Table Of ContentDedicated to our wives Eva and Dale
K. Weber· W. Burgdorfer (Eds.) . Coeditor: G. Schierz
Aspects of
Lyme Borreliosis
With 42 Tables and 138 Illustrations
Springer-Verlag
Berlin Heidelberg New York London Paris Tokyo
Hong Kong Barcelona Budapest
Dr.med.K1aus Weber
Dermatologist in Private Practice
Rosenstr.6
8000 Munchen 2
Germany
Willy Burgdorfer, Ph.D., M.D. (h.c.)
Laboratory of Vectors and Pathogens
Rocky Mountain Laboratories
Hamilton, MT 59840
USA
ISBN-13:978-3-642-77616-8 e-ISBN-13: 978-3-642-77614-4
DOl: 1O.l 007/978-3-642-77614-4
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© Springer-Verlag Berlin Heidelberg 1993
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Preface
The story of Lyme borreliosis started in Europe at the end of the last century and is
still continuing today. The aim of this book is to present current knowledge of Lyme
borreliosis primarily as it occurs in Europe. Despite providing such a regional view,
observations made in the United States of America and elsewhere are also considered.
Thus "Aspects of Lyme Borreliosis" may serve within these limits as a presentation of
the disease in general.
The various stages of preparation in completing this book included sending invita
tions to authors from different departments and even different countries as far as this
was practicable, and arranging manuscript evaluation by one or two anonymous
reviewers and at least one of the editors. Dr. W. Burgdorfer was mainly responsible for
editing the nonclinical part, and Dr.K. Weber for editing the clinical part. The clinical
chapters, when feasible follow a specific outline.
The term "Lyme borreliosis" has only recently been introduced. European authors
describing aspects of this disease fmd themselves, therefore, to a certain extent, in a
nomenclatural dilemma (see Chap. 7). The majority of the authors of this book elected
to use the designation "Lyme borreliosis" rather than "erythema migrans borre1iosis"
or both terms concomitantly.
We are deeply indebted to our fellow authors for their contributions. Our gratitude
is also extended to the reviewers and to Mrs. U. Perschau-lendreizig und Mrs. K.
Baade in the editorial office.
April 1992 Klaus Weber Willy Burgdoifer
List of Contributors
Aberer, Elisabeth, ll. Universitats-Hautklinik Wien, AlserstraBe 4, 1090 Wien,
Austria
Aeschlimann, A., University of Neuchatel, Zoological Institute, Chantemerle 22, 2007
Neuchatel, Switzerland
Asbrink, Eva, Department of Dermatology, Karolinska Institute at S6dersjukhuset,
11883 Stockholm, Sweden
Ballmer, P.E., Department of Internal Medicine, University of Bern, Inselspital, 3010
Bern, Switzerland
Btichner, S.A., Dermatologische Universitatsklinik, Kantonsspital Basel, Petersgraben
4, 4031 Basel, Switzerland
Burgdorfer, W., Department of Health and Human Services, Public Health Service,
National Institutes of Health, National Institute of Allergy and Infectious Diseases,
Laboratory of Vectors and Pathogens, Hamilton, MT 59840, USA
Christen, H.-J., Kinderklinik und Poliklinik, Universitat G6ttingen, Robert-Koch
StraBe 40, W-3400 G6ttingen, Germany
Detmar, U., Dermatologist in Private Practice, HauptstraBe 12, 8939 Bad W6rishofen,
Germany
Duray, P.H., Department of Pathology, Brigham and Women's Hospital, 75 Francis
Street, Boston, Mass. 02115, USA
Gem, Lise, University of Neuchatel, Zoological Institute, Chantemerle 22, 2007
Neuchatel, Switzerland
Hanefeld, F., Kinderklinik und Poliklinik, Universitat G6ttingen, Robert-Koch-StraBe
40, W-3400 G6ttingen, Germany
Hassler, D., General Practioner in Private Practice, Untere Hofstatt 3, 7527 Kraichtal,
Germany
Hayes, S.F., Department of Health and Human Services, Public Health Service,
National Institutes of Health, National Institute of Allergy and Infectious Diseases,
Laboratory of Vectors and Pathogens, Hamilton, MT 59840, USA
Herzer, P., Medizinische Poliklinik der Universitat Mtinchen, PettenkoferstraBe 8a,
8000 Miinchen 2, Germany
Hovmark, A., Department of Dermatology, Karolinska Institute at SOdersjukhuset,
11883 Stockholm, Sweden
Kaudewitz, P., Dermatologische Klinik und Poliklinik, Universitat Mtinchen,
FrauenlobstraBe 9-11, 8000 Mtinchen 2, Germany
Kohlhepp, W., Neurologische Klinik, Universitat Wtirzburg, Josef-Schneider-StraBe
11, 8700 Wtirzburg, Germany
de Koning, J., Laboratorium voor de Volksgezondheid in Friesland, Postbus 21020,
8900 JA Leeuwarden, The Netherlands
Krampitz, H.E., Abteilung Infektions-und Tropenmedizin, Ludwig-Maximilians
