Skin manifestations of lyme borreliosis: Diagnosis and management

American Journal of Clinical Dermatology

Volumn 9, Issue 6, 2008, Pages 355-368

  Müllegger, Robert R ^a,c   Glatz, Martin ^b  

^a Wiener Neustadt General Hospital   (Austria)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

^c General Hospital Wiener Neustadt   (Austria)

Author keywords

Doxycycline, therapeutic use; Lyme disease, general

Indexed keywords

AMOXICILLIN; AZITHROMYCIN; CEFUROXIME AXETIL; DOXYCYCLINE; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; PENICILLIN V;

ACRODERMATITIS CHRONICA ATROPHICANS; ANAPLASMA PHAGOCYTOPHILUM; ANTIMICROBIAL THERAPY; BORRELIA BURGDORFERI; CLINICAL ASSESSMENT; CLINICAL FEATURE; DRUG CONTRAINDICATION; DRUG INDICATION; ENZYME LINKED IMMUNOSORBENT ASSAY; EOSINOPHILIC FASCIITIS; ERYTHEMA CHRONICUM MIGRANS; FALSE NEGATIVE RESULT; HISTOPATHOLOGY; HUMAN; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; LYME DISEASE; LYMPHOCYTOMA; MIXED INFECTION; PHOTOSENSITIVITY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGNOSIS; REVIEW; SERODIAGNOSIS; SEROPREVALENCE; SKIN LYMPHOMA; SKIN MANIFESTATION; SPIROCHETE; TICK; TICK BITE; TREATMENT DURATION;

ACRODERMATITIS; ANIMALS; BORRELIA BURGDORFERI GROUP; ERYTHEMA CHRONICUM MIGRANS; HUMANS; LYME DISEASE; LYMPHATIC DISEASES; LYMPHOMA, B-CELL; SKIN DISEASES, BACTERIAL;

EID: 55249122136     PISSN: 11750561     EISSN: None     Source Type: Journal    
DOI: 10.2165/0128071-200809060-00002     Document Type: Review

References (181)

1. Steere AC. Lyme disease. N Engl J Med 2001; 345: 115-25
2. Stanek G, Strle F. Lyme borreliosis. Lancet 2003; 362: 1639-47
3. Dennis DT, Hayes EB. Epidemiology of Lyme borreliosis. In: Gray J, Kahl O, Lane RS, et al., editors. Lyme borreliosis: biology, epidemiology and control. Oxon (NY): CABI Publishing, 2002: 251-80
4. O'Connell S, Granström M, Gray JS, et al. Epidemiology of European Lyme borreliosis. Zentralbl Bakteriol 1998; 287: 229-40
5. Orloski KA, Hayes EB, Campbell GL, et al. Surveillance for Lyme disease: United States, 1992-1998. MMWR CDC Surveill Summ 2000; 49: 1-11
6. Strle F, Maraspin V, Furlan-Lotric S, et al. Epidemiological study of a cohort of adult patients with erythema migrans registered in Slovenia in 1993. Eur J Epidemiol 1996; 12: 503-7
7. Picken RN, Strle F, Picken MM, et al. Identification of three species of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto, B. garinii, and B. afzelii) among isolates from acrodermatitis chronica atrophicans lesions. J Invest Dermatol 1998; 110: 211-4
8. Van Dam AP, Kuiper H, Vos K, et al. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis 1993; 17: 708-17
9. Wang G, van Dam AP, Spanjaard L, et al. Molecular typing of Borrelia burgdorferi sensu lato by randomly amplified polymorphic DNA fingerprinting analysis. J Clin Microbiol 1998; 36: 768-76
10. Nigrovic LE, Thompson KM. The Lyme vaccine: a cautionary tale. Epidemiol Infect 2007; 135: 1-8
11. Mullegger RR. Dermatological manifestations of Lyme borreliosis. Eur J Dermatol 2004; 14: 296-309
12. Berger BW. Dermatologic manifestations of Lyme disease. Rev Infect Dis 1989; 11 Suppl. 6: S1475-81
13. Nadelman RB, Nowakowski J, Förseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996; 100: 502-8
14. Steere AC, Bartenhagen NH, Craft JE, et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983; 99: 76-82
15. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med 1995; 98 Suppl. 4A: 15S-24S
16. 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: 421-8
17. Müllegger RR. Clinical aspects and diagnosis of erythema migrans and borrelial lymphocytoma. Acta Dermatoven APA 2001; 10: 152-8
