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Background: There is a general assumption that after deposition into skin, Lyme borreliae disseminate hematogenously to other organs, resulting in extracutaneous manifestations of Lyme borreliosis, including Lyme neuroborreliosis. However, our experience over the past 40 years, along with several published case reports that observed colocalization of radicular pain and erythema migrans (EM) in patients with borrelial meningoradiculoneuritis (Bannwarth syndrome), argues against hematogenous dissemination in Lyme neuroborreliosis., Methods: We compared the location of EM in 112 patients with Bannwarth syndrome to 12315 EM patients without neurological involvement. Moreover, we assessed the colocalization of EM and radicular pain in patients with Bannwarth syndrome., Results: Compared to >12000 EM patients without neurological involvement, patients with Bannwarth syndrome had a significantly higher frequency of EM on head/neck (6% vs 1%; P=.0005) and trunk (47% vs 24%; P<.0001), similar frequency on arms (16% vs 16%; P=.91), but lower frequency on legs (30% vs 59%; P<.0001). Moreover, in 79% (89/112) of patients the site of EM matched the dermatomes of radicular pain. The odds for a congruent location of EM and radicular pain were highly significant with the highest odds ratios (OR) observed for head (OR=221), followed by neck (OR=159), legs (OR=69), arms (OR=48), and trunk (OR=33)., Conclusions: The greater frequency of EM on head/neck and trunk and the colocalization of EM with radicular pain in patients with Bannwarth syndrome suggest that central nervous system involvement in Lyme neuroborreliosis is due to a retrograde spread of borrelia from skin to the spinal cord via peripheral nerves., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis.

Lyme disease, or Lyme borreliosis, is the most common tickborne disease in the United States and Europe. In both locations, Ixodes species ticks transmit the Borrelia burgdorferi sensu lato bacteria species responsible for causing the infection. The diversity of Borrelia species that cause human infection is greater in Europe; the 2 B. burgdorferi s.l. species collectively responsible for most infections in Europe, B. afzelii and B. garinii, are not found in the United States, where most infections are caused by B. burgdorferi sensu stricto. Strain differences seem to explain some of the variation in the clinical manifestations of Lyme disease, which are both minor and substantive, between the United States and Europe. Future studies should attempt to delineate the specific virulence factors of the different species of B. burgdorferi s.l. responsible for these variations in clinical features.

Acrodermatitis chronica atrophicans is a late manifestation of European Lyme borreliosis and is characterized by high levels of borrelial IgG antibodies, slowly expanding skin redness usually beginning on distal parts of extremities, and corresponding histologic findings. It very rarely develops in children. The main prerequisite for the diagnosis is clinical suspicion. In the present article we report on two children with acrodermatitis chronica atrophicans and on the findings of a PubMed literature search on acrodermatitis chronica atrophicans in childhood, published in the past three decades., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The aims of the study were to determine and compare the concentration of CXCL13 in cerebrospinal fluid (CSF) of patients with Lyme neuroborreliosis (LNB) and various other neurological disorders applying a Luminex based assay and ELISA, and to find factors associated with CXCL13 concentration. CSF samples obtained from four clinically well-defined groups of patients (proven LNB, suspected LNB, tick-borne encephalitis (TBE), and aseptic meningitis/meningoencephalitis other than TBE) - 25 samples per group - were analyzed. The performance of the Luminex recomBead CXCL13 assay (Microgen, Neuried, Germany) and ELISA (Euroimmun, Lübeck, Germany) was assessed by receiver operating characteristics. CXCL13 cut-off values were presented as functions of CSF lymphocyte/monocyte counts. Demographic variables, CSF findings, and history of erythema migrans were assessed as possible predictors for CXCL13 CSF concentrations by a general linear model. The calculated cut-off values determined by the maximum of the Youden index were >131 pg/mL for recomBead and >259 pg/mL for the ELISA. RecomBead showed a sensitivity of 88% (68.8-97.5%) and a specificity of 94% (83.5-98.7%). For the ELISA the corresponding values were 84% (63.9-95.5%) and 98% (89.4-99.9%). The CXCL13 concentration positively correlated with CSF lymphocyte/monocyte count and Borrelia-specific intrathecal antibody index (p < 0.05). High CXCL13 concentrations were only found in the group with proven LNB. CXCL13 levels above cut-off value were established in some patients with viral meningitis/meningoencephalitis but were not detected in patients with suspected LNB without pleocytosis. Applying a linearized cut-off of the CXCL13 concentration in the CSF which is dependent on the CSF cell count is a novel approach in the laboratory diagnosis of LNB., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Clinical characteristics associated with isolation of Borrelia burgdorferi sensu lato from skin have not been fully evaluated. To gain insight into predictors for a positive EM skin culture, we compared basic demographic, epidemiologic, and clinical data in 608 culture-proven and 501 culture-negative adult patients with solitary EM. A positive Borrelia spp. skin culture was associated with older age, a time interval of >2 days between tick bite and onset of the skin lesion, EM ≥ 5 cm in diameter, and location of the lesion on the extremities, whereas several other characteristics used as clinical case definition criteria for the diagnosis of EM (such as tick bite at the site of later EM, information on expansion of the skin lesion, central clearing) were not. A patient with a 15-cm EM lesion had almost 3-fold greater odds for a positive skin culture than patients with a 5-cm lesion. Patients with a free time interval between the tick bite and onset of EM had the same probability of a positive skin culture as those who did not recall a tick bite (OR=1.02); however, the two groups had >3-fold greater odds for EM positivity than patients who reported a tick bite with no interval between the bite and onset of the lesion. In conclusion, several yet not all clinical characteristics used in EM case definitions were associated with positive Borrelia spp. skin culture. The findings are limited to European patients with solitary EM caused predominantly by B. afzelii but may not be valid for other situations.

