LymeNet Newsletter Volume 1 Issue 12

Volume: 1
Issue: 12
Date: 03-Jun-93

Table of Contents:

NEWS: Upstate NY County Declared Endemic ANNOUNCEMENT: Support Group in Montgomery County, PA HARTFORD COURANT: Victim of Lyme disease settles malpractice suit SPECIAL SECTION: LDF Conference Summary - part 1 (with Consensus Diagnostic Categories and Treatment Guidelines)

Newsletter:

***************************************************************************** * Lyme Disease Electronic Mail Network * * LymeNet Newsletter * ***************************************************************************** Volume 1 - Number 12 - 6/03/93

I. Introduction II. Announcements III. News from the wires IV. ** Special ** LDF Conference Summary V. Jargon Index VI. How to Subscribe, Contribute and Get Back Issues

I. ***** INTRODUCTION *****

In this issue, Dr. Lloyd Miller reports from the 6th Annual Lyme Disease Scientific Conference that took place last month in Atlantic City, NJ. He has compiled a series of notes that provide us with a synopsis of the information presented at the conference. Thanks to Dr. Miller for submitting this information for publication.

Dr. Miller also informs us that Albany County, NY, has been declared endemic. Such declarations are important, as they warn residents of the risks and add credibility to patients who are seeking treatment for LD.

A new support group has formed in Montgomery County, PA -- details are printed below.

Finally, we learn of Connecticut's first publicly announced malpractice settlement against a doctor who failed to recognize LD. I'm keeping a close eye on the legal ramifications of LD as they may have an effect on how doctors treat (or fail to treat) patients.

-Marc.

II. ***** ANNOUNCEMENTS *****

Sender: "Lloyd E. Miller,DVM" <[email protected]> Subject: Upstate NY County Declared Endemic Date: May 26, 1993

Albany County, New York has been declared *endemic* for Lyme disease. The New York State Health Department has identified infected ticks in the county. Many of us up here have felt there have been infected ticks here for a long time. This is a very important announcement because it validates what we have been observing -- that the ticks and the disease have been spreading into upstate New York State. Dr. Dennis White, the Director of the Tick-Borne Disease Institute, in his statement emphasized that although they have only identified infected ticks in Albany County, so far, that all residents of the area and surrounding counties must take notice because it is likely infected ticks already are present.

The listed reference although a couple of years old is excellent and highly recommended to New York State residents. An update of the article would prove very interesting. White DJ,Chang H et al: The geographic spread and temporal increase of the Lyme disease epidemic. Journal of the American Medical Society 1991;266(9):1230-1236.

=====*=====

A new support group has formed in south-eastern Pennsylvania. This SG meets at the Holy Trinity Lutheran Church in Abington (Montgomery County) on a monthly basis. For more information, contact: Phil Rudolph 215-721-9424 (W) 215-659-0718 (H) Barbara Caruso 215-991-8534 (W) 215-627-8135 (H)

III. ***** NEWS FROM THE WIRES *****

SOURCE: The Hartford Courant [Connecticut] DATE: May 18, 1993, A Edition HEADLINE: Victim of Lyme disease settles malpractice suit; Victim of Lyme disease settles suit BYLINE: LYNNE TUOHY; Courant Staff Writer

An Old Saybrook woman has secured what may be the state's first medical malpractice settlement against doctors for misdiagnosis of Lyme disease, which has left the 30-year-old almost totally disabled.

Deborah Heiney suffers chronic pain from neurological damage caused by the disease and will receive $350,000 from the insurance company representing Dr. Richard O. Gritzmacher and the late Dr. Donald E. Cook, Heiney's lawyer said Monday.

Emmet L. Cosgrove of New London filed a lawsuit on Heiney's behalf three years ago in Middlesex Superior Court, alleging she is permanently disabled from complications of late-stage Lyme disease because of the negligence of the Old Saybrook doctors.

