Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Lyme Disease: A Review


Lyme disease is the most common vector-borne illness in the United States and is also endemic in Europe and Asia. It is caused by the spirochete Borrelia burgdorferi and transmitted by the bite of the Ixodes (deer) tick. It occurs most frequently during spring and summer and may involve the skin, nervous system, heart, and joints. This article reviews the pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Bacon RM, Kugeler KJ, Mead PS: Surveillance for Lyme disease—United States, 1992–2006. MMWR Surveill Summ 2008, 57:1–9.

  2. 2.

    Steere AC, Malawista SE, Snydman DR, et al.: Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum 1977, 20:7–17.

  3. 3.

    Burgdorfer W, Barbour AG, Hayes SF, et al.: Lyme disease—a tick-borne spirochetosis? Science 1982, 216:1317–1319.

  4. 4.

    Terekhova D, Iyer R, Wormser GP, Schwartz I: Comparative genome hybridization reveals substantial variation among clinical isolates of Borrelia burgdorferi sensu stricto with different pathogenic properties. J Bacteriol 2006, 188:6124–6134.

  5. 5.

    Stewart PE, Byram R, Grimm D, et al.: The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen. Plasmid 2005, 53:1–13.

  6. 6.

    Pal U, de Silva AM, Montgomery RR, et al.: Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. J Clin Invest 2000, 106:561–569.

  7. 7.

    Schwan TG, Piesman J, Golde WT, et al.: Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A 1995, 92:2909–2913.

  8. 8.

    Tilly K, Krum JG, Bestor A, et al.: Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection. Infect Immun 2006, 74:3554–3564.

  9. 9.

    Lagal V, Postic D, Rubic-Sabljic E, Baranton G: Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness. J Clin Microbiol 2003, 41:5059–5065.

  10. 10.

    Seinost G, Dykhuizen DE, Dattwyler RJ, et al.: Four clones of Borrelia burgdorferi sensu stricto cause invasive infection in humans. Infect Immun 1999, 67:3518–3524.

  11. 11.

    Labandeira-Rey M, Seshu J, Skare JT: The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms. Infect Immun 2003, 71:4608–4613.

  12. 12.

    Coutte L, Botkin DJ, Gao L, Norris SJ: Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS Pathog 2009, 5:e1000293.

  13. 13.

    Hirschfeld M, Kirschning CJ, Schwandner R, et al.: Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by Toll-like receptor 2. J Immunol 1999, 163:2382–2386.

  14. 14.

    Salazar JC, Pope CD, Sellati TJ, et al.: Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans. J Immunol 2003, 171:2660–2670.

  15. 15.

    Bolz DD, Sundsbak RS, Ma Y, et al.: MyD88 plays a unique role in host defense but not arthritis development in Lyme disease. J Immunol 2004, 173:2003–2010.

  16. 16.

    Petzke MM, Brooks A, Krupna MA, et al.: Recognition of Borrelia burgdorferi, the Lyme disease spirochete, by TLR7 and TLR9 induces a type I IFN response by human immune cells. J Immunol 2009, 183:5279–5292.

  17. 17.

    Miller JC, Ma Y, Bian J, et al.: A critical role for type I IFN in arthritis development following Borrelia burgdorferi infection of mice. J Immunol 2008, 181:8492–8503.

  18. 18.

    Zeidner NS, Schneider BS, Rutherford JS, Dolan MC: Suppression of Th2 cytokines reduces tick-transmitted Borrelia burgdorferi load in mice. J Parasitol 2008, 94:767–769.

  19. 19.

    Ekerfelt C, Andersson M, Olausson A, et al.: Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice. Clin Exp Immunol 2007, 150:189–197.

  20. 20.

    Muller-Doblies UU, Maxwell SS, Boppana VD, et al.: Feeding by the tick, Ixodes scapularis, causes CD4(+) T cells responding to cognate antigen to develop the capacity to express IL-4. Parasite Immunol 2007, 29:485–499.

  21. 21.

    Piesman J, Mather TN, Sinsky RJ, Spielman A: Duration of tick attachment and Borrelia burgdorferi transmission. J Clin Microbiol 1987, 25:557–558.

