March 2025

Summary:

• • • Tick season starts earlier and lasts longer due to climate change – increased risk for TBE, Lyme disease, and HGE
    • Lyme disease progresses in three stages, with erythema migrans appearing as the first symptom in 70-80% of cases
    • Diagnosis requires a combination of clinical symptoms, exposure history, and serological testing
    • Two-tier testing strategy: Highly sensitive CLIA screening test followed by immunoblot for confirmation
    • Cross-reactions with other infections and timing of testing can lead to false-positive or false-negative results

The season for tick-borne diseases such as TBE (tick-borne encephalitis), Lyme disease (Lyme borreliosis), and HGE (human granulocytic ehrlichiosis) typically begins in April and reaches its peak during the warmer months. However, due to climate change, the season now starts earlier and lasts longer than in the past.

Lyme disease, caused by various species of Borrelia bacteria (Borrelia burgdorferi sensu lato complex), is among the most common tick-borne diseases. The disease progresses in three stages, with erythema migrans – an expanding skin rash – appearing as an early symptom in 70–80% of cases. Without treatment, the risk increases for systemic spread to the joints (Lyme arthritis), the nervous system (neuroborreliosis), or the heart (Lyme carditis). For reliable diagnosis, the combination of three aspects is of significant relevance: clinical presentation, exposure history, and serological testing.

The standard approach to serological laboratory diagnosis follows a two-tier testing strategy. In the first stage, a screening test using a highly sensitive chemiluminescence immunoassay (CLIA) is performed. If this test is positive or borderline, a confirmatory immunoblot is performed, which enables the detection of antibodies against multiple structures of the pathogen. In early Lyme disease, antibodies against VlsE and OspC proteins are typically detectable. In late Lyme disease, particularly with organ involvement, the antibody response is broader and includes reactivities against p100, ErpB, BmpA, VlsE, p28, DbpA, and DbpB.

However, it should be noted that cross-reactions with infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19, syphilis, and Yersinia, particularly in IgM assays, can lead to false-positive results. Testing too early (for example, with erythema migrans) can lead to false-negative results, as antibodies are only produced with a delay. Persistent IgM antibodies complicate the distinction between past and active infection. Additionally, some patients, particularly those treated early with antibiotics, may remain seronegative. Given these challenges, additional clinical information with the test request is very helpful to enable individual interpretation of results for each patient.

In rare cases, PCR testing can also be used for clarification. Suitable sample materials are cerebrospinal fluid and aspirates from affected joints.