Laura Frankel, a lawyer with Updike, Kelly Spellacy, the firm representing the doctors and their insurance company, confirmed that a settlement had been reached, but declined to discuss any of its provisions.

In the summer of 1987, Heiney sought treatment from Gritzmacher and Cook for severe headaches, muscle aches and flu-like symptoms. Cosgrove said the doctors first diagnosed her as having the flu and prescribed pain medication. They later concluded she had post-viral encephalitis and gave her an anti- inflammatory drug, Cosgrove said.

Her condition did not improve, and Heiney consulted an orthopedic specialist in July 1988 -- 13 months after her first visit to Gritzmacher and Cook. Tests done by the specialist revealed the Lyme disease, concentrated in her spinal fluid. Intravenous antibiotic therapy failed to eradicate the damage done by the disease, which had migrated to her brain, Cosgrove said.

The disease impaired Heiney's memory and now causes chronic pain that often forces her to use a wheelchair. She is unable to work, Cosgrove said.

"There is always a high degree of pain, but there are times when it becomes debilitating," Cosgrove said. "It is intermittent in that sense, but not in the sense that there are days she feels great.

"It's very frightening. It can happen pretty quickly," Cosgrove said of the permanent damage that Lyme disease can cause. "If it's not picked up, there can be very serious consequences."

Cosgrove said Heiney's doctors could not be faulted for their first misdiagnosis of her symptoms in June 1987, but should have suspected Lyme disease when her symptoms, which Cosgrove called "classic," persisted. She was a prime candidate for the disease, living as she did then on the edge of a salt marsh, owning several pets that could have been carriers of the bacteria -- laden deer ticks that transmit the disease to humans, and exhibiting her symptoms at the height of the Lyme disease season, Cosgrove said.

In addition, the state Department of Health Services sent notices to all Connecticut doctors in June 1987 requiring them to report any new cases of Lyme disease within 24 hours. The notices should have heightened awareness, Cosgrove said.

Lyme disease was first identified by a Yale University physician in 1975 in Lyme and Old Lyme. Cosgrove said Heiney did not experience the "bull's eye" rash that characterizes the onset of the disease in more than half of Lyme disease sufferers, but she had virtually all the other symptoms, including the persistent muscle ache and other flu-like symptoms.

Cosgrove said he could find no other Lyme disease malpractice settlement on record in the state.

IV. ***** SPECIAL LDF CONFERENCE SUMMARY ******

Sender: "Lloyd E. Miller,DVM" <[email protected]> Subject: 6th Annual Lyme Disease Scientific Conference

NOTES AND OTHER INFORMATION FROM THE 6th ANNUAL LYME DISEASE SCIENTIFIC CONFERENCE -- ATLANTIC CITY, NEW JERSEY -- MAY 5th - 6th, 1993

Every effort has been made to be accurate as possible -- corrections, additions, clarifications and comments on anything in the notes are welcome.

Items bracketed by >*< are my own comments - LEM >*<

The title of the paper is given first followed by the primary authors name followed by excerpts from the authors abstract and notes taken during his presentation.

Lloyd E. Miller,DVM May 1993 ------------------------------------------------------------------------------

1993 LYME DISEASE DIAGNOSTIC CATEGORIES

Consensus opinion of 50 physician panel in association with the Lyme Disease Foundation - Tolland, Connecticut

EARLY LOCALIZED

Single Erythema Migrans rash per bite and no other symptoms, with no signs or symptoms that disseminated disease could be present.