18. Strle F, Nelson JA, Ruzic-Sabljic E, et al. European Lyme borreliosis: 231 culture-confirmed cases involving patients with erythema migrans. Clin Infect Dis 1996; 23: 61-5
19. Strle F, Videcnik J, Zorman P, et al. Clinical and epidemiological findings for patients with erythema migrans: comparison of cohorts from the years 1993 and 2000. Wien Klin Wochenschr 2002; 114: 493-7
20. Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance: Lyme disease (revised 9/96). MMWR Morb Mortal Wkly Rep 1997; 46 (RR-10): 1-51
21. Arnez M, Pleterski-Rigler D, Ahcan J, et al. Demographic features, clinical characteristics and laboratory findings in children with multiple erythema migrans in Slovenia. Wien Klin Wochenschr 2001; 113: 98-101
22. Oksi J, Marttila H, Soini H, et al. Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans. APMIS 2001; 109: 581-8
23. Stanek G, O'Connell S, Cimmino M, et al. European Union concerted action on risk assessment in Lyme borreliosis: clinical case definitions for Lyme borreliosis. Wien Klin Wochenschr 1996; 108: 741-7
24. Strle F, Nadelman RB, Cimperman J, et al. Comparison of culture-confirmed erythema migrans caused by Borrelia burgdorferi sensu stricto in New York and by Borrelia afzelii in Slovenia. Ann Intern Med 1999; 130: 32-6
25. Wormser GP, Masters E, Nowakowski J, et al. Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions. Clin Infect Dis 2005; 41: 958-65
26. Jones KL, Müllegger RR, Means TK, et al. Higher mRNA levels of chemokines and cytokines associated with macrophage activation in erythema migrans skin lesions in American than Austrian patients with Lyme borreliosis. Clin Infect Dis 2008; 46: 85-92
27. Weber K, Neubert U. Clinical features of early erythema migrans disease and related disorders. Zentralbl Bakteriol 1986; 263: 209-28
28. Åsbrink E, Hovmark A. Early and late cutaneous manifestations in Ixodes-borne borreliosis (erythema migrans borreliosis, Lyme borreliosis). Ann N Y Acad Sci 1988; 539: 4-15
29. Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med 2005; 142: 751-5
30. Åsbrink E. Erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans: early and late manifestations of Ixodes ricinus-borne Borrelia spirochetes. Acta Derm Venereol Suppl (Stockh) 1985; 118: 1-63
31. Maraspin V, Cimperman J, Lotric-Furlan S, et al. Cerebrospinal fluid findings in adult patients with multiple erythema migrans. Wien Klin Wochenschr 2002; 114: 505-9
32. Rahn DW, Malawista SE. Lyme disease: recommendations for diagnosis and treatment. Ann Intern Med 1991; 114: 472-81
33. Lipsker D, Lieber-Mbomeyo A, Hedelin G. How accurate is a clinical diagnosis of erythema chronicum migrans? Prospective study comparing the diagnostic accuracy of general practitioners and dermatologists in an area where Lyme borreliosis is endemic. Arch Dermatol 2004; 140: 620-1
34. Åsbrink E. Cutaneous manifestations of Lyme borreliosis: clinical definitions and differential diagnoses. Scand J Infect Dis Suppl 1991; 77: 44-50
35. Wormser GP, Masters E, Liveris D, et al. Microbiologic evaluation of patients from Missouri with erythema migrans. Clin Infect Dis 2005; 40: 423-8
36. Goldberg NS, Forseter G, Nadelman RB, et al. Vesicular erythema migrans. Arch Dermatol 1992; 128: 1495-8
37. Brooke CJ, Riley TV. Erysipelothrix rhusiopathiae: bacteriology, epidemiology and clinical manifestations of an occupational pathogen. J Med Microbiol 1999; 48: 789-99
38. Hovmark A, Åsbrink E, Olsson I. The spirochetal etiology of lymphadenosis benigna cutis solitaria. Acta Derm Venereol (Stockh) 1986; 66: 479-84