Universitat Mtinchen, Germany (deceased)
List of Contributors VII
Kristoferitsch, W., Neurologische Abteilung, SMZ-Ost-Krankenhaus, Langobarden
straBe 122, 1220 Wien, Austria
van der Linde, M.R., Department of Cardiology, Thoraxcenter, University Hospital of
Groningen, Oostersinge159, 9713 EZ Groningen, The Netherlands
Maciejewski, W., Stadtisches Krankenhaus Munchen-Schwabing, KtHner Platz, 8000
Munchen 440, Germany
Marget, W., Kinderklinik:, Universitat Munchen, Editor-in-Chief, Infection, Munchner
Str.l, 8000 Munchen 70, Germany
Martin, R., Neurologische Klinik:, Universitat Tubingen, Hoppe-Seyler-StraBe 3, 7400
Tubingen, Germany
Mayer-Berger, W., Klinische Abteilung IV, Klinik: Hohenried fur Herz-und
Kreislaufkrankheiten, 8139 Bernried, Germany
Meier, c., St. Gallische Hohenklinik: Walenstadtberg, 8881 Knoblisbuhl, Switzerland
Mertens, H.G., Neurologische Klinik:, Universitat Wurzburg, Josef-Schneider-StraBe
11, 8700 Wurzburg, Germany
Neubert, U., Dermatologische Klinik: und Poliklinik:, Universitat Munchen,
FrauenlobstraBe 9-11, 8000 Munchen 2, Germany
Pfister, H.-W., Neurologische Klinik: der Universitat Munchen, Klinikum GroBhadem,
MarchioninistraBe 15,8000 Munchen 70, Germany
Preac-Mursic, Vera, Max von Pettenkofer-Institut fur Hygiene und Medizinische
Mikrobiologie der Ludwig-Maximilians-Universitat Munchen, PettenkoferstraBe
9a, 8000 Munchen 2, Germany
Reimers, C.D., Friedrich Baur-Institut bei der Medizinischen Klinik: Innenstadt,
Ludwig Maximilians-Universitat Munchen, ZiemssenstraBe lA, 8000 MUnchen 2,
Germany
Rufli, T., Dermatologische Universitatsklinik, Kantonsspital Basel, Petersgraben 4,
4031 Basel, Switzerland
Satz, N., Medizinische Klinik:, Kantonsspital Winterthur, Winterthur, Switzerland
Schierz G., Max von Pettenkofer-Institut fur Hygiene und Medizinische Mikro
biologie der Ludwig-Maximilians-Universitat Munchen, PettenkoferstraBe 9a,
8000 Munchen 2, Germany
Schmutzhard, E., Klinik: fur Neurologie, Universitat Innsbruck, AnichstraBe 35, 6020
Innsbruck,Austria
Schonherr, U., Augenklinik: mit Poliklinik der Universitat Erlangen-Numberg,
Schwabachanlage 6, 8520 Erlangen, Germany
SkOldenberg, Birgit, Department of Infectious Diseases, Karolinska Institute,
Danderyd Hospital, 18288 Danderyd, Sweden
Stanek, G., Hygiene-Institut der Universitat Wien, Kinderspitalgasse 15, 1095 Wien,
Austria
Strle, F., University Medical Center LjUbljana, Department of Infectious Diseases,
Japljeva 2,61000 Ljubljana, Slovenia
Weber, K., Dermatologist in Private Practice, RosenstraBe 6,8000 Munchen 2,
Germany
Wilske, Bettina, Max von Pettenkofer-Institut fur Hygiene und Medizinische
Mikrobiologie der Ludwig-Maximilians-Universitat Munchen, Pettenk<;>ferstraBe
9a, 8000 Munchen 2, Germany
Contents
Preface .. v
I History
1 History of Lyme Borreliosis in Europe
K. WEBER and H.-W. PFISTER .....
2 The Historical Road to the Discovery of Borrelia burgdorferi
W. BURGDORFER . . . . . . . . . . . . . . . . . . . . . . . . 21
II Characteristics of Borrelia burgdorferi
3 Ultrastructure of Borrelia burgdorferi
S.P. HAYES and W. BURGDORFER . 29
4 Biology of Borrelia burgdorferi
V. PREAC-MuRSIC and B. WILSKE . 44
III Ecology and Histopathology of Lyme Borreliosis
5 The Ecology of Lyme Borreliosis in Europe
L. GERN, W. BURGDORFER, A. AESCHLIMANN, and H.E. KRAMPITZ . 59
6 Histopathology of Human Lyme Borreliosis
J. DE KONING and P.H. DURAY .................. . 70
IV Clinical Features of Lyme Borreliosis
7 Clinical Overview
K. WEBER, H.-W. PFISTER, and C.D. REIMERS 93
8 Erythema Migrans and Early Signs and Symptoms
K. WEBER, U. NEUBERT, and S.A. BUCHNER .... 105
9 Borrelial Lymphocytoma
A. HOVMARK, E. ASBRINK, K. WEBER, and P. KAUOEWITZ 122
10 Lyme Carditis
M.R. VAN DER LINDE and P.E. BALLMER ........ . 131
11 Early Neurological Involvement (Bannwarth's Syndrome)
H.W. PFISTER, W. KRISTOFERITSCH, and C. MEIER 152
12 Joint Manifestations
P. HERZER ............. . 168
13 Myalgia, Myositis, and Fasciitis
C.D. REIMERS and E. SCHMUTZHARD 185
14 Acrodermatitis Chronica Atrophicans
E. ASBRINK, A. HOVMARK, and K. WEBER 193
Contents IX
15 Chronic Central Nervous System Involvement
R. MARTIN, W. KOHLHEPP, and H.G. MERTENS 205
16 Chronic Peripheral Neuropathy
W. KRISTOFERITSCH ............. . 219
17 Lyme Borreliosis in Childhood and Pregnancy
H.-J. CHRISTEN and F. HANEFELD ....... . 228
18 Localized Scleroderma and Lichen Sclerosus et Atrophicus:
Manifestations of a Borrelia burgdorferi Infection?