DISSEMINATED DISEASE A. EARLY DISSEMINATED * General - Fever, flu-like symptoms, lymphadenopathy. * Neurologic - severe headache, meningitis (aseptic), cranial neuritis, radiculitis, meningioradiculitis (Bannwarth's), stroke. * Dermatologic - Multiple lesions per bite, lymphocytomas. * Muscular - Myalgias. * Skeletal - Arthralgias. * Ophthalomologic - conjunctivitis, ocular keratitis, uveitis, chorioiditis, exudative retinal detachments, pars planitis, diplopia, neuroretinitis, optic neuritis. B. LATE DISSEMINATED * General - Profound fatigue. * Neurologic - Chronic encephalomyelitis, demyelinating-like syndromes, axonal polyneuropathies, cognitive and behavioral changes. * Psychiatric * Ophthalmologic - Optic atrophy * Dermatologic - Acrodermatitis Chronica Atrophans * Cardiac - Heart block, myocarditis, vasculitis * Skeletal - Arthritis, asymmetric, pauciarticular, intermittent or chronic

REFRACTORY DISEASE A. Persisting signs and symptoms responsive to additional therapy. Patient is responsive to additional antibiotic therapy and improves, the patient has a J-H reaction to additional therapy, or the patient's condition degenerates upon discontinuing antibiotic therapy. Varying the antibiotic or method of administration may help. B. Persisting signs and symptoms not responsive to additional therapy. The patients signs and symptoms are in no way affected by use (despite varying antibiotic choice or method of administration) or lack of use of antibiotics. Discontinue antibiotic use and move to supportive therapies.

>*< These classifications make more sense to me than the stage 1-2-3 descriptions of the past for they more closely describe what is happening. They help validate for those patients with refractory disease their situation -- no they really aren't crazy after all!!! >*< -----------------------------------------------------------------------------

1993 LYME DISEASE TREATMENT CATEGORIES

Consensus opinion of 50 physician panel in association with the Lyme Disease Foundation -- Tolland, Connecticut

EARLY LOCALIZED (30 - 45 days) * Amoxicillin 1000 mg plus probenecid 500mg TID * Doxycycline 100 mg BID (not in pregnancy or children) * Minocin 1.5 mg per kg per day (not in pregnancy or children) * Ceftin 500 mg BID

DISSEMINATED DISEASE A. EARLY DISSEMINATED ( minimum of 6 weeks) * Amoxicillin 1000 mg plus probenecid 500 mg TID * Doxycycline 200 - 400 mg per day (not in pregnancy or children) * Minocin 200 - 400 mg per day (not in pregnancy or children) * Azithromycin 250 - 500 mg per day * Clarithromycin 500 - 1000 mg per day * Ceftin 1500 mg per day * Use IV therapy if oral not producing a satisfactory response B. LATE DISSEMINATED (minimum of 6 - 8 weeks with option to extend) * Claforan 6 grams per day (2 grams TID) * Rocephin 2 grams daily * Penicillin G 20 - 25 million units per day * Ampicillin 4 - 6 grams per day (divided 4 times per day)

REFRACTORY DISEASE A. Persisting signs and symptoms responsive to antibiotic * Increase duration of treatment * Increase doses of antibiotics * Check peak and trough blood levels of antibiotic adjust dose accordingly * Change to different antibiotic * Change from oral to IV antibiotic * Consider continuous IV infusion of antibiotic * Consider combining antibiotics - use antibiotics from different classes B. Persisting signs and symptoms not responsive to antibiotic * Reassess patient * Supportive treatment based on symptoms - physical therapy, non- steroidal anti-inflammatory drugs, muscle relaxants, antidepressants, tricyclics, plaquenil, immunoglobins, synovectomy * Psychiatric support and evaluation * Continue testing as newer tests become available * Adjunctive treatment - B-vitamins, acidophilus - no alcohol * Consider retreatment if conditions change

NOTES: * Patients on long term oral antibiotic treatment should have monthly follow-ups and laboratory tests. * Patients on long term IV antibiotics should have weekly laboratory tests. * Laboratory tests to include as a minimum SMA 12 (including liver function tests). Lytes, CBC with differential

>*< Note that this is a consensus opinion -- several antibiotics which have been used in the past are not mentioned (e.g. Suprax) -- much longer term antibiotic treatment is still practiced by many of the physicians on the panel -- it is still important that treatment of each patient be individualized and be a decision made by the patient and physician working together -- no combination therapies are mentioned in the consensus but it was clear from comments made that several of the physicians do prescribe combination therapy if he feels that the case warrants such treatment >*< ------------------------------------------------------------------------------

