Suspected early Lyme neuroborreliosis in patients with erythema migrans.

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.

[1]  G Stanek,et al.  Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[2]  F. Harrell,et al.  Regression models in clinical studies: determining relationships between predictors and response. , 1988, Journal of the National Cancer Institute.

[3]  F. Strle,et al.  Comparison of Erythema Migrans Caused by Borrelia afzelii and Borrelia garinii , 2004, Infection.

[4]  F. Strle,et al.  Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  B. Svenungsson,et al.  Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis , 1990, Journal of clinical microbiology.

[6]  J. Halperin,et al.  The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[8]  V. Fingerle,et al.  EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis , 2010, European journal of neurology.

[9]  A. Pachner,et al.  Lyme neuroborreliosis: infection, immunity, and inflammation , 2007, The Lancet Neurology.

[10]  J. Booth,et al.  Resampling-Based Multiple Testing. , 1994 .

[11]  E. Steyerberg.  Clinical Prediction Models , 2008, Statistics for Biology and Health.

[12]  J. Halperin.  Nervous system involvement. , 2011 .

[13]  K. Dohi,et al.  Clinical and epidemiological findings for patients with erythema migrans. Comparison of cohorts from the years 1993 and 2000. , 1912 .

[14]  B. Wilske,et al.  European Borrelia burgdorferi isolated from humans and ticks culture conditions and antibiotic susceptibility. , 1986, Zentralblatt fur Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical microbiology, infectious diseases, virology, parasitology.

[15]  F. Strle,et al.  Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis , 2005, Scandinavian journal of infectious diseases.

[16]  Hansotto Reiber,et al.  Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs , 2001, Journal of the Neurological Sciences.

[17]  F. Strle,et al.  Clinical and epidemiological findings for patients with erythema migrans. Comparison of cohorts from the years 1993 and 2000. , 2002, Wiener Klinische Wochenschrift.

[18]  Jean Côté,et al.  Lyme Disease , 1991, International journal of dermatology.

[19]  B. Svenungsson,et al.  Clinical Manifestations and Diagnosis of Neuroborreliosis , 1988, Annals of the New York Academy of Sciences.

[20]  B. Luft,et al.  Lyme borreliosis. , 1994, International journal of antimicrobial agents.

[21]  G. Baranton,et al.  Guidelines for the diagnosis of tick-borne bacterial diseases in Europe. , 2004, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  F. Strle,et al.  Humoral Immune Responses in Patients with Lyme Neuroborreliosis , 2010, Clinical and Vaccine Immunology.

[23]  W. Burgdorfer,et al.  Aspects of Lyme Borreliosis , 1993, Springer Berlin Heidelberg.

[24]  H. Pfister,et al.  Early Neurological Involvement (Bannwarth’s Syndrome) , 1993 .

[25]  F. Strle,et al.  Characterisation of Borrelia burgdorferi sensu lato strains isolated from patients with skin manifestations of Lyme borreliosis residing in Slovenia. , 2000, Journal of medical microbiology.

[26]  E. Skogvoll,et al.  Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial , 2008, The Lancet Neurology.

[27]  F. Strle,et al.  Genotypic and phenotypic characterisation of Borrelia burgdorferi sensu lato strains isolated from human blood. , 2001, Journal of medical microbiology.

[28]  Martha Sajatovic,et al.  Clinical Prediction Models , 2013 .

[29]  F. Strle,et al.  Characterization of Borrelia burgdorferi sensu lato isolates by pulsed-field gel electrophoresis after MluI restriction of genomic DNA. , 2008, Research in microbiology.

[30]  G. Baranton,et al.  Diversity of Borrelia burgdorferi sensu lato evidenced by restriction fragment length polymorphism of rrf (5S)-rrl (23S) intergenic spacer amplicons. , 1994, International journal of systematic bacteriology.

[31]  J. Halperin,et al.  Erratum: The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America (Clinical Infectious Diseases (2006) 43, (1089-1134)) , 2007 .

[32]  A. Steere,et al.  The T-cell proliferative assay in the diagnosis of Lyme disease. , 1991, Annals of internal medicine.

[33]  J. Halperin.  Lyme disease: an evidence-based approach. , 2011 .

[34]  F. Strle,et al.  Characterization of Borrelia burgdorferi sensu lato strains isolated from human material in Slovenia. , 2002, Wiener klinische Wochenschrift.