title: Efficacy and safety of pharmacological agents in the treatment of erythema migrans in early Lyme borreliosis-systematic review protocol.
abstract: BACKGROUND
  Erythema migrans represents an early cutaneous and most common manifestation of Lyme borreliosis. Recommendations regarding pharmacological agents, dose and duration of treatment are subject of intense debate. This review aims to explore differences in efficacy and safety between pharmacological treatments and control treatment.
  
  
  METHODS
  To identify relevant studies, we will conduct a systematic literature search. We will include randomised controlled trials (RCTs) and non-RCTs. Eligible comparative studies need to (1) consider patients with a diagnosis of erythema migrans resulting from Lyme borreliosis and (2) compare different pharmacological agents against each other, against any other non-pharmacological treatment, placebo or no treatment. Two review authors will independently assess included studies for risk of bias according to the methods of the Cochrane Handbook for Systematic Reviews of Interventions and related to specific study designs. We will address patient-relevant outcomes including clinical remission of cutaneous symptoms, any treatment-related adverse events, quality of life and progressive symptoms such as neuroborreliosis or Lyme carditis and flu-like symptoms. Provided that the identified trials are comparable in terms of clinical issues, combined estimates will be provided. Estimations of treatment effects will be calculated based on a random effects model. Heterogeneity will be evaluated based on I (2) and chi-square test. In case of significant heterogeneity, a pooled estimate will not be provided, but heterogeneity will be investigated on the basis of methodological and clinical study aspects. We plan subgroup analysis to reveal potential differences in the effect estimates between patient populations and treatment specifications. We will consider risk of bias using sensitivity analyses to decide whether to rely on the pooled estimates. The quality of a body of evidence for individual outcomes will be assessed using the GRADE approach.
  
  
  CONCLUSIONS
  Benefits and harms of pharmacological treatment in erythema migrans have not yet been adequately assessed. This systematic review will evaluate and summarise available evidence addressing benefits and harms of different pharmacological treatments. In addition, this summary of clinical evidence will inform decision-making between clinicians and patients and will play an important part in patient care.
  
  
  BACKGROUND
  
  CRD42016037932.
authors.affiliation: Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, Freiburg, 79110, Germany. torbahn@cochrane.de.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Torbahn
authors.affiliation: Department of Dermatology and Allergology, Technical University of Munich, Munich, Germany.
authors.forename: Heidelore
authors.initials: H
authors.lastname: Hofmann
authors.affiliation: Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, Freiburg, 79110, Germany.|Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Allert
authors.affiliation: Department of Health Services Research, University of Oldenburg, Oldenburg, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Freitag
authors.affiliation: Department of Neurology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Rick
authors.initials: R
authors.lastname: Dersch
authors.affiliation: German National Reference Centre for Borrelia-Bavarian Health and Food Safety Authority (LGL), Oberschleißheim, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Fingerle
authors.affiliation: Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, Freiburg, 79110, Germany.|Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Harriet
authors.initials: H
authors.lastname: Sommer
authors.affiliation: Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Edith
authors.initials: E
authors.lastname: Motschall
authors.affiliation: Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, Freiburg, 79110, Germany.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Meerpohl
authors.affiliation: Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, Freiburg, 79110, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Schmucker
mesh_terms: D000658:Amoxicillin / Q000008:administration & dosage* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018450:Disease Progression; D004318:Doxycycline / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D061345:Early Medical Intervention; D015787:Erythema Chronicum Migrans / Q000188:drug therapy*; D006801:Humans; D008193:Lyme Disease / Q000188:drug therapy; D020852:Lyme Neuroborreliosis; D011788:Quality of Life; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D004318:Doxycycline
keywords: Decision-making; Erythema migrans; Lyme borreliosis; Non-RCT; Pharmacological treatment; RCT; Skin manifestation; Systematic review