Conspecifity of Ixodes scapularis and Ixodes dammini James H. Oliver, Jr., PhD

Significance of determination that Ixodes dammini (Ix.d.) and Ixodes scapularis (Ix.s.) are one in the same: Data from the North can be extrapolated to the South -- helps to refute that "Lyme doesn't exist in the South." Crossing Ix.d. with Ix.s. produced all fertile ticks through third generation. However crossing Ix. pacificus with Ix.d produced all sterile offspring in first generation. Therefore, these are separate species. Under laboratory conditions the life cycle of Ix.d. and Ix.s. are the same and they both have the same vector competence. ------------------------------------------------------------------------------

Evaluation of a human Lyme disease vaccine for safety and immunogenicity John P. May, PhD

Vaccine using OspA was effective in protecting mice by challenge by injection. Speaker described safety trials of the vaccine in people. *This was not an efficacy trial.* The vaccine was administered to healthy volunteers from a non-endemic area. Safety profile reported "no adverse reactions what-so-ever." There were some local reactions at the site of injection which all resolved within 72 hours. Two of the 36 had a fever of 99.5F which resolved within 24 hours. Irritability, joint pain and headache were infrequent. A six month follow up of the safety study is about to be conducted. Conclusion drawn from the study was it is a very safe vaccine. Preliminary results of vaccine in people using IgG response to the vaccine showed a mild immune response to the first dose of the vaccine with a strong immune response following the second dose four weeks later. Growth inhibition assay done by incubating B.b. in sera and Guinea pig complement resulted in B.b. growth inhibition in the sera of those vaccinated with
both the adjuvanted and non-adjuvanted vaccine and no inhibition in those vaccinated with a placebo.

A question was asked if the vaccine might be effective against B.b. strains that do not contain OspA for which there was no current answer.

>*< There was some concern expressed by some in attendance that the outer surface proteins my produce immune-mediated adverse responses in people and that OspA may be a poor vaccine candidate because of this possibility. It was also expressed by many that they felt a human vaccine was still years away.>*< ------------------------------------------------------------------------------

Symptoms based on physician specialty and geographic distribution: Similar or differing presentations? Irwin T. Vanderhoof, FSA, PhD, ACAS, CFA, CLU, BS

No regional differences in presentation of Lyme disease were found by diagnosing specialist or geographic region; recollection of tick bite or rash vs no recollection; or on results of serologic tests. Presentations essentially followed the same patterns and involved the same body systems in the same proportions. ------------------------------------------------------------------------------

Interactions of B. burgdorferi with skin fibroblasts Mark S. Klempner, MD

Experiments were conducted to examine whether fibroblasts might provide a protective niche for the spirochete. Can spirochetes be isolated from co-cultures with human fibroblasts after treatment with ceftriaxone? Ceftriaxone does not enter fibroblasts. Cultured Bb plus fibroblasts plus ceftriaxone at 3 times minimum inhibitory concentration (MIC) and recovered Bb from 26 of 26 cultures. Also demonstrated recovery of Bb from infected fibroblast co-cultures despite treatment of the cell cultures with > 10 times the Minimum Bacteriacidal Concentration (MBC). He showed that protection required viable fibroblasts. He also demonstrated that Bb was killed in the growth medium so recovery was from the cells not outside the cells. The length of protection was "considerable" -- 14 days in ceftriaxone. He also clearly demonstrated the presence of whole Bb organisms inside the fibroblasts. Bb were inside the fibroblasts within 24 hours. He showed that Bb binds to and invades fibroblasts. No sugars have been found that
inhibit Bb from binding to fibroblasts. Monoclonal Antibodies to P41 or P39 did not inhibit binding. Fibroblasts in vitro did protect Bb from antibiotic. ------------------------------------------------------------------------------

Extracellular components of Borrelia burgdorferi - possible role in the pathogenesis of Lyme disease Claude F. Garon, PhD

Hypothesis: Few spirochetes produce an enormous amount of vesicular (extracellular) material which results in disease expression. Bb appears during periods of growth to shed membranous materials from its surface. This material is found in infected ticks, human cultures, and in infected animals. It has not been found in uninfected ticks or animals. This material appears to be present wherever active growth of the organism is taking place. Whether this can be used to provide evidence of persistent infection is not yet known. It may be a useful marker for active infection and/or treatment effectiveness.