Background: Our objective was to obtain data on patients with erythema migrans (EM) who have symptoms/signs suggesting nervous system involvement and to compare epidemiologic, clinical, and microbiologic findings in patients with and without cerebrospinal fluid (CSF) pleocytosis., Methods: Adult patients with EM and suspected early Lyme neuroborreliosis were included in this study., Results: Of 161 patients, 31 (19%) had elevated and 130 (81%) had normal CSF cell counts. In contrast to patients with normal CSF cell counts, those with pleocytosis (1) more often reported radicular pain and more often presented with meningeal signs but less frequently complained of malaise; (2) had larger EM skin lesions despite similar duration; (3) more commonly had Borrelia garinii isolated from EM skin lesions (odds ratio for pleocytosis was 31 times higher in patients with established B. garinii skin infection compared to patients with other Borrelia species isolated from their EM skin lesion) and from CSF; and (4) more frequently fulfilled microbiologic criteria for established borrelial infection of the central nervous system. The positive predictive value of pleocytosis for microbiologically proven borrelial infection of the central nervous system (defined by isolation of Borrelia from CSF and/or demonstration of intrathecal synthesis of borrelial antibodies) was 67.9%, whereas normal CSF white cell counts ruled out Lyme neuroborreliosis with a predictive value of 91.9%., Conclusions: Comparison of European patients with EM who had symptoms/signs suggesting early Lyme neuroborreliosis revealed several differences in the clinical presentation and in microbiologic test results according to CSF findings.

Basic epidemiological findings on Lyme borreliosis in Slovenia are presented. Data on vertebrate reservoir hosts are relatively modest. The presence of Borrelia burgdorferi sensu lato was demonstrated in about 20% of deer and 15-41% of examined small mammals. The presence of B. burgdorferi sensu lato was found by polymerase chain reaction in one half of 34 examined small mammals. Ixodes ricinus ticks have been found infected in all geographical regions of Slovenia examined till now. The highest infection rate was detected in the central part of Slovenia where almost 50% of adult ticks and one third of nymphs were positive by culture. The first isolation of B. burgdorferi sensu lato from material of Slovene patients succeeded in 1988 while the first isolates from ticks were obtained as late as 1993. The source material of human isolates has been skin, blood, cerebrospinal fluid, as well as synovial tissue and fluid. Thus far four Borrelia species were found by isolation to cause disease in humans: B. afzelii, B. garinii, B. burgdorferi sensu stricto, and B. bissettii. The majority of typed isolates belong to B. afzelii, but B. garinii slightly predominates among strains cultured from cerebrospinal fluid. Lyme borreliosis has been mandatory reportable in Slovenia for the last 11 years. It is the most common tick-borne disease and is present all over the country. The incidence has been increasing. In 1997 155/100,000 cases were recorded; in some regions the incidence was even substantially higher. The disease affects both sexes (as a rule more often women than men) and all age groups. The incidence is the highest in persons 30-50 years of age, followed by children aged 6-15 years. Erythema migrans is by far the most common recorded manifestation.

Background: The clinical manifestations of Lyme borreliosis in North America and Europe seem to differ, but a systematic comparison has never been done., Objective: To compare European and U.S. patients with culture-confirmed erythema migrans., Design: Prospective, clinical cohort study., Setting: University medical centers in Westchester County, New York, and Ljubljana, Slovenia., Patients: 119 U.S. patients with Borrelia burgdorferi sensu stricto infection and 85 Slovenian patients with B. afzelii infection., Measurements: Interview, physical examination, and laboratory assays., Results: Compared with Slovenian patients, U.S. patients had erythema migrans for a briefer duration (median duration, 4 days compared with 14 days; P < 0.001) but were more likely to have systemic symptoms (P = 0.01), abnormal findings on physical examination (P < 0.001), and seroreactivity (P < 0.001). Central clearing of erythema migrans lesions was more likely in Slovenian patients (P < 0.001)., Conclusions: Erythema migrans caused by B. afzelii in Slovenia and erythema migrans caused by B. burgdorferi in New York have distinct clinical presentations. Caution should be used when clinical and laboratory experience from one side of the Atlantic is applied to patients on the other.

In spring 1993, Ixodes ricinus ticks were collected from six regions of Slovenia to determine their overall rate of infection with Borrelia burgdorferi sensu lato and to assess the frequency of individual species in these tick populations. Ticks were dissected and midgut tissue inoculated into modified Barbour-Stoenner-Kelly (BSK II) medium. Borrelia isolates were differentiated into separate species using species-specific polymerase chain reaction (PCR) primers and by large restriction fragment pattern (LRFP) analysis. Infected ticks were found in all six regions surveyed. Spirochaetes were isolated from 69 of 363 ticks (19%): the isolation rate from adult female ticks was 35% (23/66 ticks cultured), from adult male ticks 22% (20/91), and from nymphal ticks 13% (26/206). Determination of the species of 60 isolates revealed that 32 were Borrelia afzelii (53%), 20 were Borrelia garinii (33%), and 8 were Borrelia burgdorferi sensu stricto (13%). In the Ljubljana region Borrelia afzelii and Borrelia garinii predominated (43% and 40%, respectively), whereas Borrelia burgdorferi sensu stricto constituted only 17% of isolates. In three other regions of the country Borrelia afzelii was isolated exclusively, although the number of isolates investigated was small. This study demonstrates the presence of all three European species of Borrelia burgdorferi sensu lato within the Slovenian tick population and also within a geographic area of less than 100 m2.

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations. [ABSTRACT FROM AUTHOR]