LymeNet Newsletter Volume 3 Issue 11

Volume: 3
Issue: 11
Date: 19-Jul-95

Table of Contents:

I. LYMENET: Vancouver LD Conference Notes - Part 2 II. About The LymeNet Newsletter

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * LymeNet Newsletter * ***********************************************************************

IDX# Volume 3 - Number 11 - 7/19/95 IDX# INDEX IDX# IDX# I. LYMENET: Vancouver LD Conference Notes - Part 2 IDX# II. About The LymeNet Newsletter IDX#

I. LYMENET: Vancouver LD Conference Notes - Part 2 ----------------------------------------------------- Sender: Lloyd E. Miller, DVM <[email protected]>

Notes from the VIII Annual Lyme Disease Foundation Scientific Conference on Lyme Borreliosis and other Spirochetal and Tick-Borne Diseases - Held April 28-29 1995 -- at Vancouver, British Columbia, Canada.

Part 2

Prepared by Lloyd E. Miller, DVM

Every effort has been made to be accurate. Please report any additions or corrections. Always confirm drug doses and names of medications with another source before using.

18. Detection of Borrelia burgdorferi sequences in clinical specimens by a PCR capture assay - M.Manak, M.D.

The development of a PCR test was described. In this test which was used on samples of urine, blood, serum, joint fluid and CSF it was felt that whole blood and serum were a more reliable indicator of active infection than was urine. It is noted that 89% of patients with a positive PCR also had other positive serologic evidence (WB, ELISA, IgM capture) of Lyme disease yet it was felt that PCR was a valuable adjunct to the other tests.

19. Detection of Borrelia burgdorferi-DNA in urine from patients with Lyme borreliosis - B. Schmidt, Ph.D.

A PCR test is described which was used to test urine for the presence of Bb-DNA. Of 90 EM patients 80 (88.9%) had positive urine PCR tests. In comparison serology was reactive for IgG in 11.1 to 16.7% and only 2 of 66 tested sera had antibodies to p39 antigen. IgM was detected in 6 to 40% depending on the test used. The conclusion made was that by using this urine PCR test detection of Bb infection can be improved dramatically. This work was done in Austria.

20. A Solid phase ELISA-antigen detection system for LD - R.C. Tilton, Ph.D.

The development of a urine test to detect Bb antigens in urine using an ELISA system was described. It was said to be able to detect less than 10 organisms. This test may be commercially available in a few months. Also being investigated is the use of this test with other body fluids.

An interesting rhetorical question was asked by Dr. Tilton: Is it the antibody tests that are not reliable or the LD patient's antibody that is not reliable?

21. Surrogate markers of active infection in Lyme disease - S. Schutzer, M.D.

A specific antibody may be found bound to an infectious agent (immune complex), especially in early and during active infection. That this could be occurring in Lyme disease was tested. Complexed antibody to Bb was found in 10 of 11 very early cases, 55 of 56 symptomatic patients, 0 of 50 healthy controls, 2 of 50 patients from endemic areas with other diseases including those likely to have elevated levels of immune complexes, 13 of 13 persistently seronegative patients who had EM and a subset of 4 of 4 who were also positive on a T cell proliferative assay to Bb, and 0 of 8 patients who had recovered. In early acute cases complexed IgM was the first antibody to be detected. This study suggested that testing for complexed antibody may help improve the diagnosis of LD by testing.

22. New tools in the diagnosis of neurologic Lyme disease - P.K. Coyle, M.D.

Diagnosis of neurologic disease caused by Bb can be very difficult. Many of the tests currently being used were discussed (basic CSF tests, CSF culture, antigen detection, PCR, intrathecal antibody detection, immune complex detection, neuroimaging, neurophysiologic, neuropsychiatric testing). All have short comings. *No single test can be relied upon to confirm or deny a diagnosis of CNS Lyme disease*. This does not mean the testing should not be done but that the results must be interpreted in the light of the known problems inherent in the tests. Comment was made that intrathecal antibody production can not be used to diagnose LD in North America because intrathecal antibodies are not often produced. When oligoclonal bands are found consider MS before LD. Significant slowing in reaction times is seen in LD. Also affected are attention and learning retrieval. Nerve conduction times can be slower than normal.