  22. 22.

    Nadelman RB, Nowakowski J, Forseter G, et al.: The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996, 100:502–508.

  23. 23.

    Strle F, Nadelman RB, Cimperman J, et al.: Comparison of culture-confirmed erythema migrans caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann Intern Med 1999, 130:32–36.

  24. 24.

    Steere AC, Dhar A, Hernandez J, et al.: Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease. Am J Med 2003, 114:58–62.

  25. 25.

    Steere AC, Schoen RT, Taylor E: The clinical evolution of Lyme arthritis. Ann Intern Med 1987, 107:725–731.

  26. 26.

    Drouin EE, Glickstein LJ, Kwok WW, et al.: Searching for borrelial T cell epitopes associated with antibiotic-refractory Lyme arthritis. Mol Immunol 2008, 45:2323–2332.

  27. 27.

    Steere AC, Klitz W, Drouin EE, et al.: Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med 2006, 203:961–971.

  28. 28.

    Gross DM, Forsthuber T, Tary-Lehmann M, et al.: Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 1998, 281:703–706.

  29. 29.

    Drouin EE, Glickstein LJ, Kwok WW, et al.: Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis. Mol Immunol 2008, 45:180–189.

  30. 30.

    Jones KL, McHugh GA, Glickstein LJ, Steere AC: Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: high frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis. Arthritis Rheum 2009, 60:2174–2182.

  31. 31.

    Codolo G, Amedei A, Steere AC, et al.: Borrelia burgdorferi NapA-driven Th17 cell inflammation in lyme arthritis. Arthritis Rheum 2008, 58:3609–3617.

  32. 32.

    Iliopoulou BP, Alroy J, Huber BT: CD28 deficiency exacerbates joint inflammation upon Borrelia burgdorferi infection, resulting in the development of chronic Lyme arthritis. J Immunol 2007, 179:8076–8082.

  33. 33.

    Halperin JJ, Volkman DJ, Wu P: Central nervous system abnormalities in Lyme neuroborreliosis. Neurology 1991, 41:1571–1582.

  34. 34.

    Halperin J, Luft BJ, Volkman DJ, Dattwyler RJ: Lyme neuroborreliosis. Peripheral nervous system manifestations. Brain 1990, 113:1207–1221.

  35. 35.

    Hemmer B, Gran B, Zhao Y, et al.: Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat Med 1999, 5:1375–1382.

  36. 36.

    Feder HM Jr, Johnson BJ, O’Connell S, et al.: A critical appraisal of “chronic Lyme disease.” N Engl J Med 2007, 357:1422–1430.

  37. 37.

    Marques A: Chronic Lyme disease: a review. Infect Dis Clin North Am 2008, 22:341–360, vii–viii.

  38. 38.

    Effect of electronic laboratory reporting on the burden of lyme disease surveillance—New Jersey, 2001–2006. MMWR Morb Mortal Wkly Rep 2008, 57:42–45.

  39. 39.

    Klempner MS, Schmid CH, Hu L, et al.: Intralaboratory reliability of serologic and urine testing for Lyme disease. Am J Med 2001, 110:217–219.

  40. 40.

    Wormser GP, Liveris D, Hanincova K, et al.: Effect of Borrelia burgdorferi genotype on the sensitivity of C6 and 2-tier testing in North American patients with culture-confirmed Lyme disease. Clin Infect Dis 2008, 47:910–914.

  41. 41.

    Strle F, Ruzic-Sabljic E, Cimperman J, et al.: Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. Clin Infect Dis 2006, 43:704–710.

  42. 42.

    Wormser GP, Brisson D, Liveris D, et al.: Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008, 198:1358–1364.

  43. 43.

    Nowakowski J, Schwartz I, Liveris D, et al.: Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin Infect Dis 2001, 33:2023–2027.

  44. 44.

    Cerar T, Rusic-Sabljic E, Glinsek U, et al.: Comparison of PCR methods and culture for the detection of Borrelia spp. in patients with erythema migrans. Clin Microbiol Infect 2008, 14:653–658.

  45. 45.

