burr2008.pdf

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ADVANCED TOPICS IN

LYME DISEASE

DIAGNOSTIC HINTS AND TREATMENT

GUIDELINES FOR LYME AND OTHER

TICK BORNE ILLNESSES

Sixteenth Edition

JOSEPH J. BURRASCANO JR., M.D.

Board Member,

International Lyme and Associated

Diseases Society

DISCLAIMER: The information contained in this monograph is meant for informational

purposes only. The management of tick-borne illnesses in any given patient must be

approached on an individual basis using the practitioner’s best judgment.

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TABLE OF CONTENTS

BACKGROUND INFORMATION

What is Lyme Disease .........................................................................................................3

General Principles................................................................................................................3

Hypothalamic-Pituitary Axis..................................................................................................4

Co-Infection .........................................................................................................................4

Collateral Conditions ............................................................................................................5

LYME BORRELIOSIS

Diagnostic Hints ..................................................................................................................6

Erythema Migrans................................................................................................................7

Diagnosing Later Disease .....................................................................................................7

The CD-57 Test....................................................................................................................8

SYMPTOM CHECKLIST...................................................................................................................9-10

DIAGNOSTIC CHECKLIST.............................................................................................................. 11

LYME DISEASE TREATMENT GUIDELINES

LYME BORRELIOSIS

General Information ............................................................................................................ 12

Treatment Resistance ........................................................................................................ 12

Combination Therapy.......................................................................................................... 12

Borrelia Neurotoxin............................................................................................................. 13

TREATING LYME BORRELIOSIS

Treatment Information......................................................................................................... 13

Antibiotics......................................................................................................................... 13

Course During Therapy ....................................................................................................... 16

ANTIBIOTIC CHOICES AND DOSES

Oral Therapy...................................................................................................................... 17

Parenteral Therapy............................................................................................................. 18

TREATMENT CATEGORIES

Prophylaxis ....................................................................................................................... 19

Early Localized.................................................................................................................. 19

Disseminated .................................................................................................................... 19

Chronic Lyme Disease (persistent/recurrent infection) ........................................................... 20

Indicators for Parenteral Therapy ......................................................................................... 20

ADVANCED TREATMENT OPTIONS

Pulse Therapy ................................................................................................................... 20

Combination Therapy.......................................................................................................... 21

LYME DISEASE AND PREGNANCY............................................................................................... 21

MONITORING THERAPY AND SAFETY .......................................................................................... 21

CO-INFECTIONS IN LYME

Piroplasmosis (Babesiosis)................................................................................................. 22

Bartonella-Like Organisms.................................................................................................. 23

Ehrlichia/Anaplasma .......................................................................................................... 24

Sorting Out Co-Infections.................................................................................................... 24

SUPPORTIVE THERAPY

Rules... . .......................................................................................................................... 26

Nutritional Supplements...................................................................................................... 27

Rehabilitation..................................................................................................................... 30

Rehab/Physical Therapy Prescription................................................................................... 31

Managing Yeast Overgrowth................................................................................................ 32

BITE PREVENTION AND TICK REMOVAL....................................................................................... 34

SUGGESTED READING AND RESOURCES ................................................................................... 35

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WELCOME!

Welcome to the sixteenth edition of the “Guidelines” .

Amazingly, this edition is not only the sixteenth in the series, but as the first edition appeared in 1984, this

reflects twenty four years of effort!

Since the last edition, enough new information has become available to justify this revision. New insights

regarding co-infections, tests and treatment regimens are included. Nearly every item has been revised, but

despite great effort to condense the information, the huge amount of new information included here has resulted

in more pages than ever. Information included here is based on the literature, presentations at scientific

meetings, the many valuable observations noted by my colleagues, plus experience from caring for my own

patients. I have tried to make this information as up-to-date as possible and as inclusive as is practical. Please

use the information presented in this document as an information resource and guide. It can never replace your

own experience and clinical judgment.

I once again extend my best wishes to the many Lyme patients and their caregivers whose wisdom I deeply

appreciate, and a sincere thank you to my colleagues whose endless contributions have helped me shape my

approach to tick borne illnesses. I hope that this new edition proves to be useful. Happy reading!

BACKGROUND INFORMATION

WHAT IS LYME DISEASE?

I take a broad view of what Lyme Disease actually is. Traditionally, Lyme is defined an infectious illness caused

by the spirochete, Borrelia burgdorferi (Bb). While this is certainly technically correct, clinically the illness often

is much more than that, especially in the disseminated and chronic forms.

