Dermatology OPEN ACCESS Guideline Cutaneous Lyme borreliosis: Guideline of the German Dermatology Society Kutane Lyme-Borreliose: Leitlinie der Deutschen Dermatologischen Gesellschaft Abstract This guideline of the German Dermatology Society primarily focuses on Heidelore Hofmann1 the diagnosis and treatment of cutaneous manifestations of Lyme bor- Volker Fingerle2 reliosis. It has received consensus from 22 German medical societies 3 and 2 German patient organisations. It is the first part of an AWMF Klaus-Peter Hunfeld (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesell- Hans-Iko Huppertz4 schaften e.V.) interdisciplinary guideline: “Lyme Borreliosis – Diagnosis Andreas Krause5 and Treatment, development stage S3”. 6 The guideline is directed at physicians in private practices and clinics Sebastian Rauer who treat Lyme borreliosis. Objectives of this guideline are recommen- Bernhard Ruf7 dations for confirming a clinical diagnosis, recommendations for a stage- Consensus group related laboratory diagnosis (serological detection of IgM and IgG Bor- relia antibodies using the 2-tiered ELISA/immunoblot process, sensible use of molecular diagnostic and culture procedures) and recommenda- 1 Klinik für Dermatologie und tions for the treatment of the localised, early-stage infection (erythema Allergologie der TU München, migrans, erythema chronicum migrans, and borrelial lymphocytoma), München, Germany the disseminated early-stage infection (multiple erythemata migrantia, 2 Bayerisches Landesamt für flu-like symptoms) and treatment of the late-stage infection (acro- Gesundheit und dermatitis chronica atrophicans with and without neurological manifest- Lebensmittelsicherheit (LGL) ations). In addition, an information sheet for patients containing recom- Oberschleißheim, Germany mendations for the prevention of Lyme borreliosis is attached to the 3 Zentralinstitut für guideline. Labormedizin, Mikrobiologie & Krankenhaushygiene, Zusammenfassung Krankenhaus Nordwest, Frankfurt, Germany Diese Leitlinie der Deutschen Dermatologischen Gesellschaft bezieht 4 Professor-Hess-Kinderklinik sich primär auf die Diagnostik und Therapie von kutanen Manifestatio- Klinikum Bremen-Mitte, nen der Lyme-Borreliose. Sie ist Teil 1 der geplanten interdisziplinären Bremen, Germany AWMF Gesamtleitlinie „Lyme-Borreliose – Diagnostik und Therapie 5 Immanuel Krankenhaus Entwicklungsstufe S3“. Berlin, Berlin, Germany Sie wurde interdisziplinär von 22 deutschen Fachgesellschaften und 2 deutschen Patientenorganisationen konsentiert und richtet sich an 6 Neurologische Universitätsklinik, Freiburg, Ärzte in Praxis und Klinik, die mit der Behandlung der Lyme-Borreliose Germany befasst sind. Ziel der Leitlinie ist es, Empfehlungen zur Absicherung der klinischen 7 Klinik für Infektiologie Klinik Diagnosen, Empfehlungen zur stadiengerechten Labordiagnostik (sero- St Georg, Leipzig, Germany logischer Nachweis von IgM- und IgG-Borrelienantikörpern mit dem 2-Stufenverfahren ELISA/Immunoblot sowie der sinnvolle Einsatz mole- kulardiagnostischer und kultureller Verfahren) und Empfehlungen zur Therapie der lokalisierten Frühmanifestationen (Erythema migrans, Erythema chronicum migrans und Borrelienlymphozytom), zur Therapie der disseminierten Frühmanifestationen (Multiple Erythemata migrantia und/oder grippeartige Symptomatik nach Zeckenstich) und zur Therapie der Spätmanifestationen (Acrodermatitis chronica atrophicans mit und ohne neurologische Manifestationen) zu geben. Außerdem werden Empfehlungen für Patienten zur Prävention der Lyme-Borreliose und zur Nachbeobachtung eines Zeckenstiches formuliert. GMS German Medical Science 2017, Vol. 15, ISSN 1612-3174 1/31 Hofmann et al.: Cutaneous Lyme borreliosis: Guideline of the German ... Preamble 1 Introduction This guideline primarily focuses on the diagnosis and The infectious disease most frequently transmitted by treatment of cutaneous manifestations of Lyme borrelio- ticks in Europe is Lyme borreliosis. The Borrelia are sis. It is the first part of the scheduled interdisciplinary transferred to the skin during the blood sucking process guideline: “Lyme Borreliosis – Diagnosis and Treatment, of the hard-bodied tick Ixodes ricinus. There the Borrelia No. 013-080, Development Stage S3”. are either killed off by the (unspecific, innate) immune This part has already received consensus from 22 med- system, or a localised infection occurs which leads to ill- ical societies and 2 patient organisations. The German ness in only a small percentage of those infected. Most Cochrane Centre, Freiburg (Cochrane Germany) is cur- often there is an inflammation of the skin, typically in the rently conducting systematic review and assessment of form of an erythema migrans or, seldom, as borrelial the literature to