How long should a patient with EM be treated?
IDSA Draft Guideline Recommendation:
“We recommend that patients with EM be treated with either a 10-day course of doxycycline or a 14-day course of amoxicillin, cefuroxime axetil or phenoxymethylpenicillin rather than longer treatment courses (strong recommendation, moderate quality of evidence).”
IDSA guidelines recommending a 14-day course of antibiotics rely heavily upon research by Dr. Wormser, andcolleagues, (1) and (2)
In the more recent Wormser study, the authors concluded that a 12-day course of antibiotics was highly effective, even though 4 of 24 subjects had PTLDS. As pointed out by Rosalie Greenberg, (5) this translates into roughly 70,000 cases annually.The actual rate of treatment failure in this study is greater than the 16.7% with PTLDS: 4 patients developed “PTLDS” and 2 more having had recurrent EM. That means 6/22 or 27% failed treatment.
Symptoms of PTLDS are generally considered “subjective” and not included in studies of Lyme Disease. They include disabling headache, fatigue, brain fog, paresthesia, and dizziness. But behind these subjective symptoms are small fiber peripheral neuropathy and dysautonomia. Recent studies show evidence of biological causes: glial activation and cerebral hypoperfusion: Novak has postulated that the low blood pressure and hypoperfusion of the brain may be responsible for the brain fog. (3,4)
Another referenced study by Wormser, (7) studied 120 patients with EM rash with a varying length of time of Doxycycline treatment, up to 20 days. Outcome measures were “objective” findings at up to 30 months. PTLDS or “subjective” findings was defined as “partial response.” Two patients in the 20-day treatment developed Bell’s palsy but was considered a success at 30 months. One patient in the 10-day treatment group was considered a complete failure, with development of meningitis. Thirteen patients divided between all groups developed recurrence of EM rash., which was attributed to a second illness rather than recurrence. These patients alone may be considered a 13% failure rate. But additionally, there was a 17% rate of PTLDS. A reasonable conclusion is that 30% of patients failed all treatment interventions.
The conclusion was that “More than 83% of the evaluable patients in each treatment group had a complete response at 30 months” which means that 17% of patients developed PTLDS
Because we do not have studies at this time which show any effective treatment which does not result in a failure rate approaching 30%, a recommendation for 14 days of antibiotics cannot be made.
References
G.P. Wormser, K.C. Brady, M.S. Cho, C.A. Scavanda, D. McKenna.Efficacy of a 14-day course of amoxicillin for patients with erythema migrans.
Diagn Microbiol Infect Dis (2019), 10.1016/j.diagmicrobio.2019.01.003
(2) Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2003; 138(9): 697- 704.
- Novak et al., 2019
- Novak, D. Felsenstein, C. Mao, N.R. Octavien, N. ZubcevikAssociation of small fiber neuropathy and post treatment Lyme disease syndrome
PLoS One, 14 (2) (2019), Article e0212222, 10.1371/journal.pone.0212222
J.M. Coughlin, T. Yang, A.W. Rebman, K.T. Bechtold, Y. Du, W.B.Mathews, et al.Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [11C]DPA-713 PET
J Neuroinflammation, 15 (346) (2018), 10.1186/s12974-018-1381-4
(5) Rosalie Greenberg, comment: https://doi.org/10.1016/j.diagmicrobio.2019.03.008
Jane Marke, MD