When is the best time to order a Western blot and how should it be interpreted?

Despite significant progress in the diagnostics of Lyme borreliosis, including molecular methods, the detection of a specific antibody response remains the mainstay in the laboratory diagnosis of the disease. Current guidelines propose the combination of highly sensitive screening assays, such as ELISAs, with very specific confirmatory tests, such as immunoblots, to guarantee a cost-effective, sensitive and specific diagnostic approach. For a correct interpretation of the serological findings, the investigator must always consider a whole series of clinical and laboratory facts. Here, we summarize current laboratory algorithms in the diagnosis of Lyme borreliosis, with a special emphasis on when to order a Western blot and how to interpret it correctly in the context of additional clinical and laboratory information.