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Table 2 Current European clinical case definitions of Lyme borreliosis manifestations and indications for serological testing adapted from Stanek [2] and Dessau [1]

From: Serodiagnosis of Lyme borreliosis—is IgM in serum more harmful than helpful?

Manifestation Clinical case definition [2] Laboratory evidence essential [2] Laboratory/clinical evidence: supporting [2] Detection of antibodies to Borrelia burgdorferi s.l. [1]
Erythema migrans Expanding red or bluish-red rash (≥ 5 cm in diameter)a with or without central clearing. Advancing edge typically distinct, often intensely colored, not markedly elevated. None Detection of B. burgdorferi s.l. by culture and/or PCR from skin biopsy. Not recommended
Borrelial lymphocytoma Painless bluish-red nodule or plaque, usually on ear lobe, ear helix, nipple, or scrotum; more frequent in children (especially on ear) than in adults. Seroconversion or positive serologyb Histology in unclear cases Histology. Detection of B. burgdorferi s.l. by culture and/or PCR from skin biopsy. Recent or concomitant EM. Serum IgG and/or IgM
Acrodermatitis chronica atrophicans Long-standing red or bluish-red lesions, usually on the extensor surfaces of extremities. Initial doughy swelling. Lesions eventually become atrophic. Possible skin induration and fibroid nodules over bony prominences. High level of specific serum IgG antibodies Histology. Detection of B. burgdorferi s.l. by culture and/or PCR from skin biopsy. Serum IgG
Lyme neuroborreliosis In adults, mainly meningo-radiculitis, meningitis; rarely encephalitis, myelitis; very rarely cerebral vasculitis. In children mainly meningitis and facial palsy. Pleocytosis and demonstration of intrathecal-specific antibody synthesisc Detection of B. burgdorferi s.l. by culture and/or PCR from CSF. Intrathecal synthesis of total IgM, and/or IgG and/or IgA. Specific serum antibodies. Recent or concomitant EM. Specific CSF/serum antibody index
Lyme arthritis Recurrent attacks or persisting objective joint swelling in one or a few large joints. Alternative explanations must be excluded. Specific serum IgG antibodies, usually in high concentrations Synovial fluid analysis. Detection of B. burgdorferi s.l. by PCR and/or culture from synovial fluid and/or tissue. Serum IgG
Lyme carditis Acute onset of atrio-ventricular (I–III) conduction disturbances, rhythm disturbances, sometimes myocarditis or pancarditis. Alternative explanations must be excluded Specific serum antibodies Detection of B. burgdorferi s.l. by culture and/or PCR from endomyocardial biopsy. Recent or concomitant erythema migrans and/or neurologic disorders. Serum IgG and/or IgM
Ocular manifestations Conjunctivitis, uveitis, papillitis, episcleritis, keratitis. Specific serum antibodies Recent or concomitant Lyme borreliosis manifestations. Detection of B. burgdorferi s.l. by culture and/or PCR from ocular fluid. Serum IgG
  1. aIf < 5 cm in diameter, a history of tick bite, a delay in appearance (after the tick bite) of at least 2 days, and an expanding rash at the site of the tick bite is required
  2. bAs a rule, initial and follow-up samples have to be tested in parallel in order to avoid changes by inter-assay variation
  3. cIn early cases, intrathecally produced specific antibodies may still be absent
  4. EM, erythema migrans; B. burgdorferi s.l., Borrelia burgdorferi sensu lato; CSF, cerebrospinal fluid; PCR, polymerase chain reaction