39. 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: 92-7
40. 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: 232-40
41. Åsbrink E, Hovmark A, Olsson I. Lymphadenosis benigna cutis solitaria: Borrelia lymphocytoma in Sweden. Zentralbl Bakteriol 1989; Suppl. 18: 156-63
42. Maraspin V, Cimperman J, Lotric-Furlan S, et al. Solitary borrelial lymphocytoma in adult patients. Wien Klin Wochenschr 2002; 114: 515-23
43. Strle F, Pleterski-Rigler D, Stanek G, et al. Solitary borrelial lymphocytoma: report of 36 cases. Infection 1992; 20: 201-6
44. Strle F, Maraspin V, Pleterski-Rigler D, et al. Treatment of borrelial lymphocytoma. Infection 1996; 24: 80-4
45. Grange F, Wechsler J, Guillaume JC, et al. Borrelia burgdorferi-associated lymphocytoma cutis simulating a primary cutaneous large B-cell lymphoma. J Am Acad Dermatol 2002; 47: 530-4
46. Armstrong DK, Walsh MY, Dawson JF. Granulomatous contact dermatitis due to gold earrings. Br J Dermatol 1997; 136: 776-8
47. Hovmark A, Åsbrink E, Weber K, et al. Borrelial lymphocytoma. In: Weber K, Burgdorfer W, editors. Aspects of Lyme borreliosis. Berlin: Springer, 1993: 122-30
48. DiCaudo DJ, Su WP, Marshall WF, et al. Acrodermatitis chronica atrophicans in the United States: clinical and histopathologic features of six cases. Cutis 1994; 54: 81-4
49. Ohlenbush A, Matuscha FR, Richter D, et al. Etiology of acrodermatitis chronica atrophicans lesion in Lyme disease. J Infect Dis 1996; 174: 421-3
50. Müllegger RR, Means TK, Shin JJ, et al. Chemokine signatures in the skin disorders of Lyme borreliosis in Europe: predominance of CXCL9 and CXCL10 in erythema migrans and acrodermatitis and CXCL13 in lymphocytoma. Infect Immun 2007; 75: 4621-8
51. Zalaudek I, Leinweber B, Kerl H, et al. Acrodermatitis chronica atrophicans in a 15-year-old girl misdiagnosed as venous insufficiency for 6 years. J Am Acad Dermatol 2005; 52: 1091-4
52. Åsbrink E, Hovmark A, Olsson I. Clinical manifestations of acrodermatitis chronica atrophicans in 50 Swedish patients. Zentralbl Bakteriol Mikrobiol Hyg A 1986; 263: 253-61
53. Åsbrink E, Hovmark A, Weber K. Acrodermatitis chronica atrophicans. In: Weber K, Burgdorfer W, editors. Aspects of Lyme borreliosis. Berlin: Springer, 1993: 193-204
54. Weber K, Schierz G, Wilske B, et al. European erythema migrans disease and related disorders. Yale J Biol Med 1984; 57: 463-71
55. Marsch WC, Mayet A, Wolter M. Cutaneous fibroses induced by Borrelia pepburgdorferi. Br J Dermatol 1993; 128: 674-8
56. Binder B, Kerl H, Müllegger RR. Differential diagnosis of acrodermatitis chronica atrophicans with emphasis on chronic venous insufficiency. Phlebologie 2004; 33: 191-8
57. Fagrell B, Stiernstedt G, Ostergren J. Acrodermatitis chronica atrophicans Herxheimer can often mimic a peripheral vascular disorder. Acta Med Scand 1986; 220: 485-8
58. Kindstrand E, Nilsson BY, Hovmark A, et al. Peripheral neuropathy in acrodermatitis chronica atrophicans: a late Borrelia manifestation. Acta Neurol Scand 1997; 95: 338-45
59. Brehmer-Andersson E, Hovmark A, Asbrink E. Acrodermatitis chronica atrophicans: histopathologic findings and clinical correlations in 111 cases. Acta Derm Venereol (Stockh) 1998; 78: 207-13
60. Panelius J, Lahdenne P, Heikkila T, et al. Recombinant OspC from Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii in the serodiagnosis of Lyme borreliosis. J Med Microbiol 2002; 51: 731-9
61. Weiss NL, Sadock VA, Sigal LH, et al. False positive seroreactivity to Borrelia burgdorferi in systemic lupus erythematosus: the value of immunoblot analysis. Lupus 1995; 4: 131-7
