"Treatment of the Early Manifestations of Lyme Disease"

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

"Treatment of the Early Manifestations of Lyme Disease"

Post by duncan » Thu 20 Nov 2014 17:20

By Steere et al in July, 1983. Anyone know if there is a published version of this available to the public?

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by Lorima » Fri 21 Nov 2014 2:00

Here's the abstract. Full text is still behind a paywall.

http://www.ncbi.nlm.nih.gov/pubmed/6407378
Ann Intern Med. 1983 Jul;99(1):22-6.
Treatment of the early manifestations of Lyme disease.
Steere AC, Hutchinson GJ, Rahn DW, Sigal LH, Craft JE, DeSanna ET, Malawista SE.

Abstract
During 1980 and 1981, we compared antibiotic regimens in 108 adult patients with early Lyme disease. Erythema chronicum migrans and its associated symptoms resolved faster in penicillin- or tetracycline-treated patients than in those given erythromycin (mean duration, 5.4 and 5.7 versus 9.2 days, F = 3.38, p less than 0.05). None of 39 patients given tetracycline developed major late complications (meningoencephalitis, myocarditis, or recurrent attacks of arthritis) compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin (chi square with 2 degrees of freedom = 5.33, p = 0.07). In 1982, all 49 adult patients were given tetracycline; again, none of them developed major complications. However, with all three antibiotic agents nearly half of the patients had minor late symptoms such as headache, musculoskeletal pain, and lethargy. These complications correlated significantly with the initial severity of illness. For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin.
PMID: 6407378 [PubMed - indexed for MEDLINE]
"I have to understand the world, you see."
Richard Feynman

Martian
Posts: 1944
Joined: Thu 26 Jul 2007 18:29
Location: Friesland, the Netherlands

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by Martian » Fri 21 Nov 2014 3:07

Lorima wrote:
Ann Intern Med. 1983 Jul;99(1):22-6.
Treatment of the early manifestations of Lyme disease.
Steere AC, Hutchinson GJ, Rahn DW, Sigal LH, Craft JE, DeSanna ET, Malawista SE.

(...)

However, with all three antibiotic agents nearly half of the patients had minor late symptoms such as headache, musculoskeletal pain, and lethargy.

(...)
And the big question is: what causes such post-treatment symptoms?

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by duncan » Fri 21 Nov 2014 11:57

Thank you, Lorima. And yes, Martian, that is the $20 million question, isn't it? But that's not why I want the article in its entirety.

I believe this may be the study that touched off the Lyme wars; , or if it didn't actually trigger them, it certainly may have helped set the stage. In fact, I think this is the effort Pamela Weintraub alluded to in "Cure Unknown" as being the flash point (my paraphrase).

According to Weintraub, if this is the correct study, its Methodology section in part discusses how Steere reorganized his data on late manifestations of symptoms into major and minor. If I understand her correctly, she says he was then able to claim tetracycline cured most patients by pointing to the decline in what he had decided were major symptoms - despite the fact that those symptoms he had categorized as minor (and were supposedly anything but minor in many patients), remained in sufferers.

I want to see if this is correct, and I want to see if he justifies, or rather explains, his decision. I want to know precisely what his logic was.

TicksSuck
Posts: 100
Joined: Thu 31 May 2012 20:25

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by TicksSuck » Fri 21 Nov 2014 14:07

Within 3 weeks after completion of therapy, two patients developed facial palsy alone, but were other- wise well. Two weeks after finishing tetracycline therapy, one patient had intermittent palpitations for 1 month that were found to be due to supraventricular tachycardia. However, she also felt well. Retreatment with tetracy- cline, aspirin, and then prednisone did not change the frequency of the arrhythmia, which was suppressed with quinidine.
The remaining 45 patients reported recurrent episodes of headache or pain in joints, tendons, bursae, or muscles, often accompanied by lethargy; some patients com- plained primarily of fatigue. However, findings on physi- cal examination were normal, except for 5 patients who had pain on motion of a joint or tendon, or mild joint effusion on one examination (brief arthritis for less than 2 weeks). Symptoms were reminiscent of those at the beginning of the illness, but were generally briefer and less severe. In a given attack, pain usually occurred in one or two sites and lasted from hours to days. With frequent attacks, the pain was often migratory.
despite antibiotic therapy, nearly 50% of pa- tients had minor late complications, an observation not previously reported. These complications consisted pri- marily of recurrent episodes of headache, migratory mus- culoskeletal pain, or lethargy that were often reminiscent of their initial symptoms but generally milder. The occur- rence of such complications correlated significantly with the initial severity of illness. Compared with patients with mild or moderate initial symptoms, those with se- vere illness had a twofold greater risk of developing late disease.
The pathogenesis of these symptoms is unclear. Be- cause patients were told about possible late manifesta- tions, psychogenic factors, particularly in patients subject to suggestion, may account for the responses of some per- sons. However, if this were the only explanation, one would not expect such complications to correlate with the initial severity of illness. A severely depleted number of live spirochetes may continue to produce these less serious but sometimes debilitating symptoms. However, the symptoms occurred with equal frequency in each an- tibiotic-treatment group, and two patients with such symptoms did not respond to high-dose intravenous peni- cillin. It is also possible that minor late symptoms do not require the persistence of an intact organism. Perhaps these symptoms result from retained antigen that is diffi- cult to degrade (14), or from autoimmunity.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by duncan » Fri 21 Nov 2014 14:41

Thank you, TicksSuck.

