This text is a comment about a study. I consider it dead wrong. This is why I post it here.
http://www.nejm.org/doi/pdf/10.1056/NEJMe1502350[*quote*]
Editorials
The new england journal of medicine
n engl j med 374;13 nejm.org
March 31, 2016
1277
Time for a Different Approach to Lyme Disease and Long-Term SymptomsMichael T. Melia, M.D., and Paul G. Auwaerter, M.D.
The condition of most patients with Lyme disease improves after initial antibiotic therapy; however, 10 to 20% of treated patients may have lingering symptoms of fatigue, musculoskeletal pains, disrupted sleep, and lack of customary mental functions. The plausible idea that additional antimicrobial therapy for potentially persistent bacterial infection would foster improvement has been a touchstone of hope in the 40 years since discovery of the disease in the mid-1970s. Patients with long-standing symptoms and well-documented, previously treated Lyme disease have been the focus of a number of randomized, placebo-controlled studies in North America that assessed whether additional antibiotic therapy offers a reduction in symptoms. 1
Because molecular or culture methods did not find evidence of persistent infection in the enrolled patients, it was perhaps not surprising that additional antimicrobial therapy yielded neither clinically significant nor durable reductions in symptoms as compared with placebo. Despite these findings, proponents of longer-term antibiotic therapy prescribe them for people living with stubborn symptoms — whether the symptoms are called the post-treatment Lyme disease syndrome or the more nebulous chronic Lyme disease that is often not associated with
customary, objective measures of Borrelia burgdorferi infection. 2
Weaker evidence, including findings from observational studies that suggest an improvement driven by antibiotic treatment, are commonly cited as a rationale for longer-term therapy, though such conclusions should be moderated to take into account the placebo response of 36% that was observed in the randomized, controlled trials. 3
In this issue of the Journal, Berende and colleagues report the results of the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, which again investigated whether longer-term antibiotic therapy provides relief for subjective symptoms (lasting an average of more than 2 years) attributed to Lyme disease. 4
The trial design is interesting in several respects. First,
the trial involved a European population, and the species of B. burgdorferi sensu lato that circulate in Europe, including B. afzelii and B. garinii, differ from those that circulate in North America. The infections associated with these species can manifest differently than do infections from North American species, such as with a longer initial duration of illness. 5
Second,
only 96 of 280 participants (34%) had objective evidence of Lyme disease such as the characteristic rash, erythema migrans. This means that nearly two thirds of their study population had nonspecific symptoms that were attributed to Lyme disease solely on the basis of positive IgM or IgG (or both) immunoblot assays for B. burgdorferi. Such laboratory findings do not necessarily imply causation and could represent either false positive results or remote infection, since antibody titers can remain elevated for decades. 6,7
Finally, all patients in the three study groups that were included in this trial received intravenous ceftriaxone for 2 weeks before the 12-week randomized phase, which means that there was no true placebo component; the two active oral study regimens (doxycycline and clarithromycin with hydroxychloroquine) that were used in the 12-week randomized phase are both known to produce antiinflammatory effects in addition to their antimicrobial properties. 1278
The takeaway from this well-performed study is that 12 weeks of therapy with either doxycycline or clarithromycin plus hydroxychloroquine yielded no additional benefit over placebo with respect to serial mental and physical health-related quality-of-life measures that spanned the duration of the study through 38 weeks after the active study drugs or placebo were discontinued.
Although some may attribute the improvement seen in all three study groups to the initial 2 weeks of ceftriaxone received by everyone, this improvement might be explained by the 11% of patients who had not received any previous antibiotic therapy before study entry.
Critics may rightly say that this trial does not truly capture with certainty the consequences of bona fide Lyme disease. However, studies with more stringent inclusion criteria have already been conducted, and the approach used by Berende and colleagues probably reflects the common practice in ambulatory care settings, in which patient presentations of fatigue or nonspecific pain prompt serologic checks for Lyme disease, despite evidence suggesting that these tests will not identify a probable cause or result in a treatment benefit. 8
Because antibiotics that target infection generally return a benefit before 12 weeks, arguments for a favorable delayed-onset outcome with even longer courses are weak. Moreover,
although the side effects were mostly minor, 68.6% of the patients reported at least one adverse reaction that was thought to be drug related, which should lessen the temptation among physicians to prescribe longer courses of antibiotics just in case they might help.Where does this leave patients who are living with symptoms possibly related to Lyme disease, and where does this lead their clinicians? The report by Berende et al. is an important contribution and contains a simple message, regardless of the diagnosis given to those enrolled in the trial. Patients with subjective, vexing symptoms attributed to Lyme disease should not anticipate that even longer courses of antibiotics will produce relief, a finding that is in concert with results from previous trials. These patients may, however, take small comfort in a recent study of longer-term outcomes after culture-confirmed Lyme disease that showed that mental and physical health scores had returned to baseline scores similar to those of the age-adjusted U.S. population. 9
Though prolonged antibiotic therapy is not the answer, we do not know what is truly helpful. Our personal approach is centered on making thorough assessments for alternative diagnoses such as sleep disorders and providing recommendations borrowed from practices in general medicine. Such a patchwork approach should make it clear that chronic health problems such as fatigue and pain that afflict millions of people worldwide urgently require answers with respect to the causal mechanisms and better approaches for a quicker recovery, regardless of whether the problems were triggered by B. burgdorferi or by some other process. One example of an innovative investigation is the recent finding of differential gene expression suggesting postinfectious cytokine or metabolic changes after Lyme disease, as compared with other acute infections. 10
Future research efforts should continue to explore such different strategies that may lead to proven options for helping our patients.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
From the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore.