62. Berglund J, Eitrem R, Norrby SR. Long-term study of Lyme borreliosis in a highly endemic area in Sweden. Scand J Infect Dis 1996; 28: 473-8
63. Hilton E, DeVoti J, Benach JL, et al. Seroprevalence and seroconversion for tick-borne diseases in a high-risk population in the northeast United States. Am J Med 1999; 106: 404-9
64. Guy EC, Robertson JN, Cimmino M, et al. European interlaboratory comparison of Lyme borreliosis serology. Zentralbl Bakteriol 1998; 287: 241-7
65. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995; 44: 590-1
66. Robertson J, Guy E, Andrews N, et al. A European multicenter study of immunoblotting in serodiagnosis of Lyme borreliosis. J Clin Microbiol 2000; 38: 2079-102
67. Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol 1995; 33: 419-27
68. Dressler F, Whalen JA, Reinhardt BN, et al. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 1993; 167: 392-400
69. Batsford S, Rust C, Neubert U. Analysis of antibody response to the outer surface protein family in Lyme borreliosis patients. J Infect Dis 1998; 178: 1676-83
70. Liang FT, Philipp MT. Analysis of antibody response to invariable regions of VlsE, the variable surface antigen of Borrelia burgdorferi. Infect Immun 1999; 67: 6702-6
71. Mathiesen MJ, Hansen K, Axelsen N, et al. Analysis of the human antibody response to outer surface protein C (OspC) of Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii. Med Microbiol Immunol 1996; 185: 121-9
72. Wilske B, Fingerle V, Herzer P, et al. Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Med Microbiol Immunol 1993; 182: 255-70
73. Aguero-Rosenfeld ME, Nowakowski J, Bittker S, et al. Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans. J Clin Microbiol 1996; 34: 1-9
74. Lebech AM, Hansen K, Bandrup 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: 139-50
75. Picken MM, Picken RN, Han D, et al. A two-year prospective study to compare culture and polymerase chain reaction amplification for the detection and diagnosis of Lyme borreliosis. Mol Pathol 1997; 50: 186-93
76. Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev 2005; 18: 484-509
77. Rauter C, Mueller M, Diterich I, et al. Critical evaluation of urine-based PCR assay for diagnosis of Lyme borreliosis. Clin Diag Lab Immunol 2005; 12: 910-2
78. Luft BJ, Dattwyler RJ, Johnson RC, et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans: a double-blind, randomized, controlled trial. Ann Intern Med 1996; 124: 785-91
79. 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: 2023-7
80. 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: 1187-99
81. 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: 3990-6
82. Philipp MT, Wormser GP, Marques AR, et al. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin Diagn Lab Immunol 2005; 12: 1069-74
83. Sillanpäa H, Lahdenne P, Sarvas H, et al. Immune responses to borrelial VlsE IR6 peptide variants. Int J Med Microbiol 2007; 297: 45-52
84. Brettschneider S, Bruckbauer H, Klugbauer N, et al. Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis. J Clin Microbiol 1998; 36: 2658-65
85. 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: 606-9
86. Coulter P, Lema C, Flayhart D, et al. Two-year evaluation of Borrelia burgdorferi culture and supplemental tests for definitive diagnosis of Lyme disease. J Clin Microbiol 2005; 43: 5080-4
87. Ruzic-Sabljic E, Lotric-Furlan S, Maraspin V, et al. Comparison of isolation rate of Borrelia burgdorferi sensu lato in MKP and BSK-II medium. Int J Med Microbiol 2006; 296 Suppl. 40: 267-73
88. Maraspin V, Ruzic-Sabljic E, Cimperman J, et al. Isolation of Borrelia burgdorferi sensu lato from blood of patients with erythema migrans. Infection 2001; 29: 65-70
89. Wormser GP, Bittker S, Cooper D, et al. Comparison of the yields of blood cultures using serum or plasma from patients with early Lyme disease. J Clin Microbiol 2000; 38: 1648-50
90. 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: 1249-53
91. Dumler JS. Molecular diagnosis of Lyme disease: review and meta-analysis. Mol Diagn 2001; 6: 1-11
92. Weger W, Müllegger RR. Histopathology and immunohistochemistry of dermato-borreliosis. Acta Dermatoven APA 2001; 10: 135-42
93. Åsbrink E, Hovmark A, Hederstedt B. Serologic studies of erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans with indirect immunofluorescence and enzyme-linked immunosorbent assays. Acta Derm Venereol (Stockh) 1985; 65: 509-14
94. De Koning J, Duray PH. Histopathology of human Lyme borreliosis. In: Weber K, Burgdorfer W, editors. Aspects of Lyme borreliosis. Berlin: Springer, 1993: 70-92
95. Wilske B, Preac-Mursic V. Microbiological diagnosis of Lyme borreliosis. In: Weber K, Burgdorfer W, editors. Aspects of Lyme borreliosis. Berlin: Springer, 1993: 267-99
96. Lebech AM. Polymerase chain reaction in diagnosis of Borrelia burgdorferi infections and studies on taxonomic classification. APMIS Suppl 2002; 105: 1-40
97. Müllegger RR, Zöchling N, Schlüpen EM, et al. Polymerase chain reaction control of antibiotic treatment in dermatoborreliosis. Infection 1996; 24: 76-9
98. Von Stedingk LV, Olsson I, Hanson HS, et al. Polymerase chain reaction for detection of Borrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis. Eur J Clin Microbiol Infect Dis 1995; 14: 1-5
99. Rijpkema SG, Tazelaar DJ, Molkenboer MJ, et al. Detection of Borrelia afzelii, Borrelia burgdorferi sensu stricto, Borrelia garinii and group VS116 by PCR in skin biopsies of patients with erythema migrans and acrodermatitis chronica atrophicans. Clin Microbiol Infect 1997; 3: 109-16
100. Åsbrink E, Olsson I, Hovmark A. Erythema chronicum migrans Afzelius in Sweden: a study on 231 patients. Zentralbl Bakteriol 1986; 263: 229-36
101. Weber K. Therapy of cutaneous manifestations. In: Weber K, Burgdorfer W, editors. Aspects of Lyme borreliosis. Berlin: Springer, 1993: 312-27
102. Weber K, Pfister HW. Clinical management of Lyme borreliosis. Lancet 1994; 343: 1017-20
103. Kuiper H, van Dam AP, Spanjaard L, et al. Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. J Clin Microbiol 1994; 32: 715-20
104. Barsic B, Maretic T, Majerus L, et al. Comparison of azithromycin and doxycycline in the treatment of erythema migrans. Infection 2000; 28: 153-6
105. 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 Disease Society of America. Clin Infect Dis 2006; 43: 1089-134
106. Dattwyler RJ, Volkman DJ, Conaty SM, et al. Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 1990; 336: 1404-6
107. Dattwyler RJ, Luft BJ, Kunkel MJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997; 337: 289-94
108. Luger SW, Paparone P, Wormser GP, et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother 1995; 39: 661-7
109. Massarotti EM, Luger SW, Rahn DW, et al. Treatment of early Lyme disease. Am J Med 1992; 92: 396-403
110. Nadelman RB, Luger SW, Frank E, et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med 1992; 117: 273-80
111. Nowakowski J, Nadelman RB, Forseter G, et al. Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans. J Am Acad Dermatol 1995; 32: 223-7
112. Strle F, Ruzic E, Cimperman J. Erythema migrans: comparison of treatment with azithromycin, doxycycline, and phenoxymethyl penicillin. J Antimicrob Chemother 1992; 30: 543-50
113. Strle F, Maraspin V, Lotric-Furlan S, et al. Azithromycin and doxycycline for treatment of Borrelia culture-positive erythema migrans. Infection 1996; 24: 64-8
114. Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2003; 138: 697-704
115. Weber K, Wilske B, Preac-Mursic V, et al. Azithromycin versus penicillin V for the treatment of early Lyme borreliosis. Infection 1993; 21: 367-72
116. Bennet L, Danell S, Berglund J. Clinical outcome of erythema migrans after treatment with phenoxymethyl penicillin. Scand J Infect Dis 2003; 35: 129-31
117. Breier F, Kunz G, Klade H, et al. Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis. Infection 1996; 24: 69-72
118. Neumann R, Aberer E, Stanek G. Treatment and course of erythema chronicum migrans. Zentralbl Bakteriol 1987; 263: 372-6
119. Weber K, Preac-Mursic V, Wilske B, et al. A randomized trial of ceftriaxone versus oral penicillin for the treatment of early European Lyme borreliosis. Infection 1990; 18: 91-6
120. Aberer E, Kahofer P, Binder B, et al. Comparison of a two- or three-week regimen and a review of treatment of erythema migrans with phenoxymethylpenicillin. Dermatology 2006; 212: 160-7
121. Weber K, Preac-Mursic V, Neubert U, et al. Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica atrophicans. Ann N Y Acad Sci 1988; 539: 324-45
122. Müllegger RR, Zöchling N, Soyer HP, et al. No detection of Borrelia burgdorferi- specific DNA in erythema migrans lesions after minocycline treatment. Arch Dermatol 1995; 131: 678-82
123. Steere AC, Hutchinson GJ, Rahn DW, et al. Treatment of the early manifestations of Lyme disease. Ann Intern Med 1983; 99: 22-6
124. Terekhova D, Sartakova ML, Wormser GP, et al. Erythromycin resistance in Borrelia burgdorferi. Antimicrob Agents Chemother 2002; 46: 3637-40
125. Hansen K, Hovmark A, Lebech A-M, et al. Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo animal susceptibility study and a clinical trial in patients with erythema migrans. Acta Derm Venereol 1992; 72: 297-300
126. Dattwyler RJ, Grunwaldt E, Luft BJ. Clarithromycin in treatment of early Lyme disease: a pilot study. Antimicrob Agents Chemother 1996; 40: 468-9
127. Nowakowski J, McKenna D, Nadelman RB, et al. Failure of treatment with cephalexin for Lyme disease. Arch Fam Med 2000; 9: 563-7
128. Arnez M, Radsel-Medvescek A, Pleterski-Rigler D, et al. Comparison of cefuroxime axetil and phenoxymethyl penicillin for the treatment of children with solitary erythema migrans. Wien Klin Wochenschr 1999; 111: 916-22
129. Arnez M, Pleterski-Rigler D, Luznik-Bufon T, et al. Solitary erythema migrans in children: comparison of treatment with azithromycin and phenoxymethyl penicillin. Wien Klin Wochenschr 2002; 114: 498-504
130. Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics 2002; 109: 1173-7
131. Maraspin V, Cimperman J, Lotric-Furlan S, et al. Erythema migrans in pregnancy. Wien Klin Wochenschr 1999; 111: 933-40
132. Strobino BA, 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: 711-6
133. Elliott DJ, Eppes SC, Klein JD. Teratogen update: Lyme disease. Teratology 2001; 64: 276-81
134. Walsh CA, Mayer EW, Baxi LV. Lyme disease in pregnancy: case report and review of the literature. Obstet Gynecol Surv 2007; 62: 41-50
135. Shapiro LE, Knowles SR, Shear NH. Comparative safety of tetracycline, minocycline, and doxycycline. Arch Dermatol 1997; 133: 1224-30
136. Arnez M, Ruzic-Sabljic E, Ahcan J, et al. Isolation of Borrelia burgdorferi sensu lato from blood of children with solitary erythema migrans. Pediatr Infect Dis J 2001; 20: 251-5
137. Nowakowski J, Nadelman RB, Sell R, et al. Long-term follow-up of patients with culture-confirmed Lyme disease. Am J Med 2003; 115: 91-6