Speculation: The vesicles on Bb become coated with antibody making it less visible to the system: bind IgM tightly -- mechanism to avoid immune system? The extracellular components are involved in the packaging and protection of intact DNA molecules containing a few known and many unknown genes and gene products.

They possess potent, non-specific mitogen activity which may cause an inappropriate and non-effective stimulation of the immune system triggering autoimmune disease components.

Any vaccine which contains any of these components has the potential to produce autoimmune sequella.

Four outer surface proteins have now been identified - OspA, B, C, D ------------------------------------------------------------------------------

The immune response and its application toward diagnosis Steven E. Schutzer, MD

As specific antibody may be found bound to an infectious agent, especially early in the infection. the author's hypothesis was that this could be happening in Lyme disease. The predominance of antibody may be found bound to the agent in an antigen-antibody or immune complex. With current antibody tests for a positive test there must be excess of antibody over antigen. Until there is an excess all antibody will be complexed. Serum immune complexes were isolated and dissociated from Lyme disease patients fulfilling modified CDC criteria and controls. Bb complexes were found in 10 of 11 early cases, 55 of 56 symptomatic patients with Lyme disease, 0 of 50 healthy controls, 2 of 50 with other disease including those likely to have elevated levels of immune complexes, 13 of 13 persistently seronegative patients who had erythema migrans, 4 of 4 who were also positive on t cell proliferation assay to Bb, and 0 of 8 patients who had recovered. In early acute cases complexes to IgM was the first antibody to be detected. The authors conclusion: this relatively simple
technique has potential to support or exclude a clinical diagnosis of early as well as active Lyme disease. ------------------------------------------------------------------------------

Lyme disease, Abdominal pain and the gastrointestinal tract Martin D. Fried, MD

Twelve children with clinical and laboratory evidence of Lyme disease were evaluated. Abdominal symptoms of Lyme disease can occur early; 6 to 12 months prior of diagnosis and antibiotic treatment. GI symptoms may occur before other symptoms. Types of pain exhibited were: chest, epigastric, periumbilical, left lower quadrant banding to the right, and vomiting. In these patients the disease involved 8 different organ systems and 9 of 12 had laboratory evidence of LD. An extensive rule out was conducted on these patients. All had normal ultrasounds.

Endoscopic exam results: 9 of 12 had inflammation of either the stomach or duodenum. 75% of the patients had gastrointestinal inflammation. 2 of 12 had spirochetes in duodenal mucosa. 1 of the 2 was seronegative. Lymphocytes and plasma cells were the predominant inflammatory cells. Colonic biopsies were consistent with Crohn's disease.

Speculations of the etiology of the inflammation: excess stomach acid, antibiotics (most patients had had no previous antibiotic treatment), infection, histamine/prostaglandin release, immune response.

Treatment: Tagmet and Zantac were not particularly effective. Omeprazole (which stops stomach acid production) was administered for 2 months along with antibiotics. The pain improved but was not entirely eliminated.

Conclusion: gastritis and duodenitis occurs in children with Lyme disease and abdominal pain.

