What Makes It Tick: Exploring the Mechanisms of Post-treatment Lyme Disease Syndrome

Post-treatment Lyme disease syndrome (PTLDS), which may also be referred to incorrectly as "chronic Lyme disease," is defined by the Infectious Diseases Society of America (IDSA) as the presence of fatigue, pain, and/or cognitive complaints with the functional impact that persists for more than six months after completing treatment for Lyme disease (LD). These symptoms occur in 10%-20% of patients previously diagnosed with LD caused by the bacteria Borrelia burgdorferi and appropriately treated with a course of antibiotics. The symptoms of PTLDS can be easily overlooked or misdiagnosed as a psychiatric manifestation in geographic locations that rarely see LD. In contrast, geographic locations with a higher prevalence of LD may be more aware of PTLDS symptoms and have higher clinical suspicion leading to this diagnosis. The pathophysiology behind the persistent symptoms some people experience from a primary infection is still largely unknown. Some mechanisms that have been proposed include permanent tissue damage and inflammation, immune system dysfunction, autoimmune response, co-infection, and even persistent infection refractory to treatment. We propose that ongoing PTLDS symptoms seem to be related to an autoimmune response to the tissue damage and inflammation caused by the viable or nonviable spirochete pathogen. At this point, PTLDS is diagnosed clinically as no quantifiable methods are available from laboratory or tissue diagnostics as of 2024. Similar pathophysiological features of PTLDS are seen in diseases such as COVID-19 or chronic fatigue syndrome (CFS). More effective diagnostic approaches might include further studies looking at a possible connection in the genomes of individuals developing PTLDS, quantifiable biomarkers, common inflammatory markers/pathways, and careful histopathological studies of human tissues.