serologic confirmation. It seems that polymerase chain reaction has little role in detection of B. burgdorferi in urine, blood, and spinal fluid samples, but it is most useful in evaluating the effectiveness of antibiotic therapy of Lyme arthritis. Infectious Diseases Society of America had prepared new guidelines for selective treatment of Lyme disease. Vaccination is still the best way of prevention for people living in high-risk areas.

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A Multiplexed Serologic Test for Diagnosis of Lyme Disease for Point-of-Care Use

Journal of Clinical Microbiology ◽

10.1128/jcm.01142-19 ◽

2019 ◽

Vol 57 (12) ◽

Cited By ~ 5

Author(s):

Siddarth Arumugam ◽

Samiksha Nayak ◽

Taylor Williams ◽

Francesco Serra di Santa Maria ◽

Mariana Soares Guedes ◽

...

Keyword(s):

Lyme Disease ◽

Confidence Interval ◽

Point Of Care ◽

Laboratory Diagnosis ◽

Lyme Arthritis ◽

Disease Stage ◽

Serologic Test ◽

Content Type ◽

Disease Stages ◽

Late Stages

ABSTRACT Single multiplexed assays could replace the standard 2-tiered (STT) algorithm recommended for the laboratory diagnosis of Lyme disease if they perform with a specificity and a sensitivity superior or equal to those of the STT algorithm. We used human serum rigorously characterized to be sera from patients with acute- and convalescent-phase early Lyme disease, Lyme arthritis, and posttreatment Lyme disease syndrome, as well as the necessary controls (n = 241 samples), to select the best of 12 Borrelia burgdorferi proteins to improve our microfluidic assay (mChip-Ld). We then evaluated its serodiagnostic performance in comparison to that of a first-tier enzyme immunoassay and the STT algorithm. We observed that more antigens became positive as Lyme disease progressed from early to late stages. We selected three antigens (3Ag) to include in the mChip-Ld: VlsE and a proprietary synthetic 33-mer peptide (PepVF) to capture sensitivity in all disease stages and OspC for early Lyme disease. With the specificity set at 95%, the sensitivity of the mChip-Ld with 3Ag ranged from 80% (95% confidence interval [CI], 56% to 94%) and 85% (95% CI, 74% to 96%) for two panels of serum from patients with early Lyme disease and was 100% (95% CI, 83% to 100%) for serum from patients with Lyme arthritis; the STT algorithm detected early Lyme disease in the same two panels of serum from patients with early Lyme disease with a sensitivity of 48.5% and 75% and Lyme arthritis in serum from patients with Lyme arthritis with a sensitivity of 100%, and the specificity was 97.5% to 100%. The mChip-Ld platform outperformed the STT algorithm according to sensitivity. These results open the door for the development of a single, rapid, multiplexed diagnostic test for point-of-care use that can be designed to identify the Lyme disease stage.

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