    Liveris D, Wang G, Girao G, et al.: Quantitative detection of Borrelia burgdorferi in 2-millimeter skin samples of erythema migrans lesions: correlation of results with clinical and laboratory findings. J Clin Microbiol 2002, 40:1249–1253.

  46. 46.

    Nocton JJ, Dressler F, Rutledge BJ, et al.: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 1994, 330:229–234.

  47. 47.

    Nocton JJ, Bloom BJ, Rutledge BJ, et al.: Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J Infect Dis 1996, 174:623–627.

  48. 48.

    Lebech AM, Hansen K, Brandrup F, et al.: Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis. Mol Diagn 2000, 5:139–150.

  49. 49.

    Zore A, Ruzic-Sabljic E, Maraspin V, et al.: Sensitivity of culture and polymerase chain reaction for the etiologic diagnosis of erythema migrans. Wien Klin Wochenschr 2002, 114:606–609.

  50. 50.

    Bacon RM, Biggerstaff BJ, Schriefer ME, et al.: Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J Infect Dis 2003, 187:1187–1199.

  51. 51.

    Glatz M, Fingerle V, Wilske B, et al.: Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with erythema migrans. Dermatology 2008, 216:93–103.

  52. 52.

    Kalish RA, McHugh G, Granquist, J, et al.: Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10–20 years after active Lyme disease. Clin Infect Dis 2001, 33:780–785.

  53. 53.

    Guidelines for laboratory evaluation in the diagnosis of Lyme disease. American College of Physicians. Ann Intern Med 1997, 127:1106–1108.

  54. 54.

    Notice to readers: caution regarding testing for Lyme disease. MMWR CDC Surveill Summ 2005, 54:125.

  55. 55.

    Marques A, Brown MR, Fleisher TA: Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin Vaccine Immunol 2009, 16:1249–1250.

  56. 56.

    Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995, 44:590–591.

  57. 57.

    Liang FT, Steere AC, Marques AR, et al.: Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi vlsE. J Clin Microbiol 1999, 37:3990–3996.

  58. 58.

    Ledue TB, Collins MF, Young J, Schriefer ME: Evaluation of the recombinant VlsE-based liaison chemiluminescence immunoassay for detection of Borrelia burgdorferi and diagnosis of Lyme disease. Clin Vaccine Immunol 2008, 15:1796–1804.

  59. 59.

    Steere AC, McHugh G, Damle N, Sikand VK: Prospective study of serologic tests for lyme disease. Clin Infect Dis 2008, 47:188–195.

  60. 60.

    Blanc F, Jaulhac B, Fleury M, et al.: Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients. Neurology 2007, 69:953–958.

  61. 61.

    Bakken JS, Dumler S: Human granulocytic anaplasmosis. Infect Dis Clin North Am 2008, 22:433–448, viii.

  62. 62.

    Vannier E, Gewurz BE, Krause PJ: Human babesiosis. Infect Dis Clin North Am 2008, 22:469–488, viii–ix.

  63. 63.

    Wormser GP, Dattwyler RJ, Shapiro ED, 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. Clin Infect Dis 2006, 43:1089–1134.

  64. 64.

    Masters EJ, Grigery CN, Masters RW: STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness. Infect Dis Clin North Am 2008, 22:361–376, viii.

  65. 65.

    Steere AC: Lyme borreliosis in 2005, 30 years after initial observations in Lyme Connecticut. Wien Klin Wochenschr 2006, 118:625–633.

  66. 66.

    Ball R, Shadomy SV, Meyer A, et al.: HLA type and immune response to Borrelia burgdorferi outer surface protein A in people in whom arthritis developed after Lyme disease vaccination. Arthritis Rheum 2009, 60:1179–1186.

Download references


This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.


No potential conflict of interest relevant to this article was reported.

Author information

Correspondence to Adriana R. Marques.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Marques, A.R. Lyme Disease: A Review. Curr Allergy Asthma Rep 10, 13–20 (2010). https://doi.org/10.1007/s11882-009-0077-3

Download citation


  • Lyme disease
  • Borrelia burgdorferi
  • Infection
  • Tick-borne illness