Instead, I think of Lyme as the illness that results from the bite of an infected tick. This includes infection not

only with B. burgdorferi , but the many co-infections that may also result. Furthermore, in the chronic form of

Lyme, other factors can take on an ever more significant role- immune dysfunction, opportunistic infections, co-

infections, biological toxins, metabolic and hormonal imbalances, deconditioning, etc. I will refer to infection

with B. burgdorferi as “Lyme Borreliosis” (LB), and use the designation “Lyme” and “Lyme Disease” to refer to

the more broad definition I described above.

GENERAL PRINCIPLES

In general, you can think of LB as having three categories: acute, early disseminated, and chronic. The sooner

treatment is begun after the start of the infection, the higher the success rate. However, since it is easiest to

cure early disease, this category of LB must be taken VERY seriously. Undertreated infections will inevitably

resurface, usually as chronic Lyme, with its tremendous problems of morbidity and difficulty with diagnosis and

treatment and high cost in every sense of the word. So, while the bulk of this document focuses of the more

problematic chronic patient, strong emphasis is also placed on earlier stages of this illness where closest

attention and care must be made.

A very important issue is the definition of “Chronic Lyme Disease”. Based on my clinical data and the latest

published information, I offer the following definition. To be said to have chronic LB, these three criteria must be

present:

1. Illness present for at least one year (this is approximately when immune breakdown attains clinically

significant levels).

2. Have persistent major neurologic involvement (such as encephalitis/encephalopathy, meningitis, etc.)

or active arthritic manifestations (active synovitis).

3. Still have active infection with B. burgdorferi (Bb), regardless of prior antibiotic therapy (if any).

Chronic Lyme is an altogether different illness than earlier stages, mainly because of the inhibitory effect on the

immune system (Bb has been demonstrated in vitro to both inhibit and kill B- and T-cells, and will decrease the

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count of the CD-57 subset of the natural killer cells). As a result, not only is the infection with Bb perpetuated

and allowed to advance, but the entire issue of co-infections arises. Ticks may contain and transmit to the host

a multitude of potential pathogens. The clinical presentation of Lyme therefore reflects which pathogens are

present and in what proportion. Apparently, in early infections, before extensive damage to the immune system

has occurred, if the germ load of the co-infectors is low, and the Lyme is treated, many of the other tick-

transmitted microbes can be contained and eliminated by the immune system. However, in the chronic patient,

because of the inhibited defenses, the individual components of the co-infection are now active enough so that

they too add to features of the illness and must be treated. In addition, many latent infections which may have

pre-dated the tick bite, for example herpes viruses, can reactivate, thus adding to the illness.

An unfortunate corollary is that serologic tests can become less sensitive as the infections progress, obviously

because of the decreased immune response upon which these tests are based. In addition, immune complexes

form, trapping Bb antibodies. These complexed antibodies are not detected by serologic testing. Not

surprisingly the seronegative patient will convert to seropositive 36% of the time after antibiotic treatment has

begun and a recovery is underway. Similarly, the antibody titer may rise, and the number of bands on the

western blot may increase as treatment progresses and the patient recovers. Only years after a successfully

treated infection will the serologic response begin to diminish.

The severity of the clinical illness is directly proportional to the spirochete load, the duration of infection, and the

presence of co-infections. These factors also are proportional to the intensity and duration of treatment needed

for recovery. More severe illness also results from other causes of weakened defenses, such as from severe

stress, immunosuppressant medications, and severe intercurrent illnesses. This is why steroids and other

immunosuppressive medications are absolutely contraindicated in Lyme. This also includes intra-

articular steroids.

Many collateral conditions result in those who have been chronically ill so it is not surprising that damage to

virtually all bodily systems can result. Therefore to fully recover not only do all of the active infections have to be

treated, but all of these other issues must be addressed in a thorough and systematic manner. No single

treatment or medication will result in full recovery of the more ill patient. Only by addressing all of

these issues and engineering treatments and solutions for all of them will we be able to restore full

health to our patients. Likewise, a patient will not recover unless they are completely compliant with every

single aspect of the treatment plan. This must be emphasized to the patient, often on repeated occasions.

It is clear that in the great majority of patients, chronic Lyme is a disease affecting predominantly the nervous

system. Thus, careful evaluation may include neuropsychiatric testing, SPECT and MRI brain scans, CSF

analysis when appropriate, regular input from Lyme-aware neurologists and psychiatrists, pain clinics, and

occasionally specialists in psychopharmacology.