U. NEUBERT, E. ABERER, and T. RUFLI 240
19 Ocular Manifestations
U. SCHONHERR and F. STRLE. . . . . . 248
20 Borrelial Dermatomyositis-like Syndrome
U. DETMAR and W. MACIEJEWSKY ..... 259
V Microbiological Diagnosis of Lyme Borreliosis
21 Microbiological Diagnosis of Lyme Borreliosis
B. WILSKE and V. PREAc-MURSIC ........................ 267
VI Therapy of Lyme Borreliosis
22 Antibiotic Susceptibility of Borrelia burgdorferi. In Vitro and In Vivo
V. PREAc-MURSIC . . . . . . . . . . . 301
23 Therapy of Cutaneous Manifestations
K. WEBER . . . . . . . . . . . . . 312
24 Therapy of Lyme Neuroborreliosis
H.W. PFISTER, W. KRISTOFERITSCH, and B. SKOLDENBERG 328
25 Therapy of Joint Manifestations
P. HERZER ............ . 340
26 Therapy of Lyme Carditis
W. MAYER-BERGER, M.R. VAN DER LINDE, and D. HASSLER 344
27 Therapy of Tick Bite
K. WEBER and W. BURGDORFER . . . . . 350
28 Critical Remarks on Antibiotic Therapy
K. WEBER and W. MARGET . . . . . 352
VII Epidemiology of Lyme Borreliosis
29 Epidemiology of Lyme Borreliosis
G. STANEK, N. SATZ, F. STRLE, and B. WILSKE 358
Subject Index . . 371
Color plates I-IV between pp 118 and 119
I History
1 History of Lyme Borreliosis in Europe
K. WEBER and H.-W. PFISTER
1.1 Introduction
Knowledge of Lyme borreliosis in Europe has roughly developed in three phases.
Between 1883 and 1945, basic descriptions of dermatological and neurological mani
festations were presented. The beneficial effect of penicillin and other antibiotics noted
in the late 1940s and early 1950s gave a new impetus to the study of the cause and
nature of these manifestations, especially the dermatological ones; this phase lasted
until 1975. Following the first description of Lyme disease in 1977 and the discovery
of the causative organism in the United States in 1982, a third and this time broader
look into the disease and much of its surroundings ensued in Europe.
1.2 First Phase (1883-1945)
Knowledge of the various dermatological and neurological manifestations developed
mostly independently from each other during the first phase.
1.2.1 Acrodermatitis Chronica Atrophicans
In 1883, Alfred Buchwald from Breslau, Germany, described "diffuse idiopathic skin
atrophy" of 16 years duration in a 36-year-old man; some histologic features were pre
sented. We now regard this report as the earliest description of acrodermatitis chronica
atrophicans (ACA), a late manifestation of Lyme borreliosis. Until 1902, more than a
dozen case reports appeared in the literature (cited in Herxheimer and Hartmann
1902). Buchwald and others reported on the atrophic phase of ACA, while a variety of
authors described the first inflammatory phase of ACA shortly afterwards. In 1902,
Karl Herxheirner and Kuno Hartmann combined these observations, added a further 12
patients of their own, and discussed at some length that acrodermatitis chronica atroph
icans, a term introduced by them, develops from an early inflammatory phase into a
late atrophic one. By about 1906, most of the important clinical signs associated with
ACA had been desbribed, i.e., hair loss (Buchwald 1883), macular atrophy (Pellizari
1884), which was later called anetoderma by Jadassohn, sclerodermatous changes
(Touton 1886; Rusch 1906), ulnar bands (Herxheimer and Hartmann 1902), and
fibrous nodules (Herxheimer 1905, cited in Herxheirner and Schmidt 1910). Pospelow
described atrophic ACA skin as resembling "crumpled cigarette paper" (1886).
In a monograph on atrophic conditions of the skin, Finger and Oppenheim (1910)
reported on 202 patients with atrophia cutis, 134 of whom can be regarded as having
had ACA. Most of these patients were collected from the literature. The authors sum
marized the findings on age, sex ratio and occupation, mentioned the rare involvement
of the face, sole of the foot, palms, trunk, mucous membranes and the entire skin and