23. Morphologic diversity of Borreliae: a review - A. McDonald, M.D.

Dr. McDonald showed an impressive number of various forms of spirochetes as they appear in tissues described by various pathologist. To visualize these forms requires a dark field microscope in many cases. Comment was made that unfortunately most of these microscopes have been taken out of service and the expertise to use them is being lost.

[Comment - Several promising tests were described at this meeting. Still, none of them is the gold standard. It would seem reasonable to do a panel of tests of various types in an effort to make a laboratory confirmation of Lyme disease. The test results must be interpreted by physicians knowledgeable about the inherent problems of each test. Even then some cases will be missed. *Lyme disease is still a clinical diagnosis.*]

CLINICAL MANIFESTATIONS OF LYME DISEASE

24. Clinical presentations of Lyme borreliosis in lower Midwest - E. Masters, M.D.

A report on the on going saga of "Master's disease". Still no agreement from the CDC that Master's and Lyme diseases are one and the same. The possibility that they are both clinically indistinguishable but caused by variants of similar organisms exists. The borrelia found is not typical of North American forms described so far. Stay tuned!

Differentiation of EM vs. brown recluse spider bite was demonstrated. Spider bite is extremely painful. The bite is not usually in the center of the lesion. Spider bite displays the red (erythema) White (ischemia) and blue (necrosis) sign.

Dr. Masters made the point that "Hypochondria does not develop out of the blue in a 45 year old with no previous history of disease."

25. Lyme arthritis in British Columbia - G. Price, M.D

The first known locally acquired case of Lyme arthritis in B.C. was described. Comment was made that compared to other areas there are few cases of arthritis caused by Lyme disease in British Columbia. No explanation is yet offered.

26. Cardiovascular manifestations of Lyme Disease - B. McManus, M.D.

A high frequency of electrophysiological perturbations has been documented in LD. First, second and third degree heart block are described with third degree being most common. Patients with Lyme carditis may exhibit presyncope, syncope (fainting), palpitations, shortness of breath, chest pain and electrocardiographic abnormalities. In some patients a *temporary* pace maker may be required. Rarely is there permanent heart muscle damage or chronic heart disease as the result of Lyme disease.

27. Lyme disease cases in the Lower Mainland - E. Murakami

A case of Lyme disease acquired within the boundaries of B.C. was described.

A new technique for removal of ticks from patients was demonstrated. The removal method involves the injection of Xylocaine intradermally producing a bubble of liquid which produces hydrostatic pressure at the site of the bite causing the tick to release and fall off.

28. Acrodermatitis chronica atrophicans - R, Scrimenti. M.D.

ACA was describe. It is primarily seen in Europe but has been described in North American patients. It is an excellent example of prolonged latency and chronic infection with Bb. Bb titers in these patients are usually high. The usual treatment is doxycycline. If neurologic and/or arthritic complications are present then Benzyl penicillin IV and oral doxycycline are then used to treat.

29. Symptoms and characteristics of chronic LD patients - Smithon, Ph.D., I. Vanderhoof, Ph.D.

Information is based on studies of questionnaires provided to the Lyme Disease Foundation by patients. Symptom patterns of Lyme disease showed no difference based on geographic location. Symptom patterns were also the same whether the patient was diagnosed by a general practitioner or a specialist. Becoming symptom free seems to depend on getting *early* treatment. The earlier the diagnosis is made and the earlier treatment is administered the more favorable the outcome. The more severe the EM rash is the more likely it is that the patient will recover with no residual symptoms. It is presumed that the more severe the rash the more likely it is that a patient will seek and receive medical attention. Profound exhaustion appears to be a marker indicating that recovery is less likely. Continuous symptoms indicate continuing disease and is also indicative of a poorer prognosis for full recovery. Severity of symptoms, except EM rash, is not a good indicator of prognosis. The information presented was considered preliminary. However, this does appear to
agree with anecdotal information currently available. A poster on this topic was also presented by Robert C. Smithson and Kathryn A. Robbins.

CHRONIC/PERSISTING LYME BORRELIOSIS

30. Antibiotic resistance in spirochetes - J. Davis, M.D.

Apparently there is no work on antibiotic resistance by Bb. Mechanisms of microbial resistance to antibiotics were discussed in general terms. Reasons for resistance include: failure of the antibiotic to enter the microbe; active removal of the antibiotic from the microbe before it can cause damage; sequestration of the drug within the microbe; detoxification of the antibiotic by the microbe; damage caused is repaired resulting in no harm; genetic gene transfer mechanisms both acquired and mutation; target on the microbe is missing, modified or amplified. His best guess in the case of Bb would be the active removal mechanism.