develop this guideline to stage 3. lymphocytoma. In the course of the infection the Borrelia The interdisciplinary guideline group is currently preparing can disseminate and attack various organs. They part 2 “Neuroborreliosis” which will be followed by part primarily affect the skin, joints and nervous system. Acro- 3 “Lyme Arthritis, Lyme Carditis and Other Rare Manifest- dermatitis chronica atrophicans can develop as a chronic ations”. or late-form of skin manifestation. Synonyms 1.1 Target group Cutaneous borreliosis, cutaneous manifestations of Lyme This guideline is directed at physicians in private practices borreliosis, skin borreliosis, cutaneous Lyme borreliosis, and clinics who treat Lyme borreliosis. cutaneous Lyme disease 1.2 Objectives of this guideline Search terms • Recommendations for confirming a clinical diagnosis Borrelia burgdorferi infection, hard-bodied tick borreliosis, • Recommendations for a stage-related laboratory dia- Lyme disease, cutaneous Lyme borreliosis, erythema gnosis: serological detection of IgM and IgG Borrelia migrans disease, erythema migrans, erythema chronicum antibodies using the 2-tiered ELISA/immunoblot pro- migrans, lymphadenosis cutis benigna, borrelial lympho- cess; sensible use of molecular-diagnostic and culture cytoma, multiple erythemata migrantia, multiple erythema procedures migrans, acrodermatitis chronica atrophicans. • Treatment of the localised, early-stage infection ICD-10-No: A69.2, L90.4 (erythema migrans, erythema chronicum migrans and AWMF Register No 013-044 borrelial lymphocytoma) • Treatment of the disseminated early-stage infection (multiple erythemata migrantia, flu-like symptoms) List of abbreviations • Treatment of the late-stage infection (acrodermatitis chronica without neurological manifestations) • ACA – Acrodermatitis chronica atrophicans • Treatment of the late-stage infection (acrodermatitis • BL – Borrelial lymphocytoma chronica with neurological manifestations) • EM – Erythema migrans • Prevention of Lyme borreliosis • ECM – Erythema chronicum migrans Recommendations for observing the area around the • i.v. – Intravenous tick bite • BW – Body weight Information sheet for patients (Annex 1 in • LB – Lyme borreliosis Attachment 1) • LTT – Lymphocyte transformation test • MEM – Multiple Erythemata migrantia 1.3 Participating medical societies • MiQ – Quality standards in microbiological-infectiolo- gical diagnostics Steering group • NAT – Nucleic acid amplification techniques • NSAID – Nonsteroidal anti-inflammatory drugs • Responsible: • PCR – Polymerase chain reaction Prof. Dr. med. Heidelore Hofmann – coordinator • p.o. – Per os German Dermatology Society (DDG) • PPI – Proton pump inhibitor • Prof. Dr. med. Sebastian Rauer – coordinator, deputy • RCT – Randomised controlled trial Dr. Stephan Kastenbauer • SNRI – Serotonin-norepinephrine reuptake inhibitor German Society of Neurology (DGN) • Dr. med. Volker Fingerle German Society for Hygiene and Microbiology (DGHM) GMS German Medical Science 2017, Vol. 15, ISSN 1612-3174 2/31 Hofmann et al.: Cutaneous Lyme borreliosis: Guideline of the German ... • Prof. Dr. med. Klaus-Peter Hunfeld 1.4 Methods The German United Society of Clinical Chemistry and Laboratory Medicine (DGKL) and INSTAND e.V. This guideline is based on an update of AWMF Guideline • Prof. Dr. med. Hans-Iko Huppertz No. 013-044 “Cutaneous Manifestations of Lyme Borrel- German Society of Paediatrics and Adolescent Medi- iosis”, development stage S1, which was created by a cine (DGKJ) and German Society of Paediatric Infecto- committee of experts in 2009. logy (DGPI) The guideline was created in accordance with the meth- • Prof. Dr. med. Andreas Krause odological requirements of the Association of the Scientif- German Society of Rheumatology (DGRh) ic Medical Societies in Germany (AWMF) for developing • Prof. Dr. med. Bernhard Ruf and further developing diagnosis and treatment German Society of Infectious Diseases (DGI) guidelines. It is an S2k guideline in accordance with the Consensus group AWMF’s three-stage concept. The composition of the guideline group was interdisciplinary (IDA) and the appoint- • Prof. Dr. med. Elisabeth Aberer ed mandate holders of the expert medical societies were Austrian Society of Dermatology and Venerology informed of the scheduled update on 11/2/2014. (ÖGDV) Uniform formulations are used in order to standardise • Prof. Dr. med. Karl Bechter the recommendations of the guideline. The German Association of Psychiatry, Psychotherapy The following gradations shall apply here: and Psychosomatics (DGPPN) • Prof. Dr. med. Michael H. Freitag • Strong recommendation: “shall” German College of General Practitioners and Family • Recommendation: “should” Physicians (DEGAM) • Open recommendation: “may