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Clinical manifestations of Lyme disease in adults

Linden Hu, MD
Section Editor
Allen C Steere, MD
Deputy Editor
Jennifer Mitty, MD, MPH


Lyme disease is a tick-borne illness, which is typically caused by three pathogenic species of the spirochete Borrelia burgdorferi sensu lato. B. burgdorferi is the primary cause of the disease in the United States. All three pathogenic species, B. burgdorferi, Borrelia afzelii, and Borrelia garinii, occur in Europe, and the latter two species have been identified in Asia. Lyme disease has a broad spectrum of clinical manifestations, and it also varies in severity due, in part, to differences in the infecting species.

Lyme disease was first described in 1977 as "Lyme arthritis" in studies of a cluster in Connecticut of children who were thought to have juvenile rheumatoid arthritis [1]. The multisystem nature of the infection became clear as involvement of other systems was subsequently identified [2,3].

An overview of the clinical manifestations of Lyme disease in adults will be reviewed here. Issues related to bacteriology, epidemiology, diagnosis, and treatment of Lyme disease, as well as more detailed discussions of the clinical manifestations of Lyme disease, are reviewed separately.

(See "Microbiology of Lyme disease".)

(See "Epidemiology of Lyme disease".)

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Literature review current through: Dec 2017. | This topic last updated: Aug 17, 2016.
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  1. 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.
  2. Steere AC, Malawista SE, Hardin JA, et al. Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum. Ann Intern Med 1977; 86:685.
  3. Steere AC. Lyme disease. N Engl J Med 2001; 345:115.
  4. Steere AC. Lyme disease. N Engl J Med 1989; 321:586.
  5. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012; 379:461.
  6. 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.
  7. Jones KL, Muellegger RR, Means TK, et al. Higher mRNA levels of chemokines and cytokines associated with macrophage activation in erythema migrans skin lesions in patients from the United States than in patients from Austria with Lyme borreliosis. Clin Infect Dis 2008; 46:85.
  8. 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.
  9. Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review. JAMA 2016; 315:1767.
  10. Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med 2003; 348:2472.
  11. 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.
  12. Edlow JA. Erythema migrans. Med Clin North Am 2002; 86:239.
  13. Hengge UR, Tannapfel A, Tyring SK, et al. Lyme borreliosis. Lancet Infect Dis 2003; 3:489.
  14. Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med 2002; 136:421.
  15. Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med 2005; 142:751.
  16. Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983; 99:76.
  17. 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.
  18. Nowakowski J, McKenna D, Nadelman RB, et al. Blood cultures for patients with extracutaneous manifestations of Lyme disease in the United States. Clin Infect Dis 2009; 49:1733.
  19. Halperin JJ. Nervous system Lyme disease. Infect Dis Clin North Am 2008; 22:261.
  20. Reimers CD, Neubert U. Garin-Bujadoux-Bannwarth syndrome. Lancet 1990; 336:128.
  21. Stanek G, Strle F. Lyme disease: European perspective. Infect Dis Clin North Am 2008; 22:327.
  22. Ogrinc K, Lusa L, Lotrič-Furlan S, et al. Course and Outcome of Early European Lyme Neuroborreliosis (Bannwarth Syndrome): Clinical and Laboratory Findings. Clin Infect Dis 2016; 63:346.
  23. Sauer A, Hansmann Y, Jaulhac B, et al. Five cases of paralytic strabismus as a rare feature of lyme disease. Clin Infect Dis 2009; 48:756.
  24. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep 2013; 62:993.
  25. Forrester JD, Meiman J, Mullins J, et al. Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death--United States. MMWR Morb Mortal Wkly Rep 2014; 63:982.
  26. Stanek G, Strle F. Lyme borreliosis. Lancet 2003; 362:1639.
  27. Mikkilä HO, Seppälä IJ, Viljanen MK, et al. The expanding clinical spectrum of ocular lyme borreliosis. Ophthalmology 2000; 107:581.
  28. Strle F, Pleterski-Rigler D, Stanek G, et al. Solitary borrelial lymphocytoma: report of 36 cases. Infection 1992; 20:201.
  29. Mullegger RR. Dermatological manifestations of Lyme borreliosis. Eur J Dermatol 2004; 14:296.
  30. Colli C, Leinweber B, Müllegger R, et al. Borrelia burgdorferi-associated lymphocytoma cutis: clinicopathologic, immunophenotypic, and molecular study of 106 cases. J Cutan Pathol 2004; 31:232.
  31. Picken RN, Strle F, Ruzic-Sabljic E, et al. Molecular subtyping of Borrelia burgdorferi sensu lato isolates from five patients with solitary lymphocytoma. J Invest Dermatol 1997; 108:92.
  32. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987; 107:725.
  33. Dinerman H, Steere AC. Lyme disease associated with fibromyalgia. Ann Intern Med 1992; 117:281.
