The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.

Erythema migrans is by far the most frequent manifestation of Lyme borreliosis in Europe, amounting to nearly 90 % of all cases [13]. Clinical presentation of erythema migrans is pathognomonic, and therefore, usually no laboratory tests are necessary for diagnosis [26]. Because serology is frequently negative at this stage, antibodies should not be determined. In rare cases of atypical erythema migrans, clinical diagnosis may be difficult. In these cases, the present extent of the erythema may be marked with a pen and should be reexamined 1–2 days later. If the erythema has expanded, the diagnosis of erythema migrans is most likely correct. PCR of skin biopsy is a good test to confirm a diagnosis of erythema migrans, and results are truly positive in about 70 % of cases when good biopsy and laboratory techniques are used [3]. However, skin biopsy is seldom justified. Response to antibiotic treatment is only confirmed by disappearance of erythema migrans and not by serological means.

When other manifestations of Lyme borreliosis are suspected, and erythema migrans is not present, serological assays should be performed [31].

Lyme borreliosis should be considered in patients with cranial nerve palsy, in particular, seventh nerve palsy, and signs of meningitis with or without headache, lethargy, or irritability for about 9 days on average before admission [25, 27]. Stiffness of the neck is often very mild or absent and must be searched for carefully. In contrast, patients with aseptic/viral meningitis usually display obvious nuchal rigidity and have a history of less than 6 days, often 1 or 2 days only [4, 27]. Especially in the absence of cranial nerve palsy, the possible diagnosis of Lyme borreliosis is not being considered often enough. Patients with headache as a sole manifestation usually do not have neuroborreliosis. In comparison to patients with noninflammatory headaches of frequent and various causes, the headaches of patients with neuroborreliosis usually have a clearly indicated beginning and a short duration of less than a month [27]. To confirm neuroborreliosis, antibodies against Borrelia burgdorferi are assessed in serum and cerebrospinal fluid. In the case of early neuroborreliosis, there is lymphocytic pleocytosis in the cerebrospinal fluid, but often, intrathecal antibody production cannot yet be found [24]. If cerebrospinal fluid yields pleocytosis with ≥90 % mononuclear cells, there are no other remaining causes apart from tuberculous meningitis. In very early stages of the disease, serological results in serum may still be negative [4]. In typical cases, antibodies of the immunoglobulin IgM class against B. burgdorferi are found by enzyme immunoassay and are confirmed by two or more bands by IgM immunoblot. Later, IgG antibodies may be detected by enzyme immunoassay, and the number of bands in the IgG immunoblot increases gradually. Therefore, in case of a negative serology and continuing suspicion of neuroborreliosis, it may be useful to determine antibodies in serum again 2 or 3 or 4 weeks later to find seroconversion. PCR in cerebrospinal fluid often is positive only in very early cases when there are not yet antibodies against B. burgdorferi present. Although a positive PCR supports the diagnosis of neuroborreliosis, a negative PCR does not exclude it [18]. Therefore, PCR should not be used routinely to make a diagnosis of neuroborreliosis, but only in complex cases.

In the case of newly appearing arthritis, a borrelial serology should be obtained, especially in mono- or oligoarthritis, including the knee joint [14]. In case of Lyme arthritis, the enzyme immunoassay is highly positive for IgG antibodies against B. burgdorferi; the results of which are confirmed by immunoblot with a multitude of bands. PCR in synovial fluid may be positive. The rate of correctly positive results by PCR may be increased by using synovial tissue. However, the suspicion of Lyme arthritis is not sufficient justification for performing a synovial biopsy, and laboratory confirmation of the diagnosis primarily relies on serum antibody determination.

There is a variety of further rare manifestations of Lyme borreliosis. When there is a reasonable suspicion of Lyme borreliosis, diagnosis is supported by serology. The expected serological results vary with the stage of the disease, i.e., if the patient has an early or late manifestation of Lyme borreliosis. Eyes may be involved by keratitis, iridocyclitis, or uveitis intermedia. Cardiac involvement may appear as AV block or carditis. Acrodermatitis chronica atrophicans is a late skin manifestation of borreliosis and very rare in children. In borrelial lymphocytoma, usually found at earlobes, nipples, or testicular sacks, serology is not infrequently false negative. Therefore, diagnosis may be established exclusively by clinical means, as is the case for erythema migrans. The issue of summer flu, including fever, joint pain, and fatigue without signs of mucous membrane involvement is still unclear, although it may be a manifestation of early Lyme borreliosis. The clinical presentation is too varied, and serological examinations often are still negative, or false positive serological results lead to misdiagnosis and unnecessary treatment [23]. The disease usually is self-limiting after a few days.

The following consequences should be drawn: