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John Aucott, M.D., of LymeMD delivered the following remarks.


Most clinicians are aware that an abundant literature exists on classic untreated Lyme disease and its typical early and late manifestations. In contrast, the literature and clinicians’ experience with persistent symptoms following antibiotic treatment of Lyme disease are more limited. Regardless of whether one names it chronic Lyme disease or post-Lyme disease syndrome, patients and clinicians are confused about how to proceed when patients report symptoms after a course of antibiotic treatment. A recent survey reported that 48 percent of Connecticut physicians are undecided as to whether chronic Lyme disease exists (Johnson and Feder, 2009). This controversy leaves clinicians uncertain about how to help patients who continue to report symptoms following antibiotic treatment.

The Centers for Disease Control and Prevention (CDC) “definite criteria” for classical signs and symptoms of Lyme disease include: erythema migrans (EM) rash, joint disease with inflammatory synovitis, and neurological disease with objective findings. Even with these straightforward criteria, a gap exists between the textbook descriptions of the disease and clinical practice. Retrospective studies (Aucott et al., 2009) have shown that frequent misdiagnosis occurs in community practices. For example, 23 percent of EM rashes and 54 percent of patients who did not present with a rash were misdiagnosed. Further complicating the clinical practice, as noted throughout the workshop, are the gaps in understanding the serologic response to the disease—how to use the laboratory tests that exist and what the limitations of these tests are.

The CDC has developed a “probable” case definition of Lyme disease that has a viral-like presentation. These patients present with symptoms and a positive serologic test result, but without physical findings or signs of an EM rash. This area of Lyme disease is poorly understood. For example, it is not known whether a subset of late (or chronic) Lyme disease patients may lack physical signs or symptoms and only present with constitutional symptoms such as fatigue. In the recent review by Feder and colleagues (Feder et al., 2007), this scenario would be equivalent to their category 3—“Patients do not have a history of objective clinical findings that are consistent with Lyme disease, but their serum samples contain antibodies against B. burgdorferi, as determined by means of standardized assays that were ordered to investigate chronic, subjective symptoms of unknown cause.” The question for the clinician is whether this category exists; no studies have been done on the treatment and the outcomes for early or late probable Lyme disease—a research gap.

Another category is patients who experience persistent symptoms following antibiotic treatment of confirmed Lyme disease. It is called different names, but for this discussion, it will be referred to as “Post-Treatment Lyme disease Syndrome.” It is known that the visible, physical signs of early Lyme disease respond to appropriate antibiotic treatment, but 10 percent of late Lyme disease patients with Lyme disease arthritis still have joint disease after antibiotic treatment. In fact, in all stages of Lyme disease, persistent symptoms without the classic signs have been observed after antibiotic treatment. For this class of patients (Post-Treatment Lyme disease Syndrome), there are more unknowns than knowns, such as the magnitude of the problem, and the range of severity of the illness.

Some factors that increase the likelihood for poor treatment outcomes and Post-Treatment Lyme Disease Syndrome such as delayed diagnosis or treatment with non-ideal antibiotics. Whether the combination of high rates of misdiagnosis and non-ideal antibiotic therapy result in a population of patients who experience persistent symptoms is unknown. Furthermore, there is a gap in the clinicians’ ability to identify patients who have persistent symptoms following antibiotic treatment in part due to the insensitivity of serologic tests, the lack of biomarkers, the lack of pathological material, or the lack of a clinically useful definition. In my community based clinical practice, when we tried to apply the Infectious Disease Society of America (IDSA) guideline definition for post-Lyme disease syndrome (Wormser et al., 2006) to our patient population, the definition did not match the patients we were seeing. Those patients who were most likely to have post-Lyme disease syndrome based on our clinical history and evaluation ultimately could not meet the IDSA case definition because they were misdiagnosed initially and had not received appropriate initial antibiotic treatment (both of which preclude inclusion in the IDSA case definition).

One gap echoed repeatedly during the workshop is that gap between the existing research on the disease and the knowledge that clinicians need in order to care for patients in the clinical setting. One way to address this gap is to establish a multicenter network for clinical evaluation and treatment of Lyme disease and other TBDs. This network would follow a translational clinical model as a way to link the laboratory study of pathogenesis to community-based patient care. The hallmark of this approach would be the use of a multidisciplinary, coordinated approach to patient evaluation.

The goals would include:

  • Formalizing reproducible case definitions or phenotypes of Post Treatment Lyme Disease Syndrome;
  • Performing uniform evaluations of clinical symptoms and signs with validated instruments from a variety of medical disciplines;
  • Developing better tests for indentifying biomarkers that can be used for diagnosis, measuring the efficacy of therapy, and establishing prior exposure in patients being evaluated for Post Treatment Lyme Disease Syndrome;
  • Establishing a biorepository of blood and tissue from patients with various stages or categories of Lyme disease;
  • Analyzing measurement tools and tests for sex-based differences in performance;
  • Developing an evidence-based clinical guideline for Post-Treatment Lyme Disease Syndrome that is based on knowledge of the pathophysiology of the illness.