>*< This is a significant paper. For several years Dr. Dorothy Pietrucha has been reporting abdominal pain in pediatric patients (often quite severe ) which has been blamed on (confused with) possible GI ulceration, or in females on gynecological problems. This paper convincingly demonstrates yet another organ system that Lyme disease affects and Bb invades. Over the past three years I have heard many anecdotal reports that Lyme patients have been diagnosed with inflammatory bowel disease and/or Crohn's disease. This report helps to validate these reports. We should hope the same investigations will be conducted in adults. >*< ------------------------------------------------------------------------------

Pediatric cardiac involvement with Lyme disease Michael B. Alpert, MD, FAAP, FACC

Lyme carditis: literature reports 3:1 - male : female ; the author believes it is the reverse. 10% of kids with Lyme have cardiac involvement

Electocardiogram abnormalities described were: first, second, and third degree heart block, right bundle branch block, premature ventricular contractions (seeing more an more of this ), abnormal polarization (inverted T wave) Symptoms: chest pain, palpitations, irregular heart beat, low heart rates

Chest pain from: (1) costochondritis which isn't very responsive to antiinflammatory treatment but does improve with antibiotic treatment; (2) myocarditis which can be serious and cause death; (3) unexplained

Palpatation: (1) supraventricular tachycardia which is not well controlled unless Lyme is treated; (2) unexplained

Irregular heart beat: (1) premature ventricular contractions; (2) premature atrial contractions; (3) unexplained

Slow heart rate; (1) complete heart block; (2) sinus bradycardia ------------------------------------------------------------------------------

Evidence for rapid nervous system invasion by Borrelia burgdorferi Patricia K. Coyle

Pseudotumor Cerebri seems to be age related - seen in children

Study of 25 patients (serum and CSF) -- 12 female/13 male -- ages 15 - 80 -- 10 had completed antibiotic treatment -- length of illness = 1 day to 3 months 68% had EM, 16% Bell's palsy, 8% recollected tick bite associated with headache and stiff neck, 4% meningitis, 4% acute polyradiculopathy

CSF contained OspA antigen in 36% and 72% had Borrelia specific immune complexes. All-in-all 88% of patients had either antibody, antigen or immune complex in their CSF; in contrast only 17% had elevated intrathecal production, 24% had elevated protein levels and 20% increased cell count.

Authors conclusion: Findings support early central nervous system invasion by Borrelia burgdorferi. Headache, in particular, is a suggestive symptom. The CSF shows frequent abnormalities with regard to B. burgdorferi antigen and specific complexes, but not with regard to routine studies. This is in contrast to what has been reported from Europe, and suggests clinical differences from American Lyme disease. ------------------------------------------------------------------------------

Eye findings in Lyme disease Robert Lesser, MD

Eye findings in Lyme disease have been reported to include conjunctivitis, keratitis, uveitis and neuroretinitis. Neuro-ophthalmologic findings include papilledema, cranial nerve palsy, pupillary abnormalities and optic neuropathy. ------------------------------------------------------------------------------

Dermatologic manifestations of Borreliosis Rudolph J. Scrimenti, MD

Authors comment: Annular (round) lesions although described the most are not really the most common.

*Important tip*: To help make diagnosis of EM use a strong light and a hair dryer -- the heat helps bring out the EM which rapidly fades.

EM lesion on face or hands in adults are not well defined - making it difficult to make the diagnosis - EM is seldom on palms or soles but when they are the are fleeting.

V. ***** JARGON INDEX *****

Bb - Borrelia burgdorferi - The scientific name for the LD bacterium. CDC - Centers for Disease Control - Federal agency in charge of tracking diseases and programs to prevent them. CNS - Central Nervous System. ELISA - Enzyme-linked Immunosorbent Assays - Common antibody test EM - Erythema Migrans - The name of the "bull's eye" rash that appears in ~60% of the patients early in the infection. IFA - Indirect Fluorescent Antibody - Common antibody test. LD - Common abbreviation for Lyme Disease. NIH - National Institutes of Health - Federal agency that conducts medical research and issues grants to research interests. PCR - Polymerase Chain Reaction - A new test that detects the DNA sequence of the microbe in question. Currently being tested for use in detecting LD, TB, and AIDS. Spirochete - The LD bacterium. It's given this name due to it's spiral shape. Western Blot - A more precise antibody test.

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