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rarely develop a facial nerve palsy or meningitis. [1,2,6] positive results after antibiotic re‑administration
Cranial neuritis, in most cases, appears to be benign, suggesting that this retreatment was not specific nor
and it is attributed not to a persistent infection but to sustainable. In addition, in some cases, retreatment
residual, irreversible neurologic damage. Conversely, was associated with adverse events. [8,9,14] By analyzing
if Lyme meningitis was developed shortly after the these conclusions, ILADS raises issues on the bias,
completion of a course of oral antimicrobial therapy, precision, consistency, and generalization of the
the patient undergoes another cycle of treatment results. Therefore, it can be concluded that current
with either ceftriaxone or with a similar parenteral evidence supports persistent infection, although other
[6]
antibiotic. The presence of such symptoms during mechanisms may coexist. In addressing this issue,
the first several weeks to months after treatment ILADS also suggests that the potential benefits of
most often appears to be due to a slow resolution of retreatment are sufficient to support those physicians
the inflammatory process associated with a highly who wish to treat but cannot mandate retreatment. [12]
prolonged or disseminated Borrelia burgdorferi
infection. However, there is no scientific evidence In 2012, two critical analyses of the 4 RCTs [8,9,14] were
that Borrelia burgdorferi persists in such patients. [1,2] published. A first biostatistical review concluded that
[9]
[8]
Another study on patients with refractory late Lyme all primary outcomes in Klempner and Krupp.
arthritis showed that these symptoms may persist for trials, except for fatigue in the Krupp trial, were likely
several years, but the incidence and severity of the underpowered. [15] In the same year, a reappraisal of US
symptoms do decrease over time, and the estimated clinical trials highlighted the limited generalization of
number of individuals who continue to have the results and the reduced likelihood of identifying
recurrences is reduced by 10‑20% each year. [7] significant treatment effects. This specific study
concludes that antibiotic retreatment is potentially
The use of antibiotic regimen for a long time is not beneficial at least in a fraction of the PTLDS group.
recommended, in fact, it does not improve patient Thus, the recommendation of not re‑administering
outcome. Instead, it can also promote the development antimicrobials should be carefully reconsidered.
of drug‑resistant infections. Valid placebo‑controlled Additionally, it suggests that immune dysregulation
randomized trials do not support long‑term treatment as a contributor to pathogenesis should be taken into
for Lyme disease and have failed to demonstrate any account in future studies. [16]
benefit over placebo. In fact, these randomized clinical
studies have shown that approximately one‑third of Interestingly, brain abnormalities were detected in
patients benefit from placebo. [8,9] Additionally, there chronic Lyme patients using neuroimaging based on
is no clear evidence supporting the hypothesis that single photon emission computed tomography. The
Lyme disease is a chronic, actively infectious disease authors concluded that the use of antibiotics with
requiring ongoing antibiotic therapy. [2,10,11] intracellular activity resulted in an increased resolution
or improvement of clinical symptoms detected by
TO TREAT PTLDS imaging in 70% of patients over a 1‑2 years period. [17]

In 2014, the International Lyme and Associated COMMENT
Diseases Society (ILADS) published its own treatment
guidelines [12] for the management of Lyme disease The consequences of the lack of a worldwide accepted
patients, after adopting the GRADE scheme. [13] definitive diagnosis and the lack of an established
Among others, ILADS guidelines address the issue treatment regimen include poor patient health,
of antibiotic retreatment in patients with persistent discomfort, additional expensive diagnostic testing,
symptoms. After performing an individualized lack of health care effectiveness, and deterioration of
risk‑benefit assessment, the initiation of a 4‑6 weeks the doctor‑patient relationship. [18] Currently, PTLDS is
antibiotic regimen is recommended in previously the paradigm of this scenario.
treated Lyme disease patients. This is then followed
by a reassessment which will determine whether In this situation, three challenging questions need to
modifications or discontinuation of the treatment is be addressed by the scientific community: First, how
necessary. Even longer treatments may be chosen. [12] do we precisely define PTLDS? Second, how do we
diagnose PTLDS? And third, is PTLDS a fully treatable
Furthermore, ILADS is critical in interpreting the condition?
results of the 4 randomized control trials (RCTs), [8,9,14]
based on which the IDSA and other authorities There is a common believe that in order to define
support the idea that there is no infectious mechanism PTLDS, an expert panel and subsequently a consensus
underlying PTLDS. The 4 RCTs did not provide any report seems to be the best solution. To address the

Neuroimmunol Neuroinfammation | Volume 3 | Issue 1 | January 20, 2016 11