1.
Klempner MS, Baker PJ, Shapiro ED, et al. Treatment trials for post-Lyme disease symptoms revisited. Am J Med 2013; 126:665-9.
2.
Feder HM Jr, Johnson BJB, O’Connell S, et al. A critical appraisal of “chronic Lyme disease.” N Engl J Med 2007; 357:1422-30.
3.
Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001; 345: 85-92.
4.
Berende A, ter Hofstede HJM, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med 2016;
374:1209-20.
5.
Strle F, Nadelman RB, Cimperman J, et al. Comparison of culture-confirmed erythema migrans caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann Intern Med 1999; 130: 32-6.
6.
Seriburi V, Ndukwe N, Chang Z, Cox ME, Wormser GP. High frequency of false positive IgM immunoblots for Borrelia burgdorferi in clinical practice. Clin Microbiol Infect 2012; 18: 1236-40.
7.
Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin Infect Dis 2001; 33: 780-5.
8.
Markowicz M, Kivaranovic D, Stanek G. Testing patients with non-specific symptoms for antibodies against Borrelia burgdorferi sensu lato does not provide useful clinical information about their aetiology. Clin Microbiol Infect 2015; 21: 1098-103.
9.
Wormser GP, Weitzner E, McKenna D, et al. Long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease. Clin Infect Dis 2015; 61: 244-7.
10.
Bouquet J, Soloski MJ, Swei A, et al. Longitudinal transcriptome analysis reveals a sustained differential gene expression signature in patients treated for acute Lyme disease. MBio 2016; 7(1): e00100-16.
DOI: 10.1056/NEJMe1502350
The New England Journal of Medicine
For personal use only. No other uses without permission.
Copyright © 2016 Massachusetts Medical Society. All rights reserved.
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Second,
only 96 of 280 participants (34%) had objective evidence of Lyme disease such as the characteristic rash, erythema migrans. This means that nearly two thirds of their study population had nonspecific symptoms that were attributed to Lyme disease solely on the basis of positive IgM or IgG (or both) immunoblot assays for B. burgdorferi. Such laboratory findings do not necessarily imply causation and could represent either false positive results or remote infection, since antibody titers can remain elevated for decades. 6,7
[*/quote*]
This is nonsense, because an erythema migrans only occurs in a fraction of the cases of infection!
[*quote*]
Finally, all patients in the three study groups that were included in this trial received intravenous ceftriaxone for 2 weeks before the 12-week randomized phase, which means that there was no true placebo component; the two active oral study regimens (doxycycline and clarithromycin with hydroxychloroquine) that were used in the 12-week randomized phase are both known to produce antiinflammatory effects in addition to their antimicrobial properties. [/b]
[*/quote*]
This indeed is a bad spot.
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although the side effects were mostly minor, 68.6% of the patients reported at least one adverse reaction that was thought to be drug related, which should lessen the temptation among physicians to prescribe longer courses of antibiotics just in case they might help.[*/quote*]
"thought to be drug related"! And what is real!?
[*quote*]
Though prolonged antibiotic therapy is not the answer, we do not know what is truly helpful. Our personal approach is centered on making thorough assessments for alternative diagnoses such as sleep disorders and providing recommendations borrowed from practices in general medicine. Such a patchwork approach should make it clear that chronic health problems such as fatigue and pain that afflict millions of people worldwide urgently require answers with respect to the causal mechanisms and better approaches for a quicker recovery, regardless of whether the problems were triggered by B. burgdorferi or by some other process.[*/quote*]
This is the crucial part of the whole approach. Melia and Auwaerter do write
"urgently require answers with respect to the causal mechanisms and better approaches for a quicker recovery, regardless of whether the problems were triggered by B. burgdorferi or by some other process."But the second part is:
"and better approaches for a quicker recovery", leaving a universe of opportunities for charlatans to claim to better the health conditions. Exactly this is the entrance for the frauds from homeopaths to psychic healers.
The key to all medicine is: solid diagnosing. But the huge entrance for charlatans does not exclude any putting the patients into the "psych" bin. But that is where they end up, sooner or later.
Considering LYME DISEASE please read this brand-new study published in December 2017:
"Study finds Lyme bacteria can survive antibiotic treatment months after infection"
http://www.transgallaxys.com/~kanzlerzwo/index.php?topic=9412.0