31. Spectrum of antibiotic-responsive menigoencephalomyelitides - K.B. Liegner, M.D.

This presentation was to document four very difficult and severe cases histories of Lyme disease, one of which resulted in death. Unfortunately there was not enough time for Dr. Liegner to present these cases. It is hoped he will do so in another forum and in the literature because this information is very important to the understanding of how very serious this disease can be. What information he was able to present (including a short video) demonstrated how very difficult it can be to diagnose LD in severely ill patients with no serologic evidence of the disease.

32. Management chronic Lyme disease - J. J. Burrascano, Jr., M.D.

Citing several literature reports to make his point, Dr. Burrascano said "It is truly a myth that a patient with disseminated disease is cured with four weeks of antibiotic therapy." He enumerated several reasons why Bb resists eradication; latency and S-layers, localization in privileged sites (intracellular and intraocular), inadequate understanding of how antibiotics kill Bb, ignoring the pharmacologic principles of antibiotic half lives, cell penetration and CSF and tissue levels. He made and strongly emphasized the need to do serum peek and trough levels whenever oral antibiotics are used. The peek level should be in the mid-teens and the trough level *must* be above three. In his studies he has documented 100 fold variability in serum ampicillin levels in patients matched by age, body size and drug dose. Unless oral antibiotics are absorbed from the GI tract in sufficient amount to produce serum and tissue levels high enough to inhibit Bb there is little or no chance the antibiotic will be effective. He commented that intramuscular
benzathine penicillin has been shown to be unexpectedly effective.

Also, IV doxycycline has been more effective than oral doxycycline. He also pointed out that IV antibiotics have big advantages in efficacy over oral regimens. By using strategies such as interrupted and pulse dosing IV antibiotic use has been quite safe and effective. His studies have shown that many patients with resistant infections have deficiencies in B, T, and/or killer cell function. If these abnormalities can be corrected then treatment response improves. The stated end point of treatment is when the patient is *totally* free of symptoms.

His suggested that the starting oral dose of doxycycline should now be 300mg per day. Do peak and trough levels and adjust the dose accordingly. He said Augmentin is not an appropriate antibiotic choice for use in LD. To reduce the side effects if IV Rocephin he suggested a dosage regime of 5 days on and 2 days off using up to 4 grams per day. Dosage for benzathine penicillin was suggested to be 1.2 million units once or twice weekly long term. It was suggested that vitamin B-12 levels be checked and corrected if they are low.

To help improve T cell function he suggested Sinequan 5 to 50 mg daily.

[Comment - Dr. Paul LaVoie advocated the same end point of treatment (that is to treat until there are zero symptoms - including the minor symptoms). He estimated that if treatment is taken to this end point the relapse rate is about 10%; otherwise relapse rate approximates 60%. Dr. Burrascano noted that copies of his latest treatment protocols are available from the Lyme Disease Foundation.]

33. Chronic encephalopathy: to treat or not to treat? - B. Fallon, M.D.

Problems with fatigue, memory, attention, depression and mental disorganization are features of Lyme encephalopathy. When a patient has been treated for several months with antibiotics and still has problems the following questions must be asked and answered; 1 - Is the diagnosis of Lyme encephalopathy correct? 2 - are there other coexisting problems that could be better treated (depression, panic disorder, ADD). 3 - Are somatoform features involved (psycogenic seizures). 4 - what has been the previous response to antibiotic treatment?

Preliminary results of a study involving patients who have Lyme encephalopathy who had received no more than 16 weeks of IV antibiotic was reported. The response was assessed in the patients who received additional course of IV therapy vs. the response in patients who did not receive additional IV antibiotic. Patients who received additional IV antibiotic therapy had a marked improvement in general health, emotional well being and physical functioning. Those who received additional oral antibiotic therapy or no additional therapy did not have this marked response. The number of patients in the study is small which may affect the results. The study, however, is on going and as the sample size increases the results will become more reliable.

Comment was also made that IM benzathine penicillin has given some unexpectedly good results. The suggestion was made that ADD can be treated with Wellbutrin and stimulants.

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