  34. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990; 323:1438.
  35. Halperin JJ, Luft BJ, Anand AK, et al. Lyme neuroborreliosis: central nervous system manifestations. Neurology 1989; 39:753.
  36. Oschmann P, Dorndorf W, Hornig C, et al. Stages and syndromes of neuroborreliosis. J Neurol 1998; 245:262.
  37. Logigian EL, Steere AC. Clinical and electrophysiologic findings in chronic neuropathy of Lyme disease. Neurology 1992; 42:303.
  38. Balmelli T, Piffaretti JC. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol 1995; 146:329.
  39. Asbrink E, Hovmark A, Olsson I. Clinical manifestations of acrodermatitis chronica atrophicans in 50 Swedish patients. Zentralbl Bakteriol Mikrobiol Hyg A 1986; 263:253.
  40. Asbrink E, Hovmark A. Early and late cutaneous manifestations in Ixodes-borne borreliosis (erythema migrans borreliosis, Lyme borreliosis). Ann N Y Acad Sci 1988; 539:4.
  41. Moreno C, Kutzner H, Palmedo G, et al. Interstitial granulomatous dermatitis with histiocytic pseudorosettes: a new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA. J Am Acad Dermatol 2003; 48:376.
  42. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001; 345:85.
  43. Kaplan RF, Trevino RP, Johnson GM, et al. Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology 2003; 60:1916.
  44. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003; 60:1923.
  45. Bockenstedt LK, Mao J, Hodzic E, et al. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis 2002; 186:1430.
  46. Hodzic E, Feng S, Holden K, et al. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother 2008; 52:1728.
  47. Halperin JJ, Shapiro ED, Logigian E, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2007; 69:91.
  48. Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of "chronic Lyme disease". N Engl J Med 2007; 357:1422.
  49. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008; 70:992.
  50. Nelson C, Elmendorf S, Mead P. Neoplasms misdiagnosed as "chronic lyme disease". JAMA Intern Med 2015; 175:132.
  51. Lightfoot RW Jr, Luft BJ, Rahn DW, et al. Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis. Ann Intern Med 1993; 119:503.
  52. Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995; 38:19.
  53. Nadelman RB, Wormser GP. Reinfection in patients with Lyme disease. Clin Infect Dis 2007; 45:1032.
  54. Krause PJ, Foley DT, Burke GS, et al. Reinfection and relapse in early Lyme disease. Am J Trop Med Hyg 2006; 75:1090.
  55. Nadelman RB, Hanincová K, Mukherjee P, et al. Differentiation of reinfection from relapse in recurrent Lyme disease. N Engl J Med 2012; 367:1883.
  56. Steere AC. Reinfection versus relapse in Lyme disease. N Engl J Med 2012; 367:1950.
  57. Schlesinger PA, Duray PH, Burke BA, et al. Maternal-fetal transmission of the Lyme disease spirochete, Borrelia burgdorferi. Ann Intern Med 1985; 103:67.
  58. MacDonald AB, Benach JL, Burgdorfer W. Stillbirth following maternal Lyme disease. N Y State J Med 1987; 87:615.
  59. Weber K, Bratzke HJ, Neubert U, et al. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. Pediatr Infect Dis J 1988; 7:286.
  60. Markowitz LE, Steere AC, Benach JL, et al. Lyme disease during pregnancy. JAMA 1986; 255:3394.
  61. Williams CL, Strobino B, Weinstein A, et al. Maternal Lyme disease and congenital malformations: a cord blood serosurvey in endemic and control areas. Paediatr Perinat Epidemiol 1995; 9:320.
  62. Silver HM. Lyme disease during pregnancy. Infect Dis Clin North Am 1997; 11:93.
  63. Strobino BA, Williams CL, Abid S, et al. Lyme disease and pregnancy outcome: a prospective study of two thousand prenatal patients. Am J Obstet Gynecol 1993; 169:367.
  64. Maraspin V, Cimperman J, Lotric-Furlan S, et al. Treatment of erythema migrans in pregnancy. Clin Infect Dis 1996; 22:788.
  65. Strobino B, Abid S, Gewitz M. Maternal Lyme disease and congenital heart disease: A case-control study in an endemic area. Am J Obstet Gynecol 1999; 180:711.
  66. Gerber MA, Zalneraitis EL. Childhood neurologic disorders and Lyme disease during pregnancy. Pediatr Neurol 1994; 11:41.
  67. Swanson SJ, Neitzel D, Reed KD, Belongia EA. Coinfections acquired from ixodes ticks. Clin Microbiol Rev 2006; 19:708.
  68. Krause PJ, McKay K, Thompson CA, et al. Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease. Clin Infect Dis 2002; 34:1184.
  69. Steere AC, McHugh G, Suarez C, et al. Prospective study of coinfection in patients with erythema migrans. Clin Infect Dis 2003; 36:1078.
  70. Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA 1996; 275:1657.
  71. Belongia EA, Reed KD, Mitchell PD, et al. Clinical and epidemiological features of early Lyme disease and human granulocytic ehrlichiosis in Wisconsin. Clin Infect Dis 1999; 29:1472.
  72. Horowitz HW, Aguero-Rosenfeld ME, Holmgren D, et al. Lyme disease and human granulocytic anaplasmosis coinfection: impact of case definition on coinfection rates and illness severity. Clin Infect Dis 2013; 56:93.