title: Decreased Th1-type inflammatory cytokine expression in the skin is associated with persisting symptoms after treatment of erythema migrans.
abstract: BACKGROUND
  Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e.g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome.
  
  
  METHODS
  A prospective follow-up study of 109 patients with EM was conducted at the Åland Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-γ, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines.
  
  
  RESULTS
  None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-γ in the EM biopsies (p=0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels.
  
  
  CONCLUSIONS
  Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.
authors.affiliation: Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sjöwall
authors.forename: Linda
authors.initials: L
authors.lastname: Fryland
authors.forename: Marika
authors.initials: M
authors.lastname: Nordberg
authors.forename: Florence
authors.initials: F
authors.lastname: Sjögren
authors.forename: Ulf
authors.initials: U
authors.lastname: Garpmo
authors.forename: Christian
authors.initials: C
authors.lastname: Jansson
authors.forename: Sten-Anders
authors.initials: SA
authors.lastname: Carlsson
authors.forename: Sven
authors.initials: S
authors.lastname: Bergström
authors.forename: Jan
authors.initials: J
authors.lastname: Ernerudh
authors.forename: Dag
authors.initials: D
authors.lastname: Nyman
authors.forename: Pia
authors.initials: P
authors.lastname: Forsberg
authors.forename: Christina
authors.initials: C
authors.lastname: Ekerfelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D025065:Borrelia burgdorferi / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D015787:Erythema Chronicum Migrans / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012867:Skin / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma