The CDC defines the persistent symptoms of fatigue, pain, or joint and muscle aches, lasting greater than 6 months in Lyme disease patient after proper treatment, as “Post-Treatment Lyme Disease Syndrome” (PTLDS) 6. On the other hand, the IDSA refers to this consolation of symptoms as Post-Lyme Syndrome and argues that there is no concrete evidence that spirochetes persist in these patients. The IDSA propose that the chronic symptoms are due to an autoimmune response. Therefore they disagree with the use of long-term antibiotics for persistent symptoms of Lyme disease. In contrast, the International Lyme and Associated Diseases Society (ILADS) insist that the chronic symptoms are due to the persistence of spirochetes and define these symptoms as “chronic Lyme disease” (CLD). The ILADS conclude that the bacteria are undetected by traditional assay test. They contend that long term antibiotics should be used to combat Chronic Lyme Disease.
In 2006, the IDSA developed and released treatment guidelines, which advised against long- term antibiotic treatment. However the resultant guidelines failed to address persistent spirochetal infection in chronic Lyme disease patients, who often remain symptomatic after short-term antibiotic therapy 14. These guidelines influenced medical practitioners’ treatment decisions and had been used by insurance companies as justification to deny coverage 15.
This severely diminishes the ability to obtain long-term antibiotic treatment for those patients who have persistent symptoms and who cannot afford to pay out-of-pocket.
In 2008, Richard Blumenthal, the Connecticut Attorney General initiated an investigation into the development of the 2006 IDSA disease treatment guidelines 16. He accused the IDSA panel of undisclosed conflicts of interest of panel members and its chairman and disregarding the existence of chronic Lyme disease 15.
The New England Journal of Medicine (NEJM) and the American Academy of Neurology (AAN) provided “independent corroboration” that the 2006 guidelines were developed from evidence-based medicine 16. However, it was later revealed that 11 members of the IDSA guidelines panel were authors of the NEJM article. The AAN had similar overlapping authorship 17. Both the NEJM and the AAN failed to disclose this obvious conflict of interest.
The investigation was terminated and the IDSA did agree to an independent review of the 2006 guidelines 15. The independent review by an expert panel was published in 2010. The panel unanimously supported the 2006 guidelines, stating, “No changes or revisions to the 2006 Lyme guidelines are necessary at this time”. They also purported that long-term antibiotics are “unproven and potentially dangerous” 17.
The 2006 IDSA’s Lyme Disease treatment guidelines remain unchanged and appear validated. However, several states have enacted laws that allow licensed physicians to prescribe long-term antibiotics for therapeutic reasons for patients clinically diagnosed with Lyme disease. Additionally, Connecticut and Rhode Island have passed laws mandating insurance coverage when long-term antibiotic therapy is deemed medically necessary.
Furthermore, there is still a difference in recommended treatment for certain manifestations of Lyme Disease (Table 3).
Table 3.
Comparison of Infectious Diseases Society of America (IDSA) and International Lyme and Associated Diseases Society (ILADS) recommendations for Lyme disease treatment10,11,12.
Treatment Focus |
IDSA |
ILADS |
Treatment of a tick bite without symptoms of Lyme disease |
Doxycycline 200 mg single dose |
Doxycycline, 100 mg bid for 20 days |
Erythema migrans |
Doxycycline, amoxicillin, or cefuroxime for 14-21 days |
Doxycycline, amoxicillin, or cefuroxime for 28-42 days or azithromycin for at least 21 days |
“Persisting symptoms of Lyme disease” |
No antibiotic therapy |
Multiple agents (individually or in combination) are mentioned without specific doses or duration recommended |
Diagnosis
When the hallmark, bull’s eye rash or erythema migrans is present during the early stage, the diagnosis is clinically based on history and physical exam and no blood test is required. When there is no erythema migrans rash, the diagnosis is still made clinically and a blood test can help confirm the diagnosis.
The CDC recommends a two-step process when testing blood 6. These blood tests are most reliable about 2 weeks post-innoculation, as the body has had time to make antibodies. The following diagram shows the steps as laid out by the CDC 6: (Figure 3).
Figure 3.

The first test, an enzyme immunoassay, has high sensitivity, meaning however, there could be false positives and therefore must be confirmed by the second test. The second test, an immunoblot test, commonly called a “Western Blot” which has high specificity yet, this means there could be some false negatives. Theoretically when a highly sensitivity test is followed by a highly specific test, only a few true positives are excluded and rarely any false positives are included6. Nevertheless for specific laboratory case ascertainment, a positive B. burgodorferi culture plus a positive result from the two-tier testing is sufficient in the diagnosis of Lyme Disease for patient with symptoms onset less than 30 days 18.
Differential Diagnosis
Lyme disease is known as the “Great Imitator” because it has very nonspecific symptoms that can look like many other conditions. Patients of Lyme disease are frequently misdiagnosed with chronic fatigue syndrome, fibromyalgia, multiple sclerosis, and various psychiatric illnesses, including depression. Misdiagnosis with these other diseases may delay the correct diagnosis and treatment as the underlying infection progresses unchecked 18.
As previously stated systemic symptoms of Lyme Disease can be nonspecific and look very much like the flu. Consequently this can make diagnosing Lyme disease very difficult in some patients. One major difference in the constellation symptoms characteristic to the flu, is that in early Lyme disease these symptoms are intermittent with a longer duration in comparison to the flu 1, 2.
Finally, it is important to always consider other conditions as well as possible co- infections when Lyme disease is suspected. There are at least four known pathogens in addition to Lyme disease that is transmitted by the black-legged or the Ixodes ticks. The most common co-infections that occur with Lyme disease are Anaplasma
Phagocytophilum, which causes Human Granulocytic Anaplasmosis, previously known as Human Granulocytic Ehrlichiosis; and Babesia Microti, the primary cause of Babesiosis. These co-infections are an emerging problem and may exacerbate clinical features of Lyme disease 19.
Prognosis
When treated early, Lyme disease is easily and rapidly cleared, preventing later stages of disease. However, these later stages of Lyme disease also respond well to treatment if therapy is commenced soon after the appearance of symptoms 1, 2.
Although there continues to be percentage of patients infected with Borrelia burgodoreri who develop chronic Lyme Disease, most patients recover fully from this infection 1, 2. It is critical to identify chronic lyme disease patient as their conditions may be intermittent but debilitating.