"...patients subject to suggestion..." Gotta love that. :) Doesn't it seem that sometimes for clinicians and researchers when confronted with data they can't explain, or don't agree with, that psychology is the refuge of choice?

I think I will order this thing in its entirety and eat the fee. It's worth it.

dlf
Posts: 294
Joined: Sun 7 Apr 2013 15:36

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by dlf » Fri 21 Nov 2014 15:06

Duncan,

Before you order that manuscript, you may want to have another look at:

http://www.ncbi.nlm.nih.gov/pmc/article ... 0-0016.pdf

THE YALE JOURNAL OF BIOLOGY AND MEDICINE 57 (1984), 453-461
The Clinical Spectrum and Treatment of Lyme Disease
ALLEN C. STEERE, M.D., STEPHEN E. MALAWISTA, M.D.,
NICHOLAS H. BARTENHAGEN, M.D., PHYLLIS N. SPIELER, M.D.,
JAMES H. NEWMAN, M.D., DANIEL W. RAHN, M.D.,
GORDON J. HUTCHINSON, M.D., JERRY GREEN, M.D.,
DAVID R. SNYDMAN, M.D., AND ELISE TAYLOR, B.A.
Department of Internal Medicine, Yale University School of Medicine,
New Haven, Connecticut
Received November 28, 1983

I think this was the next publication that spelled out the thinking derived from the one you are focused on.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by duncan » Fri 21 Nov 2014 15:48

This is good stuff, dlf. Reading through it now. Some of the observations made are keepers. Thank you.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by duncan » Fri 21 Nov 2014 16:08

WOW! If I am reading this correctly, nearly 50% of patients continued to be symptomatic following treatment in the November '83 Steere et al study. In what universe does close to a 50% failure rate constitute successful therapy??

dlf
Posts: 294
Joined: Sun 7 Apr 2013 15:36

Re: "Treatment of the Early Manifestations of Lyme Disease"

Post by dlf » Fri 21 Nov 2014 21:01

Only in a universe where treatment failure has an extremely limited definition! It is a universe where resolution of symptoms is not considered to be a factor in "cure" or for "treatment failure". We have entered the twilight zone.

You will have to look at the full article to see the definition for treatment failure and the cases they characterized as having antibiotic failure. Then take a really good look at Table 4.

http://cid.oxfordjournals.org/content/50/4/512.full
Antibiotic Treatment Duration and Long-Term Outcomes of Patients with Early Lyme Disease from a Lyme Disease–Hyperendemic Area
Todd J. Kowalski1, Sujatha Tata2, Wendy Berth3, Michelle A. Mathiason3, and William A. Agger1

Abstract

Background. The length of antibiotic therapy and long-term outcomes in patients with early Lyme disease are incompletely described. We report the long-term clinical outcomes of patients with early localized and early disseminated Lyme disease based on the duration of antibiotic therapy prescribed.

Methods. A retrospective cohort study and follow-up survey of patients diagnosed as having early localized and early disseminated Lyme disease from 1 January 2000 through 31 December 2004 was conducted in a Lyme disease–hyperendemic area.

Results. Six hundred seven patients met the study inclusion criteria. Most patients (93%) were treated with doxycycline for treatment durations of ⩽10 days, 11–15 days, or ⩾16 days in 17%, 33%, and 47% of doxycycline-treated patients, respectively. Treatment failure criteria, defined before performing the study, were met in only 6 patients (1%). Although these 6 patients met a priori treatment failure criteria, 4 of these patients' clinical details suggested reinfection, 1 was treated with an inappropriate antibiotic, and 1 developed facial palsy early in therapy. Reinfection developed in 4% of patients. The 2-year treatment failure–free survival rates of patients treated with antibiotics for ⩽10 days, 11–15 days, or ⩾16 days were 99.0%, 98.9%, and 99.2%, respectively. Patients treated with antibiotics for ⩾16 days had lower 36-item Short-Form Health Survey social functioning scores on the follow-up survey. No other differences were found in follow-up clinical status or 36-item Short-Form Health Survey scores by duration of antibiotic treatment.

Conclusions. Patients treated for ⩽10 days with antibiotic therapy for early Lyme disease have long-term outcomes similar to those of patients treated with longer courses. Treatment failure after appropriately targeted short-course therapy, if it occurs, is exceedingly rare.

<snip>

Survey results. Of the 607 patients included in the study, 12 were deceased at the time the clinical status questionnaire and SF-36 survey were sent. Of the 595 questionnaires and surveys sent, 299 (50%) were completed and included in the analysis. Mean duration from diagnosis to survey results was 4.5 years in the combined cohort. Questionnaire and survey results of patients with definite and probable early Lyme disease, stratified by duration of antibiotic treatment, are given in Tables 4 and 5. Presence of persistent symptoms was not significantly different based on duration of antibiotic treatment in the definite, probable, or combined cohorts (table 4).

Post Reply