138. Lipsker D, Antoni-Bach N, Hansmann Y, et al. Long-term prognosis of patients treated for erythema migrans in France. Br J Dermatol 2002; 146: 872-6
139. Glatz M, Golestani M, Kerl H, et al. Clinical relevance of different IgG and IgM serum antibody responses to Borrelia burgdorferi after antibiotic therapy for erythema migrans: long-term follow-up study of 113 patients. Arch Dermatol 2006; 142: 862-8
140. Hulshof MM, Vandenbroucke JP, Nohlmans LM, et al. Long-term prognosis in patients treated for erythema chronicum migrans and acrodermatitis chronica atrophicans. Arch Dermatol 1997; 133: 33-7
141. 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: 85-92
142. Feder Jr HM, Gerber MA, Luger SW, et al. Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. Clin Infect Dis 1992; 15: 788-93
143. Hammers-Berggren S, Lebech AM, Karlsson M, et al. Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis. J Clin Microbiol 1994; 32: 1519-25
144. Lomholt H, Lebech AM, Hansen K, et al. Long-term serological follow-up of patients treated for chronic cutaneous borreliosis or culture-positive erythema migrans. Acta Derm Venereol (Stockh) 2000; 80: 362-6
145. 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: 780-5
146. Krbkova L, Stanek G. Therapy of Lyme borreliosis in children. Infection 1996; 24: 170-3
147. Aberer E, Breier F, Stanek G, et al. Success and failure in the treatment of acrodermatitis chronica atrophicans. Infection 1996; 24: 85-7
148. Kindstrand E, Nilsson BY, Hovmark A, et al. Peripheral neuropathy in acrodermatitis chronica atrophicans: effect of treatment. Acta Neurol Scand 2002; 106: 253-7
149. Olsson I, Asbrink E, von-Stedingk M, et al. Changes in Borrelia burgdorferi-specific serum IgG antibody levels in patients treated for acrodermatitis chronica atrophicans. Acta Derm Venereol (Stockh) 1994; 74: 424-8
150. Åsbrink E. Acrodermatitis chronica atrophicans. Clin Dermatol 1993; 11: 369-75
151. Plörer A, Sepp N, Schmutzhard E, et al. Effects of adequate versus inadequate treatment of cutaneous manifestations of Lyme borreliosis on the incidence of late complications and late serologic status. J Invest Dermatol 1993; 100: 103-9
152. Trevisan G, Cattonar P, Nobile C, et al. Dermatological manifestations of Lyme borreliosis. Acta Dermatoven APA 1996; 3-4: 101-7
153. Aberer E, Stanek G, Ertl M, et al. Evidence for spirochetal origin of circumscribed scleroderma (morphea). Acta Derm Venereol (Stockh) 1987; 67: 225-31
154. Breier F, Klade H, Stanek G, et al. Lymphoproliferative responses to Borrelia burgdorferi in circumscribed scleroderma. Br J Dermatol 1996; 134: 285-91
155. Buechner SA, Lautenschlager S, Itin P, et al. Lymphoproliferative responses to Borrelia burgdorferi in patients with erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis benigna cutis, and morphea. Arch Dermatol 1995; 131: 673-7
156. Akimoto S, Ishikawa O, Miyachi Y. The absence of antibodies against Borrelia burgdorferi in the sera of Japanese patients with localized scleroderma. J Rheumatol 1996; 23: 573-4
157. Alonso-Llamazares J, Persing DH, Anda P, et al. No evidence for Borrelia burgdorferi infection in lesions of morphea and lichen sclerosus et atrophicus in Spain: a prospective study and literature review. Acta Derm Venereol (Stockh) 1997; 77: 299-304
158. Hoesly JM, Mertz LE, Winkelmann RK. Localized scleroderma (morphea) and antibody to Borrelia burgdorferi. J Am Acad Dermatol 1987; 17: 455-8
159. Raguin G, Boisnic S, Souteyrand P, et al. No evidence for a spirochetal origin of localized scleroderma. Br J Dermatol 1992; 127: 218-20