HYPOTHALAMIC-PITUITARY AXIS

As an extension of the effect of chronic Lyme Disease on the central nervous system, there often is a

deleterious effect on the hypothalamic-pituitary axis. Varying degrees of pituitary insufficiency are being seen in

these patients, the correction of which has resulted in restoration of energy, stamina and libido, and resolution

of persistent hypotension. Unfortunately, not all specialists recognize pituitary insufficiency, partly because of

the difficulty in making the laboratory diagnosis. However, the potential benefits of diagnosing and treating this

justify the effort needed for full evaluation. Interestingly, in a significant number of these patients, successful

treatment of the infections can result in a reversal of the hormonal dysfunction, and hormone replacement

therapies can be tapered off!

CO-INFECTION

A huge body of research and clinical experience has demonstrated the nearly universal phenomenon in chronic

Lyme patients of co-infection with multiple tick-borne pathogens. These patients have been shown to potentially

carry Babesia species, Bartonella-like organisms, Ehrlichia, Anaplasma, Mycoplasma, and viruses. Rarely,

yeast forms have been detected in peripheral blood. At one point even nematodes were said to be a tick-borne

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pathogen. Studies have shown that co-infection results in a more severe clinical presentation, with more organ

damage, and the pathogens become more difficult to eradicate. In addition, it is known that Babesia infections,

like Lyme Borreliosis, are immunosuppressive.

There are changes in the clinical presentation of the co-infected patient as compared to when each infection is

present individually. There may be different symptoms and atypical signs. There may be decreased reliability of

standard diagnostic tests, and most importantly, there is recognition that chronic, persistent forms of each of

these infections do indeed exist. As time goes by, I am convinced that even more pathogens will be found.

Therefore, real, clinical Lyme as we have come to know it, especially the later and more severe presentations,

probably represents a mixed infection with many complicating factors. I will leave to the reader the implications

of how this may explain the discrepancy between laboratory study of pure Borrelia infections, and what front

line physicians have been seeing for years in real patients.

I must very strongly emphasize that all diagnoses of tick-borne infections remains a clinical one.

Clinical clues will be presented later in this monograph, but testing information is briefly summarized below.

In Lyme Borreliosis , western blot is the preferred serologic test. Antigen detection tests (antigen capture and

PCR), although insensitive, are very specific and are especially helpful in evaluating the seronegative patient

and those still ill or relapsing after therapy. Often, these antigen detection tests are the only positive markers of

Bb infection, as seronegativity has been reported to occur in as many as 30% to 50% of cases. Nevertheless,

active LB can be present even if all of these tests are non-reactive! Clinical diagnosis is therefore required.

In Babesiosis , no single test is reliable enough to be used alone. Only in early infections (less than two weeks

duration) can the standard blood smear be helpful. In later stages, one can use serology, PCR, and fluorescent

in-situ hybridization (“FISH”) assay. Unfortunately, many other protozoans can be found in ticks, most likely

representing species other than B. microti , yet commercial tests for only B. microti and B duncani (Formerly

known as WA-1) are available at this time! In other words, the patient may have an infection that cannot be

tested for. Here, as in Borrelia, clinical assessment is the primary diagnostic tool.

In Ehrlichiosis and Anaplasmosis , by definition you must test for both the monocytic and granulocytic forms.

This may be accomplished by blood smear, PCR and serology. Many presently uncharacterized Ehrlichia-like

organisms can be found in ticks and may not be picked up by currently available assays, so in this illness too,

these tests are only an adjunct in making the diagnosis. Rarely, Rocky Mountain Spotted Fever can coexist,

and even be chronic. Fortunately, treatment regimens are similar for all agents in this group.

In Bartonella , use both serology and PCR. PCR can be performed not only on blood and CSF, but as in LB,

can be performed on biopsy specimens. Unfortunately, in my experience, these tests, even when both types

are done, will presently miss over half the cases diagnosed clinically.

Frequent exposures to Mycoplasmas are common, resulting in a high prevalence of seropositivity, so the best

way to confirm active infection is by PCR.

Chronic viral infections may be active in the chronic patient, due to their weakened immune response. PCR

testing, and not serologies, should be used for diagnosis. Commonly seen viruses include HHV-6, CMV, and

EBV.

COLLATERAL CONDITIONS

Experience has shown that collateral conditions exist in those who have been ill a long time. The evaluation

should include testing both for differential diagnosis and for uncovering other subtle abnormalities that may

coexist.

Test B12 levels , and be prepared to aggressively treat with parenteral formulations. If neurologic involvement is

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