160. Schempp C, Bocklage H, Lange R, et al. Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification. J Invest Dermatol 1993; 100: 717-20
161. Weide B, Schittek B, Klyscz T, et al. Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction. Br J Dermatol 2000; 143: 780-5
162. Breier F, Khanakah G, Stanek G, et al. Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Br J Dermatol 2001; 144: 387-92
163. Weber K, Preac-Mursic V, Reimers CD. Spirochetes isolated from two patients with morphea. Infection 1988; 16: 26
164. Fujiwara H, Fujiwara K, Hashimoto K, et al. Detection of Borrelia burgdorferi DNA (B. garinii or B. afzelii) in morphea and lichen sclerosus et atrophicus tissues of German and Japanese but not of US patients. Arch Dermatol 1997; 133: 41-4
165. Goodlad JR, Davidson MM, Gordon P, et al. Morphoea and Borrelia burgdorferi: results from the Scottish Highlands in the context of the world literature. Mol Pathol 2002; 55: 374-8
166. Ozkan S, Atabey N, Fetil E, et al. Evidence for Borrelia burgdorferi in morphea and lichen sclerosus. Int J Dermatol 2000; 39: 278-83
167. Dillon WI, Saed GM, Fivenson DP. Borrelia burgdorferi DNA is undetectable by polymerase chain reaction in skin lesions of morphea, scleroderma, or lichen sclerosus et atrophicus of patients from North America. J Am Acad Dermatol 1995; 33: 617-20
168. Coyle PK. Advances and pitfalls in the diagnosis of Lyme disease. FEMS Immunol Med Microbiol 1997; 19: 103-9
169. Ross SA, Sanchez JL, Taboas JO. Spirochetal forms in the dermal lesions of morphea and lichen sclerosus et atrophicus. Am J Dermatopathol 1990; 12: 357-62
170. Abele DC, Bedingfield RB, Chandler FW, et al. Progressive facial hemiatrophy (Parry-Romberg syndrome) and borreliosis. J Am Acad Dermatol 1990; 22: 531-3
171. Stern HS, Elliott LF, Beegle Jr PH. Progressive hemifacial atrophy associated with Lyme disease. Plast Reconstr Surg 1992; 90: 479-83
172. Granter SR, Barnhill RL, Hewins ME, et al. Identification of Borrelia burgdorferi in diffuse fasciitis with peripheral eosinophilia: borrelial fasciitis. JAMA 1994; 272: 1283-5
173. Hashimoto Y, Takahashi H, Matsuo S, et al. Polymerase chain reaction of Borrelia burgdorferi flagellin gene in Shulman syndrome. Dermatology 1996; 192: 136-9
174. Sommer A, Gambichler T, Bacharach-Buhles M, et al. Clinical and serological characteristics of progressive facial hemiatrophy: a case series of 12 patients. J Am Acad Dermatol 2006; 54: 227-33
175. Jelic S, Filipovic-Ljeskovic I. Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it fortuitous finding? Hematol Oncol 1999; 17: 107-16
176. Kutting B, Bonsmann G, Metze D, et al. Borrelia burgdorferi-associated primary cutaneous B cell lymphoma: complete clearing of skin lesions after antibiotic pulse therapy or intralesional injection of interferon alfa-2a. J Am Acad Dermatol 1997; 36: 311-4
177. Cerroni L, Zöchling N, Pütz B, et al. Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma. J Cutan Pathol 1997; 24: 457-61
178. Goodlad JR, Davidson MM, Hollowood K, et al. Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the highlands of Scotland. Am J Surg Pathol 2000; 24: 1279-85
179. Wood GS, Kamath NV, Guitart J, et al. Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United States. J Cutan Pathol 2001; 28: 502-7
180. Munksgaard L, Frisch M, Melbye M, et al. Incidence patterns of Lyme disease and cutaneous B-cell non-Hodgkin's lymphoma in the United States. Dermatology 2000; 201: 351-2
181. Kodama K, Massone C, Chott A, et al. Primary cutaneous large B-cell lymphomas: clinicopathologic features, classification, and prognostic factors in a large series of patients. Blood 2005; 106: 2491-7